Interventions for Tuberculosis Control and Elimination 2002

tis risk per 1,000 subjects was zero for those aged less than 20 years, 2.4
for those aged 20 to 34 years, 9.2 for those aged 35 to 49 years, and 19.2
for those aged 50 to 64 years. 111 Isoniazid and rifampicin given together
may potentiate the risk of hepatitis, and cases of hepatitis caused by the
two drugs in combination have been reported. 124,125
Patients abusing alcohol may be treated with isoniazid provided they
do not display signs of overt alcoholic hepatitis. Careful clinical control,
limitation of alcohol consumption and (where feasible) control of liver
enzymes in such patients are recommended.
Interactions. Isoniazid is an inhibitor of oxidative and demethylation metabolism
as well as other cytochrome P-450 dependent microsomal pathways.
126,127 It is also a monoamine and diamine oxidase inhibitor. 128,129
These properties bear on the various interactions that have been reported, 130
in that the most important interaction leads to a potentiation of the companion
drug (opposite to the usual interactions seen with rifampicin).
Scombroid fishes (such as mackerel, tuna and salmon) have a high histidin
content which is converted to histamine by bacteria, if improperly
refrigerated. Eating such fish while taking isoniazid may lead to the typical
signs of scombroid fish poisoning, with erythematous and urticarial
rash, facial flushing, diarrhea, palpitations, headache, nausea, paresthesias,
abdominal cramps, and dizziness. 131-134 It may progress to bronchospasm
and hypotensison.
Certain types of cheeses rich in monoamines may also lead to hypersensitivity
reactions. 135-138 With wine, such reactions have also been
reported. 128
Effects of isoniazid potentiated: para-aminosalicylic acid, 139 insulin, 140 carbamazepine,
141 valproic acid (a single report, usually the effect is the opposite),
142 theophylline. 143
Effects of isoniazid opposed: prednisolone, 59 ketoconazole. 144 After intake
of ethanol, most is metabolized to acetaldehyde in the liver. Acetaldehyde
appears to form acetaldehyde-adducts with isoniazid in vitro, and thus may
lower its bioavailability, but the adduct itself may increase the toxicity of
either drug. 145
Effect of drug potentiated by isoniazid:
• acetominophen hepatotoxicity is increased by isoniazid; 103,104
25