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IV Bisphosphonate (Paget's Disease / Bone Metastases / Hypercalcaemia) Pregnancy: Contraindicated — animal studies show fetal harm; risk may persist after discontinuation due to bone retention

Pamidronate Disodium

Brand names: Aredia, Pamidronate

Adult dose

Dose: Paget's disease: 30 mg IV over 4 hours on 3 consecutive days (90 mg total); Hypercalcaemia of malignancy: 15–90 mg IV single infusion by corrected calcium; Bone metastases pain: 90 mg every 3–4 weeks
Route: IV infusion only (never bolus — nephrotoxic)
Frequency: Variable by indication
Max: 90 mg per infusion
Must be diluted and given as slow IV infusion (minimum 4 hours); ensure adequate hydration before infusion; maximum infusion rate 1 mg/min; renal function mandatory before each dose

Paediatric dose

Dose: 0.5–1 mg/kg
Route: IV
Frequency: Variable by indication
Max: 60 mg/dose
Used in osteogenesis imperfecta — specialist paediatric metabolic bone centre only; protocol varies by severity

Dose adjustments

Renal

Avoid if eGFR <30 mL/min; reduce infusion rate in moderate impairment; post-infusion renal function check at 2 weeks

Hepatic

No dose adjustment required

Paediatric weight-based calculator

Used in osteogenesis imperfecta — specialist paediatric metabolic bone centre only; protocol varies by severity

Clinical pearls

  • Paget's disease: pamidronate or zoledronate is first-line for symptomatic Paget's — biochemical response (ALP normalisation) in 60–70% after 3-day course; biochemical remission can last 1–3 years; re-treat when ALP rises more than 25% above nadir
  • Osteogenesis imperfecta in children: pamidronate infusions every 3–4 months significantly reduce fracture frequency and increase vertebral bone density — Glorieux et al. NEJM 1998 landmark study; managed exclusively in specialist paediatric metabolic bone services
  • Acute phase reaction: occurs in ~30% after FIRST IV bisphosphonate infusion — fever, myalgia, transient lymphopenia; resolves within 48–72 hours; does NOT recur with subsequent infusions; manage with paracetamol and reassurance
  • Renal toxicity: nephrotoxicity is dose and infusion-rate dependent — focal segmental glomerulosclerosis reported; strict maximum rate 1 mg/min; check creatinine before each cycle; zoledronate now often preferred for bone metastases (15-minute infusion)
  • ONJ risk higher with IV vs oral bisphosphonates and with oncological vs osteoporosis doses — dental review mandatory before starting in cancer patients; MHRA 2009 and AAOMS 2014 guidelines apply

Contraindications

  • Uncorrected hypocalcaemia
  • eGFR <30 mL/min
  • Bolus injection (nephrotoxic)

Side effects

  • Acute phase reaction (fever, myalgia, flu-like symptoms — first infusion ~30%)
  • Hypocalcaemia
  • Nephrotoxicity (focal segmental glomerulosclerosis)
  • Osteonecrosis of jaw (ONJ)
  • Atypical femoral fracture (long-term)
  • Uveitis or scleritis (rare)

Interactions

  • Aminoglycosides — additive hypocalcaemia and nephrotoxicity
  • Thalidomide in myeloma — possible renal impairment increase
  • Antacids/calcium — oral bisphosphonate absorption reduced (IV unaffected)

Monitoring

  • Serum calcium (corrected) before each infusion
  • Renal function (U&E, creatinine) before each cycle
  • ALP for Paget's response
  • Urine protein (nephrotic syndrome surveillance)
  • Dental review before starting

Reference: BNFc; BNF 90; Glorieux et al. NEJM 1998 (OI); SIGN 142 (Paget's Disease); MHRA Drug Safety Update 2009 (ONJ); SPC Aredia. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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