Prolia

Prolia is a prescription medication used to treat osteoporosis. Prolia is also used to treat bone loss in patients receiving certain treatments for prostate cancer as breast cancer. 

Prolia belongs to a group of drugs called RANK ligand inhibitors. These work by decreasing the breakdown of bone and increasing bone strength and thickness. 

This medication comes in an injectable form to be given under the skin (subcutaneously) and is given once every 6 months.

Common side effects of Prolia include red, dry, and itchy skin, back pain, and headache.

Prolia is part of the drug class:

• Other drugs affecting bone structure and mineralization

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Prolia, there are no specific foods you must exclude from your diet when receiving this medication.

Denosumab is a monoclonal antibody. Monoclonal antibodies are made to target and destroy only certain cells in the body. This may help to protect healthy cells from damage.

The Prolia brand of denosumab is used to treat osteoporosis in postmenopausal women who have high risk of bone fracture. Prolia is also used to increase bone mass in women and men with a high risk of bone fracture caused by receiving treatments for certain types of cancer.

This medication guide provides information about the Prolia brand of denosumab. Xgeva is another brand of denosumab used to prevent bone fractures and other skeletal conditions in people with tumors that have spread to the bone.

Denosumab may also be used for purposes not listed in this medication guide.

Denosumab is injected under the skin of your stomach, upper thigh, or upper arm. A healthcare provider will give you this injection.

Prolia is usually given once every 6 months.

Your doctor may have you take extra calcium and vitamin D while you are being treated with denosumab. Take only the amount of calcium and vitamin D that your doctor has prescribed.

If you need to have any dental work (especially surgery), tell the dentist ahead of time that you are receiving denosumab.

Pay special attention to your dental hygiene. Brush and floss your teeth regularly while receiving this medication. You may need to have a dental exam before you begin treatment with Prolia. Follow your doctor's instructions.

Your risk of bone fractures can increase when you stop using Prolia. Do not stop using this medicine without first talking to your doctor.

If you keep this medicine at home, store it in the original container in a refrigerator. Protect from light and do not freeze.

You may take the medicine out of the refrigerator and allow it to reach room temperature before the injection is given. Do not heat the medicine before using.

Do not shake the prefilled syringe or you may ruin the medicine. Do not use the medicine if it looks cloudy or has particles in it. Call your pharmacist for a new prescription.

Each prefilled syringe of this medicine is for one use only. Throw away after one use, even if there is still some medicine left in it after injecting your dose.

After you have taken Prolia out of the refrigerator, you may keep it at room temperature for up to 14 days. Store in the original container away from heat and light.

Use a disposable needle and syringe only once. Follow any state or local laws about throwing away used needles and syringes. Use a puncture-proof "sharps" disposal container (ask your pharmacist where to get one and how to throw it away). Keep this container out of the reach of children and pets.

Do not share this medicine with another person, even if they have the same symptoms you have.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Get emergency medical help if you have signs of an allergic reaction: hives, itching, rash; difficult breathing, feeling light-headed; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• new or unusual pain in your thigh, hip, or groin;

• severe pain in your joints, muscles, or bones;

• skin problems such as dryness, peeling, redness, itching, blisters, bumps, oozing, or crusting; or

• low levels of calcium in your blood (hypocalcemia)--numbness or tingly feeling around your mouth or in your fingers or toes, muscle tightness or contraction, overactive reflexes.

Serious infections may occur during treatment with Prolia. Call your doctor right away if you have signs of infection such as:

• fever, chills, night sweats;

• swelling, pain, tenderness, warmth, or redness anywhere on your body;

• pain or burning when you urinate;

• increased or urgent need to urinate;

• severe stomach pain; or

• cough, feeling short of breath.

Common side effects may include:

• bladder infection (painful or difficult urination);

• back pain, muscle pain; or

• pain in your arms or legs.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Other drugs may interact with denosumab, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

General

• Correct preexisting hypocalcemia prior to initiating denosumab.1 2

• All patients receiving denosumab (Prolia) for treatment of osteoporosis or treatment of bone loss associated with androgen deprivation or aromatase inhibitor therapy should receive 1 g of calcium and at least 400 units of vitamin D daily.1

• Patients receiving denosumab (Xgeva) for prevention of SREs or treatment of giant cell tumor of bone should receive calcium, vitamin D, and magnesium supplementation as necessary.2

Administration

Sub-Q Administration

Administer by sub-Q injection into upper arm, upper thigh, or abdomen;1 2 do not inject into muscle or blood vessels.1

Manufacturer states Prolia should be administered by a health-care professional.1

Prior to administration, may warm to room temperature by allowing drug to stand in original packaging at room temperature (≤25°C) for approximately 15–30 minutes.1 2 Do not warm using any other method.1 2

Solution should appear clear, colorless to pale yellow; may contain trace amounts of translucent to white proteinaceous particles.1 2 Do not use if solution is discolored, cloudy, or contains many particles or foreign matter.1 2

Single-use prefilled syringe (Prolia): Remove gray needle cap and inject entire solution.1 After injection is complete, activate needle guard by pointing needle away from body and gently sliding green safety guard toward needle until locked securely in place.1 The needle cap contains dry natural rubber (latex) and should not be handled by individuals sensitive to latex.1 (See Latex Sensitivity under Cautions.)

Single-use vial (Prolia, Xgeva): Use 27-gauge needle to withdraw and inject entire vial contents.1 2 Do not re-enter vial; discard any remaining solution along with the vial.1 2

Dosage

Pediatric Patients

120 mg once every 4 weeks; during first month of treatment, give additional 120-mg dose on day 8 and 15.2

Adults

60 mg once every 6 months.1

Administer a missed dose as soon as patient is available; give subsequent doses every 6 months from date of last dose.1

60 mg once every 6 months.1

Administer a missed dose as soon as patient is available; give subsequent doses every 6 months from date of last dose.1

60 mg once every 6 months.1

Administer a missed dose as soon as patient is available; give subsequent doses every 6 months from date of last dose.1

60 mg once every 6 months.1

Administer a missed dose as soon as patient is available; give subsequent doses every 6 months from date of last dose.1

120 mg once every 4 weeks.2

120 mg once every 4 weeks; during first month of treatment, give additional 120-mg dose on day 8 and 15.2

Special Populations

Hepatic Impairment

Pharmacokinetics not evaluated in patients with hepatic impairment.1 2

Renal Impairment

Dosage adjustment not necessary in patients with renal impairment.1 27 However, those with severe renal impairment (Clcr <30 mL/minute) or receiving dialysis are at greater risk of developing hypocalcemia.1 2 (See Hypocalcemia and Mineral Metabolism under Cautions.)

• Denosumab, a fully human monoclonal IgG2 antibody, is a bone resorption inhibitor.1 2 10 25

• Denosumab is specific for and binds to RANKL, and acts as a RANKL inhibitor preventing interaction with its receptor (RANK).1 2 10 25 The interaction between RANK and RANKL is integral to normal bone resorption process.10 As a result, denosumab inhibits osteoclast formation, function, and survival and, ultimately, bone resorption.1 10

• In postmenopausal women with osteoporosis, denosumab increases BMD and reduces incidence of vertebral, nonvertebral, and hip fractures.1 4

• In patients with bone loss associated with androgen deprivation or aromatase inhibitor therapy, denosumab increases BMD;1 17 18 also reduces incidence of vertebral fractures in men with prostate cancer receiving androgen deprivation therapy.1 17

• In patients with solid tumors and metastases to the bone, denosumab delays time to first SRE.2 19 20 21

• Effects of denosumab are considered reversible since bone turnover markers and BMD return to baseline within 12 months after the drug is discontinued.1 10 12

• In giant cell tumors of bone, stromal cells express RANKL and osteoclast-like giant cells express RANK receptor;2 signaling through the RANK receptor contributes to osteolysis and tumor growth.2 Denosumab (Xgeva) prevents RANKL from activating the receptor on the surfaces of osteoclasts, their precursors, and osteoclast-like giant cells.2

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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:

• 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 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.
• Dizziness or passing out.
• This medicine may cause jawbone problems. The chance may be higher the longer you take Prolia (denosumab injection (prolia)). The chance may be higher if you have cancer, dental problems, dentures that do not fit well, anemia, blood clotting problems, or an infection. The chance may also be higher if you are having dental work, getting chemo or radiation, or taking other drugs that may cause jawbone problems like some steroid drugs. There are many drugs that can do this. Ask your doctor or pharmacist if you are not sure. Call your doctor right away if you have jaw swelling or pain.
• 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 a pancreas problem (pancreatitis) like very bad stomach pain, very bad back pain, or very bad upset stomach or throwing up.
• Very bad skin irritation.
• Bladder pain or pain when passing urine or change in how much urine is passed.
• Passing urine more often.

1.1       Treatment of Postmenopausal Women with Osteoporosis at High Risk for Fracture

Prolia is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy.  In postmenopausal women with osteoporosis, Prolia reduces the incidence of vertebral, nonvertebral, and hip fractures [see Clinical Studies (14.1)].

1.2       Treatment to Increase Bone Mass in Men with Osteoporosis

Prolia is indicated for treatment to increase bone mass in men with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy [see Clinical Studies (14.2)].

1.3       Treatment of Bone Loss in Men Receiving Androgen Deprivation Therapy for Prostate Cancer

Prolia is indicated as a treatment to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer. In these patients Prolia also reduced the incidence of vertebral fractures [see Clinical Studies (14.3)].

1.4       Treatment of Bone Loss in Women Receiving Adjuvant Aromatase Inhibitor Therapy for Breast Cancer

Prolia is indicated as a treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer [see Clinical Studies (14.4)].

In subjects with postmenopausal osteoporosis, Prolia (60 mg subcutaneous injection) did not affect the pharmacokinetics of midazolam, which is metabolized by cytochrome P450 3A4 (CYP3A4), indicating that it should not affect the pharmacokinetics of drugs metabolized by this enzyme in this population [see Clinical Pharmacology (12.3)].  

Applies to denosumab: subcutaneous solution

Along with its needed effects, denosumab (the active ingredient contained in Prolia) 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 while taking denosumab:

• Back pain
• blistering, crusting, irritation, itching, or reddening of the skin
• bloody or cloudy urine
• cracked, dry, or scaly skin
• difficult, burning, or painful urination
• frequent urge to urinate
• muscle or bone pain
• pain in the arms or legs
• rash
• skin rash, encrusted, scaly, and oozing
• swelling

• Abdominal or stomach cramps
• arm or jaw pain
• bloating or swelling of the face, arms, hands, lower legs, or feet
• body aches or pain
• chest pain or discomfort
• chest tightness or heaviness
• confusion
• congestion
• convulsions
• cough
• difficulty with breathing
• difficulty with moving
• dryness or soreness of the throat
• ear congestion
• fast or irregular heartbeat
• fever or chills
• headache
• hoarseness
• joint pain
• loss of voice
• muscle cramps in the hands, arms, feet, legs, or face
• muscle stiffness
• numbness and tingling around the mouth, fingertips, hands, or feet
• pain in the lower back, bottom, or hips
• pain in the upper leg
• painful blisters on the trunk of the body
• pale skin
• rapid weight gain
• runny or stuffy nose
• sneezing
• swollen joints
• tender, swollen glands in the neck
• tremor
• trouble swallowing
• troubled breathing with exertion
• unusual bleeding or bruising
• unusual tiredness or weakness
• unusual weight gain or loss
• voice changes

• Abdominal or stomach discomfort
• blood in the stool
• change in bowel habits
• clear or bloody discharge from the nipple
• constipation
• darkened urine
• difficulty with swallowing or eating
• dimpling of the breast skin
• indigestion
• inverted nipple
• itching, pain, redness, swelling, tenderness, or warmth on the skin
• loss of appetite
• lower back or side pain
• lump in the breast or under the arm
• lump or swelling in the abdomen or stomach
• nausea
• pains in the stomach, side, or abdomen, possibly radiating to the back
• persistent crusting or scaling of the nipple
• raised, firm, and bright red patches of the skin on the arm or leg
• redness or swelling of the breast
• sore on the skin of the breast that does not heal
• unexplained weight loss
• vomiting
• yellow eyes or skin

• Heavy feeling in the jaw
• loose teeth
• pain, swelling, or numbness in the mouth or jaw

Some side effects of denosumab 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:

• Dizziness or lightheadedness
• excess air or gas in the stomach or intestines
• feeling of constant movement of self or surroundings
• full feeling
• heartburn
• lack or loss of strength
• passing gas
• redness, pain, itching, burning, swelling, or a lump under your skin where the shot was given
• sensation of spinning
• trouble sleeping
• upper abdominal or stomach pain