isoniazid [IM]

Adult Dosing

Active tuberculosis

5 mg/kg IM qd; Max: 300 mg IM qd
Alt: 15 mg/kg IM 2-3 times per wk; Max: 900 mg IM 2-3 times per wk
In combination with other antitubercular drugs

Latent tuberculosis

5 mg/kg IM qd x 6-9 months; Max: 300 mg IM qd
Alt: 15 mg/kg IM 2-3 times per wk; Max: 900 mg IM 2-3 times per wk

Pediatric Dosing

Active tuberculosis

10-15 mg/kg IM qd x 6-18 months; Max: 300 mg IM qd
Alt: 20-40 mg/kg IM 2-3 times per wk; Max: 900 mg IM 2-3 times per wk

Latent tuberculosis

10-15 mg/kg IM qd x 6-9 months; Max: 300 mg IM qd
Alt: 20-40 mg/kg IM 2-3 times per wk; Max: 900 mg IM 2-3 times per wk

[Outline]

Adult Dosing
Pediatric Dosing

Indications ⬆ ⬇

Treatment of susceptible tuberculosis infections
Treatment of latent tuberculosis infection (LTBI)

Contraindications ⬆ ⬇

Hypersensitivity to any of the ingredients of the product
Acute liver disease
Previous history of hepatic damage during isoniazid therapy

Black Box Warnings ⬆ ⬇

Severe and fatal hepatitis may occur; usually occurs within the first 3 months of treatment, although may develop even after many months of treatment with isoniazid. The risk of hepatitis is age related (although isoniazid-induced hepatotoxicity has been reported in children), and can increase with consumption of alcohol, chronic liver disease and injection drug use.
Monitor and interview patient monthly while on therapy. For persons 35 and older, hepatic enzymes, specifically AST and ALT (formerly SGOT and SGPT respectively) should be measured before therapy and periodically throughout treatment.
Increased risk of fatal hepatitis associated with therapy has been reported among women, especially in black and hispanic women. The risk may also be increased during the post partum period. Closely monitor such patients including frequent laboratory examination.
Consider discontinuation of isoniazid if abnormalities of liver function exceed 3-5 times the upper limit of normal.
Advise patient to report signs or symptoms related to liver damage, or other adverse effects such as unexplained anorexia, nausea, vomiting, dark urine, icterus, rash, persistent paresthesias of the hands and feet, persistent fatigue, weakness or fever of greater than 3 days duration, and abdominal tenderness, especially right upper quadrant discomfort
If signs suggestive of hepatic damage are detected, isoniazid should be discontinued, since continued use of the drug in these cases has been reported to cause severe liver damage
Preventive treatment should be deferred in persons with acute hepatic diseases.

Dosing Adjustment ⬆ ⬇

Renal Dose Adjustment

Renal impairment: No dose adjustments
CrCl <10: Consider decrease dose up to 50% in slow acetylators
Hemodialysis: Give dose after dialysis

Hepatic Dose Adjustment

Hepatic impairment: No adjustment required, however, use with caution, may accumulate and additional liver damage may occur in patients with pre-existing liver disease. For ALT or AST > 3 times the upper limit of normal, discontinue or temporarily withhold treatment. Treatment with isoniazid for latent tuberculosis infection should be deferred in patients with acute hepatic diseases.

Warnings/Precautions ⬆ ⬇

See Supplemental Patient Information

Severe and fatal hepatitis may occur - see US Black Box Warning

Cautions: Use cautiously in

Hepatic impairment
Severe renal impairment
Peripheral neuropathy
HIV infection
Alcohol abuse
IV drug abuse
Patient >35years
Use of any chronically administered medication

Supplemental Patient Information

Should be administered 1 hour before or 2 hours after meals on an empty stomach.

Pregnancy/Breast Feeding ⬆ ⬇

Pregnancy Category:C

Breastfeeding: Breastfeeding should not be discouraged in women taking isoniazid. Because of the low levels of isoniazid in breastmilk and safe administration directly to infants, it is unlikely to cause adverse reactions in infants, but infants should be monitored for rare instances jaundice. Giving the maternal once-daily dose before the infant's longest sleep period will decrease the dose the infant receives. The amount of isoniazid in milk is insufficient to treat tuberculosis in the breastfed infant. This information is based upon LactMed database (available at http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT last accessed 11 March 2011) Manufacturer advises caution..

Adverse Reactions ⬆ ⬇

CNS: Seizures, paresthesias, memory impairment, malaise
NEURO: Optic neuritis and atrophy, peripheral neuropathy
PSYCHIATRY: Toxic psychosis
GI: Nausea, vomiting, epigastric discomfort, anorexia
HEMA: Agranulocytosis, aplastic anemia, thrombocytopenia, eosinophilia
HEPA: Sever hepatotoxicity, elevated liver transaminases, bilirubinemia, bilirubinuria, jaundice
METABOLIC: Pyridoxine deficiency, pellagra, hyperglycemia, metabolic acidosis, gynecomastia
MISC: Fatigue, rheumatic syndrome, lupus erythematosus syndrome
HYPERSENSITIVITY: Fever, skin eruptions, lymphadenopathy, vasculitis

Clinical Pharmacology ⬆ ⬇

Antituberculosis agent; inhibits the synthesis of mycoloic acids, an essential component of the bacterial cell wall
Metabolized by liver; CYP450: 2C19, 3A4 inhibitor
Excreted in urine (50-70%)
Half-life

Fast acetylators: 0.5-1.6 hrs
Slow acetylators: 2-5 hrs

Brands and Availability ⬆ ⬇