CYP3A4 inhibitors Buprenorphine

Theoretically buprenorphine metabolism could be inhibited by itraconazole, ketoconazole, grapefruit juice, and erythromycin or any other CYP3A4 inhibitor the effects may be greater than expected for the dose of buprenorphine being given may need to decrease buprenorphine dose. 

Interactions concomitant treatment with CYP3A4 inhibitors may lead to elevated plasma concentrations with intensified efficacy of buprenorphine. Co-ad-ministration of buprenorphine and CYP3A4 enzyme inducers could lead to increased clearance which might result in reduced efficacy. 

Drug-drug interactions Treatment of pain with opiates can be complicated by respiratory depression and lethargy from overmedication. Buprenorphine is hepatically metabolised by the CYP3A4. Coadministration with a CYP3A4 inhibitor, ketoconazole had no effect on the metabolism of buprenorphine from a transdermal patch delivering drug at 10 Tg/h [91 -]. 

Drugs that may interact with buprenorphine hydrochloride include barbiturate anesthetics, benzodiazepines, CNS depressants, CYP3A4 inducers and inhibitors, and MAOIs. 

ALFENTANIL, BUPRENORPHINE, FENTANYL, TRAMADOL PROTEASE INHIBITORS Possibly t adverse effects when buprenorphine is co administered with indinavir, ritonavir (with or without lopinavir) or saquinavir Inhibition of CYP3A4 (CYP2D6 in the case of tramadol) Halve the starting dose and titrate to effect. For single injection of fentanyl, monitor sedation and respiratoiy function closely. If continued use of fentanyl, i dose may be required. Concomitant use of ritonavir and transdermal fentanyl is not recommended... 

In an in vitro stndy of the effects of the HIV-1 protease inhibitors, ritonavir, indinavir, and saquinavir, which are metabolized by the liver CYP3A4, all three protease inhibitors inhibited methadone demethylation and buprenorphine dealkylation in rank order of potency ritonavir > indinavir > saquinavir (35). Clinical studies are required to establish the further relevance of these observations. 

Buprenorphine is a substrate for the cytochrome P450 isoenzyme CYP3A4 and inducers of CYP3A enzymes such as efavirenz would be expected to increase buprenorphine clearance, whereas delavirdine, which is an inhibitor of CYP3A, would be expected to reduce the CYP3A-mediated metabolism of buprenorphine to norbuprenorphine. 

Ritonavir decreases pethidine (meperidine) and increases norpethidine levels, which may possibly increase toxicity on long-term use. Similarly, ritonavir and other protease inhibitors increase buprenorphine levels. Ritonavir may increase the metabolism of morphine, and decrease the metabolism of dextropropoxyphene (CYP3A4 substrate) and tramadol or other CYP2D6 substrates (such as codeine). 

Fluoxetine inhibits the activity of the cytochrome P450 isoenzyme CYP2D6 within the liver so that the metabolism of oxycodone to an aetive metabolite oxymorphone is reduced. The metabolism of hydroeodone and similar opioids may also be affected by CYP2D6 inhibitors, see Opioids Codeine and related drugs + Quinidine , p.l84. Buprenorphine and morphine are not metabolised by CYP2D6, so their metabolism would not be expeeted to be affected by fluoxetine. Buprenorphine is metabolised by CYP3A4 and so fluvoxamine might be expected to inhibit its metabolism to some extent. 

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