Rifampicin Alcohol

Theophylline is a narrow therapeutic index drug with significant difference in bioavailability following oral administration. The half-life of the drug is increased by heart failure, cirrhosis and viral infections, in elderly patients, and by certain drugs, such as cimetidine, ciprofloxacin, oral contraceptives and fluvoxamine. The half-life is decreased in smokers, chronic alcoholism, and by certain drugs, such as phenytoin, rifampicin and carbamazepine. 

There are some clinically important pharmacodynamic drug-drug interactions to be mentioned. Antipsychotics will potentiate the central depressant effects of sedatives and of alcohol. They will also increase the risk of respiratory-depressant effects of opiates. Inducers of drug metabolic enzymes like for example rifampicin and several antiepileptics, may increase the elimination rate of antipsychotic agents and thus decrease their efficacy. 

Sustained-release formulations can produce stable serum concentrations with once or twice daily dosage. Therapeutic effects occur at blood levels > 5 mg/1, and side effects increase considerably at levels > 15 mg/1. Smoking, alcohol, anticonvulsants, and rifampicin induce the drug-metabolizing enzyme system in liver and reduce the half-life of theophylline. On the other hand, heart and liver failure, sustained fever, old age and drugs such as cimeti-dine, ciprofloxacin, and oral contraceptives reduce theophylline clearance and thereby increase serum concentrations. 

Beta-blockers interact with a large number of other medications. The combination of beta-blockers with calcium antagonists should be avoided, given the risk for hypotension and cardiac arrhythmias. Cimetidine, hydralazine, and alcohol all increase blood levels of beta-blockers, whereas rifampicin decreases their concentrations. Beta-blockers may increase blood levels of phenothiazines and other neuroleptics, clonidine, phen-ytoin, anesthetics, lidocaine, epinephrine, monoamine oxidase inhibitors and other antidepressants, benzodiazepines, and thyroxine. Beta-blockers decrease the effects of insulin and oral hypoglycemic agents. Smoking, oral contraceptives, carbamazepine, and nonsteroidal anti-inflammatory analgesics decrease the effects of beta-blockers (Coffey, 1990). 

Interactions. Drugs that lower gastric acidity, e.g. antacids, histamine H2 receptor antagonists, impair the absorption of ketoconazole from the gastrointestinal tract. Like all imidazoles, ketoconazole binds strongly to several cytochrome P450 isoenzymes and thus inhibits the metabolism (and increases effects of) oral anticoagulants, phenytoin and cyclosporin, and increases the risk of cardiac arrhythmias with terfenadine. A disulfiram-like reaction occurs with alcohol. Concurrent use of rifampicin, by enzyme induction of CYP 3A, markedly reduces the plasma concentration of ketoconazole. 

A 42-year-old Asian man developed clinical, biochemical, and imaging features of acute pancreatitis 11 days after starting to take rifampicin, isoniazid, and pyrazi-namide for spinal tuberculosis (33). He had no history of excessive alcohol or other drug therapy. He improved after withdrawal of all drugs, but the pancreatitis recurred on reintroduction of isoniazid and resolved after withdrawal. 

However, in 531 eligible patients enrolled in a US Public Health Service Cooperative Trial of Short-Course Chemotherapy of Pulmonary Tuberculosis, of whom 58% were classified as alcoholic, although the alcoholics had more abnormal concentrations of aspartate transaminase before and during therapy, there was no significant difference between the alcoholics and non-alcoholics in the incidence of adverse reactions, including hepatotoxic reactions (92). The authors concluded that in the absence of clinically significant and persistent pretreatment abnormalities of hepatic function tests, rifampicin and isoniazid are not contraindicated in patients categorized as alcoholic. 

Thompson JE. The effect of rifampicin on liver morphology in tuberculous alcoholics. Aust NZ J Med 1976 6(2) lll-6. 

Clinically important, potentially hazardous interactions with alcohol, cimetidine, erythromycin, imipramine, ketoconazole, promethazine, rifampicin, rifampin, thioridazine... 

Thus, the importance of enzyme induction is that it may alter the toxicity of a foreign compound. This can have important clinical consequences and underlie drug interactions. Thus, the antitubercular drug rifampicin is thought to increase the hepatotoxicity of the drug isoniazid, and alcohol may increase susceptibility to the hepatotoxicity of... 

Hepatotoxicity can occur with several antituberculous drugs including ethionamide, isoniazid, pyrazinamide and rifampicin and high alcohol consumption/chronic alcoholism has been reported to increase the risk. However, one study in patients with active tuberculosis taking rifampicin and pyrazinamide, found that of the 14 patients who developed hepatotoxicity, only 5 of these reported alcohol use (not quantified), and alcohol was not found to be associated with an increased risk of hepatotoxicity. Similarly, another study found that alcohol consumption was not a risk factor for antimycobacterial-induced hepatotoxicity. ... 

Neither cimetidine nor rifampicin had any clinically relevant effect on the pharmacokinetics of nicorandil. Nicorandil did not alter the anticoagulant effects of acenocoumarol. Although animal studies surest antagonism of effects, a study in patients found no pharmacodynamic interaction between nicorandil and glibenclamide. Nicorandil may potentiate the hypotensive effects of other vasodilators, tricyclic antidepressants and alcohol. 

The serum levels of the active metabolite of leflunomide are reduced by activated charcoal, and colestyramine. The manufacturers advise against the concurrent use of alcohol because of the potential for hepatotoxicity. Methotrexate may also increase leflunomide hepatotoxicity, so in general the combination is not recommended. A case of fatal fulminant hepatic failure has been reported in a patient taking leflunomide and itraconazole. A case of peripheral neuropathy has been reported in a patient taking leflunomide and tegafiir/uraciL The manufacturers predict interactions between leflunomide and phenytoin or tolbutamide, and advise caution with rifampicin as it may increase leflunomide metabolite levels. No clinically relevant interaction occurs with cime-tidine, corticosteroids or NSAIDs. 

With combined therapy, it was suggested that the effects of rifampicin might be more apparent during the initial 7 days, but that by week 4 the effect of isoniazid might predominate, because of its reduced inactivation by rifampicin combined with a reduction in the effect of rifampicin by auto-induction of its own metabolism. High theophylline levels in the isolated ease above may have been due to liver impairment brought about by the eombined use of rifampicin and isoniazid, or alcoholism. ... 

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