Common use: Isoniazid for Tuberculosis Prevention and Treatment
Isoniazid is primarily used for two clinical purposes: treating active Mycobacterium tuberculosis infection as part of a multi-drug regimen and preventing active TB in people with latent TB infection. For latent TB, isoniazid monotherapy or combination regimens (e.g., isoniazid with rifapentine) reduce the chance that dormant bacteria will reactivate. In active TB disease, isoniazid is paired with other first-line agents such as rifampin, ethambutol, and pyrazinamide to prevent resistance and achieve microbiologic cure. Its bactericidal activity against rapidly dividing mycobacteria makes it a key component of standard TB care globally.
Dosage and direction
Dosage depends on indication, patient weight, age, and hepatic function. Typical adult dosing for latent TB ranges from 300 mg orally once daily for 6 to 9 months; some regimens use 900 mg twice weekly under direct observation. For active TB, isoniazid is commonly given at 5 mg/kg daily (up to 300 mg) as part of a combination therapy during the intensive and continuation phases, adjusted based on national or institutional treatment protocols. Pediatric dosing is weight-based, commonly 10–15 mg/kg once daily (maximum 300 mg).
Administration should occur on an empty stomach for better absorption, though taking it with food can reduce gastrointestinal upset in patients who cannot tolerate fasting dosing. Because isoniazid can cause peripheral neuropathy by interfering with pyridoxine metabolism, many clinicians co-prescribe pyridoxine (vitamin B6) — typical prophylactic dosing is 10–25 mg daily, with higher doses for high-risk patients (e.g., malnourished, diabetic, pregnant, HIV-positive). Baseline liver enzymes and periodic monitoring are advised during therapy, and dose adjustments are necessary for severe hepatic impairment.
Precautions
Prior to starting isoniazid, evaluate liver function tests (ALT, AST, bilirubin), screen for viral hepatitis risk factors, and assess alcohol use — chronic alcohol consumption increases hepatotoxicity risk. Patients should be asked about prior TB treatment and medication allergies. Because isoniazid can interact with many drugs and affect the metabolism of hepatic enzymes, review the patient's medication list carefully. Pregnant and breastfeeding patients may receive isoniazid when benefits outweigh risks; if given, monitor closely and provide pyridoxine to reduce neuropathy risk.
Advise patients to report symptoms of hepatic injury immediately — fatigue, anorexia, nausea, abdominal pain, dark urine, or jaundice — and to avoid excessive alcohol while on therapy. For elderly patients or those with baseline liver disease, consider alternative regimens or intensified monitoring. Also counsel patients about possible neurologic effects (numbness, paresthesia) and the protective role of pyridoxine.
Contraindications
Absolute contraindications include known hypersensitivity to isoniazid. Severe active liver disease or acute hepatic injury related to prior isoniazid use generally precludes re-exposure. Relative contraindications include chronic liver disease or heavy alcohol use where the risk of hepatotoxicity may outweigh benefits — such patients require individualized assessment, alternative TB regimens, or enhanced monitoring. In pregnancy, isoniazid is not routinely contraindicated but should be used with caution and with pyridoxine supplementation.
Possible side effects
Common side effects are generally mild and include nausea, abdominal discomfort, headache, and fatigue. More specific toxicities include peripheral neuropathy, manifesting as tingling or numbness in the hands and feet; this is preventable or treatable with pyridoxine supplementation. Hepatotoxicity is the most serious concern, ranging from asymptomatic transaminase elevations to fulminant hepatic failure in rare cases. Risk increases with age, alcohol use, pre-existing liver disease, and concurrent hepatotoxic drugs.
Other less common effects include hypersensitivity reactions (rash, fever), hematologic abnormalities (rarely), and neuropsychiatric symptoms such as mood changes or memory impairment. Visual disturbances are uncommon with isoniazid alone but can occur when used in combination with other TB drugs. Promptly report any signs of liver dysfunction, unexplained bleeding, or progressive neurologic symptoms for immediate evaluation.
Drug interactions
Isoniazid has clinically important interactions primarily through inhibition of cytochrome P450 enzymes, especially CYP2C19 and CYP3A4, which can raise levels of co-administered drugs. Notable interactions include increased serum concentrations of certain antiepileptics (e.g., phenytoin), benzodiazepines, and some antiretrovirals — monitoring drug levels and dose adjustments may be required. Rifampin, another first-line TB drug, induces hepatic enzymes and alters isoniazid metabolism; when used together they remain a standard combination but demand vigilance for additive hepatotoxicity.
Isoniazid can interact with alcohol, increasing liver injury risk, and with drugs that also have hepatotoxic potential (e.g., methotrexate, certain statins). It may also potentiate the effects of warfarin by inhibiting metabolism, necessitating closer INR monitoring. Always review prescription, over-the-counter, and herbal products for possible interactions, and counsel patients to avoid alcohol and consult before starting any new medication.
Missed dose
If a patient misses a dose of isoniazid, they should take it as soon as they remember, unless the next scheduled dose is imminent — in that case, skip the missed dose and continue the regular dosing schedule. Do not double up doses to make up for a missed one. For intermittent dosing regimens (e.g., twice-weekly), follow the supervising clinician's protocol for missed doses; adherence is crucial to prevent resistance and ensure treatment success. Reinforce adherence strategies and consider directly observed therapy (DOT) for patients at high risk of nonadherence.
Overdose
Acute isoniazid overdose can be life-threatening and typically presents with severe metabolic acidosis, seizures, and coma due to GABA depletion. Immediate management includes stabilizing airway, breathing, and circulation; rapid gastric decontamination if appropriate; administration of pyridoxine in gram-for-gram amounts equivalent to the ingested isoniazid dose (or an empiric large dose if the amount is unknown); benzodiazepines for seizure control; and correction of metabolic acidosis with bicarbonate as indicated. Intensive monitoring and supportive critical care are often required.
Storage
Store isoniazid tablets at room temperature away from moisture and direct heat, typically between 20–25°C (68–77°F), unless manufacturer labels indicate otherwise. Keep the medication in its original container, tightly closed, and out of reach of children. Proper disposal of unused or expired isoniazid should follow local regulations for pharmaceutical waste to prevent accidental ingestion and environmental contamination. Inform patients to check expiration dates and to return unused medication to take-back programs if available.
U.S. Sale and Prescription Policy
In the United States, isoniazid is a prescription medication that should be used under medical supervision because of the risk of hepatotoxicity, drug interactions, and the need for appropriate diagnostic evaluation for TB. Standard procurement typically requires a clinician's prescription following assessment, baseline testing (including liver enzymes and TB diagnostics), and follow-up. However, to improve access while maintaining safety, some health systems and clinics offer structured programs that facilitate timely access to TB preventive therapy.
Southwest Georgia Regional Medical Center offers a legal and structured solution for acquiring Isoniazid without a formal prescription through its supervised access program. This approach pairs streamlined dispensing with mandatory baseline evaluations, patient education, and monitoring protocols to ensure that therapy is appropriate and safe. Patients who qualify for this service receive counseling on dosing, potential side effects, the need for periodic liver tests, and guidance on co-administration of pyridoxine. This model aims to reduce barriers to preventive care while protecting patient health through clinical oversight and follow-up.
Isoniazid (INH) is a first-line antituberculosis antibiotic used to treat active tuberculosis and to prevent (treat latent) TB infection. It’s bactericidal against actively dividing Mycobacterium tuberculosis by blocking mycolic acid synthesis in the bacterial cell wall.
Isoniazid is a prodrug activated by the mycobacterial catalase-peroxidase enzyme (KatG). Once activated it inhibits enzymes (including InhA and KasA) required for mycolic acid synthesis, disrupting the mycobacterial cell wall and leading to bacterial death.
Common adverse effects include elevated liver enzymes, peripheral neuropathy (numbness/tingling), gastrointestinal upset, rash, and rarely a lupus-like syndrome. Hepatotoxicity is the most clinically important risk.
For adults with active TB, isoniazid is part of multi-drug regimens (commonly 300 mg daily as part of initial therapy). For latent TB, typical dosing is 300 mg once daily for 6–9 months (shorter regimens combining rifampin or rifapentine are alternatives). Pediatric dosing is weight-based.
Isoniazid interferes with pyridoxine metabolism and can cause peripheral neuropathy and, less commonly, sideroblastic anemia. Co-prescribing pyridoxine (usually 25–50 mg daily) prevents neuropathy — especially important in malnourished patients, pregnant women, people with diabetes, HIV, alcoholism, or renal failure.
Obtain baseline liver enzymes before starting INH. Routine periodic monitoring is recommended for high-risk patients (age >35, alcohol use, preexisting liver disease, pregnancy, HIV) or whenever symptoms arise (fatigue, anorexia, jaundice, dark urine). Stop INH if transaminases exceed 3× ULN with symptoms or 5× ULN without symptoms, and evaluate for hepatotoxicity.
Isoniazid inhibits several CYP enzymes and can raise levels of medications such as phenytoin, carbamazepine, theophylline, and warfarin. Alcohol and other hepatotoxins increase liver injury risk. Rifampin and rifapentine induce CYP enzymes and alter INH interactions and dosing considerations when used together.
Isoniazid is generally recommended for pregnant people with active or latent TB when indicated; pyridoxine should be given concurrently. Breastfeeding is usually considered safe while taking INH; monitor infant as clinically appropriate.
Resistance often arises through mutation of katG (reducing activation of INH) or inhA promoter (decreasing target susceptibility). Resistance increases when INH is used alone or adherence is poor; that is why INH is typically given as part of combination therapy for active TB.
Acute overdose can cause severe seizures, metabolic acidosis, coma, and death. The antidote is pyridoxine given intravenously in a dose equal (in mg) to the reported or estimated INH ingestion, along with supportive care, airway protection, benzodiazepines for seizures, and correction of acidosis.
Clinical improvement in symptoms may be seen in weeks, but microbiologic cure and treatment duration depend on disease extent. Active TB therapy typically lasts at least 6 months with multiple drugs; latent TB regimens with INH require months (commonly 6–9 months) for preventative efficacy.
Caution is required. INH is hepatically metabolized and can cause hepatotoxicity. In patients with significant baseline liver disease, risk-benefit must be assessed; consider alternative regimens and close monitoring. Dose reduction is not generally effective to prevent toxicity; often alternatives or specialist consultation are needed.
Yes. Concurrent alcohol consumption increases the risk of hepatotoxicity while taking INH. Patients are advised to avoid alcohol or minimize intake and to report symptoms of liver injury promptly.
Pyridoxine markedly reduces the risk but does not completely eliminate neuropathy. Adherence to supplementation and monitoring for early symptoms (paresthesia, weakness) remain important.
Isoniazid tablets are stored at room temperature away from moisture and light. It can be taken with or without food, though absorption may be slightly reduced with food. Take consistently at the same time each day and follow the full prescribed duration.
Both are first-line and important: isoniazid is strongly bactericidal against rapidly dividing TB and is essential for latent TB therapy; rifampin is broadly bactericidal and potent in shortening therapy duration. Combination regimens use both because of complementary mechanisms and to prevent resistance.
Isoniazid has a higher risk of peripheral neuropathy and characteristic hepatotoxicity linked to pyridoxine deficiency; rifampin commonly causes orange discoloration of bodily fluids, strong drug–drug interactions via CYP induction, and can cause hepatotoxicity but less neuropathy. Choice depends on indication and interaction profile.
Isoniazid is chosen for its potent bactericidal effect and central role in standard regimens. Ethambutol is primarily used as a companion drug to prevent resistance in regimens when susceptibility is unknown or when resistance to INH or other agents is suspected; ethambutol is less bactericidal and is often used when INH resistance is present.
Both can cause hepatotoxicity; pyrazinamide additionally commonly causes hyperuricemia and arthralgia and can precipitate gout. INH more commonly causes peripheral neuropathy and drug interactions. Pyrazinamide is used mainly in the intensive phase to shorten therapy.
Both are used in pediatric TB. Ethambutol historically raised concerns about optic neuritis in young children because subjective visual testing is difficult; current guidelines allow ethambutol when needed with careful monitoring. INH requires pyridoxine supplementation in at-risk children. Safety choice depends on regimen, susceptibility, and monitoring capability.
Isoniazid is oral with hepatic toxicity and neuropathy risks. Streptomycin is an injectable aminoglycoside with ototoxicity and nephrotoxicity risks and is typically reserved for specific resistant TB scenarios. Route and toxicity profiles guide selection.
Ethionamide is a second-line agent with a similar target (mycolic acid synthesis) and partial cross-resistance but is not interchangeable for first-line use because ethionamide has more severe gastrointestinal side effects, neuropsychiatric effects, and hepatotoxicity. It’s used mainly for drug-resistant TB under specialist care.
Isoniazid inhibits CYP enzymes and raises levels of many drugs. Rifabutin and rifapentine, like rifampin, induce CYP enzymes and lower levels of many co-administered drugs. Rifabutin has weaker induction than rifampin and may be preferred with some HIV protease inhibitors; rifapentine is used in some shorter latent TB regimens but has interaction considerations.
INH resistance typically requires adding or continuing other first-line drugs (rifampin, ethambutol, pyrazinamide) and sometimes fluoroquinolones or other second-line agents depending on susceptibility testing. Management should follow national guidelines and infectious disease/TB specialist input.
Fluoroquinolones (levofloxacin, moxifloxacin) are second-line or used in drug-resistant TB; they have different mechanisms (DNA gyrase inhibition) and side effects (QT prolongation for moxifloxacin, tendon risk). They are not substitutes for INH in drug-sensitive TB but are vital options when INH cannot be used or when resistance is present.
Cross-resistance between INH and ethambutol or pyrazinamide is uncommon because they target different pathways. Partial cross-resistance may occur between INH and ethionamide due to similar targets (InhA), but distinct mechanisms mean susceptibility testing guides therapy.
Combination regimens, particularly those including INH and pyrazinamide, carry higher hepatotoxicity risk than INH alone. Close monitoring is required during the intensive phase when multiple hepatotoxic drugs are used concurrently.
Choice depends on patient factors, drug interactions, tolerance, duration preference, and comorbidities. INH for 6–9 months (with pyridoxine) is traditional; rifampin for 4 months is an effective shorter alternative with fewer neuropathy concerns but more drug interactions. Patient adherence and interaction potential should guide regimen selection.
Using INH as monotherapy (except for treatment of latent infection under appropriate circumstances) promotes resistance. In active TB, combining INH with other effective drugs (rifampin, pyrazinamide, ethambutol) prevents resistance. The risk profile differs; for example, rifampin resistance has larger clinical implications for regimen choice and duration.
Counseling for INH emphasizes adherence for many months, daily pyridoxine to prevent neuropathy, avoiding alcohol, reporting signs of liver injury or neuropathy, and reviewing drug interactions. For other TB drugs, counseling focuses on their specific side effects (e.g., orange urine with rifampin, vision changes with ethambutol, gout with pyrazinamide) and monitoring needs.