Antimycobacterial

Isoniazid

Approved 24 Aug 1972OralTablet

The FDA lists this product in 43 strengths and forms.

Boxed warningThe FDA label of this medicine carries a boxed warning, the strongest warning the FDA gives. Read it under warnings and precautions.

Indications

Isoniazid tablets are recommended for all forms of tuberculosis in which organisms are susceptible. However, active tuberculosis must be treated with multiple concomitant anti-tuberculosis medications to prevent the emergence of drug resistance. Single-drug treatment of active tuberculosis with isoniazid or any other medication, is inadequate therapy. Isoniazid tablets are recommended as preventive therapy for the following groups, regardless of age.

(Note: the criterion for a positive reaction to a skin test (in millimeters of induration) for each group is given in parenthesis): 1. Persons with human immunodeficiency virus (HIV) infection (greater than or equal to 5 mm) and persons with risk factors for HIV infection whose HIV infection status is unknown but who are suspected of having HIV infection. Preventive therapy may be considered for HIV infected persons who are tuberculin-negative but belong to groups in which the prevalence of tuberculosis infection is high.

Candidates for preventive therapy who have HIV infection should have a minimum of 12 months of therapy. 2. Close contacts of persons with newly diagnosed infectious tuberculosis (greater than or equal to 5 mm). In addition, tuberculin-negative (less than 5 mm) children and adolescents who have been close contacts of infectious persons within the past 3 months are candidates for preventive therapy until a repeat tuberculin skin test is done 12 weeks after contact with the infectious source.

If the repeat skin test is positive (greater than 5 mm), therapy should be continued. 3. Recent converters, as indicated by a tuberculin skin test (greater than or equal to 10 mm increase within a 2-year period for those less than 35 years old; greater than or equal to 15 mm increase for those greater than or equal to 35 years of age). All infants and children younger than 4 years of age with a greater than 10 mm skin test are included in this category. 4.

Persons with abnormal chest radiographs that show fibrotic lesions likely to represent old healed tuberculosis (greater than or equal to 5 mm). Candidates for preventive therapy who have fibrotic pulmonary lesions consistent with healed tuberculosis or who have pulmonary silicosis should have 12 months of isoniazid or 4 months of isoniazid and rifampin, concomitantly. 5. Intravenous drug users known to be HIV-seronegative (greater than 10 mm). 6.

At a glance

Brand name: Isoniazid
Pharmacologic class: Antimycobacterial
Route: Oral
Dosage form: Tablet
Applicant: Genus
Status: Discontinued
FDA approval: 24 Aug 1972
Application: ANDA080937-002

Indications

Interactions

Drug Interactions Food Isoniazid should not be administered with food. Studies have shown that the bioavailability of isoniazid is reduced significantly when administered with food. Tyramine- and histamine-containing foods should be avoided in patients receiving isoniazid. Because isoniazid has some monoamine oxidase inhibiting activity, an interaction with tyramine-containing foods (cheese, red wine) may occur. Diamine oxidase may also be inhibited, causing exaggerated response (e.g., headache, sweating, palpitations, flushing, hypotension) to foods containing histamine (e.g., skipjack, tuna, other tropical fish).

Acetaminophen A report of severe acetaminophen toxicity was reported in a patient receiving isoniazid. It is believed that the toxicity may have resulted from a previously unrecognized interaction between isoniazid and acetaminophen and a molecular basis for this interaction has been proposed. However, current evidence suggests that isoniazid does induce P-450IIE1, a mixed-function oxidase enzyme that appears to generate the toxic metabolites, in the liver.

Furthermore it has been proposed that isoniazid resulted in induction of P-450IIE1 in the patient’s liver which, in turn, resulted in a greater proportion of the ingested acetaminophen being converted to the toxic metabolites. Studies have demonstrated that pretreatment with isoniazid potentiates acetaminophen hepatotoxicity in rats 1,2 . Carbamazepine Isoniazid is known to slow the metabolism of carbamazepine and increase its serum levels.

Carbamazepine levels should be determined prior to concurrent administration with isoniazid, signs and symptoms of carbamazepine toxicity should be monitored closely and appropriate dosage adjustment of the anticonvulsant should be made 3 . Ketoconazole Potential interaction of ketoconazole and isoniazid may exist. When ketoconazole is given in combination with isoniazid and rifampin the AUC of ketoconazole is decreased by as much as 88 percent after 5 months of concurrent isoniazid and rifampin therapy 4 .

Phenytoin Isoniazid may increase serum levels of phenytoin. To avoid phenytoin intoxication, appropriate adjustment of the anticonvulsant should be made 5,6 . Theophylline A recent study has shown that concomitant administration of isoniazid and theophylline may cause elevated plasma levels of theophylline and in some instances a slight decrease in the elimination of isoniazid. Since the therapeutic range of theophylline is narrow, theophylline serum levels should be monitored closely and appropriate dosage adjustments of theophylline should be made 7 .

Valproate A recent case study has shown a possible increase in the plasma level of valproate when co-administered with isoniazid. Plasma valproate concentration should be monitored when isoniazid and valproate are co-administered and appropriate dosage adjustments of valproate should be made 5 .

Adverse reactions

The most frequent reactions are those affecting the nervous system and the liver. Nervous System Reactions Peripheral neuropathy is the most common toxic effect. It is dose-related, occurs most often in the malnourished and in those predisposed to neuritis (e.g., alcoholics and diabetics) and is usually preceded by paresthesias of the feet and hands. The incidence is higher in “slow inactivators”. Other neurotoxic effects, which are uncommon with conventional doses, are convulsions, toxic encephalopathy, optic neuritis and atrophy, memory impairment and toxic psychosis.

Hepatic Reactions See boxed warning . Elevated serum transaminase (SGOT; SGPT), bilirubinemia, bilirubinuria, jaundice and occasionally severe and sometimes fatal hepatitis. The common prodromal symptoms of hepatitis are anorexia, nausea, vomiting, fatigue, malaise and weakness. Mild hepatic dysfunction, evidenced by mild and transient elevation of serum transaminase levels occurs in 10 to 20 percent of patients taking isoniazid.

This abnormality usually appears in the first 1 to 3 months of treatment but can occur at any time during therapy. In most instances, enzyme levels return to normal and generally, there is no necessity to discontinue medication during the period of mild serum transaminase elevation. In occasional instances, progressive liver damage occurs, with accompanying symptoms. If the SGOT value exceeds three to five times the upper limit of normal, discontinuation of the isoniazid should be strongly considered.

The frequency of progressive liver damage increases with age. It is rare in persons under 20, but occurs in up to 2.3 percent of those over 50 years of age. Gastrointestinal Reactions Nausea, vomiting, epigastric distress, and pancreatitis. Hematologic Reactions Agranulocytosis; hemolytic, sideroblastic or aplastic anemia, thrombocytopenia; and eosinophilia. Hypersensitivity Reactions Fever, skin eruptions (morbilliform, maculopapular, purpuric or exfoliative), lymphadenopathy, vasculitis, toxic epidermal necrolysis, and drug reaction with eosinophilia syndrome (DRESS).

Metabolic and Endocrine Reactions Pyridoxine deficiency, pellagra, hyperglycemia, metabolic acidosis and gynecomastia. Miscellaneous Reactions Rheumatic syndrome and systemic lupus erythematosus-like syndrome.

Isoniazid

Indications

At a glance

Two medicines in one question?

Isoniazid

Indications

At a glance

Two medicines in one question?

Contraindications

Warnings and precautions

Interactions

Pregnancy and breastfeeding

Adverse reactions

Composition

Strengths and forms

Official product information