Zometa

🔹 1. Basic Information

Generic name: Zoledronic acid
Brand name: ZOMETA
Drug class: Bisphosphonate (inhibitor of osteoclastic bone resorption)
Formulation: Concentrate for solution for IV infusion
Strength: 4 mg/5 mL vial
Mechanism of Action:
Inhibits osteoclast-mediated bone resorption → reduces calcium release from bone → stabilizes bone structure and prevents skeletal complications in cancer-related bone disease.

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🔹 2. Indications

• Tumour-induced hypercalcaemia (TIH): Rapid correction of malignancy-related hypercalcaemia.

• Prevention of skeletal-related events (pathological fractures, spinal cord compression, bone pain, need for radiation or surgery) in patients with:

  • Advanced breast, prostate, or lung cancer

  • Multiple myeloma

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🔹 3. Dosing & Administration

• Standard dose: 4 mg IV infusion over at least 15 minutes every 3–4 weeks (skeletal events).

• Hypercalcaemia: Single 4 mg IV infusion.

• Renal impairment: Dose adjustment required based on creatinine clearance.

• Hydration: Ensure adequate fluid intake before infusion.

• Supplementation: Calcium and vitamin D should be given during treatment (unless contraindicated).

• Administer via separate infusion line by trained healthcare personnel.

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🔹 4. Dose Modifications

• Renal impairment:

  • Reduce dose for CrCl < 60 mL/min.

  • Withhold if renal deterioration occurs until function recovers.

• Hypocalcaemia: Correct before starting therapy.

• Monitor renal profile and electrolytes (calcium, phosphate, magnesium) before each dose.

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🔹 5. Contraindications

• Hypersensitivity to zoledronic acid or other bisphosphonates

• Pregnancy and breastfeeding

• Severe renal impairment (unless treating TIH under specialist supervision)

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🔹 6. Warnings & Precautions

• Renal toxicity: Monitor serum creatinine; avoid infusions <15 minutes and concurrent nephrotoxic drugs.

• Osteonecrosis of the jaw (ONJ): Increased risk with dental procedures, steroids, or chemotherapy. Perform dental evaluation before treatment.

• Hypocalcaemia: May cause cramps, paraesthesia, or seizures — ensure calcium and vitamin D supplementation.

• Flu-like reaction: Common after first dose; resolves spontaneously within days.

• Bone, joint, or muscle pain: Usually self-limiting.

• Rare effects: Osteonecrosis of ear, atypical femur fractures (long-term use), interstitial lung disease.

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🔹 7. Drug Interactions

• Aminoglycosides, calcitonin, loop diuretics: Additive hypocalcaemia risk.

• Nephrotoxic drugs (e.g. thalidomide): May worsen renal function.

• Anti-angiogenic agents: Increased risk of ONJ.

• Avoid concurrent use with other bisphosphonates or other zoledronic acid–containing medicines.

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🔹 8. Side Effects & Management

Very common (>10%)
Flu-like symptoms, fever, fatigue, bone or joint pain, hypophosphataemia
→ Supportive care (paracetamol for fever, symptomatic management)

Common (1–10%)
Hypocalcaemia, anaemia, nausea, vomiting, conjunctivitis, infusion-site reactions
→ Monitor electrolytes; give calcium/vitamin D supplements

Uncommon (0.1–1%)
Osteonecrosis of the jaw, atrial fibrillation, rash, dizziness, chest pain
→ Dental assessment and early reporting of jaw pain

Rare (<0.1%)
Severe renal impairment, Fanconi syndrome, seizures due to hypocalcaemia
→ Hospitalisation and supportive management

Very rare (<0.01%)
Osteonecrosis of ear, interstitial lung disease
→ Discontinue and treat symptomatically

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🔹 9. Monitoring Requirements

• Serum creatinine and renal function before each dose

• Electrolytes: calcium, phosphate, magnesium (baseline and periodically)

• Dental assessment before initiation in high-risk patients

• Hydration status before and after infusion

• Evaluate bone pain and mobility during therapy

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🔹 10. Use in Special Populations

• Elderly: No dose adjustment needed; monitor renal function.

• Renal impairment: Dose adjustment required; contraindicated in severe impairment.

• Hepatic impairment: No adjustment required.

• Paediatrics: Not recommended (<18 years).

• Pregnancy / Lactation: Contraindicated.

 

REFERENCES: 

https://pi-pil-repository.sahpra.org.za/wp-content/uploads/2021/08/zometa-pil-16082021.pdf