Fixcom 2/Fixcom 3/Fixcom 4 Drug Interactions

Fixcom 2: Isoniazid tends raise plasma concentrations of phenytoin and carbamazepine by inhibiting their metabolism in the liver. The absorption of isoniazid is impaired by aluminum hydroxide.
Rifampicin induces hepatic enzymes, and may increase the dosage requirements of drugs metabolized in the liver. These include corticosteroids, steroid contraceptives, oral hypoglycaemic agents, oral anticoagulants, phenytoin, cimetidine, cyclosporine and digitalis glycosides. Since rifampicin reduce the effectiveness of oral contraceptives, women should be advised to choose between one of the following options for contraception. Following consultation with a clinician, the patient may use an oral contraceptive pill containing a higher dose of estrogen (50 µg). Alternatively, a nonhormonal method of contraception may be used throughout rifampicin treatment and for at least one month subsequently.
Current antiretroviral drugs interact with rifampicin. This may result ineffectiveness of antiretroviral drugs, ineffective treatment of TB or an increased risk of drug toxicity. Biliary excretion of radiocontrast media and sulfobromopthalein sodium may be reduced and microbiological assays for folic acid and vitamin B₁₂ disturbed.
Fixcom 3: Rifampicin: Rifampicin accelerates the metabolism of some drugs by inducing the microsomal liver enzymes and possibly interfering with hepatic uptake. Although most drugs involved may require an increase in dosage to maintain effectiveness, women taking oral contraceptives should change to another form of contraception.
The absorption of rifampicin may be reduced by administration with antacids, drugs that reduce gastric motility (anticholinergics and opioids), ketoconazole or preparations containing bentonite. However, such reactions can be overcome by giving rifampicin in a few hrs before any of these drugs.
Isoniazid: The risk of hepatotoxicity may be increased in patients receiving isoniazid in combination with rifampicin or other potentially hepatotoxic drugs.
Isoniazid can inhibit the hepatic metabolism of a number of drugs, in some cases leading to increased toxicity. These include the antiepileptics carbamazepine, ethosuximide and phenytoin, the benzodiazepines diazepam, triazolam, chlorzoxazone and theophylline. The metabolism of enflurane may be increased in patients receiving isoniazid resulting in potentially nephrotoxic levels of fluoride. Isoniazid has been associated with increased concentrations or toxicity of clofazimine, cycloserine and warfarins.
The metabolism of isoniazid may be increased in chronic alcoholics; this may lead to reduced isoniazid effectiveness. These patients may also be at increased risk of developing isoniazid-induced peripheral neuropathies and hepatic damage.
Oral absorption of isoniazid is reduced by aluminum-containing antacids; isoniazid should be given 1 hr before the antacid.
Fixcom 4: Pyrazinamide: Probenecid is known to block the excretion of pyrazinamide.