Prolia (Generic name: Denosumab) is a monoclonal antibody that binds to the RANK ligand and inhibits the activation of osteoclasts. Thus, it inhibits bone loss and prevents & treats osteoporosis. It also inhibits giant cell bone tumors by inhibiting the RANK activation. It is a preferred drug for the treatment of osteoporosis and other conditions in patients with renal impairment. It has an onset of action of about 3 days with the maximal response is seen in about a month. In patients with hypercalcemia of malignancy, it takes about 9 days to act and 23 days for a complete response When the treatment is discontinued, the markers of bone resorption return to baseline within 12 months. It has a bioavailability of about 62% and a half-life elimination of about 25 - 28 days. The time to reach the peak serum concentration is about 10 days (ranging from 3 - 21 days).

Prolia Uses:

• It prevents bone metastases from solid tumors.

• It is used to treat unresectable Giant cell tumors of the bone in adults and mature adolescents. It may be also be used to treat giant cell tumors in patients where resection may result in more morbidity.

• It is used to treat patients with glucocorticoid-induced osteoporosis in patients:

  • who are at a high risk of fracture (such as those with a history of osteoporotic fracture, multiple risk factors for a fracture, and patients who are intolerant to other therapies).

  • in patients who are initiating glucocorticoid treatment at a daily dose of 7.5 mg or more of prednisone or equivalent for an anticipated duration of six months or more.

• It is used to treat patients with Hypercalcemia of malignancy that is refractory to bisphosphonates therapy.

• Treatment of mutiple myeloma (prevention of skeletal events).

• Treatment of osteoporosis and bone loss in:

  • postmenopausal women

  • men at a high risk of fracture

  • men receiving antiandrogen therapy such as those receiving treatment for prostatic cancer

  • Women receiving aromatase inhibitors for breast cancer.

• It may also be used in the treatment of bony destruction caused by Rheumatoid arthritis.

Prolia (Denosumab) Dosage:

Prolia (Denosumab) dosage in the prevention of skeletal-related events and treatment of bone metastases from solid tumors:

• Xgeva 120 mg subcutaneous every month

Prolia Dose in the treatment of Giant cell tumor of bone:

• 120 mg subcutaneous every month
• Additional doses of 120 mg may be given on days 8 and 15 during the first month

Prolia (denosumab) dose in the treatment of Hypercalcemia of malignancy:

• 120 mg subcutaneous every month
• Additional doses of 120 mg may be given on days 8 and 15 during the first month

Xgeva (Denosumab) dose in the treatment and prevention of skeletal-related events in patients with Multiple myeloma:

• 120 mg subcutaneous every month
• Since, its action is reversible, it should not be abruptly stopped.

Prolia dose in the treatment of bony destruction caused by rheumatoid arthritis:

• 60 mg or 180 mg subcutaneous once every six months as a single dose in combination with methotrexate.

Prolia Dosage in the treatment of Osteoporosis:

• Dose in men on anti-androgens (for prostatic cancer):

  • 60 mg subcutaneous once every six months as a single dose

• For women with breast cancer on aromatase inhibitor-induced bone loss:

  • 60 mg subcutaneous once every six months as a single dose

• For the treatment of glucocorticoid-induced osteoporosis:

  • 60 mg subcutaneous once every six months as a single dose

• For the treatment of osteoporosis in postmenopausal women or men at a high risk of fracture:

  • 60 mg subcutaneous once every six months as a single dose

When to discontinue therapy (for osteoporosis):

Discontinuation of the treatment may result in a return of the baseline bone mineral density, discontinuation of treatment interruption is therefore not recommended. Alternative therapies such as bisphosphonates may be considered if denosumab is discontinued. Note: All patients should receive calcium and vitamin D supplements to prevent hypocalcemia

Xgeva dose in children for the treatment of Giant cell tumor of the bone:

• Skeletally mature Adolescents weighing 45 kgs or more:

  • 120 mg subcutaneous once every 4 weeks.
  • Additional doses of 120 mg may be given on days 8 and 15.

Denosumab (Prolia, Xgeva) side effects:

Common Side Effects of Denosumab Include:

• Cardiovascular:

  • Peripheral Edema
  • Hypertension

• Central Nervous System:

  • Fatigue
  • Headache

• Dermatologic:

  • Skin Rash
  • Dermatitis
  • Eczema

• Endocrine & Metabolic:

  • Hypophosphatemia
  • Hypocalcemia

• Gastrointestinal:

  • Diarrhea
  • Nausea
  • Decreased Appetite
  • Vomiting
  • Constipation

• Hematologic & Oncologic:

  • Anemia
  • Thrombocytopenia

• Neuromuscular & Skeletal:

  • Asthenia
  • Back Pain
  • Arthralgia
  • Limb Pain

• Respiratory:

  • Dyspnea
  • Cough
  • Upper Respiratory Tract Infection

Less Common Side Effects Of Denosumab Include:

• Cardiovascular:

  • Angina Pectoris

• Central Nervous System:

  • Sciatica

• Endocrine & Metabolic:

  • Hypercholesterolemia
  • Hypokalemia;
  • Hypomagnesemia
  • Severe Hypocalcemia

• Gastrointestinal:

  • Upper Abdominal Pain
  • Flatulence

• Genitourinary:

  • Urinary Tract Infection

• Hematologic & Oncologic:

  • Malignant Neoplasm

• Infection:

  • Serious Infection

• Neuromuscular & Skeletal:

  • Musculoskeletal Pain
  • Ostealgia
  • Myalgia
  • Osteonecrosis Of The Jaw
  • Polymyalgia Rheumatic

• Ophthalmic:

  • Cataract

• Respiratory:

  • Pneumonia
  • Nasopharyngitis
  • Bronchitis

Denosumab: Drug Interaction

Monitoring parameters while using Prolia:

• Monitor during the first few weeks of initiating the treatment:
  • serum creatinine,
  • serum calcium,
  • Serum phosphorus and
  • Serum magnesium
• Pregnancy test before initiating the treatment in women of reproductive potential
• Clinical features of hypocalcemia like Chvosteks sign, carpopedal spasm, and trousseaus sign (especially in patients with renal disease, thyroidectomy, parathyroid surgery, malabsorption syndromes, and hyperparathyroidism.
• Clinical and laboratory evidence of hypercalcemia in patients with giant cell tumor of the bone and growing skeleton following treatment discontinuation
• infections
• Dermatologic reactions
• routine oral and dental examination for osteonecrosis of the jaw
• monitor for allergic reactions
• Monitor bone mineral density 1 - 2 years after treatment initiation for osteoporosis
• Monitor the height, weight, calcium, vitamin D levels, markers of bone turnover, and assessment of back pain in patients treated for osteoporosis.

How to administer Denosumab (Prolia, Xgeva):

It is intended for subcutaneous administration only.

Intramuscular, intradermal, and intravenous administration should be avoided.

Before administering denosumab, bring down the injection to room temperature by allowing it to stand at room temperature for 15 - 30 minutes.

Do not warm the injection by any other method.

Avoid injecting it if the solution is cloudy or contains foreign particles (trace amount of white particles may be there). Vigorous shaking should also be avoided. It should be administered via subcutaneous injection in the upper arm, upper thigh, or abdomen (just like insulin). In case a dose is missed, it should be administered as soon as possible and the next dose should be given six months after the last injection.

Denosumab Brand Names (International):

• Prolia
• Xgeva
• Ranmark

Denosumab Brand Name in Pakistan:

• Prolia
• Xgeva