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

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.