What are the common side effects of leflunomide 10 mg. How to manage potential adverse reactions to leflunomide. When to seek medical attention for leflunomide side effects. What precautions should be taken while using leflunomide 10 mg.

Understanding Leflunomide and Its Therapeutic Uses

Leflunomide is a disease-modifying antirheumatic drug (DMARD) primarily used to treat rheumatoid arthritis and psoriatic arthritis. It works by reducing inflammation and slowing down joint damage. The standard dosage is often 10 mg once daily, though this may vary based on individual patient needs and medical conditions.

How does leflunomide work in the body? Leflunomide inhibits an enzyme called dihydroorotate dehydrogenase, which is crucial for the rapid multiplication of certain cells involved in inflammation. By doing so, it helps reduce the overactive immune response associated with rheumatoid arthritis.

Common Side Effects of Leflunomide 10 mg

While leflunomide can be highly effective in managing rheumatoid arthritis, it may cause various side effects. It’s important to note that not everyone experiences these side effects, and their severity can vary from person to person. Some of the more common side effects include:

• Diarrhea
• Nausea and vomiting
• Loss of appetite
• Headache
• Dizziness
• Hair loss
• Skin rash
• Weight loss
• Back pain
• Heartburn

Are these side effects permanent? In many cases, these side effects are temporary and may subside as your body adjusts to the medication. However, if they persist or worsen, it’s crucial to consult your healthcare provider.

Serious Side Effects Requiring Immediate Medical Attention

While less common, some side effects of leflunomide 10 mg can be more severe and require prompt medical attention. These include:

• Yellowing of the skin or eyes (jaundice)
• Severe abdominal pain
• Persistent fever or signs of infection
• Unusual bleeding or bruising
• Chest pain or rapid heartbeat
• Difficulty breathing or tightness in the chest
• Severe skin reactions (blistering, peeling)
• Signs of liver problems (dark urine, persistent nausea/vomiting, loss of appetite)

When should you seek emergency medical care while taking leflunomide? If you experience any of the above symptoms or any other severe or unusual reactions, it’s crucial to seek immediate medical attention. These could be signs of serious complications that require prompt treatment.

Gastrointestinal Side Effects and Management

Gastrointestinal issues are among the most commonly reported side effects of leflunomide. These may include:

1. Diarrhea
2. Nausea
3. Vomiting
4. Abdominal pain
5. Indigestion

How can you manage gastrointestinal side effects of leflunomide? Here are some strategies that may help:

• Take the medication with food to reduce stomach upset
• Stay well-hydrated to combat diarrhea
• Eat smaller, more frequent meals
• Avoid spicy, fatty, or hard-to-digest foods
• Consider over-the-counter antidiarrheal medications (after consulting your doctor)

If gastrointestinal symptoms persist or become severe, it’s important to consult your healthcare provider. They may adjust your dosage or recommend additional treatments to manage these side effects.

Hematological and Immunological Concerns

Leflunomide can affect blood cell production and immune function, potentially leading to:

• Increased risk of infections
• Anemia
• Decreased white blood cell count (leukopenia)
• Decreased platelet count (thrombocytopenia)

Why is regular blood monitoring important while taking leflunomide? Regular blood tests are crucial to monitor for these potential effects. Your doctor will likely schedule periodic blood tests to check your blood cell counts and liver function. This allows for early detection and management of any abnormalities.

Infection Risk and Precautions

Due to its immunosuppressive effects, leflunomide may increase your susceptibility to infections. It’s important to:

• Practice good hygiene
• Avoid close contact with people who have contagious illnesses
• Report any signs of infection (fever, chills, persistent sore throat) to your doctor promptly
• Ensure you’re up to date on recommended vaccinations (discuss with your doctor before receiving any live vaccines)

Dermatological and Hair-related Side Effects

Leflunomide can sometimes cause skin-related side effects, including:

• Skin rash
• Itching
• Acne
• Hair loss (alopecia)

Is hair loss from leflunomide permanent? Hair loss associated with leflunomide is usually temporary and reversible. Hair growth typically resumes once the medication is stopped or the body adjusts to it. However, if hair loss is significant or distressing, discuss it with your healthcare provider.

Managing Skin-related Side Effects

To manage skin-related side effects:

• Use gentle, fragrance-free skincare products
• Avoid hot showers or baths, which can dry out the skin
• Apply moisturizer regularly
• Protect your skin from sun exposure
• Consult your doctor about topical treatments if needed

Cardiovascular and Respiratory Considerations

While less common, leflunomide can occasionally affect the cardiovascular and respiratory systems. Potential effects include:

• Hypertension (high blood pressure)
• Chest pain
• Palpitations
• Shortness of breath
• Cough

How often should blood pressure be monitored while taking leflunomide? Regular blood pressure monitoring is recommended for patients on leflunomide. Your doctor may advise checking your blood pressure at home or during office visits. If you have a history of cardiovascular issues, more frequent monitoring may be necessary.

Respiratory Precautions

Patients with pre-existing lung conditions should be closely monitored while taking leflunomide. Report any new or worsening respiratory symptoms to your healthcare provider immediately.

Neurological Side Effects and Cognitive Impacts

Leflunomide can sometimes affect the nervous system, leading to neurological side effects such as:

• Headache
• Dizziness
• Peripheral neuropathy (tingling or numbness in hands and feet)
• Anxiety
• Confusion (rare)

Can leflunomide affect cognitive function? While cognitive effects are not commonly reported, some patients may experience difficulty concentrating or mild confusion. If you notice any significant changes in your cognitive function, discuss this with your healthcare provider.

Managing Neurological Side Effects

To manage neurological side effects:

• Ensure adequate rest and sleep
• Practice stress-reduction techniques
• Avoid alcohol and other substances that may exacerbate dizziness or confusion
• Report any persistent or severe symptoms to your doctor

Interactions with Other Medications and Substances

Leflunomide can interact with various medications and substances, potentially altering its effectiveness or increasing the risk of side effects. Some notable interactions include:

• Other immunosuppressants
• Certain antibiotics
• Cholesterol-lowering medications
• Warfarin and other blood thinners
• NSAIDs (in high doses)

Why is it crucial to inform your healthcare provider about all medications and supplements you’re taking? Full disclosure of your medication regimen, including over-the-counter drugs and herbal supplements, is essential to prevent potentially harmful interactions. Your doctor can assess the risks and adjust your treatment plan accordingly.

Alcohol and Leflunomide

Alcohol consumption should be limited or avoided while taking leflunomide, as both can affect liver function. Discuss safe alcohol consumption limits with your healthcare provider.

Pregnancy, Breastfeeding, and Fertility Considerations

Leflunomide is contraindicated during pregnancy due to the potential risk of birth defects. Women of childbearing age should use effective contraception while taking leflunomide and for a period after discontinuation.

How long should contraception be continued after stopping leflunomide? Due to the long half-life of leflunomide, contraception should be continued for at least two years after stopping the medication, unless a drug elimination procedure is performed.

Breastfeeding

Leflunomide is not recommended during breastfeeding, as it may pass into breast milk and potentially harm the infant. Discuss alternative feeding options with your healthcare provider if you’re considering breastfeeding.

Fertility

While the effects of leflunomide on human fertility are not fully known, animal studies have shown potential impacts on male fertility. If you’re planning to conceive, discuss this with your doctor well in advance.

Long-term Use and Monitoring

Long-term use of leflunomide requires ongoing monitoring to ensure safety and effectiveness. This typically includes:

• Regular blood tests to check liver function and blood cell counts
• Blood pressure monitoring
• Periodic assessment of kidney function
• Monitoring for signs of infection or other adverse effects

How often should follow-up appointments be scheduled while on leflunomide? The frequency of follow-up appointments and tests can vary based on individual factors, but typically, more frequent monitoring is needed in the first few months of treatment, followed by less frequent (but regular) check-ups thereafter.

Discontinuation and Washout Procedures

If leflunomide needs to be discontinued due to side effects or other reasons, a washout procedure may be recommended to rapidly eliminate the drug from the body. This typically involves taking cholestyramine or activated charcoal for a specified period.

Alternative Treatments and Combination Therapies

For patients who cannot tolerate leflunomide or experience inadequate response, alternative treatments or combination therapies may be considered. These might include:

• Other DMARDs (e.g., methotrexate, sulfasalazine)
• Biologic agents (e.g., TNF inhibitors, IL-6 inhibitors)
• JAK inhibitors
• Combination therapy with leflunomide and other DMARDs

How do combination therapies compare to leflunomide monotherapy in terms of efficacy and side effects? Combination therapies can sometimes offer improved efficacy, but they may also increase the risk of side effects. The choice of treatment should be individualized based on the patient’s specific condition, comorbidities, and response to previous treatments.

Lifestyle Modifications

In addition to medication, lifestyle modifications can play a crucial role in managing rheumatoid arthritis and minimizing side effects. These may include:

• Regular exercise and physical therapy
• Stress management techniques
• Healthy diet rich in anti-inflammatory foods
• Adequate rest and sleep
• Smoking cessation

Leflunomide (Oral Route) Side Effects

Side Effects

Drug information provided by: IBM Micromedex

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

1. 
   Bloody or cloudy urine
2. 
   cough
3. 
   difficult or painful breathing
4. 
   difficult, burning, or painful urination
5. 
   dizziness
6. 
   fever
7. 
   frequent urge to urinate
8. 
   headache
9. 
   loss of appetite
10. 
    nausea or vomiting
11. 
    sneezing
12. 
    sore throat
13. 
    tightness in the chest
14. 
    yellow eyes or skin

Less common

1. 
   Burning feeling in the chest or stomach
2. 
   burning, prickling, or tingling sensation in the fingers or toes
3. 
   chest pain
4. 
   diarrhea
5. 
   fast or pounding heartbeat
6. 
   indigestion
7. 
   joint or muscle pain or stiffness
8. 
   severe stomach pain
9. 
   tenderness in the stomach area
10. 
    unusual tiredness or weakness

Incidence not known

1. 
   Area rash
2. 
   black or tarry stools
3. 
   bleeding gums
4. 
   blistering, peeling, or loosening of the skin
5. 
   bloating
6. 
   blood in the stools
7. 
   burning, numbness, tingling, or painful sensations
8. 
   chills
9. 
   clay-colored stools
10. 
    confusion
11. 
    constipation
12. 
    continuing vomiting
13. 
    cough or hoarseness
14. 
    dark urine
15. 
    fainting
16. 
    fever with or without chills
17. 
    general feeling of tiredness or weakness
18. 
    high fever
19. 
    large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
20. 
    light-colored stools
21. 
    lightheadedness
22. 
    lower back or side pain
23. 
    pains in the stomach, side, or abdomen, possibly radiating to the back
24. 
    pale skin
25. 
    pinpoint red spots on the skin
26. 
    rapid, shallow breathing
27. 
    red skin lesions, often with a purple center
28. 
    red, irritated eyes
29. 
    sores, ulcers, or white spots in the mouth or on the lips
30. 
    swollen glands
31. 
    unexplained bleeding or bruising
32. 
    unpleasant breath odor
33. 
    unsteadiness or awkwardness
34. 
    unusual bleeding or bruising
35. 
    upper right abdominal or stomach pain
36. 
    vomiting of blood
37. 
    weakness in the arms, hands, legs, or feet

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

1. 
   Back pain
2. 
   hair loss
3. 
   heartburn
4. 
   skin rash
5. 
   stomach pain
6. 
   weight loss (unexplained)

Less common

1. 
   Acne
2. 
   anxiety
3. 
   decreased appetite
4. 
   dry mouth
5. 
   gas
6. 
   irritation or soreness of the mouth
7. 
   itching of the skin
8. 
   pain or burning in the throat
9. 
   runny nose

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Portions of this document last updated: July 01, 2021

Copyright © 2021 IBM Watson Health. All rights reserved. Information is for End User’s use only and may not be sold, redistributed or otherwise used for commercial purposes.

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leflunomide oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing

Diarrhea, nausea, and dizziness may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if you have any serious side effects, including: cough, numbness/tingling of hands/feet, hair loss, chest pain, fast/pounding heartbeat, increased thirst/urination, muscle cramp/pain, mental/mood changes, vision changes, easy bruising/bleeding, unusual growths/lumps, unexplained weight loss, unusual tiredness.

This medication may raise your blood pressure. Check your blood pressure regularly and tell your doctor if the results are high.

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. Get medical help right away if you have any signs of infection (such as sore throat that doesn’t go away, fever, swollen lymph nodes, chills).

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, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

Leflunomide can commonly cause a mild rash that is usually not serious. However, you may not be able to tell it apart from a rare rash that could be a sign of a severe allergic reaction. Get medical help right away if you develop any rash.

This is not a complete list of possible side effects. If you notice other 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.

Leflunomide: MedlinePlus Drug Information

Do not take leflunomide if you are pregnant or plan to become pregnant. Leflunomide may harm the fetus. You should not begin taking leflunomide until you have taken a pregnancy test with negative results and your doctor tells you that you are not pregnant. You must use an effective method of birth control before you begin taking leflunomide, during your treatment with leflunomide, and for 2 years after treatment. If your period is late or you miss a period during treatment with leflunomide, call your doctor immediately. Talk to your doctor if you plan to become pregnant within 2 years after stopping treatment with leflunomide. Your doctor can prescribe a treatment that will help to remove this medication more quickly from your body.

Leflunomide may cause liver damage that can be life-threatening and even cause death. The risk for liver damage is greatest in people taking other medications known to cause liver damage, and in people who already have liver disease. Tell your doctor if you have or have ever had hepatitis or any other type of liver disease and if you if you drink or have ever drunk large amounts of alcohol. Tell your doctor and pharmacist if you are taking acetaminophen (Tylenol, in other over-the-counter products), aspirin and other nonsteroidal anti-inflammatory medications (NSAIDs such as ibuprofen [Advil, Motrin] and naproxen [Aleve, Naprosyn], cholesterol-lowering medications (statins), hydroxychloroquine, iron products, isoniazid (Laniazid, in Rifamate, in Rifater), methotrexate (Trexall), niacin (nicotinic acid), or rifampin (Rifadin, Rimactane, in Rifamate, in Rifater). If you experience any of the following symptoms, call your doctor immediately: nausea, extreme tiredness, unusual bleeding or bruising, lack of energy, loss of appetite, pain in the upper right part of the stomach, yellowing of the skin or eyes, dark-colored urine, or flu-like symptoms.

Keep all appointments with your doctor and the laboratory. Your doctor will order certain tests to check your body’s response to leflunomide.

Talk to your doctor about the risks of taking leflunomide.

Leflunomide| Side-effects, uses, time to work

You may find your body adjusts to leflunomide without any side effects. Some people find it gives them loose bowel movements or diarrhoea (dy-a-ree-ah) but this usually settles down after a couple of weeks.

Other side effects include:

• feeling sick
• mouth ulcers
• weight loss
• stomach pain
• unusual tiredness
• headaches
• dizziness
• weakness or pins and needles
• dry skin or a rash
• a slight rise in blood pressure.

Some people do experience hair loss, but this is quite rare and usually minor.

Speak to your doctor or rheumatology nurse as soon as possible if you experience any of these side effects or any other changes that concern you.

Leflunomide reduces the amount of blood cells your body makes, which means you could pick up infections more easily.

Tell your doctor or rheumatology nurse straight away if you develop any signs of infection, such as:

• a sore throat or fever
• any unexplained bruising or bleeding
• breathlessness
• jaundice, when the eyes and skin turn yellow
• any other symptoms that worry you.

Tips to reduce your risk of infection

• Try to avoid close contact with people you know have an infection.
• Wash your hands regularly and carry around a small bottle of antibacterial hand gel.
• Keep your mouth clean by brushing your teeth regularly.
• Stop smoking if you’re a smoker.
• Make sure your food is stored and prepared properly.
• Try to keep your house clean and hygienic, especially the kitchen, bathrooms and toilets.

Chickenpox and shingles

You should also see your doctor if you come into contact with anyone who has chickenpox or shingles, or if you develop chickenpox or shingles yourself.

These viruses can affect you badly when you’re taking leflunomide. You may need antiviral treatment, and your leflunomide may be stopped until you’re better.

Liver problems

Leflunomide can affect your liver.

You’ll have regular blood tests throughout your treatment to check for any changes in how your liver is working.

If you have any history of liver problems, you must tell your doctor before they prescribe you leflunomide. If you have a serious liver problem, it’s unlikely you’ll be prescribed leflunomide.

Allergies

Talk to your doctor if you’re lactose intolerant or allergic to peanuts or soya. Some leflunomide tablets have a lactose coating. And some contain a substance called lecithin, which can be harmful to people allergic to peanuts or soya.

Skin reactions

If you have psoriasis and find your skin becomes inflamed or infected once you’ve started taking leflunomide, speak to your doctor.

What if I experience side effects?

Talk to your doctor or rheumatology nurse if you feel you’re experiencing side effects or a reaction to the treatment. If you have a bad reaction to leflunomide your doctor may suggest you stop the drug.

What if I have a bad reaction to leflunomide?

If your doctor thinks your reaction is serious they may suggest you have a washout treatment to remove the leflunomide from your body quickly.

A washout treatment consists of taking either activated powdered charcoal or a drug called cholestyramine (co-la-sti-ra-meen) for 11 days. These should rapidly flush the leflunomide out of your body.

You may have blood tests during the treatment to make sure the level of leflunomide in your body is dropping. If it doesn’t drop enough you will probably be given a second washout.

If you just stop taking leflunomide it can stay in your body for up to two years, unless you receive a washout treatment.

You will also be recommended to have a washout treatment to remove leflunomide from your body quickly if:

• you become pregnant or want to start a family
• you need to start another treatment which could interact with leflunomide.

Sandoz Leflunomide – Uses, Side Effects, Interactions

How does this medication work? What will it do for me?

Leflunomide belongs to the class of medications called immunomodulators. It is used to treat some of the symptoms associated with rheumatoid arthritis, such as inflammation, swelling, stiffness, and joint pain. It works by blocking the body’s ability to produce the immune cells that cause these problems.

This medication may be available under multiple brand names and/or in several different forms. Any specific brand name of this medication may not be available in all of the forms or approved for all of the conditions discussed here. As well, some forms of this medication may not be used for all of the conditions discussed here.

Your doctor may have suggested this medication for conditions other than those listed in these drug information articles. If you have not discussed this with your doctor or are not sure why you are taking this medication, speak to your doctor. Do not stop taking this medication without consulting your doctor.

Do not give this medication to anyone else, even if they have the same symptoms as you do. It can be harmful for people to take this medication if their doctor has not prescribed it.

What form(s) does this medication come in?

10 mg
Each white, circular, biconvex, film-coated tablet, plain on one side and debossed “L10” on the other side, contains 10 mg of leflunomide. Nonmedicinal ingredients: cornstarch, colloidal silicon dioxide, hydroxypropyl cellulose, hydroxypropyl methylcellulose, lactose anhydrous, lactose monohydrate, magnesium stearate, polyethylene glycol, povidone, and titanium dioxide.

20 mg
Each light yellow, triangular, biconvex, film-coated tablet, plain on one side and debossed “L20” on the other side, contains 20 mg of leflunomide. Nonmedicinal ingredients: cornstarch, colloidal silicon dioxide, hydroxypropyl cellulose, hydroxypropyl methylcellulose, lactose anhydrous, lactose monohydrate, magnesium stearate, polyethylene glycol, povidone, titanium dioxide, and yellow ferric oxide.

How should I use this medication?

The recommended starting dose of leflunomide is 100 mg once daily for the first 3 days, followed by 20 mg once a day.

Many things can affect the dose of medication that a person needs, such as body weight, other medical conditions, and other medications. If your doctor has recommended a dose different from the ones listed here, do not change the way that you are taking the medication without consulting your doctor.

Leflunomide may be taken with or without food, but it should be taken at the same time every day with a full glass of water or other fluid.

This medication should be taken on a regular basis for it to work effectively. It may take up to a month to see any benefit, and 4 to 6 months to get the maximum benefit of this medication.

It is important to take this medication exactly as prescribed by your doctor. If you miss a dose, take it as soon as possible and continue with your regular schedule. If it is almost time for your next dose, skip the missed dose and continue with your regular schedule. Do not take a double dose to make up for a missed one. If you are not sure what to do after missing a dose, contact your doctor or pharmacist for advice.

Store this medication at room temperature, away from direct light and moisture. Keep it out of the reach of children.

Do not dispose of medications in wastewater (e.g. down the sink or in the toilet) or in household garbage. Ask your pharmacist how to dispose of medications that are no longer needed or have expired.

Who should NOT take this medication?

Do not take this medication if you:

• are allergic to leflunomide, teriflunomide, or any ingredients of the medication
• are pregnant or may become pregnant, unless you use reliable contraception before, during, and for a period of 2 years after treatment with leflunomide
• are breast-feeding
• are under 18 years old
• have an immunodeficiency due to causes other than rheumatoid arthritis (e.g., AIDS, transplant recipients taking medications that suppress the immune system)
• have an impaired bone marrow function or other blood disorders due to causes other than rheumatoid arthritis
• have extremely low levels of protein in the blood
• have impaired liver function
• have moderate-to-severe kidney function impairment
• have severe infections










What side effects are possible with this medication?




Many medications can cause side effects. A side effect is an unwanted response to a medication when it is taken in normal doses. Side effects can be mild or severe, temporary or permanent.

The side effects listed below are not experienced by everyone who takes this medication. If you are concerned about side effects, discuss the risks and benefits of this medication with your doctor.

The following side effects have been reported by at least 1% of people taking this medication. Many of these side effects can be managed, and some may go away on their own over time.

Contact your doctor if you experience these side effects and they are severe or bothersome. Your pharmacist may be able to advise you on managing side effects.

• dizziness
• dry skin
• hair loss
• headache
• itching of the skin
• loss of appetite
• mild diarrhea
• nausea
• sensation of tingling skin
• stomach pain
• unexplained weight loss
• vomiting
• weakness

Although most of the side effects listed below don’t happen very often, they could lead to serious problems if you do not seek medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

• fast or pounding heartbeat
• fever
• increased blood pressure
• mouth sores
• nausea or vomiting
• severe diarrhea with or without blood in the stool
• severe stomach pain
• signs of bleeding (e.g., bloody nose, blood in urine or stools, coughing blood, cuts that don’t stop bleeding, unusual bleeding or bruising, black, tarry stools)
• signs of decreased red blood cells (anemia; e.g., pale skin, fatigue, shortness of breath, rapid heartbeat)
• signs of infection (e.g., cough, fever or chills, severe diarrhea, shortness of breath, prolonged dizziness, headache, stiff neck, weight loss, or listlessness)
• signs of liver problems (e.g., nausea, vomiting, diarrhea, loss of appetite, weight loss, yellowing of the skin or whites of the eyes, dark urine, pale stools)
• tendon pain or swelling
• swelling of feet or lower legs
• unusual tiredness or weakness
• vision changes
• worsening arthritis symptoms (e.g., joint pain or stiffness)

Stop taking the medication and seek immediate medical attention if any of the following occur:

• signs of a serious allergic reaction (e.g., abdominal cramps, difficulty breathing, nausea and vomiting, or swelling of the face and throat)
• signs of a severe skin reaction (e.g., blistering, peeling, a rash covering a large area of the body, a rash that spreads quickly, or a rash combined with fever or discomfort)
• signs of serious breathing problems (interstitial lung disease; e.g., new or worsening shortness of breath with or without fever; new or worsening cough with or without fever, difficult or painful breathing, chest congestion)

Some people may experience side effects other than those listed. Check with your doctor if you notice any symptom that worries you while you are taking this medication.









Are there any other precautions or warnings for this medication?




Before you begin using a medication, be sure to inform your doctor of any medical conditions or allergies you may have, any medications you are taking, whether you are pregnant or breast-feeding, and any other significant facts about your health. These factors may affect how you should use this medication.

Alcohol: The liver helps to break down leflunomide into chemicals that are active in the body. Alcohol is also broken down by the liver. The combination of leflunomide and alcohol may result in more harm to the liver than if either one were used on its own. To reduce the risk of severe liver injury, you should avoid alcohol during treatment with leflunomide.

Birth defects: Leflunomide can cause birth defects in children whose fathers were using it at the time of conception. For this reason, a man planning a family must first stop taking the medication and consult with his doctor. Otherwise, he should use condoms during sexual intercourse.

If either partner is taking leflunomide, a reliable method of birth control should always be used throughout the course of treatment with leflunomide. Women should avoid pregnancy, and men should avoid fathering a child for 2 years after taking leflunomide (or for as long as a certain level of the medication and its byproducts remain in the body).

Blood clotting: This medication can reduce the number of platelet cells in the blood. Platelets help the blood to clot, and a shortage could make you bleed more easily. Tell your doctor of any signs that your blood is not clotting as quickly. Such symptoms may include black and tarry stools.

Blood pressure: Leflunomide frequently causes increased blood pressure. For this reason, it is important to monitor your blood pressure on a regular basis while taking this medication.

Infection: Leflunomide works on the immune system to help reduce the damage that parts of the immune system cause to the body. It can reduce the number of cells that fight infection in the body (white blood cells). As a result, leflunomide may reduce the body’s ability to fight severe infections.

Tell your doctor immediately if you notice signs of an infection, such as fever or chills, severe diarrhea, shortness of breath, prolonged dizziness, headache, stiff neck, weight loss, or listlessness. Your doctor will do regular blood tests to monitor the number of specific types of blood cells in your blood.

Avoid immunizations without your doctor’s approval.

Kidney function: The kidneys help to remove this medication from the body. When the kidneys are not working well, leflunomide can build up in the body and cause serious side effects. If you have reduced kidney function or kidney disease, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

This medication should not be used by anyone who has moderately to severely reduced kidney function.

Liver function: Leflunomide can cause damage to the liver, including liver failure, and should not be used by anyone who has reduced liver function or liver disease.

If you experience symptoms of liver problems such as fatigue, feeling unwell, loss of appetite, nausea, yellowing of the skin or whites of the eyes, dark urine, pale stools, abdominal pain or swelling, and itchy skin, contact your doctor immediately.

Lung inflammation: Lung inflammation (interstitial lung disease), causing difficulty breathing has occurred rarely in some people taking this medication. This complication can be serious and sometimes fatal. If you experience new or worsening shortness of breath or cough (with or without fever) at any time while you are taking leflunomide contact your doctor immediately.

Red blood cells: Leflunomide may cause low levels of red blood cells. If you experience symptoms of reduced red blood cell count (anemia) such as shortness of breath, feeling unusually tired, or pale skin, contact your doctor as soon as possible.

Pregnancy: This medication is likely to cause serious harm and birth defects to the unborn baby if it is taken by a pregnant mother. It is important that leflunomide is not used during pregnancy or by women who may become pregnant. If you become pregnant while taking this medication, contact your doctor immediately.

Breast-feeding: This medication may pass into breast milk. If you are a breast-feeding mother and are taking leflunomide it may affect your baby. Due to the seriousness of the effects that a breast-feeding infant would experience, women taking this medication should be advised not to breast-feed.

Children: The safety and effectiveness of leflunomide has not been established for children under the age of 18 years.







What other drugs could interact with this medication?




There may be an interaction between leflunomide and any of the following:

• activated charcoal
• alcohol
• amiodarone
• azathioprine
• BCG
• cancer chemotherapy (e.g., cisplatin, cytarabine, doxorubicin, nivolumab, paclitaxel, vincristine)
• cholestyraminecolesevelam
• colestipol
• corticosteroids (e.g., budesonide, hydrocortisone, prednisone)
• cyclosporine
• denosumab
• echinacea
• enzalutamide
• erlotinib
• fluoxetine
• other immunosuppressants (e.g., etanercept, fingolimod, hydroxychlorquine, infliximab, mycophenolate)
• imiquimod
• lenalidomide
• methotrexate
• natalizumab
• pimecrolimus
• pioglitazone
• repaglinide
• rifampin
• rituximab
• roflumilast
• romidepsin
• rosiglitazone
• tacrolimus
• teriflunomide
• tofacitinib
• trastuzumab
• tretinoin
• vaccines
• warfarin
• zopiclone

If you are taking any of these drugs, speak with your doctor or pharmacist. Depending on your specific circumstances, your doctor may want you to:

• stop taking one of the medications,
• change one of the medications to another,
• change how you are taking one or both of the medications, or
• leave everything as is.

An interaction between two medications does not always mean that you must stop taking one of them. Speak to your doctor about how any drug interactions are being managed or should be managed.

Medications other than those listed above may interact with this medication. Tell your doctor or prescriber about all prescription, over-the-counter (non-prescription), and herbal medications that you are taking. Also tell them about any supplements you take. Since caffeine, the nicotine from cigarettes, or street drugs can affect the action of many medications, you should let your prescriber know if you use them.

All material copyright MediResource Inc. 1996 – 2021. Terms and conditions of use. The contents herein are for informational purposes only. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Source: www.medbroadcast.com/drug/getdrug/Sandoz-Leflunomide

Arava (leflunomide) dosing, indications, interactions, adverse effects, and more

Leflunomide (Arava)

Leflunomide can cause serious birth defects. If you are pregnant or are considering having a child, you should discuss this issue with your rheumatology provider before beginning the medication. For this reason, it usually is not prescribed to young women. Breastfeeding while taking leflunomide is not recommended. Use of an effective form of birth control is critical throughout the course of this treatment and for up to two years after it is stopped. This is important, because leflunomide lasts in the body a long time, even after stopping the medication, and could still cause birth defects during this time. Men taking leflunomide who wish to have a child also should talk with their rheumatology provider about how to discontinue the medication. Cholestyramine is a medication you can take to help remove leflunomide from your system.

Be sure to tell your rheumatology provider about all of the medications you are taking, including over-the-counter drugs and natural remedies, as these may reduce the effectiveness of leflunomide. The following medications are among those that may interfere with leflunomide: cholestyramine (Questran), tolbutamide (Orinase), and rifampin (Rifadin or Rimactane). Any medications that can affect the liver should be used with caution with leflunomide.

Live vaccinations should be avoided while taking this medication. Be sure to discuss any vaccines with your rheumatology provider before receiving them. It may be important to receive certain vaccines before starting this medication, such as the Pneumovax (pneumonia vaccine), hepatitis B, or the tetanus booster for some patients.

Because this medication can lower your immunity, it is important you discuss this with any provider treating you for an infection, as this may lead to a different evaluation or treatment. Also, be sure to notify your provider before any surgeries while taking this medication, as leflunomide can increase the risk of post-operative infections and/or slow the healing of your wounds.

Side effects of leflunomide in the treatment of rheumatoid arthritis

Rudenko I.B., Shirobokova M.M., Tikhonov V.V., Baulina T.N., Pecherskikh Ya.V., Sazhina M.N., Zhiltsova E.G.

The leading pathological process that determines the development of rheumatoid arthritis (RA) is chronic immune inflammation, which is characterized by high stability and resistance to drug effects. It usually cannot be controlled satisfactorily with a single drug.Therefore, RA treatment is traditionally complex and is carried out using drugs of various classes. The central place in the drug treatment of RA is occupied by disease-modifying drugs, or, as they are also called, “basic drugs.” A common property of basic drugs is the ability to suppress certain links of the immune process, expressed to varying degrees. However, even the best of the basic drugs cannot solve the problem of RA treatment, since the occurrence of side effects, insufficient effectiveness or loss of the initial effect often lead to the need to replace them.Therefore, the appearance in the mid-1990s. a new powerful basic remedy has become a real event in rheumatology. Leflunomide (Arava, Aventis Pharma) was the first drug that was developed specifically for the treatment of RA. Over the past 10 years, the anti-inflammatory and basic properties of leflunomide, as well as its satisfactory tolerability, have been proven in numerous clinical studies in patients with RA both abroad and in Russia. In 1998, it was approved by the FDA for the treatment of patients with active RA, and with the indication that the drug inhibits the structural damage associated with RA.
Purpose of the study. To assess the clinical tolerance of leflunomide and its effect on biochemical parameters in patients with rheumatoid arthritis.

Materials and research methods. We analyzed the case histories of patients who received treatment at the rheumatology department of the Izhmash Municipal Healthcare Institution for the period from 2006 to 2009. As a result, we selected 38 stories, of which the main group included 18 patients taking leflunomide as basic therapy, and the comparison group, where 20 patients took methotrexate.All patients had systemic manifestations in the form of rheumatoid nodules, anemia, amyotrophy, low-grade fever, weight loss, Raynaud’s syndrome, myalgia, myocardial dystrophy. In addition to taking basic drugs, patients took as symptomatic therapy: NSAIDs, antiplatelet agents, metabolic drugs, glucocorticosteroids, vitamins. Patients of the main group took Arava for 4 years – 4 people, 3 years – 6 people, 2 years – 4 people, 1 year – 4 people. Arava was prescribed in the amount of a “saturating dose”, i.e.e. 100 mg for 3 days, then the patients were transferred to a dose of 20 mg per day. Some patients periodically took the drug at a dose of 10 mg per day. Patients in the comparison group took methotrexate 10 mg IM 1 time per week.

Leflunomide is well tolerated. Generally, intolerance reactions occurred in the first months of treatment, were not severe and did not lead to discontinuation of the drug. The most frequent reactions were from the gastrointestinal tract – diarrhea 11% and nausea – 8.4%, as well as skin rash – 7.3%, headache – 11%. All these symptoms were not severe, in some cases a short-term discontinuation of the drug or a decrease in the daily dose to 10 mg for 7–10 days was required, then a return to a dose of 20 mg / day made it possible to continue treatment. Influenza-like syndrome, expressed by the appearance of periods of malaise, chilling, low-grade fever, myalgia and increased joint pain associated with taking the drug, developed in 2 cases and passed after a short-term interruption in treatment.

Unstable leukopenia (3.8 x 109 / l) was observed in 2 patients, which did not serve as a reason for long interruptions in treatment (usually a break was made until the control analysis of peripheral blood after 1 week). At the stages of treatment, there was also an increase in the level of transaminases, γ-glutamyl transpeptidase in some patients (not much higher than the norm), an increase in the concentration of these indicators by more than 1.5 times higher than the norm was noted in 4 patients, but in no case was it a reason to stop treatment by Arava.

The likelihood of adverse reactions from the liver necessitates appropriate laboratory control during treatment with leflunomide. In accordance with the manufacturer’s recommendations, before prescribing the drug, it is necessary to determine the content of alanine aminotransferase (ALT) in the blood serum. Against the background of treatment, this indicator is examined monthly.

If the ALT level is 2-3 times higher than the upper limit of the norm, the study should be repeated, and if the result is confirmed, the dose of leflunomide should be reduced to 10 mg / day.
As for methotrexate, it has more serious side effects on the patient’s body. The following side effects were revealed: ulcerative stomatitis in 2 patients, infectious skin lesions in 3 patients, a third of patients had a decrease in the number of platelets to 110 • 109 / l, leukopenia to 3.5 • 109 / l. In most patients, an increase in the level of transaminases was also noted, to a greater extent – of alkaline phosphatase and γ-glutamyl transpeptidase, more than 2 times higher than the norm was noted in 7 patients.An increase in the level of creatinine in the blood has been noticed.

Conclusion. The practice of clinical use confirms the reputation of leflunomide as a promising and fairly safe drug used in the basic therapy of rheumatoid arthritis.

To the section “Articles”

Leflunomide in the treatment of rheumatoid arthritis

This Cochrane Review summary presents research findings on the effects of leflunomide on rheumatoid arthritis. This review found that in people with rheumatoid arthritis:

– Leflunomide probably relieves pain.

– Leflunomide has a positive effect on the number of tender or swollen joints and other outcomes such as pain and disability.
– Leflunomide causes side effects such as diarrhea, indigestion, increased liver function tests, and allergic reactions. We often do not have accurate information about the side effects and complications. This is especially true for rare but serious side effects.

What is rheumatoid arthritis and what is leflunomide?

If you have rheumatoid arthritis, your immune system, which normally fights infection, becomes overactive and attacks the lining of your joints.This causes the joints to become swollen, stiff, and sore. The small joints of the hands and feet are usually the first to be affected. There is currently no cure for rheumatoid arthritis. Therefore, treatment is aimed at reducing pain, stiffness and improving the ability to move.

Leflunomide is a disease-modifying antirheumatic drug (DMARD). It works by stabilizing over-active cells of the immune system that cause joint inflammation.Reducing inflammation can prevent joint damage. Leflunomide is taken as a tablet. It is more expensive than other BMARS, so doctors usually prescribe it if other BMARS are ineffective.

Best estimate of what happens to people with rheumatoid arthritis who took leflunomide for 6 months:

Pain (higher score means more pain):

– Patients who took leflunomide rated their pain 10 points lower on a scale from 0 to 100 points (10% absolute improvement).This could be an accident.
– Patients who took leflunomide rated their pain 14 points lower on a scale of 0 to 100.
– Patients who took placebo rated their pain 4 points lower on a 0-100 scale.

ACR 50 (number of tender or swollen joints and other outcomes such as pain and disability).

– 19 people out of 100 who took placebo improved their condition (19% absolute improvement).

– 33 more people out of 100 who took leflunomide experienced improvement in their rheumatoid arthritis symptoms.90,029 – 14 out of 100 people who took a placebo had a decrease in the severity of their rheumatoid arthritis symptoms.

Side effects

– 10 more people who took leflunomide dropped out of the trial due to side effects (10% absolute difference).

– 16 people out of 100 who took leflunomide dropped out of the trial due to side effects.

– 6 people out of 100 who took a placebo dropped out of the trial due to side effects.

Publications in mass media

Immunotherapeutic agents are currently presented in four groups of drugs • Immunosuppressants • Anti-TNF drugs • Immunoglobulins for intravenous administration (IVIg) • IFN

IMMUNODEPRESSANTS

The choice of immunosuppression protocol (dose, combination of drugs, duration of therapy) depends on the disease, the type of transplantation and the degree of histocompatibility between the donor and recipient.

Indications for the use of immunosuppressants: • treatment of autoimmune diseases • prevention and treatment of graft versus host reaction after bone marrow transplantation • prevention and treatment of transplant rejection.

GK have systemic anti-inflammatory and immunosuppressive activity.

• Mechanism of action and changes in the immune system •• After passive diffusion through the cytoplasmic membrane, they bind to the intracellular receptor.During translocation of the formed complex in the cell nucleus, it interacts with specific DNA sequences ( GREs , from English glucocorticoid responsive elements ) and gene transcription factors ••• For example, HA activates gene I kappa B alpha , which negatively regulates NF- k B (from the English nuclear factor k B – the nuclear factor k V). NF- k B – transcription factor of genes of granulocyte-monocyte colony-stimulating factor (GM-CSF – from the English. granulocyte-macrophage colony-stimulating factor ), IL-2, IL-6, IL-8. Thus, steroid-induced suppression of NF- k B causes a decrease in the secretion of these cytokines. plasminogen activator •• HA reduce the number of all circulating leukocytes with the exception of neutrophils. However, due to a decrease in adhesion to endothelial cells, neutrophils lose their ability to leave the bloodstream and penetrate into infected and damaged areas.The bactericidal activity of neutrophils and monocytes is also suppressed •• The immunosuppressive effect depends on the dose of HA. At low to moderate doses (<2 mg / kg / day of prednisone equivalent dose for children and <40 mg / day for adults), cutaneous anergy is observed. The number of circulating T-lymphocytes is moderately reduced, with CD4 ⁺ cells being to a greater extent than CD8 + cells. Doses of prednisone> 2 mg / kg / day for children and> 40 mg / day for adults suppress lymphocyte activation and AT production.

• The risk of infectious complications of glucocorticoid therapy is significantly increased with a prednisone dose> 10 mg / day. The relative risk of opportunistic infections (Pneumocystis pneumonia) is significantly higher than that of typical viral (herpes viruses), bacterial ( Staphylococcus aureus , etc.) and fungal (Candida ) infections. Protozoal infections and helminthiases are atypical, with the exception of endemic pathogens (eg Plasmodium falciparum ).

• Some properties of commonly used HA •• Betamethasone: half-life 5.6 hours, relative glucocorticoid activity 25, relative mineralocorticoid activity 0 •• Dexamethasone: half-life 3.3 hours, relative glucocorticoid activity 30, relative mineralocorticoid activity 0 •• Hydrocortisone : half-life 1-2 hours, relative glucocorticoid activity 1, relative mineralocorticoid activity 2 •• Methylprednisolone: ​​half-life 2-3 hours, relative glucocorticoid activity 5, relative mineralocorticoid activity 0 •• Prednisolone: ​​half-life 2.6-3 hours, relative glucocorticoid activity 4, relative mineralocorticoid activity 1 •• Prednisone: half-life 1.7-3 hours, relative glucocorticoid activity 3.5, relative mineralocorticoid activity 1 •• Triamcinolone: ​​half-life 2-3 hours, relative glucocorticoid activity 5, relative miner alocorticoid activity 0

Methotrexate inhibits dihydrofolate reductase, inhibiting the synthesis of thymidine and some amino acids, and slows down cell division • At a dose of> 20 mg / kg, used for the treatment of cancer, the drug suppresses the primary and secondary cellular and humoral immune response and can cause bone marrow depression , hemorrhages and sepsis • With the basic therapy of rheumatoid arthritis and other rheumtoid diseases (1 / 5-1 / 10 of the immunosuppressive dose – 7.5-15 mg / week once orally, i / m, i / v), methotrexate has an anti-inflammatory effect, inhibiting the expression of adhesion molecules and cytokines • At a dose of 10–25 mg / week, methotrexate is used once to treat psoriasis.

Mycophenolate mofetil is a new effective immunosuppressant for the prevention of renal transplant rejection. The drug is in the phase of clinical trials in the treatment of rheumatoid arthritis and SLE.

• After ingestion, mycophenolate mofetil undergoes hydrolysis with the formation of the active component – mycophenolic acid, which is excreted mainly in the urine. The half-life is 6 hours.

• Mycophenolic acid reversibly inhibits the enzyme inosine monophosphate dehydrogenase, thereby inhibiting purine biosynthesis de novo .Lymphocytes are significantly dependent on the synthesis of purines de novo and, to a lesser extent, on the hypoxanthine-guanine phosphoribosyl transferase-mediated pathway of purine biosynthesis. Therefore, the drug acts mainly on lymphocytes, in which the concentration of guanine nucleotides is significantly reduced, which limits the synthesis of DNA and RNA and suppresses proliferation.

• Mycophenolic acid inhibits: •• production of AT •• cytotoxic T-lymphocytes •• activity of NK cells •• production of cytokines IL-1 a , IL-1 b , IL-2, IL-3, IL- 4, IL-5, IL-6, IL-10, IFN- g , IFN- a , TNF- b , GM-CSF •• expression of selectins by lymphocytes and monocytes •• recruitment of neutrophils, lymphocytes and monocytes …

• Dosage: 1 g 2 r / day inside.

• Side effects: fever, headache, infections, arterial hypertension, skin rash, insomnia, anemia, thrombocytopenia, leukopenia, dyslipidemia, hyperglycemia, electrolyte disturbances.

Leflunomide is an isoxazole derivative with an antiproliferative effect.

• The drug is used to prevent transplant rejection. Leflunomide is also approved for the treatment of rheumatoid arthritis as monotherapy or in combination with methotrexate.

• Mechanism of action •• The active metabolite of leflunomide – A77 1726 – has a half-life of more than 2 weeks and is excreted in urine and feces •• The antiproliferative effect of A77 1726 in lymphocytes is realized by two mechanisms: ••• in low concentrations the drug inhibits de novo biosynthesis of pyrimidines in the G phase ₁ of the cell cycle ••• at high concentrations A77 1726 inhibits IL-2-induced phosphorylation of Jak1 and Jak3 kinases and b -chain of the receptor to IL-2 •• Leflunomide also inhibits the humoral response, i.e.because it inhibits the proliferation of B-lymphocytes in the S-phase of the cell cycle, as well as the adhesion of peripheral blood mononuclear cells and synovial fluid.

• Dosage: on days 1–3, 100 mg orally in one dose, then 10–20 mg orally in one dose.

• Side effects: gastrointestinal disorders, infections of the respiratory and urinary systems, arterial hypertension, headache, baldness, skin rash, hypokalemia, diabetes mellitus, dyslipidemia, anemia, leukopenia, thrombocytopenia.

Cyclosporin is a cyclic peptide consisting of 11 amino acid residues produced by the fungus Tolypocladium inflatum .

• The drug is used for organ transplantation and autoimmune diseases.

• Mechanism of action •• Cyclosporin binds to the cytoplasmic receptor protein cyclophyllin. The resulting complex inhibits the calcium-dependent phosphatase calcineurin, which is responsible for the activation of the transcription factor NF-AT (from the English nuclear factor of activated T cells – the nuclear factor of activated T cells). This molecule is necessary for the transcription of genes of a number of cytokines (GM-CSF, IL-2, IL-3, IL-4, IL-5, IL-8, IL-13, TNF, TNF g ) and the membrane molecule CD40L (CD40 ligand) •• In addition, cyclosporin inhibits the activation of TCR-dependent (TCR – T-lymphocyte receptor, from the English. T cell receptor ) signaling pathway in T-lymphocytes and Ar-representing function of monocytes / macrophages. Thus, the drug predominantly suppresses cellular immunity; however, its action is not associated with significant lymphopenia or leukopenia.

• Dosage: maintain a therapeutic serum concentration of 100–300 mcg / l; shows dynamic control of serum levels of cyclosporine.

• Side effects: nephrotoxicity, arterial hypertension, electrolyte disturbances, hepatotoxicity, hirsutism, acne, viral, bacterial pneumonia, fungal sepsis.

Sirolimus – a macrolide of fungal origin, forms a complex with FK-binding proteins from the family of cyclophyllins, other than cyclosporin-binding cyclophyllins. The drug is used to prevent transplant rejection. Sirolimus does not inhibit calcineurin • Mechanism of action •• Sirolimus binds to a specific cytosolic protein – immunophilin (FK-binding protein-12 [FKPB-12]), the FKPB-12-sirolimus complex inhibits the activation of the mammalian rapamycin target kinase (from the English.mTOR – mammalian target of rapamycin ), which plays a major role in the cell cycle •• Inhibition of mTOR leads to blockage of several specific signal transduction pathways and, ultimately, suppression of lymphocyte activation and a decrease in immune forces • Dosage: starting dose of 6 mg, then 2 mg orally 1 r / day or under control of serum concentration (therapeutic concentration 4–12 ng / ml in combination with cyclosporine for the first 2-3 months, after discontinuation of cyclosporine — 12–20 ng / ml).

ANTI-TNF PREPARATIONS

Tumor necrosis factor a (TNF a ) is a pro-inflammatory cytokine that plays an important role in the pathogenesis of rheumatic and inflammatory diseases. New data on the significance of TNF a in the pathophysiology of rheumatoid arthritis and Crohn’s disease have led to the development of a new class of anti-TNF a drugs.

Infliximab (humanized monoclonal antibodies against TNF a ) – approved for the treatment of rheumatoid arthritis and Crohn’s disease in the active phase • Dosage: 5 mg / kg for 2 hours IV • Side effects: viral infections, bronchitis, pneumonia, sinusitis , urinary tract infections, vomiting, diarrhea, headache, dizziness, arterial hypertension • Contraindications: sepsis, manifest infection, abscess, pregnancy, age less than 17 years.

IMMUNOGLOBULINS FOR INTRAVENOUS ADMINISTRATION

Immunoglobulins for intravenous administration (IVIg) are the standard of therapy for humoral and combined immunodeficiencies, as well as for a number of autoimmune diseases.

• Manufacturing method. All IVIg are prepared by cold ethanol precipitation. Sera of several thousand donors, after screening for infectious pathogens, are mixed to produce a preparation of one batch. IVIg contains antibodies against the most common native viral and bacterial Ags, as well as Ag vaccines.To reduce the risk of transmission of pathogens, pasteurization or treatment with detergents is used. The final product usually contains more than 99% IgG in terms of protein. Up to 10% of IgG molecules form polymer complexes. The serum half-life ranges from 15 to 30 days. IgA and complement components vary from manufacturer to manufacturer.

• Mechanisms of action of IVIG: •• blockade and modulation of the expression of Fc g -receptors •• suppression of the proliferative response of lymphocytes •• modulation of production and secretion of cytokines (IL-1, IL-1ra [antagonist of the receptor to IL-1], TNF a , TGF- b 1 [from the English. transformating growth factor b – transforming growth factor b ], IL-2, IL-10) •• inhibition of the damaging effects of complement •• suppression of endothelial cell proliferation •• stimulation of catabolism of autoantibodies of the IgG class •• suppression of Fas-mediated apoptosis (Fas – one of the glycoproteins of the cell membrane) •• regulation of idiotype-anti-idiotypic interactions.

• Indications for use •• Indications approved by the FDA: ••• X-linked agammaglobulinemia ••• Hyper-IgM syndrome ••• Transient hypogammaglobulinemia of newborns ••• IgG subclass deficiency ••• AT deficiency syndrome •• Severe combined immunodeficiency ••• Common variable immunodeficiency ••• DiGeorge syndrome ••• Wiskott-Aldrich syndrome ••• Ataxia-telangiectasia ••• Chediak-Higashi syndrome ••• X-linked lymphoproliferative syndrome • E•• Hypertension ••• Chronic lymphocytic leukemia with hypogammaglobulinemia ••• Immunoprophylaxis ( varicella ) ••• Kawasaki disease ••• Recurrent infections in bone marrow transplantation ••• Idiopathic thrombocytopenic purpura ••• HIV infection in children •• Indications based on the results of controlled clinical trials: ••• Prevention of RSV and CMV infections ••• Guillain – Barré syndrome ••• Chronic inflammatory demyelinating polyneuropathy.

• Conditions under which the efficacy of IVIg is being studied: •• autoimmune neutropenia •• autoimmune hemolytic anemia •• bronchial asthma •• atopic dermatitis •• chronic urticaria •• lupus nephritis •• Wegener’s granulomatosis •• autoimmune glomerular thyroid syndrome •• autoimmune glomerulitis syndrome • •• secondary immunodeficiencies.

• Dosing. The serum IgG concentration in patients with hypogammaglobulinemia should be above 500 mg%. The dose of IVIG required to achieve and maintain this level depends on the initial IgG concentration, the frequency of administration of the drug, and the intensity of immunoglobulin catabolism in an individual patient.For most patients, a dose of 300 mg / kg every 3 weeks or 400 mg / kg every 4 weeks is sufficient.

• Side effects •• From 5 to 15% of patients experience adverse reactions to IVIg: facial flushing, back pain, nausea, chills. Symptoms may disappear when the infusion rate is reduced. The first dose of the drug should be administered at a rate of 30 ml / h in adults and 10-15 ml / h in children. With good tolerance, subsequent infusions begin at a rate of 40 ml / h and increase the rate by 25% every 30 minutes •• Other side effects include acute renal failure, thrombosis, migraine, aseptic meningitis, and hemolytic anemia.

INTERFERONS

• Pharmacological effects: antiviral, antiproliferative, immunomodulatory.

• Indications: chronic viral hepatitis, various acute viral infections, multiple sclerosis, chronic granulomatosis.

• Side effects: fever, sweating, fatigue, arthralgia, myalgia, arrhythmias, depression, tremors, paresthesias, gastrointestinal disorders, hair loss, exanthema, itching.

• Contraindications: heart disease, central nervous system disease, renal failure, liver failure, bone marrow suppression.

Abbreviations. NF- k B – nuclear factor k B (from the English nuclear factor k B), GM-CSF – granulocyte-monocyte colony-stimulating factor (from the English granulocyte-macrophage colony-stimulating factor ), IVIG – immunoglobulins for intravenous administration.

Note. FDA – The US Federal Service for the Control of the Production, Storage and Marketing of Food, Drugs and Cosmetics ( The Food and Drug Administration ).

Leflunomide Canon tab. p / p / o 10mg No. 30

Composition

Dosage 10 mg:

One film-coated tablet contains:

Active substance : Leflunomide 10 mg.

Excipients: hyprolose (hydroxypropyl cellulose) 4.6, mg, calcium hydrogen phosphate dihydrate 48.2 mg, corn starch 22.8 mg, croscarmellose sodium (primellose) 5 mg, magnesium stearate 1 mg, microcrystalline cellulose 28.4 mg.

Shell composition:

Selecoat AQ-02003 4 mg, including: hypromellose (hydroxypropyl methylcellulose) 2.4 mg, macrogol 6000 (polyethylene glycol 6000) 0.8 mg, titanium dioxide 0.8 mg.

Dose 20 mg:

One film-coated tablet contains:

Active substance : Leflunomide 20 mg.

Excipients: hyprolose (hydroxypropyl cellulose) 6.7 mg, calcium hydrogen phosphate dihydrate 72 mg, corn starch 31.7 mg, croscarmellose sodium (primellose) 7.5 mg, magnesium stearate 1.5 mg, microcrystalline cellulose 40, 6 mg.

Shell composition:

Selecoat AQ-02003 6 mg, including: hypromellose (hydroxypropyl methylcellulose) 3.6 mg, macrogol 6000 (polyethylene glycol 6000) 1.2 mg, titanium dioxide 1.2 mg.

Dosage 100 mg:

One film-coated tablet contains:

Active ingredient: leflunomide 100 mg.

Excipients: hyprolose (hydroxypropyl cellulose) 7.5 mg, calcium hydrogen phosphate dihydrate 90 mg, corn starch 54.1 mg, croscarmellose, sodium (primellose) 12.9 mg, magnesium stearate 2.5 mg, microcrystalline cellulose 43 mg.

Coating composition:

Selecoat AQ-02003 10 mg, including: hypromellose (hydroxypropyl methylcellulose) 6 mg, macrogol 6000 (polyethylene glycol 6000) 2 mg, titanium dioxide 2 mg.

Dosage form

film-coated tablets

Description

Film-coated tablets of white or almost white color, round, biconvex: On the cross section – almost white.

Pharmacodynamics

Leflunomide belongs to the class of basic antirheumatic drugs and has antiproliferative, immunomodulatory, immunosuppressive and anti-inflammatory properties.The active metabolite leflunomide A771726 inhibits the enzyme dehydroorotate dehydrogenase and has antiproliferative activity. A771726 in vitro inhibits mitogen-induced proliferation and synthesis of deoxyribonucleic acid (DNA) of T-lymphocytes. The antiproliferative activity of A771726 is evidently manifested at the level of pyrimidine biosynthesis, since the addition of uridine to the cell culture eliminates the inhibitory effect of the A771726 metabolite. Using radioisotope ligands, it was shown that A771726 selectively binds to the enzyme dehydroorotate dehydrogenase, which explains its property to inhibit this enzyme and the proliferation of lymphocytes at the G1 stage.Lymphocyte proliferation is one of the key stages in the development of rheumatoid arthritis.

At the same time, A771726 inhibits the expression of receptors for interleukin-2 (CB-25) and antigens of the nucleus Ki-67 and PCNA associated with the cell cycle.

The therapeutic effect of leflunomide has been shown in several experimental models of autoimmune diseases, including rheumatoid arthritis.

Leflunomide reduces symptoms and slows down the progression of joint damage in active rheumatoid arthritis.

Therapeutic: the effect usually appears after 4-6 weeks and may increase further over the course of 4-6 months.

Pharmacokinetics

Leflunomide is rapidly converted to its active metabolite A771726 (primary metabolism in the intestinal wall and liver). Only traces of unchanged leflunomide were seen in plasma, urine, or feces. The only detectable metabolite is A771726, which is responsible for the main properties of the drug in vivo.

When ingested, from 82 to 95% of the drug is absorbed.The maximum plasma concentrations of A771726 are determined from 1 to 24 hours after a single dose. Leflunomide can be taken with food. Due to the very long half-life (T1 / 2) of A771726 (about 2 weeks), a loading dose of 100 mg per day was used for 3 days: This made it possible to quickly reach an equilibrium state of the plasma concentration of A771726. Without a loading dose, a 2-month dose would be required to reach equilibrium concentration. In studies with repeated use of the drug.Pharmacokinetic parameters of A771726 were dose-dependent in the dose range from 5 to 25 mg. In these studies, the clinical effect was closely related to the plasma concentration of A771726 and the daily dose of leflunomide. At a dose of ¹ 20 mg per day, the average plasma concentrations of A771726 at equilibrium were 35 μg / ml.

Rapid binding of A771726 to albumin occurs in plasma. The unbound fraction A771726 is approximately. 0.62%. The binding of A771726 is more variable, and is somewhat reduced in patients with rheumatoid arthritis or chronic renal failure.

Leflunomide is metabolized to one major (A771726) and several minor metabolites, including 4-trifluoromethylalanine. Biotransformation of leflunomide into A771726 and the subsequent metabolism of A771726 itself is controlled by several enzymes and occurs in microsomal and other cellular fractions. Interaction studies with cimetidine (a non-specific inhibitor of cytochrome P450) and rifampicin (a non-specific inducer of cytochrome P450) showed that in vivo CYP enzymes are involved in the metabolism of leflunomide only to a small extent.Excretion of A771726 from the body is slow and is characterized by a clearance of 31 ml / hour. Leflunomide is excreted in feces (probably by biliary excretion) and in urine. (T1 / 2) is about 2 weeks.

Pharmacokinetics of A771726 in patients on chronic ambulatory peritoneal dialysis (CAPD) is similar to that in healthy volunteers. A faster excretion of A771726 is observed in patients on hemodialysis, which is associated not with the extraction of the drug into the dialysate, but with its displacement from the protein bond.Although the clearance of A771726 increases approximately 2 times, the final (T1 / 2) is similar to that in healthy individuals, since the volume of distribution increases simultaneously.

There are no data on the pharmacokinetics of the drug in patients with hepatic insufficiency.

Pharmacokinetic characteristics in patients under 18 years of age have not been studied. In elderly patients (65 years and older), pharmacokinetic data approximately correspond to the middle age group.

Indications for use

– As a basic agent for the treatment of adult patients with active rheumatoid arthritis in order to reduce the symptoms of the disease and delay the development of structural damage to the joints,

– Active form of psoriatic arthritis.

Contraindications

Symptoms

There have been reports of chronic overdose in patients receiving leflunomide at a dose up to five times the recommended daily dose, as well as reports of acute overdose in adults and children. In most cases of overdose, no adverse reactions have been reported. The resulting adverse reactions were comparable to the safety profile of leflunomide. The most frequently observed adverse reactions were diarrhea, abdominal pain, leukopenia, anemia, and increased liver function tests.

Treatment

In case of overdose or toxicity, it is recommended to take cholestyramine or activated charcoal to speed up the cleansing of the body.

Kolestyramine, taken orally 8 g 3 times a day for a day, reduces the content of A771726 in plasma by about 40% after 24 hours, by 49-65 % after 48 hours. The introduction of activated carbon (in the form of a suspension) orally or through a gastric tube (50 g every 6 hours during the day) reduces the concentration of the active metabolite A771726 in plasma by 37% after 24 hours, and by 48% after 48 hours.

These procedures can be repeated if clinically indicated.

Studies with hemodialysis and CAPD indicate that A771726, the major metabolite of leflunomide, cannot be cleared by dialysis.

Use during pregnancy and lactation

Leflunomide should not be used by pregnant women or women of childbearing age who do not use reliable contraception during treatment with leflunomide and for a certain time after this treatment (waiting period or shortened washing period, see.below). Before starting treatment with Leflunomide Canon, you must make sure that there is no pregnancy.

Patients should be informed that as soon as menstruation is delayed or if there is another reason to suspect pregnancy, they should immediately inform the doctor about this in order to take a pregnancy test. In the case of a positive pregnancy test, the doctor should discuss with the patient the possible risks to which the pregnancy is exposed. It is possible that a rapid decrease in the level of the active metabolite in the blood using the procedure for removing the drug described below will help to reduce the risk to the fetus from leflunomide at the first delay in menstruation.

Women who are taking leflunomide and want to become pregnant are advised to follow one of the procedures below to ensure that the fetus will not be exposed to toxic concentrations of A771726 (control concentration below 0.02 mg / L).

Waiting period

It can be expected that the concentration of A771726 in blood plasma may be higher than 0.02 mg / L for a long period. It is believed that its concentration may become less than & lt, 0.02 mg / L 2 years after stopping leflunomide treatment.The first time the concentration of A771726 in blood plasma is measured after a two-year waiting period.

After that, it is necessary to measure the concentration of A771726 in the blood plasma, at least after 14 days. If both measurements are below 0.02 mg / L, no teratogenic risk is expected.

Washing procedure

– cholestyramine 8 g is injected 3 times a day for 11 days,

– alternatively 50 g of powdered activated carbon is injected 4 times a day for 11 days.

Regardless of the chosen washing procedure, it is necessary to check in two separate tests with an interval of at least 14 days and wait a month and a half from the moment when the concentration of the drug in the plasma is first recorded below 0.02 mg / l, until the moment of fertilization.

Women of childbearing age should be informed that it must take 2 years after stopping leflunomide treatment before they can try to become pregnant. If a 2-year waiting period with reliable contraception seems unreasonable, a preventive laundering procedure may be advised.

Both cholestyramine and activated charcoal can interfere with the absorption of estrogens and progestogens, therefore reliable oral contraception is not 100% guaranteed during the washout period with cholestyramine or activated charcoal. It is recommended to use alternative methods of contraception.

Animal studies have shown that leflunomide or its metabolites pass into breast milk, therefore women who are breastfeeding should not take the drug.

Side effects

The frequency of side effects is given in the following gradation: very often (more than 1/10), often (more than 1/100, less than 1/10), infrequently (more than 1/1000, less than 1/100), rarely (more than 1/10000, less than 1/1000), very rarely (less than 1/10000), including individual messages.

On the part of the cardiovascular system

Often: moderate increase in blood pressure,

Rarely: marked increase in blood pressure,

Frequency unknown: angina pectoris, migraine, palpitations, variations, tachycardia veins, vasculitis, vasodilation.

From the gastrointestinal tract

Often: diarrhea, nausea, vomiting, diseases of the oral mucosa (for example, aphthous stomatitis, ulceration of the lips), pain in the abdominal cavity,

Uncommon: taste disorders ,

Very rare: pancreatitis,

Frequency unknown: gingivitis, oral candidiasis, esophagitis, gastritis, gastroenteritis, dyspepsia, colitis, constipation, flatulence, melena.

From the side of the hepato-biliary system

Often: increased activity of hepatic transaminases (alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP),

hepatica 9000 , jaundice, cholelithiasis,

Very rare: severe liver damage (including liver failure, acute liver necrosis), which can be fatal.

Respiratory system

Often: respiratory infections of the upper respiratory tract, cough,

Rare: interstitial pulmonary process (including interstitial pneumonia and pulmonary fibrosis) with possible death,

Frequency unknown: asthma, shortness of breath, epistaxis.

Metabolic and nutritional disorders

Often: increase in creatine phosphokinase (CPK),

Uncommon: hypokalemia, hyperlipidemia, hypophosphatemia,

Rarely: unknown Rarely: increase in the level of : hypouricemia, diabetes mellitus, hyperthyroidism, peripheral edema.

From the nervous system

Often: headache, dizziness, paresthesia,

Uncommon: anxiety,

Very rare: peripheral depression, anxiety,

Frequency unknown: dryness of the oral mucosa, sleep disturbances, neuralgia, neuritis, increased sweating.

From the musculoskeletal system

Often: tendovaginitis,

Uncommon: tendon rupture,

Frequency unknown: arthralgia, synovitis, muscle necrosis, arthrosis, arthrosis.

Skin and subcutaneous tissue disorders

Often: increased hair loss, alopecia, eczema, skin rash (including maculopapular), itching, dry skin,

Uncommon: 9000 urticaria Very rare: toxic epidermal necrolysis (Lyell’s syndrome), erythema multiforme, Stevens-Johnson syndrome,

Frequency unknown: acne, contact dermatitis, fungal dermatitis, hair discoloration, herpes simplex, herpes zoster, nail damage, pigmentation disorders skin, skin ulceration.

From the immune system

Often: allergic reactions,

Very rare: serious anaphylactic / anaphylactoid reactions, angioedema.

Infections and infestations

Rare: severe infections (including opportunistic and sepsis), which can be fatal,

Increased risk of infectious diseases such as rhinitis, bronchitis and pneumonia.

Hematopoietic and lymphatic system

Often: leukopenia (leukocytes & gt, 2000 / μl),

Uncommon: anemia, mild thrombocytopenia (platelets & gt), 9000 / μl REDCO : pancytopenia (apparently due to antiproliferative action), eosinophilia, leukopenia (leukocytes & lt, 2000 / μl),

Very rare: agranulocytosis.

Recent, concomitant or subsequent use of potentially myelotoxic agents may be associated with a greater risk of hematological effects.

Reproductive system

Frequency unknown : slight decrease in sperm concentration, total sperm count and motility.

From the kidneys and urinary system

Frequency unknown: infections of the urinary system, renal failure, albuminuria, cystitis, dysuria, hematuria, prostate damage, frequent urination, vaginal candidiasis.

From the senses

Frequency unknown : blurred vision, cataract, conjunctivitis, taste disturbances.

General

Often: anorexia, weight loss (usually slight), asthenia,

Frequency unknown: fever, weakness.

Other

The risk of malignant, especially lymphoproliferative, diseases increases with the use of certain immunosuppressive drugs.

Interaction

Increased side effects may occur in the case of recent or concomitant use of hepatotoxic (including alcohol) or hematotoxic and immunosuppressive drugs, or when these drugs are started after treatment with leflunomide without washing (see.Special instructions).

In patients with rheumatoid arthritis, no pharmacokinetic interaction was found between leflunomide (10-20 mg per day) and methotrexate (10-25 mg per week).

Patients taking leflunomide are not recommended to take colestyramine or activated charcoal at the same time, as this leads to a rapid and significant decrease in the concentration of A771726 in the blood plasma. It is believed that this is due to impaired recirculation of A771726 in the liver and small intestine and / or impaired gastrointestinal dialysis.

If the patient is already taking non-steroidal anti-inflammatory drugs (NSAIDs) and / or corticosteroids, they can be continued after starting leflunomide treatment.

The enzymes involved in the metabolism of leflunomide and its metabolites are not precisely known. Study in vivo of its interaction with cimetidine (a nonspecific inhibitor of cytochrome P450) showed no significant interaction. After concomitant administration of a single dose of leflunomide to subjects receiving multiple doses of rifampicin (non-specific, cytochrome P450 inducer), peak A771726 levels increased by about 40%, while the area under the concentration-time curve did not significantly change.The mechanism of this effect is not clear. Studies in vitro showed that A771726 inhibits the activity of cytochrome P4502C9 (CYP2C9). In clinical studies, no problems were observed with the combined use of leflunomide and NSAIDs metabolized by CYP2C9. Leflunomide should be used with extreme caution in conjunction with other non-NSAID drugs that are metabolized by CYP2C9, such as phenytoin, warfarin, and tolbutamide. An increase in prothrombin time has been reported with the simultaneous use of leflunomide and warfarin.

In a study in which leflunomide was given to healthy female volunteers in conjunction with three-phase oral contraceptives containing 30 μg of ethinyl estradiol, no decrease in the contraceptive effect of contraceptives was found, and the pharmacokinetics of A771726 fully corresponded to the prescribed range.

There is currently no information on the combined use of leflunomide with antimalarial drugs used in rheumatology (for example, chloroquine and hydroxychloroquine), gold preparations (intramuscularly or orally), D-penicillamine, azathioprine, and other immunosuppressive drugs (with the exception of methotrexate) …The risk associated with combination therapy is unknown, especially with long-term treatment. Since this kind of therapy can lead to the development of additional or even synergistic toxicity (for example, hepato- or hematoxicity), combinations of this drug with other basic drugs (for example, methotrexate) are undesirable. Recent concomitant or subsequent use of potentially myelotoxic agents may be associated with a greater risk of haematological exposures.

Immunosuppressants increase the risk of developing infections, as well as malignant, especially lymphoproliferative diseases.

Vaccination

There are no clinical data regarding the efficacy and safety of vaccination under the conditions of leflunomide treatment. However, it is not recommended to vaccinate with live vaccines. When planning vaccination with a live vaccine, long-term T1 / 2 of leflunomide after drug withdrawal should be taken into account.

Route of administration and dosage

Treatment with leflunomide should begin under the supervision of a physician experienced in the treatment of rheumatoid arthritis and psoriatic arthritis.

For recommendations for monitoring treatment, see the Special Instructions section.

The tablets must be taken regardless of the meal, swallowed whole with a sufficient amount of liquid.

Treatment with leflunomide begins with a loading dose of 100 mg orally once a day for 3 days. As a maintenance dose for rheumatoid arthritis, it is recommended to take from 10 mg to 20 mg of leflunomide once a day, in psoriatic arthritis – 20 mg once a day.

The therapeutic effect usually appears after 4-6 weeks and can increase further up to 4-6 months.

No dose adjustment is required for patients over 65 years of age.

Overdose

Symptoms

There have been reports of chronic overdose in patients receiving leflunomide at a dose up to five times the recommended daily dose, as well as reports of acute overdose in adults and children. In most cases of overdose, no adverse reactions have been reported. The resulting adverse reactions were comparable to the safety profile of leflunomide.The most frequently observed adverse reactions were diarrhea, abdominal pain, leukopenia, anemia, and increased liver function tests.

Treatment

In case of overdose or toxicity, it is recommended to take cholestyramine or activated charcoal to speed up the cleansing of the body.

Kolestyramine, taken orally 8 g 3 times a day for a day, reduces the content of A771726 in plasma by about 40% after 24 hours, by 49-65 % after 48 hours.The introduction of activated carbon (in the form of a suspension) orally or through a gastric tube (50 g every 6 hours during the day) reduces the concentration of the active metabolite A771726 in plasma by 37% after 24 hours, and by 48% after 48 hours.

These procedures can be repeated if clinically indicated.

Studies with hemodialysis and CAPD indicate that A771726, the major metabolite of leflunomide, cannot be cleared by dialysis.

Special instructions

Leflunomide can be used in patients only after a thorough medical examination.

Washing procedure

The washing procedure is carried out according to the following scheme:

– cholestyramine 8 g is injected 3 times a day for 11 days,

– alternatively – 50 g of activated carbon, crushed into powder, is injected 4 times a day for 11 days.

Adverse reactions

Before starting treatment with Leflunomide Canon, it is necessary to remember about the possible increase in the number of adverse reactions in patients who previously received other basic drugs for the treatment of rheumatoid arthritis, which have hepato- and hematotoxic effects.The active metabolite of leflunomide, A771726, is characterized by a long T1 / 2, usually ranging from 1 to 4 weeks. Due to the long half-life of the active metabolite of leflunomide, even if treatment with leflunomide is discontinued, serious adverse effects may occur or persist. In this case, the washing procedure should be carried out according to the above scheme. The procedure can be repeated according to clinical indications. If severe immunological / allergic reactions such as Stevens-Johnson syndrome or Lyell’s syndrome are suspected, a complete laundering procedure is mandatory.

In the event of similar cases of toxicity or when switching to another ₍ basic drug (for example, methotrexate) after treatment with leflunomide, it is necessary to carry out the washing procedure (see above).

Liver reactions

Since the active metabolite of leflunomide is A771726 with proteins and is excreted through hepatic metabolism and bile secretion, it is assumed that the level of A771726 in the blood plasma may increase in patients with hypoproteinemia.Leflunomide is contraindicated in patients with severe hypoproteinemia or impaired liver function (see section Contraindications). It is not recommended to take leflunomide in patients with previous acute or chronic liver disease, as well as in patients whose ALT level before starting treatment is 2 times higher than the upper limit of the norm.

Rare cases of severe liver damage, in some cases fatal, have been reported with leflunomide treatment. Most of these cases were observed during the first six months of treatment.Although the causal relationship of these adverse events to leflunomide has not been established, and in most cases there were several additional suspicious factors, strict adherence to treatment monitoring recommendations is considered imperative.

ALT should be checked before starting leflunomide therapy, and then every 2 weeks during the first 6 months of treatment, followed by a check once every 6-8 weeks. There are the following recommendations for correcting the dosage regimen or discontinuing the drug, depending on the severity and persistence of the increase in ALT levels.With a confirmed 2-3-fold excess of the upper limit of the ALT norm, a decrease in the dose from 20 mg to 10 mg per day may allow the continuation of leflunomide, provided that this indicator is carefully monitored. If 2-3 times the upper limit of the ALT limit persists, or if there is a confirmed rise in the ALT level exceeding the upper limit of the norm by more than 3 times, leflunomide should be discontinued and the laundering procedure should be started.

Due to possible additional hepatotoxic effects, it is recommended to refrain from drinking alcohol during treatment with Leflunomide Canon.

Hematological reactions

A complete clinical blood test, including determination of the leukocyte formula and platelet count, should be performed before starting treatment with leflunomide, and also every 2 weeks during the first 6 months of treatment and then every 6-8 weeks.

Patients with pre-existing anemia, leukopenia and / or thrombocytopenia, as well as patients with impaired bone marrow function or at risk of developing such disorders, increase the risk of hematological disorders.If this kind of phenomenon occurs, the washing procedure should be used to reduce the level of A771726 in the blood plasma.

In case of development of serious hematological reactions, including pancytopenia, it is necessary to stop taking the drug Leflunomide Canon and any other concomitant drug that suppresses bone marrow hematopoiesis, and start the washing procedure.

Co-administration with other treatments

There is currently no information on co-administration of leflunomide with antimalarial drugs used in rheumatology (for example, chloroquine and hydroxychloroquine) administered intramuscularly or orally, gold preparations, D-penicillamine, azathioprine and other immunosuppressive agents, with the exception of methotrexate.The risk associated with the use of combination therapy is not known, especially with long-term treatment. Since this kind of therapy can lead to the development of additional or even synergistic toxicity (for example, hepato- or hematotoxicity), combinations of this drug with other basic drugs (for example, methotrexate) are not desirable.

Switching to other types of treatment

Since leflunomide remains in the body for a long time, switching to another basic drug (for example, methotrexate) without an appropriate laundering procedure may increase the possibility of additional risk even long after the switch interaction, organotoxicity).

Similarly, recent treatment with hepatotoxic or hematotoxic drugs (eg, methotrexate) may lead to an increase in the number of side effects, therefore, when starting treatment with leflunomide, it is necessary to carefully consider all the positive and negative aspects associated with taking this drug.

Skin reactions

If ulcerative stomatitis develops, you should stop taking leflunomide.

Very rare cases of Stevens-Johnson syndrome or toxic epidermal necrolysis have been reported in patients treated with leflunomide.In the event of skin reactions and / or reactions from the mucous membranes, it is necessary to stop taking the drug Leflunomide Canon and any other related drug and immediately start the washing procedure. It is necessary to achieve complete elimination of the drug from the body. In such cases, re-administration of the drug is contraindicated.

Infections

It is known that drugs like leflunomide and having immunosuppressive properties make patients more susceptible to various kinds of infections, including opportunistic infections (infections caused by fungi and microorganisms that can cause infections only in conditions of reduced immunity).Emerging infectious diseases are usually difficult and require early and intensive treatment. In the event of a severe infectious disease, it may be necessary to interrupt treatment with leflunomide and start the laundering procedure.

Patients who test positive for tuberculin should be closely monitored due to the risk of reactivation of tuberculosis.

Airway reactions

Rare cases of interstitial pulmonary disease have been reported with leflunomide therapy.Symptoms such as cough and dyspnoea may cause you to stop taking leflunomide.

Blood pressure

Before starting treatment with leflunomide and periodically after it starts, blood pressure should be monitored.

Interactions

Care should be taken when using drugs metabolized by CYP2C9 (phenytoin, warfarin, tolbutamide), with the exception of NSAIDs.

Recommendations for men

There are no data on the risk of fetotoxicity associated with the toxic effect of the drug on the father’s sperm when using leflunomide in men.To minimize the possible risk, men who are planning to have a baby should stop taking leflunomide and carry out a laundering procedure.

Application for impaired renal function

Use is contraindicated in moderate or severe renal failure (due to little experience of clinical observations). There are no specific dosage recommendations in patients with mild renal impairment.

Effects on the ability to drive vehicles and use mechanisms

Taking the drug may be accompanied by headache, dizziness.In this regard, patients taking leflunomide should exercise caution when driving dangerous mechanical means, including a car.

Release form

Film-coated tablets of 10 mg, 20 mg or 100 mg.

Conditions for dispensing from pharmacies

By prescription

Storage conditions

In a dry, dark place at a temperature not exceeding 25 C.

Keep out of the reach of children.

Expiry date

2 years.Do not use after the expiration date.

Memorial Sloan Kettering Cancer Center

This document, provided by Lexicomp ^® , contains all the information you need to know about the drug, including the indications, route of administration, side effects, and when you should contact your healthcare provider.

Trade names: USA

Arava

Trade names: Canada

ACCEL-Leflunomide; APO-Leflunomide; Arava; PMS-Leflunomide; SANDOZ Leflunomide; TEVA-Leflunomide

Warning

• If used during pregnancy, this drug could cause fetal harm or fetal death.
• If you are pregnant or may become pregnant and are not using birth control to prevent pregnancy, do not take this drug. Before you start taking this drug, you will have a pregnancy test to confirm that you are NOT pregnant. Use a contraceptive you can trust to prevent pregnancy while taking this drug. Continue using this contraceptive while you are clearing excess leflunomide from your body.You will need to have a blood test to confirm that there is no leflunomide in your body before you stop taking the contraceptive. If you become pregnant while taking this drug, call your doctor right away.
• Very bad and sometimes deadly liver problems have happened with this drug. Consult your doctor if you have liver disease. This medication should not be used in people with certain liver problems.Monitor liver function as directed by your doctor.
• If you are taking any medications that may increase your risk of liver problems, tell your doctor. There are many medications that can cause these problems. If you are unsure, check with your doctor or pharmacist.

What is this drug used for?

• Used to treat rheumatoid arthritis.

What do I need to tell my doctor BEFORE taking this drug?

• If you are allergic to leflunomide or any of the other ingredients of this drug.
• If you are allergic to this drug, any of its ingredients, other drugs, foods or substances. Tell your doctor about your allergy and how it manifested itself.
• If you have any of the following health problems: bone marrow disease or low blood cell counts.
• In case of infection.
• If you have a weakened immune system.
• If you are taking teriflunomide.
• If you are breastfeeding. Do not breast-feed while taking this drug.

This list of drugs and diseases that may be adversely associated with this drug is not exhaustive.

Tell your doctor and pharmacist about all medicines you take (both prescription and over-the-counter, natural products and vitamins) and your health problems.You need to make sure that this drug is safe for your medical condition and in combination with other drugs you are already taking. Do not start or stop taking any drug or change the dosage without your doctor’s approval.

What do I need to know or do while I am taking this drug?

• Tell all healthcare providers that you are taking this drug.These are doctors, nurses, pharmacists and dentists.
• Perform blood tests as directed by your healthcare practitioner. Please consult your doctor.
• High blood pressure has happened with this drug. Monitor your blood pressure as directed by your doctor.
• Talk to your doctor before getting any vaccine while using this drug or after you stop using this drug. Vaccination while using this drug may increase the risk of infection or reduce the effectiveness of the vaccine.Consult your doctor.
• You may be at increased risk of developing an infection. Wash your hands often. Avoid contact with carriers of the infection, including people with colds or flu. Some infections can be very serious and sometimes deadly.
• There is an increased likelihood of bleeding. Be careful and avoid injury. Use a soft toothbrush and electric shaver.
• Must be tested for tuberculosis before starting the drug.
• This drug will remain in your body for some time after treatment is stopped. In some cases, your doctor may prescribe other drugs to help clear the drug faster. Consult your doctor.
• This drug may increase the risk of certain types of cancer. Consult your doctor.
• Neurological problems have happened with this drug.Typically, these neurological problems resolved when the drug was stopped. In some cases, people have neurological problems that did not go away even after the drug was stopped. Consult your doctor.
• A serious reaction has occurred that can be fatal. In most cases, this reaction was accompanied by symptoms such as fever, rash, inflammation of the lymph nodes, and dysfunction of various organs such as the liver, kidneys, blood, heart, muscles, joints and lungs.If you have any questions, please consult your doctor.
• If you are 60 years of age or older, use this drug with caution. You may have more side effects.
• If your sexual partner is able to become pregnant or if you are planning to conceive a child, consult your doctor.
• If you have a delayed period, have had unprotected sex, or think your contraceptive has not been effective, see your doctor immediately.

What side effects should I report to my doctor immediately?

WARNING. In rare cases, some people with this drug can have serious and sometimes deadly side effects. Call your doctor or get medical help right away if you have any of the following signs or symptoms, which may be associated with serious side effects:

• Signs of an allergic reaction such as rash, hives, itching, reddened and swollen skin with blistering or scaling, possibly associated with fever, wheezing or wheezing, tightness in the chest or throat, difficulty breathing, swallowing or speaking, unusual hoarseness, swelling in the mouth, face, lips, tongue, or throat.
• Signs of liver problems such as dark urine, feeling tired, lack of appetite, nausea or abdominal pain, light stools, vomiting, yellowing of the skin and eyes.
• Signs of high blood pressure, such as very severe headache, or dizziness, or loss of consciousness, or blurred vision.
• Unusual burning, numbness, or tingling sensations.
• Pale skin.
• Cases of decreased blood cell count have been reported during treatment with this drug.A marked decrease in the number of blood cells can lead to bleeding, infection, or anemia. See your doctor right away if you develop symptoms of an infection such as high fever, chills, or sore throat; any unexplained bruising or bleeding; or when you are very tired or weak.
• Possible severe skin reaction (Stevens-Johnson syndrome / toxic epidermal necrolysis). This can lead to serious and permanent health problems and sometimes death.Get immediate medical attention if you experience symptoms such as redness, skin swelling with blistering or scaling (with or without a high fever), redness or irritation of the eyes, and ulceration in the mouth, throat, nose, or eyes.
• Some people have had a lung problem with this drug. In some cases, this has been fatal. See your doctor right away if you have signs of lung disease, such as shortness of breath or other breathing problems, coughing or worsening cough, or fever.

What are some other side effects of this drug?

Any medicine can have side effects. However, many people have little or no side effects. Call your doctor or get medical help if these or any other side effects bother you or do not go away:

• Nausea or vomiting.
• Abdominal pain or diarrhea.
• Hair loss.
• Feeling dizzy, tired, or weak.
• Back pain.
• Headache.

This list of potential side effects is not comprehensive. If you have any questions about side effects, please contact your doctor. Talk to your doctor about side effects.

You can report side effects to the National Health Office.

You can report side effects to the FDA at 1-800-332-1088. You can also report side effects at https: // www.fda.gov/medwatch.

What is the best way to take this drug?

Use this drug as directed by your healthcare practitioner. Read all the information provided to you. Follow all instructions strictly.

• Take this drug with or without food.
• Continue taking this drug as directed by your doctor or other healthcare professional, even if you feel well.

What to do if a dose of a drug is missed?

• Take the missed dose as soon as you can.
• If it is time for your next dose, do not take the missed dose and then return to your normal dose schedule.
• Do not take 2 doses at the same time or an additional dose.

How do I store and / or discard this drug?

• Store at room temperature.
• Protect from light.
• Store in a dry place. Do not store in the bathroom.
• Store all medicines in a safe place. Keep all medicines out of the reach of children and pets.
• Dispose of unused or expired drugs. Do not empty into toilet or drain unless directed to do so. If you have any questions about the disposal of your medicinal products, consult your pharmacist.Your area may have drug recycling programs.

General information about medicines

• If your health does not improve or even worsens, see your doctor.
• Do not give your medicine to anyone or take other people’s medicines.
• Some medicines may come with other patient information sheets. If you have questions about this drug, talk with your doctor, nurse, pharmacist, or other healthcare professional.
• Some medicines may come with other patient information sheets. Check with your pharmacist. If you have questions about this drug, talk with your doctor, nurse, pharmacist, or other healthcare professional.
• If you think an overdose has occurred, call a Poison Control Center immediately or seek medical attention. Be prepared to tell or show which drug you took, how much and when it happened.

Consumer use of information and limitation of liability

This information should not be used to make decisions about taking this or any other drug. Only the attending physician has the necessary knowledge and experience to make decisions about which drugs are appropriate for a particular patient. This information does not guarantee that the drug is safe, effective, or approved for the treatment of any disease or specific patient.Here are only brief general information about this drug. It does NOT contain all available information on the possible use of the drug with instructions for use, warnings, precautions, information about interactions, side effects and risks that may be associated with this drug. This information should not be construed as a treatment guide and does not replace information provided to you by your healthcare professional. Please consult your doctor for complete information on the possible risks and benefits of taking this drug.