Title: CYP3A4 inducing agents may cause opioid withdrawal in patients on buprenorphine <br/>Author: Hong Kim<br/><a href='http://umem.org/profiles/faculty/526/'>[Click to email author]</a><hr/><p>
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Buprenorphine (BUP) is increasingly prescribed/used to treat opioid use disorder (OUD) in the United State. BUP is mainly metabolized by CYP3A4 where its enzymatic activity can be either induced or inhibited by many agents. </p>
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For example, a study showed that Rifampin administration for 15 days, a potent 3A4 inducer, resulted in (1): </p>
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Reduction of plasma BUP concentration (70% reduction in area under the curve [AUC]) </li>
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50% of the study subjects (12 out of 24) experienced opioid withdrawal symptoms (OWS)</li>
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4 out of 12 who experience OWS received transient increase in their BUP dose (25-100%)</li>
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On the contrary, exposure to voriconazole – strong 3A4 inhibitor - resulted in (n=12 health volunteers) (2):</p>
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Increased the plasma BUP AUC by 4.3 fold</li>
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Increased peak BUP concentration by 3.9 fold</li>
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Documented adverse effects were dizziness and nausea only</li>
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Cannabis use – (CBD is a CYP 3A4 inhibitor) also increased the BUP concentration by 2.7 fold. (3)</p>
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Bottom line:</p>
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Be mindful of drug-drug interaction when initiating a new medication in patients with OUD on BUP</li>
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Inquire about any recent medication change in patients who may be experiencing OWS while on steady dose of BUP for their OUD. </li>
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<fieldset><legend>References</legend>
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1. <a href="https://www-ncbi-nlm-nih-gov.proxy-hs.researchport.umd.edu/pubmed/21596492" title="Drug and alcohol dependence.">Drug Alcohol Depend.</a> 2011 Nov 1;118(2-3):326-34. doi: 10.1016/j.drugalcdep.2011.04.013. Epub 2011 May 19.</p>
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<strong>Rifampin, but not rifabutin, may produce opiate withdrawal in buprenorphine-maintained patients.</strong></p>
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<a href="https://www-ncbi-nlm-nih-gov.proxy-hs.researchport.umd.edu/pubmed/?term=McCance-Katz%20EF%5BAuthor%5D&cauthor=true&cauthor_uid=21596492">McCance-Katz EF</a><sup>1</sup>, <a href="https://www-ncbi-nlm-nih-gov.proxy-hs.researchport.umd.edu/pubmed/?term=Moody%20DE%5BAuthor%5D&cauthor=true&cauthor_uid=21596492">Moody DE</a>, <a href="https://www-ncbi-nlm-nih-gov.proxy-hs.researchport.umd.edu/pubmed/?term=Prathikanti%20S%5BAuthor%5D&cauthor=true&cauthor_uid=21596492">Prathikanti S</a>, <a href="https://www-ncbi-nlm-nih-gov.proxy-hs.researchport.umd.edu/pubmed/?term=Friedland%20G%5BAuthor%5D&cauthor=true&cauthor_uid=21596492">Friedland G</a>, <a href="https://www-ncbi-nlm-nih-gov.proxy-hs.researchport.umd.edu/pubmed/?term=Rainey%20PM%5BAuthor%5D&cauthor=true&cauthor_uid=21596492">Rainey PM</a>.</p>
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2. <a href="https://www-ncbi-nlm-nih-gov.proxy-hs.researchport.umd.edu/pubmed/30167757" title="European journal of clinical pharmacology.">Eur J Clin Pharmacol.</a> 2018 Dec;74(12):1615-1622. doi: 10.1007/s00228-018-2548-8. Epub 2018 Aug 30.</p>
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<strong>Voriconazole greatly increases the exposure to oral buprenorphine.</strong></p>
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<a href="https://www-ncbi-nlm-nih-gov.proxy-hs.researchport.umd.edu/pubmed/?term=Fihlman%20M%5BAuthor%5D&cauthor=true&cauthor_uid=30167757">Fihlman M</a><sup>1,2</sup>, <a href="https://www-ncbi-nlm-nih-gov.proxy-hs.researchport.umd.edu/pubmed/?term=Hemmil%C3%A4%20T%5BAuthor%5D&cauthor=true&cauthor_uid=30167757">Hemmilä T</a><sup>2</sup>, <a href="https://www-ncbi-nlm-nih-gov.proxy-hs.researchport.umd.edu/pubmed/?term=Hagelberg%20NM%5BAuthor%5D&cauthor=true&cauthor_uid=30167757">Hagelberg NM</a><sup>1,2</sup>, <a href="https://www-ncbi-nlm-nih-gov.proxy-hs.researchport.umd.edu/pubmed/?term=Backman%20JT%5BAuthor%5D&cauthor=true&cauthor_uid=30167757">Backman JT</a><sup>3</sup>, <a href="https://www-ncbi-nlm-nih-gov.proxy-hs.researchport.umd.edu/pubmed/?term=Laitila%20J%5BAuthor%5D&cauthor=true&cauthor_uid=30167757">Laitila J</a><sup>3</sup>, <a href="https://www-ncbi-nlm-nih-gov.proxy-hs.researchport.umd.edu/pubmed/?term=Laine%20K%5BAuthor%5D&cauthor=true&cauthor_uid=30167757">Laine K</a><sup>4,5</sup>, <a href="https://www-ncbi-nlm-nih-gov.proxy-hs.researchport.umd.edu/pubmed/?term=Neuvonen%20PJ%5BAuthor%5D&cauthor=true&cauthor_uid=30167757">Neuvonen PJ</a><sup>3</sup>, <a href="https://www-ncbi-nlm-nih-gov.proxy-hs.researchport.umd.edu/pubmed/?term=Olkkola%20KT%5BAuthor%5D&cauthor=true&cauthor_uid=30167757">Olkkola KT</a><sup>6</sup>, <a href="https://www-ncbi-nlm-nih-gov.proxy-hs.researchport.umd.edu/pubmed/?term=Saari%20TI%5BAuthor%5D&cauthor=true&cauthor_uid=30167757">Saari TI</a><sup>7,8</sup>.</p>
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3. <a href="https://www-ncbi-nlm-nih-gov.proxy-hs.researchport.umd.edu/pubmed/31907614" title="European archives of psychiatry and clinical neuroscience.">Eur Arch Psychiatry Clin Neurosci.</a> 2020 Jan 6. doi: 10.1007/s00406-019-01091-0. [Epub ahead of print]</p>
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<strong>Buprenorphine-cannabis interaction in patients undergoing opioid maintenance therapy.</strong></p>
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<a href="https://www-ncbi-nlm-nih-gov.proxy-hs.researchport.umd.edu/pubmed/?term=Vierke%20C%5BAuthor%5D&cauthor=true&cauthor_uid=31907614">Vierke C</a><sup>1</sup>, <a href="https://www-ncbi-nlm-nih-gov.proxy-hs.researchport.umd.edu/pubmed/?term=Marxen%20B%5BAuthor%5D&cauthor=true&cauthor_uid=31907614">Marxen B</a><sup>2</sup>, <a href="https://www-ncbi-nlm-nih-gov.proxy-hs.researchport.umd.edu/pubmed/?term=Boettcher%20M%5BAuthor%5D&cauthor=true&cauthor_uid=31907614">Boettcher M</a><sup>3</sup>, <a href="https://www-ncbi-nlm-nih-gov.proxy-hs.researchport.umd.edu/pubmed/?term=Hiemke%20C%5BAuthor%5D&cauthor=true&cauthor_uid=31907614">Hiemke C</a><sup>4</sup>, <a href="https://www-ncbi-nlm-nih-gov.proxy-hs.researchport.umd.edu/pubmed/?term=Havemann-Reinecke%20U%5BAuthor%5D&cauthor=true&cauthor_uid=31907614">Havemann-Reinecke U</a><sup>2,5</sup>.</p>
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