Pamidronic acid (Pamidronate)

Indications

Pamidronic acid (Pamidronate) is used for: Paget's disease of bone, Osteolytic bone metastases, Osteolytic lesions associated with, multiple myeloma, Hypercalcaemia of malignancy

Adult Dose

Intravenous Osteolytic bone metastases; Osteolytic lesions associated with multiple myeloma Adult: 90 mg as a single infusion 3-4 wkly. Max infusion rate: 60 mg/hr. Hypercalcaemia of malignancy Adult: 15-90 mg (based on initial plasma Ca concentration) as a single infusion or in divided doses over 2-4 consecutive days. Plasma Ca levels generally start declining 24-48 hr after a dose w/ normalisation w/in 3-7 days; may repeat treatment if normocalcaemia is not achieved w/in this time or if hypercalcaemia recurs. Max infusion rate: 60 mg/hr. Paget's disease of bone Adult: 30 mg once wkly by infusion for 6 wk (total dose: 180 mg), alternatively, 30 mg in the 1st wk, then 3 doses of 60 mg every other wk (total dose: 210 mg); may repeat course 6 mthly (total dose may be increased up to 360 mg) when clinically indicated. Max infusion rate: 60 mg/hr. Elderly: Initiate at lower end of adult dosing range.

Child Dose

Renal Dose

Renal impairment: Max infusion rate: 20 mg/hr. CrCl (ml/min) Dosage Recommendation <30 Avoid, unless in life-threatening cases.

Administration

Contra Indications

Hypersensitivity, Lactation.

Precautions

Renal impairment. Elderly. Pregnancy. Patient w/ cardiac disease, previous thyroid surgery; pre-existing anaemia, leucopenia or thrombocytopenia. Patient Counselling. Rarely, this drug may cause somnolence and/or dizziness, if affected, do not drive or operate machinery. Maintain good oral hygiene and adequate hydration. Monitoring Parameters Monitor renal function; serum electrolytes, including Ca, phosphate, Mg and K; CBC w/ differential. Perform routine dental check up.

Pregnancy-Lactation

Pregnancy Category: D Lactation: not known if crosses in to breast milk, avoid

Interactions

Concomitant use w/ other bisphosphonates, other antihypercalcaemic agents and calcitonin may lead to hypocalcaemia w/ associated clinical symptoms (e.g. paraesthesia, tetany, hypotension). Enhanced hypocalcaemic effect w/ aminoglycosides. Increased nephrotoxic effect w/ thalidomide. Enhanced adverse effects w/ NSAIDs. Synergistic effect w/ calcitonin in patients w/ severe hypercalcaemia.

Side Effects

Side effects of Pamidronic acid (Pamidronate) : Renal toxicity, HTN, fever and flu-like symptoms, anaemia, thrombocytopenia, lymphocytopenia; CNS effects (e.g. agitation, confusion, dizziness, lethargy, insomnia, somnolence), seizures, hallucinations, hypocalcaemia, hypophosphataemia, hypomagnesaemia, hypokalaemia, hypotension, osteonecrosis of the jaw (cancer patient), femoral fractures (long term treatment). Rarely, hypernatraemia, hyperkalaemia, bronchospasm, interstitial pneumonitis.

Mode of Action

The mechanism of action of pamidronate is inhibition of bone resorption. Pamidronate adsorbs to calcium phosphate (hydroxyapatite) crystals in bone and may directly block dissolution of this mineral component of bone. In vitro studies also suggest that inhibition of osteoclast activity contributes to inhibition of bone resorption. Pamidronate also targets farnesyl pyrophosphate (FPP) synthase. Nitrogen-containing bisphosphonates (such as pamidronate, alendronate, risedronate, ibandronate and zoledronate) appear to act as analogues of isoprenoid diphosphate lipids, thereby inhibiting FPP synthase, an enzyme in the mevalonate pathway. Inhibition of this enzyme in osteoclasts prevents the biosynthesis of isoprenoid lipids (FPP and GGPP) that are essential for the post-translational farnesylation and geranylgeranylation of small GTPase signalling proteins. This activity inhibits osteoclast activity and reduces bone resorption and turnover. In postmenopausal women, it reduces the elevated rate of bone turnover, leading to, on average, a net gain in bone mass.