What are the common side effects of Capecitabine 500mg. How should Capecitabine be taken for optimal effectiveness. What precautions should be considered when using Capecitabine. How does Capecitabine interact with other medications.

Understanding Capecitabine: An Overview of the Oral Chemotherapy Drug

Capecitabine is an oral chemotherapy medication primarily used in the treatment of various types of cancer, including colon, rectal, and breast cancer. As a prodrug of 5-fluorouracil (5-FU), it is designed to be converted into its active form within tumor cells, potentially reducing systemic side effects compared to intravenous 5-FU administration.

The 500mg dosage of Capecitabine is commonly prescribed, but it’s crucial to understand that dosing can vary based on individual patient factors such as body surface area, overall health status, and specific cancer type. Patients should always follow their oncologist’s instructions regarding dosage and administration schedule.

How does Capecitabine work?

Capecitabine functions as an antimetabolite, interfering with DNA synthesis and cellular division. Once ingested, it undergoes a three-step enzymatic conversion process, with the final step occurring preferentially within tumor cells due to higher concentrations of the enzyme thymidine phosphorylase. This targeted activation mechanism aims to enhance the drug’s efficacy while potentially reducing systemic toxicity.

Common Side Effects of Capecitabine 500mg: What to Expect

While Capecitabine can be an effective treatment option, it’s associated with a range of side effects that patients and caregivers should be aware of. Understanding these potential reactions can help in early recognition and management, improving overall treatment outcomes.

• Nausea and vomiting
• Diarrhea
• Fatigue and weakness
• Loss of appetite
• Hand-foot syndrome
• Changes in taste
• Constipation
• Headache and dizziness
• Sleep disturbances

Nausea and vomiting are frequently reported side effects of Capecitabine. How can these symptoms be managed effectively? Oncologists often prescribe antiemetic medications prophylactically or as needed. Additionally, patients may find relief by eating smaller, more frequent meals, avoiding strong odors, and staying hydrated. In some cases, adjusting the timing of Capecitabine administration in relation to meals can help mitigate these symptoms.

Diarrhea is another common side effect that requires careful management. Why is prompt attention to diarrhea crucial for patients on Capecitabine? Severe or prolonged diarrhea can lead to dehydration and electrolyte imbalances, potentially compromising treatment efficacy and overall health. Patients are typically advised to increase fluid intake and may be prescribed antidiarrheal medications such as loperamide. It’s essential to report persistent or severe diarrhea to the healthcare team promptly.

Hand-Foot Syndrome: A Unique Side Effect of Capecitabine

Hand-foot syndrome, also known as palmar-plantar erythrodysesthesia, is a distinctive side effect associated with Capecitabine therapy. This condition manifests as redness, swelling, and pain in the palms of the hands and soles of the feet. In severe cases, it can progress to blistering and peeling of the skin, significantly impacting quality of life.

How can patients reduce the risk or severity of hand-foot syndrome? Preventive measures include:

• Avoiding hot water when bathing or washing dishes
• Using moisturizing creams regularly
• Wearing comfortable, well-fitting shoes
• Avoiding activities that put excessive pressure on the hands and feet

Early recognition and intervention are key in managing hand-foot syndrome. Patients should be encouraged to report any symptoms promptly, as dose modifications or supportive treatments may be necessary to alleviate discomfort and prevent progression.

Dosage Guidelines and Administration of Capecitabine 500mg

The appropriate dosage of Capecitabine varies depending on several factors, including the specific cancer type, stage of disease, body surface area, and individual patient characteristics. Typically, Capecitabine is administered in cycles, with periods of treatment followed by rest periods to allow for recovery from side effects.

Standard Dosing Regimen

A common dosing schedule for Capecitabine involves:

1. Taking the medication twice daily (morning and evening) for 14 days
2. Followed by a 7-day rest period
3. This 21-day cycle is then repeated as prescribed by the oncologist

The total daily dose is usually calculated based on body surface area, with 1250 mg/m² twice daily being a standard starting dose for many indications. However, this may be adjusted based on individual patient factors and tolerability.

Administration Guidelines

How should Capecitabine be taken for optimal absorption and efficacy? Patients are typically advised to:

• Take Capecitabine tablets with water within 30 minutes after a meal
• Swallow tablets whole, without crushing or chewing
• Maintain consistent timing of doses in relation to meals throughout the treatment course

Why is it important to take Capecitabine with food? Food intake can help improve the absorption of the medication and may reduce the likelihood of certain gastrointestinal side effects. However, patients should consult their healthcare provider regarding specific dietary recommendations during treatment.

Monitoring and Managing Side Effects: Strategies for Patients and Caregivers

Effective management of Capecitabine side effects requires a proactive approach from both patients and their care team. Regular monitoring and open communication are essential for identifying and addressing adverse reactions promptly.

Blood Count Monitoring

Why are regular blood tests crucial during Capecitabine treatment? Capecitabine can affect blood cell production, potentially leading to anemia, neutropenia, or thrombocytopenia. Routine complete blood count (CBC) tests help healthcare providers assess these parameters and make necessary adjustments to the treatment plan.

Liver and Kidney Function Tests

Monitoring liver and kidney function is also important, as Capecitabine metabolism and excretion can be affected by impairments in these organs. Regular biochemical tests allow for early detection of any changes that may require dose modifications or supportive care.

Symptom Tracking

Patients are often encouraged to keep a symptom diary, noting the occurrence and severity of side effects. This information can be invaluable during follow-up appointments, helping healthcare providers tailor the treatment approach and implement supportive measures as needed.

Drug Interactions and Precautions with Capecitabine 500mg

Understanding potential drug interactions and necessary precautions is crucial for safe and effective Capecitabine therapy. Patients should provide a comprehensive list of all medications, supplements, and herbal products they are taking to their healthcare team.

Notable Drug Interactions

Several medications can interact with Capecitabine, potentially affecting its efficacy or increasing the risk of side effects. Some significant interactions include:

• Warfarin and other anticoagulants: Capecitabine may enhance the anticoagulant effect, necessitating closer monitoring of coagulation parameters
• Phenytoin: Capecitabine may increase phenytoin levels, requiring dose adjustments and monitoring
• Allopurinol: Concurrent use may decrease the effectiveness of Capecitabine
• Leucovorin: May enhance both the effectiveness and toxicity of Capecitabine

How do these interactions impact patient care? Healthcare providers may need to adjust dosages, increase monitoring frequency, or consider alternative treatments to manage these interactions effectively.

Special Precautions

Certain patient populations require special consideration when using Capecitabine:

• Elderly patients: May be more susceptible to side effects and may require lower starting doses
• Patients with renal impairment: Dose adjustments may be necessary due to altered drug clearance
• Individuals with known dihydropyrimidine dehydrogenase (DPD) deficiency: At increased risk for severe toxicity and may require alternative treatments
• Pregnant or breastfeeding women: Capecitabine is contraindicated due to potential fetal harm and unknown risks to nursing infants

Why is screening for DPD deficiency important before initiating Capecitabine therapy? DPD is a key enzyme in the metabolism of fluoropyrimidines like Capecitabine. Patients with DPD deficiency may experience severe, life-threatening toxicity even at standard doses. Genetic testing for DPD mutations or enzyme activity assessment can help identify at-risk individuals and guide treatment decisions.

Long-term Considerations and Follow-up Care for Capecitabine Users

While Capecitabine treatment typically focuses on immediate cancer control and symptom management, it’s essential to consider long-term effects and follow-up care strategies. Patients and healthcare providers should be aware of potential late-onset side effects and the importance of ongoing monitoring even after treatment completion.

Cardiovascular Monitoring

Why is cardiovascular monitoring important for patients who have undergone Capecitabine therapy? Some studies have suggested a potential link between fluoropyrimidine-based chemotherapies, including Capecitabine, and an increased risk of cardiovascular events. Long-term follow-up may include:

• Regular electrocardiograms (ECGs)
• Echocardiograms to assess cardiac function
• Monitoring of blood pressure and lipid profiles

Neuropathy Assessment

Peripheral neuropathy, characterized by numbness, tingling, or pain in the extremities, can persist or develop even after treatment cessation. Ongoing neurological assessments may be necessary to identify and manage these symptoms effectively.

Fertility and Reproductive Health

For patients of reproductive age, discussions about fertility preservation and family planning should be initiated before starting Capecitabine treatment. How long after completing Capecitabine therapy should patients wait before considering pregnancy? Generally, healthcare providers recommend waiting at least 6 months after the last dose before attempting conception, but individual recommendations may vary based on specific circumstances.

Psychological Support

The psychological impact of cancer treatment can extend well beyond the active treatment phase. Providing access to mental health resources, support groups, and counseling services can be crucial for patients’ long-term well-being and quality of life.

Emerging Research and Future Directions in Capecitabine Therapy

As with many areas of oncology, research into optimizing Capecitabine therapy is ongoing. Several avenues of investigation show promise for improving treatment outcomes and patient experiences.

Biomarker-Guided Therapy

Can biomarkers help predict Capecitabine efficacy and toxicity? Researchers are exploring various genetic and molecular markers that may indicate which patients are most likely to benefit from Capecitabine treatment or be at higher risk for severe side effects. This personalized medicine approach could lead to more tailored treatment strategies in the future.

Combination Therapies

Ongoing clinical trials are investigating the potential of combining Capecitabine with novel targeted therapies or immunotherapies. These combinations may enhance anticancer effects while potentially allowing for lower doses of Capecitabine, thus reducing side effects.

Alternative Dosing Schedules

Research into alternative dosing schedules, such as intermittent or metronomic dosing, aims to improve tolerability without compromising efficacy. These approaches may be particularly beneficial for patients who struggle with standard dosing regimens due to side effects.

Improved Formulations

Efforts to develop new formulations of Capecitabine, such as extended-release versions or combination pills with supportive medications, could enhance patient compliance and reduce pill burden.

As research progresses, patients and healthcare providers should stay informed about emerging data and potential new treatment options. Participating in clinical trials, when appropriate, can provide access to cutting-edge therapies and contribute to the advancement of cancer treatment.

In conclusion, Capecitabine 500mg remains a valuable tool in the oncologist’s arsenal, offering an oral chemotherapy option for various cancer types. While side effects can be significant, careful monitoring, proactive management, and ongoing research continue to improve the therapeutic index of this medication. As with all cancer treatments, individualized care plans that consider the unique needs and circumstances of each patient are essential for optimizing outcomes and quality of life.

Capecitabine Oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing

Nausea, vomiting, loss of appetite, constipation, tiredness, weakness, headache, dizziness, trouble sleeping, or changes in taste may occur. Nausea and vomiting can be severe. In some cases, your doctor may prescribe medication to prevent or relieve nausea and vomiting. Eating several small meals, not eating before treatment, or limiting activity may help lessen some of these effects. If any of these effects last or get worse, tell your doctor or pharmacist promptly.

Diarrhea is a common side effect of this medication. Drink plenty of fluids unless directed otherwise. Your doctor may also prescribe medication (such as loperamide) to help lessen diarrhea. Vomiting or diarrhea that doesn’t stop may result in a serious loss of body water (dehydration). Contact your doctor promptly if you notice any symptoms of dehydration, such as unusual decreased urination, unusual dry mouth/thirst, or dizziness/lightheadedness.

Temporary hair loss may occur. Normal hair growth should return after treatment has ended. Also, temporary nail changes may occur.

People using this medication may have serious side effects. However, your doctor has prescribed this drug because he or she has judged that the benefit to you is greater than the risk of side effects. Careful monitoring by your doctor may decrease your risk.

Stop taking capecitabine and tell your doctor right away if any of these very serious side effects occur: severe nausea/vomiting (vomiting 2 or more times per day, unable to eat or keep food/fluids in your stomach), painful redness/swelling/sores in mouth or on your tongue.

Capecitabine may make you develop a skin problem called hand-foot syndrome. To help prevent this, protect your hands and feet from heat or increased pressure. Avoid activities such as using hot dishwater, taking tub baths, jogging, long walks, or using garden or household tools such as screwdrivers. Symptoms may include pain, swelling, redness, blisters, or numbness of the hands/feet. Your doctor may prescribe medication (such as balm) to help with symptoms. If symptoms affect your usual activities, get medical help right away.

For men and women of childbearing age, this medication may affect your ability to have children. Ask your doctor for more details.

This medication may lower your ability to fight infections. This may make you more likely to get a serious (rarely fatal) infection or make any infection you have worse. Tell your doctor right away if you have any signs of infections (such as sore throat that doesn’t go away, fever, chills, cough).

Tell your doctor right away if you have any serious side effects, including: easy bruising/bleeding, mental/mood changes (such as depression), swelling of the ankles/feet, vision changes, signs of kidney problems (such as change in the amount of urine), yellowing eyes/skin, dark urine.

Get medical help right away if you have any very serious side effects, such as: chest/jaw/left arm pain, unusual sweating, fainting, slow/fast/irregular heartbeat.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, such as: rash/blisters/peeling, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other side effects not listed above, contact your doctor or pharmacist.

In the US –

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.

In Canada – Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Effectiveness, Ease of Use, and Satisfaction

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20 People found this comment helpful

Switched to this in place of FOLFIRI i.v. medications. Avastin used in combo with present pills and previous FOLFIRI. Main side effects with both are extreme fatigue and nausea. Fatigue was much worse with only i.v. meds. Nausea seemed worse with the pills, but probably because you take them for 2 weeks. I prefer nausea that can be relieved with a pill than fatigue that keeps me in the bed al…

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My mother took this medication for two weeks
as a precaution. She had severe diarhea, became dehydrated requiring hospitalization.
I believe this medication caused her death.

Shared reviews and ratings

Condition: Colon and Rectal Cancer that has Spread to Another Area EffectivenessEase of UseSatisfaction

only side effect skin issues with my hands and feet

9 ShapeCreated with Sketch.thumb_up copy 5Created with Sketch.Report this postFill 3Created with Sketch. Condition: Breast Cancer that has Spread to Another Part of the Body EffectivenessEase of UseSatisfaction

Some nausea initially, however, went away after a few doses. This is my fourth cancer drug and I feel better on this one than all the others. Hopefully, it will keep me alive until another cure comes along.

5 ShapeCreated with Sketch. 1 thumb_up copy 5Created with Sketch.Report this postFill 3Created with Sketch. Condition: Breast Cancer that has Spread to Another Part of the Body EffectivenessEase of UseSatisfaction

When I first started these meds I had some vomiting. Mostly once a day but there were days when I vomited twice. My doc lowered the dose and increased my anti nausea meds. I was best kind after that. No hand

4 ShapeCreated with Sketch. 1 thumb_up copy 5Created with Sketch.Report this postFill 3Created with Sketch. Condition: Breast Cancer that has Spread to Another Part of the Body EffectivenessEase of UseSatisfaction

The generic from Mylan caused severe gastric pain and bloating after two days of use. Discontinued use and returned to Xeloda, which does not have this side effect. Maybe it was an allergic reaction to an inactive ingredient, but there is no way to find out. So, I am reluctant to try other generics.

4 ShapeCreated with Sketch.thumb_up copy 5Created with Sketch.Report this postFill 3Created with Sketch. Condition: Colon and Rectal Cancer that has Spread to Another Area EffectivenessEase of UseSatisfaction

my wife had bad side effects from this medication 500mg in each pill,taken as follows 2 in the morning and 2 at night. After 7 days, her body just shut down, no eating, drinking vomiting 30 minute. she only she is 4’11 and at that time was only 83 pounds.she passed away 2 months later.

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Capecitabine – Drug Information – Chemocare

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Brand Name: Xeloda®

Capecitabine is the generic name for the trade name drug Xeloda. In some cases, health care professionals may use the trade name Xeloda when referring to the generic drug name capecitabine.

Drug Type:

Capecitabine is an anti-cancer (“antineoplastic” or “cytotoxic”) chemotherapy drug. Capecitabine is classified as an “antimetabolite.” (For more detail, see “How Capecitabine Works” section below).

What Capecitabine Is Used For:

• Colon or rectal cancer
• Metastatic breast cancer
• Esophageal, gastric, hepatobiliary, neuroendocrine, pancreatic, ovarian, fallopian tube, peritoneal or unknown primary cancers (off-label use)

Note: If a drug has been approved for one use, physicians may elect to use this same drug for other problems if they believe it may be helpful.

How Capecitabine Is Given:

• Taken as a pill by mouth.
• Take after food (within 30 minutes of a meal) with water. (Usually taken in a divided dose 12 hours apart).
• Tablets come in 2 sizes; 150mg and 500mg.
• Do not crush, chew or dissolve tablets.
• If you miss a dose, skip the missed dose and go back to your normal time. Do not take 2 doses at the same time or extra doses.

The amount of capecitabine that you will receive depends on many factors, including your height and weight, your general health or other health problems, and the type of cancer or condition being treated. Your doctor will determine your dose and schedule.

Side Effects:

Important things to remember about the side effects of capecitabine:

• Most people will not experience all of the capecitabine side effects listed.
• Capecitabine side effects are often predictable in terms of their onset, duration, and severity.
• Capecitabine side effects will improve after therapy is complete.
• Capecitabine side effects may be quite manageable. There are many options to minimize or prevent the side effects of capecitabine.

The following side effects are common (occurring in greater than 30%) for patients taking capecitabine:

These side effects are less common side effects (occurring in about 10-29%) of patients receiving capecitabine:

Not all side effects are listed above. Some that are rare (occurring in less than 10% of patients) are not listed here. However, you should always inform your health care provider if you experience any unusual symptoms.

When To Contact Your Doctor or Health Care Provider:

Contact your health care provider immediately, day or night, if you should experience any of the following symptoms:

• Fever of 100. 4° F (38° C) or higher, chills (possible signs of infection)

The following symptoms require medical attention, but are not an emergency. Contact your health care provider within 24 hours of noticing any of the following:

• Nausea (interferes with ability to eat and unrelieved with prescribed medication).
• Vomiting (vomiting more than 4-5 times in a 24 hour period)
• Diarrhea (4-6 episodes in a 24-hour period)
• Unusual bleeding or bruising
• Black or tarry stools, or blood in your stools or urine
• Constipation
• Extreme fatigue (unable to carry on self-care activities)
• Mouth sores (painful redness, swelling or ulcers)
• Swelling, redness and/or pain in one leg or arm and not the other
• Yellowing of the skin or eyes
• Tingling or burning, redness, swelling of the palms of the hands or soles of the feet.
• Confusion, loss of balance, excessive sleepiness

Always inform your health care provider if you experience any unusual symptoms.

Precautions:

• Before starting capecitabine treatment, make sure you tell your doctor about any other medications you are taking (including prescription, over-the-counter, vitamins, herbal remedies, etc.). Do not take aspirin, products containing aspirin unless your doctor specifically permits this.
• Avoid use of antacids within 2 hours of taking capecitabine.
• If you are on warfarin (Coumadin®) as a blood-thinner, adjustments may need to be made to your dose based on blood work.
• Capecitabine may be inadvisable if you have had a hypersensitivity (allergic) reaction to fluorouracil.
• Do not receive any kind of immunization or vaccination without your doctor’s approval while taking capecitabine.
• Inform your health care professional if you are pregnant or may be pregnant prior to starting this treatment. Pregnancy category D (capecitabine may be hazardous to the fetus. Women who are pregnant or become pregnant must be advised of the potential hazard to the fetus).
• For both men and women: Do not conceive a child (get pregnant) while taking capecitabine. Barrier methods of contraception, such as condoms, are recommended. Discuss with your doctor when you may safely become pregnant or conceive a child after therapy.
• Do not breast feed while taking capecitabine.

Self-Care Tips:

• Drink at least two to three quarts of fluid every 24 hours, unless you are instructed otherwise.
• You may be at risk of infection so try to avoid crowds or people with colds, and report fever or any other signs of infection immediately to your health care provider.
• Wash your hands often.
• To help treat/prevent mouth sores, use a soft toothbrush, and rinse three times a day with 1/2 to 1 teaspoon of baking soda and/or 1/2 to 1 teaspoon of salt mixed with 8 ounces of water.
• Use an electric razor and a soft toothbrush to minimize bleeding.
• Avoid contact sports or activities that could cause injury.
• To reduce nausea, take anti-nausea medications as prescribed by your doctor, and eat small, frequent meals.
• Prevention of hand-foot syndrome. Modification of normal activities of daily living to reduce friction and heat exposure to hands and feet, as much as possible during treatment with capecitabine. (for more information see – Managing side effects: hand foot syndrome).
• Keeps palms of hands and soles of feet moist using emollients such as Aveeno®, Udder cream, Lubriderm® or Bag Balm®.
• Follow regimen of anti-diarrhea medication as prescribed by your health care professional.
• Eat foods that may help reduce diarrhea (see managing side effects – diarrhea).
• Avoid sun exposure. Wear SPF 30 (or higher) sunblock and protective clothing.
• You may experience drowsiness or dizziness; avoid driving or engaging in tasks that require alertness until your response to the drug is known.
• In general, drinking alcoholic beverages should be kept to a minimum or avoided completely. You should discuss this with your doctor.
• Get plenty of rest.
• Maintain good nutrition.
• If you experience symptoms or side effects, be sure to discuss them with your health care team. They can prescribe medications and/or offer other suggestions that are effective in managing such problems.

Monitoring and Testing While Taking Capecitabine:

You will be checked regularly by your doctor while you are taking capecitabine, to monitor side effects and check your response to therapy. Periodic blood work to monitor your complete blood count (CBC) as well as the function of other organs (such as your kidneys and liver) will also be ordered by your doctor.

How Capecitabine Works:

Cancerous tumors are characterized by cell division, which is no longer controlled as it is in normal tissue. “Normal” cells stop dividing when they come into contact with like cells, a mechanism known as contact inhibition. Cancerous cells lose this ability. Cancer cells no longer have the normal checks and balances in place that control and limit cell division. The process of cell division, whether normal or cancerous cells, is through the cell cycle. The cell cycle goes from the resting phase, through active growing phases, and then to mitosis (division).

The ability of chemotherapy to kill cancer cells depends on its ability to halt cell division. Usually, the drugs work by damaging the RNA or DNA that tells the cell how to copy itself in division. If the cells are unable to divide, they die. The faster the cells are dividing, the more likely it is that chemotherapy will kill the cells, causing the tumor to shrink. They also induce cell suicide (self-death or apoptosis).

Chemotherapy drugs that affect cells only when they are dividing are called cell-cycle specific. Chemotherapy drugs that affect cells when they are at rest are called cell-cycle non-specific. The scheduling of chemotherapy is set based on the type of cells, rate at which they divide, and the time at which a given drug is likely to be effective. This is why chemotherapy is typically given in cycles.

Chemotherapy is most effective at killing cells that are rapidly dividing. Unfortunately, chemotherapy does not know the difference between the cancerous cells and the normal cells. The “normal” cells will grow back and be healthy but in the meantime, side effects occur. The “normal” cells most commonly affected by chemotherapy are the blood cells, the cells in the mouth, stomach and bowel, and the hair follicles; resulting in low blood counts, mouth sores, nausea, diarrhea, and/or hair loss. Different drugs may affect different parts of the body.

Capecitabine belongs to the category of chemotherapy called antimetabolites. Antimetabolites are very similar to normal substances within the cell. When the cells incorporate these substances into the cellular metabolism, they are unable to divide. Antimetabolites are cell-cycle specific. They attack cells at very specific phases in the cycle. Antimetabolites are classified according to the substances with which they interfere.

Note: We strongly encourage you to talk with your health care professional about your specific medical condition and treatments. The information contained in this website is meant to be helpful and educational, but is not a substitute for medical advice.

Capecitabine (Xeloda) | Cancer information

• Capecitabine is a type of chemotherapy drug you might have it on its own or with other types of chemotherapy drugs.
• It is also called Xeloda.
• It is a treatment for several types of cancer.
• It is a tablet you take twice a day morning and evening.
• It can cause side effects which vary from person to person.
• Some side effects are more serious than others – contact your advice line if you have severe side effects, if they aren’t getting better or they are getting worse.

How capecitabine works

Capecitabine is a type of chemotherapy called an anti metabolite. The body changes capecitabine into a common chemotherapy drug called fluorouracil. It stops cells making and repairing DNA. Cancer cells need to make and repair DNA so they can grow and multiply.

How you have capecitabine

Capecitabine comes as a tablet that you swallow whole, with plenty of water.  You take it twice a day, morning and evening. You might have two different strengths of tablets to make up the correct dose.

Take the tablets up to 30 minutes after a meal, with plenty of water.

Tell your doctor or pharmacist if you have difficulty swallowing.

Taking your tablets

You must take tablets according to the instructions your doctor or pharmacist gives you.

Speak to your pharmacist if you have problems swallowing the tablets.

Whether you have a full or an empty stomach can affect how much of a drug gets into your bloodstream.

You should take the right dose, no more or less.

Talk to your specialist or advice line before you stop taking a cancer drug.

When you have capecitabine

You might have capecitabine as a course of several cycles of treatment. Each cycle is often over 3 weeks, but this depends on the type of cancer you have.

For example, you may take capecitabine every day for 2 weeks. Then have a week with no treatment. You then start the next cycle. Or you may take capecitabine every day for a few months.

Your doctor will tell you:

• what dose of capecitabine you need to take
• when to take it
• how long to take it for

Tests

You have blood tests before and during your treatment. They check your levels of blood cells and other substances in the blood. They also check how well your liver and kidneys are working.

Side effects

We haven’t listed all the side effects. It is very unlikely that you will have all of these side effects, but you might have some of them at the same time.

How often and how severe the side effects are can vary from person to person. They also depend on what other treatment you are having. For example, your side effects could be worse if you are also having other drugs or radiotherapy.

When to contact your team

Your doctor or nurse will go through the possible side effects. They will monitor you closely during treatment and check how you are at your appointments. Contact your advice line as soon as possible if:

• you have severe side effects
• your side effects aren’t getting any better
• your side effects are getting worse

Early treatment can help manage side effects better. 

Contact your advice line or your doctor or nurse immediately if you have signs of infection, such as a temperature above 37.5C or below 36C, or if you develop a severe skin reaction. Signs of a severe skin reaction include peeling or blistering of the skin.

Common side effects

These side effects happen in more than 10 in 100 people (10%). You might have one or more of them. They include:

Tiredness and weakness (fatigue) during and after treatment

Tiredness and weakness (fatigue) can happen during and after treatment – doing gentle exercises each day can keep your energy up. Don’t push yourself, rest when you start to feel tired and ask others for help.

Loss of appetite

You might lose your appetite for various reasons when you are having cancer treatment. Sickness, taste changes or tiredness can put you off food and drinks.

Diarrhoea

Contact your advice line if you have diarrhoea, such as if you’ve had 4 or more loose watery poos (stools) in 24 hours. Or if you can’t drink to replace the lost fluid. Or if it carries on for more than 3 days.

Your doctor may give you anti diarrhoea medicine to take home with you after treatment. Eat less fibre, avoid raw fruits, fruit juice, cereals and vegetables, and drink plenty to replace the fluid lost.

Diarrhoea can be severe. 

Mouth sores and ulcers

Mouth sores and ulcers can be painful.  Keep your mouth and teeth clean; drink plenty of fluids; avoid acidic foods such as oranges, lemons and grapefruits; chew gum to keep the mouth moist and tell your doctor or nurse if you have ulcers.

Feeling or being sick

Feeling or being sick can be severe. It can start a few hours after treatment and last for a few days. Anti sickness injections and tablets can control it. Contact your doctor or nurse straight away if you’ve been sick more than once in a day.

Soreness, redness and peeling on palms and soles of feet

The skin on your hands and feet may become sore, red, or may peel. You may also have tingling, numbness, pain and dryness. This is called hand-foot syndrome or palmar plantar syndrome.

Moisturise your skin regularly. Your doctor or nurse will tell you what moisturiser to use.

Tummy (abdominal) pain

Tell your treatment team if you have this. They can check the cause and give you medicine to help. 

Occasional side effects

These side effects happen in between 1 and 10 out of every 100 people (1 to 10%). You might have one or more of them. They include:

• low levels of white blood cells in your blood which can increase your risk of getting an infection
• low levels of red blood cells in your blood (anaemia) that can cause breathlessness and looking pale
• constipation
• headaches and dizziness
• eye problems such as watery eyes and redness (conjunctivitis)
• hair loss that usually grows back once your chemotherapy treatment has finished
• skin and nail problems such as skin rashes, dry skin, itching and brittle nails
• liver changes that are usually very mild and unlikely to cause symptoms
• pain in your joints, arms, legs and back
• depression
• difficulty sleeping (insomnia)
• high temperature (fever)
• an allergic reaction that can cause a rash, shortness of breath, redness or swelling of the face and dizziness

Rare side effects

These side effects happen in fewer than 1 in 100 people (1%). You might have one or more of them. They include:

• a drop in the number of platelets that can cause bruising, bleeding gums or nosebleeds
• changes to how your heart works that can cause changes to your heart rhythm and swelling of your ankles
• skin sensitivity to sunlight
• numbness or tingling in fingers and toes can make it difficult to do fiddly things such as doing up buttons
• blood clots in the deep veins of your body
• a severe skin reaction that may start as tender red patches which leads to peeling or blistering of the skin. You might also feel feverish and your eyes may be more sensitive to light. This is serious and could be life threatening

Coping with side effects

We have more information about side effects and tips on how to cope with them.

What else do I need to know?

DPD deficiency

Between 2 and 8 out of 100 people (2 to 8%) have low levels of an enzyme called DPD in their bodies. A lack of DPD can mean you’re more likely to have severe side effects from capecitabine or fluorouracil. It might take you a bit longer to recover from the chemotherapy. These side effects can rarely be life threatening.

Low DPD levels don’t cause symptoms so you won’t know if you have a deficiency. You should have a test before you start this treatment to check if you have a DPD deficiency. 

Some people have severe side effects from capecitabine or fluorouracil even if they don’t have low DPD levels. Contact your doctor or nurse if your side effects are severe.

Other medicines, foods and drink

Cancer drugs can interact with some other medicines and herbal products. Tell your doctor or pharmacist about any medicines you are taking. This includes vitamins, herbal supplements and over the counter remedies.

Lactose intolerance 

This drug contains lactose (milk sugar). If you have an intolerance to lactose, contact your doctor before taking this medicine.

Contraception and pregnancy

This treatment might harm a baby developing in the womb. It is important not to become pregnant or father a child while you’re having treatment and for 6 months afterwards. Talk to your doctor or nurse about effective contraception before starting treatment.

Loss of fertility

You may not be able to become pregnant or father a child after treatment with this drug. Talk to your doctor before starting treatment if you think you may want to have a baby in the future.

Men might be able to store sperm before starting treatment. And women might be able to store eggs or ovarian tissue. But these services are not available in every hospital, so you would need to ask your doctor about this.    

Breastfeeding

Don’t breastfeed during this treatment and for 2 weeks after your final treatment. This is because the drug may come through into your breast milk.

Treatment for other conditions

Always tell other doctors, nurses, pharmacists or dentists that you’re having this treatment if you need treatment for anything else, including teeth problems.

Immunisations

Don’t have immunisations with live vaccines while you’re having treatment and for up to 12 months afterwards. The length of time depends on the treatment you are having. Ask your doctor or pharmacist how long you should avoid live vaccinations.

In the UK, live vaccines include rubella, mumps, measles, BCG, yellow fever and the shingles vaccine (Zostavax).

You can:

• have other vaccines, but they might not give you as much protection as usual
• have the flu vaccine (as an injection)

Contact with others who have had immunisations – You can be in contact with other people who have had live vaccines as injections. Avoid close contact with people who have recently had live vaccines taken by mouth (oral vaccines) such as the oral typhoid vaccine.

If your immune system is severely weakened, you should avoid contact with children who have had the flu vaccine as a nasal spray. This is for 2 weeks following their vaccination.

Babies have the live rotavirus vaccine. The virus is in the baby’s poo for about 2 weeks and could make you ill if your immunity is low. Get someone else to change their nappies during this time if you can. If this isn’t possible, wash your hands well after changing their nappy.

More information about this treatment

For further information about this treatment go to the electronic Medicines Compendium (eMC) website.

You can report any side effect you have to the Medicines Health and Regulatory Authority (MHRA) as part of their Yellow Card Scheme.

iWantGreatCare lets patients leave feedback on their experience of taking a particular drug. The feedback is from individual patients. It is not information, or specialist medical advice, from Cancer Research UK.

Capecitabine (Xeloda) | Breast Cancer Now

1. What is capecitabine?
2. When is capecitabine given?
3. Before starting capecitabine
4. How is capecitabine taken?
5. Side effects of capecitabine
6. Other important information 
7. Further support

1. What is capecitabine? 

Capecitabine is a chemotherapy drug. 

Capecitabine is the non-branded name of the drug, but you may also hear it called by its brand name Xeloda. 

2. When is capecitabine given? 

When breast cancer has spread

Capecitabine is used to treat breast cancer that has come back after previous treatment and has:

For some people with primary breast cancer

Studies have shown that some people with primary breast cancer may benefit from capecitabine. 

This includes people with breast cancer that is triple negative. 

People who have chemotherapy before surgery may be offered capecitabine after their surgery. 

Your treatment team will discuss with you if this is an option. 

As part of a clinical trial

Capecitabine may be offered as part of a clinical trial. 

3. Before starting capecitabine

Before starting your treatment many hospitals will arrange a chemotherapy information session. 

A nurse will explain how and when you’ll have your chemotherapy and how side effects can be managed. 

You should have blood tests and some people will have an ECG (electrocardiogram), a simple test that checks your heart rhythm. 

It’s recommended everyone starting capecitabine has a blood test to check levels of a protein called DPD.

Your height and weight will also be measured, to work out the correct dose of chemotherapy for you.

You’ll be given contact numbers so you know who to phone if you have any questions or concerns.

4. How is capecitabine taken? 

Capecitabine is taken as a tablet (orally).

You should swallow the tablets whole with water within half an hour of eating a meal.

You usually take the capecitabine tablets twice a day (in the morning and evening) for 14 days and then have a 7-day break from taking the tablets. This 21-day period is one treatment cycle.

If you’re prescribed capecitabine differently to the 21-day cycle your doctors will explain why. 

Capecitabine is available in two different tablet strengths: 150mg or 500mg. You’ll be told how many of each tablet to take to make sure you get the right amount each day for your body size. 

It’s often given on its own, but can be given alongside other chemotherapy drugs such as docetaxel.  

What happens if I miss a dose? 

If you miss a dose of capecitabine, do not take an extra dose to make up for the one you missed. Take the next dose at the usual time and speak to someone in your treatment team. 

How long will I have to take capecitabine for? 

This will vary from person to person. 

People with secondary breast cancer will usually keep taking capecitabine until it’s no longer helping control the cancer or they have significant side effects. 

If you have primary breast cancer your treatment team will talk to you about what’s best for you. 

5. Side effects of capecitabine

Most people tolerate capecitabine well as the side effects are often mild and can usually be controlled. However, everyone reacts differently to drugs.

Some people have more side effects than others, and the side effects described here will not affect everyone. 

If you’re taking other drugs at the same time as capecitabine, you may have side effects from these drugs too. 

If you’re concerned about any side effects, regardless of whether they’re listed here, talk to your chemotherapy nurse or cancer specialist (oncologist) as soon as possible. 

Your specialist can reduce or delay the dose of capecitabine you take if the side effects become too severe. Reducing the dose of capecitabine is common and the treatment can still be effective at a lower dose. 

Common side effects

Effects on the blood

Capecitabine can temporarily affect the number of blood cells in the body. 

You’ll have regular blood tests to check your blood count. Blood is made up of red cells, white cells and platelets. If the number of blood cells is too low, your next cycle of treatment may be delayed or the dose of chemotherapy reduced.

Risk of infection

Not having enough white blood cells can increase the risk of getting an infection.

Your treatment team may give you guidelines to follow for reporting signs of an infection, but generally you should contact your hospital immediately if you experience any of the following:

• A high temperature (over 37.5°C) or low temperature (under 36°C), or whatever your chemotherapy team has advised
• Suddenly feeling unwell, even with a normal temperature
• Symptoms of an infection, for example a sore throat, a cough, a need to pass urine frequently or feeling cold or shivery

Before starting chemotherapy you should be given a 24-hour contact number or told where to get emergency care by your treatment team. You may need antibiotics.

Sometimes your doctor may recommend injections of drugs called growth factors. This helps the body produce more white blood cells to reduce your risk of infection.  

Anaemia 

Having too few red blood cells is called anaemia. If you feel particularly tired, breathless or dizzy, let your treatment team know. 

Bruising and bleeding

Capecitabine can reduce the number of platelets, which help the blood to clot. You may bruise more easily, have nosebleeds or your gums may bleed when you brush your teeth. Tell your treatment team if you experience any of these symptoms. 

Diarrhoea 

Diarrhoea is common during treatment and can sometimes be severe. 

Tell your chemotherapy nurse or treatment team as they can prescribe medication and may consider stopping your capecitabine for a time to help control it. 

Speak to them immediately if you have any of the following symptoms: 

• Four or more episodes of diarrhoea in 24 hours 
• Blood in your stools when you go to the toilet 
• Tummy (abdominal) pain 

Skin reactions 

Hand-foot syndrome, often called Palmar-Plantar syndrome, is a common side effect of some chemotherapy drugs used to treat breast cancer. 
The palms of the hands and the soles of the feet can become red and sore. Sometimes you may also notice a tingling sensation, numbness or some swelling. 

The skin on your hands and feet may also become red, dry and flaky. This should improve if the treatment is delayed or if the dose is reduced. 

Your treatment team can recommend moisturising creams to help with skin reactions. 

Nausea and vomiting 

You may feel sick (nausea) during treatment. 

Although most people will not be sick (vomit), anti-sickness drugs can help reduce or stop this happening, so take these as prescribed. Steroids may also be given to make the anti-sickness drugs work more effectively. 

Contact your treatment team or GP if symptoms don’t go away.

Sore mouth 

Your mouth and gums can become sore and small ulcers may develop. This is usually worse if you’re taking capecitabine at the same time as other chemotherapy drugs. 

Your chemotherapy nurse or treatment team will advise you about suitable mouthwashes or medicine if these problems occur. 

Looking after your mouth, including your teeth and gums, is very important during treatment. 

It’s advisable to see your dentist for a dental check-up before chemotherapy begins and to avoid dental treatment during chemotherapy if possible. If you do need to have dental treatment during chemotherapy, talk with your oncologist about the best time to have this. 

Loss of appetite 

You can lose your appetite while taking capecitabine. Your sense of taste can also change and some foods and drink may taste different. 

Talk to your treatment team about this. They will give you advice and information to help, or refer you to a dietitian if needed. 

Find out more about diet during treatment. 

Extreme tiredness 

Cancer-related fatigue is extreme tiredness that doesn’t go away with rest or sleep. It’s a very common side effect of breast cancer treatment and may affect you physically and emotionally. 

If you think you have fatigue, tell your GP or treatment team. They can assess you and offer advice on how to manage your energy levels.

Find out more about managing fatigue.

Hair loss 

When used on its own, capecitabine occasionally causes some temporary hair thinning. It very rarely causes complete hair loss. 

If capecitabine is taken in combination with another chemotherapy drug, most people will lose all their hair including eyebrows, eyelashes and body hair.

Find out more about hair loss. 

Rare side effects 

Allergic reaction 

Very occasionally allergic reactions to a drug can occur. Reactions can vary from mild to severe, although severe reactions are uncommon. 

If you have any swelling, wheezing, chest pain or difficulty breathing after taking capecitabine, let your treatment team or chemotherapy nurse know immediately. 

DPD deficiency (very rare) 

DPD is a type of protein (enzyme) made naturally in the body. 

Not having enough DPD can cause chemotherapy to build up in the body, resulting in severe side effects. In very rare cases this can be life-threatening.

It’s recommended that everyone starting capecitabine has a blood test to check levels of DPD. 

If you’re found to have low levels of DPD, known as a DPD deficiency, you may not be given the drug.

At your pre-assessment appointment, a member of the oncology team will explain the blood test.

Cancer Research UK has more information on DPD deficiency.

6. Other important information

Blood clots 

People with breast cancer have a higher risk of blood clots. Their risk is higher because of the cancer itself and some treatments for breast cancer. If the cancer has spread to other parts of the body (secondary breast cancer), this also increases the risk.

Having capecitabine increases the risk of blood clots such as deep vein thrombosis (DVT). 

People with a DVT are at risk of developing a pulmonary embolism (PE). This is when part of the blood clot breaks away and travels to the lung. 
Blood clots can be harmful but are treatable so it’s important to report symptoms as soon as possible. 

If you experience any of the following symptoms contact your local A&E department, GP or treatment team straight away:

• Pain, redness/discolouration, heat and swelling of the calf or thigh 
• Shortness of breath 
• Pain or tightness in the chest 
• Unexplained cough or coughing up blood

Find out more about blood clots.

Driving and using machinery 

Capecitabine may make you feel dizzy, sick or tired. This could affect your ability to drive or operate machinery safely. 

Avoid driving or using machinery if you have any symptoms that may affect your ability to do this. 

Can I take capecitabine with other drugs? 

Tell your treatment team about any other drugs or supplements you’re taking. 

If you take drugs to thin the blood (anti-coagulants), such as warfarin, capecitabine can increase your risk of bleeding. Your specialist may check more often how quickly your blood clots, adjust your dose of blood-thinning drugs or, more commonly, change you to an injection to thin the blood instead. 

Sex, contraception and pregnancy

You’re advised not to become pregnant while having treatment because capecitabine can harm a developing baby. If you haven’t been through the menopause, talk to your team about the most suitable method of contraception for you. It’s still possible to become pregnant even if your periods become irregular or stop. 

You can still have sex during treatment. It’s thought that chemotherapy drugs can’t pass into vaginal fluids or semen, but this can’t be completely ruled out as chemotherapy drugs can pass into the blood and some other body fluids. Most hospital specialists will advise using barrier methods of contraception, such as condoms during treatment, and for a few days after chemotherapy is given.   

Find out more about how breast cancer and its treatment can affect sex and intimacy and read our tips on how to manage these changes. 

Travel and vaccinations

If you’re planning a holiday or need to travel overseas, check with your treatment team first.

You should not have any live vaccines while you are having chemotherapy. Live vaccines include mumps, measles, rubella (German measles), polio, BCG (tuberculosis), shingles and yellow fever.

Live vaccines contain a small amount of live virus or bacteria. If you have a weakened immune system, which you may do during chemotherapy, they could be harmful.

It is safe to have these vaccines six months after your chemotherapy finishes. Talk to your GP or treatment team before having any vaccinations.
If someone you have close contact with needs to have a live vaccine speak to your treatment team or GP. They can advise what precautions you may need to take depending on the vaccination.

Coronavirus (Covid-19) vaccination

People having chemotherapy are advised to speak to their treatment team before having the coronavirus (Covid-19) vaccination.

Find out more about the coronavirus vaccine.

Flu vaccination

Anyone at risk of a weakened immune system, and therefore more prone to infection, should have the flu vaccine. This includes people due to have or already having chemotherapy.

The flu vaccine is not a live vaccine so does not contain any active viruses. Talk to your chemotherapy specialist or breast care nurse about the best time to have your flu jab.

7. Further support

If you would like any further information and support about breast cancer or just want to talk things through, you can speak to one of our experts by calling our free Helpline on 0808 800 6000.

Being diagnosed with breast cancer can make you feel lonely and isolated. You might find it helpful to visit our online Forum.

Capecitabine tablets

What is this medicine?

CAPECITABINE (ka pe SITE a been) is a chemotherapy drug. It slows the growth of cancer cells. This medicine is used to treat breast cancer, and also colon or rectal cancer.

This medicine may be used for other purposes; ask your health care provider or pharmacist if you have questions.

COMMON BRAND NAME(S): Xeloda

What should I tell my health care provider before I take this medicine?

They need to know if you have any of these conditions:

• bleeding disorders
• dehydration
• dihydropyrimidine dehydrogenase (DPD) deficiency
• heart disease
• infection (especially a virus infection such as chickenpox, cold sores, or herpes)
• kidney disease
• liver disease
• low blood counts, like low white cell, platelet, or red cell counts
• an unusual or allergic reaction to capecitabine, fluorouracil, other medicines, foods, dyes, or preservatives
• pregnant or trying to get pregnant
• breast-feeding

How should I use this medicine?

Take this medicine by mouth with a glass of water, within 30 minutes of the end of a meal. Do not cut, crush or chew this medicine. Follow the directions on the prescription label. Take your medicine at regular intervals. Do not take it more often than directed. Do not stop taking except on your doctor’s advice.

Your doctor may want you to take a combination of 150 mg and 500 mg tablets for each dose. It is very important that you know how to correctly take your dose. Taking the wrong tablets could result in an overdose (too much medication) or underdose (too little medication).

Talk to your pediatrician regarding the use of this medicine in children. Special care may be needed.

Overdosage: If you think you have taken too much of this medicine contact a poison control center or emergency room at once.

NOTE: This medicine is only for you. Do not share this medicine with others.

What if I miss a dose?

If you miss a dose, do not take the missed dose at all. Do not take double or extra doses. Instead, continue with your next scheduled dose and check with your doctor.

What may interact with this medicine?

This medicine may interact with the following medications:

• allopurinol
• leucovorin
• phenytoin
• warfarin

This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.

What should I watch for while using this medicine?

Visit your doctor for checks on your progress. This drug may make you feel generally unwell. This is not uncommon, as chemotherapy can affect healthy cells as well as cancer cells. Report any side effects. Continue your course of treatment even though you feel ill unless your doctor tells you to stop.

In some cases, you may be given additional medicines to help with side effects. Follow all directions for their use.

Call your doctor or health care professional for advice if you get a fever, chills or sore throat, or other symptoms of a cold or flu. Do not treat yourself. This drug decreases your body’s ability to fight infections. Try to avoid being around people who are sick.

This medicine may increase your risk to bruise or bleed. Call your doctor or health care professional if you notice any unusual bleeding.

Be careful brushing and flossing your teeth or using a toothpick because you may get an infection or bleed more easily. If you have any dental work done, tell your dentist you are receiving this medicine.

Avoid taking products that contain aspirin, acetaminophen, ibuprofen, naproxen, or ketoprofen unless instructed by your doctor. These medicines may hide a fever.

Do not become pregnant while taking this medicine or for 6 months after stopping it. Women should inform their doctor if they wish to become pregnant or think they might be pregnant. There is a potential for serious side effects to an unborn child. Talk to your health care professional or pharmacist for more information. Do not breast-feed an infant while taking this medicine or for 2 weeks after stopping it.

Men are advised not to father a child while taking this medicine or for 3 months after stopping it.

This medicine may make it more difficult to get pregnant or father a child. Talk with your doctor or health care professional if you are concerned about your fertility.

What side effects may I notice from receiving this medicine?

Side effects that you should report to your doctor or health care professional as soon as possible:

• allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue
• diarrhea
• low blood counts – this medicine may decrease the number of white blood cells, red blood cells and platelets. You may be at increased risk for infections and bleeding
• nausea, vomiting
• redness, blistering, peeling or loosening of the skin, including inside the mouth (this can be added for any serious or exfoliative rash that could lead to hospitalization)
• redness, swelling, or sores on hands or feet
• signs and symptoms of kidney injury like trouble passing urine or change in the amount of urine
• signs and symptoms of liver injury like dark yellow or brown urine; general ill feeling or flu-like symptoms; light-colored stools; loss of appetite; nausea; right upper belly pain; unusually weak or tired; yellowing of the eyes or skin
• signs of decreased platelets or bleeding – bruising, pinpoint red spots on the skin, black, tarry stools, blood in the urine
• signs of decreased red blood cells – unusually weak or tired, fainting spells, lightheadedness
• signs of infection – fever or chills, cough, sore throat, pain or difficulty passing urine

Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):

• changes in vision
• constipation
• loss of appetite
• mouth sores
• pain, tingling, numbness in the hands or feet

This list may not describe all possible side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Where should I keep my medicine?

Keep out of the reach of children.

Store at room temperature between 15 and 30 degrees C (59 and 86 degrees F). Keep container tightly closed. Throw away any unused medicine after the expiration date.

NOTE: This sheet is a summary. It may not cover all possible information. If you have questions about this medicine, talk to your doctor, pharmacist, or health care provider.

Genentech: Xeloda® (capecitabine) – Information for Patients

Support & Resources

What it Treats

Xeloda is a prescription medicine used to treat people with:

• cancer of the colon that has spread to lymph nodes in the area close to the colon (Dukes’ C stage), after they have surgery.
• cancer of the colon or rectum (colorectal) that has spread to other parts of the body (metastatic).
• breast cancer that has spread to other parts of the body (metastatic) together with another medicine called docetaxel after treatment with certain other anticancer medicines have not worked.
• breast cancer that has spread to other parts of the body and has not improved after treatment with paclitaxel and certain other anti-cancer medicines, or who cannot receive any more treatment with certain anti-cancer medicines.

It is not known if Xeloda is safe and effective in children.

Important Safety Information

IMPORTANT SIDE EFFECT INFORMATION

What is the most important information I should know about XELODA?

XELODA can cause serious side effects, including:

• XELODA can interact with blood thinner medicines, such as warfarin (COUMADIN^®). Taking XELODA with these medicines can cause changes in how fast your blood clots, and can cause bleeding that can lead to death. This can happen as soon as a few days after you start taking XELODA, or later during treatment, and possibly even within 1 month after you stop taking XELODA. Your risk may be higher because you have cancer, and if you are over 60 years of age.
  • Before taking XELODA, tell your doctor if you are taking warfarin (COUMADIN) or another blood thinner medicine.
  • If you take warfarin (COUMADIN) or another blood thinner that is like warfarin (COUMADIN) during treatment with XELODA, your doctor should do blood tests often, to check how fast your blood clots during and after you stop treatment with XELODA. Your doctor may change your dose of the blood thinner medicine if needed.

Who should not take Xeloda?

Do not take Xeloda if you:

• have severe kidney problems
• are allergic to capecitabine, 5-fluorouracil, or any of the ingredients in Xeloda.

What should I tell my doctor before taking Xeloda?

Before you take Xeloda, tell your doctor if you:

• have had heart problems
• have kidney or liver problems
• have been told that you lack the enzyme DPD (dihydropyrimidine dehydrogenase)
• have any other medical conditions
• are pregnant or plan to become pregnant. Xeloda can harm your unborn baby. You should not become pregnant during treatment with Xeloda. Talk to your doctor about birth control choices that may be right for you during treatment with Xeloda.
• are breastfeeding or plan to breastfeed. It is not known if Xeloda passes into breast milk. Do not breastfeed during treatment with Xeloda.

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

What are the possible side effects of Xeloda?

Xeloda may cause serious side effects including:

• diarrhea. Diarrhea is common with XELODA and can sometimes be severe. Stop taking XELODA and call your doctor right away if the number of bowel movements you have in a day increases by 4 or more than is usual for you. Ask your doctor about what medicines you can take to treat your diarrhea. If you have severe bloody diarrhea with severe abdominal pain and fever, call your doctor or go to the nearest emergency room right away.
• heart problems. XELODA can cause heart problems including: heart attack and decreased blood flow to the heart, chest pain, irregular heartbeats, changes in the electrical activity of your heart seen on an electrocardiogram (ECG), problems with your heart muscle, heart failure, and sudden death. Stop taking XELODA and call your doctor right away if you get any of the following symptoms:
  • chest pain
  • shortness of breath
  • feeling faint
  • irregular heartbeats or skipping beats
  • sudden weight gain
  • swollen ankles or legs

• unexplained tiredness
• loss of too much body fluid (dehydration) and kidney failure. Dehydration can happen with XELODA and may cause sudden kidney failure that 45 can lead to death. You are at higher risk if you have kidney problems before taking XELODA and also take other medicines that can cause kidney problems.

  Nausea, and vomiting are common with XELODA. If you lose your appetite, feel weak, and have nausea, vomiting, or diarrhea, you can quickly become dehydrated.

  Stop taking XELODA and call your doctor right away if you:

  • vomit 2 or more times in a day.
  • are only able to eat or drink a little now and then, or not at all due to nausea.
  • have diarrhea. See “diarrhea” above.

• serious skin and mouth reactions.
  • XELODA can cause serious skin reactions that may lead to death. Tell your doctor right away if you develop a skin rash, blisters and peeling of your skin. Your doctor may tell you to stop taking XELODA if you have a serious skin reaction. Do not take XELODA again if this happens.
  • XELODA can also cause “hand and foot syndrome.” Hand and foot syndrome is common with XELODA and can cause you to have numbness and changes in sensation in your hands and feet, or cause redness, pain, swelling of your hands and feet. Stop taking XELODA and call your doctor right away if you have any of these symptoms and you are not able to do your usual activities. Hand and foot syndrome can lead to loss of fingerprints which could impact your identification.
  • you may get sores in your mouth or on your tongue when taking XELODA. Stop taking XELODA and call your doctor if you get painful redness, swelling, or ulcers in your mouth and tongue, or if you are having problems eating. Tell your doctor if you have any side effect that bothers you or that does not go away.

• increased level of bilirubin in your blood and liver problems. Increased bilirubin in your blood is common with XELODA. Your doctor will check you for these problems during treatment with XELODA.
• decreased white blood cells, platelets, and red blood cell counts. Your doctor will do blood tests during treatment with XELODA to check your blood cell counts.

If your white blood cell count is very low, you are at increased risk for infection. Call your doctor right away if you develop a fever of 100.5º F or greater or have other signs and symptoms of infection. People 80 years of age or older may be more likely to develop severe or serious side effects with XELODA.

What are the most common side effects of Xeloda?

The most common side effects of Xeloda include:

• diarrhea
• hand and foot syndrome
• nausea
• vomiting
• stomach-area (abdominal) pain
• tiredness
• weakness
• increased amounts of red blood cell breakdown products (bilirubin) in your blood

If you have any questions about your condition or treatment, talk to your doctor.

You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555.

Please see full Product Information for additional important safety information.

CAPECITABIN KRKA instructions for use, price in pharmacies in Ukraine, analogues, composition, indications | CAPECITABIN KRKA film-coated tablets from KRKA d.d. Novo Mesto »

Composition

active substance: capecitabine;

1 film-coated tablet contains 150 mg or 500 mg of capecitabine;

excipients: lactose, microcrystalline cellulose, croscarmellose sodium, hypromellose, magnesium stearate

film shell: hypromellose, talc, titanium dioxide (E 171), iron oxide red (E172), iron oxide yellow (E 172).

Dosage form

Film-coated tablets.

Basic physical and chemical properties:

for dosage of 150 mg: oblong, biconvex, light peach color, engraved “150” on one side and smooth on the other side film-coated tablets

for dispensing 500 mg: oblong, biconvex, peach color, engraved with “500” on one side and smooth on the other side, film-coated tablets.

Pharmacological group

Antineoplastic agents. Structural analogs of pyrimidine. ATX code L01B C06.

Pharmacological properties

Pharmacodynamics.

Capecitabine is a non-cytotoxic derivative of fluoropyrimidine carbamate, an oral precursor of the cytotoxic compound 5-fluorouracil (5-FU). Capecitabine activates several enzymatic steps. The final conversion to 5-FU occurs under the action of thymidine phosphorylase in tumor tissue, as well as in healthy tissues of the body, however, as a rule, at a low level.In models of human cancer xenografts, capecitabine has shown a synergistic effect in combination with docetaxel, which may be associated with an increase in the activity of thymidine phosphorylase by docetaxel.

The metabolism of 5-FU has been shown to block the methylation reaction of deoxyuridylic acid to thymidylic acid by an anabolic pathway, thus interfering with the synthesis of deoxyribonucleic acid (DNA). The incorporation of 5-FU also inhibits RNA and protein synthesis. Since DNA and RNA are essential for cell division and growth, 5-FU can cause thymidine deficiency, which contributes to imbalanced cell growth and death.The effects on DNA and RNA are more pronounced in cells with more intensive proliferation and with a high level of 5-FU metabolism.

Pharmacokinetics.

The pharmacokinetics of capecitabine was determined in the dose range 502-3514 mg / m ² / day. The parameters of capecitabine, 5′-deoxy-5-fluorocytidine (5′-DFCT) and 5′-deoxy-5-fluoruridine (5′-DFUR) on day 1 and 14 were similar. On day 14, the 5-FU AUC was 30-35% higher. Reducing the dose of capecitabine resulted in a more than dose-proportional decrease in 5-FU exposure as a result of the nonlinear pharmacokinetics of the active metabolite.

Suction

After administration, capecitabine is rapidly and completely absorbed, after which it is biotransformed into metabolites 5′-DFCT and 5′-DFUR. Food intake reduces the rate of absorption of capecitabine, but does not significantly affect the area under the concentration-time curve (AUC) of 5′-DFUR and the subsequent metabolite 5-FU. When using the drug after a meal at a dose of 1250 mg / m2 on the 14th day, the maximum concentrations of Cmax capecitabine, 5′-DFCT, 5′-DFUR, 5-FU and α-fluoro-β-alanine (FBAL) were, respectively, 4, 67, 3.05, 12.1, 0.95 and 5.46 μg / ml.The time to reach the maximum concentration Tmax is 1.50, 2.00, 2.00, 2.00 and 3.34 h, and the AUC is 7.75, 7.24, 24.6, 2.03 and 36.3 μg × h / ml, respectively.

Distribution

In vitro plasma studies have shown that for capecitabine, 5′-DFCT, 5′-DFUR and 5-FU, the protein binding (mainly albumin) is 54%, 10%, 62% and 10%, respectively.

Metabolism

Metabolized in the liver by carboxylesterase to the 5′-DFCT metabolite, which is then transformed into 5′-DFUR by cytidine deaminase, which is found mainly in the liver and tumor tissues.Further catalytic activation of 5′-DFUR occurs due to thymidine phosphorylase. Enzymes involved in catalytic activation are found in both tumor tissues and normal tissues, but usually at low levels. Further enzymatic biotransformation of capecitabine to 5-FU leads to higher concentrations in tumor tissues. In the case of colorectal tumors, a significant portion of 5-FU is localized in the stromal cells of the tumor. After oral administration of capecitabine in colorectal cancer patients, the ratio of 5-FU in colorectal tumors to adjacent tissue was 3.2 (range, 0.9 to 8.0).The ratio of the concentration of 5-FU in the tumor to the concentration in the blood plasma was 21.4 (range from 3.9 to 59.9, N = 8), while the ratio of the concentration in healthy tissues to the concentration in blood plasma was 8.9 (range 3.0 to 25.8, N = 8). The activity of thymidine phosphorylase was 4 times higher in the primary colorectal tumor compared to adjacent normal tissues. According to immunohistochemical studies, most of the thymidine phosphorylase is localized in the stromal cells of the tumor.

5-FU is then catabolized by dihydropyrimidine dehydrogenase (DPD) to form the less toxic dihydro-5-fluorouracil (FUG2). Dihydropyrimidinase cleaves the pyrimidine ring to form 5-fluoroureidopropionic acid (FUPA). The final reaction is the cleavage of β-ureidopropionase FUPA to α-fluoro-β-alanine (FBAL), which is manifested in urine. The activity of dihydropyrimidine dehydrogenase limits the rate of the reaction. DPD deficiency can lead to an increase in the toxicity of capecitabine (see Sections “Contraindications” and “Peculiarities of use”).

Excretion: half-life (T1 / 2) of capecitabine, 5′-DFCT, 5′-DFUR, 5-FU and FBAL is 0.85, 1.11, 0.66, 0.76 and 3.23, respectively hours. Capecitabine and capecitabine metabolites are mainly excreted in the urine. Excretion with urine – 95.5%, with feces – 2.6%. The main metabolite in urine is FBAL, which accounts for 57% of the dose taken. Approximately 3% of the dose taken is excreted in the urine unchanged.

Combination therapy

Phase I studies did not detect the effect of capecitabine on the pharmacokinetics of docetaxel and paclitaxel (Cmax and AUC) and the effect of docetaxel and paclitaxel on the pharmacokinetics of capecitabine and 5′-DFUR.

Pharmacokinetics in special clinical groups

Population pharmacokinetic analysis was performed after treatment with capecitabine at a dose of 1250 mg / m ² twice a day in 505 patients with colorectal cancer. Gender, presence or absence of liver metastases before treatment, the patient’s general condition index according to Karnovsky, the concentration of total bilirubin, serum albumin, the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) did not have a significant effect on the pharmacokinetics of 5′-DFUR, 5-FU and FBAL.

Patients with metastatic liver disease. According to pharmacokinetic studies, in patients with mild to moderate liver dysfunction caused by metastases, the bioavailability of capecitabine and 5-FU exposure may increase compared with patients without liver dysfunction. There are no pharmacokinetic data in patients with severe hepatic impairment.

Patients with impaired renal function. With varying degrees (from mild to severe) renal failure in cancer patients, the pharmacokinetics of the unchanged drug and 5-FU does not depend on creatinine clearance (CC).CC affects the value of AUC 5′-DFUR (an increase in AUC by 35% – with a decrease in CC by 50%) and FBAL (an increase in AUC by 114% with a decrease in CC by 50%). FBAL is a metabolite, has no antiproliferative activity.

Old age. According to the population pharmacokinetic analysis, which included patients of a wide age range (27-86 years), of which 234 patients (46%) were over 65 years old, age does not affect the pharmacokinetics of 5′-DFUR and 5-FU. AUC FBAL increases with age (with an increase in age by 20%, AUC FBAL increased by 15%), which is probably due to changes in renal function.

Ethnic factors. After oral administration of 825 mg / m2 capecitabine twice a day for 14 days in patients of Japanese nationality (N = 18), the Cmax of capecitabine was 36% lower, and the AUC was 24% lower than in patients of the Caucasian race (N = 22) … Patients of Japanese nationality also had 25% lower Cmax and 34% lower AUC FBAL compared with Caucasian patients. The clinical significance of this difference is unknown. There is no significant difference in the exposure of other metabolites (5′-DFCT, 5′-DFUR and 5-FU).

Clinical characteristics

Readings.

Breast cancer:

– locally advanced or metastatic breast cancer – the drug is used in combination with docetaxel after ineffective chemotherapy, which included anthracycline drugs;

– locally advanced or metastatic breast cancer – the drug is used as monotherapy if chemotherapy, including taxanes and anthracycline drugs, is ineffective, or if there is a contraindication to anthracyclines therapy.

Colon cancer, colorectal cancer:

– colon cancer – the drug is used in adjuvant therapy after surgical treatment of stage III cancer (Duke stage C)

– metastatic colorectal cancer.

Stomach cancer:

– used as a first-line drug for the treatment of advanced gastric cancer in combination with platinum-based drugs.

Contraindications.

Severe, including unexpected reactions to treatment with fluoropyrimidines in history.Hypersensitivity to capecitabine or to any component of the drug or fluorouracil. Known complete lack of activity of dihydropyrimidine dehydrogenase (DPD) (see section “Peculiarities of use”). Pregnancy and breastfeeding. Severe leukopenia, neutropenia, thrombocytopenia. Severe liver dysfunction. Severe renal impairment (creatinine clearance <30 ml / min). Simultaneous administration of sorivudine or its structural analogs such as brivudine (see Section "Interaction with other medicinal products and other types of interactions").Contraindications to the use of any drug used in combination.

Interaction with other medicinal products and other types of interactions.

Interaction studies were conducted only in adult patients.

Interaction with other medicinal products

Substrates of cytochrome P450 2C9. Studies on the interaction of capecitabine and other drugs metabolized by the isoenzyme 2C9 of the cytochrome P450 system, with the exception of warfarin, have not been conducted.Care must be taken when using capecitabine with these drugs (eg phenytoin).

Anticoagulants – coumarin derivatives. Capecitabine enhances the effects of indirect anticoagulants (warfarin and phenprocoumon), which can lead to bleeding disorders and bleeding within a few days or months from the start of capecitabine therapy, and in some cases – within one month after the end of treatment with Capecitabine CRCA. In a clinical pharmacokinetic study of the interaction after a single injection of warfarin at a dose of 20 mg, capecitabine treatment led to an increase in the AUC of S-warfarin by 57% and the MES (international normalized ratio) by 91%.Since the metabolism of R-warfarin was not impaired, this indicates that capecitabine inhibits the 2C9 isoenzyme and does not affect the 1A2 and 3A4 isoenzymes. In patients who simultaneously take capecitabine and oral anticoagulants-coumarin derivatives, it is necessary to carefully monitor blood coagulation parameters (MES or prothrombin time) and select the dose of the anticoagulant.

Phenytoin. With the simultaneous use of capecitabine and phenytoin, there have been isolated cases of an increase in the concentration of phenytoin in the blood plasma, accompanied by the onset of symptoms of phenytoin intoxication.In patients taking capecitabine concomitantly with phenytoin, it is recommended to regularly monitor the concentration of phenytoin in blood plasma.

Folinic / folic acid. Folinic acid does not significantly affect the pharmacokinetics of capecitabine and its metabolites. However, folinic acid affects the pharmacodynamics of capecitabine, which can lead to an increase in the toxicity of capecitabine: the maximum tolerated dose of capecitabine in monotherapy with an intermittent dosing regimen is 3000 mg / m2 ² per day, and when combined with folinic acid (30 mg orally twice per day) – only 2000 mg / m ² per day.Increased toxicity may occur when switching from 5-FU / LV (5-fluorouracil and leucovorin) to a capecitabine regimen. This phenomenon can also be observed when folic acid is used to correct folate deficiency due to the similarity between folic and folic acid.

Sorivudin and its analogues. The literature describes a clinically significant interaction between sorivudine and 5-FU as a result of inhibition of dihydropyrimidine dehydrogenase by sorivudine. This interaction has the potential to lead to a lethal increase in the toxicity of fluoropyrimidines.Therefore, Capecitabine CRCA should not be used concomitantly with sorivudine or its structural analogs such as brivudine (see section “Contraindications”). The period between the start of capecitabine treatment and the end of treatment with sorivudine or its structural analogs should be at least 4 weeks.

Antacids. The effect of antacids containing aluminum and magnesium hydroxide on the pharmacokinetics of capecitabine has been studied. Antacids containing aluminum and magnesium hydroxide slightly increase the concentration of capecitabine and one metabolite (5′-DFCT) in plasma; they do not affect the three main metabolites (5′-DFUR, 5-FU and FBAL) of capecitabine.

Allopurinol. An interaction was observed between allopurinol and 5-fluorouracil, with a possible decrease in the effectiveness of 5-fluorouracil. In this regard, the simultaneous use of Capecitabine KRKA and allopurinol should be avoided.

Interferon alpha . The maximum tolerated dose of capecitabine is 2000 mg / m2 per day when combined with interferon alpha-2a (3 million IU / m ² per day) compared to 3000 mg / m ² per day when using capecitabine alone.

Radiation therapy. The maximum tolerated dose of capecitabine in monotherapy with an intermittent dosing regimen is 3000 mg / m ² per day, when combined with radiation therapy for rectal cancer – 2000 mg / m ² per day with a continuous course of radiation therapy or daily 6 – a weekly course of radiation therapy from Monday to Friday.

Oxaliplatin. With the combined use of capecitabine and oxaliplatin with or without bevacizumab, there was no clinically significant difference in the exposure of capecitabine or its metabolites, free platinum and total platinum.

Bevacizumab. There was no clinically significant effect of bevacizumab on the pharmacokinetic parameters of capecitabine and its metabolites in the presence of oxaliplatin.

Interaction with food

In all studies, patients were instructed to take capecitabine within 30 minutes after meals. Since the available safety and efficacy data are based on dietary capecitabine, it is recommended that Capecitabine CRCA be taken with food.Taking capecitabine with food slows down the rate of absorption of capecitabine.

Application features.

Toxic effect, depends on the dose: diarrhea, abdominal pain, nausea, stomatitis, palmar-plantar syndrome (palmar-plantar skin reactions, palmar-plantar erythrodysesthesia). Most of the undesirable effects are reversible and do not require complete discontinuation of the drug, although it may be necessary to adjust the dose or temporarily discontinue the drug.

Diarrhea. Patients with severe diarrhea should be closely monitored for rehydration and restoration of electrolyte loss during dehydration. Standard antidiarrheal drugs (eg, loperamide) may be prescribed. Grade II diarrhea according to the criteria of the National Cancer Institute of Canada (NCIC CTC) is defined as an increase in the number of bowel movements up to 4-6 times a day or at night, grade III diarrhea – as an increase in the number of bowel movements up to 7-9 times a day or fecal incontinence and malabsorption.Grade IV diarrhea is defined as an increase in the number of bowel movements ≥10 / day or massive diarrhea with an admixture of blood, or the need for parenteral infusion. If necessary, the dose of the drug should be reduced (see Section “Dosage and Administration”).

Dehydration. It is necessary to prevent the development of dehydration and correct dehydration if it occurs. Dehydration can develop rapidly in people with anorexia, asthenia, nausea, vomiting, or diarrhea.If dehydration of the II degree (or higher) appears, it is necessary to immediately stop treatment with Capecitabine CRKA and to correct the dehydration. Recovery of treatment is possible with adequate correction of dehydration and correction / control of the causes of precipitation. Dose adjustment in case of precipitating side effects is carried out if necessary (see Section “Dosage and Administration”). Possible acute renal failure (potentially fatal) in patients with existing impaired renal function or in the case of concomitant treatment with nephrotoxic drugs.

Palmar-plantar syndrome (synonyms: palmar-plantar skin reactions, palmar-plantar erythrodysesthesia, peripheral erythema caused by chemotherapy). Grade I palmoplantar syndrome does not affect the patient’s daily activity and is manifested by numbness, paresthesia, dysesthesia, tingling, painless swelling or redness of the palms and / or soles and / or discomfort.

Grade II palmoplantar syndrome is manifested by painful redness and swelling of the hands and / or soles; the discomfort caused by these manifestations disrupts the daily activity of the patient.

Grade III palmoplantar syndrome is defined as wet desquamation, ulceration, blistering, severe pain in the palms and / or soles, and / or severe discomfort that prevents patients from working or performing daily activities.

In case of grade II or III hand-foot syndrome, capecitabine should be discontinued until symptoms disappear or decrease to grade I; at the next onset of grade III syndrome, the dose of capecitabine should be reduced.Patients who receive Capecitabine CRKA and cisplatin at the same time are not advised to use vitamin B6 (pyridoxine) for symptomatic or secondary prophylactic treatment of palmoplantar syndrome, since published data indicate that this can lead to a decrease in the effectiveness of cisplatin. There is some evidence that dexpanthenol is effective for the prevention of palmoplantar syndrome in patients who received capecitabine.

Cardiotoxicity. The spectrum of manifestations of cardiotoxicity in the treatment of capecitabine is similar to that in the use of other fluoropyrimidines and includes myocardial infarction, angina pectoris, arrhythmias, cardiogenic shock, sudden death, cardiac arrest, heart failure, and ECG changes (including very rare cases of prolongation of the QT interval). These side effects are more common in patients with coronary artery disease. When using capecitabine, cases of cardiac arrhythmias (including ventricular fibrillation, ventricular tachycardia pirouette, bradycardia), angina pectoris, myocardial infarction, heart failure, cardiomyopathy have been reported.Use Capecitabine KRKA with caution in patients with clinically significant heart disease, arrhythmias and angina pectoris.

Hypo- or hypercalcemia. Hypo- or hypercalcemia has been reported during capecitabine treatment. Use Capecitabine CRKA with caution in patients with severe hypo- or hypercalcemia.

Diseases of the central or peripheral nervous system. Precautions should be taken to prescribe Capecitabine CRCA to patients with diseases of the central or peripheral nervous system, for example, with brain metastases or neuropathy.

Diabetes mellitus or electrolyte disturbance. Capecitabine CRCA should be used with caution in patients with diabetes mellitus or electrolyte disturbances, since the use of capecitabine can lead to complications of their course.

Anticoagulants – coumarin derivatives. In a study of interaction with a single use of warfarin, a significant increase in the average area under the concentration-time curve (AUC) of S-warfarin (by 57%) was observed, which indicates the presence of an interaction, probably as a result of inhibition of cytochrome P450 2C9 enzyme by capecitabine.In patients who simultaneously take capecitabine and oral anticoagulants – coumarin derivatives, it is necessary to conduct detailed monitoring of blood coagulation parameters (international normalized ratio or prothrombin time) and select the dose of the anticoagulant.

Liver dysfunction. Due to the lack of safety and efficacy data in patients with impaired liver function when using Capecitabine CRKA, it is necessary to carefully monitor the condition of patients with mild to moderate hepatic impairment, regardless of the presence of liver metastases.If, as a result of capecitabine treatment, hyperbilirubinemia is observed, which exceeds the upper limit of the norm by more than 3 times, or the activity of hepatic aminotransferases (ALT, ACT) increases by more than 2.5 times compared to the upper limit of the norm, the use of capecitabine should be discontinued. The use of capecitabine as monotherapy can be restored when the level of bilirubin and the activity of hepatic transaminases fall below the specified limit.

Renal dysfunction. The incidence of grade III and IV adverse reactions in patients with moderate renal dysfunction (creatinine clearance – 30-50 ml / min) is increased compared to that in the general group of patients.

Dihydropyrimidine dehydrogenase (DPD) deficiency: Occasionally, due to deficiency in DPD activity, unexpected severe toxicity (eg stomatitis, diarrhea, mucosal inflammation, neutropenia and neurotoxicity) associated with 5-fluorouracil (5-FU) has been observed.

Patients with low activity of DPD or lack of activity of DPD, an enzyme that is involved in the breakdown of fluorouracil, has an increased risk of severe, life-threatening or fatal adverse reactions caused by fluorouracil.Although DPD deficiency cannot be determined with certainty, it is known that patients with certain homozygous or some combined heterozygous mutations at the DPYD genetic locus, which can lead to complete or almost complete absence of DPD enzyme activity (as determined by laboratory tests), have a high risk of life-threatening or lethal toxicity, and such patients should not be treated with Capecitabine CRKA (see section “Contraindications”). For patients with complete inactivity of DPD, forum doses with proven safety.

Patients with partial DPD deficiency (in particular, heterozygous DPYD mutations) and for whom the benefits of using capecitabine outweigh the risks (given the feasibility of prescribing alternative chemotherapy regimens other than fluoropyrimidine) should be treated with extreme caution and frequent monitoring with dose adjustments depending on toxicity. There are insufficient data to recommend a specific dose for patients with partial DPD activity based on the results of a specific test.

Patients with unidentified DPD deficiency who have been treated with capecitabine may experience life-threatening toxicity similar to acute overdose (see Overdose section). In case of acute toxicity of II-IV degrees, treatment should be stopped immediately. Consideration should be given to definitive discontinuation of treatment based on clinical assessment of the occurrence, duration and severity of observed toxicity.

Ophthalmic complications. Patients should be carefully monitored for ophthalmic complications such as keratitis or corneal abnormalities, especially if there is a history of visual impairment.If clinically necessary, treatment of visual impairment should be initiated.

Complex skin reactions. Treatment with Capecitabine CRKA may cause skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis. The use of Capecitabine CRKA should be permanently discontinued in patients who have developed severe skin reactions during the course of the drug.

Since the drug contains anhydrous lactose as an excipient, patients with congenital galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption should not use Capecitabine CRKA.

Application during pregnancy or lactation.

Women of reproductive age / contraception for men and women

Women of reproductive age should be advised to avoid pregnancy during capecitabine treatment. When pregnancy occurs during treatment, the patient should be educated about the potential negative effect on the fetus. Effective contraceptive methods should be used during treatment.

Pregnancy

The use of capecitabine in pregnant women has not been studied, however, it can be assumed that the use of Capecitabine CRCA may be harmful to the fetus when used in pregnant women.In reproductive toxicity studies in animals, capecitabine caused embryo and teratogenicity, which are the expected effects of fluoropyrimidine derivatives. The use of capecitabine during pregnancy is contraindicated.

Breastfeeding

There is no data on the penetration of capecitabine into breast milk. Significant amounts of capecitabine and its metabolites were found in the breast milk of lactating mice. Therefore, breastfeeding is not recommended for capecitabine treatment.

Fertility

There is no evidence of the effect of capecitabine on fertility. Pivotal capecitabine studies included only those men and women of reproductive age who agreed to use acceptable birth control methods to prevent pregnancy during the study and thereafter. An effect on fertility has been observed in animal studies.

The ability to influence the reaction rate when driving or driving other mechanisms.

The drug has a slight or moderate effect on the ability to drive vehicles and work with complex mechanisms. Capecitabine may cause dizziness, weakness, and nausea.

Method of administration and dosage.

Capecitabine KRKA can only be prescribed by a qualified physician experienced in the use of antineoplastic drugs. Careful monitoring of the condition during the first cycle of treatment is recommended for all patients.

Treatment should be withdrawn if disease progresses or unacceptable toxicity develops.

The drug is taken orally, no later than 30 minutes after a meal, with water.

Monotherapy

Colon cancer, colorectal cancer and breast cancer The recommended starting daily dose of Capecitabine CRKA as adjuvant therapy is 2500 mg / m ² and is used in three-week cycles: taken daily for 2 weeks, after which they take a week break.The total daily dose of Capecitabine KRKA is divided into two doses (1250 mg / m ² in the morning and in the evening). The recommended total duration of adjuvant therapy for patients with stage III colon cancer is 6 months.

Combination therapy

Breast cancer: when capecitabine is used in combination with docetaxel, the recommended starting dose for the treatment of metastatic breast cancer is 1250 mg / m ² 2 times a day for 2 weeks, followed by a week break (in combination with docetaxel 75 mg / m ² 1 time in 3 weeks in the form of intravenous infusion).Premedication with oral corticosteroids, such as dexamethasone, is done before docetaxel is administered according to the docetaxel instructions for use in patients receiving capecitabine plus docetaxel.

Colon cancer, colorectal cancer, stomach cancer: in the combined treatment regimen, the initial dose of Capecitabine CRKA should be reduced to 800-1000 mg / m2 2 times a day for 2 weeks, followed by a weekly break or to 625 mg / m2 ² 2 times a day with continuous use.With the combination of irinotecan (200 mg / m2 on day 1), the recommended initial dose is 800 mg / m2 2 times a day for 2 weeks, followed by a weekly break. The inclusion of bevacizumab in the combination regimen does not affect the initial dose of Capecitabine CRCA.

Antiemetics and premedication to ensure adequate hydration are prescribed to patients who receive Capecitabine CRKA in combination with cisplatin or oxaliplatin before cisplatin administration according to the cisplatin and oxaliplatin instructions for use.The general recommended duration of adjuvant therapy for patients with stage III colon cancer is 6 months.

The dose of Capecitabine KRKA is calculated from the body surface area. Tables 1, 2 show the calculations of the standard and reduced dose (see “Dose adjustment during treatment”) for the initial dose of Capecitabine KRKA 1250 mg / m ² or 1000 mg / m ² .

Calculations of the standard and reduced initial dose of Capecitabine KRKA 1250 mg / m ² depending on body surface area

Calculations of the standard and reduced initial dose of Capecitabine KRKA 1000 mg / m ² depending on body surface area

Dose adjustment during treatment

The toxicity phenomena in the treatment of Capecitabine CRKA can be eliminated by symptomatic therapy and / or by changing the dose of Capecitabine CRKA (by interrupting treatment or reducing the dose of the drug).If the dose has to be reduced, it is not further increased.

In case of toxicity phenomena that, in the opinion of the doctor, will not become serious and will not threaten life (for example, alopecia, changes in taste, changes in nails), the use of the drug can be continued at the same dose without interrupting treatment and without reducing the dose of the drug.

Patients receiving treatment with Capecitabine CRCA should be warned that treatment should be discontinued if moderate or severe toxic reactions develop.If several doses of capecitabine have been missed due to toxic effects, then the missed doses do not need to be applied additionally.

Hematological toxicity

Patients with a baseline neutrophil count <1.5 × 109 / L and / or platelets <100 × 109 / L should not be treated with capecitabine. Therapy should be suspended if, during laboratory tests, a decrease in the level of neutrophils <1.0 × 109 / L or platelets <75 × 109 / L is detected.

Table 3 provides recommendations for changing the dose in the event of toxic events in accordance with the criteria for signs of toxicity, often found in the clinic.The criteria were developed by the National Cancer Institute of Canada (NCIC CTC version 1).

Capecitabine KRKA dose reduction regimen (3-week cycle or continuous treatment)

Dose change in case of toxicity when using capecitabine during a 3-week cycle in combination with other drugs

Dose change in the event of toxicity when using Capecitabine KRKA during a 3-week cycle in combination with other drugs should be carried out in accordance with Table 3 for capecitabine and in accordance with the instructions for use of other drugs.

At the beginning of the course of treatment, if it is necessary to postpone therapy with Capecitabine KRKA or another drug, the use of other drugs should also be postponed until the use of all components of the regimen is possible.

If toxic phenomena occur during treatment, according to the doctor, are not associated with the use of capecitabine, Capecitabiom CRKA therapy must be continued and the dose of other drugs-components of the scheme must be adjusted in accordance with the instructions for use.

If it is necessary to cancel other drugs, components of the regimen, treatment with Capecitabine CRCA, you can continue when the necessary conditions are reached for re-prescribing Capecitabine CRCA.

These recommendations apply to all indications for use and all patient groups.

Dose change in the event of toxicity with continuous use of capecitabine in combination with other drugs

Dose change in the event of toxicity with continuous use of Capecitabine KRKA in combination with other drugs should be carried out in accordance with Table 3 for capecitabine and in accordance with the instructions for use of other drugs.

Dose adjustment in special cases

Patients with impaired liver function

There is insufficient data on safety and efficacy in patients with impaired liver function to provide recommendations for dose adjustment. There is no information on liver dysfunctions due to cirrhosis or hepatitis.

Patients with impaired renal function

Capecitabine is contraindicated in patients with severe renal impairment (creatinine clearance below 30 ml / min with Cockcroft-Gault at the initial level).The incidence of grade III or IV adverse reactions in patients with moderate renal impairment (creatinine clearance of 30-50 ml / min at the baseline) is increased compared to that in the general population. For patients with initial moderate renal insufficiency, it is recommended to reduce the initial dose to 75% of the standard (1250 mg / m ² ). For patients with initial moderate renal impairment, a reduction in the initial dose of 1000 mg / m ² is not required. Patients with mild renal insufficiency (creatinine clearance 51-80 ml / min) do not require adjustment of the initial dose.

We recommend careful monitoring and immediate interruption of treatment in the event of side effects of II, III or IV degree, as well as further dose adjustment in accordance with Table 3. If the creatinine level drops below 30 ml / min, treatment with Capecitabine CRKA should be discontinued. The recommendations for dose adjustment in moderate renal impairment are the same for both capecitabine monotherapy and combination therapy.

Elderly patients

No initial dose adjustment is necessary for capecitabine monotherapy.However, in patients aged 60 years and older, the phenomena of III and IV degrees of toxicity developed more often than in younger patients.

It is recommended to carefully monitor the condition of patients over the age of 60 years. When using capecitabine in combination with other drugs in elderly patients (over 65 years of age), there was a high frequency of undesirable effects of III and IV degrees of toxicity, which led to the cancellation of treatment, compared with younger patients.

Treatment with capecitabine in combination with docetaxel in patients over 60 years of age showed an increase in the frequency of undesirable effects of III and IV degrees of toxicity.For patients of this age group, with combined treatment with Capecitabine CRKA and docetaxel, it is recommended to reduce the initial dose of Capecitabine CRKA to 75% (950 mg / m ² 2 times a day). In the absence of toxicity in patients aged 60 years and older during treatment with a reduced initial dose of capecitabine in combination with docetaxel, the dose of capecitabine can be gradually increased to 1250 mg / m ² 2 times a day.

Children.

The safety and efficacy of capecitabine in children have not been studied.

Overdose.

Symptoms of acute overdose: nausea, vomiting, diarrhea, mucositis, irritation of the gastrointestinal tract and bleeding, as well as bone marrow suppression. Treatment should include standard therapeutic and supportive measures to correct clinical manifestations and prevent possible complications.

Adverse reactions.

The general safety profile of capecitabine is based on data from more than 3000 patients treated with capecitabine alone or in combination with different chemotherapy regimens for different indications.The safety profile of capecitabine monotherapy in metastatic breast cancer, metastatic colorectal cancer, and colon cancer in adjuvant therapy is comparable.

The most frequent and / or clinically significant treatment-related adverse reactions were gastrointestinal reactions (diarrhea, nausea, vomiting, abdominal pain, stomatitis), palmar-plantar syndrome (palmar-plantar erythrodysesthesia), weakness, asthenia, anorexia, cardiotoxicity, progression of renal dysfunction in patients with renal failure, thrombosis / embolism.

Adverse reactions that were considered likely to be related to the use of capecitabine have been observed with capecitabine monotherapy and in studies of capecitabine in combination with different chemotherapy regimens for different indications.

The following categories are used to describe the frequency of adverse reactions: very often (≥1 / 10), often (from ≥1 / 100 to <1/10), infrequently (from ≥1 / 1000 to <1/100), rarely (from ≥ 1/10000 to <1/1000), very rare (<1/10000). In each group, adverse reactions are presented in decreasing order of severity.

Capecitabine monotherapy

Table 4 lists adverse reactions associated with capecitabine monotherapy.

Adverse reactions in patients with capecitabine monotherapy

Combination therapy

Table 5 shows the adverse reactions reported with capecitabine in combination with different chemotherapy regimens for different indications in more than 3000 patients.

Some adverse reactions are often observed with chemotherapy (for example, peripheral sensory neuropathy with docetaxel or oxaliplatin, hypersensitivity reactions with bevacizumab).However, an increase in these side effects cannot be ruled out when using capecitabine.

Adverse reactions in patients with capecitabine monotherapy

Frequency includes all degrees of severity, with the exception of adverse reactions marked with “*”, which included only III-IV degree adverse reactions.

Selected adverse reactions

Palmar-plantar syndrome

When using capecitabine at a dose of 1250 mg / m ² twice a day for 2 weeks, followed by a one-week break Palmar-plantar syndrome of all severity in monotherapy (adjuvant therapy of colon cancer, treatment of metastatic colorectal cancer, treatment of breast cancer ) was recorded in 53-60% of patients and in 63% of patients with metastatic breast cancer in the capecitabine / docetaxel treatment group.When capecitabine was used at a dose of 1000 mg / m ² twice a day for 2 weeks with a subsequent one-week break, palmoplantar syndrome of all severity was observed in 22-30% of patients receiving combined treatment with capecitabine.

Diarrhea

The occurrence of diarrhea during treatment with capecitabine was observed in almost 50% of patients. An increased risk of diarrhea was associated with: an increase in the initial dose of capecitabine (in grams), an increase in the duration of treatment (weeks), an increase in the patient’s age (an increase by 10 years), and female sex.The following were associated with a decrease in the risk of diarrhea: an increase in the cumulative dose of capecitabine (0.1 * kg) and the relative dose intensity in the first 6 weeks of treatment.

Cardiotoxicity

In addition to these adverse reactions, adverse reactions with a frequency of less than 0.1% were reported with capecitabine monotherapy: cardiomyopathy, heart failure, ventricular premature beats, sudden death.

Encephalopathy

In addition to these adverse reactions, capecitabine monotherapy was associated with encephalopathy with a frequency of less than 0.1%.

Adverse reactions in special patient groups

Elderly patients: patients aged 60 years and older who received capecitabine monotherapy and combination treatment with capecitabine and docetaxel had an increased incidence of grade III and IV adverse reactions and serious treatment-related adverse reactions compared with patients in under 60 years of age. There were more patients aged 60 years and older who received combined treatment with capecitabine and docetaxel and had previously discontinued treatment due to adverse reactions compared with patients under 60 years of age.

Floor

Female sex is statistically significantly associated with an increased risk of developing palmoplantar syndrome and diarrhea, as well as a reduced risk of developing neutropenia.

Patients with impaired renal function

In patients with impaired renal function before treatment, receiving monotherapy with capecitabine (for colorectal cancer), there was an increase in the incidence of grade III and IV adverse reactions associated with treatment, compared with patients with normal renal function 41% – in patients with renal mild failure and 54% in patients with moderate renal failure.Patients with moderate renal insufficiency were more likely to need to reduce the dose (44%) compared with 33% and 32% of patients without renal insufficiency and mild renal insufficiency, respectively, and premature discontinuation of treatment was observed more often (in 21% of patients during the first two courses ) compared with 5% and 8% in patients with no renal impairment and mild renal failure.

Expiry date

3 years.

Storage conditions

Store at a temperature not exceeding 25 ° C.Keep out of the reach of children.

Packaging

There are 10 tablets in a blister, 3, 6 or 12 blisters in a cardboard box.

Vacation category

By prescription.

Manufacturer

KRKA, d.d., Novo mesto / KRKA, d.d., Novo mesto.

Location of the manufacturer and address of the place of business

Smarjeska cesta 6, 8501 Novo mesto, Slovenia / Smarjeska cesta 6, 8501 Novo mesto, Slovenia.

Capecitabine tablets p.o. 500mg 120 pcs.

Short description

Ozone LLC, Russian Federation, antineoplastic agent – antimetabolite

Roster

Capecitabine 500 mg. Excipients: lactose – 91.11 mg, microcrystalline cellulose – 91.11 mg, croscarmellose sodium – 32.8 mg, hypromellose – 2.02 mg, magnesium stearate – 10.93 mg. Shell composition: film coating – 6.56 mg (hypromellose – 38.46%, talc – 30.77%, titanium dioxide (E171) – 29.41%, iron dye red oxide (E172) – 0.68%, iron dye yellow oxide (E172) – 0.68%). & Lt / p>

Pharmacological action

Antineoplastic agent. Has a selective cytotoxic effect. In tumor tissue, capecitabine is converted to 5-fluorouracil by thymidine phosphorylase (tumor angiogenic factor). The activity of thymidine phosphorylase in the primary tumor is 4 times higher than in healthy tissue; therefore, the concentration of 5-fluorouracil in tumor tissue is higher than in healthy tissue and in plasma.In both healthy and tumor cells, 5-fluorouracil is metabolized to form 5-fluoro-2-deoxyuridine monophosphate and 5-fluorouridine triphosphate, which have a cytotoxic effect.

Readings

Locally advanced or metastatic breast cancer, with the ineffectiveness of chemotherapy, including paclitaxel and an anthracycline drug, or in the presence of contraindications to anthracyclines therapy.

Way
application and dosage

Set individually, depending on the indications and stage of the disease, the state of the hematopoietic system, the scheme of anticancer therapy.

Side effects

From the digestive system: diarrhea, nausea, vomiting, stomatitis, abdominal pain, constipation, epigastric pain, dyspepsia, dry mouth, flatulence, soft stools, anorexia, poor appetite, oral candidiasis, hyperbilirubinemia, taste disturbance. From the side of the nervous system: increased fatigue, weakness, severe drowsiness, headache, paresthesia, dizziness, sleep disturbances, asthenia. Skin and subcutaneous tissue disorders: palmar-plantar syndrome, dermatitis, dry skin, alopecia, itching, focal peeling, skin hyperpigmentation, skin cracks.Others: increased tearing, fever, possibly dehydration, weight loss, possible shortness of breath, cough, limb pain, back pain, myalgia, cardiotoxic effect (most likely in patients with coronary artery disease), edema of the lower extremities, anemia.

Contraindications

History of severe unpredictable reactions during treatment with fluoropyrimidine, hypersensitivity to capecitabine and 5-fluorouracil.

Special
guidance

During treatment, patients with mild to moderate liver dysfunction caused by liver metastases and the elderly require close medical supervision.In moderate to severe hyperbilirubinemia, capecitabine should be temporarily discontinued until values ​​return to mild severity. The safety and efficacy of capecitabine in children has not been studied. Influence on the ability to drive vehicles and control mechanisms Use with caution in patients engaged in potentially hazardous activities that require a high concentration of attention and speed of psychomotor reactions.

Interaction with other drugs

With the simultaneous use of capecitabine with coumarin anticoagulants, a violation of blood coagulation parameters and the development of bleeding are possible (it is necessary to regularly monitor the coagulation parameters).

instructions for use, analogs, articles »Drug Handbook

From the digestive system: diarrhea, nausea, vomiting, abdominal pain, stomatitis, constipation, epigastric pain, dyspepsia, dry mouth, flatulence, loss of appetite, oral candidiasis , esophagitis, gastritis, duodenitis, colitis, hiccups, gastrointestinal bleeding, cholestatic hepatitis, hyperbilirubinemia. From the nervous system: increased fatigue, weakness, paresthesia, sleep disturbances (including drowsiness, insomnia), asthenia, headache, dizziness, peripheral polyneuropathy, confusion, encephalopathy, ataxia, dysarthria, imbalance and coordination, depression …
On the part of the skin: palmar-plantar syndrome (paresthesia; edema, hyperemia and peeling of the skin, blistering), dermatitis, erythematous rash, dryness, itching, hyperpigmentation, cracks and peeling of the skin, photosensitivity.
From the senses: violation of taste, increased lacrimation, conjunctivitis, stenosis of the lacrimal canal. From the side of metabolism: dehydration, weight loss. From the respiratory system: shortness of breath, cough, sore throat, nosebleeds, dysphonia.
From the musculoskeletal system: myalgia, pain in the limbs, lower back.
From the side of hematopoiesis: anemia, neutropenia, lymphocytopenia, granulocytopenia, thrombocytopenia, pancytopenia. From the CVS: manifestations of cardiotoxic action (most likely in patients with coronary artery disease), cardialgia, angina pectoris, cardiomyopathy, myocardial ischemia, myocardial infarction, heart failure, tachycardia, supraventricular arrhythmia (including atrial fibrillation), ventricular extrasystole, sudden death.
Laboratory indicators: increased activity of “hepatic” transaminases, hypercreatininemia, increased alkaline phosphatase activity, hyperglycemia, hypo and / or hypercalcemia, hypoalbuminemia, hyponatremia, hypokalemia.
Others: fever, edema of the lower extremities, alopecia, impaired structure and discoloration of nails, onycholysis, inflammation of the mucous membranes, infections, sepsis.
Overdose. Symptoms: suppression of bone marrow hematopoiesis, nausea, vomiting, diarrhea, bleeding.
Treatment: symptomatic, hemodialysis.

Xeloda film-coated tablets 500mg No. 120 (Capecitabine)

Locally advanced or metastatic breast cancer, with the ineffectiveness of chemotherapy, including paclitaxel and an anthracycline drug, or in the presence of contraindications to anthracyclines therapy.

History of severe unpredictable reactions during treatment with fluoropyrimidine, hypersensitivity to capecitabine and 5-fluorouracil.Application during pregnancy and lactation
There have been no adequate and well-controlled clinical studies of the safety of capecitabine during pregnancy. Experimental studies have shown that capecitabine has fetotoxic and teratogenic effects. Use during pregnancy is not recommended. Women of childbearing age should use reliable methods of contraception during treatment.
It is not known whether capecitabine is excreted in breast milk.If it is necessary to use it during lactation, the expected benefit of the treatment for the mother and the existing risk for the child should be assessed.

Active ingredient: capecitabine.
Release form: Tablets, film-coated 500 mg No. 120.

Set individually, depending on the indications and stage of the disease, the state of the hematopoietic system, the scheme of anticancer therapy.

Special instructions: During the period of treatment, patients with mild to moderate liver dysfunction caused by liver metastases, and the elderly require careful medical supervision.
In moderate to severe hyperbilirubinemia, capecitabine should be temporarily discontinued until values ​​return to mild severity.
The safety and efficacy of capecitabine in children has not been studied.

Influence on the ability to drive vehicles and use mechanisms
Use with caution in patients engaged in potentially hazardous activities that require a high concentration of attention and speed of psychomotor reactions.Storage conditions
At a temperature not exceeding 30 ° C.
Interaction with other drugs: With the simultaneous use of capecitabine with coumarin anticoagulants, a violation of blood coagulation parameters and the development of bleeding are possible (it is necessary to regularly monitor the coagulation parameters).
Side effects: From the digestive system: diarrhea, nausea, vomiting, stomatitis, abdominal pain, constipation, epigastric pain, dyspepsia, dry mouth, flatulence, soft stools, anorexia, impaired appetite, oral candidiasis, hyperbilirubinemia, taste disturbance sensations.From the side of the nervous system: increased fatigue, weakness, severe drowsiness, headache, paresthesia, dizziness, sleep disturbances, asthenia.
Skin and subcutaneous tissue disorders: palmar-plantar syndrome, dermatitis, dry skin, alopecia, itching, focal peeling, skin hyperpigmentation, skin cracks.
Others: increased tearing, fever, possibly dehydration, weight loss, possible shortness of breath, cough, limb pain, back pain, myalgia, cardiotoxic effect (most likely in patients with coronary artery disease), edema of the lower extremities, anemia.

Apsibin instruction, price in pharmacies for Apsibin

Composition and form of release

Composition

active ingredient: sarecitabine;

1 tablet contains 150 mg or 500 mg of capecitabine;

Excipients: sodium croscarmellose, microcrystalline cellulose (Avicel Ph212), hypromellose (6 cps), lactose DCL22, magnesium stearate, pink opadry 03A540004 (hypromellose, titanium dioxide (E 171), talc, iron oxide, iron oxide red (E172) yellow (E172)) – for tablets of 150 mg, opadry pink 03A540003 (hypromellose, titanium dioxide (E 171), talc, iron oxide red (E172), iron oxide yellow (E172)) – for tablets of 500 mg.

Form of issue

Film-coated tablets:

• 150 mg: 10 tablets in a blister. 1 or 6 blisters in a cardboard box.
• 500 mg: 10 tablets in a blister. 1 or 12 blisters in a cardboard box

Pharmacological action

Pharmacodynamics

Capecitabine is a fluoropyrimidine carbamate derivative, an oral cytostatic agent, which is activated in the tumor tissue and has a selective cytotoxic effect on it.Capecitabine itself does not have a cytotoxic effect, but it turns into a cytotoxic compound – fluorouracil (5-FU). The formation of 5-FU occurs in the tumor tissue under the action of the tumor angiogenic factor thymidine phosphorylase, which, thus, minimizes the systemic effect of 5-FU on healthy tissues of the body.

Sequential enzymatic biotransformation of capecitabine to 5-FU creates higher concentrations of capecitabine in tumor cells than in surrounding healthy tissues. After taking capecitabine in patients with colon cancer, the concentration of 5-FU in the tumor tissue is 3.2 times higher than in healthy tissues.The ratio of 5-FU concentrations in tumor tissue and plasma is 21.4, the ratio of its concentration in healthy tissues and in plasma is 8.9. The activity of thymidine phosphorylase in the primary colorectal tumor is 4 times higher than in the surrounding healthy tissues.

Tumor cells in breast, stomach, colon, cervical and ovarian cancer patients contain more thymidine phosphorylase, which is able to convert 5 “-DFUR (5” -deoxy-5-fluoruridine) into 5-FU than in the corresponding healthy tissues …

Both healthy and tumor cells metabolize 5-FU to 5-fluoro-2-deoxyuridine monophosphate (FdUMP) and 5-fluoruridine triphosphate (FUTP). These metabolites damage cells through two distinct mechanisms. First, FdUMP and folate cofactor N ⁵ “ ¹⁰ – methylenetetrahydrofolate bind with thymidylate synthase (TS) to form a covalently bound tertiary complex. This bond inhibits the formation of thymidylate from uracil. Thymidylate is necessary in turn as a precursor of thymidine, which is triphosphate, which is thymidine. , is very important for DNA synthesis, since the lack of this substance can lead to inhibition of cell division.second, in the process of RNA synthesis, nuclear transcriptional enzymes may mistakenly include FUTP in it instead of uridine triphosphate (UTP). This abolic error disrupts RNA processing and protein synthesis.

Pharmacokinetics

Suction

After taking capecitabine is rapidly and completely absorbed, after which it is biotransformed into metabolites 5 “-deoxy-5-fluorocytidine (5” -DFCT) and 5 “-DFUR. Food intake reduces the absorption rate of capecitabine, but does not significantly affect the value the area under the concentration-time curve (AUC) of 5 “-DFUR and the subsequent metabolite 5-FU.When the drug was prescribed after a meal at a dose of 1250 mg / m ² on the 14th day, the maximum concentrations of C _max capecitabine, 5 “-DPCR, 5” -DFUR, 5-FU and FBAL were 4.47, 3, respectively. , 05, 12, 1, 0.95 and 5.46 μg / ml. The time to reach the maximum concentration T _max is 1.50, 2.00, 2.00, 2.00 and 3.34 hours, and AUC is 7.75, 7.24, 24.6, 2.03 and 36 , 3 μg x h / ml, respectively.

Communication with proteins

For capecitabine, 5 “-DFCT, 5” -DFUR and 5-FU, the bond with proteins (mainly albumin) is 54%, 10%, 62% and 10%, respectively.

Metabolism

Metabolized in the liver under the action of carboxylesterase to the 5 “-DFCT metabolite, which is then transformed into 5” -DFUR under the action of cytidine deaminase, which is found mainly in the liver and tumor tissues. The concentrations of 5-FU and its active phosphorylated anabolic in the tumor significantly exceed the levels in healthy tissues, which ensures the relative selectivity of the cytotoxic effect.

AUC for 5-FU is 6-22 times less than after jet injection of 5-FU at a dose of 600 mg / m ² .Capecitabine metabolites become cytotoxic only after conversion to 5-FU and 5-FU anabolites.

Then 5-FU is catabolized with the formation of inactive metabolites – dihydro-5-fluorouracil (fu ₂ ), 5-fluoroureidopropionic acid (FUPA) and α-fluorine (3-alanine (FBAL)), this process takes place under the influence of dihydropyrimidine dehydrogenase (DPP) , the activity of which limits the reaction rate.

Output

The half-life (T _1/2 ) of capecitabine, 5 “-DFCR, 5” -DFUR, 5-FU and FBAL is 0.85, 1.11, 0.66, 0.76 and 3.23 hours, respectively …The pharmacokinetics of capecitabine was studied for the dose range 502-3514 mg / m ² / day. Pharmacokinetic parameters of capecitabine, 5 “-DFCT and 5” -DFUR on the 1st and 14th day are the same. The 5-FU AUC increases by 30-35% until the 14th day and no longer increases (22nd day). In the therapeutic dose range, the pharmacokinetic parameters of capecitabine and its metabolites, with the exception of 5-FU, are dose-dependent.

After administration, the metabolites of capecitabine are mainly excreted in the urine. Excretion with urine – 95.5%, with feces – 2.6%.The main metabolite in urine is FBAL, which accounts for 57% of the dose taken. Approximately 3% of the dose taken is excreted in the urine unchanged.

Indications for use

Breast cancer:

• local advanced or metastatic breast cancer, in combination with docetaxel after ineffective anthracycline chemotherapy;
• local advanced or metastatic breast cancer, with the ineffectiveness of chemotherapy, including taxanes and anthracycline drugs, or in the presence of contraindications to anthracyclines therapy.

Colon cancer, colorectal cancer:

• colon cancer, in adjuvant therapy
• first-line drug for the treatment of metastatic colorectal cancer.

Cancer of the esophagus and stomach:

first-line drug for the treatment of advanced cancer of the esophagus and stomach.

Contraindications

Severe, including unexpected, reactions to treatment with fluoropyrimidines. Hypersensitivity to capecitabine or to any component of the drug, or fluorouracil.Known deficiency of dihydropyrimidine dehydrogenase. Severe leukopenia, neutropenia, thrombocytopenia. Severe liver dysfunction. Severe renal impairment (creatinine clearance <30 ml / min). Concomitant administration of sorivudine or its structural analogs such as brivudine.

Special security measures.

Disposal of an unused product and a product with an expired shelf life of the product entering the environment should be minimized. The drug should not be disposed of in waste water and household waste.For disposal, it is necessary to use the so-called “waste collection system”, if available.

Method of administration and dosage

Standard dosage

The drug is taken orally, no later than 30 minutes after a meal, with water.

Monoteratia

Colon cancer, colorectal cancer and breast cancer The recommended daily dose of capecitabine is 2500 mg / m2 ² body surface and is given in 3-week cycles; take daily for 2 weeks, then take a week break.The total daily dose of capecitabine is divided into two doses (1250 mg / m ² body surface in the morning and evening).

combination therapy

Breast cancer in combination with docetaxel at 1250 mg / m ³ 2 times a day for 2 weeks, followed by a weekly break in combination with docetaxel (75 mg / m ² 1 time in 3 weeks). Premedication is carried out before the administration of docetaxel in accordance with the instructions for use of docetaxel.

Colon cancer, colorectal cancer, stomach and esophageal cancer: in the combined treatment regimen, the initial dose of capecitabine should be reduced to 800-1000 mg / m ² 2 times a day for 2 weeks, followed by a weekly break or to 625 mg / m ² 2 times a day with continuous use. The inclusion of the biological agent in the combination regimen did not affect the initial dose of capecitabine. The general recommended duration of adjuvant therapy in patients with stage III colon cancer is 6 months.

Antiemetics and premedication to ensure adequate hydration are prescribed for patients who receive capecitabine in combination with cisplatin or oxaliplatin before cisplatin administration according to the cisplatin and oxaliplatin instructions for use.

Dose of capecitabine is calculated from body surface area. Tables 1, 2 show the calculations of the standard and reduced dose (see “Dose adjustment during treatment”) for the initial dose of capecitabine 1250 mg / m ² or 1000 mg / m ² .

Calculations of the standard and reduced starting dose of capecitabine 1250 mg / m ² depending on body surface area

Calculations of the standard and reduced starting dose of capecitabine 1000 mg / m ² depending on body surface area

Dose adjustment during treatment

general recommendations

The phenomena of toxicity in the treatment of capecitabine can be eliminated by symptomatic therapy or by changing the dose of the drug (by interrupting the treatment or reducing the dose of the drug).If the dose has to be reduced, it is not further increased.

In case of toxicity phenomena that, in the opinion of the doctor, are unlikely to become serious, they will be life-threatening, the use of the drug can be continued at the same dose without interrupting treatment and without reducing the dose of the drug.

Dose adjustments for grade I toxicity. For grade II or III toxicity, capecitabine should be discontinued until toxicity disappears or symptoms decrease to grade I. Capecitabine can be resumed at full dose or adjusted according to the following guidelines (Table 3).With the development of signs of grade IV toxicity, treatment should be discontinued until symptoms decrease (up to grade I), after which the drug is resumed at a dose of 50% of the original. Patients receiving capecitabine treatment should be warned to discontinue treatment if moderate or severe toxic reactions develop. If several doses of capecitabine have been missed due to toxic effects, then the missed doses do not need to be used additionally, but the planned cycles of therapy should be continued.

Hematological toxicity

Patients with a baseline neutrophil level <1.5 × 10 ⁹ / L and / or platelets <100 x 10 ⁹ / L should not be treated with capecitabine. Therapy should be suspended in the event of grade III and IV hematological toxicity.

The following are recommendations for adjusting the dose in case of toxicity in accordance with the criteria for signs of toxicity, often found in the clinic. The criteria were developed by the National Cancer Institute of Canada (NCIC CTC version 1).

Capecitabine dose reduction regimen

General combination therapy

Dose changes in the event of toxicity when using capecitabine in combination with other drugs should be carried out in accordance with Table 3 for capecitabine and in accordance with the instructions for use of other drugs.

At the beginning of the course of treatment, if it is necessary to postpone therapy with capecitabine or another drug, the appointment of other drugs should also be postponed until the period when all components of the regimen can be prescribed.

In the event of toxic phenomena during treatment, which, in the opinion of the doctor, are not related to the use of capecitabine, the drug must be continued and the dose of other drugs-components of the scheme must be adjusted in accordance with the instructions for use,

If it is necessary to cancel other medicinal products-components of the capecitabine treatment regimen, it is possible to continue when the necessary conditions for re-administration of capecitabine are achieved.

These recommendations apply to all indications for use and all patient groups.Dose adjustment in special cases

Patients with impaired liver function due to metastases

For patients with liver metastases and mild to moderate hepatic impairment, it is not necessary to change the initial dose. However, these patients should be closely monitored. The use of the drug in patients with severely impaired liver function has not been studied.

Patients with impaired renal function

For patients with initial moderate renal failure (creatinine clearance 30-50 ml / min), it is recommended to reduce the initial dose to 75% of the standard (1250 mg / m ² ).Patients with mild renal insufficiency (creatinine clearance 51-80 ml / min) do not require dose adjustment.

In the event of grade II, III or IV side effects, careful monitoring, immediate discontinuation of treatment or dose change in accordance with Table 3 is recommended. When creatinine levels drop to less than 30 ml / min, capecitabine treatment should be discontinued. The recommendations for dose adjustment in moderate renal impairment are the same for both capecitabine monotherapy and combination therapy.Recommendations for calculating the dose are given in Tables 1 and 2.

Elderly patients

No initial dose adjustment is necessary for capecitabine monotherapy. However, in patients over 80 years of age, the phenomena of III and IV degrees of toxicity developed more often than in young patients.

It is recommended to carefully monitor the condition of elderly patients. When using capecitabine in combination with other drugs in elderly patients (≥ 65 years), there was a higher frequency of undesirable effects of III and IV degrees of toxicity, which led to the cancellation of treatment, compared with younger patients.

In the treatment of capecitabine in combination with docetaxel in patients over 60 years of age, an increase in the frequency of undesirable effects of III and IV degrees of toxicity was noted. For patients of this age group, when combined treatment with capecitabine and docetaxel, it is recommended to reduce the initial dose of capecitabine to 75% (950 mg / m ² times a day). Calculations are shown in Table 2.

When treating capecitabine in combination with irinotecan, patients over 65 are recommended to reduce the initial dose of capecitabine to 800 mg / m ² times a day.

Side effects

The overall safety profile of capecitabine is based on data from over 3000 patients treated with capecitabine alone or in combination with different chemotherapy regimens for different indications. The safety profile of capecitabine monotherapy in metastatic breast cancer, metastatic colorectal cancer, and colon cancer in adjuvant therapy is comparable.

The most frequent and / or clinically significant adverse reactions associated with treatment were reactions from the digestive tract (diarrhea, nausea, vomiting, abdominal pain, stomatitis), palmar-plantar syndrome (palmar-plantar erythrodysesthesia), weakness, asthenia, anorexia, cardiotoxicity, progression of renal impairment in patients with renal failure, thrombosis / embolism.

Adverse reactions likely or distantly related to the use of capecitabine have been reported in studies of capecitabine monotherapy (in the adjuvant treatment of colon cancer, treatment of metastatic colorectal cancer and metastatic breast cancer) and in studies of the use of capecitabine in combination of chemotherapy regimens for various indications for application.

The following categories are used to describe the frequency of adverse reactions: very often (? 1/10), often (? 1/100 to <1/10), infrequent (from? 1/1000 to <1/100).

capecitabine monotherapy

The safety profile of capecitabine monotherapy is comparable in patients treated with adjuvant colon cancer and in patients treated with metastatic colorectal cancer and metastatic breast cancer.

Toxicity criteria are in accordance with the National Cancer Institute of Canada (NCIC CTC version 1).

Infections and invasions: adverse reactions associated with bone marrow suppression, dysfunction of the immune system and / or disorders of the mucous membranes, such as local and lethal systemic infections (including bacterial, viral and fungal etiology).

Often – herpes (viral infection), nasopharyngitis, lower respiratory tract infections infrequently – sepsis, urinary tract infections, cellulitis (inflammation of loose tissue), tonsillitis, pharyngitis, oral candidiasis, influenza, gastroenteritis, fungal infection, infection, gum abscess.

Neoplasms, benign, malignant and of uncertain etiology: infrequently – lipoma.

From the side of the blood and lymphatic system: often – anemia, neutropenia; infrequently – febrile neutropenia, pancytopenia, granulocytopenia, thrombocytopenia, leukopenia, hemolytic anemia, increased international normalized ratio (INR) / increased prothrombin time.

From the immune system: infrequently – hypersensitivity reactions.

From the side of metabolism, metabolism: very often – anorexia, often – dehydration, loss of appetite, weight loss, infrequently – diabetes mellitus, hypokalemia, appetite disorders, low nutrition, hypertriglyceridemia.

From the side of the psyche: often – insomnia, depression, rare confusion, acute anxiety with a reaction of panic, depressed mood, decreased libido.

From the nervous system: often – headache, lethargy, dizziness, paresthesia, taste perversion; infrequently – aphasia, memory impairment, ataxia, fainting, balance disorders, sensory disorders, peripheral neuropathy.

From the side of the organs of vision: often – lacrimation, conjunctivitis, irritation; infrequently – decreased visual acuity, diplopia.

On the part of the hearing organs: infrequently – vertigo, ear pain.

From the heart: unstable angina pectoris, angina pectoris, myocardial ischemia, atrial fibrillation, arrhythmia, tachycardia, sinus tachycardia, palpitations.Also, edema of the lower extremities, chest pain, cardiomyopathy, heart failure, sudden death, atrial arrhythmias, including atrial fibrillation, ventricular extrasystoles were recorded.

From the side of the vessels: often – deep vein thrombosis, arterial hypertension, petechiae, arterial hypotension, peripheral cold sensation, thrombophlebitis.

From the respiratory system: often – shortness of breath, nosebleeds, cough, rhinorrhea; infrequently – pulmonary embolism, pneumothorax, hemoptysis, bronchial asthma, shortness of breath on exertion.

From the digestive system: very often – diarrhea, nausea, vomiting, stomatitis, abdominal pain, often – gastrointestinal bleeding, constipation, pain in the upper abdomen, dyspepsia, flatulence, dry mouth rarely – intestinal obstruction, ascites, enteritis , gastritis, dysphagia, pain in the lower abdomen, esophagitis, abdominal discomfort, gastroesophageal reflux disease, colitis, blood in the stool.

From the digestive system: often – hyperbilirubinemia, deviation in the level of functional liver tests; infrequently – jaundice.

On the part of the skin and its derivatives: very often – palmar-plantar syndrome; often – rash, alopecia, erythema, dry skin, itching, hyperpigmentation of the skin, macular rash, peeling of the skin, dermatitis, pigmentation disorders, abnormalities of the nails; infrequently – the formation of skin ulcers, rash, urticaria, photosensitivity, symmetrical non-visible acroeuritema, facial edema, purpura.

From the musculoskeletal system and connective tissue: often – pain in the limbs, back pain, arthralgia infrequently – joint swelling, bone pain, face pain, stiffness of the musculoskeletal system, muscle weakness.

From the urinary system: infrequently – hydronephrosis, urinary incontinence, hematuria, nocturia, increased creatinine levels.

Disorders of the reproductive system and mammary glands: infrequently – vaginal bleeding.

General disorders: very often – weakness, asthenia, often – fever, lethargy, peripheral edema, malaise, chest pain infrequently – edema, chills, flu-like symptoms, fever.

Damage (trauma, wounds), poisoning: infrequently – blisters, overdose.

In this context, under “frequent adverse reactions” in the subsection “capecitabine monotherapy” are indicated severe and / or life-threatening (grade III-IV) adverse reactions or medically significant adverse reactions.

The following adverse reactions are known toxicities with fluoropyrimidine therapy and have been reported as distantly related to capecitabine in less than 5% of patients.

From the digestive system: dry mouth, bloating, adverse reactions associated with inflammation / ulceration of the mucous membranes (esophagitis, gastritis, duodenitis, colitis, gastrointestinal bleeding).

From the heart: edema of the lower extremities, chest pain, including angina pectoris, cardiomyopathy, myocardial ischemia / myocardial infarction, heart failure, tachycardia, atrial arrhythmias, including atrial fibrillation, ventricular extrasystoles, sudden death.

From the nervous system: taste disturbance, insomnia, dizziness, encephalopathy, cerebellar symptoms: ataxia, dysarthria, imbalance, lack of coordination.

Blood and lymphatic system disorders: anemia, bone marrow suppression / pancytopenia.

From the side of the skin and its derivatives: itching, focal peeling, hyperpigmentation of the skin, violation of the structure and discoloration of nails, photosensitivity, a syndrome similar to radiation dermatitis.

General disorders: asthenia, pain in the limbs, lethargy, chest pain (noncardiac).

From the side of the organ of vision: irritation of the mucous membrane of the eyes.

Respiratory system: shortness of breath, cough.

From the musculoskeletal system and connective tissue: back pain, arthralgia, myalgia.

From the side of the psychodepression.

Liver failure and cholestatic hepatitis have been reported during research and post-marketing use. A causal relationship with capecitabine treatment has not been established.

combination therapy

Below are the adverse reactions reported with capecitabine in combination with various chemotherapy regimens for various indications for use in addition to those already registered with monotherapy and / or as observed with a high frequency.The safety profile was similar for all indications and combination treatment regimens. Some adverse reactions are often observed with chemotherapy (for example, peripheral sensory neuropathy with docetaxel or oxaliplatin, hypersensitivity reactions with bevacizumab). However, an increase in these side effects cannot be ruled out when using capecitabine.

Infections and infestations: often – herpes zoster, urinary tract infections, oral candidiasis, upper respiratory tract infections, rhinitis, influenza, infections *, oral herpes.

Blood and lymphatic system disorders: very often – neutropenia *, leukopenia *, febrile fever *, thrombocytopenia *, anemia *; often – bone marrow suppression, febrile neutropenia.

From the immune system: often – hypersensitivity reactions.

From the side of metabolism, metabolism: very often – decreased appetite; often – hypokalemia, weight loss, hyponatremia, hypomagnesemia, hypocalcemia, hyperglycemia.

From the side of the psyche: often – insomnia, anxiety.

From the nervous system: very often – taste disturbance, paresthesia and dysesthesia, peripheral neuropathy, peripheral sensitive neuropathy, taste perversion, headache, neuropathy; often – neurotoxicity, tremor, neuralgia, hypersensitivity reactions, hypesthesia.

From the side of the organs of vision: very often – lacrimation; often – blurred vision, dry eyes, eye pain, blurred vision, blurry vision.

On the part of the hearing organs: infrequently – ringing in the ears, incomplete deafness.

From the side of the heart: often – atrial fibrillation, ischemia / infarction.

From the side of the vessels: very often – edema of the lower extremities, arterial hypertension, thrombosis / embolism *; often – hot flashes, arterial hypotension, hypertensive crisis, hyperemia, phlebitis.

From the respiratory system: very often – angina, pharyngeal dysesthesia, often – hiccups, pharyngolaryngeal pain, dysphonia, nosebleeds, rhinorrhea, shortness of breath.

From the digestive system: very often – constipation, dyspepsia, often – bleeding from the upper gastrointestinal tract, ulcers of the oral mucosa, gastritis, bloating, gastroesophageal reflux disease, pain in the mouth, dysphagia, rectal bleeding, pain in the lower parts abdomen, dysesthesia of the oral cavity, paresthesia of the oral cavity, hypoesthesia of the cavity cavity, abdominal discomfort.

From the digestive system: often – a deviation in the level of liver function tests. From the side of the skin and its derivatives: very often – alopecia, violation of the structure and discoloration of the nails; often – hyperhidrosis, erythematous rash, urticaria, night sweating.

From the musculoskeletal system and connective tissue: very often – arthralgia, myalgia, pain in the extremities; often – jaw pain, back pain, muscle spasms, trismus, muscle weakness.

From the urinary system: often – hematuria, proteinuria, decreased renal creatinine clearance, dysuria.

General disorders: very often – fever, weakness, lethargy *, sensitivity to fever, asthenia, often – inflammation of the mucous membranes, pain in the limbs, pain, chills, chest pain, flu-like symptoms, fever *, infusion reactions , reactions at the injection site, pain at the infusion site, pain at the injection site.

Damage (trauma, wounds), poisoning: often – bruise.

Frequency includes all degrees of severity, with the exception of adverse reactions marked with “*”, which included only III-IV degree adverse reactions.

Hypersensitivity reactions (2%) and cardiac ischemia / myocardial infarction (3%) were often reported when capecitabine was used in combination with other chemotherapeutic agents in less than 5% of patients.

Changes in laboratory parameters (regardless of the connection with the intake of capecitabine): increased ALT / AST activity, increased alkaline phosphatase activity, hypocalcemia, hypercalcemia, granulocytopenia, decreased hemoglobin levels, lymphocytopenia, neutropenia, neutropenia / granulocytopenia, thrombocytopenia, hypokatalemia, hyperkatremia hyperbilirubinemia, hyperglycemia.

Post-marketing experience ki

Very rare – stenosis of the lacrimal duct.

Liver failure and cholestatic hepatitis have been reported very rarely during the study and post-marketing use. A causal relationship with capecitabine treatment has not been established.

Separate by side reactions

Palmar-plantar syndrome

When using capecitabine at a dose of 1250 mg / m ² times a day for 2 weeks with a subsequent break for a week palm-plantar syndrome of all severity in monotherapy (adjuvant therapy for colon cancer, treatment of metastatic colorectal cancer, treatment of breast cancer) was recorded in 53-60% of patients and in 63% of patients with metastatic breast cancer in the capecitabine / docetaxel treatment group.When using capecitabine at a dose of 1000 mg / m2 ² times a day for 2 weeks followed by a one-week break, palm-plantar syndrome of all severity was observed in 22-30% of patients receiving combined treatment with capecitabine.

Palmar-plantar syndrome of all severity with the use of capecitabine in monotherapy or combined treatment with various chemotherapy regimens for various indications for use (colon cancer, colorectal cancer, stomach cancer, breast cancer) occurred in 43% of patients on average after 239 days after starting capecitabine treatment.A covariant increase in the initial dose of capecitabine (in grams), a decrease in the cumulative dose of capecitabine (0.1 * kg), an increase in the relative dose intensity in the first 6 weeks of treatment, an increase in the duration of treatment (weeks ), an increase in the patient’s age (increase by 10 years), female sex, a satisfactory initial general status of the patient (0 versus ≥ 1).

diarrhea

The occurrence of diarrhea during capecitabine treatment was observed in 50% of patients.According to the results of a meta-analysis of 14 clinical studies, the following covariates were statistically significantly associated with an increased risk of diarrhea: an increase in the initial dose of capecitabine (in grams), an increase in the duration of treatment (weeks), an increase in the patient’s age (an increase by 10 years), and female sex. The following covariates were statistically significantly associated with a decrease in the risk of diarrhea: an increase in the cumulative dose of capecitabine (0.1 * kg) and the relative dose intensity in the first 6 weeks of treatment.

cardiotoxicity

In addition to the indicated cardiac adverse reactions, such adverse reactions with a frequency of less than 0.1% were recorded: cardiomyopathy, heart failure, ventricular extrasystoles, sudden death.

encephalopathy

In addition to these adverse reactions, capecitabine monotherapy was associated with encephalopathy with an incidence of less than 0.1%.

Special instructions

Use during pregnancy and lactation

Capecitabine should be considered a potential human teratogen.The use of capecitabine in pregnant women has been studied, however, based on the pharmacological and toxicological properties of the drug, it can be assumed that the use of capecitabine may be harmful to the fetus when used in pregnant women. In reproductive toxicity studies in animals, capecitabine caused embryo and teratogenicity, which are the expected effects of fluoropyrimidine derivatives. Capecitabine should not be used during pregnancy. If capecitabine is prescribed during pregnancy or a patient who is already taking this drug becomes pregnant, she should be warned of the potential risk to the fetus.Women of reproductive age should be advised to avoid pregnancy during capecitabine treatment.

It is not known whether capecitabine penetrates into breast milk. Significant amounts of capecitabine metabolites have been found in the breast milk of lactating animals. Therefore, it is not recommended to breastfeed infants during capecitabine treatment.

Children

The safety and efficacy of capecitabine in children have been studied.

Overdose.Symptoms of acute overdose: nausea, vomiting, diarrhea, mucositis, gastrointestinal irritation and bleeding, and bone marrow suppression. Treatment is symptomatic.

Ability to influence the reaction rate when driving motor transport or other mechanisms

The drug affects the ability to drive vehicles and work with complex mechanisms. Capecitabine may cause dizziness, weakness, and nausea.

Interaction with other medicinal products and other forms of interaction

Coumarin anticoagulants.Capecitabine enhances the effects of indirect anticoagulants (warfarin and phenprocoumon), which can lead to impaired clotting parameters and bleeding within a few days or months from the start of capecitabine therapy, and in some cases – within one month after the end of treatment. In the course of studies, after a single injection of S-warfarin at a dose of 20 mg, capecitabine treatment led to an increase in the AUC of warfarin by 57% and INR by 91%. Since the metabolism of R-warfarin was not impaired, this indicates that capecitabine inhibits the 2C9 isoenzyme and does not affect the 1A2 and 3A4 isoenzymes.In patients who simultaneously take capecitabine and oral anticoagulants – coumarin derivatives, it is necessary to conduct detailed monitoring of blood coagulation parameters (INR or prothrombin time) and select the dose of the anticoagulant.

Substrates of cytochrome P450 2C9. Studies on the interaction of capecitabine and other drugs metabolized by the isoenzyme 2C9 of the cytochrome P450 system have not been conducted. Care must be taken when using capecitabine with these drugs.

Phenytoin.With the simultaneous use of capecitabine and phenytoin, it was reported about individual cases of an increase in the concentration of phenytoin in the blood plasma, accompanied by symptoms of phenytoin intoxication. In patients taking capecitabine concomitantly with phenytoin, it is recommended to regularly monitor the concentration of phenytoin in plasma. Studies on the interaction of capecitabine and phenytoin have not been carried out, however, it is assumed that it is based on inhibition of the CYP2C9 enzyme under the influence of capecitabine.

Leucovorin (folinic acid).Leucovorin does not significantly affect the pharmacokinetics of capecitabine and its metabolites. However, leucovorin affects the pharmacodynamics of capecitabine, which can lead to an increase in the toxicity of the drug: the maximum tolerated dose of capecitabine in monotherapy with an intermittent dosing regimen is 3000 mg / m ² per day, and when combined with leucovorin (30 mg orally twice a day ) – only in 2000 mg / m ² per day.

Sorivudin and its analogues.There is evidence of a clinically significant interaction between sorivudine and 5-FU as a result of inhibition of dihydropyrimidine dehydrogenase by sorivudine. This interaction has the potential to lead to a lethal increase in the toxicity of fluoropyrimidines. Therefore, capecitabine should not be used concomitantly with sorivudine or its structural analogs such as brivudine (see section “Contraindications”). The period between the start of capecitabine treatment and the end of treatment with sorivudine or its structural analogs should be at least 4 weeks.

Antacids. The effect of antacids containing aluminum and magnesium hydroxide on the pharmacokinetics of capecitabine has been studied in patients with tumors. Antacids containing aluminum and magnesium hydroxide (Maalox) slightly increase the concentration of capecitabine and one metabolite (5′-DPCR) in the blood plasma; they do not affect the three main metabolites (5′-DFUR, 5-FU and PBA) of capecitabine.

Allopurinol. An interaction was observed between allopurinol and 5-fluorouracil, with a possible decrease in the effectiveness of 5-fluorouracil.In this regard, the simultaneous use of capecitabine and allopurinol should be avoided.

Interferon alpha. The maximum tolerated dose of capecitabine is 2000 mg / m ² per day when combined with interferon alpha-2a (3 million IU / m ² per day) compared to 3000 mg / m ² per day when using capecitabine in monotherapy regimen.

Radiation therapy. The maximum tolerated dose of capecitabine in monotherapy with an intermittent dosing regimen is 3000 mg / ⁷ per day, when combined with radiation therapy for rectal cancer – 2000 mg / m ² per day with a continuous course of radiation therapy or daily, during the period Monday through Friday, a 6-week course of radiation therapy.

Oxaliplatin. With the combined use of capecitabine and oxaliplatin with or without bevacizumab, there was no clinically significant difference in the exposure of capecitabine or its metabolites, free platinum and total platinum.

Bevacizumab. There was no clinically significant effect of bevacizumab on the pharmacokinetic parameters of capecitabine and its metabolites.

Storage conditions

Store in its original packaging out of reach of children at a temperature not exceeding 25 ° C.

Shelf life – 2 years.

Pay attention!

Description of the drug Apsibin on this page is a simplified author’s version of the apteka911 website, created on the basis of the instructions for use. Before purchasing or using the drug, you should consult your doctor and familiarize yourself with the original manufacturer’s instructions (attached to each package of the drug).

Information about the drug is provided for informational purposes only and should not be used as a guide to self-medication.Only a doctor can decide on the appointment of the drug, as well as determine the doses and methods of its use.

instructions for use, analogs, composition, indications

Inside, washed down with water, no later than 30 minutes after eating.
Standard dosing regimen.
Capecitabine, film-coated tablets, 500 mg, can be used in a standard dosing regimen for an initial dose of 1250 mg / m ² only for patients with a body surface area of ​​ ² ; from 1.53 to 1.66 m ² and from 1.93 to 2.06 m ² :
– Standard dosage for an initial dose of 1250 mg / m ² for patients with body surface area ² – 3 tablets (500 mg) 2 times a day.
– Standard dosage for an initial dose of 1250 mg / m ² for patients with a body surface area from 1.53 to 1.66 m ² – 4 tablets (500 mg) 2 times day.
– Standard dosage for an initial dose of 1250 mg / m ² for patients with a body surface area of ​​1.93 to 2.06 m ² – 5 tablets (500 mg) 2 times day.
Capecitabine, film-coated tablets, 500 mg, can be used in a standard dosing regimen for an initial dose of 1000 mg / m2 ² only for patients with a body surface area of ​​1.93 to 2.06 m2 ² :
– Standard dosage for an initial dose of 1000 mg / m ² for patients with a body surface area of ​​1.93 to 2.06 m ² – 4 tablets (500 mg) 2 times a day.
For all other cases (patients with a different body surface area, the need for dose adjustment (reduction)) Capecitabine, film-coated tablets, 500 mg, cannot provide the recommended dosage regimen, since the required 150 mg tablet is not available , see Tables 1 and 2.
Monotherapy
Colon cancer, colorectal cancer and breast cancer
As monotherapy, the recommended starting dose of capecitabine in the adjuvant treatment of colon cancer, metastatic colorectal cancer, or locally advanced or metastatic breast cancer is 1250 mg / m2 ² administered twice daily (morning and evening; 2500 mg / m2 ² in terms of the total daily dose) for 14 days, followed by an interval of 7 days.For patients with stage III colon cancer, adjuvant therapy is recommended for a total period of 6 months.
Combination therapy
Colon cancer, colorectal cancer and gastrointestinal cancer
As a combination therapy, the recommended starting dose of capecitabine should be reduced to 800-1000 mg / m ² when taken twice a day for 14 days, followed by a suspension for 7 days or to 625 mg / m ² when taken twice once a day with prolonged use.In combination with irinotecan, the recommended initial dose is 800 mg / m ² when applied twice a day for 14 days, followed by an interval of 7 days in combination with irinotecan 200 mg / m ² in 1 day. The inclusion of bevacizumab in the combination regimen does not affect the starting dose of capecitabine. Patients receiving combination therapy with cisplatin and capecitabine are advised to undergo premedication to maintain adequate water balance and prescribe antiemetic drugs according to the cisplatin medical instructions before prescribing this drug.Antiemetic premedication is recommended for patients receiving combination therapy with oxaliplatin and capecitabine prior to oxaliplatin. For patients with stage III colon cancer, adjuvant therapy is recommended for a total period of 6 months.
Breast cancer
In combination with docetaxel, the recommended starting dose of capecitabine for the treatment of metastatic breast cancer is 1250 mg / m2 ² twice daily for 14 days, followed by a 7-day suspension in combination with 75 mg / m2 docetaxel ² c as an hourly intravenous infusion every 3 weeks.Premedication is recommended by taking corticosteroids such as oral dexamethasone according to the docetaxel drug label for patients receiving a combination of capecitabine and docetaxel.
Calculation of the dose for the drug Capecitabine.
Table 1. Standard and reduced dose Capecitabine for an initial dose of 1250 mg / m ² , calculated as a function of body surface area

Table 2.Standard and reduced dose Capecitabine for an initial dose of 1000 mg / m2 ² calculated as a function of body surface area

Legend:
* Usage Capecitabine, film-coated tablets, 500 mg, cannot provide the recommended dosing regimen.
Dose adjustment during treatment
General recommendations
The toxicity associated with capecitabine can be reduced by symptomatic treatment and / or dose adjustments (interruption of treatment or dose reduction). When the dose is reduced, its level should not increase further. For those toxicity levels that, in the opinion of the attending physician, do not pose a serious threat or threat to the patient’s life, for example, alopecia, taste disturbances, changes in the nail plates, treatment should be continued at the same dose without reducing or stopping treatment.Patients taking capecitabine should be advised to stop treatment immediately if moderate to severe toxicity occurs. Doses of capecitabine that have been missed due to toxicity are not substituted. Recommended dosage changes due to toxicity are listed below:
Table 3. Capecitabine dosage reduction plan (3-week course of treatment or long-term treatment)

* According to the General Criteria of Toxicity (version 1) of the Clinical Research Group of the National Cancer Institute of Canada (NCIC CTG) or the Common Terminological Criteria for Adverse Events (CTSAE) or Cancer Therapy Evaluation Program, US National Cancer Institute, version 4 …0. Information on the palmar-plantar syndrome and elevated serum bilirubin content is described in detail in the “Special Instructions” section
Hematology
For patients with a baseline neutrophil count of ⁹ / L and / or platelets ⁹ / L, the use of capecitabine is contraindicated. If the results of unscheduled laboratory tests during the course of treatment reveal the number of neutrophils below 1.0 × 10 ⁹ / L or the number of platelets below 75 × 10 ⁹ / L, then the use of capecitabine should be discontinued.
Dose change due to toxicity when using capecitabine over a 3-week course of treatment in combination with other drugs.
Dosage adjustments due to toxicity when using capecitabine during a 3-week course of treatment in combination with other drugs should be made in accordance with Table 3 above for capecitabine and in accordance with the medical instructions for the other drug (s). (s) funds (funds).
At the initial stage of treatment, if a break in the use of either capecitabine or other drug (s) is indicated, all therapy should be suspended until the conditions allowing the resumption of use of all drugs are met.
During the course of treatment, in the event of toxic effects that, in the opinion of the attending physician, are not associated with the use of capecitabine, the administration of capecitabine should be continued, while the dose of the other drug should be adjusted in accordance with the appropriate instructions for medical use.
If the other drug (s) is canceled permanently, capecitabine treatment may be resumed, provided that all capecitabine resumption requirements are met.
This recommendation applies to all indications and all individual populations.
Dose change due to toxicity with prolonged use of capecitabine in combination with other drugs.
Dose changes due to toxicity with long-term use of capecitabine in combination with other drugs should be carried out in accordance with Table 3 above for capecitabine and in accordance with the instructions for medical use for the other drug (s) ( funds).
Dose adjustment in special cases.
Liver dysfunction
There is no adequate information on safety and efficacy in patients with impaired liver function to recommend dose adjustment. There is no information on liver dysfunction caused by cirrhosis or hepatitis.
Functional impairment and kidney
Capecitabine is contraindicated in patients with severe renal impairment (baseline creatine clearance below 30 ml / min [Cockcroft and Gault]).The incidence of grade 3 or 4 adverse reactions in patients with moderate renal impairment (baseline creatine clearance 30-50 ml / min) is increased compared to the general population. In patients with moderate renal impairment, it is recommended to reduce the starting dose of 1250 mg / m ² by 75%. A reduction in the starting dose of 1000 mg / m ² is not required in patients with moderate renal impairment. In patients with mild renal impairment (baseline creatine level 51-80 ml / min), dose adjustment is not required.Careful monitoring and prompt decision-making on the interruption of therapy is recommended in patients with the development of adverse reactions of 2, 3 and 4 degrees, and the corresponding dose adjustment, as shown in Table 3. With a decrease in creatine levels during treatment below 30 ml / min, taking the drug capecitabine should stop. These recommendations for dose adjustment in renal impairment apply to both monotherapy and combination therapy (see the Elderly Patients section below).
Elderly patients
There is no need to adjust the starting dose during capecitabine monotherapy. However, treatment-related grade 3 or 4 adverse reactions are more common in patients ≥ 60 years of age than in younger patients.
When capecitabine is used in combination with other drugs, elderly patients (≥ 65 years) develop a greater number of grade 3 and 4 adverse events, including reactions leading to an interruption in therapy, compared with younger patients.Close monitoring of patients ≥ 60 years of age is recommended.
– In combination with docetaxel: in patients aged 60 years and older, there was an increased incidence of treatment-related grade 3 or 4 adverse reactions and therapy-related severe adverse reactions (see Pharmacodynamics section). For patients aged 60 years and older, a reduction of the initial dose of up to 75% (950 mg / m ² twice a day) is recommended.If there are no signs of toxicity in patients ≥ 60 years of age who have used a reduced starting dose of capecitabine in combination with docetaxel, the dose of capecitabine can be gradually increased to 1250 mg / m2 ² twice daily.
Children
There are no data on the use of capecitabine in the pediatric population for indications of colon cancer, colorectal cancer and breast cancer. 90,000 website for online appointment with doctors, analysis and booking procedures.

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