Active tuberculosis infections
Latent tuberculosis infection (LTBI)

Isoniazid inhibits the synthesis of mycoloic acids, an essential component of the bacterial cell wall. At therapeutic levels isoniazid is bacteriocidal against actively growing intracellular and extracellular Mycobacterium tuberculosis organisms.

Absorption: Oral, IM: Rapid and complete; food reduces rate and extent of absorption
Distribution: All body tissues and fluids including CSF
Protein binding: 10% to 15%
Metabolism: Hepatic to acetylisoniazid with decay rate determined genetically by acetylation phenotype; undergoes further hydrolysis to isonicotinic acid and acetylhydrazine
Half-life: May be prolonged in patients with impaired hepatic function or severe renal impairment
Fast acetylators: 30 to 100 minutes
Slow acetylators: 2 to 5 hours
Time to peak, serum: 1 to 2 hours
Excretion: Urine (75% to 95% as unchanged drug and metabolites); small amounts excreted in feces and saliva

Hypersensitivity to isoniazid or any component of the formulation, including drug-induced hepatitis; acute liver disease; previous history of hepatic injury during isoniazid therapy; previous severe adverse reaction (drug fever, chills, arthritis) to isoniazid.

Isoniazid crosses the human placenta.
Due to the risk of tuberculosis to the fetus, treatment is recommended when the probability of maternal disease is moderate to high. Drug-susceptible TB guidelines recommend isoniazid as part of the initial treatment regimen; close monitoring is recommended during pregnancy and postpartum (due to increased risk of hepatitis). Isoniazid is also recommended for the treatment of TB in pregnant women with HIV-coinfection. Pyridoxine supplementation is recommended to decrease the risk of peripheral neurotoxicity (ATC/CDC/IDSA 2003; Nahid 2016). Due to biologic changes during pregnancy and early postpartum, pregnant women may have increased susceptibility to tuberculosis infection or reactivation of latent disease (Mathad 2012).

Isoniazid and the acetylisoniazid metabolite are present in breast milk (Berlin 1979).
The relative infant dose (RID) of isoniazid is 12% to 25% when calculated using the highest breast milk concentration located and compared to an infant therapeutic dose of 10 to 20 mg/kg/day.
In general, breastfeeding is considered acceptable when the RID of a medication is <10%; when the RID is >25% breastfeeding should generally be avoided (Anderson 2016; Ito 2000).

Hepatic: Increased serum transaminases (mild and transient 10% to 20%)

Tuberculosis, active (drug susceptible): Oral, IM:
Dosing:
Once-daily therapy: 5 mg/kg/dose (usual dose: 300 mg) once daily Note: The preferred frequency of administration is once daily during the intensive and continuation phases; however, 5-days per week administration by directly observed therapy (DOT) is an acceptable alternative.
Three-times-weekly DOT: 15 mg/kg/dose (usual dose: 900 mg) administered 3 times weekly
Twice-weekly DOT: 15 mg/kg/dose (usual dose: 900 mg) administered twice weekly
Once-weekly DOT: 15 mg/kg/dose (usual dose: 900 mg) administered once weekly
Tuberculosis, latent infection (LTBI): Oral, IM: Note: Concomitant administration of pyridoxine 10 to 50 mg daily is recommended in malnourished patients or those prone to neuropathy (eg, patients with HIV-infection, diabetes or chronic alcohol abusers).
Nontuberculous mycobacterium (M. kansasii) (off-label use): 5 mg/kg/day (maximum: 300 mg daily) for duration to include 12 months of culture-negative sputum; typically used in combination with ethambutol and rifampin (Griffith 2007).

Tuberculosis, active (drug-susceptible) (excludes meningitis): Oral, IM:
Dosing:
Once-daily therapy: Note: The preferred frequency of administration is once daily during the intensive and continuation phases; however, 5-days-per-week administration by directly observed therapy (DOT) is an acceptable alternative.
Infants, Children and Adolescents <15 years and ?40 kg: 10 to 15 mg/kg/dose once daily; maximum dose: 300 mg/dose
Children and Adolescents <15 years and >40 kg and Adolescents ?15 years: 5 mg/kg/dose once daily (typical dose: 300 mg)
Three-times-weekly DOT: Note: Although suggested dosing based on experience with twice-weekly regimen; experts suggest 3-times-weekly regimens are more effective than twice-weekly DOT regimens; 3-times-weekly DOT may be used as part of an intensive phase and/or continuation phase dosing regimen; consult guidelines for specific information.
Infants, Children and Adolescents <15 years, weighing ?40 kg: 20 to 30 mg/kg/dose 3 times weekly; maximum dose: 900 mg/dose; in adolescents, some experts would use 15 mg/kg/dose (maximum dose: 900 mg/dose) Children and Adolescents <15 years weighing >40 kg or Adolescents ?15 years: 15 mg/kg/dose 3 times weekly (typical dose: 900 mg)
Regimens : Treatment regimens for pulmonary tuberculosis consist of an initial 2-month phase of a 4-drug regimen, followed by a continuation phase of an additional 4 to 7 months of isoniazid and rifampin. Isoniazid frequency and dosing differs depending on treatment regimen selected; consult current Drug-sensitive TB guidelines (Nahid 2016).
Tuberculosis, latent infection (LTBI), treatment:
Isoniazid combination therapy: Note: Should not be used in individuals presumed to be infected with isoniazid or rifampin resistant strains of TB. Isoniazid combination therapy with rifapentine is the CDC-preferred regimen for LTBI (CDC [Borisov 2018]).
Rifapentine combination (preferred): Regardless of HIV status: Note: May be administered by DOT or self-administered therapy (SAT) at the clinician's discretion based on local practice, patient attributes/preferences, and other factors including risk for TB disease progression (CDC [Borisov 2018]). Rifapentine combination is preferred in persons with HIV, including AIDS, and taking antiretroviral therapy (ART) with acceptable drug-drug interactions when guided by experienced clinicians (CDC [Borisov 2018]).
Children 2 to 11 years, weighing at least 10 kg: Oral: 25 mg/kg/dose once weekly of isoniazid for 12 weeks (12 doses); maximum dose: 900 mg/dose (CDC [Borisov 2018]; Cruz 2018; Villarino 2015)
Children ?12 years and Adolescents: Oral: 15 mg/kg/dose once weekly of isoniazid for 12 weeks (12 doses), round dose up to nearest 50 or 100 mg; maximum dose: 900 mg/dose (CDC [Borisov 2018]; Cruz 2018; Villarino 2015)
Rifampin combination: HIV-exposed/-positive: Children: Oral: 10 to 15 mg/kg/dose once daily; maximum dose: 300 mg/dose; treatment duration: 3 to 4 months (HHS [OI pediatric 2013])
Isoniazid monotherapy: Note: Intermittent regimens (once or twice weekly) should be administered by DOT.
Infants and Children:
Non-HIV-exposed/-positive: Oral: 10 to 20 mg/kg/dose once daily; maximum dose: 300 mg/dose or 20 to 40 mg/kg/dose twice weekly as DOT; maximum dose: 900 mg/dose; treatment duration: 9 months (270 daily doses or 76 twice-weekly doses) (CDC 2013)
HIV-exposed/-positive: Oral: 10 to 15 mg/kg/dose once daily (maximum dose: 300 mg/dose) or 20 to 40 mg/kg/dose (maximum dose: 900 mg/dose) twice weekly as DOT; treatment duration: 9 months (CDC 2013; HHS [OI pediatric 2013])
Adolescents:
Non-HIV-exposed/-positive: Oral: 10 to 20 mg/kg/dose once daily; maximum dose: 300 mg/dose or 20 to 40 mg/kg/dose twice weekly as DOT; maximum dose: 900 mg/dose; treatment duration: 9 months (270 daily doses or 76 twice weekly doses) (CDC 2013)
HIV-exposed/-positive: Oral: 300 mg once d

CrCl <30 mL/minute: Treatment of drug-susceptible TB: 300 mg once daily or 900 mg administered 3 times weekly (Nahid 2016)
ESRD receiving intermittent hemodialysis (IHD):
Administer dose postdialysis (Aronoff 2007; Nahid 2016); Dialyzable (50% to 100%);
Treatment of drug-susceptible TB: 300 mg once daily or 900 mg administered 3 times weekly (Nahid 2016)

There are no dosage adjustments provided in the manufacturer's labeling; however, use with caution, may accumulate and additional liver damage may occur in patients with preexisting liver disease. Contraindicated in patients with acute liver disease or previous isoniazid-associated hepatic injury. For ALT or AST >3 times the ULN: discontinue or temporarily withhold treatment. Treatment with isoniazid for latent tuberculosis infection should be deferred in patients with acute hepatic diseases.