Aclasta

Approved Indications (Osteoporosis):

• Treatment of postmenopausal osteoporosis to reduce the risk of vertebral, hip, and other fractures.
• Treatment of osteoporosis in men.
• Prevention and treatment of glucocorticoid-induced osteoporosis in men and women.

Other Approved Uses (non-osteoporotic):

• Treatment of Paget’s disease of bone.
• Treatment of hypercalcemia of malignancy.
• Prevention of skeletal-related events in patients with bone metastases from solid tumors and in multiple myeloma.

Important Off-label / Clinically Accepted Uses:

• Prevention of aromatase inhibitor-associated bone loss in women with breast cancer.
• Management of bone loss in patients receiving androgen-deprivation therapy for prostate cancer.
• Occasionally used in osteogenesis imperfecta and other bone fragility syndromes.

রেজিস্টার্ড চিকিৎসকের পরামর্শ ছাড়া ওষুধ সেবন করবেন না।

Postmenopausal and Male Osteoporosis:

• 5 mg IV infusion once yearly, administered over no less than 15 minutes.

Glucocorticoid-induced Osteoporosis:

• 5 mg IV infusion once yearly, for men and women on systemic glucocorticoids.

Paget’s Disease:

• Single 5 mg IV infusion.
• Ensure adequate calcium (≥1500 mg/day) and vitamin D (800 IU/day) supplementation, especially for 2 weeks post-infusion.

Hypercalcemia of Malignancy:

• 4 mg IV infusion over at least 15 minutes.
• May repeat after 7 days if necessary.

Bone Metastases / Multiple Myeloma:

• 4 mg IV every 3 to 4 weeks.
• Renal adjustment required:
• CrCl 50–60 mL/min: 3.5 mg
• CrCl 40–49 mL/min: 3.3 mg
• CrCl 30–39 mL/min: 3.0 mg
• Avoid use if CrCl <30 mL/min.

Special Populations:

• Elderly: No dose adjustment, but monitor renal function.
• Renal impairment: Adjust dose or avoid as per creatinine clearance.
• Pediatrics: Safety and efficacy not established.

Administration Notes:

• Ensure proper hydration before administration.
• Use a separate IV line; do not mix with calcium-containing solutions.

Zoledronic acid is a nitrogen-containing bisphosphonate that selectively binds to hydroxyapatite in bone, particularly at sites of active resorption. It inhibits farnesyl pyrophosphate synthase, an enzyme in the mevalonate pathway, thereby blocking the prenylation of small GTPase signaling proteins essential for osteoclast function. This leads to osteoclast apoptosis and reduced bone resorption, resulting in increased bone mineral density and reduced fracture risk.

• Absorption: Not applicable; administered intravenously.
• Distribution: Rapid uptake by bone; plasma protein binding ~22%.
• Metabolism: Not metabolized.
• Elimination: Excreted unchanged by kidneys; terminal elimination half-life approx. 146 hours.
• Renal Clearance: Primary route of elimination; accumulation occurs in renal impairment.
• Skeletal Retention: Prolonged due to high bone affinity.

• Pregnancy:
• Category D.
• Evidence of fetal skeletal toxicity and impaired bone development in animal studies.
• Avoid use during pregnancy; may remain in bone for years.
• Lactation:
• Unknown if excreted in human milk.
• Not recommended during breastfeeding due to potential risk to the infant.
• Use caution if therapy is necessary.

• Primary Class: Bisphosphonate
• Subclass: Nitrogen-containing bisphosphonate (third generation)

• Hypersensitivity to zoledronic acid or other bisphosphonates
• Hypocalcemia
• Severe renal impairment (CrCl <35 mL/min for osteoporosis; <30 mL/min for other uses)
• Pregnancy and breastfeeding
• Concurrent use with other bisphosphonates

• Renal Toxicity: Risk of acute renal failure; monitor renal function before each dose.
• Hypocalcemia: Must correct before initiating treatment; supplement with calcium and vitamin D.
• Osteonecrosis of the Jaw (ONJ): Rare but serious; ensure dental evaluation prior to treatment.
• Atypical Femur Fractures: Rare; monitor for thigh or groin pain.
• Acute Phase Reactions: Flu-like symptoms (fever, myalgia) common after first dose.
• Severe Bone, Joint, or Muscle Pain: May occur days to months after treatment.
• Vision Disorders: Cases of ocular inflammation reported.
• Seizures: May occur with severe hypocalcemia.

Common Side Effects:

• Fever, fatigue, flu-like symptoms
• Myalgia, arthralgia, bone pain
• Headache, dizziness
• Nausea, vomiting, constipation
• Anemia

Serious/Rare Side Effects:

• Osteonecrosis of the jaw
• Acute renal failure
• Severe hypocalcemia
• Atypical femur fractures
• Uveitis, scleritis, episcleritis
• Severe musculoskeletal pain
• Allergic reactions, including anaphylaxis

• Loop Diuretics: Increased risk of hypocalcemia.
• Aminoglycosides: Additive effects on calcium lowering.
• Nephrotoxic Drugs (e.g., NSAIDs): Increased risk of renal toxicity.
• Other Bisphosphonates: Avoid concomitant use.
• Calcium or Mineral Supplements: Avoid IV administration within same line.
• CYP System: No significant interactions with CYP450 enzymes.
• Alcohol: May worsen dizziness or GI effects; caution advised.

• Warning updates regarding atypical femur fractures and osteonecrosis of the jaw.
• Dose adjustments and safety monitoring reinforced for patients with renal impairment.
• Ongoing inclusion in global osteoporosis management guidelines as a first-line agent in high-risk fracture patients.

• Store at 20–25°C (68–77°F); excursions permitted to 15–30°C (59–86°F).
• Protect from light and freezing.
• Once opened, use immediately or store diluted solution at 2–8°C for up to 24 hours.
• Do not mix with calcium-containing or other IV solutions.
• Use dedicated infusion line; infuse over a minimum of 15 minutes.