Aredia (pamidronate) is one of the bisphosphonate series of drugs, considerably more potent that earlier drugs such as etidronate and clodronate, probably less potent than the recently approved Fosamax. (Fosamax is intended for oral use, but patients report discomfort with side effects.) Aredia is administered by IV, with a standard dosage of 90 mg over a 4-hour infusion once monthly.

Aredia is of interest to myeloma patients because it can slow the bone destruction which is typical of the disease. Patients on Aredia suffer about half as many fractures, and have much less bone pain. This is important as it allows not only a reduction in analgesic use, but a reduction in radiation treatments, which can badly reduce bone marrow reserve. It is also claimed (unpublished data from Jim Berenson at UCLA) that Aredia downregulates IL-6 production by the bone-marrow stroma. This could directly impact the progress of the underlying myeloma; however, researchers have told me that they could not find that clodronate or pamidronate treatment improves survival.

Aredia is also highly effective in treatment of hypercalcemia, another common complication of multiple myeloma; a single 90-mg dose normalized serum calcium in 100% of patients treated (n=17).

Aredia is claimed to have few serious side-effects, and this is confirmed by patient response (via Internet), which has been quite positive. The potential for hypocalcemia is obvious. Hypokalemia also sometimes occurs (but this might be considered a positive for renal patients!) Serum magnesium and phosphorus may also be reduced. Anemia may be aggravated in a few patients. There is a possibility, apparently fairly remote, that Aredia may cause seizures in susceptible patients. Long-term effects of Aredia are not certain, as studies have extended only to nine months of treatment.

Aredia is excreted by the kidneys. Mild renal impairment therefore affects clearance of the drug, but because of the low toxicity and infrequent dosage schedule, reduction of dosage in these patients is not required. However, the Berenson myeloma studie did not include patients with creatinine > 5.0 mg/dL. In a different study, though, reduced doses (30-60 mg single treatments) were used in patients with ESRD without apparent adverse effects. In a study of cancer patients with no renal impairment, pamidronate at 90 mg/week for four weeks caused no significant change in renal function. However, animal experiments did find some nephrotoxicity from pamidronate, and renal toxicity has been associated with other bisphosphonates.

Based on the information at hand, it appears to me that Aredia presents little risk of renal toxicity. However, the available evidence is insufficient to draw solid conclusions, and the known nephotoxicity of the less potent bisphosphonates argues for some caution, especially for long-term use.

The use of a single dose of Aredia for treatment of hypercalcemia looks pretty safe even in ESRD patients. When it comes to long-term use for bone lesions, a judgment call is needed. The possibility of renal toxicity is there, and the myeloma patient must consider that loss of kidney function is a major blow to quality of life and is a very negative factor for survival time. On the other hand, bone lesions not only can be extremely painful; fractures, especially of the hip, cause loss of mobility, and spinal lesions can lead to paralysis. One can wait to use Aredia until bone lesions start to become serious; but it must be realized that Aredia does not seem to able to reverse, or even completely arrest, osteolysis; it can only slow it down. These issues must be carefully weighed, and a decision made based on the patient's values and quality of life concerns as well as his specific disease parameters.