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Isoniazid

Pronunciation

Pronunciation

(eye soe NYE a zid)

Index Terms

  • INH
  • Isonicotinic Acid Hydrazide

Dosage Forms

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

Pharmacologic Category

  • Antitubercular Agent

Pharmacology

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

Metabolism

Hepatic to acetylisoniazid with decay rate determined genetically by acetylation phenotype; undergoes further hydrolysis to isonicotinic acid and acetylhydrazine

Excretion

Urine (75% to 95% as unchanged drug and metabolites); small amounts excreted in feces and saliva

Time to Peak

Serum: 1 to 2 hours

Half-Life Elimination

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

Protein Binding

10% to 15%

Use: Labeled Indications

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

Latent tuberculosis infection (LTBI): Treatment of LTBI caused by Mycobacterium tuberculosis (also referred to as prophylaxis or preventive therapy). Note: To identify candidates for LTBI treatment, refer to CDC guidelines (http://www.cdc.gov/tb/publications/ltbi/pdf/TargetedLTBI.pdf) for current recommendations.

Use: Unlabeled

Treatment on nontuberculous mycobacterium (eg. M. kansasii)

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

Dosing: Adult

Recommendations often change due to resistant strains and newly-developed information; consult CDC for current recommendations. Intramuscular injection is available for patients who are unable to either take or absorb oral therapy.

Tuberculosis, active (drug susceptible; excludes meningitis): Oral, IM: Always given in combination with other antitubercular drugs. Note: Concomitant administration of pyridoxine is recommended in malnourished patients or those prone to neuropathy (eg, patients with HIV-infection, diabetes, or chronic alcohol abusers). In the initial dosing phase, ethambutol may be discontinued if drug susceptibility studies demonstrate susceptibility to isoniazid, rifampin and pyrazinamide (CDC 2011).

CDC recommendations (MMWR 2003): Initial: 5 mg/kg/day once daily (usual dose: 300 mg daily) with concomitant rifampin, pyrazinamide and with or without ethambutol for 8 weeks.

Continuation phase: 5 mg/kg/day once daily (usual dose: 300 mg daily) with concomitant rifampin for 18 weeks.

Note: The above is the CDC preferred regimen (CDC 2011)

or

Initial phase: 5 mg/kg/day once daily (usual dose: 300 mg daily) with concomitant rifampin, pyrazinamide and with or without ethambutol for 2 weeks, followed by 15 mg/kg/dose 2 times weekly (maximum: 900 mg per dose) with concomitant rifampin, pyrazinamide and with or without ethambutol for 6 weeks.

Continuation phase: 15 mg/kg/dose 2 times weekly (maximum: 900 mg per dose) with concomitant rifampin for 18 weeks.

or

Initial: 15 mg/kg/dose 3 times weekly (maximum: 900 mg per dose) with concomitant rifampin, pyrazinamide and with or without ethambutol for 8 weeks.

Continuation phase: 15 mg/kg/dose 3 times weekly (maximum: 900 mg per dose) with concomitant rifampin for 18 weeks.

Note: Treatment may be defined by the number of doses administered (eg, CDC preferred regimen involves 182 doses of INH and rifampin, and 56 doses of pyrazinamide [CDC 2011]).

Tuberculosis, active, meningitis (drug susceptible): Oral, IM: Always given in combination with other antitubercular drugs. Note: Concomitant administration of pyridoxine is recommended in malnourished patients or those prone to neuropathy (eg, patients with HIV-infection, diabetes or chronic alcohol abusers).

CDC recommendations (MMWR 2003): Initial: 5 mg/kg once daily (usual dose: 300 mg) with concomitant rifampin, pyrazinamide and ethambutol for 8 weeks; dexamethasone is given concomitantly in the first 6 weeks

Continuation phase: 5 mg/kg/day once daily (maximum: 300 mg daily) with concomitant rifampin for 7 to 10 months.

Note: The above is the CDC preferred regimen (MMWR 2003)

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).

CDC recommendations (CDC 2013):

Non-HIV exposed/infected: 5 mg/kg (maximum: 300 mg per dose) once daily for 6 or 9 months or 15 mg/kg (maximum: 900 mg per dose) twice weekly for 6 or 9 months. Note: 9 months is optimal; 6 months may be considered to reduce costs of therapy and improve adherence.

HIV-exposed/-infected patients who are receiving antiretroviral therapy: 5 mg/kg (maximum: 300 mg per dose) once daily for 9 months or 15 mg/kg (maximum: 900 mg per dose) twice weekly for 9 months. Note: LTBI treatment is recommended in HIV-infected patients testing positive for LTBI (but have no evidence of TB disease and no history of treatment for active or LTBI) or in HIV-infected close contacts of anyone who has infectious TB (regardless of screening tests for LTBI). LTBI treatment is not associated with clinical benefit or recommended in HIV infected patients who are anergic and who have not had recent contact with anyone with infectious TB (HHS [OI adult 2015])

Alternate regimen: 15 mg/kg/dose (maximum 900 mg) once weekly in combination with rifapentine for 12 weeks. Note: The rifapentine-containing regimen may only be used in patients who are not pregnant and/or not expecting to become pregnant; if used in HIV-infected patients, it may only be used in otherwise healthy HIV-infected patients not receiving antiretroviral therapy (ART) (high risk of drug-drug interactions with rifapentine) (CDC 2013; HHS [adult] 2015).

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).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Recommendations often change due to resistant strains and newly-developed information; consult CDC for current recommendations. Intramuscular injection is available for patients who are unable to either take or absorb oral therapy.

Tuberculosis, active (drug susceptible; excludes meningitis): Always given in combination with other antitubercular drugs. In the initial dosing phase, ethambutol may be discontinued if drug susceptibility studies demonstrate susceptibility to isoniazid, rifampin and pyrazinamide (CDC 2011).

Infants, Children, and Adolescents: Oral, IM:

CDC recommendations (MMWR 2003): Initial: 10 to 15 mg/kg/day once daily (maximum dose: 300 mg daily) with concomitant rifampin and pyrazinamide, with or without ethambutol for 8 weeks.

Continuation phase: 10 to 15 mg/kg/day once daily (maximum dose: 300 mg daily) with concomitant rifampin for 18 weeks.

Note: The above is the CDC preferred regimen (CDC 2011)

or

Initial phase 1: 10 to 15 mg/kg/day once daily (maximum dose: 300 mg daily) with concomitant rifampin, pyrazinamide and with or without ethambutol for 2 weeks, followed by:

Initial phase 2: 20 to 30 mg/kg/dose 2 times weekly (maximum: 900 mg per dose) with concomitant rifampin, pyrazinamide and with or without ethambutol for 6 weeks.

Continuation phase: 20 to 30 mg/kg/dose 2 times weekly (maximum: 900 mg per dose) with concomitant rifampin for 18 weeks.

Alternate recommendations (Red Book [AAP 2012]): Initial: 10 to 15 mg/kg once daily (maximum dose: 300 mg) or 20 to 30 mg/kg 2 times weekly (maximum dose: 900 mg) with concomitant rifampin, pyrazinamide and ethambutol for 2 months

Continuation phase: 10 to 15 mg/kg once daily (maximum dose: 300 mg) or 20 to 30 mg/kg 2 times weekly (maximum dose: 900 mg) with concomitant rifampin for 4 months.

Tuberculosis, active, meningitis (drug susceptible): Always given in combination with other antitubercular drugs. Note: Concomitant administration of pyridoxine is recommended in malnourished patients or those prone to neuropathy (eg, patients with HIV-infection, diabetes or chronic alcohol abusers).

Infants, Children, and Adolescents: Oral, IM:

CDC recommendations (MMWR 2003): Initial: 10 to 15 mg/kg once daily (maximum dose: 300 mg) with concomitant rifampin, pyrazinamide and ethambutol for 8 weeks; dexamethasone is given concomitantly in the first 6 weeks.

Continuation phase: 10 to 15 mg/kg/day once daily (maximum: 300 mg daily) with concomitant rifampin for 7 to 10 months.

Note: The above is the CDC preferred regimen (MMWR 2003)

Alternate recommendations (Red Book [AAP 2012]): Initial: 10 to 15 mg/kg once daily (maximum dose: 300 mg) with concomitant rifampin, pyrazinamide and an aminoglycoside, ethambutol or ethionamide for 8 weeks.

Continuation phase: 10 to 15 mg/kg once daily (maximum dose: 300 mg) or 20 to 30 mg/kg 2 times weekly (maximum dose: 900 mg) with concomitant rifampin for 7 to 10 months.

Tuberculosis, latent infection (LTBI):

Infants and Children <12 years: Oral, IM:

CDC recommendation (CDC 2013): 10 to 20 mg/kg/day once daily (maximum: 300 mg per dose)(preferred regimen) or 20 to 40 mg/kg (maximum: 900 mg per dose) twice weekly for 9 months.

Note: Once weekly regimen of isoniazid and rifapentine may also be considered in children ≥2 or <12 years if completion of 9 month regimen (preferred) is unlikely and the hazard of tuberculosis is great (CDC 2013). Refer to Children ≥ 12 years and Adolescents dosing.

Alternate recommendations (Red Book [AAP 2012]): 10 to 15 mg/kg/day once daily (maximum: 300 mg per dose) for 9 months.

Children ≥12 years and Adolescents: Oral, IM:

CDC recommendations (CDC 2013): 10 to 20 mg/kg/day once daily (maximum: 300 mg per dose) (preferred regimen) or 20 to 40 mg/kg (maximum: 900 mg per dose) twice weekly for 9 months (CDC 2013), or 15 mg/kg/dose (maximum: 900 mg per dose) once weekly in combination with rifapentine for 12 weeks (CDC 2013). Note: The rifapentine-containing regimen may be used in otherwise healthy HIV-infected patients, but only in patents not receiving antiretroviral therapy (ART) (CDC 2013; HHS [adult] 2015).

Alternate recommendation (Red Book [AAP 2012]): 10 to 15 mg/kg/day once daily (maximum: 300 mg per dose) for 9 months

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer’s labeling; use with caution in severe renal impairment.

ESRD receiving intermittent hemodialysis (IHD): Administer dose postdialysis (Aronoff 2007); Dialyzable (50% to 100%)

Dosing: Hepatic Impairment

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.

Extemporaneously Prepared

Note: Commercial oral solution is available (50 mg/mL)

A 10 mg/mL oral suspension may be made with tablets, purified water, and sorbitol. Crush ten 100 mg tablets in a mortar and reduce to a fine powder. Add 10 mL of purified water and mix to a uniform paste. Mix while adding sorbitol in incremental proportions to almost 100 mL; transfer to a graduated cylinder, rinse mortar with sorbitol, and add quantity of sorbitol sufficient to make 100 mL (do not use sugar-based solutions). Label "shake well" and "refrigerate". Stable for 21 days refrigerated.

Nahata MC, Pai VB, and Hipple TF, Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.

Administration

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.

Dietary Considerations

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

Storage

Tablet: Store at 20°C to 25°C (68°F to 77°F). Protect from moisture and light.

Oral solution: Store at 15°C to 30°C (59°F to 86°F). Protect from light.

Injection: Store at 20°C to 25°C (68°F to 77°F). Protect from light. Isoniazid injection may crystallize at low temperatures. If this occurs, warm the vial to room temperature before use to redissolve the crystals.

Drug Interactions

Acetaminophen: Isoniazid may enhance the adverse/toxic effect of Acetaminophen. Monitor therapy

Antacids: May decrease the absorption of Isoniazid. Consider therapy modification

ARIPiprazole: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy

Artesunate: CYP2A6 Inhibitors may decrease serum concentrations of the active metabolite(s) of Artesunate. CYP2A6 Inhibitors may increase the serum concentration of Artesunate. Avoid combination

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

Chlorzoxazone: Isoniazid may increase the serum concentration of Chlorzoxazone. Monitor therapy

Cilostazol: CYP2C19 Inhibitors may increase the serum concentration of Cilostazol. Management: Consider reducing the cilostazol dose to 50 mg twice daily in patients who are also receiving inhibitors of CYP2C19. Consider therapy modification

Citalopram: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Citalopram. Management: Limit citalopram dose to a maximum of 20 mg/day if used with a moderate CYP2C19 inhibitor. Patients using this combination should be monitored closely for evidence of citalopram toxicity (e.g., serotonin syndrome, QT prolongation, etc.). Consider therapy modification

Clopidogrel: CYP2C19 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Clopidogrel. Management: Due to a risk for impaired clopidogrel effectiveness with such a combination, carefully consider the need for a moderate CYP2C19 inhibitor in patients receiving clopidogrel. Monitor patients closely for evidence of a diminished response to clopidogrel. Consider therapy modification

CloZAPine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of CloZAPine. Monitor therapy

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

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

CYP2A6 Substrates: CYP2A6 Inhibitors (Moderate) may decrease the metabolism of CYP2A6 Substrates. Monitor therapy

CYP2C19 Substrates: CYP2C19 Inhibitors (Moderate) may decrease the metabolism of CYP2C19 Substrates. Monitor therapy

CYP2E1 Substrates: CYP2E1 Inhibitors (Moderate) may decrease the metabolism of CYP2E1 Substrates. Monitor therapy

Cyproterone: May decrease the serum concentration of CYP2E1 Substrates. Monitor therapy

Disulfiram: May enhance the adverse/toxic effect of Isoniazid. Disulfiram may increase the serum concentration of Isoniazid. Monitor therapy

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

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

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

Fosphenytoin: Isoniazid may increase the serum concentration of Fosphenytoin. Management: Consider alternatives. If concomitant therapy cannot be avoided, monitor for increased phenytoin concentrations/effects with isoniazid initiation/dose increase, or decreased concentrations/effects with isoniazid discontinuation/dose decrease. Consider therapy modification

HYDROcodone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of HYDROcodone. Monitor therapy

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

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

Levodopa: Isoniazid may diminish the therapeutic effect of Levodopa. Monitor therapy

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. Consider therapy modification

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

Phenytoin: Isoniazid may increase the serum concentration of Phenytoin. Management: Consider alternatives. If concomitant therapy cannot be avoided, monitor for increased phenytoin concentrations/effects with isoniazid initiation/dose increase, or decreased concentrations/effects with isoniazid discontinuation/dose decrease. Consider therapy modification

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

Propacetamol: Isoniazid may enhance the hepatotoxic effect of Propacetamol. Monitor therapy

Rifamycin Derivatives: May enhance the hepatotoxic effect of Isoniazid. Even so, this is a frequently employed combination regimen. Monitor therapy

Tegafur: CYP2A6 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Tegafur. Specifically, CYP2A6 inhibitors may inhibit the conversion of tegafur into its active metabolite, 5-fluorouracil. Avoid combination

Theophylline Derivatives: Isoniazid may increase the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. Monitor therapy

TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use cannot be avoided, initiate tizanidine at an adult dose of 2 mg and increase in 2-4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification

Test Interactions

False-positive urinary glucose with Clinitest®

Adverse Reactions

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

Frequency not defined.

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

<1% (Limited to important or life-threatening): Hepatotoxicity (idiosyncratic) (Chalasani 2014)

ALERT: U.S. 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.

Warnings/Precautions

Concerns related to adverse effects:

• Hepatitis: [U.S. Boxed Warning]: Severe and sometimes fatal hepatitis may occur; usually occurs within the first 3 months of treatment, although may develop even after many months of treatment. The risk of developing hepatitis is age-related, although isoniazid-induced hepatotoxicity has been reported in children; daily ethanol consumption, chronic liver disease, or injection drug use may also increase the risk. Patients given isoniazid must be monitored carefully and interviewed at monthly intervals. Fatal hepatitis associated with isoniazid may be increased in women (particularly black and Hispanic and in any woman in the postpartum period). Closer monitoring may be considered in these groups. Patients ≥35 years should also have AST and ALT measured at baseline and periodically throughout treatment. Patients must report any prodromal symptoms of hepatitis, such as fatigue, paresthesias of hands and feet, weakness, dark urine, rash, anorexia, nausea, fever >3 days’ duration, and/or abdominal pain (especially right upper quadrant discomfort), icterus, or vomiting. Patients should be instructed to immediately hold therapy if any of these symptoms occur, and contact their prescriber. If abnormalities of liver function exceed 3 to 5 times the upper limit of normal (ULN), strongly consider discontinuation of isoniazid. If isoniazid must be reinstituted, wait for symptoms and laboratory abnormalities to resolve and use very small and gradual increasing doses, withdrawing therapy immediately if an indication of recurrent hepatic involvement.

• Peripheral neuropathies: Pyridoxine supplementation is recommended in individuals at risk for development of peripheral neuropathies (eg, HIV infection, nutritional deficiency, diabetes, pregnancy).

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with hepatic impairment; contraindicated in patients with acute liver disease or previous isoniazid-associated hepatic injury. Treatment with isoniazid for latent tuberculosis infection (LTBI) should be deferred in patients with acute hepatic diseases.

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

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

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

• Monitoring: 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.

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

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.

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events were observed in some animal reproduction studies. 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. The CDC recommends isoniazid as part of the initial treatment regimen. Pyridoxine supplementation is recommended (25 mg/day) (CDC 2003). 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).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea, vomiting, or injection site irritation. Have patient report immediately to prescriber signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of pancreatitis (severe abdominal pain, severe back pain, severe nausea, or vomiting), signs of high blood sugar (confusion, fatigue, increased thirst, increased hunger, polyuria, flushing, fast breathing, or breath that smells like fruit), signs of lupus (rash on the cheeks or other body parts, sunburn easy, muscle or joint pain, angina or shortness of breath, or swelling in the arms or legs), signs of acidosis (confusion, fast breathing, tachycardia, abnormal heartbeat, severe abdominal pain, nausea, vomiting, fatigue, shortness of breath, or loss of strength and energy), burning or numbness feeling, vision changes, chills, joint pain, joint edema, memory impairment, enlarged breasts, mood changes, seizures, confusion, bruising, bleeding, severe loss of strength and energy, or confusion (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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