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Rifampicin: Antacids, opiates and anticholinergic drugs reduce the bioavailability of rifampicin when it is given concomitantly by mouth. The same applies to PAS preparations containing bentonite. To avoid this interaction, rifampicin must be administered a few hours before these preparations.
Owing to its enzyme-inducing effect, rifampicin accelerates the metabolism of many concomitantly administered drugs, whose activity may thus be reduced and the success of treatment with them jeopardized.
The activity of the following drugs may be impaired, and their dosage must therefore be re-assessed during and after treatment with rifampicin:
Oral anticoagulants; oral antidiabetic agents; digitalis preparations; antiarrhythmic agents (disopyramide, pirmenol, quinidine; mexiletine, tocainide; lorcainide, propafenone); methadone (withdrawal signs may set in); hydantoins [phenytoins (see also under isoniazid), ethotoin, mephenytoin]; hexobarbital; nortriptyline; benzodiazepines; corticosteroids (Addison patients may develop a crisis; exacerbation of pemphigus may occur; treatment for corticoid-dependent asthma may become more difficult or impossible); sex hormones (menstrual disorders may appear); oral contraceptives (their effect can no longer be relied upon); theophylline; dapsone; chloramphenicol; antifungal agents (ketoconazole; itraconazole), cyclosporin A, azathioprine (transplants may be rejected); β-blockers; calcium-channel blockers (nifedipine, verapamil); enalapril, cimetidine.
Although concurrent use of isoniazid, pyrazinamide and rifampicin is common and therapeutically valuable, hepatic toxicity may be increased.
Rifampicin can delay the biliary excretion of contrast media employed in the x-ray of the gallbladder.
Microbiological techniques for assaying folic acid and vitamin B12 in the serum are unsuitable for use during treatment with Rimactazid. Rifampicin causes temporary competitive inhibition of bromsulphthalein excretion. To guard against false-positive results, the bromsulphthalein test should be performed in the morning before administration of Rimactazid.
Isoniazid: The absorption of isoniazid is reduced by antacids. Isoniazid retards the metabolism of various concomitantly administered drugs, whose toxicity thus becomes increased. Clinically relevant interactions of this kind can occur with hydantoins (phenytoin, ethotoin, mephenytoin), carbamazepine, primidone and valproic acid, the dosages of which may have to be reduced. Concurrent administration of disulfiram may lead to mental disturbances; the mechanism underlying this interaction has not been clarified. It is not advisable to employ disulfiram concomitantly with isoniazid.
Concomitant use of halothane and isoniazid (and possibly rifampicin) may increase the risk of hepatotoxic reactions.
As alcohol tolerance is decreased under isoniazid, the consumption of alcoholic beverages should be avoided. The metabolism of isoniazid is increased in chronic alcoholics.
Pyrazinamide: The effect of uricosuric drugs eg, probenecid and sulfinpyrazone is antagonized by pyrazinamide, and the elimination half-life of probenecid is increased. Allopurinol increases the plasma concentration of pyrazinoic acid which is directly responsible for the inhibition of renal urate secretion. It should be used with caution in patients with diabetes mellitus as their management may become more difficult. Pyrazinamide may interfere with the Acetest and Ketostix urine tests for Ketones.
Incompatibilities: Not applicable.
