Interventions for Tuberculosis Control and Elimination 2002

Idiosyncratic reactions from isoniazid include lupus erythematosus, 85,86
rheumatic-like syndromes and various hematologic disorders, such as
hemolytic anemia, 87 agranulocytosis, 88,89 pure red cell aplasia, 90-92 and other
blood dyscrasias. 93 Other rare, probably idiosyncratic reactions, include
alopecia. 94 These reactions are reported to subside promptly with withdrawal
of the drug. 15
Hypersensitivity reactions from isoniazid include drug fever, 95 asthma, 96,97
dermatitis, 98-100 and hepatitis. 77,101,102 Hepatotoxicity might be increased with
the concomitant use of acetaminophen. 103-105
Clinically, the most relevant and frequent adverse drug events from
isoniazid are neuropathy and liver injury.
Routine use of pyridoxine (vitamin B6) for prevention of neuropathy
is not indicated. 79 Preventive treatment with small dosages of pyridoxine
(6 mg/day, not to exceed 10 to 15 mg 106,107 ) is indicated for patients with
increased requirements (e.g., during pregnancy), patients with nutritional
deficiencies (alcoholics and aged patients), patients with a history of seizure
disorder, and patients otherwise predisposed to the development of peripheral
neuropathy, such as uremic patients or patients with diabetes. 79
Treatment of isoniazid-associated peripheral neuropathy (paresthesia) is with
100 to 200 mg pyridoxine per day. 79 It should be noted that there is antagonism
between isoniazid and pyridoxine, 108 and thus the potential of inactivation
of isoniazid with very high doses of pyridoxine. Therefore many
clinicians prefer lower dosages (50 mg per day).
Liver enzyme elevations are frequent, but overt clinical hepatitis (with
symptoms such as gastrointestinal distress, nausea, vomiting, and jaundice)
occurs in less than five per cent of patients 109 and is age-dependent, 110-114
and may differ in frequency in different populations, 114 being virtually absent
among, e.g., Filipinos, 115 and is increased in patients with pre-existent liver
injury. 110 The hepatic damage caused by isoniazid is predominantly cytolysis.
116 The AUC for monoacetyl hydrazine, the putative precursor of the
responsible agent, was greater in slow acetylators in a pharmacokinetic
study, though the AUCs for acetyl isoniazid and diacetyl hydrazine were
higher in rapid acetylators. 117 The association of differences in pharamcokinetics
of isoniazid and its metabolites with hepatitis risk is poorly understood,
118 and has not been shown to be of great importance. 119 Indeed,
evidence obtained from patients in Hong Kong and Singapore showed that
elevated transaminase levels during treatment with isoniazid-containing regimens
were no higher in rapid than in slow acetylators. 120-122 In the
IUATLD trial on preventive chemotherapy with isoniazid in patients with
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