Pamidronate indications

There is considerable interest in using injectable bisphosphonates, such as pamidronate and zoledronic acid, in patients unable to tolerate or absorb oral bisphosphonates. Zoledronic acid in particular has a potential advantage of once-yearly dosing. Currently, neither drug has received FDA approval for this indication. Ibandronate has recently been approved for this indication. 

Bisphosphonates structurally mimic endogenous pyrophosphate, which inhibits precipitation and dissolution of bone minerals. They retard bone resorption by osteoclasts and, in part, also decrease bone mineralizatioa Indications include tumor osteolysis, hypercalcemia, and Paget s disease. Qinical trials with etidronate, administered as an intermittent regimen, have yielded favorable results in osteoporosis. With the newer drugs clodronate, pamidronate, and alendronate, inhibition of osteoclasts predominates a continuous regimen would thus appear to be feasible. 

Renal function impairment- In patients receiving pamidronate for bone metastases who show evidence of deterioration in renal function, withhold treatment until renal function returns to baseline. In a clinical study, renal deterioration was defined as follows for patients with normal baseline creatinine, an increase of 0.5 mg/dL for patients with abnormal baseline creatinine, an increase of 1 mg/dL. In this clinical study, pamidronate treatment was resumed only when the creatinine returned to within 10% of the baseline value. In other indications, clinical judgment should determine whether the potential benefit outweighs the potential risk in such patients. 

Agents include etidronic acid, pamidronic acid, clodronic acid, alendronic acid, ibandronic acid, rise-dronic acid, zoledronic acid and tiludronic acid. Formulations of clodronic acid and pamidronic acid are available for intravenous administration. The indications for the use of bisphosphonates include treatment of postmenopausal osteoporosis, hypercal-caemia of malignancy and Paget s disease. 

Pamidronate, 60-90 mg, infused over 2-4 hours, and zole-dronate, 4 mg, infused over at least 15 minutes, have been approved for the treatment of hypercalcemia of malignancy and have largely replaced the less effective etidronate for this indication. The effects generally persist for weeks, but treatment can be repeated after a 7-day interval if necessary and if renal function is not impaired. Some patients experience a self-limited flu-like syndrome after the infusion. Repeated doses of these drugs have been linked to renal deterioration and osteonecrosis of the jaw, but this adverse effect is rare. 

General Category Bisphosphonates Examples Alendronate (Fosamax) Etidronate (Didronel) Ibandronate (Boniva) Pamidronate (Aredia) Risedronate (Actonel) Treatment Rationale and Principal Indications Appear to block excessive bone resorption and formation is used to normalize bone turnover in conditions such as osteoporosis and Paget disease, and to prevent hypercalcemia resulting from excessive bone resorption in certain forms of cancer... 

Giving intravenous phosphate is probably the fastest and surest way to reduce serum calcium, but it is a hazardous procedure if not done properly. Intravenous phosphate should be used only after other methods of treatment (pamidronate, calcitonin, saline diuresis with furosemide, and plicamycin) have failed to control symptomatic hypercalcemia. Phosphate must be given slowly (50 mmol or 1.5 g elemental phosphorus over 6-8 hours) and the patient switched to oral phosphate (1-2 g/d elemental phosphorus, as one of the salts indicated below) as soon as symptoms of hypercalcemia have cleared. The risks of intravenous phosphate therapy include sudden hypocalcemia, ectopic calcification, acute renal failure, and hypotension. Oral phosphate can also lead to ectopic calcification and renal failure if serum calcium and phosphate levels are not carefully monitored, but the risk is less and the time of onset much longer. Phosphate is available in oral and intravenous forms as the sodium or potassium salt. Amounts required to provide 1 g of elemental phosphorus are as follows ... 

Uses. Three bisphosphonates (alendronate, etidronate, risedronate) are currently licensed in the UK for the treatment of osteoporosis (zoledronate is also effective), and the others are used in Paget s disease of bone, and hypercalcaemia due to cancer (pamidronate, clodronate, zoledronate). Bisphosphonates may also provide benefit for neoplastic disease that has spread to bone evidence indicates that clodronate by mouth and pamidronate i.v. are effective in the secondary prevention of bone metastases due to multiple myeloma and breast cancer. 

Bisphosphonates are widely used for the prevention and treatment of osteopenia and osteoporosis and for the reduction of skeletal complications in patients with malignant bone disease. Several oral bisphosphonates, including alendronate, risedronate, and ibandronate, are approved worldwide for the treatment of osteoporosis in postmenopausal women, as are intravenous (i.v.) formulations of ibandronate (3 mg quarterly) and zoledronic acid (5 mg annually). Several i.v. bisphosphonates are available for the treatment of the skeletal complications that frequently occur in malignant disease, such as hypercalcaemia of malignancy (HCM), multiple myeloma, and bone metastases associated with solid tumours. Pamidronate is approved worldwide for the treatment of HCM, multiple myeloma, and breast cancer bone metastases. Although not registered for oncology indications in the United States, i.v. ibandronate is widely available elsewhere for HCM and breast cancer bone metastases. 

Some patients cannot tolerate oral bisphosphonates. Zoledronic acid is not FDA-approved for osteoporosis treatment, but is sometimes administered intravenously once yearly in patients for whom bisphosphonates are indicated. It improved BMD similarly to oral bisphosphonates, but the impact on fracture rates is under investigation. Quarterly administration of intravenous pamidronate or ihandronate also improves BMD. 

Pamidronate disodium is a bisphosphonate that inhibits normal and abnormal bone resorption. It is indicated in the treatment of moderate to severe hypercalcemia associated... 

HYPERCALCEMIA Pamidronate is used parenterally in the management of malignancy-associated hypercalcemia. Zoledronate is also FDA-approved for this indication and appears to be more effective than pamidronate, at least as safe, and can be infused over 15 minutes rather than 4 hours. 

Pamidronate is one of the first drugs that has been proven to reduce the incidence of skeletal complications of metastatic breast cancer and prostate cancer. It also relieves bone pain caused by metastatic bone lesions. Other indications include treatment of osteolytic bone lesions of multiple myeloma, moderate-to-severe hypercalcemia of malignancy, and moderate-to-severe bone lesions due to Paget s disease. 

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