home > drugs a-z list > aredia (pamidronate disodium) drug center > aredia (pamidronate disodium) drug - warnings and precautions

Deterioration in Renal Function

Bisphosphonates, including Aredia (pamidronate disodium) , have been associated with renal toxicity manifested as deterioration of renal function and potential renal failure.

DUE TO THE RISK OF CLINICALLY SIGNIFICANT DETERIORATION IN RENAL FUNCTION, WHICH MAY PROGRESS TO RENAL FAILURE, SINGLE DOSES OF AREDIA SHOULD NOT EXCEED 90 MG (see DOSAGE AND ADMINISTRATION for appropriate infusion durations). Renal deterioration, progression to renal failure, and dialysis have been reported in patients after the initial or a single dose of Aredia (pamidronate disodium) .

Focal segmental glomerulosclerosis (including the collapsing variant) with or without nephrotic syndrome, which may lead to renal failure, has been reported in Aredia (pamidronate disodium) -treated patients, particularly in the setting of multiple myeloma and breast cancer. Some of these patients had gradual improvement in renal status after Aredia (pamidronate disodium) was discontinued.

Patients who receive Aredia (pamidronate disodium) should have serum creatinine assessed prior to each treatment. Patients treated with Aredia (pamidronate disodium) for bone metastases should have the dose withheld if renal function has deteriorated. (See DOSAGE AND ADMINISTRATION.)

PREGNANCY: AREDIA (pamidronate disodium) SHOULD NOT BE USED DURING PREGNANCY

Aredia (pamidronate disodium) may cause fetal harm when administered to a pregnant woman. (See PRECAUTIONS, Pregnancy Category D.)

There are no studies in pregnant women using Aredia (pamidronate disodium) . If the patient becomes pregnant while taking this drug, the patient should be apprised of the potential harm to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant.

Studies conducted in young rats have reported the disruption of dental dentine formation following single-and multi-dose administration of bisphosphonates. The clinical significance of these findings is unknown.

General

Standard hypercalcemia-related metabolic parameters, such as serum levels of calcium, phosphate, magnesium, and potassium, should be carefully monitored following initiation of therapy with Aredia (pamidronate disodium) . Cases of asymptomatic hypophosphatemia (12%), hypokalemia (7%), hypomagnesemia (11%), and hypocalcemia (5%-12%), were reported in Aredia (pamidronate disodium) -treated patients. Rare cases of symptomatic hypocalcemia (including tetany) have been reported in association with Aredia (pamidronate disodium) therapy. If hypocalcemia occurs, short-term calcium therapy may be necessary. In Paget's disease of bone, 17% of patients treated with 90 mg of Aredia (pamidronate disodium) showed serum calcium levels below 8 mg/dL.

Patients with a history of thyroid surgery may have relative hypoparathyroidism that may predispose to hypocalcemia with Aredia (pamidronate disodium) .

Renal Insufficiency

Aredia (pamidronate disodium) is excreted intact primarily via the kidney, and the risk of renal adverse reactions may be greater in patients with impaired renal function. Patients who receive Aredia (pamidronate disodium) should have serum creatinine assessed prior to each treatment. In patients receiving Aredia (pamidronate disodium) for bone metastases, who show evidence of deterioration in renal function, Aredia (pamidronate disodium) treatment should be withheld until renal function returns to baseline (see WARNINGS and DOSAGE AND ADMINISTRATION).

In clinical trials, patients with renal impairment (serum creatinine > 3.0 mg/dL) have not been studied. Limited pharmacokinetic data exist in patients with creatinine clearance < 30 ml/min (See CLINICAL PHARMACOLOGY, Pharmacokinetics.) For the treatment of bone metastases, the use of Aredia (pamidronate disodium) in patients with severe renal impairment is not recommended. In other indications, clinical judgment should determine whether the potential benefit outweighs the potential risk in such patients.

Osteonecrosis of the Jaw

Osteonecrosis of the jaw (ONJ) has been reported predominantly in cancer patients treated with intravenous bisphosphonates, including Aredia (pamidronate disodium) . Many of these patients were also receiving chemotherapy and corticosteroids which may be risk factors for ONJ. Postmarketing experience and the literature suggest a greater frequency of reports of ONJ based on tumor type (advanced breast cancer, multiple myeloma), and dental status (dental extraction, periodontal disease, local trauma including poorly fitting dentures). Many reports of ONJ involved patients with signs of local infection including osteomyelitis.

Cancer patients should maintain good oral hygiene and should have a dental examination with preventive dentistry prior to treatment with bisphosphonates.

While on treatment, these patients should avoid invasive dental procedures if possible. For patients who develop ONJ 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 ONJ. Clinical judgment of the treating physician should guide the management plan of each patient based on individual benefit/risk assessment (See ADVERSE REACTIONS).

Musculoskeletal Pain

In post-marketing experience, severe and occasionally incapacitating bone, joint, and/or muscle pain has been reported in patients taking bisphosphonates. However, such reports have been infrequent. This category of drugs includes Aredia (pamidronate disodium for injection). The time to onset of symptoms varied from one day to several months after starting the drug. Most patients had relief of symptoms after stopping. A subset had recurrence of symptoms when rechallenged with the same drug or another bisphosphonate.

Laboratory Tests

Patients who receive Aredia (pamidronate disodium) should have serum creatinine assessed prior to each treatment. Serum calcium, electrolytes, phosphate, magnesium, and CBC, differential, and hematocrit/hemoglobin must be closely monitored in patients treated with Aredia (pamidronate disodium) . Patients who have preexisting anemia, leukopenia, or thrombocytopenia should be monitored carefully in the first 2 weeks following treatment.

Carcinogenesis, Mutagenesis, Impairment of Fertility

In a 104-week carcinogenicity study (daily oral administration) in rats, there was a positive dose response relationship for benign adrenal pheochromocytoma in males (PO.00001). Although this condition was also observed in females, the incidence was not statistically significant. When the dose calculations were adjusted to account for the limited oral bioavailability of Aredia (pamidronate disodium) in rats, the lowest daily dose associated with adrenal pheochromocytoma was similar to the intended clinical dose. Adrenal pheochromocytoma was also observed in low numbers in the control animals and is considered a relatively common spontaneous neoplasm in the rat. Aredia (pamidronate disodium) (daily oral administration) was not carcinogenic in an 80-week study in mice.

Aredia (pamidronate disodium) was nonmutagenic in six mutagenicity assays: Ames test, Salmonella and Escherichia/liver-microsome test, nucleus-anomaly test, sister-chromatid-exchange study, point-mutation test, and micronucleus test in the rat.

In rats, decreased fertility occurred in first-generation offspring of parents who had received 150 mg/kg of Aredia (pamidronate disodium) orally; however, this occurred only when animals were mated with members of the same dose group. Aredia (pamidronate disodium) has not been administered intravenously in such a study.

Pregnancy Category

(See WARNINGS)

There are no adequate and well-controlled studies in pregnant women.

Bolus intravenous studies conducted in rats and rabbits determined that Aredia (pamidronate disodium) produces maternal toxicity and embryo/fetal effects when given during organogenesis at doses of 0.6 to 8.3 times the highest recommended human dose for a single intravenous infusion. As it has been shown that Aredia (pamidronate disodium) can cross the placenta in rats and has produced marked maternal and nonteratogenic embryo/fetal effects in rats and rabbits, it should not be given to women during pregnancy.

Bisphosphonates are incorporated into the bone matrix, from where they are gradually released over periods of weeks to years. The extent of bisphosphonate incorporation into adult bone, and hence, the amount available for release back into the systemic circulation, is directly related to the total dose and duration of bisphosphonate use. Although there are no data on fetal risk in humans, bisphosphonates do cause fetal harm in animals, and animal data suggest that uptake of bisphosphonates into fetal bone is greater than into maternal bone. Therefore, there is a theoretical risk of fetal harm (e.g., skeletal and other abnormalities) if a woman becomes pregnant after completing a course of bisphosphonate therapy. The impact of variables such as time between cessation of bisphosphonate therapy to conception, the particular bisphosphonate used, and the route of administration (intravenous vs oral) on this risk has not been established.

Nursing Mothers

It is not known whether Aredia (pamidronate disodium) is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Aredia (pamidronate disodium) is administered to a nursing woman.

Pediatric Use

Safety and effectiveness of Aredia (pamidronate disodium) in pediatric patients have not been established.

Geriatric Use

Of the total number of subjects in clinical studies of Aredia (pamidronate disodium) , approximately 20% were 65 and over, while approximately 15% were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Last reviewed on RxList: 5/23/2011
This monograph has been modified to include the generic and brand name in many instances.