Methadone Amprenavir

Drugs that might affect amprenavir include abacavir, aldesleukin, antacids, anticonvulsants, azole antifungals, clarithromycin, cyclosporine, dexamethasone, buffered didanosine, disulfiram, ethanol, indinavir, methadone, metronidazole, nelfinavir, nonnucleoside reverse transcriptase inhibitors, oral contraceptives, rifamycins, ritonavir, saquinavir, St. John s wort, tacrolimus, and zidovudine. 

Drugs that might be affected by amprenavir include antiarrhythmics, anticonvulsants, azole antifungals, benzodiazepines, calcium channel blockers, cisapride, clarithromycin, cyclosporine, ergot alkaloids, fentanyl, HMG-CoA reductase inhibitors, indinavir, methadone, nelfinavir, oral contraceptives, pimozide, rifabutin, ritonavir, saquinavir, sildenafil, tacrolimus, trazodone, tricyclic antidepressants, warfarin, and zidovudine. 

St. John s wort, rifamycins, and ritonavir. Drugs that may be affected by efavirenz include phenytoin, phenobarbital, carbamazepine, itraconazole, ketoconazole, methadone, ritonavir, amprenavir, benzodiazepines, clarithromycin, ethinyl estradiol, indinavir, nelfinavir, saquinavir, and warfarin. 

Nevirapine is a moderate inducer of CYP3A metabolism, resulting in decreased levels of amprenavir, indinavir, lopinavir, saquinavir, efavirenz, and methadone (Table 49-4). Drugs that induce the CYP3A system, such as tipranavir, rifampin, rifabutin, and St. John s wort, can decrease levels of nevirapine, whereas those that inhibit CYP3A activity, such as fluconazole, ketoconazole, and clarithromycin, can increase nevirapine levels. 

Efavirenz inhibits the plasma levels of indinavir, saquinavir and amprenavir and increases the concentrations of ritonavir and nelfinavir. It also lowers the plasma levels of methadone, phenytoin, carbamazepine and phenobarbital. Drugs that stimulate the cytochrome P-450 system will increase its clearance and should not be coadministered. 

The drugs that induce cytochrome P-450 system isoenzyme CYP3A4 will inhibit the blood levels of amprenavir. It decreases the plasma levels of methadone and delavirdine and increases the plasma levels of rifabutin, ketoconazole and atorvas-tatin. This may be the result of the ability of amprenavir to inhibit as well as induce CYP3A4. 

METHADONE, PETHIDINE PROTEASE INHIBITORS 1 efficacy of methadone, with risk of withdrawal, when coadministered with amprenavir, nelfinavir, ritonavir (with or without lopinavir) or saquinavir Uncertain possibly due to induction of CYP3A4 and CYP2D6 Monitor closely for opioid withdrawal, and t dose of methadone as necessary. This advice includes co-administration of methadone with low-dose ritonavir. Short-term use of pethidine is unlikely to cause a problem... 

Amprenavir is extensively metabolized by and induces CYP3A4. Plasma methadone concentrations fell by 35 % when amprenavir was used (11). 

Bart PA, Rizzardi PG, Gallant S, Golay KP, Baumann P, Pantaleo G, Eap CB. Methadone blood concentrations are decreased by the administration of abacavir plus amprenavir. Ther Drug Monit 2001 23(5) 553-5. 

Clinically important, potentially hazardous interactions with adefovir, alprazolam, amprenavir, anisindione, anticoagulants, buprenorphine, carbamazepine, dicumarol, dihydroergotamine, ergot, fosamprenavir, indinavir, ixabepilone, lovastatin, methadone, methysergide, midazolam, phenobarbital, phenytoin, quinidine, rifabutin, rifampin, sildenafil, simvastatin, triazolam, warfarin... 

Clinically important, potentially hazardous interactions with alcohol, amprenavir, barbiturates, buprenorphine, chlorpheniramine, clarithromycin, CNS depressants, efavirenz, esomeprazole, eucalyptus, fluoroquinolones, imatinib, indinavir, ivermectin, macrolide antibiotics, MAO inhibitors, methadone, mianserin, nalbuphine, narcotics, nelfinavir, nilutamide, phenothiazines, ritonavir, SSRIs... 

Acetaminophen, aldrin, alfentanil, amiodarone, aminopyrine, amitriptyline, amprenavir, androstenedione,antipyrine, astemizole, benzphetamine, budesonide, carbamazepine, celecoxib, chlorpromazine, chlorzoxazone, cisapride, clarithromycin, clozapine, cocaine, codeine, cortisol, cyclophosphamide,cyclosporin, dapsone, delavirdine, dextromethorphan, digitoxin, diltiazem, diazepam, erythromycin, 17j3-estradiol, ethinylestradiol, etoposide, felbamate, fentanyl, flutamide, hydroxyarginine, ifosphamide, imipramine, indinavir, ketoconazole, lansoprazole, loratidine, losartan, lovastatin, (iS)"mephen3d in, methadone, mianserin, miconazole, mifepristone, nelfinavir, nevirapine, nicardipine, nifedipine, odansetron, omeprazole, orphenadrine, proguanil, propafenone, quinidine, quinine, rapamycin, retinoic acid, ritonavir, saquinavir, selegiline, serindole, sufentanil, sulfinpyrazone, tacrolimus, tamoxifen, tamsulosin, taxol, teniposide, terfenadine, tetrahydrocannabinol, theophylline, toremifene, triazolam, trimethadone, trimethoprim, troleandomycin, verapamil, warfarin, zatosetron, Zolpidem, zonisamide... 

Hendrix, C. W., Wakeford, J., Wire, M. B., Lou, Y., Bigelow, G. E., Martinez, E., Christopher, J., Fuchs, E. J., and Snidow, J. W. (2004) Pharmacokinetics and pharmacodynamics of methadone enantiomers after coadministration with amprenavir in opioid-dependent subjects. Pharmacotherapy 24,1110-1121. 

Methadone serum levels can be reduced by amprenavir, nelfina-vir, lopinavir/ritonavir, saquinavir/ritonavir, tipranavir/ritona-vir, and possibly ritonavir. In addition, amprenavir levels may be reduced by methadone. No interaction appears to occur between methadone and indinavir, or possibly atazanavir or saquinavir, alone. 

A study involving 16 opioid-dependent subjects found that amprenavir 1.2 g twice daily for 10 days decreased the AUCs for both f -methadone (active enantiomer) and 5-methadone (inactive enantiomer) by 13% and 40%, respectively. No clinically significant changes were noted in opioid effects and there was no evidence of opioid withdrawal. However, in another study methadone levels were reduced by 35% (range 28% to 87%) in 5 patients within 17 days of starting to take amprenavir 1.2 g twice daily and abacavir 600 mg twice daily. Two patients reported nausea before their daily methadone dose, which can be a sign of opiate withdrawal. Note that abacavir , (p.l75), may modestly reduce methadone levels, and could therefore have contributed to this effect. 

The first study also found that amprenavir and methadone resulted in a 30% decrease in amprenavir AUC compared with non-matched historical controls. ... 

Note that amprenavir plasma levels may also be reduced by methadone. The US manufaeturer says that amprenavir may be less effective if taken eoneurrently with nareotie analgesies and alternative antiretroviral therapy should be eonsidered. ... 

Hendrix CW, Wakeford J, Wire MB, Lou Y, Bigelow GE, Martinez E, Christopher J, Fuchs EJ, Snidow JW. Pharmacokinetics and pharmacod3fnamics of methadone enantiomers after coadministration widi amprenavir in opioid-dependent subjects. Pharmacoffterapy (2004) 24,1110-21. 

Simultaneous didanosine, folic acid, ganciclovir, lamivudine, nevirapine, pyrazinamide, ranitidine, rifampin, stavudine, sulfamethoxazole, trimethoprim, zidovudine Noninterfering adefovir, amprenavir, delavirdine, efavirenz, fluconazole, indinavir, itraconazole, methadone, nelfinavir, oxazepam, pyrimethamine, rifampin, ritonavir, saquinavir, zalcitabine... 

---