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Isoniazid: Drug information

Isoniazid: Drug information
(For additional information see "Isoniazid: Patient drug information" and see "Isoniazid: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Hepatitis:

Severe and sometimes fatal hepatitis associated with isoniazid therapy has been reported and may occur or may develop even after many months of treatment. The risk of developing hepatitis is age related. Approximate case rates by age are as follows: less than 1/1,000 for persons younger than 20 years of age, 3/1,000 for persons in the 20 to 34 year age group, 12/1,000 for persons in the 35 to 49 year age group, 23/1,000 for persons in the 50 to 64 year age group, and 8/1,000 for persons older than 65 years. The risk of hepatitis is increased with daily consumption of alcohol. Precise data to provide a fatality rate for isoniazid-related hepatitis are not available; however, in a US Public Health Service surveillance study of 13,838 persons taking isoniazid, there were 8 deaths among 174 cases of hepatitis.

Therefore, carefully monitor patients given isoniazid and interview patients at monthly intervals. For persons 35 years and older, in addition to monthly symptom reviews, measure hepatic enzymes (specifically, AST and ALT) prior to starting isoniazid therapy and periodically throughout treatment. Isoniazid-associated hepatitis usually occurs during the first 3 months of treatment. Usually, enzyme levels return to normal despite continuance of drug, but, in some cases, progressive liver dysfunction occurs. Other factors associated with an increased risk of hepatitis include daily use of alcohol, chronic liver disease, and injection drug use. A recent report suggests an increased risk of fatal hepatitis associated with isoniazid among women, particularly black and Hispanic women. The risk may also be increased during the postpartum period. Consider more careful monitoring in these groups, possibly including more frequent laboratory monitoring. If abnormalities of liver function exceed 3 to 5 times the upper limit of normal (ULN), strongly consider discontinuation of isoniazid. Liver function tests are not a substitute for a clinical evaluation at monthly intervals or for the prompt assessment of signs or symptoms of adverse reactions occurring between regularly scheduled evaluations. Instruct patients to immediately report signs or symptoms consistent with liver damage or other adverse reactions. These include any of the following: unexplained anorexia, nausea, vomiting, dark urine, icterus, rash, persistent paresthesia of the hands and feet, persistent fatigue, weakness or fever of greater than 3-day duration or abdominal tenderness, especially right upper quadrant discomfort. If these symptoms appear or if signs suggestive of hepatic damage are detected, promptly discontinue isoniazid, because continued use of the drug in these cases has been reported to cause a more severe form of liver damage.

Give patients with tuberculosis who have hepatitis attributed to isoniazid appropriate treatment with alternative drugs. If isoniazid must be reinstituted, do so only after symptoms and laboratory abnormalities have cleared. Restart the drug in very small and gradually increasing doses and withdraw immediately if there is any indication of recurrent liver involvement.

Defer preventive treatment in persons with acute hepatic diseases.

Brand Names: Canada
  • Isotamine;
  • PDP-Isoniazid
Pharmacologic Category
  • Antitubercular Agent
Dosing: Adult

Note: Concomitant pyridoxine is recommended in any patient at risk for neuropathy (eg, patients with HIV infection, diabetes, alcoholism, nutritional deficiency, chronic renal failure, advanced age) and in pregnant or breastfeeding women (ATS/CDC/IDSA [Nahid 2016]; WHO 2020; manufacturer's labeling).

Tuberculosis, active

Tuberculosis, active:

Drug susceptible: Note: Always administer in combination with other antitubercular drugs.

6-month regimen:

Once-daily therapy: Oral, IM: 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 (ATS/CDC/IDSA [Nahid 2016]).

Three-times-weekly DOT: Oral, IM: 15 mg/kg/dose (usual dose: 900 mg) administered 3 times weekly (ATS/CDC/IDSA [Nahid 2016]).

Twice-weekly DOT: Oral, IM: 15 mg/kg/dose (usual dose: 900 mg) administered twice weekly (ATS/CDC/IDSA [Nahid 2016]).

Once-weekly DOT: Oral, IM: 15 mg/kg/dose (usual dose: 900 mg) administered once weekly (ATS/CDC/IDSA [Nahid 2016]).

Regimens: Traditional treatment regimens for pulmonary tuberculosis and tuberculous meningitis 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 for pulmonary tuberculosis and a continuation phase of an additional 7 to 10 months of isoniazid and rifampin for tuberculous meningitis (optimal duration is not defined although continuation phase must continue for a minimum of 7 additional months). Adjunctive corticosteroid therapy (eg, dexamethasone, prednisolone) tapered over 6 to 8 weeks is also recommended for tuberculous meningitis. Isoniazid frequency and dosing differs depending on treatment regimen selected; consult current Drug-sensitive tuberculosis (TB) guidelines (ATS/CDC/IDSA [Nahid 2016]).

4-month rifapentine-moxifloxacin-based regimen:

Note: Reserve use for patients ≥40 kg with pulmonary TB who are not pregnant or breastfeeding; for patients with HIV infection, only use if CD4 count ≥100 cells/mm3 and in patients on an efavirenz-based antiretroviral regimen (CDC [Carr 2022]; Dorman 2021). In the clinical study evaluating this regimen, ≥5 doses per week were given by DOT (Dorman 2021).

Initial phase: Oral: 300 mg once daily in combination with rifapentine, moxifloxacin, and pyrazinamide for 8 weeks (56 doses) (CDC [Carr 2022]; Dorman 2021).

Continuation phase: Oral: 300 mg once daily in combination with rifapentine and moxifloxacin for 9 weeks (63 doses) (CDC [Carr 2022]; Dorman 2021).

Drug-resistant (alternative agent):

Note: Use should only be considered in patients with low-level isoniazid resistance; do not use in patients with high-level isoniazid resistance. Expert consultation for optimal regimen and duration of treatment is advised (ATS/CDC/ERD/IDSA [Nahid 2019]).

Oral, IM: 15 mg/kg once daily as part of an appropriate combination regimen (ATS/CDC/ERS/IDSA [Nahid 2019]; Dooley 2020; Schluger 2022; Walsh 2019; WHO 2020).

Tuberculosis, latent infection

Tuberculosis, latent infection:

Isoniazid and rifapentine combination regimen: Oral: 15 mg/kg/dose (round up to nearest 50 or 100 mg; maximum dose: 900 mg/dose) once weekly in combination with rifapentine for 3 months by DOT (preferred) or self-administered therapy (CDC [Borisov 2018]; HHS [OI adult 2020]; NTCA/CDC [Sterling 2020]; Sterling 2011; Sterling 2016). Note: The once-weekly rifapentine-containing regimen may only be used in patients who are not pregnant and/or not expecting to become pregnant; if used in patients with HIV, it may only be used in those receiving antiretroviral therapy (ART) with acceptable drug-drug interactions with rifapentine (CDC [Borisov 2018]; HHS [OI adult 2020]; NTCA/CDC [Sterling 2020]).

Isoniazid and rifampin combination regimen: Oral: 5 mg/kg (maximum: 300 mg/dose) once daily in combination with rifampin for 3 months. Note: If used in patients with HIV, it may only be used in those receiving antiretroviral therapy with acceptable drug-drug interactions with rifampin (NTCA/CDC [Sterling 2020]).

Isoniazid monotherapy (alternative regimen): Oral, IM: 5 mg/kg (maximum: 300 mg/dose) once daily for 6 or 9 months or 15 mg/kg (maximum: 900 mg/dose) twice weekly under DOT for 6 or 9 months. Note: 9 months of daily isoniazid therapy may be more effective than 6 months, but no clinical trial data are available that directly compare the 2 durations (NTCA/CDC [Sterling 2020]).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Note: Acetylator status (eg, slow vs rapid), rather than kidney function, is considered to be the primary contributor to isoniazid clearance (Weber 1979). Although no dosage adjustments of isoniazid are recommended in patients with end-stage kidney disease, including patients on dialysis, use with caution due to an increased risk of neurotoxicity (Chaitanya 2016; Cheung 1993; Constantinescu 2017; Low 2019; Si 2018); close monitoring and concomitant pyridoxine therapy is recommended (ATS/CDC/IDSA [Nahid 2016]; WHO 2020).

Oral, IM:

Altered kidney function: No dosage adjustment necessary for any degree of kidney dysfunction (ATS/CDC/ERS/IDSA [Nahid 2019]; ATS/CDC/IDSA [Nahid 2016]; Gold 1976; Weber 1979).

Hemodialysis, intermittent (thrice weekly): Slightly dialyzable (9.2%) (Malone 1999): No dosage adjustment necessary (ATS/CDC/IDSA [Nahid 2016]; Malone 1999); when scheduled dose falls on a dialysis day, administer after hemodialysis (ATS/CDC/IDSA [Nahid 2016]).

Peritoneal dialysis: Slightly dialyzable (CAPD accounts for 1.3% of total clearance): No dosage adjustment necessary (Ahn 2003).

CRRT: No dosage adjustment necessary (expert opinion).

PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (expert opinion).

Dosing: Hepatic Impairment: Adult

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.

Dosing: Pediatric

(For additional information see "Isoniazid: Pediatric drug information")

Note: Concomitant pyridoxine is recommended in patients at risk for isoniazid-induced neuropathy, including breastfeeding infants and patients who are pregnant or have HIV, diabetes, malnutrition, alcoholism, or chronic renal failure (ATS/CDC/IDSA [Nahid 2016]; WHO 2020).

Tuberculosis, active; treatment for drug-susceptible

Tuberculosis, active; treatment for drug-susceptible (ATS/CDC/IDSA [Nahid 2016]):

Note: Always use in combination with other antitubercular drugs. Any regimens using less than once-daily dosing should administer dosing as directly observed therapy (DOT). Some experts recommend DOT for all pediatric patients. Isoniazid dosing differs depending on frequency of dosing/treatment regimen selected; consult current guidelines for detailed information (ATS/CDC/IDSA [Nahid 2016]; Red Book [AAP 2018]).

Once daily or 5 times weekly (DOT):

Infants, Children, and Adolescents <15 years, weighing ≤40 kg: Oral, IM: 10 to 15 mg/kg/dose once daily (or 5 days/week by DOT); maximum dose: 300 mg/dose.

Children and Adolescents <15 years weighing >40 kg or Adolescents ≥15 years: Oral, IM: 5 mg/kg/dose once daily (or 5 days/week by DOT); typical dose: 300 mg/dose.

Three-times-weekly DOT: Note: Three-times-weekly DOT may be used as an alternative to daily therapy in patients without HIV with noncavitary and/or smear-negative disease. Though three-times-weekly regimen is preferred to twice-weekly, data to guide dosing are limited; suggested dosing based on twice-weekly regimen.

Infants, Children, and Adolescents <15 years, weighing ≤40 kg: Oral, IM: 20 to 30 mg/kg/dose three times weekly by DOT; maximum dose: 900 mg/dose.

Children and Adolescents <15 years weighing >40 kg or Adolescents ≥15 years: Oral, IM: 15 mg/kg/dose three times weekly by DOT (typical dose: 900 mg).

Twice-weekly DOT: Note: Regimen not generally recommended; do not use in HIV patients or those with smear-positive and/or cavitary disease, and only use after completion of a 2-week once-daily (or 5-times-weekly) regimen in the intensive phase. Missed doses result in the equivalent of once-weekly dosing which has been shown to be inferior and is associated with treatment failure, relapse, and development of drug resistance.

Infants, Children, and Adolescents <15 years, weighing ≤40 kg: Oral, IM: 20 to 30 mg/kg/dose twice weekly by DOT; maximum dose: 900 mg/dose.

Children and Adolescents <15 years weighing >40 kg or Adolescents ≥15 years: Oral, IM: 15 mg/kg/dose twice weekly by DOT; typical dose: 900 mg/dose.

Duration of therapy: Treatment regimens consist of an initial 2-month intensive phase of a 4-drug regimen, followed by a continuation phase of isoniazid and rifampin. Duration of continuation phase is ≥4 months; should be longer for cavitary disease with positive cultures at completion of intensive phase (7 months), bone and joint disease (≥4 to 7 months), and CNS disease (7 to 10 months).

Tuberculosis, active; treatment for drug-resistant

Tuberculosis, active; treatment for drug-resistant: Note: Use should only be considered in patients with low-level isoniazid resistance; do not use in patients with high-level isoniazid resistance. Always use in combination with other antitubercular drugs; expert consultation for optimal regimen and duration of treatment is advised (ATS/CDC/ERS/IDSA [Nahid 2019]).

Infants, Children, and Adolescents: Oral, IM: 15 to 20 mg/kg/day as part of an appropriate combination regimen (ATS/CDC/ERS/IDSA [Nahid 2019]; Harausz 2018; WHO 2019). Administer in combination with pyridoxine (WHO 2019).

Tuberculosis, latent infection; treatment

Tuberculosis, latent infection; treatment: Preferred regimen varies between guidelines and based on patient characteristics (HHS [OI adult 2019]; HHS [OI pediatric 2019]; NTCA/CDC [Sterling 2020]); regimens should not be used in patients known or presumed to be infected with resistant strains of tuberculosis (TB) (NTCA/CDC [Sterling 2020]).

Isoniazid combination therapy: Note: Preferred regimens (NTCA/CDC [Sterling 2020]):

Rifapentine combination: Independent 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]). Only use in HIV-infected patients if antiretroviral therapy has acceptable drug-drug interactions with rifapentine (CDC [Borisov 2018]; NTCA/CDC [Sterling 2020]).

Children 2 to 11 years: Oral: Isoniazid 25 mg/kg/dose once weekly for 12 weeks (12 doses); maximum dose: 900 mg/dose (NTCA/CDC [Sterling 2020]).

Children ≥12 years and Adolescents: Oral: Isoniazid 15 mg/kg/dose once weekly for 12 weeks (12 doses), round dose up to nearest 50 or 100 mg; maximum dose: 900 mg/dose (NTCA/CDC [Sterling 2020]).

Rifampin combination: Independent of HIV status: Note: Only use in HIV-infected patients if antiretroviral therapy has acceptable drug-drug interactions with rifampin (CDC [Borisov 2018]; NTCA/CDC [Sterling 2020]).

Infants, Children, and Adolescents: Oral: Isoniazid 10 to 20 mg/kg/dose once daily (maximum dose: 300 mg/dose) for 3 months (NTCA/CDC [Sterling 2020]).

Isoniazid monotherapy: Note: Alternative regimen (NTCA/CDC [Sterling 2020]):

Infants, Children, and Adolescents; independent of HIV status:

Daily regimen: Oral: 10 to 20 mg/kg/dose once daily for 6 to 9 months; maximum dose: 300 mg/dose; while the CDC recommends a 6-month duration, 9 months may be considered; direct comparative efficacy data for 6 months versus 9 months are lacking and risk of hepatotoxicity is greater with longer durations (HHS [OI adult 2019]; HHS [OI pediatric 2019]; NTCA/CDC [Sterling 2020]). Note: Some organizations recommend an upper limit of 15 mg/kg/dose (maximum dose: 300 mg/dose) (HHS [OI pediatric 2019]; Red Book [AAP 2018]; WHO 2018).

Twice-weekly regimen: Oral: 20 to 40 mg/kg/dose twice weekly for 6 to 9 months; maximum dose: 900 mg/dose; must be administered by DOT; while the CDC recommends a 6-month duration, 9 months may be considered; direct comparative efficacy data are lacking for 6 months versus 9 months and risk of hepatotoxicity is greater with longer durations (HHS [OI adult 2019]; HHS [OI pediatric 2019]; NTCA/CDC [Sterling 2020]). Note: Some organizations recommend an upper limit of 30 mg/kg/dose (maximum dose: 900 mg/dose) (HHS [OI pediatric 2019]); Red Book [AAP 2018]; WHO 2018).

Pulmonary nontuberculous mycobacterial infection; treatment

Pulmonary nontuberculous mycobacterial infection; treatment: Limited data available:

Children and Adolescents: Oral: 10 mg/kg/dose once daily as part of an appropriate combination regimen; maximum dose: 300 mg/dose (BTS [Haworth 2017]).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

Infants, Children, and Adolescents:

Altered kidney function: No dosage adjustment necessary (ATS/CDC/IDSA [Nahid 2016]; ATS/CDC/ERS/IDSA [Nahid 2019]; WHO 2010).

Hemodialysis: Dialyzable. Based on experience in adults, no dosage adjustment necessary; administer after hemodialysis on dialysis days (ATS/CDC/IDSA [Nahid 2016]).

Dosing: Hepatic Impairment: Pediatric

Infants, Children, and Adolescents:

Baseline hepatic impairment:

Acute liver disease or previous isoniazid-associated hepatic injury: Contraindicated. For latent tuberculosis infection, defer treatment with isoniazid.

Chronic liver disease: 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. Monitor laboratory and clinical parameters frequently (ATS/CDC/IDSA [Nahid 2016]).

Hepatotoxicity during therapy (ALT or AST >3 times the ULN): Discontinue or temporarily withhold treatment.

Dosing: Older Adult

Refer to adult dosing.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Injection:

Generic: 100 mg/mL (10 mL)

Syrup, Oral:

Generic: 50 mg/5 mL (473 mL)

Tablet, Oral:

Generic: 100 mg, 300 mg

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Syrup, Oral:

Isotamine: 50 mg/5 mL (500 mL)

Generic: 50 mg/5 mL (500 mL)

Tablet, Oral:

Isotamine: 100 mg, 300 mg

Generic: 100 mg, 300 mg

Administration: Adult

Oral: Do not administer with food (bioavailability is decreased).

Intramuscular: IM injection may be used for patients who are unable to either take or absorb oral therapy. Inject deep IM into a large muscle mass.

Administration: Pediatric

Oral: Administer on an empty stomach (1 hour before or 2 hours after meals with water); if unable to swallow tablets, may crush tablet and mix in a soft food or liquid, or starch-based pudding (commercial chocolate pudding) and administer as a slurry (Cruz 2018; Peloquin 2007; Villarino 2015).

Parenteral: IM: May be administered IM in patients who are unable to either take or absorb oral therapy.

Use: Labeled Indications

Tuberculosis, active: Treatment of susceptible active tuberculosis (eg, Mycobacterium tuberculosis) infections.

Tuberculosis, latent infection: Treatment of latent tuberculosis infection (LTBI) caused by M. tuberculosis (also referred to as prophylaxis or preventive therapy). Note: To identify candidates for LTBI treatment, refer to the CDC (https://www.cdc.gov/tb/publications/ltbi/default.htm) for current recommendations.

Medication Safety Issues
International issues:

Hydra [Japan] may be confused with Hydrea brand name for hydroxyurea [US, Canada, and multiple international markets]

Adverse Reactions (Significant): Considerations
Hepatic effects

Isoniazid is associated with increased serum transaminases, hyperbilirubinemia, jaundice, and hepatitis. Asymptomatic, transient serum aminotransferase elevations may occur in 10% to 20% of patients, with 3% to 5% of elevations reaching ≥5 times the upper limit of normal. The pattern of liver injury is typically hepatocellular (Ref). Some patients may also present with drug reaction with eosinophilia and systemic symptoms. Resolution of transaminase elevations often occurs with continued isoniazid use. If isoniazid is discontinued due to liver injury, resolution usually occurs within a week; although, severe and fatal hepatotoxicity may occur. Rechallenge may result in rapid recurrence (Ref).

Mechanism: Unknown; accumulation of mono-acetyl hydrazine, a toxic intermediate of its metabolism, has been postulated, as well as an immune-mediated response (Ref).

Onset: Varied; duration of therapy prior to development of hepatotoxicity ranges from 1 week to 1 year; although, most cases occur within 2 weeks to 6 months (Ref).

Risk factors:

• Older age (higher incidence in >50 years of age) (Ref)

• Heavy alcohol consumption (Ref)

• Chronic hepatitis B or C, or HIV (Ref)

• Underlying liver disease (Ref)

• Liver transplant (Ref)

• Malnutrition (Ref)

• Postpartum females (Ref)

• Concurrent hepatotoxic medications (Ref)

• Genetic polymorphisms (eg, CYP450 2E1 and N-acetyltransferase 2 (NAT2) [ie, slow acetylation rate]) (Ref)

Neurologic effects

Isoniazid is associated with peripheral neuropathy, paresthesia, and sensory impairment, which have led to treatment disruptions (Ref). Peripheral neuropathy is the most common neurologic effect; often reversible within a few months, especially following drug discontinuation and pyridoxine (vitamin B6) supplementation (Ref). Other neurologic effects may take longer to achieve complete recovery (Ref). Preemptive pyridoxine supplementation is recommended in individuals at risk for development of peripheral neuropathies (Ref). Other neurologic effects that have been reported include seizures, optic neuritis, and encephalopathy (Ref).

Mechanism: Dose-related; peripheral neuropathy is thought to be due to a vitamin B6 deficiency or competitive inhibition of vitamin B6 action mediated by the formation of pyridoxal isonicotinyl hydrazine (Ref).

Onset: Varied; peripheral neuropathy often occurs after prolonged therapy (several months); however, cases as early as 10 days have been reported. Plasma levels of pyridoxal phosphate (active vitamin B6) are significantly reduced after 7 days of therapy (Ref).

Risk factors (peripheral neuropathy):

• Higher doses (Ref)

• Alcohol use disorder (Ref)

• Chronic kidney disease (Ref)

• Diabetes (Ref)

• HIV (Ref)

• Nutritional deficiency (Ref)

• Older age (Ref)

• Slow acetylation rate (Ref)

• Pregnant or breastfeeding females (Ref)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%: Hepatic: Increased serum transaminases (increased alanine aminotransferase, increased aspartate aminotransferase; mild and transient: 10% to 20%)

Postmarketing:

Cardiovascular: Vasculitis (Bondalapati 2014)

Dermatologic: Skin rash (exfoliative dermatitis [Rosin 1982], maculopapular rash [Ye 2017], morbilliform rash, purpuric rash [Duncan 1964]), toxic epidermal necrolysis (Lehloenya 2015)

Endocrine & metabolic: Gynecomastia (Poon 2020), hyperglycemia (Ganguly 2018), metabolic acidosis (Romero 1998), pellagra (Kabengele 2021), pyridoxine deficiency (Reeves 2004)

Gastrointestinal: Epigastric discomfort, nausea, pancreatitis (Mattioni 2012), vomiting

Hematologic & oncologic: Agranulocytosis (Mehrotra 1973), anemia (aplastic anemia, hemolytic anemia, sideroblastic anemia [Piso 2011]), eosinophilia, immune thrombocytopenia (Kuwabara 2021), lymphadenopathy, pure red cell aplasia (Hoffman 1983), thrombocytopenia (Lee 2012)

Hepatic: Bilirubinuria, hepatitis (Chalasani 2021), hepatotoxicity (Chalasani 2021), hyperbilirubinemia (Chalasani 2021), jaundice (Chalasani 2021)

Immunologic: Drug reaction with eosinophilia and systemic symptoms (Lehloenya 2015; Ye 2017)

Nervous system: Encephalopathy (Low 2019), memory impairment, paresthesia peripheral neuropathy (Arsalan 2015), seizure (Tsubouchi 2014), toxic psychosis (Alao 1998)

Neuromuscular & skeletal: Lupus-like syndrome (Cerqueira 2020), rheumatism (Good 1970)

Ophthalmic: Optic atrophy (Sutton 1955), optic neuritis (Low 2019)

Miscellaneous: Fever (Dasta 1979)

Contraindications

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

Warnings/Precautions

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with hepatic impairment.

• Renal impairment: Use with caution in patients with severe renal impairment.

Other warnings/precautions:

• Appropriate use: Multidrug regimens should be utilized for the treatment of active tuberculosis to prevent the emergence of drug resistance.

Metabolism/Transport Effects

Substrate of CYP2E1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2E1 (moderate), CYP3A4 (weak); Induces CYP2E1 (weak)

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Acetaminophen: Isoniazid may enhance the hepatotoxic effect of Acetaminophen. Isoniazid may increase the metabolism of Acetaminophen. Specifically, formation of the hepatotoxic NAPQI metabolite may be increased. Risk C: Monitor therapy

Alcohol (Ethyl): May enhance the hepatotoxic effect of Isoniazid. Risk C: Monitor therapy

ALPRAZolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ALPRAZolam. Risk C: Monitor therapy

Antacids: May decrease the absorption of Isoniazid. Risk C: Monitor therapy

Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider therapy modification

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy

CarBAMazepine: May enhance the hepatotoxic effect of Isoniazid. Isoniazid may increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy

Chlorzoxazone: Isoniazid may increase the serum concentration of Chlorzoxazone. Isoniazid may decrease the serum concentration of Chlorzoxazone. Specifically, it may decrease chlorzoxazone concentrations below baseline after isoniazid discontinuation. Risk C: Monitor therapy

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination

Corticosteroids (Systemic): May decrease the serum concentration of Isoniazid. Risk C: Monitor therapy

CycloSERINE: Isoniazid may enhance the adverse/toxic effect of CycloSERINE. Specifically, CNS toxicity may be enhanced. Risk C: Monitor therapy

CycloSPORINE (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy

CYP2E1 Inhibitors (Strong): May increase the serum concentration of Isoniazid. Risk C: Monitor therapy

Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Risk C: Monitor therapy

Ethionamide: May increase the serum concentration of Isoniazid. Isoniazid may increase the serum concentration of Ethionamide. Risk C: Monitor therapy

Finerenone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Finerenone. Risk C: Monitor therapy

Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Risk C: Monitor therapy

Fosphenytoin-Phenytoin: Isoniazid may increase the serum concentration of Fosphenytoin-Phenytoin. Risk C: Monitor therapy

Immune Checkpoint Inhibitors: Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors. Risk C: Monitor therapy

Itraconazole: Isoniazid may decrease the serum concentration of Itraconazole. Risk C: Monitor therapy

Ixabepilone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ixabepilone. Risk C: Monitor therapy

Ketoconazole (Systemic): Isoniazid may decrease the serum concentration of Ketoconazole (Systemic). Risk C: Monitor therapy

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy

Lemborexant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Risk D: Consider therapy modification

Levodopa-Containing Products: Isoniazid may diminish the therapeutic effect of Levodopa-Containing Products. Risk C: Monitor therapy

Levoketoconazole: Isoniazid may decrease the serum concentration of Levoketoconazole. Risk X: Avoid combination

Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Risk D: Consider therapy modification

Lonafarnib: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lonafarnib. Management: Avoid concurrent use of lonafarnib with weak CYP3A4 inhibitors. If concurrent use is unavoidable, reduce the lonafarnib dose to or continue at a dose of 115 mg/square meter. Monitor for evidence of arrhythmia, syncope, palpitations, or similar effects. Risk D: Consider therapy modification

Methoxyflurane: Isoniazid may increase the metabolism of Methoxyflurane. Specifically, this increased metabolism may lead to increased production of nephrotoxic metabolites. Risk X: Avoid combination

Midazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Midazolam. Risk C: Monitor therapy

NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Risk C: Monitor therapy

Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Risk X: Avoid combination

Propacetamol: Isoniazid may enhance the hepatotoxic effect of Propacetamol. Isoniazid may increase the metabolism of Propacetamol. Specifically, formation of the hepatotoxic NAPQI metabolite may be increased. Risk C: Monitor therapy

Prothionamide: Isoniazid may increase the serum concentration of Prothionamide. Prothionamide may increase the serum concentration of Isoniazid. Management: Reduce the prothionamide dose by half (do not exceed 500 mg per day in adults) if combined with isoniazid. Additionally, monitor for increased isoniazid toxicities and ensure pyridoxine supplementation is provided if these drugs are combined. Risk D: Consider therapy modification

RifAMPin: Isoniazid may enhance the hepatotoxic effect of RifAMPin. RifAMPin may decrease the serum concentration of Isoniazid. Risk C: Monitor therapy

Safinamide: May enhance the adverse/toxic effect of Isoniazid. Specifically, there is an increased risk for hypertension. Risk C: Monitor therapy

Simvastatin: CYP3A4 Inhibitors (Weak) may increase serum concentrations of the active metabolite(s) of Simvastatin. CYP3A4 Inhibitors (Weak) may increase the serum concentration of Simvastatin. Risk C: Monitor therapy

Sirolimus (Conventional): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Conventional). Risk C: Monitor therapy

Sirolimus (Protein Bound): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Protein Bound). Management: Reduce the dose of protein bound sirolimus to 56 mg/m2 when used concomitantly with a weak CYP3A4 inhibitor. Risk D: Consider therapy modification

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification

Tacrolimus (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy

Theophylline Derivatives: Isoniazid may increase the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy

Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Risk C: Monitor therapy

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification

Ubrogepant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (given at least 2 hours later if needed) of ubrogepant should be limited to 50 mg. Risk D: Consider therapy modification

Food Interactions

Administration with food significantly reduces bioavailability. Management: Avoid administration with food.

Isoniazid may decrease folic acid absorption and alters pyridoxine metabolism. Management: Increase dietary intake of folate, niacin, and magnesium.

Tyramine-containing food: Isoniazid has weak monoamine oxidase inhibiting activity and may potentially inhibit tyramine metabolism. Several case reports of mild reactions (flushing, palpitations, headache, mild increase in blood pressure, diaphoresis) after ingestion of certain types of cheese or red wine, have been reported (Self 1999; Toutoungi, 1985). Management: Manufacturer’s labeling recommends avoiding tyramine-containing foods (eg, aged or matured cheese, air-dried or cured meats including sausages and salamis; fava or broad bean pods, tap/draft beers, Marmite concentrate, sauerkraut, soy sauce, and other soybean condiments). However, the clinical relevance of the tyramine reaction for the vast majority of patients receiving isoniazid has been questioned due to isoniazid’s weak MAO inhibition and the relatively few published case reports of the interaction. Although not fully investigated, it has been proposed that the reaction has a genetic component and may only be significant in poor or intermediate acetylators since isoniazid is primarily inactivated by acetylation (DiMartini 1995; Toutoungi 1985).

Histamine-containing food: Isoniazid may also inhibit diamine oxidase resulting in headache, sweating, palpitations, flushing, diarrhea, itching, wheezing, dyspnea or hypotension to histamine-containing foods (eg, skipjack, tuna, saury, other tropical fish). Management: Manufacturer’s labeling recommends avoiding histamine-containing foods; corticosteroids and antihistamines may be administered if histamine intoxication occurs (Miki 2005).

Pregnancy Considerations

Isoniazid crosses the human placenta.

Active tuberculosis (TB) infection is associated with adverse fetal outcomes including intrauterine growth restriction, low birth weight, preterm birth, and perinatal death (Esmail 2018; Miele 2020) as well as adverse maternal outcomes, including increased risks for anemia and cesarean delivery. Placental transmission may rarely occur with active maternal disease (Miele 2020).

Due to the risks of untreated TB, isoniazid is recommended as part of the initial treatment regimen of drug-susceptible active TB when the probability of maternal disease is moderate to high. Isoniazid is associated with an increased risk of severe maternal hepatotoxicity which may require temporary drug withdrawal in pregnant and postpartum patients (Beck-Friis 2020; Gupta 2019); monthly monitoring of transaminases (ALT/AST) is recommended (HHS [OI adult 2020]). Pregnancy may increase the risk of isoniazid-associated peripheral neurotoxicity in the mother; pyridoxine supplementation is recommended in pregnant patients during treatment (ATS/CDC/IDSA [Nahid 2016]; HHS [OI adult 2020]).

Treatment of latent tuberculosis infection (LTBI) (also known as prophylaxis or preventive therapy) with isoniazid is recommended for pregnant patients with HIV coinfection who are close household contacts of persons with TB infection (HHS [OI adult 2020]; WHO 2020). Treatment of LTBI can be delayed until after delivery in some cases, considering the risk of progression to active disease (HHS [OI adult 2020]).

Pregnancy-induced physiologic changes do not alter the pharmacokinetic properties of isoniazid in a clinically significant way; dose adjustment is not needed in pregnant patients (Abdelwahab 2020).

Breastfeeding Considerations

Isoniazid and the acetylisoniazid metabolite are present in breast milk (Berlin 1979).

A range of isoniazid breast milk concentrations have been reported in the literature. Breast milk concentrations of isoniazid following oral administration vary by maternal dose and by the ability of the mother to metabolize N-acetyltransferase 2 (NAT2). Peak breast milk concentrations generally occur between 1 and 3 hours after oral administration (Berlin 1979; Garessus 2019; Hill 2019; Singh 2008). Infant exposure can be decreased by breastfeeding <0.8 or >3 hours after the maternal dose (Garessus 2019). Exposure to isoniazid via breast milk should not be considered effective treatment for the breastfeeding infant (ATS/CDC/IDSA [Nahid 2016]). Isoniazid can be detected in the urine of breastfed infants (Ricci 1954).

Isoniazid is considered compatible with breastfeeding (WHO 2002). In the treatment of drug-susceptible tuberculosis (TB), use of isoniazid is not a contraindication to breastfeeding in patients deemed noninfectious who are treated with first-line agents (ie, isoniazid) (ATS/CDC/IDSA [Nahid 2016]). Breastfed infants should be monitored for jaundice; discontinue breastfeeding or consider changing to a different maternal medication if jaundice develops (WHO 2002). Pyridoxine supplementation is recommended for the mother and infant (ATS/CDC/IDSA [Nahid 2016]).

Women with TB mastitis should breastfeed using the unaffected breast (Mathad 2012).

Dietary Considerations

Do not take with food; avoid tyramine- and/or histamine-containing foods. Increase dietary intake of folate, niacin, magnesium.

Monitoring Parameters

Baseline and periodic (more frequently in patients with higher risk for hepatitis) liver function tests (ALT and AST); sputum cultures monthly (until 2 consecutive negative cultures reported); monitoring for prodromal signs of hepatitis

Latent tuberculosis infection (LTBI) therapy: American Thoracic Society/Centers for Disease Control (ATS/CDC) recommendations: Monthly clinical evaluation, including brief physical exam for adverse events. Use should be carefully monitored in the following groups: daily users of alcohol, active chronic liver disease, severe renal dysfunction, age >35 years, concurrent use of any chronically administered drug, history of previous isoniazid discontinuation, existence of or conditions predisposing to peripheral neuropathy, pregnancy, injection drug use, women in minority groups (particularly postpartum), HIV seropositive patients. AST and ALT should be obtained at baseline and at least monthly during LTBI use. Discontinue temporarily or permanently if liver function tests >3 to 5 times ULN. Routine, periodic monitoring is recommended for any patient with an abnormal baseline or at increased risk for hepatotoxicity.

Mechanism of Action

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.

Pharmacokinetics

Note: Isoniazid is primarily metabolized by acetylation and dehydrazination. Rate of acetylation is genetically determined. Approximately 50% of Black and White patients are “slow acetylators” and the rest are “rapid acetylators.” Populations in which there is a high prevalence of “rapid acetylators” include Inuit patients (including native peoples from Alaska and Canada), East Asian patients, and patients from certain areas within Southeast Asia (eg, Thailand) (Clark 1985; Sabbagh 2011; manufacturer's labeling). Acetylation rate does not significantly alter the effectiveness, but slow acetylation may lead to higher blood levels and possibly an increase in adverse effects.

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

Pricing: US

Solution (Isoniazid Injection)

100 mg/mL (per mL): $35.21

Syrup (Isoniazid Oral)

50 mg/5 mL (per mL): $0.86

Tablets (Isoniazid Oral)

100 mg (per each): $0.15

300 mg (per each): $0.31 - $1.29

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Antimic (TH);
  • Bitub (RO, UA);
  • Cemidon (ES);
  • Curazid Forte (PH);
  • Dianicotyl (GR);
  • Dipasic (HK);
  • Eutizon (HR);
  • Fluodrazin (BR);
  • Hydra (JP);
  • I.N.H. (ZW);
  • INH Agepha (AT);
  • INH Lannacher (AT);
  • INH Waldheim (AT);
  • Inoxin (ID);
  • Iso (BD);
  • Isocid (EG);
  • Isokin (IN);
  • Isonex (ID, IN);
  • Isoniac (AR);
  • Isoniazid (AU);
  • Isoniazid Atlantic (HK);
  • Isoniazid ”Dak” (DK);
  • Isoniazid ”Oba” (DK);
  • Isoniazide Drank FNA (NL);
  • Isoniazidum (PL);
  • Isonicid (HN);
  • Isonid (BD);
  • Isozid (DE);
  • Isozide (VN);
  • Nicizina (AR);
  • Nicotibine (BE, IL, LU);
  • Nicozid (IT);
  • Nidrazid (CZ);
  • Nisozid (BD);
  • Nydrazide (PK);
  • Pulmolin (ID);
  • Pycazide (GB);
  • Rimicid (BG);
  • Rimifon (FR, GB);
  • Sheng Jun (CN);
  • Solonex (LK);
  • T.B.Zide (EG);
  • Tebilon (AT);
  • Tibinide (SE);
  • Tubilysin (FI);
  • Valifol (MX);
  • Yuhan-Zid (KR)


For country code abbreviations (show table)
  1. Abdelwahab MT, Leisegang R, Dooley KE, et al. Population pharmacokinetics of isoniazid, pyrazinamide, and ethambutol in pregnant South African women with tuberculosis and HIV. Antimicrob Agents Chemother. 2020;64(3):e01978-19. doi:10.1128/AAC.01978-19 [PubMed 31844002]
  2. Ahn C, Oh KH, Kim K, et al. Effect of peritoneal dialysis on plasma and peritoneal fluid concentrations of isoniazid, pyrazinamide, and rifampin. Perit Dial Int. 2003;23(4):362-367. [PubMed 12968844]
  3. Ahn CH, Lowell JR, Ahn SS, Ahn SI, Hurst GA. Short-course chemotherapy for pulmonary disease caused by Mycobacterium kansasii. Am Rev Respir Dis. 1983;128(6):1048-1050. doi:10.1164/arrd.1983.128.6.1048 [PubMed 6650978]
  4. Aiwale AS, Patel UA, Barvaliya MJ, Jha PR, Tripathi C. Isoniazid induced convulsions at therapeutic dose in an alcoholic and smoker patient. Curr Drug Saf. 2015;10(1):94-95. doi:10.2174/1574886309666140930151343 [PubMed 25859682]
  5. Alao AO, Yolles JC. Isoniazid-induced psychosis. Ann Pharmacother. 1998;32(9):889-891. doi:10.1345/aph.17377 [PubMed 9762376]
  6. American Academy of Pediatrics (AAP). In: Kimberlin DW, Brady MT, Jackson MA, Long SA, eds. Red Book: 2018 Report of the Committee on Infectious Diseases. 31st ed. American Academy of Pediatrics; 2018.
  7. American Academy of Pediatrics, Committee on Infectious Diseases. Chemotherapy for Tuberculosis in Infants and Children. Pediatrics. 1992;89(1):161-165. [PubMed 1728006]
  8. American Thoracic Society; CDC; Infectious Diseases Society of America. Treatment of tuberculosis. MMWR Recomm Rep. 2003;52(RR-11):1-77. [PubMed 12836625]
  9. Aronoff GR, Bennett WM, Berns JS, et al. Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children. 5th ed. American College of Physicians; 2007.
  10. Arsalan R, Sabzwari S. Isoniazid induced motor-dominant neuropathy. J Pak Med Assoc. 2015;65(10):1131-1133. [PubMed 26440850]
  11. Askgaard DS, Wilcke T, Dossing M. Hepatotoxicity Caused by the Combined Action of Isoniazid and Rifampicin. Thorax. 1995;50(2):213-214. [PubMed 7701468]
  12. Beck-Friis J, Studahl M, Yilmaz A, Andersson R, Lönnermark E. Increased risk of hepatotoxicity and temporary drug withdrawal during treatment of active tuberculosis in pregnant women. Int J Infect Dis. 2020;98:138-143. doi:10.1016/j.ijid.2020.06.069 [PubMed 32592906]
  13. Berlin CM Jr, Lee C. Isoniazid and acetylisoniazid disposition in human milk, saliva and plasma. Federation of American Societies for Experimental Biology 63rd Annual Meeting, Dallas, Texas, April 1-10, 1979. Abstracts of papers. Part I. Fed Proc. 1979;38(3, pt 1):426.
  14. Biehl JP, Nimitz HJ. Studies on the use of high dose of isoniazid. I. Toxicity studies. Am Rev Tuberc. 1954;70(3):430-441. doi:10.1164/art.1954.70.3.430 [PubMed 13189058]
  15. Blowey DL, Johnson D, Verjee Z. Isoniazid-Associated Rhabdomyolysis. Am J Emerg Med. 1995;13(5):543-544. [PubMed 7662061]
  16. Bondalapati S, V DR, Rampure D, S RR. Isoniazid induced cutaneous leukocytoclastic vasculitis in extra pulmonary tuberculosis (Pott's spine): a case report. J Clin Diagn Res. 2014;8(8):MD03-MD5. doi:10.7860/JCDR/2014/9000.4688 [PubMed 25302231]
  17. Borisov AS, Bamrah Morris S, Njie GJ, et al. Update of recommendations for use of once-weekly isoniazid-rifapentine regimen to treat latent mycobacterium tuberculosis infection. MMWR Morb Mortal Wkly Rep. 2018;67(25):723-726. doi:10.15585/mmwr.mm6725a5 [PubMed 29953429]
  18. Bredemann JA, Krechel SW, Eggers GW Jr. Treatment of Refractory Seizures in Massive Isoniazid Overdose. Anesth Analg. 1990;71(5):554-557. [PubMed 2221419]
  19. Brent J, Vo N, Kulig K, et al. Reversal of prolonged isoniazid-induced coma by pyridoxine. Arch Intern Med. 1990;150(8):1751-1753. [PubMed 2152443]
  20. Brown CV. Acute Isoniazid Poisoning. Am Rev Respir Dis. 1972;105(2):206-216. [PubMed 5009799]
  21. Carr W, Kurbatova E, Starks A, Goswami N, Allen L, Winston C. Interim guidance: 4-month rifapentine-moxifloxacin regimen for the treatment of drug-susceptible pulmonary tuberculosis - United States, 2022. MMWR Morb Mortal Wkly Rep. 2022;71(8):285-289. doi:10.15585/mmwr.mm7108a1 [PubMed 35202353]
  22. Centers for Disease Control and Prevention (CDC) and American Thoracic Society. Update: Adverse Event Data and Revised American Thoracic Society/CDC Recommendations Against the Use of Rifampin and Pyrazinamide for Treatment of Latent Tuberculosis Infection - United States, 2003. MMWR Morb Mortal Wkly Rep. 2003;52(31):735-739. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5231a4.htm. [PubMed 12904741]
  23. Centers for Disease Control and Prevention (CDC). Severe Isoniazid-Associated Liver Injuries Among Persons Being Treated for Latent Tuberculosis Infection -- United States, 2004-08. MMWR Morb Mortal Wkly Rep. 2010;59(8):224-229. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5908a3.htm [PubMed 20203555]
  24. Cerqueira A, Seco T, Paiva D, Martins H, Cotter J. Isoniazid-induced lupus: when the cure can be lethal. Cureus. 2020;12(3):e7311. doi:10.7759/cureus.7311 [PubMed 32313752]
  25. Chaitanya V, Sangeetha B, Reddy MH, et al. Isoniazid cerebellitis in a peritoneal dialysis patient. Nephrology (Carlton). 2016;21(5):442. doi:10.1111/nep.12592 [PubMed 27103355]
  26. Chalasani NP, Hayashi PH, Bonkovsky HL, et al. ACG Clinical Guideline: the diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol. 2014;109(7):950-966. [PubMed 24935270]
  27. Chalasani NP, Maddur H, Russo MW, Wong RJ, Reddy KR; Practice Parameters Committee of the American College of Gastroenterology. ACG clinical guideline: diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol. 2021;116(5):878-898. doi:10.14309/ajg.0000000000001259 [PubMed 33929376]
  28. Cheung WC, Lo CY, Lo WK, Ip M, Cheng IK. Isoniazid induced encephalopathy in dialysis patients. Tuber Lung Dis. 1993;74(2):136-139. doi:10.1016/0962-8479(93)90042-V [PubMed 8324207]
  29. Choudhary CR, Kumari J, Advani M. Isoniazid induced early-onset of motor dominant neuropathy and treatment with high dose of pyridoxine. Indian J Tuberc. 2018;65(2):175-176. doi:10.1016/j.ijtb.2017.04.004 [PubMed 29579435]
  30. Citak A, Kaya O, Uçsel R, Karaböcüoğlu M, Uzel N. Acute isoniazid neurotoxicity in childhood. Turk J Pediatr. 2002;44(1):54-57. [PubMed 11858381]
  31. Clark DW. Genetically determined variability in acetylation and oxidation. Therapeutic implications. Drugs. 1985;29(4):342-375. doi:10.2165/00003495-198529040-00003 [PubMed 2859977]
  32. Constantinescu SM, Buysschaert B, Haufroid V, Broly F, Jadoul M, Morelle J. Chronic dialysis, NAT2 polymorphisms, and the risk of isoniazid-induced encephalopathy - case report and literature review. BMC Nephrol. 2017;18(1):282. doi:10.1186/s12882-017-0703-6 [PubMed 28870161]
  33. Cruz AT, Starke JR. Completion rate and safety of tuberculosis infection treatment with shorter regimens. Pediatrics. 2018;141(2):e20172838. doi:10.1542/peds.2017-2838 [PubMed 29363561]
  34. Dasta JF, Prior JA, Kurzrok S. Isoniazid-induced fever. Chest. 1979;75(2):196-197. doi:10.1378/chest.75.2.196 [PubMed 421557]
  35. Den Boon S, Matteelli A, Ford N, Getahun H. Continuous isoniazid for the treatment of latent tuberculosis infection in people living with HIV. AIDS. 2016;30(5):797-801. doi:10.1097/QAD.0000000000000985 [PubMed 26730567]
  36. DiMartini A. Isoniazid, Tricyclics and the “Cheese Reaction." Int Clin Psychopharmacol. 1995;10(3):197-8. [PubMed 8675973]
  37. Dooley KE, Miyahara S, von Groote-Bidlingmaier F, et al; A5312 Study Team. Early bactericidal activity of different isoniazid doses for drug resistant TB (INHindsight): a randomized open-label clinical trial. Am J Respir Crit Care Med. 2020;201(11):1416–24. doi:10.1164/rccm.201910-1960OC [PubMed 31945300]
  38. Dorman SE, Nahid P, Kurbatova EV, et al. Four-month rifapentine regimens with or without moxifloxacin for tuberculosis. N Engl J Med. 2021;384(18):1705-1718. doi:10.1056/NEJMoa2033400 [PubMed 33951360]
  39. Duncan JT. Nonthrombopenic purpura resulting from sensitivity to isoniazid. Am Rev Respir Dis. 1964;89:103-104. doi:10.1164/arrd.1964.89.1.103 [PubMed 14114404]
  40. Esmail A, Sabur NF, Okpechi I, Dheda K. Management of drug-resistant tuberculosis in special sub-populations including those with HIV co-infection, pregnancy, diabetes, organ-specific dysfunction, and in the critically ill. J Thorac Dis. 2018;10(5):3102-3118. doi:10.21037/jtd.2018.05.11 [PubMed 29997980]
  41. Fernández-Villar A, Sopeña B, Vázquez R, et al. Isoniazid hepatotoxicity among drug users: the role of hepatitis C. Clin Infect Dis. 2003;36(3):293-298. doi:10.1086/345906 [PubMed 12539070]
  42. Franks AL, Binkin NJ, Snider DE Jr, Rokaw WM, Becker S. Isoniazid hepatitis among pregnant and postpartum Hispanic patients. Public Health Rep. 1989;104(2):151-155. [PubMed 2495549]
  43. Frieden TR, Sterling TR, Munsiff SS, et al. Tuberculosis. Lancet. 2003;362(9387):887-899. [PubMed 13678977]
  44. Ganguly RJ, Abraham RR, Prasad R, Rao BC. Hyperglycaemia induced by isoniazid preventive therapy. J Family Med Prim Care. 2018;7(5):1123-1125. doi:10.4103/jfmpc.jfmpc_197_18 [PubMed 30598974]
  45. Garessus EDG, Mielke H, Gundert-Remy U. Exposure of infants to isoniazid via breast milk after maternal drug intake of recommended doses is clinically insignificant irrespective of metaboliser status. A physiologically-based pharmacokinetic (PBPK) modelling approach to estimate drug exposure of infants via breast-feeding. Front Pharmacol. 2019;10:5. doi:10.3389/fphar.2019.00005 [PubMed 30723406]
  46. Gold CH, Buchanan N, Tringham V, Viljoen M, Strickwold B, Moodley GP. Isoniazid pharmacokinetics in patients in chronic renal failure. Clin Nephrol. 1976;6(2):365-369. [PubMed 954244]
  47. Good AE. Rheumatism and chemotherapy of tuberculosis. Ann Intern Med. 1970;72(5):752-753. doi:10.7326/0003-4819-72-5-752 [PubMed 5311006]
  48. Gupta A, Montepiedra G, Aaron L, et al; IMPAACT P1078 TB APPRISE Study Team. Isoniazid preventive therapy in HIV-infected pregnant and postpartum women. N Engl J Med. 2019;381(14):1333-1346. doi:10.1056/NEJMoa1813060 [PubMed 31577875]
  49. Harausz EP, Garcia-Prats AJ, Law S, et al. Treatment and outcomes in children with multidrug-resistant tuberculosis: A systematic review and individual patient data meta-analysis. PLoS Med. 2018;15(7):e1002591. doi:10.1371/journal.pmed.1002591 [PubMed 29995958]
  50. Havlir DV, Barnes PF. Tuberculosis in Patients With Human Immunodeficiency Virus Infection. N Engl J Med. 1999;340(5):367-373. [PubMed 9929528]
  51. Haworth CS, Banks J, Capstick T, et al. British Thoracic Society guidelines for the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD). Thorax. 2017;72(Suppl 2):ii1-ii64. doi:10.1136/thoraxjnl-2017-210927 [PubMed 29054853]
  52. Hill WC, Paruolo JB, Giovino AC. Prophylaxis for tuberculosis in pregnant women. Clin Obstet Gynecol. 2019;62(4):846-856. doi:10.1097/GRF.0000000000000465 [PubMed 31192819]
  53. Hoffman R, McPhedran P, Benz EJ Jr, Duffy TP. Isoniazid-induced pure red cell aplasia. Am J Med Sci. 1983;286(1):2-9. doi:10.1097/00000441-198307000-00001 [PubMed 6869413]
  54. Huang YS, Chern HD, Su WJ, et al. Cytochrome P450 2E1 genotype and the susceptibility to antituberculosis drug-induced hepatitis. Hepatology. 2003;37(4):924-930. doi:10.1053/jhep.2003.50144 [PubMed 12668988]
  55. Hughes HB, Biehl JP, Jones AP, Schmidt LH. Metabolism of isoniazid in man as related to the occurrence of peripheral neuritis. Am Rev Tuberc. 1954;70(2):266-273. doi:10.1164/art.1954.70.2.266 [PubMed 13180863]
  56. Iseman MD. Treatment of Multidrug-Resistant Tuberculosis. N Engl J Med. 1993;329(11):784-791. [PubMed 8350889]
  57. Isoniazid. In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. National Institute of Diabetes and Digestive and Kidney Diseases; 2018. [PubMed 31644063]
  58. Isoniazid injection [prescribing information]. Princeton, NJ: Sandoz Inc; April 2019.
  59. Isoniazid oral solution [prescribing information]. Farmville, NC: CMP Pharma; March 2018.
  60. Isoniazid tablets [prescribing information]. North Wales, PA: Teva Pharmaceuticals; July 2016.
  61. Jimenez-Lucho VE, del Busto R, Odel J. Isoniazid and ethambutol as a cause of optic neuropathy. Eur J Respir Dis. 1987;71(1):42-45. [PubMed 3115809]
  62. Kabengele C, M'hango H, Mweemba D, Malumani M. A peculiarly characterised case of isoniazid-induced pellagra- 2 Ds and a C: a case report. Pan Afr Med J. 2021;39:73. doi:10.11604/pamj.2021.39.73.28072 [PubMed 34422196]
  63. Karmon G, Savir H, Zevin D, Levi J. Bilateral optic neuropathy due to combined ethambutol and isoniazid treatment. Ann Ophthalmol. 1979;11(7):1013-1017. [PubMed 384871]
  64. Kergueris MF, Bourin M, Larousse C. Pharmacokinetics of Isoniazid: Influence of Age. Eur J Clin Pharmacol. 1986;30(3):335-340. [PubMed 3732371]
  65. Khan S, Mandal RK, Elasbali AM, et al. Pharmacogenetic association between NAT2 gene polymorphisms and isoniazid induced hepatotoxicity: trial sequence meta-analysis as evidence. Biosci Rep. 2019;39(1):BSR20180845. doi:10.1042/BSR20180845 [PubMed 30509962]
  66. Kopanoff DE, Snider DE Jr, Caras GJ. Isoniazid-related hepatitis: a U.S. Public Health Service cooperative surveillance study. Am Rev Respir Dis. 1978;117(6):991-1001. doi:10.1164/arrd.1978.117.6.991 [PubMed 666111]
  67. Kuwabara G, Tazoe K, Imoto W, et al. Isoniazid-induced immune thrombocytopenia. Intern Med. 2021;60(22):3639-3643. doi:10.2169/internalmedicine.6520-20 [PubMed 34053983]
  68. Lee EJ, Lee SH, Kim YE, et al. A case of isoniazid-induced thrombocytopenia: recovery with immunoglobulin therapy. Intern Med. 2012;51(7):745-748. doi:10.2169/internalmedicine.51.6296 [PubMed 22466831]
  69. Lehloenya RJ, Muloiwa R, Dlamini S, Gantsho N, Todd G, Dheda K. Lack of cross-toxicity between isoniazid and ethionamide in severe cutaneous adverse drug reactions: a series of 25 consecutive confirmed cases. J Antimicrob Chemother. 2015;70(9):2648-2651. doi:10.1093/jac/dkv158 [PubMed 26142408]
  70. Loto OM, Awowole I. Tuberculosis in pregnancy: a review. J Pregnancy. 2012;2012:379271. [PubMed 22132339]
  71. Low JM, Wong KW. Isoniazid-induced encephalopathy in an end-stage renal disease patient - a case report and literature review. Med J Malaysia. 2019;74(6):553-554. [PubMed 31929489]
  72. Lubing HN. Peripheral neuropathy in tuberculosis patients treated with isoniazid. Am Rev Tuberc. 1953;68(3):458-461. doi:10.1164/art.1953.68.3.458 [PubMed 13080603]
  73. Malone RS, Fish DN, Spiegel DM, Childs JM, Peloquin CA. The effect of hemodialysis on isoniazid, rifampin, pyrazinamide, and ethambutol. Am J Respir Crit Care Med. 1999;159(5 Pt 1):1580-1584. doi:10.1164/ajrccm.159.5.9810034 [PubMed 10228130]
  74. Martinjak-Dvorsek I, Gorjup V, Horvat M, Noc M. Acute isoniazid neurotoxicity during preventive therapy. Crit Care Med. 2000;28(2):567-568. doi:10.1097/00003246-200002000-00047 [PubMed 10708202]
  75. Mathad JS, Gupta A. Tuberculosis in pregnant and postpartum women: epidemiology, management, and research gaps. Clin Infect Dis. 2012;55(11):1532-1549. doi:10.1093/cid/cis732 [PubMed 22942202]
  76. Mattioni S, Zamy M, Mechai F, et al. Isoniazid-induced recurrent pancreatitis. JOP. 2012;13(3):314-316. [PubMed 22572141]
  77. Mehrotra TN, Gupta SK. Agranulocytosis following isoniazid. Report of a case. Indian J Med Sci. 1973;27(5):392-393. [PubMed 4746240]
  78. Miele K, Bamrah Morris S, Tepper NK. Tuberculosis in pregnancy. Obstet Gynecol. 2020;135(6):1444-1453. doi:10.1097/AOG.0000000000003890 [PubMed 32459437]
  79. Miki M, Ishikawa T, Okayama H. An outbreak of histamine poisoning after ingestion of the ground saury paste in eight patients taking isoniazid in tuberculous ward. Intern Med. 2005;44(11):1133-1136. [PubMed 16357449]
  80. Nahid P, Dorman SE, Alipanah N, et al. Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: treatment of drug-susceptible tuberculosis. Clin Infect Dis. 2016;63(7):e147-e195. doi:10.1093/cid/ciw376 [PubMed 27516382]
  81. Nahid P, Mase SR, Migliori GB, et al. Treatment of drug-resistant tuberculosis. An official ATS/CDC/ERS/IDSA clinical practice guideline. Am J Respir Crit Care Med. 2019;200(10):e93-e142. doi:10.1164/rccm.201909-1874ST [PubMed 31729908]
  82. Naidoo A, Naidoo K, Yende-Zuma N, et al. Changes to antiretroviral drug regimens during integrated TB-HIV treatment: results of the SAPiT trial. Antivir Ther. 2014;19(2):161-169. doi:10.3851/IMP2701 [PubMed 24176943]
  83. Navalkele B, Bueno Rios MX, Wofford JD, Kumar V, Webb RM. Seizures in an immunocompetent adult from treatment of latent tuberculosis infection: is isoniazid to blame? Open Forum Infect Dis. 2020;7(5):ofaa144. doi:10.1093/ofid/ofaa144 [PubMed 32462048]
  84. Noble A. Antituberculous Therapy and Acute Liver Failure. Lancet. 1995;345(8953):867.
  85. Peloquin CA, Durbin D, Childs J, Sterling TR, Weiner M. Stability of antituberculosis drugs mixed in food. Clin Infect Dis. 2007;45(4):521. [PubMed 17638210]
  86. Piso RJ, Kriz K, Desax MC. Severe isoniazid related sideroblastic anemia. Hematol Rep. 2011;3(1):e2. doi:10.4081/hr.2011.e2 [PubMed 22184524]
  87. Poon SWY, Siu KK, Tsang AMC. Isoniazid-induced gynaecomastia: report of a paediatric case and review of literature. BMC Endocr Disord. 2020;20(1):160. doi:10.1186/s12902-020-00639-9 [PubMed 33109161]
  88. Prevention and Treatment of Tuberculosis Among Patients Infected With Human Immunodeficiency Virus: Principles of Therapy and Revised Recommendations. Centers for Disease Control and Prevention. MMWR Recomm Rep. 1998;47(RR-20):1-58.
  89. Rabassa AA, Trey G, Shukla U, et al. Isoniazid-Induced Acute Pancreatitis. Ann Intern Med. 1994;121(6):433-434. [PubMed 8053617]
  90. Rana P, Roy V, Ahmad J. Drug-induced optic neuropathy in a case of extensively drug-resistant pulmonary tuberculosis. J Basic Clin Physiol Pharmacol. 2018;30(1):139-140. doi:10.1515/jbcpp-2018-0007 [PubMed 30173204]
  91. Reeves RR, Liberto V. Confusion associated with isoniazid-induced pyridoxine deficiency. Psychosomatics. 2004;45(6):537-538. doi:10.1176/appi.psy.45.6.537 [PubMed 15546832]
  92. Ricci G, Copaitich T. Elimination of orally administered isoniazid in human milk. Rass Clin Ter. 1954;53(4):209-214. [PubMed 14372127]
  93. Romero JA, Kuczler FJ Jr. Isoniazid overdose: recognition and management. Am Fam Physician. 1998;57(4):749-752. [PubMed 9490997]
  94. Rosin MA, King LE Jr. Isoniazid-induced exfoliative dermatitis. South Med J. 1982;75(1):81. doi:10.1097/00007611-198201000-00026 [PubMed 6459647]
  95. Sabbagh A, Darlu P, Crouau-Roy B, Poloni ES. Arylamine N-acetyltransferase 2 (NAT2) genetic diversity and traditional subsistence: a worldwide population survey. PLoS One. 2011;6(4):e18507. doi:10.1371/journal.pone.0018507 [PubMed 21494681]
  96. Saukkonen JJ, Cohn DL, Jasmer RM, et al. An official ATS statement: hepatotoxicity of antituberculosis therapy. Am J Respir Crit Care Med. 2006;174(8):935-952. [PubMed 17021358]
  97. Sauret J, Hernández-Flix S, Castro E, Hernández L, Ausina V, Coll P. Treatment of pulmonary disease caused by Mycobacterium kansasii: results of 18 vs 12 months' chemotherapy. Tuber Lung Dis. 1995;76(2):104-108. doi:10.1016/0962-8479(95)90550-2 [PubMed 7780090]
  98. Scharman EJ, Rosencrane JG. Isoniazid Toxicity: A Survey of Pyridoxine Availability. Am J Emerg Med. 1994;12(3):386-388.
  99. Schluger NW, Heysell SK, Friedland G. Treatment of drug-resistant pulmonary tuberculosis in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed May 25, 2022.
  100. Self TH, Chrisman CR, Baciewicz AM, et al. Isoniazid Drug and Food Interactions. Am J Med Sci. 1999;317(5):304-311. [PubMed 10334118]
  101. Sharieff G, Shad JA. Early Recognition of Isoniazid Overdose. Hosp Physician. 1995;31(5):22-22.
  102. Si M, Li H, Chen Y, Peng H. Ethambutol and isoniazid induced severe neurotoxicity in a patient undergoing continuous ambulatory peritoneal dialysis. BMJ Case Rep. 2018;2018:bcr2017223187. doi:10.1136/bcr-2017-223187 [PubMed 29776936]
  103. Sievers ML, Herrier RN. Treatment of Acute Isoniazid Toxicity. Am J Hosp Pharm. 1975;32(2):202-206. [PubMed 1136966]
  104. Singh N, Golani A, Patel Z, Maitra A. Transfer of isoniazid from circulation to breast milk in lactating women on chronic therapy for tuberculosis. Br J Clin Pharmacol. 2008;65(3):418-422. [PubMed 18093257]
  105. Snider DE Jr, Caras GJ. Isoniazid-associated hepatitis deaths: a review of available information. Am Rev Respir Dis. 1992;145(2 pt 1):494-497. doi:10.1164/ajrccm/145.2_Pt_1.494 [PubMed 1736764]
  106. Snider DE Jr. Pyridoxine supplementation during isoniazid therapy. Tubercle. 1980;61(4):191-196. doi:10.1016/0041-3879(80)90038-0 [PubMed 6269259]
  107. Starke JR. Modern Approach to the Diagnosis and Treatment of Tuberculosis in Children. Pediatr Clin North Am. 1988;35(3):441-464. [PubMed 3287309]
  108. Starke JR. Multidrug Therapy for Tuberculosis in Children. Pediatr Infect Dis J. 1990;9(11):785-793. [PubMed 2124671]
  109. Sterling TR, Njie G, Zenner D, et al. Guidelines for the treatment of latent tuberculosis infection: recommendations from the National Tuberculosis Controllers Association and CDC, 2020. MMWR Recomm Rep. 2020;69(1):1-11. doi:10.15585/mmwr.rr6901a1 [PubMed 32053584]
  110. Sterling TR, Villarino ME, Borisov AS, et al; TB Trials Consortium PREVENT TB Study Team. Three months of rifapentine and isoniazid for latent tuberculosis infection. N Engl J Med. 2011;365(23):2155-2166. doi:10.1056/NEJMoa1104875 [PubMed 22150035]
  111. Sterling TR, Scott NA, Miro JM, et al; Tuberculosis Trials Consortium; the AIDS Clinical Trials Group for the PREVENT TB Trial (TBTC Study 26ACTG 5259). Three months of weekly rifapentine and isoniazid for treatment of Mycobacterium tuberculosis infection in HIV-coinfected persons. AIDS. 2016;30(10):1607-1615. doi:10.1097/QAD.0000000000001098 [PubMed 27243774]
  112. Sutton PH, Beattie PH. Optic atrophy after administration of isoniazid with P.A.S. Lancet. 1955;268(6865):650-651. doi:10.1016/s0140-6736(55)90321-4 [PubMed 14354959]
  113. Tajender V, Saluja J. INH induced status epilepticus: response to pyridoxine. Indian J Chest Dis Allied Sci. 2006;48(3):205-206. [PubMed 18610679]
  114. Toutoungi M, Carroll RL, Enrico JF, et al. Cheese, Wine, and Isoniazid. Lancet. 1985;2(8456):671. [PubMed 2863660]
  115. Tsubouchi K, Ikematsu Y, Hashisako M, Harada E, Miyagi H, Fujisawa N. Convulsive seizures with a therapeutic dose of isoniazid. Intern Med. 2014;53(3):239-242. doi:10.2169/internalmedicine.53.1303 [PubMed 24492693]
  116. US Department of Health and Human Services (HHS) Panel on Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf. Accessed June 2020.
  117. US Department of Health and Human Services (HHS) Panel on Opportunistic Infections in HIV-Exposed and HIV-Infected Children. Guidelines for prevention and treatment of opportunistic infections in HIV-exposed and HIV-infected children. https://aidsinfo.nih.gov/contentfiles/lvguidelines/oi_guidelines_pediatrics.pdf. Updated December 9, 2019. Accessed March 3, 2020.
  118. Van Scoy RE, Wilkowske CJ. Antituberculous Agents: Isoniazid, Rifampin, Streptomycin, Ethambutol, and Pyrazinamide. Mayo Clin Proc. 1983; 58(4):233-240. [PubMed 6834890]
  119. Villarino ME, Scott NA, Weis SE, et al; International Maternal Pediatric and Adolescents AIDS Clinical Trials Group; Tuberculosis Trials Consortium. Treatment for preventing tuberculosis in children and adolescents: a randomized clinical trial of a 3-month, 12-dose regimen of a combination of rifapentine and isoniazid. JAMA Pediatr. 2015;169(3):247-255. doi:10.1001/jamapediatrics.2014.3158 [PubMed 25580725]
  120. Vir SC, Love AH. Vitamin B6 status of the hospitalized aged. Am J Clin Nutr. 1978;31(8):1383-1391. doi:10.1093/ajcn/31.8.1383 [PubMed 677075]
  121. Visser ME, Texeira-Swiegelaar C, Maartens G. The short-term effects of anti-tuberculosis therapy on plasma pyridoxine levels in patients with pulmonary tuberculosis. Int J Tuberc Lung Dis. 2004;8(2):260-262. [PubMed 15139457]
  122. Vuilleumier N, Rossier MF, Chiappe A, et al. CYP2E1 genotype and isoniazid-induced hepatotoxicity in patients treated for latent tuberculosis. Eur J Clin Pharmacol. 2006;62(6):423-429. doi:10.1007/s00228-006-0111-5 [PubMed 16770646]
  123. Walsh KF, Vilbrun SC, Souroutzidis A, et al. Improved outcomes with high-dose isoniazid in multidrug-resistant tuberculosis treatment in Haiti. Clin Infect Dis. 2019;69(4):717-719. doi:10.1093/cid/ciz039 [PubMed 30698688]
  124. Wason S, LaCoutore PG, Lovejoy FH Jr. Single High-Dose Pyridoxine Treatment for Isoniazid Overdose. JAMA. 1981;246(10):1102-1104. [PubMed 7265398]
  125. Weber WW, Hein DW. Clinical pharmacokinetics of isoniazid. Clin Pharmacokinet. 1979;4(6):401-422. doi:10.2165/00003088-197904060-00001 [PubMed 391461]
  126. World Health Organization (WHO). Breastfeeding and maternal medication, recommendations for drugs in the eleventh WHO model list of essential drugs. 2002. http://www.who.int/maternal_child_adolescent/documents/55732/en/
  127. World Health Organization (WHO). Latent tuberculosis infection: updated and consolidated guidelines for programmatic management. Geneva, Switzerland: World Health Organization; 2018. http://www.ncbi.nlm.nih.gov/books/NBK531235/. [PubMed 30277688]
  128. World Health Organization (WHO). Treatment of Tuberculosis Guidelines. 4th ed. Geneva, Switzerland: WHO Press; 2010.
  129. World Health Organization (WHO). WHO consolidated guidelines on tuberculosis: tuberculosis preventive treatment: module 1: prevention [Internet]. Geneva: World Health Organization; 2020. https://www.who.int/publications/i/item/who-consolidated-guidelines-on-tuberculosis-module-1-prevention-tuberculosis-preventive-treatment.
  130. World Health Organization (WHO). WHO consolidated guidelines on drug-resistant tuberculosis treatment. World Health Organization; 2019.
  131. Ye YM, Hur GY, Kim SH, et al. Drug-specific CD4+ T-cell immune responses are responsible for antituberculosis drug-induced maculopapular exanthema and drug reaction with eosinophilia and systemic symptoms syndrome. Br J Dermatol. 2017;176(2):378-386. doi:10.1111/bjd.14839 [PubMed 27373553]
  132. Yoshikawa TT. Tuberculosis in Aging Adults. J Am Geriatr Soc. 1992;40(2):178-187. [PubMed 1740604]
  133. Zaoui A, Abdelghani A, Ben Salem H, et al. Early-onset severe isoniazid-induced motor-dominant neuropathy: a case report. East Mediterr Health J. 2012;18(3):298-299. doi:10.26719/2012.18.3.298 [PubMed 22574487]
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