Rifampicin Barbiturates

Remember some of those drugs that are key enzyme inducers (e.g. phenytoin, barbiturates, rifampicin, etc) or enzyme inhibitors (e.g. azole antifungals, HIV-protease inhibitors, erythromycin, SSRIs). 

Inductors Tobacco smoke Barbiturates omeprazole rifampicin Carbarn azepine phenytoin barbiturates... 

Gynaecology Orai contraceptives Barbiturates, carbamazepine, dichiorai-phenazone, phenytoin, primidone, rifampicin. Reduced effect. 

CYP2C8 Liver Intestine Paclitaxel 6-a-hydroxylation (preferred1) Glitazones (preferred1) Rifampicine Barbiturates 10 %... 

RIFAMPICIN BARBITURATES i levels of these drugs, with risk of therapeutic failure Induction of hepatic metabolism Monitor for 1 clinical efficacy and t their dose as required... 

GESTRINONE 1. ANTIBIOTICS-rifampicin 2. ANTIEPILEPTICS-barbiturates, carbamazepine, phenytoin 1 gestrinone levels Induction of metabolism Watch for poor response to gestrinone... 

Several drugs, for example the oral contraceptive pill, viloxazine, thiabendazole, aminoglutethimide, antiepileptics (carbamazepine, phenytoin, barbiturates) and the antibiotic rifampicin decrease plasma concentrations of theophylline. 

Halothane also reduces liver blood flow during anesthesia, and this could increase the release of potentially hepatotoxic halothane metabolites. The role of reduced halothane metabolites and inorganic fluoride, which may covalently link to liver macromolecules, has been stressed in keeping with this hypothesis is the observation of halothane hepatitis in patients who simultaneously take enzyme-inducing agents, for example barbiturates (41) or rifampicin (42). 

Barbiturates which induce Uver drug-metaboUzing enz)mes increase the rate of metabolism of isoniazid, rifampicin, or combined antituberculosis treatment, since they may result in accelerated breakdown of these drugs (52). 

Barbiturates, which induce liver drug-metabolizing enzymes, increase the rate of metabolism of rifampicin (99). 

Anticonvulsants (barbiturates and phenytoin) and other drugs that induce liver enzymes (such as rifampicin) can accelerate the hepatic catabolism of vitamin D and can lead to reduced serum concentrations of calcifediol and osteomalacia. Prophylactic vitamin D treatment of patients taking long-term enzyme inducers can be helpful and should be given at least in cases of anticonvulsant-drug-induced osteomalacia (74,75). 

Past history of breast cancer, but no evidence of recurrence for 5 years Use of drugs that affect liver enzymes (rifampicin, rifabutin and griseofulvin) anticonvulsants (phenytoin, carbamazepine, barbiturates, topiramate, and primidone)... 

Early work with human hepatocjdes showed induction of P450 2C9 by barbiturates and rifampicin , consistent with earlier in vivo work on the induction of barbiturate metabolism . Subsequent studies have shown that P450 2C9 is the only P450 2C subfamily enzyme expressed at a significant level in untreated hepatoc5des and that expression is induced by rifampicin, dexam-ethasone, and phenobarbital - . The induction involves a glucocorticoid receptor, CAR, and PXR, with CAR and PXR apparently competing at the same site . 

Phenytoin toxicity occurred in a child following halothane anaesthesia. A near fatai hepatic reaction occurred in a woman given rifampicin (rifampin) after haiothane anaesthesia, and hepatitis occurred in a patient taking phenobarbitai who was given halothane anaesthesia. See aiso Anaesthetics, generai H- Isoniazid , p.lOO and Anaesthetics, general Methoxyflurane H- Antibacterials or Barbiturates , p.l07. 

Phenobarbital possibly modestly increases the clearance of rifampicin. The effect of rifampicin on phenobarbital levels is unknown, but note that rifampicin markedly increased the clearance of another barbiturate hexobarbital, used as a marker of drug metabolism. 

In one study, the serum levels of rifampicin were reduced by 20 to 40% in 12 of 15 patients taking phenobarbital 100 mg daily. In another study, although phenobarbital 100 mg daily for 7 days reduced the mean half-life of a single 600-mg dose of rifampicin by 15%, this was not statistically significant. However, in a further 5 patients with cirrhosis of the liver, phenobarbital did reduce the half-life of rifampicin by a mean of 2.2 hours. The effect of rifampicin on phenobarbital levels does not appear to have been studied, but rifampicin markedly increased the clearance of another barbiturate hexobarbital, used as a marker of drug metabolism. " ... 

Rifampicin is an inducer of the cytochrome P450 isoenzymes CYP3A4 and CYP2B6, which are involved in the metabolism of cyclophosphamide and ifosfamide (see also Cyclophosphamide or Ifosfamide + Barbiturates , p.623). In the clinical study cited, rifampicin did not have a positive effect on the proportion of ifosfamide undergoing activation. In addition, since rifampicin increased metabolism overall, there is the possibility of decreased efficacy, although this remains to be shown. 

Pretreatment with rifampicin 600 mg once daily for 7 days reduced the AUC of erlotinib by about 66%. In another study, the AUC of a single 450-mg dose of erlotinib, taken after 11 days treatment with rifampicin was about 57% of that of erlotinib 150 mg taken without rifampicin. The manufacturers advise that alternative treatments with no cytochrome P450 enzyme-inducing activity should be considered. If this is not possible, the starting dose of erlotinib should be adjusted to 300 mg (UK) with close monitoring, and, if tolerated, further increased after 2 weeks, in 50 mg increments, to 450 mg. They also advise caution with other CYP3A4 inducers, and specifically name barbiturates, carbamazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and St John s wort. 

Based on in vitro studies, the manufacturers surest that CYP3A inhibitors (such as ketoconazole and erythromycin) will raise docetaxel levels, whereas CYP3A inducers (such as rifampicin (rifampin) and the barbiturates) will reduce docetaxel levels. This has been seen for ketoconazole. 

There was no elear relationship between thalidomide eleatanee and the eoneunent use of enzyme inducers such as rifampicin (rifampin), or phenobarbitai in a study in patients with glioma. For the possible additive CNS depressant effect with barbiturates, see CNS depressants, above. 

The plasma levels of quetiapine are reduced by phenytoin and carbamazepine, and are predicted to be reduced by barbiturates and rifampicin. 

The manufacturers of quetiapine suggest that dosage adjustments [increases] may be necessary if quetiapine is given with carbamazepine, phenytoin or other enzyme inducers (such as barbiturates or rifampicin (rifampin). This is a reasonable prediction but no direct clinical evidence is yet available. However, be alert for the need to use an increased quetiapine dosage in patients given any of these drugs. 

The metabolism of ivabradine may be increased by CYP3A4 inducers including barbiturates, phenytoin, rifampicin, and St John s wort. 

The manufacturer says that on a theoretical basis enzyme inducers such as the barbiturates, carbamazepine, phenytoin and rifampicin may accelerate the metabolism of tibolone and thus decrease its efficacy. However, they note that no examples of these interactions have been reported in clinical practice, and pharmacokinetic studies are required to demonstrate this interaction. Nevertheless it would be prudent to monitor concurrent use. 

Besides ampicillin there are numerous other drugs which cause maculopapular eruptions. The drugs most frequently mentioned are other penicillins, streptomycin, rifampicin, sulfonamides, pyrazolidine derivatives (phenylbutazone), pyrazolones, barbiturates, tricyclic antidepressants, hydantoin derivatives, indomethacin, quinine, and meprobamate (Kauppinen 1972 Korting 1972 Louis and Schulz 1973 Schuppli 1972 Thiers et al. 1964). 

The level of P450 2C8 expression in human liver varies at least 20-fold [54, 55, 639]. Rifampicin induces P450 2C8 in hepatocyte culture [387]. The enzyme appears to be inducible by barbiturates [640]. Transcriptional regulation involves the nuclear receptors CAR, PXR, HNF-la, and the glucocorticoid receptor [641]. 

The interactions of herbal medicines with P450 3A4 have already been mentioned and are one of the worst problems with these mixtures [1448]. One of the most studied issues is St. John s wort, which induces P450 3A4 as an agonist of the receptor PXR [1449, 1450]. The induction of P450 3A4 by St. John s wort has been responsible for the loss of the effectiveness of oral contraceptives [83, 1451]. The resulting pregnancies are the resirlt of more rapid ehmi-nation of 17a-ethinylestradiol, a phenomenon previously reported for P450 3A4 induction by rifampicin and barbiturates [26, 82, 90]. 

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