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PROLIA

Last Updated: June 17, 2010

Manufacturer:

Amgen, Inc.

Pharmacological Class:

Osteoclast inhibitor (RANKL inhibitor)

Active Ingredient(s):

Denosumab 60mg/mL; soln for SC inj; preservative-free.

Indication(s):

In 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 therapy; to reduce incidence of vertebral, nonvertebral, and hip fractures.

Pharmacology:

Denosumab is a human IgG2 monoclonal antibody that binds to human receptor activator of nuclear factor kappa-B ligand (RANKL). Denosumab prevents RANKL from interacting with its receptors on the surfaces of osteoclasts and their precursors, thereby inhibiting osteoclast formation, function, and survival. This in turn decreases bone resorption and increases bone mass and strength in both cortical and trabecular bone.

Clinical Trials:

The safety and efficacy of denosumab in the treatment of postmenopausal osteoporosis was assessed in a 3-year, randomized study involving 7808 women 60–91 years of age with BMD T-score between –2.5 and –4.0 at either the lumbar spine or total hip. All subjects were supplemented with daily calcium and vitamin D, in addition to the study drug or placebo given once every 6 months. The primary efficacy variable was the incidence of new vertebral fractures at 3 years; secondary efficacy variables were the incidences of hip and nonvertebral fractures.

Denosumab significantly reduced the incidence of new vertebral fractures at 1, 2, and 3 years. At 3 years, the incidence was 7.2% in the placebo group compared to 2.3% in the study drug group (relative risk reduction 68%). At year 3, the incidence of hip fracture was 1.2% for placebo compared to 0.7% for denosumab (relative risk reduction 40%). The proportion of women with nonvertebral fracture at year 3 was 8.0% for placebo compared to 6.5% for denosumab (relative risk reduction 20%).

Treatment with denosumab significantly increased bone mineral density (BMD) at all sites measured at 3 years (lumbar spine, total hip, femoral neck). After discontinuation of denosumab, BMD returned to baseline levels within 1 year.

Legal Classification:

Adults:

Should be administered by a healthcare professional. 60mg SC once every 6 months; inject into upper arm, upper thigh, or abdomen.

Children:

Not recommended.

Contraindication(s):

Hypocalcemia.

Warnings/Precautions:

Correct hypocalcemia before starting; ensure adequate daily calcium (≥1000mg) and Vit.D (≥400IU) intake, esp. in renal impairment (CrCl<30mL/min). Monitor calcium, phosphorus, magnesium levels in susceptible patients (hypoparathyroidism, thyroid or parathyroid surgery, malabsorption, severe renal impairment, on dialysis). Monitor for infections, jaw osteonecrosis, bone oversuppression. Do baseline oral exam and preventive dentistry if risks for jaw osteonecrosis exist (eg, tooth extraction, dental implants, oral surgery, cancer, anemia, coagulopathy). Maintain good oral hygiene. Immunosuppressed. Latex allergy (prefilled syringe). Pregnancy (Cat.C). Nursing mothers: avoid (may impair mammary glands/lactation).

Interaction(s):

Concomitant immunosuppressants (increased infection risk). Corticosteroids (increased jaw osteonecrosis risk).

Adverse Reaction(s):

Pain (back, lower extremities or musculoskeletal), hypercholesterolemia, cystitis; infections (may be serious; eg, cellulitis, UTI, otic, abdominal), dermatitis, rash, eczema, osteonecrosis of jaw, suppression of bone turnover, exacerbation of hypocalcemia, pancreatitis.