Unimed Pamidronate Special Precautions

General: Pamidronate Disodium must never be given as a bolus injection, but should always be diluted and given as a slow intravenous infusion.
Patients must be assessed prior to administration of Pamidronate Disodium to assure that they are appropriately hydrated. This is especially important for patients receiving diuretic therapy.
Standard hypercalcaemia-related metabolic parameters including serum, calcium and phosphate should be monitored following initiation of therapy with Pamidronate Disodium. Patients who have undergone thyroid surgery may be particularly susceptible to developing hypocalcaemia due to relative hypoparathyroidism.
In patients with cardiac disease, especially in the elderly, additional saline overload may precipitate cardiac failure (left ventricular failure or congestive heart failure). Fever (influenza-like symptoms) may also contribute to this deterioration.
Convulsions have been precipitated in some patients with tumour-induced hypercalcaemia due to the electrolyte changes associated with this condition and its effective treatment.
Renal Insufficiency: Bisphosphonates, including Pamidronate Disodium, have been associated with renal toxicity manifested as deterioration of renal function and potential renal failure. Renal deterioration, progression to renal failure and dialysis have been reported in patients after the initial dose or a single dose of Pamidronate Disodium. Deterioration of renal function (including renal failure) has also been reported following long-term treatment with Pamidronate Disodium in patients with multiple myeloma.
Pamidronate Disodium is excreted intact primarily via the kidney, thus the risk of renal adverse reactions may be greater in patients with impaired renal function.
Due to the risk of clinically significant deterioration in renal function which may progress to renal failure, single doses of Pamidronate Disodium should not exceed 90mg, and the recommended infusion time should be observed.
As with other IV bisphosphonates renal monitoring is recommended, for instance, measurement of serum creatinine prior to each dose of Pamidronate Disodium.
Patients treated with Pamidronate Disodium for bone metastases or multiple myeloma should have the dose withheld if renal function has deteriorated.
Pamidronate Disodium should not be administered to patients with severe renal impairment (creatinine clearance < 30 mL/min) unless in cases of life-threatening tumour-induced hypercalcaemia where the benefit outweighs the potential risk. Because there is only limited pharmacokinetic data with severe renal impairment no dose recommendations for this patient population can be made. Pamidronate Disodium should not be given with other bisphosphonates because their combined effects have not been investigated. There is very little experience of the use of Pamidronate Disodium in patients receiving haemodialysis.
Hepatic Insufficiency: As there are no clinical data available in patients with severe hepatic insufficiency, no specific recommendations can be given for this patient population.
Calcium and Vitamin D Supplementation: In the absence of hypercalcaemia, patients with predominantly lytic bone metastases or multiple myeloma, who are at risk of calcium or vitamin D deficiency (e.g. through malabsorption or lack of exposure to sunlight) and patients with Paget's disease of the bone should take oral calcium and vitamin D supplementation in order to minimize the potential risk of hypocalcaemia.
Osteonecrosis of the jaw: Osteonecrosis of the jaw has been reported predominantly in cancer patients treated with bisphosphonates, including Pamidronate Disodium. Many of these patients were also receiving chemotherapy and corticosteroids. The majority of reported cases have been associated with dental procedures such as tooth extraction. Many had signs of local infection including osteomyelitis.
A dental examination with appropriate preventive dentistry should be considered prior to treatment with bisphosphonates in patients with concomitant risk factors (e.g. cancer, chemotherapy, corticosteroids, poor oral hygiene).
While on treatment, these patients should avoid invasive dental procedures if possible. For patients who develop osteonecrosis of the jaw while on bisphosphonate therapy, dental surgery may exacerbate the condition. For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis of the jaw. Clinical judgement of the treating physician should guide the management plan of each patient based on individual benefit/risk assessment.
Musculoskeletal Pain: Severe and occasionally incapacitating bone, joint, and/or muscle pain has been reported in patients taking bisphosphonates. This category of drugs includes Pamidronate Disodium for infusion. The time to onset of symptoms varied from one day to several months after starting the drug with the majority occurring within a few days. Most patients had relief or improvement of symptoms after stopping treatment. A subset had recurrence of symptoms when rechallenged with the same drug or another bisphosphonate.
Effects on the ability to drive or operate machinery: Patients should be warned that somnolence and/or dizziness may occur following Pamidronate Disodium infusion, in which case they should not drive, operate potentially dangerous machinery or engage in other activities that may be hazardous because of decreased alertness.