Isoniazid interaction with other drugs

Another cause of toxicity with diphenylhydantoin can be the result of interactions with other drugs such as isoniazid. This drug is a noncompetitive inhibitor of the aromatic hydroxylation of diphenylhydantoin. Consequently, the elimination of diphenylhydantoin is impaired in the presence of isoniazid, and the plasma level is greater than anticipated for a normal therapeutic dose. Furthermore, it was found that there was a significant correlation... 

In other words, it takes about the same length of time to kill an animal with sleep deprivation as it does to cure a person with those drugs that restore sleep to normal for the duration of their administration. Some of those alterations are variations on the theme of sleep deprivation. The total suppression of REM by isoniazid and other MAOIs is a particularly striking example. Successful treatment of depression may thus depend upon pushing the two sides of the reciprocal interaction system to such extreme limits that REM sleep is impossible. 

Lamivudine inhibits the intracellular phosphorylation of zalcitabine and antagonizes zalcitabine s antiretroviral activity in vitro, although the clinical significance of this interaction is unknown. Probenecid increases the zalcitabine AUC by about 50%, probably through inhibition of tubular secretion cimetidine increases the AUC by 36% via an unknown mechanism. Zalcitabine should be avoided in patients with a history of pancreatitis or neuropathy because the risk and severity of both complications increase. Coadministration of other drugs that cause pancreatitis or neuropathy also will increase the risk and severity of these symptoms. Ethambutol, isoniazid, vincristine, cisplatin, and pentamidine, as well as the antiretroviral drugs didanosine and stavudine, therefore, should be avoided. 

Drug Interactions Barbiturates combine with other CNS depressants to cause severe depression ethanol is the most frequent offender, and interactions with first-generation antihistamines also are common. Isoniazid, methylphenidate, and monoamine oxidase inhibitors also increase the CNS-depressant effects. Other prominent drag interactions occin as a result of the induction of hepatic drug-metabolizing enzymes by barbiturates see above). 

A study in a 3-year-old child who had responded poorly to treatment found that peak serum levels and AUC of ketoconazole were reduced by about 65 to 80% by rifampicin and/or isoniazid. The interaction also occurred when the dosages were separated by 12 hours. When all three drugs were given together the ketoconazole serum levels were undetectable. Other reports confirm these reports of decreased ketoconazole levels with rifampicin. 

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