Active tuberculosis Active tuberculosis - HIV infection HIV infection - Inactive tuberculosis Inactive tuberculosis

Systemic: Isoniazid (INH) is a synthetic, bactericidal antitubercular agent that is active against many mycobacteria, primarily those that are actively dividing.it may relate to inhibition of mycolic acid synthesis and disruption of the cell wall in susceptible organisms.

Absorption Systemic: Readily absorbed: food reduces bioavailability Distribution
Systemic: Vd: 0.57 to 0.76 L/kg Metabolism
Systemic: Hepatic Excretion
Systemic: Fecal: small amounts; Renal: 75–95% Elimination Half Life Systemic: Fast acetylators: 0.5 to 1.6 h Adults (including elderly patients) Slow acetylators: 2 to 5 h Adults (including elderly patients); 2.3 to 4.9 h Children (1.5 to 15 y); 7.8 to 19.8 h Neonates.

Acute liver disease. History of severe adverse reactions to isoniazid such as drug fever, chills, or arthritis. History of isoniazid associated hepatic injury or drug induced liver injury. Severe hypersensitivity to isoniazid.

C

Infant risk is minimal

Hepatic: Increased serum transaminases (mild and transient 10% to 20%)
Cardiovascular: Vasculitis
Central nervous system: Brain disease, memory impairment, paresthesia, peripheral neuropathy, psychosis, seizure
Dermatologic: Skin rash (morbilliform, maculopapular, pruritic, or exfoliative), toxic epidermal necrolysis
Endocrine & metabolic: Gynecomastia, hyperglycemia, metabolic acidosis, pellagra, pyridoxine deficiency
Gastrointestinal: Epigastric distress, nausea, pancreatitis, vomiting
Genitourinary: Bilirubinuria
Hematologic & oncologic: Agranulocytosis, anemia (sideroblastic, hemolytic, or aplastic), eosinophilia, lymphadenopathy, thrombocytopenia.
Hepatic: Hepatitis (risk increases with age; 2% in patients ?50 years), hyperbilirubinemia, jaundice
Immunologic: DRESS syndrome
Neuromuscular & skeletal: Lupus-like syndrome, rheumatic disease
Ophthalmic: Optic atrophy, optic neuritis
Miscellaneous: Fever

Active tuberculosis Intensive phase: 300 mg (about 5 mg/kg) QD for 8 weeks (56 doses) or 5 days per week for 8 weeks (40 doses); give in combination with rifampin 600 mg (about 10 mg/kg) QD or 5 days/week; pyrazinamide 1000 mg (40 to 55 kg), 1500 mg (56 to 75 kg), or 2000 mg (76 to 90 kg) QD or 5 days/week; and ethambutol 800 mg (40 to 55 kg), 1200 mg (56 to 75 kg), or 1600 mg (76 to 90 kg) QD or 5 days/week (guideline dosage).
Continuation phase,QD regimen: 300 mg (about 5 mg/kg) QD for 4 months (126 doses); give in combination with rifampin 600 mg (about 10 mg/kg) QD (guideline dosage). Continuation phase, 3 times weekly regimen: 900 mg (about 15 mg/kg) orally/IM 3 days/week for 4 months (54 doses); give in combination with rifampin 600 mg (about 10 mg/kg) orally/IV 3 days/week, on same days isoniazid is administered (guideline dosage). Active tuberculosis - HIV infection
Intensive phase: 300 mg (about 5 mg/kg) QD for 8 weeks (56 doses); give in combination with rifampin 600 mg (about 10 mg/kg) QD; pyrazinamide 1000 mg (40 to 55 kg), 1500 mg (56 to 75 kg), or 2000 mg (76 to 90 kg) QD; and ethambutol 800 mg (40 to 55 kg), 1200 mg (56 to 75 kg), or 1600 mg (76 to 90 kg) QD. Additionally, administer pyridoxine 25 to 50 mg QD (guideline dosage) . Continuation phase: 300 mg (about 5 mg/kg) QD for 4 months (126 doses); give in combination with rifampin 600 mg (about 10 mg/kg) QD. Additionally, administer pyridoxine 25 to 50 mg QD (guideline dosage). HIV infection - Inactive tuberculosis
300 mg QD or 900 mg orally twice weekly for 9 months, plus pyridoxine 50 mg QD (guideline dosage). (Alternative, not receiving antiretroviral therapy) 15 mg/kg (rounded up to the nearest 50 or 100 mg; MAX, 900 mg) orally in combination with rifapentine 300 mg (10 to 14 kg), 450 mg (14.1 to 25 kg), 600 mg (25.1 to 32 kg), 750 mg (32.1 to 49.9 kg), or 900 mg (50 kg or greater) orally; the combined regimen should be administered once weekly as directly observed therapy for 12 weeks (guideline dosage). Inactive tuberculosis
5 mg/kg (MAX, 300 mg) QD for 9 months OR 15 mg/kg (MAX, 900 mg) orally twice weekly as directly observed therapy for 9 months (guideline dosage) [5][6] (Alternative) 15 mg/kg (rounded up to the nearest 50 or 100 mg; MAX, 900 mg) orally once weekly in combination with rifapentine orally once weekly for 12 weeks (rifapentine dose: 300 mg (10 to 14 kg), 450 mg (14.1 to 25 kg), 600 mg (25.1 to 32 kg), 750 mg (32.1 to 49.9 kg), or 900 mg (50 kg or greater)); give only as directly observed therapy (guideline dosage).

Active tuberculosis
(Younger than 15 years and 40 kg or less) Intensive phase: 10 to 15 mg/kg QD for 8 weeks (56 doses) or 5 days/week for 8 weeks (40 doses); give in combination with rifampin 10 to 20 mg/kg QD or 5 days/week, pyrazinamide 30 to 40 mg/kg QD or 5 days/week, and ethambutol 15 to 25 mg/kg QD or 5 days/week (guideline dosage). (Younger than 15 years and 40 kg or less)Continuation phase, QD regimen: 10 to 15 mg/kg QD for 4 months; give in combination with rifampin 10 to 20 mg/kg orally/IV QD (guideline dosage). (15 years or older or greater than 40 kg) Intensive phase: 300 mg (about 5 mg/kg) QD for 8 weeks (56 doses) or 5 days per week for 8 weeks (40 doses); give in combination with rifampin 600 mg (about 10 mg/kg) QD or 5 days/week; pyrazinamide 1000 mg (40 to 55 kg), 1500 mg (56 to 75 kg), or 2000 mg (76 to 90 kg) orally once daily or 5 days/week; and ethambutol 800 mg (40 to 55 kg), 1200 mg (56 to 75 kg), or 1600 mg (76 to 90 kg) QD or 5 days/week (guideline dosage). (15 years or older or greater than 40 kg) Continuation phase, QD regimen: 300 mg (about 5 mg/kg) orally/IM once daily for 4 months (126 doses); give in combination with rifampin 600 mg (about 10 mg/kg) QD (guideline dosage). (15 years or older or greater than 40 kg) Continuation phase, 3 times weekly regimen: 900 mg (about 15 mg/kg) orally/IM 3 days/week for 4 months (126 doses); give in combination with rifampin 600 mg (about 10 mg/kg) orally/IV 3 days/week, on same days isoniazid is administered (guideline dosage). Active tuberculosis - HIV infection
(Younger than 15 years and 40 kg or less) Intensive phase: 10 to 15 mg/kg QD for 8 weeks (56 doses); give in combination with rifampin 10 to 20 mg/kg QD, pyrazinamide 30 to 40 mg/kg QD, and ethambutol 15 to 25 mg/kg QD . Additionally, administer pyridoxine 1 to 2 mg/kg (MAX 50 mg) QD(guideline dosage). (Younger than 15 years and 40 kg or less) Continuation phase: 10 to 15 mg/kg QD for 4 or 7 months; give in combination with rifampin 10 to 20 mg/kg QD. Additionally, administer pyridoxine 1 to 2 mg/kg (MAX 50 mg) QD (guideline dosage). (15 years or older or greater than 40 kg) Intensive phase: 300 mg (about 5 mg/kg) QD for 8 weeks (56 doses); give in combination with rifampin 600 mg (about 10 mg/kg) QD; pyrazinamide 1000 mg (40 to 55 kg), 1500 mg (56 to 75 kg), or 2000 mg (76 to 90 kg) QD; and ethambutol 800 mg (40 to 55 kg), 1200 mg (56 to 75 kg), or 1600 mg (76 to 90 kg) QD. Additionally, administer pyridoxine 25 to 50 mg QD (guideline dosage). (15 years or older or greater than 40 kg) Continuation phase: 300 mg (about 5 mg/kg) QD for 4 months (126 doses); give in combination with rifampin 600 mg (about 10 mg/kg) QD. Additionally, administer pyridoxine 25 to 50 mg QD(guideline dosage). HIV infection - Inactive tuberculosis
10 to 15 mg/kg (MAX, 300 mg)QD for 9 months, OR 20 to 30 mg/kg (MAX, 900 mg) orally twice weekly for 9 months (guideline dosage) [8] (Alternative, 12 years or older, not receiving antiretroviral therapy) 15 mg/kg (rounded up to the nearest 50 or 100 mg; MAX, 900 mg) orally in combination with rifapentine 300 mg (10 to 14 kg), 450 mg (14.1 to 25 kg), 600 mg (25.1 to 32 kg), 750 mg (32.1 to 49.9 kg), or 900 mg (50 kg or greater) orally; the combined regimen should be administered once weekly as directly observed therapy for 12 weeks (guideline dosage. Inactive tuberculosis
10 to 20 mg/kg (MAX, 300 mg)QDfor 9 months OR 20 to 40 mg/kg (MAX, 900 mg) orally twice weekly as directly observed therapy for 9 months (guideline dosage). (12 years or older; alternative) 15 mg/kg (rounded up to the nearest 50 or 100 mg; MAX, 900 mg) orally once weekly in combination with rifapentine orally once weekly for 12 weeks (rifapentine dose: 300 mg (10 to 14 kg), 450 mg (14.1 to 25 kg), 600 mg (25.1 to 32 kg), 750 mg (32.1 to 49.9 kg), or 900 mg (50 kg or greater)); give only as directly observed therapy (guideline dosage).

No dose adjustment necessary.

(advanced disease or AST greater than 3 times ULN and not due to TB): Isoniazid-based regimens are preferred if possible; expert consultation and dosage adjustments may be necessary. If isoniazid cannot be used, consider treatment regimens with fewer potentially hepatotoxic drugs.

Oral isoniazid should be taken on an empty stomach.