Denosumab (Subcutaneous 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 or nurse immediately if any of the following side effects occur:

More common

1. 
   Back pain
2. 
   blistering, crusting, irritation, itching, or reddening of the skin
3. 
   bloody or cloudy urine
4. 
   cracked, dry, or scaly skin
5. 
   difficult, burning, or painful urination
6. 
   frequent urge to urinate
7. 
   muscle or bone pain
8. 
   pain in the arms or legs
9. 
   rash
10. 
    skin rash, encrusted, scaly, and oozing
11. 
    swelling

Less common

1. 
   Arm or jaw pain
2. 
   bloating or swelling of the face, arms, hands, lower legs, or feet
3. 
   body aches or pain
4. 
   chest pain or discomfort
5. 
   chest tightness or heaviness
6. 
   chills
7. 
   confusion
8. 
   congestion
9. 
   cough
10. 
    difficulty with breathing
11. 
    difficulty with moving
12. 
    dryness or soreness of the throat
13. 
    ear congestion
14. 
    fast or irregular heartbeat
15. 
    fever
16. 
    headache
17. 
    hoarseness
18. 
    joint pain
19. 
    loss of voice
20. 
    muscle cramps in the hands, arms, feet, legs, or face
21. 
    muscle stiffness
22. 
    numbness and tingling around the mouth, fingertips, hands, or feet
23. 
    pain in the lower back, bottom, upper leg, or hips
24. 
    painful blisters on the trunk of the body
25. 
    pale skin
26. 
    rapid weight gain
27. 
    runny or stuffy nose
28. 
    seizures
29. 
    sneezing
30. 
    stomach cramps
31. 
    swollen joints
32. 
    tender, swollen glands in the neck
33. 
    tremor
34. 
    trouble swallowing
35. 
    troubled breathing with exertion
36. 
    unusual bleeding or bruising
37. 
    unusual tiredness or weakness
38. 
    unusual weight gain or loss
39. 
    voice changes

Rare

1. 
   Blood in the stool
2. 
   change in bowel habits
3. 
   clear or bloody discharge from the nipple
4. 
   constipation
5. 
   darkened urine
6. 
   difficulty with eating
7. 
   dimpling of the breast skin
8. 
   indigestion
9. 
   inverted nipple
10. 
    itching, pain, redness, swelling, tenderness, or warmth on the skin
11. 
    loss of appetite
12. 
    lower back or side pain
13. 
    lump in the breast or under the arm
14. 
    lump or swelling in the abdomen or stomach
15. 
    nausea
16. 
    pains in the stomach, side, or abdomen, possibly radiating to the back
17. 
    persistent crusting or scaling of the nipple
18. 
    raised, firm, and bright red patches of the skin on the arm or leg
19. 
    redness or swelling of the breast
20. 
    sore on the skin of the breast that does not heal
21. 
    stomach discomfort
22. 
    unexplained weight loss
23. 
    vomiting
24. 
    yellow eyes or skin

Incidence not known

1. 
   Heavy feeling in the jaw
2. 
   loose teeth
3. 
   pain, swelling, or numbness in the mouth or jaw

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:

Less common

1. 
   Dizziness or lightheadedness
2. 
   excess air or gas in the stomach or bowels
3. 
   feeling of constant movement of self or surroundings
4. 
   feeling of fullness
5. 
   heartburn
6. 
   lack or loss of strength
7. 
   passing gas
8. 
   redness, pain, itching, burning, swelling, or a lump under your skin where the shot was given
9. 
   sensation of spinning
10. 
    trouble sleeping
11. 
    upper abdominal or stomach pain

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.

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.

Prolia – Chemotherapy Drugs – Chemocare

Chemocare.com

Care During Chemotherapy and Beyond

Generic name: 
Denosumab

Trade names: Prolia^®, Xgeva^®  

Denosumab is the generic name for the trade name drugs Prolia^®
or Xgeva^®.  In some cases, health care professionals
may use the trade names Prolia^® or Xgeva^® when referring to the generic drug name denosumab. 
Prolia^® and  Xgeva^®
are the same generic drug (denosumab).  They were given distinct trade names
in order to differentiate between their unique dosing schedules and indications
for use.  How they are used is different, but strictly speaking, the two are
the same drug.

Drug type: 

Prolia is a monoclonal antibody that works as a RANK ligand (RANKL) inhibitor. 
This medications is classified as a “bone-modifying agent”. (For more detail see
“How denosumab works” section below).

What Prolia Is Used For:

•  Prolia
• Treatment of postmenopausal women with osteoporosis at high risk for fracture.
• Treatment to increase bone mass in men at high risk for fracture receiving androgen
  deprivation therapy for non-metastatic prostate cancer.
• Treatment to increase bone mass in women at high risk for fracture receiving adjuvant
  aromatase inhibitor therapy for breast cancer.

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

How Prolia Is Given:

• As a subcutaneous injection in the upper arm, upper thigh, or abdomen.  A subcutaneous
  injection is a shot into the layer of skin directly below the outer skin layer.
• There is no pill form of Prolia.
• The amount of Prolia you will receive depends on many factors, including your
  general health or other health problems, and the type of cancer or condition you
  have.  Your doctor will determine your dose and schedule. 

Side Effects:

Important things to remember about the side effects of Prolia:

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

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

These are less common side effects (occurring in 10-29%) for patients receiving Prolia:

Osteonecrosis of the jaw has been reported rarely in patients with cancer receiving
treatment regimens that include bone modifying agents.  Many of the reported
cases were associated with dental procedures, such as removal of a tooth. 
A dental examination with appropriate preventative dentistry should be considered
prior to treatment with denosumab, particularly in patients with additional risk
factors (ie cancer, chemotherapy, corticoseroids, poor oral hygiene). 
Invasive dental procedures should be avoided during treatment.

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

When to contact your doctor or health care provider:

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

• Difficulty breathing
• Chest pain
• Swelling of the face/throat
• Confusion

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

Muscle stiffness, twitching, spasms, or cramps (signs of low blood calcium)

Pain, numbness, swelling of or drainage from the jaw, mouth or teeth.

Any signs or symptoms of infection, especially involving the skin (redness, drainage,
pain)

Fever of 100.4° F (38° C)

Fatigue and extreme tiredness (unable to perform self-care activities)

Nausea that interferes with eating and is not relieved by medications prescribed
by your doctor.

Vomiting (more than 4-5 episodes within a 24-hour period).

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

Precautions:

• Do not use both Xgeva and Prolia at the same time.  If you are receiving one,
  you should not be receiving the other, too.
• Before starting Prolia treatment, make sure you tell your doctor about any
  other medications you are taking (including over-the-counter drugs, vitamins, or
  herbal remedies). Do not take aspirin or products containing aspirin unless your
  doctor permits this.
• Prolia may enhance the negative effects of immuno-suppressants.  Specifically,
  the risk for serious infections may be increased.  Notify your doctor of any
  immuno-suppressive medication you are taking.  
• Do not receive any kind of vaccination without your doctor’s approval while taking
  Prolia.
• Inform your health care professional if you are pregnant or may be pregnant prior
  to starting this treatment.  Pregnancy category C (use in pregnancy only if
  benefit to mother outweighs risk to fetus).
• For both men and women: Do not conceive a child (get pregnant) while taking Prolia.
  Barrier methods of contraception, such as condoms, are recommended.
• It is not known whether Prolia is excreted into human milk.  Because of the
  potential for serious adverse reactions in nursing infants from Prolia, a decision
  should be made whether to discontinue nursing or discontinue the drug taking into
  account the importance of the drug to the mother. 

Self-Care Tips:

• Take a calcium and vitamin D supplement as necessary to treat and/or prevent low
  blood calcium levels.  Go for blood tests as ordered by your provider.
• Perform proper, thorough oral hygiene and routine dental care.  Inform your
  dentist that you are being treated with Prolia.
• Avoid invasive dental procedures.
• Inform your physician or dentist if you experience persistent pain and/or slow
  healing of the mouth or jaw following invasive dental procedures. 
• Drink at least 2 to 3 quarts of fluid every 24 hours, unless you are instructed
  otherwise, as it is important to avoid becoming dehydrated.
• Acetaminophen may help relieve discomfort from fever, headache and generalized aches
  and pains, however talk with your provider prior to taking it.
• To reduce nausea, take anti-nausea medications as prescribed by your doctor, and
  eat small, frequent meals.
• Eat foods that may help reduce diarrhea (see managing side effects –
  diarrhea) and if necessary, follow the regimen of anti-diarrhea medication as
  prescribed by your health care professional.
• Use mild, unscented soaps, laundry detergents, and lotions to avoid irritating your
  skin.  Use lotion liberally to keep skin moisturized and prevent cracking.
  (see managing side effects –
  dry skin)
• Get plenty of rest.
• Maintain good nutrition.
• If you experience symptoms or side effects, be sure to discuss them with your health
  care team. They can prescribe medications and/or offer other suggestions that are
  effective in managing such problems.

Monitoring and Testing:

You will be checked regularly by your doctor while you are taking Prolia, to monitor
side effects and check your response to therapy.  Periodic blood work will
be obtained to monitor the function of your organs (such as your kidneys and
liver), as deemed necessary by your doctor.

How Prolia Works:

Cancer cells that spread to the bone can secrete substances that can cause cells
in the bone called osteoclasts to dissolve or “eat away” a portion of the bone. 
The process, during which osteoclasts break down bone and then release those minerals
such as calcium from bone fluid into the blood, is called “bone resorption”. 
These tumors or lesions in the bone weaken the bone and can lead to complications,
referred to as “skeletal related events”.  Some of the complications (skeletal
related events)  that can result from this bone breakdown are bone pain, fractures,
and the need for additional procedures such as radiation therapy to reduce pain
or surgery to fix or stabilize an affected bone.  Bone resorption also releases
growth factors that may cause growth of tumors.

Receptor activator of nuclear factor kappa-B ligand (RANKL) is a type of protein
that is important in bone metabolism.  This natural and necessary protein is
found on oteoblasts (cells that are responsible for bone formation) and serves to
activate osteoclasts (cells involved in bone resorption – as described above).  By
inhibiting RANKL we may be able to decrease bone resorption and therefore decrease
bone loss and hypercalcemia. 

Prolia binds to RANKL, a protein that is essential for the formation, function
and survival of osteoclasts, the cells responsible for bone resorption.  Prolia
inhibits osteoclast formation, function and survival thereby, decreasing bone resorption
and increasing bone mass and strength of the bone.  

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

Chemocare.com is designed to provide the latest information about chemotherapy to patients and their families, caregivers and friends. For information about the 4th Angel Mentoring Program visit www.4thangel.org

Denosumab injection

What is this medicine?

DENOSUMAB (den oh sue mab) slows bone breakdown. Prolia is used to treat osteoporosis in women after menopause and in men, and in people who are taking corticosteroids for 6 months or more. Xgeva is used to treat a high calcium level due to cancer and to prevent bone fractures and other bone problems caused by multiple myeloma or cancer bone metastases. Xgeva is also used to treat giant cell tumor of the bone.

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

COMMON BRAND NAME(S): Prolia, XGEVA

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

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

• dental disease
• having surgery or tooth extraction
• infection
• kidney disease
• low levels of calcium or Vitamin D in the blood
• malnutrition
• on hemodialysis
• skin conditions or sensitivity
• thyroid or parathyroid disease
• an unusual reaction to denosumab, other medicines, foods, dyes, or preservatives
• pregnant or trying to get pregnant
• breast-feeding

How should I use this medicine?

This medicine is for injection under the skin. It is given by a health care professional in a hospital or clinic setting.

A special MedGuide will be given to you before each treatment. Be sure to read this information carefully each time.

For Prolia, talk to your pediatrician regarding the use of this medicine in children. Special care may be needed. For Xgeva, talk to your pediatrician regarding the use of this medicine in children. While this drug may be prescribed for children as young as 13 years for selected conditions, precautions do apply.

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

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

What if I miss a dose?

It is important not to miss your dose. Call your doctor or health care professional if you are unable to keep an appointment.

What may interact with this medicine?

Do not take this medicine with any of the following medications:

• other medicines containing denosumab

This medicine may also interact with the following medications:

• medicines that lower your chance of fighting infection
• steroid medicines like prednisone or cortisone

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

What should I watch for while using this medicine?

Visit your doctor or health care professional for regular checks on your progress. Your doctor or health care professional may order blood tests and other tests to see how you are doing.

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

You should make sure you get enough calcium and vitamin D while you are taking this medicine, unless your doctor tells you not to. Discuss the foods you eat and the vitamins you take with your health care professional.

See your dentist regularly. Brush and floss your teeth as directed. Before you have any dental work done, tell your dentist you are receiving this medicine.

Do not become pregnant while taking this medicine or for 5 months after stopping it. Talk with your doctor or health care professional about your birth control options while taking this medicine. Women should inform their doctor if they wish to become pregnant or think they might be pregnant. There is a potential for serious side effects to an unborn child. Talk to your health care professional or pharmacist for more information.

What side effects may I notice from receiving this medicine?

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

• allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue
• bone pain
• breathing problems
• dizziness
• jaw pain, especially after dental work
• redness, blistering, peeling of the skin
• signs and symptoms of infection like fever or chills; cough; sore throat; pain or trouble passing urine
• signs of low calcium like fast heartbeat, muscle cramps or muscle pain; pain, tingling, numbness in the hands or feet; seizures
• unusual bleeding or bruising
• unusually weak or tired

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

• constipation
• diarrhea
• headache
• joint pain
• loss of appetite
• muscle pain
• runny nose
• tiredness
• upset stomach

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

Where should I keep my medicine?

This medicine is only given in a clinic, doctor’s office, or other health care setting and will not be stored at home.

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

Prolia, Xgeva (denosumab) dosing, indications, interactions, adverse effects, and more

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HWmo_”-

Memorial Sloan Kettering Cancer Center

This information from Lexicomp^® explains what you need to know about this medication, including what it’s used for, how to take it, its side effects, and when to call your healthcare provider.

Brand Names: US

Prolia; Xgeva

Brand Names: Canada

Prolia; Xgeva

What is this drug used for?

• It is used to treat soft, brittle bones (osteoporosis).
• It is used for bone growth.
• It is used when treating some cancers.
• It is used to treat high calcium levels in patients with cancer.
• It may be given to you for other reasons. Talk with the doctor.

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

• If you are allergic to this drug; any part of this drug; or any other drugs, foods, or substances. Tell your doctor about the allergy and what signs you had.
• If you have low calcium levels.
• If you are using another drug that has the same drug in it.
• If you are pregnant or may be pregnant. Do not take this drug if you are pregnant.
• If you are breast-feeding or plan to breast-feed.

This is not a list of all drugs or health problems that interact with this drug.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this drug with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

What are some things I need to know or do while I take this drug?

All products:

• Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists.
• This drug may raise the chance of a broken leg. Talk with the doctor.
• If treatment with this drug is stopped, skipped, or delayed, the chance of a broken bone is raised. This includes bones in the spine. The chance of having more than 1 broken bone in the spine is raised if you have ever had a broken bone in your spine. Do not stop, skip, or delay treatment with this drug without talking to your doctor.
• Have a bone density test as you have been told by your doctor. Talk with your doctor.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• Take calcium and vitamin D as you were told by your doctor.
• Have a dental exam before starting this drug.
• Take good care of your teeth. See a dentist often.
• This drug may cause harm to an unborn baby. A pregnancy test will be done before you start this drug to show that you are NOT pregnant.
• If you may become pregnant, you must use birth control while taking this drug and for some time after the last dose. Ask your doctor how long to use birth control. If you get pregnant, call your doctor right away.

Xgeva^®:

• Very low blood calcium levels have happened with this drug. Sometimes, this has been deadly. If you have questions, talk with the doctor.
• High calcium levels have happened after this drug was stopped in people whose bones were still growing and people with giant cell bone tumor. Call your doctor right away if you have signs of high calcium levels like weakness, confusion, feeling tired, headache, upset stomach or throwing up, constipation, or bone pain.

Prolia^™:

• Very bad infections have been reported with use of this drug. If you have any infection, are taking antibiotics now or in the recent past, or have many infections, talk with your doctor.
• Rarely, a pancreas problem (pancreatitis) has happened with this drug. This has included 1 death. Call your doctor right away if you have signs of pancreatitis like very bad stomach pain, very bad back pain, or very bad upset stomach or throwing up.
• This drug may lower blood calcium levels. If you already have low blood calcium, it may get worse with this drug. Sometimes, blood calcium levels have stayed low for weeks or months after use of this drug. Talk with the doctor.
• This drug is not approved for use in children. Talk with the doctor.

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

All products:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of low calcium levels like muscle cramps or spasms, numbness and tingling, or seizures.
• Mouth sores.
• Swelling in the arms or legs.
• Feeling very tired or weak.
• Any new or strange groin, hip, or thigh pain.
• Very bad bone, joint, or muscle pain.
• Shortness of breath.
• This drug may cause jawbone problems. The risk may be higher with longer use, cancer, dental problems, ill-fitting dentures, anemia, blood clotting problems, or infection. It may also be higher if you have dental work, chemo, radiation, or take other drugs that may cause jawbone problems. Many drugs can do this. Talk with your doctor if any of these apply to you, or if you have questions. Call your doctor right away if you have jaw swelling or pain.

Xgeva^®:

• Signs of low phosphate levels like change in eyesight, feeling confused, mood changes, muscle pain or weakness, shortness of breath or other breathing problems, or trouble swallowing.
• Very bad dizziness or passing out.
• Any unexplained bruising or bleeding.

Prolia^™:

• Signs of infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal.
• Signs of skin infection like oozing, heat, swelling, redness, or pain.
• Signs of high or low blood pressure like very bad headache or dizziness, passing out, or change in eyesight.
• Small bumps or patches on your skin, dry skin, or if your skin feels like leather.
• Bladder pain or pain when passing urine or change in how much urine is passed.
• Passing urine more often.

What are some other side effects of this drug?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

All products:

• Back pain.
• Headache.
• Signs of a common cold.
• Pain in arms or legs.
• Muscle or joint pain.

Xgeva^®:

• Constipation, diarrhea, stomach pain, upset stomach, throwing up, or feeling less hungry.
• Feeling tired or weak.
• Nose or throat irritation.
• Tooth pain.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to your national health agency.

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

How is this drug best taken?

Use this drug as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as a shot into the fatty part of the skin.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

How do I store and/or throw out this drug?

• If you need to store this drug at home, talk with your doctor, nurse, or pharmacist about how to store it.

General drug facts

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else’s drugs.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
• Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your doctor, nurse, pharmacist, or other health care provider.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this drug, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Consumer Information Use and Disclaimer

This generalized information is a limited summary of diagnosis, treatment, and/or medication information. It is not meant to be comprehensive and should be used as a tool to help the user understand and/or assess potential diagnostic and treatment options. It does NOT include all information about conditions, treatments, medications, side effects, or risks that may apply to a specific patient. It is not intended to be medical advice or a substitute for the medical advice, diagnosis, or treatment of a health care provider based on the health care provider’s examination and assessment of a patient’s specific and unique circumstances. Patients must speak with a health care provider for complete information about their health, medical questions, and treatment options, including any risks or benefits regarding use of medications. This information does not endorse any treatments or medications as safe, effective, or approved for treating a specific patient. UpToDate, Inc. and its affiliates disclaim any warranty or liability relating to this information or the use thereof. The use of this information is governed by the Terms of Use, available at https://www.wolterskluwer.com/en/solutions/lexicomp/about/eula.

Last Reviewed Date

2020-08-03

Copyright

© 2021 UpToDate, Inc. and its affiliates and/or licensors. All rights reserved.

Denosumab (Prolia, Xgeva) | Cancer information

Denosumab (pronounced den-oh-sue-mab) is a type of targeted therapy called a monoclonal antibody. It is made in the laboratory to recognise and find specific proteins on the outside of some cells. Denosumab is also known by its brand names, Xgeva and Prolia. 

It helps to prevent fractures and other cancer related bone problems in adults with cancer that has spread to the bones.

Prolia can reduce the risk of spinal fractures in men who have weakened bones due to hormone therapy for prostate cancer.

It also helps to slow down bone damage in people who have giant cell tumour of the bone (a non cancerous type of bone tumour).  

How it works

In healthy bones, specialised cells constantly break down and replace old tissue. These specialised bone cells are:

• osteoclasts, which break down old bone
• osteoblasts, which build new bone

This process is called bone remodelling and is very well controlled. There is a fine balance between the rates of bone breakdown and growth, which keeps bones strong and healthy.

Denosumab works by targeting a protein called RANKL which controls the activity of osteoclasts. This stops bone cells being broken down and strengthens the bone.

How you have it

You have denosumab as an injection just below the skin (subcutaneously). You, or your carer might be taught how to do these injections.

Nurse: This is a short film showing you how to give an injection just under your skin. This is called a subcutaneous or sub cut injection. This does not replace what your doctors and nurses tell you, so always follow their advice.

Voiceover:  Subcutaneous injections may be part of your cancer treatment. Or, you may need them to prevent side effects of treatment, such as blood clots after surgery. Or to help control cancer symptoms, such as pain or sickness.

Most injections come in prefilled syringes.

Nurse: So, today I am going to show you how to give a subcutaneous injection. I am going to start by giving it into a practice cushion and then you can have a go at giving one yourself. Before you start, you need to get your equipment together. What you are going to need is an alcohol wipe to clean your skin, some cotton wool, a prefilled syringe and a sharps bin. It is important that you wash your hands with soap and water and dry them thoroughly before you start. Check that you have got the correct drug and that it is in date.

You can give the injection into the back of your arm, your tummy, your thigh or the outer part of your bottom. It is important that you vary where you give the injection. So it may be that you give it one day in your tummy and the next in your thigh.

So you start by cleaning the skin with the alcohol wipe and allowing it to air dry. Then you take the cover off the needle and pinch the skin up and hold it a bit like a pen and in an upright position, in a quick dart like motion pop it straight down into the skin. Then you press the plunger right to the end, quickly pull the needle out, dab it with cotton wool, pop the needle into the sharps bin. And then you need to wash your hands again.

So here’s what you are going to need. If you start by checking the drug and the expiry date. And then with the alcohol wipe give your skin a clean. That’s it give it a few seconds for the air to dry it. Okay, and then if you want to pick up the syringe and take the cover off the needle. Then pinch your skin up and at a ninety degree angle gently push the needle in…then press the plunger…and then quickly remove it… dab your skin with the cotton wool and put the syringe in the sharps bin.

When you have it

How often you have denosumab depends on the dose and whether you have Xgeva or Prolia.

You have Xgeva every 4 weeks. If you have giant cell tumour of the bone you have an extra dose 1 week and 2 weeks after the first dose.

You have Prolia every 6 months.

Tests during treatment

You have blood tests before starting treatment and regularly during your treatment. The tests check your levels of calcium and other chemicals in the blood.

Your doctor usually asks you to see a dentist before and regularly during this treatment to check the condition of your mouth and teeth. 

Side effects

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

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

When to contact your team

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

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

Early treatment can help manage side effects better.

Common side effects

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

Low level of calcium in the blood 

Low calcium levels in the blood can cause painful muscle spasms, cramps or muscle twitching. You might also get numbness or tingling in your feet, hands or around your mouth.

You usually have calcium and vitamin d supplements to take while you’re on denosumab. 

Shortness of breath

You might find it difficult to breath or get your breath. Contact your advice line or tell your doctor or nurse. 

Diarrhoea 

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

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

Pain

You might have muscle and or bone pain. You might also have pain in your arms and legs. Let your doctor or nurse know so they can advise you on how to reduce it.

Occasional side effects

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

• damage to your jaw bone – signs include ongoing jaw pain, swelling, numbness, heavy feeling in the jaw and loosing of teeth. Contact your advice line or tell your doctor or nurse straight away
• if you are having denosumab because your cancer has spread to the bones there is a small chance you might develop another type of cancer
• low levels of phosphate in the blood – if you are feeling tired, have sore muscles, lose your appetite, feel irritable or confused contact your advice line or tell your doctor or nurse straight away
• you might need to have a tooth taken out
• you might sweat more

Other occasional side effects of Prolia

• infections such as urine infections
• pain or tingling that moves through your hip and down your leg (sciatica)
• constipation and tummy (abdominal) pain
• skin problems such as a rash and dry, itchy skin
• hair loss

Rare side effects

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

• if you are having denosumab for giant cell tumour of the bone you might have high levels of calcium in the blood after you stop treatment
• a rash skin or sores in the mouth
• new or unusual pain in your hip, groin or thigh this could be a fracture of your thigh bone

Other side effects

There isn’t enough information to work out how often this side effect might happen.

• damage to the bones in the ear – signs are ear pain, discharge from the ear with or without an infection. Contact your advice line or tell your doctor or nurse straight away if you have any of these symptoms

What else do I need to know

Other medicines, foods and drink

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

Sorbitol

This drug contains a type of sugar called sorbitol. If you have an intolerance to some sugars, ask your doctor if it is safe for you to take this drug.

Pregnancy and contraception

This drug may harm a baby developing in the womb. It is important not to become pregnant or father a child while you are having treatment with this drug and for at least 5 months afterwards. Talk to your doctor or nurse about effective contraception before starting treatment.

Fertility

It is not known whether this treatment affects fertility in people. Talk to your doctor before starting treatment if you think you may want to have a baby in the future.

Breastfeeding

It is not known whether this drug comes through into the breast milk. Doctors usually advise that you don’t breastfeed during this treatment.

Treatment for other conditions

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

More information about this treatment

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

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

Prolia instructions for use: indications, contraindications, side effects – description Prolia Solution for subcutaneous administration (32193)

Denosumab is a fully human monoclonal antibody (IgG2) with high affinity and specificity for the ligand of the nuclear factor kappa B activator receptor (RANKL) and thus prevents the activation of the only receptor RANKL – the activator of nuclear factor kB (RANK), located on the surface of osteoclasts and their precursors.Thus, prevention of the RANKL / RANK interaction inhibits osteoclast formation, activation and duration. As a result, denosumab reduces bone resorption and increases the mass and strength of the cortical and trabecular bone layers.

Pharmacodynamic effects

The administration of denosumab at a dose of 60 mg led to a rapid decrease in serum concentrations of the marker of bone resorption – 1C-telopeptide (CTX) – by approximately 70% within 6 hours after SC administration and approximately by 85% over the next 3 days.The decrease in CTX concentration remained stable over the 6-month dosing interval. The rate of decrease in the concentration of CTX in the blood serum partially decreased with a decrease in the concentration of denosumab in the blood serum, which reflects the reversibility of the effect of denosumab on bone remodeling. These effects were observed throughout the course of treatment. According to the physiological relationship between the processes of formation and resorption during bone remodeling, a decrease in the content of markers of bone formation (for example, bone-specific alkaline phosphatase and serum type 1 collagen N-terminal propeptide) was observed from the first month after the first dose of denosumab.Markers of bone remodeling (markers of bone formation and bone resorption), as a rule, reached pretreatment concentrations no later than 9 months after the last dose of the drug. After the resumption of denosumab treatment, the degree of decrease in CTX concentrations was similar to the degree of decrease in CTX concentration at the beginning of the course of denosumab treatment.

It has been shown that switching from alendronic acid treatment (mean duration of use – 3 years) to denosumab leads to an additional decrease in serum CTX concentration compared with a group of postmenopausal women with low bone mass who continued treatment with alendronic acid.At the same time, changes in serum calcium were similar in both groups.

In experimental studies, inhibition of RANK / RANKL, simultaneously with the binding of osteoprotegerin to the Fc-fragment (OPG-Fc), led to a slowdown in bone growth and impaired dentition. Therefore, treatment with denosumab can inhibit the growth of bones with open growth zones in children and lead to teething problems.

Immunogenicity

Denosumab is a human monoclonal antibody, therefore, as for other drugs of a protein nature, there is a theoretical risk of immunogenicity.More than 13,000 patients were examined for the formation of binding antibodies using the method of sensitive electrochemiluminescence in combination with immunological analysis. Less than 1% of patients taking denosumab for 5 years had antibodies (including preexisting, transient, and growing antibodies). Seropositive patients were further examined for the formation of neutralizing antibodies using chemiluminescence assay in an in vitro cell culture; no neutralizing antibodies were detected.There were no changes in the pharmacokinetic profile, toxicity profile, or clinical response due to antibody formation.

Clinical efficacy

Treatment of postmenopausal osteoporosis

In women with postmenopausal osteoporosis, Prolia increases bone mineral density (BMD), reduces the incidence of hip fractures, vertebral and non-vertebral fractures. The efficacy and safety of denosumab in the treatment of postmenopausal osteoporosis has been proven in a 3-year study.The results of the study show that denosumab significantly, in comparison with placebo, reduces the risk of vertebral and non-vertebral fractures, hip fractures in postmenopausal women with osteoporosis. The study included 7808 women, of whom 23% had frequent vertebral fractures. All three endpoints for efficacy in fracture ratios achieved statistically significant values ​​as measured by a predetermined sequential testing scheme.

The reduction in the risk of new vertebral fractures with the use of denosumab for more than 3 years remained stable and significant. The risk decreased regardless of the 10-year likelihood of major osteoporotic fractures. Risk reduction was also not affected by a history of frequent vertebral fractures, non-vertebral fractures, age, patients, BMD, level of bone remodeling, and prior therapy for osteoporosis.

In postmenopausal women over 75 years of age, denosumab reduced the incidence of new vertebral fractures and, according to post hoc analysis, reduced the incidence of hip fractures.

A decrease in the incidence of non-vertebral fractures was observed regardless of the 10-year likelihood of major osteoporotic fractures.

Denosumab significantly increased BMD in all anatomical regions compared to placebo. The BMD was determined 1 year, 2 and 3 years after the start of therapy. A similar effect on BMD was noted in the lumbar spine, regardless of age, race, body mass index (BMI), BMD, and bone remodeling.

Histological studies confirmed normal bone architectonics and, as expected, decreased bone remodeling compared to placebo. There were no pathological changes, including fibrosis, osteomalacia, and disruption of the architectonics of bone tissue.

Clinical efficacy in the treatment of bone loss caused by hormone-deprivation therapy or therapy with aromatase inhibitors

Treatment of bone loss caused by androgen deprivation

Denosumab efficacy and safety in the treatment of bone loss associated with androgen concentration was proven in a 3-year study of 1,468 patients with non-metastatic prostate cancer.

A significant increase in BMD was determined in the lumbar spine, the entire femur, the femoral neck, and the trochanter of the femur 1 month after the first dose. The increase in BMD in the lumbar spine did not depend on age, race, geographic region, BMI, initial BMD values, bone remodeling; the duration of hormone deprivation therapy and the presence of a vertebral fracture in history.

Denosumab significantly reduced the risk of new vertebral fractures over 3 years of use.A decrease in risk was observed after 1 year and 2 years after initiation of therapy. Denosumab also reduced the risk of more than one osteoporotic fracture at any location.

Treatment of bone loss in women receiving aromatase inhibitor therapy for breast cancer non-metastatic breast cancer.Denosumab significantly increased BMD in all anatomical regions compared to placebo over 2 years. An increase in BMD was observed in the lumbar spine one month after taking the first dose. A positive effect on BMD in the lumbar spine was noted regardless of age, duration of aromatase inhibitor therapy, BMI, previous chemotherapy, prior use of a selective estrogen receptor modulator (SERM), and time elapsed from the onset of menopause.

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

Prolia; Xgeva

Trade names: Canada

Prolia; Xgeva

What is this drug used for?

• Used to treat osteoporosis.
• Used to maintain normal bone growth.
• This medication is used to treat various forms of cancer.
• Used to treat elevated calcium levels in patients with malignant tumors.
• This medicinal product may be used for other indications. Consult your doctor.

What should I tell my doctor BEFORE taking 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.
• With a calcium deficiency.
• If you are using another drug that contains the same active ingredient.
• If you are or may become pregnant. Do not take this drug if you are pregnant.
• if you are breast-feeding or planning to breast-feed.

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

Tell your doctor and pharmacist about all the 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 conditions and in combination with other drugs you are already taking. Do not start or stop taking any medication or change the dosage without your doctor’s approval.

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

All forms of issue:

• Tell all healthcare providers that you are taking this drug. These are doctors, nurses, pharmacists and dentists.
• This drug may increase the risk of a broken leg. Consult your doctor.
• There was an increased risk of bone fractures when this drug was stopped, skipped, or delayed.This also applies to the bones of the spine. The risk of more than 1 bone fracture in the spine is higher if you have ever had a spinal fracture. Discontinuation, skipping, or postponement of this drug is not permitted without first consulting your doctor.
• Get a bone density test as directed by your doctor. Consult your doctor.
• Perform blood tests as directed by your healthcare practitioner. Please consult your doctor.
• Take calcium and vitamin D as directed by your healthcare professional.
• Get a dental checkup before taking this medicine.
• Take good care of your teeth. See your dentist regularly.
• Potential adverse effects of this drug on the fetus. Before you start taking this drug, you will have a pregnancy test to confirm that you are NOT pregnant.
• If you are at risk of becoming pregnant, you must use birth control during treatment and for some time after your last dose of this drug.Ask your doctor how long to use contraception. If you become pregnant, contact your doctor immediately.

Xgeva ^® :

• Very low blood calcium levels have happened with this drug. Sometimes these cases were fatal. If you have any questions, please consult your doctor.
• Patients with ongoing bone growth or giant cell tumor of the bone have had an increase in calcium levels after stopping treatment with this drug.Call your doctor right away if you have signs of high calcium levels, such as weakness, confusion, feeling tired, headache, nausea or vomiting, constipation, or bone pain.

Prolia ^™ :

• Serious infections have happened with this drug. If you have an infection, if you are currently taking antibiotics or have recently taken them, or have multiple infections, consult your doctor.
• Pancreatic problems (pancreatitis) have happened with this drug. At the same time, 1 death was recorded. If you have signs of pancreatitis, such as very severe abdominal pain, very severe back pain, or very severe nausea or vomiting, contact your doctor right away.
• This drug may lower blood calcium levels. If you already have low blood calcium levels, taking this drug may make the condition worse.Sometimes blood calcium levels remain low for weeks or months after using this drug. Consult your doctor.
• This drug is not approved for use in children. Consult your doctor.

What side effects should I report to my doctor immediately?

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

All forms of issue:

• 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 low calcium levels, such as muscle cramps or spasms, numbness or tingling, or seizures.
• Ulcers in the mouth.
• Swelling of the hands or feet.
• Feeling extremely tired or weak.
• Any new or unusual appearance of pain in the groin, buttocks, or thighs.
• Very severe bone, joint or muscle pain.
• Shortness of breath.
• This drug may cause damage to the bone in the lower jaw.This risk may increase with long-term use, cancer, dental problems, poorly fitted dentures, anemia, bleeding disorders, or infection. This risk may also be increased if you are undergoing dental treatment, chemotherapy, radiation therapy, or other drugs that can cause damage to the jaw bone. Many drugs can cause this. Check with your doctor if any of this applies to you or if you have questions.Call your doctor right away if you experience swelling or pain in the lower jaw area.

Xgeva ^® :

• Signs of low phosphate levels such as vision changes, confusion, mood swings, muscle pain or weakness, shortness of breath or other breathing problems, difficulty swallowing.
• Severe dizziness or fainting.
• Any unexplained bruising or bleeding.

Prolia ^™ :

• Signs of infection such as fever, chills, very severe sore throat, ear, or sinuses, cough, increased or discolored phlegm, pain when urinating, mouth ulcers, or an unhealed wound.
• Signs of a skin infection, such as weeping, fever, swelling, redness, or pain.
• Signs of high or low blood pressure, such as very severe headache or dizziness, fainting, or vision changes.
• Small blisters or spots on the skin, dry or rough skin.
• Pain in the bladder or when urinating, or change in the amount of urine excreted.
• Frequent urination.

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:

All forms of issue:

• Back pain.
• Headache.
• Signs of a cold.
• Pain in the arms or legs.
• Pain in joints or muscles.

Xgeva ^® :

• Constipation, diarrhea, abdominal pain, nausea, vomiting, or decreased appetite.
• Feeling tired or weak.
• Nose or throat irritation.
• Toothache.

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.

• For subcutaneous injection.

What should I do if a dose of a drug is missed?

• Call your doctor for further instructions.

How do I store and / or discard this drug?

• If you need to store this drug at home, ask your doctor, nurse, or pharmacist for information about how it is stored.

General information on medicinal products

• If your health does not improve or even worsens, see your doctor.
• You should not give your medicine to anyone and take other people’s medicines.
• 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.
• 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.

Use of information by consumer 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 guide to treatment and does not replace the information provided to you by your healthcare professional. For complete information on the possible risks and benefits of taking this drug, consult your doctor.Use of this information is governed by the Lexicomp End User License Agreement available at https://www.wolterskluwer.com/en/solutions/lexicomp/about/eula.

Copyright

© UpToDate, Inc. and its affiliates and / or licensors, 2021. All rights reserved.

90,000 4 reviews, instructions for use

Denosumab is a fully human monoclonal antibody (IgG2) with high affinity and specificity for the nuclear factor kappa B (RANKL) activator receptor ligand and thereby prevents the activation of the only RANKL receptor – the nuclear factor kB activator ( RANK) located on the surface of osteoclasts and their precursors.Thus, prevention of the RANKL / RANK interaction inhibits osteoclast formation, activation and duration. As a result, denosumab reduces bone resorption and increases the mass and strength of the cortical and trabecular bone layers.

Pharmacodynamic effects

The administration of denosumab at a dose of 60 mg led to a rapid decrease in serum concentrations of the marker of bone resorption – 1C-telopeptide (CTX) – by approximately 70% within 6 hours after SC administration and by approximately 85% during next 3 days.The decrease in CTX concentration remained stable over the 6-month dosing interval. The rate of decrease in the concentration of CTX in the blood serum partially decreased with a decrease in the concentration of denosumab in the blood serum, which reflects the reversibility of the effect of denosumab on bone remodeling. These effects were observed throughout the course of treatment. According to the physiological relationship of the processes of formation and resorption during remodeling of bone tissue, a decrease in the content of markers of bone formation (for example, bone-specific alkaline phosphatase and serum N-terminal propeptide
of type 1 collagen) was observed from the first month after the administration of the first dose of denosumab.Markers of bone remodeling (markers of bone formation and bone resorption), as a rule, reached pretreatment concentrations no later than 9 months after the last dose of the drug. Upon resumption of denosumab treatment, the
decrease in CTX concentrations was similar to the decrease in CTX concentration at the start of denosumab treatment.

It has been shown that switching from alendronic acid treatment (mean duration of use – 3 years) to denosumab leads to an additional decrease in serum CTX concentration compared with a group of postmenopausal women with low bone mass who continued treatment with alendronic acid.At the same time, changes in serum calcium were similar in both groups.

In experimental studies, inhibition of RANK / RANKL, simultaneously with the binding of osteoprotegerin to the Fc-fragment (OPG-Fc), led to a slowdown in bone growth and impaired dentition. Therefore, treatment with denosumab can inhibit the growth of bones with open growth zones in children and lead to teething disorders of
teeth.

Immunogenicity

Denosumab is a human monoclonal antibody, therefore, as for other drugs of a protein nature, there is a theoretical risk of immunogenicity.More than 13,000 patients were examined for the formation of binding antibodies using the method of sensitive electrochemiluminescence in combination with immunological analysis. Less than 1% of patients taking denosumab for 5 years had antibodies (including preexisting, transient, and growing antibodies). Seropositive patients were further examined for the formation of neutralizing antibodies using chemiluminescence assay in an in vitro cell culture; no neutralizing antibodies were detected.There were no changes in the pharmacokinetic profile, toxicity profile, or clinical response due to antibody formation.

Clinical efficacy

Treatment of postmenopausal osteoporosis

In women with postmenopausal osteoporosis, Prolia increases bone mineral density (BMD), reduces the incidence of hip fractures, vertebral and non-vertebral fractures. The efficacy and safety of denosumab in the treatment of postmenopausal osteoporosis has been proven in a 3-year study.The results of the study show that denosumab significantly, in comparison with placebo, reduces the risk of vertebral and non-vertebral fractures, hip fractures in postmenopausal women with osteoporosis. The study included 7808 women, of whom 23% had frequent vertebral fractures. All three endpoints for efficacy in fracture ratios achieved statistically significant values ​​as measured by a predetermined sequential testing scheme.

The reduction in the risk of new vertebral fractures with the use of denosumab for more than 3 years remained stable and significant. The risk decreased regardless of the 10-year likelihood of major osteoporotic fractures. Risk reduction was also not affected by a history of frequent vertebral fractures, non-vertebral fractures, age, patients, BMD, level of bone remodeling, and prior therapy for osteoporosis.

In postmenopausal women over 75 years of age, denosumab reduced the incidence of new vertebral fractures and, according to post hoc analysis, reduced the incidence of hip fractures.

A decrease in the incidence of non-vertebral fractures was observed regardless of the 10-year likelihood of major osteoporotic fractures.

Denosumab significantly increased BMD in all anatomical regions compared to placebo. The BMD was determined 1 year, 2 and 3 years after the start of therapy. A similar effect on BMD was noted in the lumbar spine, regardless of age, race, body mass index (BMI), BMD, and bone remodeling.

Histological studies confirmed normal bone architectonics and, as expected, decreased bone remodeling compared to placebo. There were no pathological changes, including fibrosis, osteomalacia, and disruption of the architectonics of bone tissue.

Clinical efficacy in the treatment of bone loss caused by hormone-deprivation therapy or therapy with aromatase inhibitors

Treatment of bone loss caused by androgen deprivation

The efficacy and safety of denosumab in the treatment of bone loss associated with a decrease in androgen concentration has been proven in 3 x year study of 1,468 patients with non-metastatic prostate cancer.

A significant increase in BMD was determined in the lumbar spine, the entire femur, the femoral neck, and the trochanter of the femur 1 month after the first dose. The increase in BMD in the lumbar spine did not depend on age, race, geographic region, BMI, initial BMD
, bone remodeling; the duration of hormone deprivation therapy and the presence of a vertebral fracture in history.

Denosumab significantly reduced the risk of new vertebral fractures over 3 years of use.A decrease in risk was observed after 1 year and 2 years after initiation of therapy. Denosumab also reduced the risk of more than one osteoporotic fracture at any location.

Treatment of bone loss in women receiving aromatase inhibitor therapy for breast cancer

The efficacy and safety of denosumab in the treatment of bone loss caused by adjuvant aromatase inhibitor therapy was evaluated in a 2-year study of 252 patients with non-metastatic cancer breast.Denosumab significantly increased BMD in all anatomical regions compared to placebo over 2 years. An increase in BMD was observed in the lumbar spine one month after taking the first dose. A positive effect on BMD in the lumbar spine was noted regardless of age, duration of aromatase inhibitor therapy, BMI, previous chemotherapy, prior use of a selective estrogen receptor modulator (SERM), and time elapsed from the onset of menopause.

Pharmacokinetics

When s / c administration, denosumab is characterized by nonlinear pharmacokinetics, dose-dependent in a wide dose range, and dose-dependent increase in exposure for a dose of 60 mg (or 1 mg / kg) and above.

Absorption

After s.c. administration of denosumab at a dose of 60 mg, bioavailability was 61% and C _max denosumab – 6 μg / ml (range 1-17 μg / ml), these parameters were observed after 10 days (range 2- 28 days). After reaching C _max , the serum concentration of the drug decreased from T _1/2 26 days (range 6-52 days) and then within 3 months (range 1.5-4.5 months). In 53% of patients, denosumab was not detected in blood serum after 6 months from the last injection of
of the drug.

Distribution

There were no changes in the pharmacokinetic parameters of denosumab, as well as cumulation during the entire time of taking multiple doses of the drug, 60 mg every 6 months.

Metabolism

Denosumab consists of amino acids and carbohydrates, like a regular immunoglobulin. Based on data from preclinical studies, it is expected that the metabolism of denosumab will occur along the pathway of clearance of immunoglobulins, the result of which will be the breakdown into small peptide chains and individual amino acids.

Elimination

Based on preclinical data, denosumab will be eliminated along the route of elimination of all immunoglobulins, the result of which will be the breakdown into small peptide chains and individual amino acids.

Selected patient groups

Age does not significantly affect the pharmacokinetics of denosumab according to pharmacokinetic analysis in a population of patients from 28 to 87 years old.

Pharmacokinetics in children has not been studied.

Pharmacokinetics of denosumab does not depend on race.

In a study on 55 patients with varying degrees of renal failure, including patients on dialysis, the degree of renal failure did not affect the pharmacokinetics and pharmacodynamics of denosumab; therefore, no correction of the denosumab dosage regimen is required in chronic renal failure.

Studies of the effect of liver failure on the pharmacokinetics of denosumab have not been conducted.

instructions, use, analogues of the drug, composition, indications, contraindications, side effects in the reference book of medicines from UNIAN

Application of Prolia

Prolia – composition and release form of the drug

Prolia: how to take the drug

Prolia – contraindications, side effects

Prolia’s analogs

Prolia – drug for the treatment of bone diseases.

Application Prolia

Treatment of osteoporosis in postmenopausal women with an increased risk of fractures (vertebrae, non-vertebral fractures and hip fractures).

Treatment of bone loss in men with an increased risk of vertebral fractures receiving hormone-suppressive therapy for prostate cancer.

Prolia – composition and release form of the drug

Composition .

active ingredients:

denosumab;

1 ml of solution contains 60 mg of denosumab;

excipients: glacial acetic acid, sodium hydroxide, sorbitol (E 420), polysorbate 20 (only in a pre-filled syringe), water for injection.

Dosage form . Injection.

Prolia: how to take the drug

The drug is used subcutaneously.

Dosage

The recommended dose of Prolia is one subcutaneous injection of 60 mg of the drug 1 time every 6 months, injected into the thigh, abdomen or outer surface of the shoulder.

In addition to this therapy, patients should receive supplements and medications containing calcium and vitamin D.

Directions for use

Preparation for subcutaneous administration.The drug should be used by persons who are properly trained in injection technique.

Before use, the Prolia solution should be inspected for hard lobules or discoloration. The solution must not be used if it has become cloudy or discolored. Do not shake. To prevent discomfort at the injection site, allow the pre-filled syringe to warm to room temperature (up to 25 ° C) before injection and inject the drug slowly. The entire contents of the pre-filled syringe must be injected.Any amount of drug remaining in the pre-filled syringe after injection should be disposed of.

Renal failure

It is not necessary to change the dose of the drug for the treatment of patients with renal failure.

Hepatic impairment

The safety and efficacy of denosumab for the treatment of patients with hepatic impairment have not been studied.

Elderly patients

It is not necessary to change the dose of the drug for the treatment of elderly patients.

Prolia – contraindications, side effects

Contraindication

Hypersensitivity to the active substance or to any of the auxiliary components of the drug. Hypocalcemia.

Adverse reactions.

Adverse reactions are classified into these groups according to their frequency of occurrence:

Within each group, adverse reactions are indicated by frequency and system and are presented in decreasing order of frequency of occurrence.