Drug Interaction Report

GENERALLY AVOID: Concomitant use of leucovorin with sulfamethoxazole-trimethoprim (SMX-TMP) for the acute treatment of Pneumocystis jiroveci pneumonia (formerly known as Pneumocystis carinii pneumonia, or PCP) has been associated with increased rates of treatment failure and morbidity. In a randomized, double-blind, placebo-controlled study consisting of 92 AIDS patients with PCP, a higher rate of both therapeutic failure (15% vs. 0%) and death (11% vs. 0%) was observed in subjects receiving SMX-TMP and leucovorin compared to subjects receiving SMX-TMP alone. The time to therapeutic failure was shorter and probability of death greater in patients receiving leucovorin, even after adjusting for baseline arterial oxygen pressure, serum lactate dehydrogenase, respiratory rate, CD4 cell count, and peak serum level of SMX or TMP. Although the incidence of neutropenia was lower in patients receiving leucovorin (23% vs. 47%), there was no significant difference in time to occurrence. Isolated case reports have also described treatment failure when SMX-TMP was administered in combination with leucovorin, both in AIDS patients and in renal transplant patients. The actual efficacy of leucovorin in mitigating adverse effects of SMX-TMP is questionable. In one study, investigators found that leucovorin use did not improve tolerance for chronic SMX-TMP prophylaxis in AIDS, even among patients taking the medication daily. In another study, leucovorin therapy did not abolish the cytopenia associated with SMX-TMP in 12 patients with PCP, and the authors recommended that leucovorin not be routinely prescribed for this purpose.

MANAGEMENT: The use of leucovorin in immunosuppressed patients receiving SMX-TMP for treatment of Pneumocystis jiroveci pneumonia should be avoided unless benefits are anticipated to outweigh the risks.