Costs of Amphotericin B Lipid Complex for Kala-Azar

IN RESPONSE:

Dr. Basnyat raises the pertinent question of the cost of the short-course (5-day) regimen of amphotericin B lipid complex (ABLC), which proved effective in Indian patients with kala-azar who had not responded to 30 days or more of standard pentavalent antimony therapy. As we pointed out, lipid formulations of amphotericin B, including ABLC, are expensive. If priced as they are in the United States, they are likely to be beyond the reach of most patients with kala-azar, who largely live in developing countries.

Nonetheless, it is still worth considering how most patients in whom antinomy treatment fails are typically managed, at least in India: more lengthy retreatment with daily antinomy despite initial unresponsiveness or, more likely, prolonged and sometimes difficult-to-tolerate therapy with conventional amphotericin B or pentamidine. The latter two agents are usually given every other day over 30- to 40-day or 60-day periods, respectively [1]. Thus, it is difficult to overlook the fact that ABLC infusions of 1 to 2 mg/kg per day for 5 days induced a high rate of long-term cure in our patients. The short-course regimen obviously reduced both length of hospital stay and related in-hospital expenses, including the costs of repeated laboratory testing, and enabled patients to return to work or school sooner. However, hospital costs are usually low in countries in which kala-azar is endemic (such as India); savings realized by reducing length of stay are not large in this setting.

A rough total cost comparison for the drugs, hospitalization, and laboratory testing needed to re-treat a 50-kg Indian patient in Bihar who has kala-azar unresponsive to antimony with 1) conventional amphotericin B (rapidly escalating to 1 mg/kg every other day, 20 infusions over 40 days [1] [in our experience, daily injections of 1 mg/kg for 20 days [1] are not well-tolerated]) or 2) ABLC (1 mg/kg per day for 5 consecutive days, as in our study) yields the following result: $460 for amphotericin B and $675 for ABLC. These estimates include approximate retail drug costs of $90 for amphotericin B and $610 for ABLC (U.S. acquisition cost, $106 per 100-mg vial plus an arbitrary 15% markup = $122 per vial × 5 vials).

Because most of our Indian patients actually weigh less than 50 kg (mean weight, about 30 kg), several approaches to reduce the cost of drug (for example, ABLC) by 50% come to mind: a 50-mg vial (now being considered) or the simultaneous sharing (with sterile technique) of a 100-mg vial by at least two patients. In our busy unit in Bihar, the latter would not be farfetched: Most patients with kala-azar are not acutely ill, and we see several new patients each week whose treatment could be ethically synchronized. Alternatively, because refrigerated ABLC is stable for 48 hours after reconstitution, a 5-day course (1 mg/kg per day) for a 50-kg person might also be delivered with 2.5 rather than five 100-mg vials.

We hope that such approaches prove feasible or that lipid formulations of amphotericin B are much less expensive in certain areas abroad. If not, Dr. Basnyat's concluding sentence seems regrettably accurate in predicting what will happen in developing countries when the economic rubber hits the road for this class of remarkably effective antileishmanial agents. One additional, less expensive approach that we and others are testing is short-course therapy with conventional amphotericin B mixed with a commercially available lipid emulsion [2]. We refer affectionately to the latter combination as a “poor man's lipid-associated amphotericin B.”

• Copyright ©2004 by the American College of Physicians