Barbiturate, enzyme inducer

Enzyme inducers [P] Barbiturates, phenytoin, and rifampin may enhance 13 -blocker metabolism other enzyme inducers may produce similar effects. 

Enzyme inducers, such as phenytoin, carbamazepine, and barbiturates, can precipitate attacks in patients with acute intermittent porphyria. 

BARBITURATES PROCARBAZINE t risk of hypersensitivity reactions in patients with brain tumours Strong correlation between therapeutic antiepileptic level and hypersensitivity reactions Consider using non-enzyme-inducing agents... 

The interactions of anticonvulsants are summarized in Table 2, Table 3, and Table 4. Phenytoin, carbamazepine, and barbiturates are enzyme inducers and can reduce the... 

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 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). 

Because of their enzyme-inducing effects, barbiturates can cause increased inactivation of other compounds (anticoagulants, phenytoin, theophylline, digoxin, glucocorticoids, etc.). This may lead to serious problems with drug interactions. 

The serum levels of both barbiturates and phenothiazines (chlorpromazine and thioridazine) can be reduced by about 30%, presumably because barbiturates are potent hepatic catabolic enzyme inducers. 

The metabolism of methyprylon is found to be extensive, and the drug is an enzyme inducer. Its pharmacologieal effeets resemble to those of the barbiturates. 

CAUTION. Phenytoin. (anticonvulsant) and phenobarbital (long-acting barbiturate) can induce hepatic microsomal enzymes and thereby retard the half-life significantly and, therefore, ultimately interfering with the prevalent efficacy of the drug . 

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). 

An established and clinically important interaction. Monitor the effects of concurrent use and anticipate the need to increase the metronidazole dosage two to threefold if phenobarbital is given. All of the barbiturates are potent liver enzyme inducers and would therefore be expected to interact similarly. 

Uncertain. These antiepileptics and barbiturates are known enzyme inducers and it seems probable that they increase the metabolism of the doxycycline by the liver, thereby increasing its clearance from the body. 

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. 

It is probable that enzyme-inducing antiepileptics increase the metabolism of paclitaxel, and therefore it is likely that patients taking these antiepileptics will require an increase in paclitaxel dose. Further study is needed. Note that barbiturates are predicted to increase the metabolism of docetaxel, see Taxanes Docetaxel + Miscellaneous , above. 

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 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. 

---