The protease inhibitor lopinavir-ritonavir may produce opiate withdrawal in methadone-maintained patients.

McCance-Katz EF, Rainey PM, Friedland G, Jatlow P.

Clin Infect Dis. 2003 Aug 15;37(4):476-82. doi: 10.1086/376907. Epub 2003 Aug 1.

This study examines the pharmacokinetic/pharmacodynamic interactions between (1) lopinavir-ritonavir (L/R), a fixed combination of protease inhibitors used for the treatment of HIV disease, and (2) ritonavir alone at the same dosage as that in the L/R formulation, with methadone, an opiate frequently used in substance abuse pharmacotherapy for opioid (heroin)-dependent injection drug users, many of whom are infected with HIV. L/R was associated with significant reductions in the methadone area under the concentration-time curve (P<.001), maximum concentration (P<.001), and minimum concentration (P<.001), as well as increased methadone oral clearance (P<.001) and increased opiate withdrawal symptoms (P=.013), whereas ritonavir use alone modestly and nonsignificantly increased methadone concentrations. Lopinavir is a potent inducer of methadone metabolism, and treatment with L/R requires clinical monitoring and increased methadone doses in some patients, whereas ritonavir has no significant effect on methadone metabolism.

PMID: 12905130

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.