Drug information of denosumab

Mechanism of effect

Denosumab is designed to target RANKL (RANK ligand), a protein that acts as the primary signal to promote bone removal/resorption. In many bone loss conditions, RANKL overwhelms the body's natural defense against bone destruction. Denosumab prevents RANKL from activating its receptor, RANK, on the surface of osteoclasts and their precursors. Prevention of the RANKL/RANK interaction inhibits osteoclast formation, function, and survival, thereby decreasing bone resorption and increasing bone mass and strength in both cortical and trabecular bone

Pharmacodynamic

In clinical studies, treatment with 60 mg of this drug  resulted in reduction in the bone resorption marker serum type 1 C-telopeptide (CTX) by approximately 85% by 3 days.

Pharmacokinetics

When 60 mg of denosumab was subcutaneously administered to healthy subjects after fasting for 12 hours, the pharmacokinetic parameters are as follows:

 Cmax = 6.75 mcg/mL; Tmax= 10 days (range of 3 to 21 days.

 Denosumab does not accumulate following multiple doses once every 6 months. The pharmacokinetics of denosumab were not affected by the formation of antibodies.

Dosage

• Usual Adult Dose for Osteoporosis

60 mg subcutaneously once every 6 months

Comments:
-If a dose is missed, the injection should be administered as soon as possible. Thereafter, injections should be scheduled every 6 months from the date of the last injection.
-This drug should be injected into the upper arm, upper thigh, or abdomen.

Uses:
-Treatment of postmenopausal women with osteoporosis at high risk for fracture
-Treatment to increase bone mass in men with osteoporosis
-Treatment of bone loss in men receiving androgen deprivation therapy for prostate cancer
-Treatment of bone loss in women receiving adjuvant aromatase inhibitor therapy for breast cancer

• Usual Adult Dose for Giant Cell Tumor of Bone
  120 mg subcutaneously every 4 weeks with additional 120 mg doses on Days 8 and 15 of the first month of therapy
  
  Comments:
  -This drug should be injected into the upper arm, upper thigh, or abdomen.
  -Calcium and vitamin D should be administered to treat or prevent hypocalcemia.
  
  Use: Treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity
• Usual Adult Dose for Osteolytic Bone Metastases of Solid Tumors

 120 mg subcutaneously every 4 weeks

Comments:
-This drug should be injected into the upper arm, upper thigh, or abdomen.
-Calcium and vitamin D should be administered to treat or prevent hypocalcemia.

Use: Prevention of skeletal-related events in patients with bone metastases from solid tumors

• Usual Adult Dose for Hypercalcemia of Malignancy

120 mg subcutaneously every 4 weeks with additional 120 mg doses on Days 8 and 15 of the first month of therapy

Comment:
-This drug should be injected into the upper arm, upper thigh, or abdomen.

Use: Treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy

• Usual Pediatric Dose for Giant Cell Tumor of Bone

120 mg subcutaneously every 4 weeks with additional 120 mg doses on Days 8 and 15 of the first month of therapy

Comment:
-Xgeva (R) was studied in adolescent patients aged 13 to 17 years with giant cell tumor of bone who had reached skeletal maturity.
Use: Treatment of skeletally mature adolescents with giant cell tumor of bone.

Drug contraindications

pregnancy , Hypersensitivity to this drug or components

Side effects

anemia , Diarrhea , Headache , nausea , vomiting , asthenia , Peripheral edema , eczema , skin rush , tiredness , shortness of breath , Hypophosphatemia

Interactions

Streptozocin , Ifosfamide , Infliximab , Budesonide , Topotecan , Daunorubicin , Fludarabine phosphate , Glatiramer acetate , Mitoxantrone , Vinorelbine , Carboplatin , cladribine , thiotepa , Pemetrexed , dinutuximab , Floxuridine , upadacitinib , Ustekinumab , Carmustine , Temsirolimus , Blinatumomab , Nilutamide , Siltuximab , alirocumab

Alerts

Concerns related to adverse effects:

Bone fractures: Atypical femur fractures have been reported in patients receiving denosumab. The fractures may occur anywhere along the femoral shaft (may be bilateral) and commonly occur with minimal to no trauma to the area. Some patients experience prodromal pain weeks or months before the fracture occurs. Because these fractures also occur in osteoporosis patients not treated with denosumab, it is unclear if denosumab therapy is the cause for the fractures; concomitant glucocorticoids may contribute to fracture risk.

 Following treatment discontinuation (in patients being treated for osteoporosis), the fracture risk increases, including risk of multiple vertebral fractures. Evaluate benefit/risk before initiating denosumab treatment for osteoporosis, especially in patients with prior vertebral fracture. If denosumab is discontinued, consider transitioning to an alternative osteoporosis therapy.

Dermatologic reactions: Dermatitis, eczema, and rash (which are not necessarily specific to the injection site) have been reported. Consider discontinuing if severe symptoms occur.

Hypersensitivity: Clinically significant hypersensitivity (including anaphylaxis) has been reported. May include throat tightness, facial edema, upper airway edema, lip swelling, dyspnea, pruritus, rash, urticaria, and hypotension. If anaphylaxis or clinically significant hypersensitivity occurs, initiate appropriate management and permanently discontinue.

Points of recommendation

If you are allergic to any drugs like Denosumab, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.

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. Some brands of this medicine are not for use during pregnancy.

This is not a list of all drugs or health problems that interact with denosumab injection.

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 medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Pregnancy level

X

Related drugs

Burosumab