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Prolia

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Prolia

Prolia Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

Prolia (denosumab) is used to treat bone loss (osteoporosis) in women who are at high risk for bone fracture after menopause. It belongs to a class of drugs called monoclonal antibodies. Common side effects include low calcium levels, especially if you have kidney problems. You may also be more likely to get a serious infection, such as a skin, ear, stomach/gut, or bladder infection. Tell your doctor if you develop signs of infection, such as: fever/chills, red/swollen/tender/warm skin (with or without pus), severe abdominal pain, ear pain, frequent/painful/burning urination, pink/bloody urine.

Prolia should be administered by a doctor. The recommended dose of Prolia is 60 mg administered as a single subcutaneous (under the skin) injection once every 6 months. The effects of some drugs can change if you take other drugs or herbal products at the same time. This can increase your risk for serious side effects or may cause your medications not to work correctly. Tell your doctor about all the products you use (including prescription drugs, nonprescription drugs, and herbal products) before starting treatment with this product. Prolia is usually used in women after menopause. It is unlikely to be used during pregnancy or breast-feeding. It is not recommended for use during pregnancy. It may harm a fetus. It is unknown if this medication passes into breast milk. Consult your doctor before breast-feeding.

Our Prolia (denosumab) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

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.

What is Patient Information in Detail?

Easy-to-read and understand detailed drug information and pill images for the patient or caregiver from Cerner Multum.

Prolia in Detail - Patient Information: Side Effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

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

  • severe itching, burning, rash, blistering, peeling, or dryness of the skin;
  • swelling, pain, tenderness, warmth, or redness anywhere on your body;
  • pain or burning when you urinate, blood in your urine;
  • severe stomach pain;
  • ear pain or drainage, trouble hearing;
  • fever, chills, night sweats;
  • cough, feeling short of breath;
  • pinpoint purple or red spots under your skin; or
  • flu symptoms, weight loss.

Call your doctor at once if you have a serious side effect such as:

  • numbness or tingly feeling around your mouth or in your fingers or toes, fast or slow heart rate, muscle cramps or contraction, overactive reflexes; or
  • severe pain in your upper stomach spreading to your back, nausea and vomiting, fast heart rate.

Less serious side effects may include:

  • weakness;
  • constipation;
  • 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.

Read the entire detailed patient monograph for Prolia (Denosumab Injection) »

What is Patient Information Overview?

A concise overview of the drug for the patient or caregiver from First DataBank.

Prolia Overview - Patient Information: Side Effects

SIDE EFFECTS: See also Precautions section.

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.

Denosumab may cause low calcium levels, especially if you have kidney problems. Take calcium and vitamin D as directed by your doctor. (See also How to Use section.) Your doctor will order calcium blood tests before your first injection and during treatment. Tell your doctor immediately if you have any symptoms of low calcium such as: muscle spasms/cramps, mental/mood changes (such as irritability or confusion), numbness/tingling (especially around lips/mouth or in fingers/toes), seizures.

Denusomab can affect your immune system. You may be more likely to get a serious infection, such as a skin, ear, stomach/gut, or bladder infection. Tell your doctor immediately if you develop any signs of infection, such as: fever/chills, red/swollen/tender/warm skin (with or without pus), severe abdominal pain, ear pain, frequent/painful/burning urination, pink/bloody urine.

Tell your doctor right away if you have any serious side effects, including: jaw pain, new or unusual thigh/hip/groin pain.

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.

Denosumab can cause skin problems such as dryness, peeling, redness, itching, small bumps/patches, or blisters. However, you may not be able to tell it apart from a rare rash that could be a sign of a severe allergic reaction. Therefore, get medical help right away if you develop any rash or if any of these symptoms persist or worsen.

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.

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

Read the entire patient information overview for Prolia (Denosumab Injection)»

What is Prescribing information?

The FDA package insert formatted in easy-to-find categories for health professionals and clinicians.

Prolia FDA Prescribing Information: Side Effects
(Adverse Reactions)

SIDE EFFECTS

The following serious adverse reactions are discussed below and also elsewhere in the labeling:

The most common adverse reactions reported with Prolia in patients with postmenopausal osteoporosis are back pain, pain in extremity, musculoskeletal pain, hypercholesterolemia, and cystitis.

The most common adverse reactions reported with Prolia in men with osteoporosis are back pain, arthralgia, and nasopharyngitis.

The most common (per patient incidence ≥ 10%) adverse reactions reported with Prolia in patients with bone loss receiving androgen deprivation therapy for prostate cancer or adjuvant aromatase inhibitor therapy for breast cancer are arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials.

The most common adverse reactions leading to discontinuation of Prolia in patients with postmenopausal osteoporosis are back pain and constipation.

The Prolia Postmarketing Active Safety Surveillance Program is available to collect information from prescribers on specific adverse events. Please see www.proliasafety.com or call 1-800-772-6436 for more information about this program.

Clinical Trials Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice.

Treatment of Postmenopausal Women with Osteoporosis

The safety of Prolia in the treatment of postmenopausal osteoporosis was assessed in a 3-year, randomized, double-blind, placebo-controlled, multinational study of 7808 postmenopausal women aged 60 to 91 years. A total of 3876 women were exposed to placebo and 3886 women were exposed to Prolia administered subcutaneously once every 6 months as a single 60 mg dose. All women were instructed to take at least 1000 mg of calcium and 400 IU of vitamin D supplementation per day.

The incidence of all-cause mortality was 2.3% (n = 90) in the placebo group and 1.8% (n = 70) in the Prolia group. The incidence of nonfatal serious adverse events was 24.2% in the placebo group and 25.0% in the Prolia group. The percentage of patients who withdrew from the study due to adverse events was 2.1% and 2.4% for the placebo and Prolia groups, respectively. Adverse reactions reported in ≥ 2% of postmenopausal women with osteoporosis and more frequently in the Prolia-treated women than in the placebo-treated women are shown in the table below.

Table 1: Adverse Reactions Occurring in ≥ 2% of Patients with Osteoporosis and More Frequently than in Placebo-treated Patients

SYSTEM ORGAN CLASS Preferred Term Prolia
(N = 3886)
n (%)
Placebo
(N = 3876)
n (%)
BLOOD AND LYMPHATIC SYSTEM DISORDERS
  Anemia 129 (3.3) 107 (2.8)
CARDIAC DISORDERS
  Angina pectoris 101 (2.6) 87 (2.2)
  Atrial fibrillation 79 (2.0) 77 (2.0)
EAR AND LABYRINTH DISORDERS
  Vertigo 195 (5.0) 187 (4.8)
GASTROINTESTINAL DISORDERS
  Abdominal pain upper 129 (3.3) 111 (2.9)
  Flatulence 84 (2.2) 53 (1.4)
  Gastroesophageal reflux disease 80 (2.1) 66 (1.7)
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS
  Edema peripheral 189 (4.9) 155 (4.0)
  Asthenia 90 (2.3) 73 (1.9)
INFECTIONS AND INFESTATIONS
  Cystitis 228 (5.9) 225 (5.8)
  Upper respiratory tract infection 190 (4.9) 167 (4.3)
  Pneumonia 152 (3.9) 150 (3.9)
  Pharyngitis 91 (2.3) 78 (2.0)
  Herpes zoster 79 (2.0) 72 (1.9)
METABOLISM AND NUTRITION DISORDERS
  Hypercholesterolemia 280 (7.2) 236 (6.1)
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS
  Back pain 1347 (34.7) 1340 (34.6)
  Pain in extremity 453 (11.7) 430 (11.1)
  Musculoskeletal pain 297 (7.6) 291 (7.5)
  Bone pain 142 (3.7) 117 (3.0)
  Myalgia 114 (2.9) 94 (2.4)
  Spinal osteoarthritis 82 (2.1) 64 (1.7)
NERVOUS SYSTEM DISORDERS
  Sciatica 178 (4.6) 149 (3.8)
PSYCHIATRIC DISORDERS
  Insomnia 126 (3.2) 122 (3.1)
SKIN AND SUBCUTANEOUS TISSUE DISORDERS
  Rash 96 (2.5) 79 (2.0)
  Pruritus 87 (2.2) 82 (2.1)

Hypocalcemia

Decreases in serum calcium levels to less than 8.5 mg/dL at any visit were reported in 0.4% women in the placebo group and 1.7% women in the Prolia group. The nadir in serum calcium level occurs at approximately day 10 after Prolia dosing in subjects with normal renal function.

In clinical studies, subjects with impaired renal function were more likely to have greater reductions in serum calcium levels compared to subjects with normal renal function. In a study of 55 subjects with varying degrees of renal function, serum calcium levels < 7.5 mg/dL or symptomatic hypocalcemia were observed in 5 subjects. These included no subjects in the normal renal function group, 10% of subjects in the creatinine clearance 50 to 80 mL/min group, 29% of subjects in the creatinine clearance < 30 mL/min group, and 29% of subjects in the hemodialysis group. These subjects did not receive calcium and vitamin D supplementation. In a study of 4550 postmenopausal women with osteoporosis, the mean change from baseline in serum calcium level 10 days after Prolia dosing was -5.5% in subjects with creatinine clearance < 30 mL/min vs. -3.1% in subjects with creatinine clearance ≥ 30 mL/min.

Serious Infections

Receptor activator of nuclear factor kappa-B ligand (RANKL) is expressed on activated T and B lymphocytes and in lymph nodes. Therefore, a RANKL inhibitor such as Prolia may increase the risk of infection.

In the clinical study of 7808 postmenopausal women with osteoporosis, the incidence of infections resulting in death was 0.2% in both placebo and Prolia treatment groups. However, the incidence of nonfatal serious infections was 3.3% in the placebo and 4.0% in the Prolia groups. Hospitalizations due to serious infections in the abdomen (0.7% placebo vs. 0.9% Prolia), urinary tract (0.5% placebo vs. 0.7% Prolia), and ear (0.0% placebo vs. 0.1% Prolia) were reported. Endocarditis was reported in no placebo patients and 3 patients receiving Prolia.

Skin infections, including erysipelas and cellulitis, leading to hospitalization were reported more frequently in patients treated with Prolia ( < 0.1% placebo vs. 0.4% Prolia).

The incidence of opportunistic infections was similar to that reported with placebo.

Dermatologic Reactions

A significantly higher number of patients treated with Prolia developed epidermal and dermal adverse events (such as dermatitis, eczema, and rashes), with these events reported in 8.2% of the placebo and 10.8% of the Prolia groups (p < 0.0001). Most of these events were not specific to the injection site [see WARNINGS AND PRECAUTIONS].

Osteonecrosis of the Jaw

ONJ has been reported in the osteoporosis clinical trial program in patients treated with Prolia [see WARNINGS AND PRECAUTIONS].

Atypical Subtrochanteric and Diaphyseal Fractures

In the osteoporosis clinical trial program, atypical femoral fractures were reported in patients treated with Prolia. The duration of Prolia exposure to time of atypical femoral fracture diagnosis was as early as 2½ years [see WARNINGS AND PRECAUTIONS].

Pancreatitis

Pancreatitis was reported in 4 patients (0.1%) in the placebo and 8 patients (0.2%) in the Prolia groups. Of these reports, 1 patient in the placebo group and all 8 patients in the Prolia group had serious events, including one death in the Prolia group. Several patients had a prior history of pancreatitis. The time from product administration to event occurrence was variable.

New Malignancies

The overall incidence of new malignancies was 4.3% in the placebo and 4.8% in the Prolia groups. New malignancies related to the breast (0.7% placebo vs. 0.9% Prolia), reproductive system (0.2% placebo vs. 0.5% Prolia), and gastrointestinal system (0.6% placebo vs. 0.9% Prolia) were reported. A causal relationship to drug exposure has not been established.

Treatment to Increase Bone Mass in Men with Osteoporosis

The safety of Prolia in the treatment of men with osteoporosis was assessed in a 1-year randomized, double-blind, placebo-controlled study. A total of 120 men were exposed to placebo and 120 men were exposed to Prolia administered subcutaneously once every 6 months as a single 60 mg dose. All men were instructed to take at least 1000 mg of calcium and 800 IU of vitamin D supplementation per day.

The incidence of all-cause mortality was 0.8% (n = 1) in the placebo group and 0.8% (n = 1) in the Prolia group. The incidence of nonfatal serious adverse events was 7.5% in the placebo group and 8.3% in the Prolia group. The percentage of patients who withdrew from the study due to adverse events was 0% and 2.5% for the placebo and Prolia groups, respectively.

Adverse reactions reported in ≥ 5% of men with osteoporosis and more frequently with Prolia than in the placebo-treated patients were: back pain (6.7% placebo vs. 8.3% Prolia), arthralgia (5.8% placebo vs. 6.7% Prolia), and nasopharyngitis (5.8% placebo vs. 6.7% Prolia).

Serious Infections

Serious infection was reported in 1 patient (0.8%) in the placebo group and no patients in the Prolia group.

Dermatologic Reactions

Epidermal and dermal adverse events (such as dermatitis, eczema, and rashes) were reported in 4 patients (3.3%) in the placebo group and 5 patients (4.2%) in the Prolia group.

Osteonecrosis of the Jaw

No cases of ONJ were reported.

Pancreatitis

Pancreatitis was reported in 1 patient (0.8%) in the placebo group and 1 patient (0.8%) in the Prolia group.

New Malignancies

New malignancies were reported in no patients in the placebo group and 4 (3.3%) patients (3 prostate cancers, 1 basal cell carcinoma) in the Prolia group.

Treatment of Bone Loss in Patients Receiving Androgen Deprivation Therapy for Prostate Cancer or Adjuvant Aromatase Inhibitor Therapy for Breast Cancer

The safety of Prolia in the treatment of bone loss in men with nonmetastatic prostate cancer receiving androgen deprivation therapy (ADT) was assessed in a 3-year, randomized, double-blind, placebo-controlled, multinational study of 1468 men aged 48 to 97 years. A total of 725 men were exposed to placebo and 731 men were exposed to Prolia administered once every 6 months as a single 60 mg subcutaneous dose. All men were instructed to take at least 1000 mg of calcium and 400 IU of vitamin D supplementation per day.

The incidence of serious adverse events was 30.6% in the placebo group and 34.6% in the Prolia group. The percentage of patients who withdrew from the study due to adverse events was 6.1% and 7.0% for the placebo and Prolia groups, respectively.

The safety of Prolia in the treatment of bone loss in women with nonmetastatic breast cancer receiving aromatase inhibitor (AI) therapy was assessed in a 2-year, randomized, double-blind, placebo-controlled, multinational study of 252 postmenopausal women aged 35 to 84 years. A total of 120 women were exposed to placebo and 129 women were exposed to Prolia administered once every 6 months as a single 60 mg subcutaneous dose. All women were instructed to take at least 1000 mg of calcium and 400 IU of vitamin D supplementation per day.

The incidence of serious adverse events was 9.2% in the placebo group and 14.7% in the Prolia group. The percentage of patients who withdrew from the study due to adverse events was 4.2% and 0.8% for the placebo and Prolia groups, respectively.

Adverse reactions reported in ≥ 10% of Prolia-treated patients receiving ADT for prostate cancer or adjuvant AI therapy for breast cancer, and more frequently than in the placebo-treated patients were: arthralgia (13.0% placebo vs. 14.3% Prolia) and back pain (10.5% placebo vs. 11.5% Prolia). Pain in extremity (7.7% placebo vs. 9.9% Prolia) and musculoskeletal pain (3.8% placebo vs. 6.0% Prolia) have also been reported in clinical trials. Additionally in Prolia-treated men with nonmetastatic prostate cancer receiving ADT, a greater incidence of cataracts was observed (1.2% placebo vs. 4.7% Prolia).

Hypocalcemia (serum calcium < 8.4 mg/dL) was reported only in Prolia-treated patients (2.4% vs. 0%) at the month 1 visit.

Postmarketing Experience

Because postmarketing reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

The following adverse reactions have been identified during post approval use of Prolia:

  • Drug-related hypersensitivity reactions: anaphylaxis, rash, urticaria, facial swelling, and erythema
  • Hypocalcemia: severe symptomatic hypocalcemia
  • Musculoskeletal pain, including severe cases
  • Parathyroid Hormone (PTH): Marked elevation in serum PTH in patients with severe renal impairment (creatinine clearance < 30 mL/min) or receiving dialysis.

Immunogenicity

Denosumab is a human monoclonal antibody. As with all therapeutic proteins, there is potential for immunogenicity. Using an electrochemiluminescent bridging immunoassay, less than 1% (55 out of 8113) of patients treated with Prolia for up to 5 years tested positive for binding antibodies (including pre-existing, transient, and developing antibodies). None of the patients tested positive for neutralizing antibodies, as was assessed using a chemiluminescent cell-based in vitro biological assay. No evidence of altered pharmacokinetic profile, toxicity profile, or clinical response was associated with binding antibody development.

The incidence of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of a positive antibody (including neutralizing antibody) test result may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of antibodies to denosumab with the incidence of antibodies to other products may be misleading.

Read the entire FDA prescribing information for Prolia (Denosumab Injection) »

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Prolia - User Reviews

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