Denosumab

What is Denosumab?

• Denosumab is drug used to prevent or treat certain bone problems, especially osteoporosis.
• It is used under the brand name Xgeva and Prolia to prevent bone problems caused by multiple myeloma or by solid tumors that have spread to the bone.
• It is also used in certain patients to treat giant cell tumor of the bone that cannot be removed by surgery, and to treat hypercalcemia that is caused by cancer and did not get better after treatment with bisphosphonates.
• Denosumab is also used under the brand name Prolia to increase bone mass in certain patients with breast cancer or prostate cancer who have a high risk of breaking bones.
• It is also used to treat osteoporosis in men and postmenopausal women who have a high risk of breaking bones.

A humanized monoclonal antibody and an inhibitor of the RANK LIGAND

What are the uses of Denosumab?

Denosumab Prolia is a RANK ligand (RANKL) inhibitor indicated for:

• Treatment of postmenopausal women with osteoporosis at high risk for fracture
• Treatment to increase bone mass in men with osteoporosis at high risk for fracture
• Treatment of glucocorticoid-induced osteoporosis in men and women at high risk for fracture
• Treatment to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer
• Treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer

How does Denosumab work?

• It binds to a protein called RANKL, which keeps RANKL from binding to another protein called RANK on the surface of certain bone cells, including bone cancer cells.
• This may help keep bone from breaking down and cancer cells from growing.
• Denosumab may also prevent the loss of calcium from the bones.
• It is a type of monoclonal antibody. Also called AMG 162.

Who Should Not Use Denosumab ?

• Hypocalcemia
• Pregnancy
• Known hypersensitivity to Denosumab

Is Denosumab FDA approved?

• Yes. Prolia was approved in the United States initially in 2020.

How should Denosumab be used?

Recommended Dosage:

• Administer calcium and vitamin D as necessary to treat or prevent hypocalcemia.

Multiple Myeloma and Bone Metastasis from Solid Tumors: Administer 120 mg every 4 weeks as a subcutaneous injection in the upper arm, upper thigh, or abdomen.

Giant Cell Tumor of Bone:

• Administer 120 mg every 4 weeks with additional 120 mg doses on Days 8 and 15 of the first month of therapy.
• Administer subcutaneously in the upper arm, upper thigh, or abdomen.

Hypercalcemia of Malignancy:

• Administer 120 mg every 4 weeks with additional 120 mg doses on Days 8 and 15 of the first month of therapy. Administer subcutaneously in the upper arm, upper thigh, or abdomen.

Administration:

• Xgeva is intended for subcutaneous route only and should not be administered intravenously, intramuscularly, or intradermally.

What are the dosage forms and brand names of Denosumab?

• Single-dose prefilled syringe containing 60 mg in a 1 mL solution

Denosumab is available in fallowing brand namesː

• Xgeva
• Prolia

What side effects can this medication cause?

• Postmenopausal osteoporosis: Most common adverse reactions (> 5% and more common than placebo) were: back pain, pain in extremity, hypercholesterolemia, musculoskeletal pain, and cystitis. Pancreatitis has been reported in clinical trials.

• Male osteoporosis: Most common adverse reactions (> 5% and more common than placebo) were: back pain, arthralgia, and nasopharyngitis.

• Glucocorticoid-induced osteoporosis: Most common adverse reactions (> 3% and more common than active-control group) were: back pain, hypertension, bronchitis, and headache.

• Bone loss due to hormone ablation for cancer: Most common adverse reactions (≥ 10% and more common than placebo) were: arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials.

What warnings and special precautions should I follow?

• Hypersensitivity including anaphylactic reactions may occur. Discontinue permanently if a clinically significant reaction occurs.
• Hypocalcemia: Must be corrected before initiating Prolia. May worsen, especially in patients with renal impairment. Adequately supplement patients with calcium and vitamin D.
• Osteonecrosis of the jaw: Has been reported with Prolia. Monitor for symptoms.
• Atypical femoral fractures: Have been reported. Evaluate patients with thigh or groin pain to rule out a femoral fracture.
• Multiple vertebral fractures have been reported following Prolia discontinuation. Patients should be transitioned to another antiresorptive agent if Prolia is discontinued.
• Serious infections including skin infections: May occur, including those leading to hospitalization. Advise patients to seek prompt medical attention if they develop signs or symptoms of infection, including cellulitis.
• Dermatologic reactions: Dermatitis, rashes, and eczema have been reported. Consider discontinuing Prolia if severe symptoms develop.
• Severe bone, joint, muscle pain may occur. Discontinue use if severe symptoms develop.
• Suppression of bone turnover: Significant suppression has been demonstrated. Monitor for consequences of bone over-suppression.
• No dose adjustment is necessary in patients with renal impairment. Patients with creatinine clearance < 30 mL/min or receiving dialysis are at risk for hypocalcemia. Supplement with calcium and vitamin D, and consider monitoring serum calcium.

What to do in case of emergency/overdose?

• In case of overdose, call the poison control helpline of your country. In the United States, call 1-800-222-1222.

• Overdose related information is also available online at poisonhelp.org/help.
• In the event that the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services. In the United States, call 911.

Can Denosumab be used in pregnancy?

• Denosumab may cause fetal harm when administered to pregnant women.
• Advise females of reproductive potential to use effective contraception during therapy, and for at least 5 months after the last dose of Prolia.

Can Denosumab be used in children?

• Safety and efficacy not established.

What are the active and inactive ingredients in Denosumab?

Active ingredient: Denosumab

Inactive ingredients:

• Sorbitol, acetate, polysorbate 20, water for Injection (USP), and sodium hydroxide

Who manufactures and distributes Denosumab?

Prolia is Manufactured by: Amgen Inc. One Amgen Center Drive Thousand Oaks, California 91320-1799

What should I know about storage and disposal of this medication?

• Keep Prolia in a refrigerator at 36°F to 46°F (2°C to 8°C) in the original carton.
• Do not freeze Prolia.
• When you remove Prolia from the refrigerator, Prolia must be kept at room temperature [up to 77°F (25°C)] in the original carton and must be used within 14 days.
• Do not keep Prolia at temperatures above 77°F (25°C). Warm temperatures will affect how Prolia works.
• Do not shake Prolia.
• Keep Prolia in the original carton to protect from light.
• Keep Prolia and all medicines out of the reach of children.

• Dailymed label info on Denosumab
• FDA Denosumab