PMC:7463108 / 105713-107502 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7463108","sourcedb":"PMC","sourceid":"7463108","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7463108","text":"There are several known drug-drug interactions between opioids and ARVs that affect systemic concentrations. The partial opioid agonist, buprenorphine, is metabolized primarily by cytochrome P450 (CYP) 3A4 and 2C8. Both buprenorphine and its active metabolite, norbuprenorphine, are glucuronidated by UDP-glucuronosyltransferase (UGT) 1A1 and then excreted in bile. Several ARVs inhibit or induce these metabolic pathways. However, not all interactions are clinically relevant. The boosted protease inhibitor combination, atazanavir/ritonavir, inhibits CYP 3A4 and UGT 1A1, leading to increases in overall systemic exposure of buprenorphine and norbuprenorphine and also results in symptoms of opioid excess, such as increased sedation and impaired cognition (McCance-Katz et al. 2007). Dose adjustments of buprenorphine are recommended when initiating therapy with atazanavir to avoid symptoms of opioid excess. Methadone is a full opioid substrate with multiple metabolic pathways, including CYP 3A4, 2B6, 2C19, 2C9, and 2D6. Several pharmacokinetic interactions are reported between methadone and protease inhibitors. However, withdrawal symptoms are rare, and therefore, dose adjustments are not recommended (Bruce et al. 2006; Meemken et al. 2015). In contrast, efavirenz and nevirapine induce CYP 3A4, resulting in decreased systemic concentrations of methadone and the development of opioid withdrawal symptoms. To avoid opioid withdrawal, increased methadone dosing is recommended when either efavirenz or nevirapine therapy is initiated (Marzolini et al. 2000; Clarke et al. 2001; Meemken et al. 2015). Oxycodone metabolism is inhibited by lopinavir/ritonavir, increasing oxycodone concentrations as well as the self-reported drug effects (Nieminen et al. 2010; Feng et al. 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