- USES: Bisphosphonates and have been used in the treatment of diseases associated with excessive bone turnover including osteoporosis, Paget’s disease of bone, hypercalcemia of malignancy, and osteolytic bone lesions of multiple myeloma. PHARMACOLOGY: Bisphosphonates have a high affinity for mineralized bone and inhibit osteoclast-mediated bone resorption resulting in a net gain in bone mass. EPIDEMIOLOGY: Overdose of this medication is rare. MILD TO MODERATE TOXICITY: Mild to moderate toxicity of bisphosphonates have resulted in hypocalcemia, paresthesia, hypotension, fever, and vomiting. SEVERE TOXICITY: Acute renal failure and death have been reported following high dose administration of tiludronate (800 mg/day IV for 2 days). ADVERSE EFFECTS: Dose-dependent upper gastrointestinal irritation (ie, esophagitis, esophageal ulcers, erosions, and dysphagia) is common. Asymptomatic decreases in calcium and phosphate may develop. Headache, musculoskeletal pain, and osteonecrosis of the jaw have been reported. Rare reports of rash and erythema have occurred.
Range of Toxicity:
- Therapeutic dose varies by agent. In general, overdose with these agents can result in clinically significant hypocalcemia, hypophosphatemia, and hypomagnesemia.
- Decontamination: Activated charcoal, gastric lavage
- Hypocalcemia: 10 ml of 10% calcium gluconate or calcium chloride IV over 10-15 min; may be repeated.
- Torsades de pointes: Correct electrolyte abnormalities. Magnesium: Adult: 2 gm IV over 2 min, may repeat bolus, infusion 3 to 20 mg/min. Child: 25-50 mg/kg diluted 10 mg/ml over 5-15 min. Isoproterenol, overdrive pacing. Avoid procainamide, disopyramide, quinidine, sotalol
- Monitoring of patient: ECG, continuous cardiac monitoring, calcium & phosphate levels. CBC, electrolytes, renal function, fluid status if GI bleed suspected. Test stool/gastric aspirate for blood.