Within 1 to 2 hours after oral administration, Isoniazid (Isoniazid) produces peak blood levels which decline to 50 percent or less within 6 hours. It diffuses readily into all body fluids (cerebrospinal, pleural, and ascitic fluids), tissues, organs, and excreta (saliva, sputum, and feces). The drug also passes through the placental barrier and into milk in concentrations comparable to those in the plasma. From 50 to 70 percent of a dose of Isoniazid (Isoniazid) is excreted in the urine within 24 hours.
Isoniazid (Isoniazid) is metabolized primarily by acetylation and dehydrazination. The rate of acetylation is genetically determined. Approximately 50 percent of Blacks and Caucasians are "slow inacti- vators", and the rest are "rapid inactivators"; the majority of Eskimos and Orientals are" rapid inactivators."
The rate of acetylation does not significantly alter the effectiveness of Isoniazid (Isoniazid) . However, slow acetylation may lead to higher blood levels of the drug and, thus, to an increase in toxic reactions.
Pyridoxine (vitamin B) deficiency is sometimes observed in adults with high doses of Isoniazid (Isoniazid) and is considered probably due to its competition with pyridoxal phosphate for the enzyme apotryptophanase.
Isoniazid (Isoniazid) is recommended for all forms of tuberculos in which organisms are susceptible. However, active tuberculosis must be treated with multiple concomitant antituberculosis medications to prevent the emergence of drug resistance. Single-drug treatment of active tuberculos with Isoniazid (Isoniazid) , or any other medication, is inadequate therapy.
Isoniazid (Isoniazid) is 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 (≥ 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 (≥ 5 mm). In addition,
tuberculin-negative (
fectious 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 (> 5 mm), therapy should be continued.
3. Recent converters, as indicated by a tuberculin skin test (≥ 10 mm increase within a 2-year
period for those
children younger than 4 years of age with a > 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 (≥ 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 (Isoniazid) or 4 months of Isoniazid (Isoniazid) and rifampin, concomitantly.
5. Intravenous drug users known to be HIV-seronegative (> 10 mm).
6. Persons with the following medical conditions that have been reported to increase the risk of
tuberculosis (≥ 10 mm): silicosis; diabetes mellitus; prolonged therapy with adrenocorti-
costeroids; immunosuppressive therapy; some hematologic and reticuloendothelial diseases,
such as leukemia or Hodgkin’s disease; end-stage renal disease; clinical situations associated
with substantial rapid weight loss or chronic under nutrition (including: intestinal bypass
surgery for obesity, the postgastrectomy state (with or without weight loss), chronic peptic
ulcer disease, chronic malabsorption syndromes, and carcinomas of the oropharynx and upper
gastrointestinal tract that prevent adequate nutritional intake). Candidates for preventive
therapy who have fibrotic pulmonary lesions consistent with healed tuberculosis or who have
pulmonary silicosis should have 12 months of Isoniazid (Isoniazid) or 4 months of Isoniazid (Isoniazid) and
rifampin, concomitantly.
Additionally, in the absence of any of the above risk factors, persons under the age of 35 with a tuberculin skin test reaction of 10 mm or more are also appropriate candidates for preventive therapy if they are a member of any of the following high-incidence groups:
Children who are less than 4 years old are candidates for Isoniazid (Isoniazid) preventive therapy if they have > 10 mm induration from a PPD Mantoux tuberculin skin test.
Finally, persons under the age of 35 who a) have none of the above risk factors (1-6); b) belong to none of the high-incidence groups; and c) have a tuberculin skin test reaction of 15 mm or more, are appropriate candidates for preventive therapy.
The risk of hepatitis must be weighed against the risk of tuberculosis in positive tuberculin reactors over the age of 35. However, the use of Isoniazid (Isoniazid) is recommended for those with the additional risk factors listed above (1-6) and on an individual basis insituations where there is likelihood of serious consequences to contacts who may become infected.
All drugs should be stopped and an evaluation made at the first sign of a hypersensitivity reaction. If Isoniazid (Isoniazid) therapy must be reinstituted, the drug should be given only after symp-
toms have cleared. The drug should be restarted in very small and gradually increasing doses and should be withdrawn immediately if there is any indication of recurrent hypersensitivity reaction.
Use of Isoniazid (Isoniazid) should be carefully monitored in the following:
Because there is a higher frequency of Isoniazid (Isoniazid) associated hepatitis among certain patient groups, including Age > 35, daily users of alcohol, chronic liver disease, injection drug use
and women belonging to minority groups, particularly in the post-partum period, transaminase measurements should be obtained prior to starting and monthly during preventative therapy, or more frequently as needed. If any of the values exceed three to five times the upper limit of normal, Isoniazid (Isoniazid) should be temporarily discontinued and consideration given to restarting therapy.
The most frequent reactions are those affecting the nervous system and the liver.
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.
See boxed warning
Patients with this degree of INH intoxication are likely to have hypoventilation. The ad- ministration of sodium bicarbonate under these circumstances can cause exacerbation of hypercarbia. Ventilation must be monitored carefully, by measuring blood carbon dioxide
levels, and supported mechanically, if there is respiratory insufficiency.
Both peritoneal and hemodialysis have been used in the management of Isoniazid (Isoniazid) overdosage. These procedures are probably not required if control of seizures and acidosis is achieved with pyridoxine, diazepam and bicarbonate.
Along with measures based on initial and repeated determination of blood gases and other laboratory tests as needed, utilize meticulous respiratory and other intensive care to protect against hypoxia, hypotension, aspiration, pneumonitis, etc.
Isoniazid (Isoniazid) Tablets, USP are available as:
300 mg: White to off-white, oval-shaped, scored, flat-faced, beveled-edge tablet. Debossed
with stylized b on one side and 071 over 300 on the other side.
NDC 51079-083-20 - Unit dose blister packages of 100 (10 cards of 10 tablets each).
Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]
Protect from moisture and light.
