Should the pamidronate (Aredia) dose be adjusted in a patient with renal failure receiving hemodial

Fråga: Should the pamidronate (Aredia) dose be adjusted in a patient with renal failure receiving hemodialysis three times per week?

Sammanfattning: Pamidronate exposure is increased in renal impairment, but the clinical implications are uncertain. There are theoretical reasons to believe that the drug could be eliminated by hemodialysis.

According to manufacturer´s recommendations, the initial pamidronate dose should be reduced by one third in dialysis patients. Pamidronate should be given directly after hemodialysis, and the first dose should be followed up with close monitoring of serum calcium levels. The interval between doses requires no adjustment in dialysis.

Svar: Pamidronate has a short half-life (approximately 30 minutes), and is almost exclusively eliminated by renal excretion (1, 2). Renal insufficiency with creatinine levels below 30 mL/min causes a three-fold increase in the AUC of pamidronate (2) and a trend toward lower total urinary recovery of the drug (3). Nevertheless, the Drugdex database states that dosage adjustment probably is unnecessary in patients with renal impairment given 90 mg pamidronate monthly, due to the low risk of excessive accumulation (3). Although the recommended pamidronate dose is 90 mg per month, there are indications that 180 mg be both tolerable and more effective in the treatment of osteolytic metastases (4). Hence, it is not self-evident whether the increased exposure seen in renally impaired patients is detrimental or advantageous.

It is not known to what extent pamidronate is cleared by hemodialysis. However, a low molecular weight (370 Dalton) and a plasma protein binding below 14 percent indicate that dialysis could be an effective means of eliminating the drug from plasma (1).

The manufacturer recommends that dialysis patients are given pamidronate at ordinary intervals (once per month), and that the drug is administered directly after a hemodialysis session. As an extra precaution, it is recommended that the initial dose is reduced by one third and that serum calcium is monitored at day 1, 2, 3, and 5 after administration. If the lower dose is well tolerated, a full 90 mg dose can be considered from the second infusion onwards (5). Dollery C Sir, editor. Therapeutic drugs. 2nd ed. Edinburgh: Churchill Livingstone; 1999 Fass 2005 Pamidronate. Drugdex(R) System; Thomson MICROMEDEX, Greenwood Village, Colorado (Cited 2005-06-17) Kouloulias EV, Kouvaris RJ, Antypas C, Mystakidou K, Matsopoulos G, Uzunoglu CN, Moulopoulos A, Vlahos JL. An intra-patient dose-escalation study of disodium pamidronate plus radiotherapy versus radiotherapy alone for the treatment of osteolytic metastases. Monitoring of recalcification using image-processing techniques. Strahlenther Onkol. 2003 179:471-9. Personal communication Karin Mjömark, Novartis (2005-06-17)