Rifampicin methadone

Methadone Rifampicin Reduced effect of methadone Increased metabolism... 

Other compounds producing some inhibition of ZDV conjugation were oxazepam, salicylic acid, and acetylsalicyclic acid. More recently, Trapnell et al. examined the inhibition of ZDV at a more relevant concentration of 20 pM in bovine serum albumin (BSA)-activated microsomes by atovaquone, methadone, fluconazole, and valproic acid at therapeutically relevant concentrations (127). Both fluconazole and valproic acid inhibited ZDV glucuronidation by more than 50% at therapeutic concentrations. Clinical interaction studies have been conducted with methadone, fluconazole, naproxen, probenecid, rifampicin, and valproic acid (see Table 10). 

Interactions are similar to those of opioid analgesics. Methadone has interactions with enzyme inducers. Withdrawal symptoms of methadone are observed upon concurrent administration with phenobarbitone, phenytoin, and rifampicin. Methadone toxicity increases if administered with cimetidine and fluvoxamine. 

Enzyme-inducing drugs, such as carbamazepine, pheno-barbital, phenytoin, and rifampicin, enhance the metabolism of methadone, leading to lower serum methadone concentrations (58). 

OPIOIDS RIFAMPICIN 1 effect of alfentanil, codeine, methadone and morphine Rifampicin t hepatic metabolism of these opioids (alfentanil by CYP3A4, codeine by CYP2D6, morphine unknown). Rifampicin is also known to induce intestinal P-gp, which may 1 bioavailability of oral morphine Be aware that alfentanil, codeine, methadone and morphine doses may need to be t... 

Clinically important, potentially hazardous interactions with amiodarone, astemizole, bepridil, carbamazepine, chloroquine, cisapride, clarithromycin, dihydroergotamine, disopyramide, ergotamine, grapefruit juice, halofantrine, haloperidol, itraconazole, ketoconazole, methadone, moxifloxacin, phenobarbital, phenytoin, pimozide, procainamide, quinidine, rifampicin, ritonavir, sotalol, St John s wort, telithromycin, terfenadine, voriconazole... 

Serum methadone levels can be markedly reduced by rifampicin, and withdrawal symptoms have occurred in some patients. Rifabutin appears to interact similarly, but to a lesser extent. 

The observation that former diamorphine (heroin) addicts taking methadone complained of withdrawal symptoms when given rifampicin, prompted a study in 30 patients taking methadone. Withdrawal symptoms developed in 21 of the 30 within 1 to 33 days of starting rifampicin 600 to 900 mg daily and isoniazid daily. In 6 of the 7 most severely affected, the symptoms developed within a week, and their plasma methadone... 

Other cases of this interaction have been reported. Some patients needed two to threefold increases in the methadone dosage while taking rifampicin to control the withdrawal symptoms. ... 

Rifampicin is a potent enzyme-inducer, which increases the aetivity of the intestinal and liver enzymes concerned with the metabolism of methadone, resulting in a marked decrease in its levels. In 4 patients in the study cited, the urinary excretion of the major metabolite of methadone rose by 150%. Rifabutin has only a small enzyme-indueing effect and therefore the effects are not as great. 

The interaction between methadone and rifampicin is established, adequately documented and of clinical importance. The ineidence is high. Two-thirds (21) of the narcotic-dependent patients in one study developed this interaction, 14 of whom were able to eontinue treatment. Withdrawal symptoms may develop within 24 hours. The analgesic effects of methadone would also be expected to be redueed. Coneurrent use need not be avoided, but the effects should be monitored and appropriate dosage increases (as much as two to threefold) made where neeessary. 

Bending MR, Skacel PO. Rifampicin and methadone withdrawal. Lancet (1977) i, 1211. 

A number of reports have recently appeared confirming that reactions of rifampicin with other concurrently administered drugs are not uncommon. Kreek etal. (33 ) reported that narcotic addicts, stabilized on a methadone maintenance programme, who were under treatment for tuberculosis with rifampicin, developed withdrawal symptoms. Withdrawal symptoms were not reported in patients treated with isoniazid or ethambu-tol or both. Plasma methadone concentrations were found to be consistently lower in the subjects receiving rifampicin and a mean 24-hour urinary excretion of pyrroUdine, a major metaboUte of methadone, was con-... 

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