Interactions between Buprenorphine and Antiretrovirals. I. The Nonnucleoside Reverse-Transcriptase Inhibitors Efavirenz and Delavirdine

McCance‐Katz, Elinore F.; Moody, David E.; Morse, Gene D.; Friedland, Gerald; Pade, Patricia; Baker, Jennifer R.; Alvanzo, Anika; Smith, Patrick F.; Ogundele, Abayomi; Jatlow, Peter; Rainey, Petrie M.

doi:10.1086/508187

Cited by 82 publications

(65 citation statements)

References 22 publications

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“…This may explain the lack of withdrawal symptoms despite the decreased peak concentrations of buprenorphine (3,9). The lack of withdrawal symptoms associated with decreased buprenorphine exposure was also observed in other drug interaction studies between buprenorphine/naloxone and antiretroviral agents (11).…”

Section: Discussionsupporting

confidence: 66%

Effect of Telaprevir on the Pharmacokinetics of Buprenorphine in Volunteers on Stable Buprenorphine/Naloxone Maintenance Therapy

Luo

Trevejo

Heeswijk

et al. 2012

Antimicrob Agents Chemother

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bThis was an open-label, single-sequence trial in hepatitis C virus-negative volunteers on stable, individualized, buprenorphine maintenance therapy. Telaprevir at 750 mg every 8 h was coadministered with buprenorphine/naloxone (4:1 ratio as sublingual tablets) for 7 days with food. Pharmacokinetic profiles of buprenorphine, norbuprenorphine, and naloxone were measured over the 24-hour dosing interval on day ؊1 (buprenorphine/naloxone alone, reference) and day 7 of telaprevir coadministration (test). Geometric least-squares mean ratios and associated 90% confidence intervals of treatment ratios (test/reference) were calculated using log-transformed pharmacokinetic parameters. Opioid withdrawal symptoms were evaluated throughout the study (via questionnaires and pupillometry). Pharmacokinetic data were available for 14 and 13 volunteers on day ؊1 and day 7, respectively. The area under the concentration-time curve (AUC) for buprenorphine was unchanged and the maximum concentration of drug in serum (C max ) for buprenorphine, C max and AUC for norbuprenorphine, and C max naxolone were modestly decreased during coadministration with telaprevir. Geometric least-squares mean ratios (90% confidence intervals) for buprenorphine were 0.80 (0.69, 0.93) for the C max and 0.96 (0.84, 1.10) for the AUC from 0 to 24 h (AUC 0 -24 ); for norbuprenorphine, values were 0.85 (0.66, 1.09) for C max and 0.91 (0.71, 1.16) for AUC 0 -24 ; for naloxone, the C max was 0.84 (0.62, 1.13). Coadministration of telaprevir did not increase withdrawal symptom frequency, and there were no serious adverse events reported during or after completion of telaprevir coadministration. Results suggest dose adjustment may not be necessary when telaprevir and buprenorphine/naloxone are coadministered.

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Section: Discussionsupporting

confidence: 66%

Effect of Telaprevir on the Pharmacokinetics of Buprenorphine in Volunteers on Stable Buprenorphine/Naloxone Maintenance Therapy

Luo

Trevejo

Heeswijk

et al. 2012

Antimicrob Agents Chemother

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“…Inhibition and induction of CYP3A4 affects buprenorphine concentration, but not necessarily its clinical effects. Co-administration of the inducer efavirenz with buprenorphine was associated with decreased buprenorphine AUC but not with withdrawal symptoms [86]. Nevirapine, which induces CYP3A4, affected neither buprenorphine concentration nor withdrawal symptoms [87].…”

Section: Sedative Hypnotics and Opioid Medicationsmentioning

confidence: 89%

A Review of the Toxicity of HIV Medications II: Interactions with Drugs and Complementary and Alternative Medicine Products

et al. 2015

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For many patients today, HIV has become a chronic disease. For those patients who have access to and adhere to lifelong antiretroviral (ARV) therapy, the potential for drugdrug interactions has become a real and life-threatening concern. It is known that most ARV drug interactions occur through the cytochrome P450 (CYP) pathway. Medications for comorbid medical conditions, holistic supplements, and illicit drugs can be affected by CYP inhibitors and inducers and have the potential to cause harm and toxicity. Protease inhibitors (PIs) tend to inhibit CYP3A4, while most nonnucleoside reverse transcriptase inhibitors (NNRTIs) tend to induce the enzyme. As such, failure to adjust the dose of coadministered medications, such as statins and steroids, may lead to serious complications including rhabdomyolysis and hypercortisolism, respectively. Similarly, gastric acid blockers can decrease several ARV absorption, and warfarin doses may need to be adjusted to maintain therapeutic concentrations. Illicit drugs such as methylenedioxymethamphetamine (MDMA, "ecstasy") in combination with PIs lead to increased toxicity, while the concomitant administration of sedative drugs such as midazolam and alprazolam in patients taking PIs can result in prolonged sedation, delayed recovery, and increased length of stay. Even supplements like St. John's Wort can alter PI concentrations. In theory, any drug that is metabolized by CYP has potential for a pharmacokinetic drug-drug interaction with all PIs, cobicistat, and most NNRTIs. When adding a new medication to an ARV regimen, use of a drug-drug interaction software and/or consultation with a clinical pharmacist/pharmacologist or HIV specialist is recommended.

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“…Both NNRTIs seem to exert their effect through marked induction of cytochrome P450 isoenzymes. Although efavirenz significantly reduces buprenorphine levels, preliminary studies indicate that this reduction is not associated with symptoms of opioid withdrawal [94].…”

Section: Drug Interactions With Hiv Therapiesmentioning

confidence: 96%

Clinical Care of the HIV-Infected Drug User

Bruce¹,

Altice²

2007

Infectious Disease Clinics of North America

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Interactions between Buprenorphine and Antiretrovirals. I. The Nonnucleoside Reverse-Transcriptase Inhibitors Efavirenz and Delavirdine

Cited by 82 publications

References 22 publications

Effect of Telaprevir on the Pharmacokinetics of Buprenorphine in Volunteers on Stable Buprenorphine/Naloxone Maintenance Therapy

Effect of Telaprevir on the Pharmacokinetics of Buprenorphine in Volunteers on Stable Buprenorphine/Naloxone Maintenance Therapy

A Review of the Toxicity of HIV Medications II: Interactions with Drugs and Complementary and Alternative Medicine Products

Clinical Care of the HIV-Infected Drug User

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