Decrease in Methodone Levels With Nelfinavir Mesylate
Mr. A, a 40-year-old man with a 25-year history of opioid dependence and use of injected drugs, had been receiving opioid-replacement therapy for 13 years. He was diagnosed with HIV in 1990. Mr. A had been stable for several years while receiving methadone, 100 mg/day. His HIV was advanced; he had a CD4+ T lymphocyte count consistently below 50 cells/mm3. He had received multiple antiretroviral treatments and had few remaining treatment options. His current antiretroviral treatment included the protease inhibitor indinavir, 800 mg three times per day, and the nucleoside reverse transcriptase inhibitor zalcitabine, 0.75 mg three times per day. The reverse transcriptase inhibitor stavudine and the protease inhibitor nelfinavir, 750 mg three times per day, were added to his drug regimen.Within 6 weeks, Mr. A began to complain of opiate withdrawal symptoms, which increased in severity over 3 months and included musculoskeletal pain, abdominal cramping, and rhinorrhea. His methadone dose was increased at 1- to 2-week intervals, and subtherapeutic methadone levels were documented until he attained a dose of 285 mg/day.Exacerbation of Mr. A’s HIV symptoms necessitated discontinuation of antiretroviral treatment in order to alter his HIV therapeutics. This required a medically monitored reduction of his methadone dose over 5 days (the minimal time necessary to reverse hepatic enzyme induction) to reach a target dose of 125 mg/day. Mr. A tolerated this with minimal discomfort; he required no clonidine or oxazepam, which were available for opiate-withdrawal symptoms.
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