Drug class: Antituberculosis Agents
- Antimycobacterial Agents
VA class: AM500
CAS number: 54-85-3

Introduction

Antituberculosis agent; synthetic isonicotinic acid derivative.^{a b c d}

Uses for Isoniazid

Tuberculosis

Treatment of active (clinical) tuberculosis (TB) in conjunction with other antituberculosis agents.^{145 176 b c d e j}

First-line agent for treatment of all forms of active TB caused by Mycobacterium tuberculosis known or presumed to be susceptible to the drug.^{145 176 j} Essential component of multiple-drug regimens used for the initial intensive treatment phase and the continuation treatment phase.^{145 176 j}

Fixed-combination preparation containing rifampin and isoniazid (Rifamate) is used for treatment of pulmonary TB.^{143 176} Isoniazid and rifampin both are used in the initial intensive treatment phase and the continuation treatment phase,¹⁷⁶ but manufacturer states that Rifamate is not recommended for initial therapy, and the fixed-combination preparation should be used only after the patient has been treated with the individual components and efficacy of these drugs has been established.¹⁴³

Fixed combination preparation containing rifampin, isoniazid, and pyrazinamide (Rifater) is used for treatment of pulmonary TB;^{141 176} designated an orphan drug by US FDA for this use.¹⁰⁴ Used only in the initial intensive treatment phase since pyrazinamide is not usually indicated for the continuation phase.^{141 176}

For initial treatment of active TB caused by drug-susceptible M. tuberculosis, recommended multiple-drug regimens consist of an initial intensive phase (2 months) and a continuation phase (4 or 7 months).^{145 176} Although the usual duration of treatment for drug-susceptible pulmonary and extrapulmonary TB (except disseminated infections and TB meningitis) is 6–9 months,^{145 176} ATS, CDC, and IDSA state that completion of treatment is determined more accurately by the total number of doses and should not be based solely on the duration of therapy.¹⁷⁶ A longer duration of treatment (e.g., 12–24 months) usually is necessary for infections caused by drug-resistant M. tuberculosis.^{145 176}

Patients with treatment failure or drug-resistant M. tuberculosis, including multidrug-resistant (MDR) TB (resistant to both isoniazid and rifampin) or extensively drug-resistant (XDR) TB (resistant to both isoniazid and rifampin and also resistant to a fluoroquinolone and at least one parenteral second-line antimycobacterial such as capreomycin, kanamycin, or amikacin), should be referred to or managed in consultation with experts in the treatment of TB as identified by local or state health departments or CDC.^{176 l}

Latent Tuberculosis Infection

Treatment of latent tuberculosis infection (LTBI).^{145 166 177 b c d g h i j}

LTBI is asymptomatic infection with M. tuberculosis; usually defined as a positive tuberculin skin test (TST) or Quantiferon-TB gold test (QFT-G) with no evidence of active (clinical) TB.^{145 166 177 j} LTBI is treated to decrease the risk of progression to active TB.^{145 166 g}

Regimen of choice for treatment of LTBI is isoniazid monotherapy, unless the patient has been in contact with an individual with drug-resistant TB.^{145 166 177 g h i j} Rifampin monotherapy is the preferred alternative and is especially useful in adults, adolescents, or children who have been exposed to isoniazid-resistant M. tuberculosis and those who cannot tolerate isoniazid.^{145 166 177 g h i j} Rifabutin is used in those who cannot receive rifampin because of intolerance or because they are receiving other drugs that have clinically important interactions with rifampin (e.g., HIV patients receiving certain antiretroviral agents).^{177 h j}

Treatment of LTBI in patients who have been exposed to a source case with drug-resistant TB, including MDR TB or XDR TB, should be managed in consultation with experts in the treatment of TB as identified by local or state health departments or CDC.^{145 166 g h i j}

Prior to initiating treatment of LTBI, clinical (active) TB must be excluded using appropriate testing (e.g., radiographs).^{145 166 177 b c d g h i j}

Mycobacterium avium Complex (MAC) Infections

Has been used for treatment of M. avium complex (MAC) infections^{† [off-label]} in conjunction with other antimycobacterials.^t

Although a multiple-drug regimen of isoniazid, rifampin, and ethambutol (with streptomycin during the initial 3–6 months) has been used for treatment of MAC pulmonary infections,^t isoniazid is not included in current ATS, CDC, NIH, or IDSA recommendations for treatment of MAC infections, including macrolide-resistant MAC.^{e f t}

Treatment of MAC infections is complicated and should be directed by clinicians familiar with mycobacterial diseases; consultation with a specialist is particularly important when the patient cannot tolerate first-line drugs or when the infection has not responded to prior therapy or is caused by macrolide-resistant MAC.^t

Mycobacterium kansasii and Other Mycobacterial Infections

Treatment of M. kansasii infections in conjunction with other antimycobacterials.^t ATS and IDSA recommend a regimen of isoniazid, rifampin, and ethambutol for treatment of pulmonary or disseminated infections caused by rifampin-susceptible M. kansasii.^t If rifampin-resistant M. kansasii are involved, ATS and IDSA recommend a 3-drug regimen based on results of in vitro susceptibility, including clarithromycin (or azithromycin), moxifloxacin, ethambutol, sulfamethoxazole, or streptomycin.^t

Treatment of M. xenopi^{† [off-label]} infections in conjunction with other antimycobacterials.¹⁰⁷ Optimum regimens not established; in vivo response may not correlate with in vitro susceptibility.¹⁰⁷ ATS and IDSA state that a regimen of clarithromycin, rifampin, and ethambutol has been used, although the rate of relapse is high.¹⁰⁷ A regimen of isoniazid, rifampin (or rifabutin), ethambutol, and clarithromycin (without or without streptomycin during initial treatment) also has been suggested.¹⁰⁷

Related/similar drugs

ciprofloxacin, levofloxacin, rifampin, Levaquin, pyrazinamide, rifabutin, bcg

Isoniazid Dosage and Administration

Administration

Administer orally.^{c d} May be given IM when oral therapy is not feasible.^b

Used in conjunction with other antimycobacterial agents for treatment of active (clinical) TB.^{176 b c d e} Used alone for treatment of LTBI.^{166 177 b c d}

Fixed-combination preparations (Rifamate containing rifampin and isoniazid; Rifater containing rifampin, isoniazid, and pyrazinamide) can be used for treatment of active TB infection to reduce the pill burden and ensure compliance, especially when directly observed (supervised) therapy (DOT) cannot be used.¹⁷⁶ A fixed-combination preparation should be used only when all drugs in the preparation are indicated.¹⁷⁶

Oral Administration

Administer orally in the fasting state.^{c d} Do not administer with food.^{c d} (See Food under Pharmacokinetics.)

Rifamate or Rifater: Administer orally with a full glass of water 1 hour before or 2 hours after a meal.^{141 143}

Dosage

Oral and IM dosage is the same.^a

Dosage of Rifamate is expressed as number of capsules;¹⁴³ dosage of Rifater is expressed as number of tablets.¹⁴¹

Concomitant administration of pyridoxine (vitamin B₆) is recommended in adults, adolescents, and pediatric patients who are malnourished (including those on meat- or milk-deficient diets) and in those predisposed to neuropathy (e.g., those with alcoholism, diabetes, HIV infection, seizure disorders, or renal failure).^{141 145 147 166 176 b c d f} Administration of pyridoxine also is recommended in pregnant or nursing women;^{145 176} breast-feeding infants do not require pyridoxine unless they are receiving isoniazid.^{145 166 176} (See Nervous System Effects under Cautions.)

Pediatric Patients

Tuberculosis

Treatment of Active (Clinical) Tuberculosis

Oral

Children: 10–15 mg/kg (up to 300 mg) once daily or 20–40 mg/kg (up to 900 mg) 2 or 3 times weekly recommended by the manufacturers.^{c d}

Children <15 years of age or weighing ≤40 kg: 10–15 mg/kg (up to 300 mg) once daily or 20–30 mg/kg (up to 900 mg) twice weekly recommended by ATS, CDC, IDSA, AAP, and others.^{145 176 f j}

Adolescents ≥15 years of age: 5 mg/kg (up to 300 mg) once daily or 15 mg/kg (up to 900 mg) 1–3 times weekly recommended by ATS, CDC, and IDSA.^{176 e}

Rifater in adolescents ≥15 years of age: 4 tablets once daily in those weighing ≤44 kg, 5 tablets once daily in those weighing 45–54 kg, or 6 tablets once daily in those weighing ≥55 kg.¹⁴¹ Used only in the initial phase of treatment.¹⁴¹

IM

Children: 10–15 mg/kg (up to 300 mg) once daily or 20–40 mg/kg (up to 900 mg) 2 or 3 times weekly.^b

Latent Tuberculosis Infection (LTBI)

Oral

Infants, children, and adolescents: 10–15 mg/kg (up to 300 mg) once daily or 20–30 mg/kg (up to 900 mg) 2 or 3 times weekly recommended by manufacturers, ATS, CDC, IDSA, AAP, USPHS, and others.^{145 147 166 b c i j}

The usual duration of isoniazid monotherapy for treatment of LTBI in children is 9 months, especially in HIV-infected individuals.^{145 147 166 i j} A 6-month regimen is not recommended for children.^{145 147 166}

ATS and CDC recommend that completion of therapy for LTBI be based on total number of administered doses rather duration of therapy alone.¹⁶⁶ When the 9-month once-daily isoniazid regimen is used, at least 270 doses should be administered within 12 months.¹⁶⁶ Ideally, patients should receive the drug on a regular dosing schedule until completed; in practice, some doses may be missed requiring the course to be lengthened.¹⁶⁶ If the regimen is resumed after an interruption of ≥2 months, a medical examination is indicated to rule out active TB.¹⁶⁶

IM

Children: 10 mg/kg (up to 300 mg) once daily or 20–30 mg/kg (up to 900 mg) twice weekly.^b

Adults

Tuberculosis

Treatment of Active (Clinical) Tuberculosis

Oral

5 mg/kg (up to 300 mg) once daily^{176 c d e j} or 15 mg/kg (up to 900 mg) 1–3 times weekly^{176 c d e j} recommended by manufacturers, ATS, CDC, IDSA, and others.

Rifamate: 2 capsules once daily.¹⁴³

Rifater: 4 tablets once daily in adults weighing ≤44 kg, 5 tablets once daily in adults weighing 45–54 kg, or 6 tablets once daily in adults weighing ≥55 kg.¹⁴¹ Used in the initial phase of treatment.¹⁴¹

IM

5 mg/kg (up to 300 mg) once daily or 15 mg/kg (up to 900 mg) 2 or 3 times weekly.^b

Latent Tuberculosis Infection (LTBI)

Oral

5 mg/kg (up to 300 mg) once daily or 15 mg/kg (up to 900 mg) twice weekly recommended by ATS, CDC, IDSA, USPHS, and others.^{124 147 166 j}

Adults weighing >30 kg: 300 mg once daily recommended by manufacturers.^c

The usual duration of isoniazid monotherapy for treatment of LTBI is 9 months.^{145 147 163 166 177 j} A 6-month regimen may be used in some adults,¹⁷⁷ but a 9-month regimen should be used in immunocompromised or HIV-infected individuals or those with fibrotic lesions on chest radiographs.^{145 147 163 166 177}

ATS and CDC recommend that completion of therapy for LTBI be based on total number of administered doses rather duration of therapy alone.¹⁶⁶ When the 9-month once-daily isoniazid regimen is used, at least 270 doses should be administered within 12 months.¹⁶⁶ When the 6-month once-daily isoniazid regimen is used, at least 180 doses should be administered within 9 months.¹⁶⁶ Ideally, patients should receive the drug on a regular dosing schedule until completed; in practice, some doses may be missed requiring the course to be lengthened.¹⁶⁶ If the regimen is resumed after an interruption of ≥2 months, a medical examination is indicated to rule out active TB.¹⁶⁶

IM

Adults weighing >30 kg: 300 mg once daily or 20–30 mg/kg (up to 900 mg) twice weekly.^b

Mycobacterium kansasii Infections† [off-label]

Treatment of Pulmonary or Disseminated Infections Caused by Rifampin-susceptible M. kansasii† [off-label]

Oral

5 mg/kg (up to 300 mg) daily in conjunction with ethambutol (15 mg/kg once daily) and rifampin (10 mg/kg [up to 600 mg] daily), and pyridoxine (50 mg daily) recommended by ATS and IDSA.^t

Continue until patient has been culture negative on treatment for 1 year.^t A longer duration may be needed in HIV-infected individuals with disseminated infections.^t

Prescribing Limits

Pediatric Patients

Active (Clinical) Tuberculosis or Latent Tuberculosis Infection (LTBI)

Oral

Maximum 300 mg per dose in once-daily regimens or 900 mg per dose in 2- or 3-times weekly regimens.^{145 166 176 c f}

When used in conjunction with rifampin, isoniazid dosage >10 mg/kg daily may increase the incidence of hepatotoxicity.^{145 f}

Adults

Active (Clinical) Tuberculosis or Latent Tuberculosis Infection (LTBI)

Oral

Maximum 300 mg per dose in once-daily regimens or 900 mg per dose in 2- or 3-times weekly regimens.^{166 176 e}

Special Populations

Hepatic Impairment

Risk of drug accumulation may be increased, but no specific dosage recommendations available.¹⁷⁶ (See Hepatic Impairment under Cautions.)

Renal Impairment

No dosage adjustment needed in patients with renal impairment, including end-stage renal disease; supplemental doses not necessary in hemodialysis patients.¹⁷⁶ (See Renal Impairment under Cautions.)

Cautions for Isoniazid

Contraindications

• History of severe hypersensitivity reactions, including drug-induced hepatitis.^{b c d}

• History of isoniazid-associated hepatic injury.^{b c d}

• History of severe adverse reactions to isoniazid (e.g., drug fever, chills, arthritis).^{b c d}

• Acute liver disease of any etiology.^{b c d}

Warnings/Precautions

Warnings

Hepatic Effects

Severe and sometimes fatal hepatitis reported.^{b c d} (See Boxed Warning.)

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions, including fever, skin eruptions (morbilliform, maculopapular, purpuric, or exfoliative), lymphadenopathy, or vasculitis reported.^{b c d}

At first sign of hypersensitivity, discontinue all drugs and evaluate patient.^{b c d} If isoniazid must be reinstituted, the drug should be restarted only after symptoms have cleared.^{b c d} Isoniazid should be restarted in very small dosages and gradually increased; discontinue immediately if there is any indication of recurrent hypersensitivity reaction.^{b c d}

General Precautions

Nervous System Effects

Peripheral neuritis (usually preceded by paresthesia of the feet and hands) reported.^{b c} Appears to be dose-related^{176 b c} and is uncommon with recommended dosages.^{176 b} Occurs most frequently in those who are malnourished or predisposed to neuritis (e.g., alcoholics, diabetics, HIV-infected, renal failure)^{176 b c} and in those who are slow inactivators of isoniazid (see Elimination under Pharmacokinetics).^{b c}

Neuropathy may be prevented or relieved by pyridoxine (vitamin B₆).^{166 176 a} ATS, CDC, IDSA, AAP, and USPHS recommend pyridoxine supplementation in adults, adolescents, and children at increased risk of neuropathy (e.g., those with malnutrition, alcoholism, diabetes, HIV infection, seizure disorders, or renal failure), pregnant or breast-feeding women, and in breast-feeding infants receiving isoniazid.^{145 147 166 176} Multivitamin preparations contain variable amounts of pyridoxine and usually will not provide adequate supplementation in these patients.¹⁷⁶ Some experts recommend a pyridoxine dosage of 10–25 mg daily during isoniazid therapy;^{166 176} higher dosage may be recommended in HIV-infected adults.¹⁴⁷

Carefully monitor patients with peripheral neuropathy or conditions that predispose to neuropathy.^{b c}

Patient Monitoring

Because of risk of isoniazid-associated hepatitis, closely monitor and interview patients once monthly.^{b c d} Determine serum transaminase concentrations prior to and periodically during treatment in those at increased risk, including daily users of alcohol, patients >35 years of age, those with chronic liver disease, those who use illicit injection drugs, and women (particularly during the postpartum period and in those who belong to minority groups).^{b c d} (See Boxed Warning.)

Carefully monitor patients who are daily users of alcohol, those who are >35 years of age, those receiving long-term concomitant therapy, those who previously discontinued isoniazid, those who use illicit injection drugs, those with a history of peripheral neuropathy or conditions predisposing to neuropathy, those with active chronic liver disease or severe renal dysfunction, women who are pregnant or in the postpartum period, women who belong to minority groups, and HIV-infected individuals.^{b c d}

Perform periodic ophthalmologic examinations if visual symptoms occur during isoniazid therapy.^b

Use of Fixed Combinations

When the fixed-combination preparations (Rifamate containing rifampin and isoniazid or Rifater containing rifampin, isoniazid, and pyrazinamide) are used, observe the usual precautions and contraindications associated with all drugs in the preparation.^{141 143} Use these preparations only when all drugs contained in the fixed combination are indicated.¹⁷⁶

Precautions Related to Treatment of Tuberculosis

Should not be used alone for treatment of active TB; must be used in conjunction with other antituberculosis agents.^{176 b c d e}

Clinical specimens for microscopic examination and mycobacterial cultures and in vitro susceptibility testing should be obtained prior to initiation of antituberculosis therapy and periodically during treatment to monitor therapeutic response.¹⁷⁶ The antituberculosis regimen should be modified as needed.¹⁷⁶ Patients with positive cultures after 4 months of treatment should be considered to have failed treatment (usually as the result of noncompliance or drug-resistant TB).¹⁷⁶

Compliance with the full course of antituberculosis therapy and all drugs included in the multiple-drug regimen is critical.¹⁷⁶ Missed doses increase the risk of treatment failure and increase the risk that M. tuberculosis will develop resistance to the antituberculosis regimen.¹⁷⁶

To ensure compliance, ATS, CDC, IDSA, and AAP recommend that directly observed (supervised) therapy (DOT) be used for treatment of active (clinical) TB and for treatment of LTBI whenever possible, especially when intermittent regimens are used, when the patient is immunocompromised or infected with HIV, or when drug-resistant M. tuberculosis is involved.^{145 166 176 e f i}

Specific Populations

Pregnancy

Category C.^{b c d}

A regimen of isoniazid, rifampin, and ethambutol is recommended by ATS, CDC, IDSA, and AAP for treatment of active (clinical) TB in pregnant women.^{145 176} Consider that the risk of fatal isoniazid-associated hepatitis may be increased in women, especially during the postpartum period.¹⁷⁶ Carefully monitor when used during pregnancy and the postpartum period (especially in women belonging to minority groups).^{b c d}

Treatment for LTBI generally should be deferred until after delivery to avoid risk to the fetus.^{b c d}

If isoniazid is used during pregnancy, consider concomitant use of pyridoxine.^{145 176} (See Nervous System Effects under Cautions.) Neonates born to women who received isoniazid during pregnancy should be carefully observed for evidence of adverse effects.^{b c d}

Lactation

Distributed into milk, but manufacturers state that breast-feeding should not be discouraged.^{b c d} Consider use of pyridoxine in breast-feeding woman; her breast-fed infant does not require pyridoxine unless also receiving isoniazid.^{145 176} (See Nervous System Effects under Cautions.)

Isoniazid concentrations in breast milk are too low to be considered therapeutic for the infant.^{b c d}

Pediatric Use

Used in infants and children for treatment of active (clinical) TB and treatment of LTBI.^{145 166 176 b c d}

Rifamate: Safety and efficacy not established in pediatric patients.¹⁴³

Rifater: Safety and efficacy not established in children <15 years of age; the ratio of rifampin and isoniazid in this preparation may not be appropriate for this age group.¹⁴¹

Infants, children, and adolescents who experience paresthesias while receiving isoniazid and those who are malnourished (including those on meat- or milk-deficient diets) or have conditions that predispose to neuropathy (e.g., HIV infection, renal failure) should receive pyridoxine supplementation during isoniazid therapy.^{145 166 176} Breast-feeding infants receiving isoniazid also should receive pyridoxine supplementation.^{145 176} Routine administration of pyridoxine in other pediatric patients is not recommended.^{145 166}

Hepatic Impairment

Risk of drug accumulation and isoniazid-associated hepatitis may be increased.^{176 b c d} (See Boxed Warning.)

Carefully monitor patients with chronic liver disease.^{176 b c d} Contraindicated in patients with acute liver disease.^{b c d}

Renal Impairment

Carefully monitor patients with severe renal impairment.^{b c d}

Common Adverse Effects

Nervous system effects (peripheral neuropathy), hepatic effects (elevated transaminase concentrations).^{b c d}

Drug Interactions

Specific Drugs, Food, and Laboratory Tests

Isoniazid Pharmacokinetics

Absorption

Bioavailability

Readily absorbed from GI tract; peak plasma concentrations achieved within 1–2 hours.^{b c d}

Readily absorbed from IM injection sites.^a

Food

Food reduces oral bioavailability.^{b c d}

Plasma Concentrations

Plasma concentrations in rapid isoniazid inactivators are 20–50% of those in slow isoniazid inactivators.^a

Distribution

Extent

Distributed into all body tissues and fluids, including pleural fluid, ascitic fluid, saliva, and sputum.^{b c d}

CSF concentrations are 90–100% of concurrent plasma concentrations.^{176 a}

Crosses the placenta.^{b c d}

Distributed into milk in concentrations comparable to those in plasma.^{176 b c d}

Plasma Protein Binding

Not substantially bound.^a

Elimination

Metabolism

Inactivated in the liver, mainly by acetylation and dehydrazination.^{b c d} The rate of acetylation is genetically determined,^{b c d} and usually is constant for each person.^a Rate of acetylation does not have a clinically important effect on efficacy, but slow acetylators may have higher blood concentrations of the drug and may be at increased risk of toxic reactions.^{b c d}

Slow inactivation is an autosomal recessive trait and results from a relative deficiency of the hepatic enzyme N-acetyltransferase.^a Approximately 50% of whites and blacks are slow inactivators of isoniazid; the majority of native Alaskans and Asians (Japanese, Chinese) are rapid inactivators.^{a b c d}

Elimination Route

Eliminated principally in urine (75–96%) as unchanged drug and metabolites.^a Small amounts excreted in saliva, sputum, and feces.^a

Removed by hemodialysis and peritoneal dialysis.^{a b c d}

Half-life

1–4 hours.^a

Special Populations

Half-life may be prolonged in patients with impaired hepatic function or severe renal impairment.^a

Stability

Storage

Oral

Oral Solution

15–30°C in tight, light-resistant container.^d

Capsules

Rifamate: Avoid excessive heat; store in a dry place in tightly closed container.¹⁴³

Tablets

20–25°C; protect from light and moisture.^c

Rifater: 15–30°C.¹⁴¹ Protect from excessive humidity.¹⁴¹

Parenteral

Injection

20–25°C; protect from light.^b May crystallize at low temperatures.^b If this occurs, warm the vial at room temperature to dissolve the crystals before use.^b

Actions and Spectrum

• Bactericidal in action.^{b c d}

• Interferes with metabolism of bacterial proteins, nucleic acids, carbohydrates, and lipids.^a Appears to inhibit mycolic acid synthesis in susceptible bacteria which results in loss of acid-fastness and disruption of the bacterial cell wall.^{a b c d}

• A highly specific antibacterial agent; active only against Mycobacterium.^a Active in vitro and in vivo against M. tuberculosis,^a M. bovis,^a and some strains of M. kansasii.^{a t} M. marinum is resistant.^{t u}

• Natural and acquired resistance to isoniazid observed in vitro and in vivo in M. tuberculosis.^a

• M. tuberculosis resistant to both isoniazid and rifampin (MDR TB) occurs.^{k l m n} There also have been recent reports of extensively drug-resistant (XDR) TB in various parts of the world, including the US.^{k l n} XDR TB is caused by M. tuberculosis resistant to rifampin and isoniazid (multiple-drug resistant strains) that also are resistant to a fluoroquinolone and at least one parenteral second-line antimycobacterial (capreomycin, kanamycin, amikacin).^{k l n}

Advice to Patients

• Advise patients that poor compliance with antituberculosis regimens can result in treatment failure and development of drug-resistant TB, which can be life-threatening and lead to other serious health risks.¹⁷⁶

• Importance of completing full course of therapy; importance of not missing any doses.^{145 176 a}

• Advise patients to take isoniazid in the fasting state.^{c d}

• Importance of informing clinicians if signs or symptoms of liver damage or other adverse effects occur, including loss of appetite, malaise, persistent fatigue, nausea, vomiting, dark urine, icterus, rash, persistent paresthesias of the hands and feet, weakness or fever lasting >3 days, and/or abdominal tenderness (especially right upper quadrant discomfort).^{b c d}

• Advise patient to avoid histamine-containing food (e.g., skipjack, tuna, tropical fish) and tyramine-containing food and beverages (e.g., cheese, red wine) during isoniazid therapy.¹⁴¹

• Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs, as well as any concomitant illnesses.^{b c d}

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{b c d}

• Importance of informing patients of other important precautionary information.^{b c d} (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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