Isoniazid is a first-line antituberculosis medication and a cornerstone of global TB control programs. As a highly specific bactericidal agent against Mycobacterium tuberculosis, it remains one of the most effective and widely used drugs for both active disease and latent infection. Its mechanism of action involves inhibition of mycolic acid synthesis, critical for the bacterial cell wall, leading to rapid killing of actively dividing bacilli. Proper use under medical supervision is essential to ensure therapeutic success and minimize the risk of resistance development.

Features

• Bactericidal activity specifically targets Mycobacterium tuberculosis
• Available in multiple formulations: tablets (100mg, 300mg) and oral syrup
• High oral bioavailability with rapid absorption
• Penetrates well into bodily fluids and tissues, including cerebrospinal fluid
• Metabolized primarily by hepatic acetylation; genetic variations may affect dosing
• Compatible with most first-line anti-TB regimens (e.g., RIPE therapy)

Benefits

• High efficacy in eradicating active tuberculosis when used in combination therapy
• Critical role in preventing reactivation of latent TB infection, reducing future disease risk by up to 90%
• Rapid reduction in bacterial load during initial phase of treatment, decreasing transmission risk
• Well-established safety profile with decades of clinical use and monitoring
• Oral administration supports outpatient treatment and improves adherence
• Cost-effective and included in WHO Essential Medicines List

Common use

Isoniazid is indicated for the treatment of all forms of active tuberculosis caused by susceptible strains of Mycobacterium tuberculosis. It must always be used in combination with other antituberculosis drugs (e.g., rifampin, pyrazinamide, ethambutol) to prevent development of drug resistance. Additionally, it is approved for chemoprophylaxis of latent tuberculosis infection in high-risk individuals, including recent converters, immunosuppressed patients, and close contacts of active TB cases. Off-label uses may include certain nontuberculous mycobacterial infections when susceptibility is confirmed.

Dosage and direction

Active tuberculosis: 5 mg/kg (usual adult dose 300 mg) orally once daily, or 15 mg/kg (max 900 mg) 2-3 times weekly in directly observed therapy (DOT) programs. Latent TB infection: 300 mg orally once daily or 900 mg twice weekly for 6-9 months. Pediatric dosing: 10-15 mg/kg/day (max 300 mg/day) or 20-30 mg/kg (max 900 mg) twice weekly. Administration should occur on an empty stomach, preferably 1 hour before or 2 hours after meals, to maximize absorption. Dosage adjustments are required in patients with slow acetylator status or hepatic impairment. Always complete the full course of therapy as prescribed.

Precautions

Baseline assessment should include liver function tests, complete blood count, and renal function. Monitor for symptoms of hepatitis (fatigue, nausea, vomiting, dark urine) throughout therapy. Patients should avoid alcohol consumption due to increased hepatotoxicity risk. Supplemental pyridoxine (vitamin B6) 25-50 mg daily is recommended to prevent peripheral neuropathy, especially in malnourished patients, alcoholics, diabetics, and those with HIV. Regular ophthalmological exams are advised for patients receiving prolonged therapy. Use with caution in patients with pre-existing liver disease, chronic alcoholism, or history of seizure disorders.

Contraindications

Absolute contraindications include previous severe hypersensitivity reactions to isoniazid, acute liver disease of any etiology, or previous isoniazid-associated hepatic injury. Relative contraindications include chronic liver disease, severe renal impairment, history of peripheral neuropathy, and concurrent use of other hepatotoxic medications. The drug should not be used as monotherapy in active tuberculosis due to rapid resistance development. Caution is warranted in patients with porphyria or history of seizure disorders.

Possible side effect

Common: Peripheral neuropathy (dose-related), elevated liver enzymes, nausea, vomiting, epigastric distress. Less common: Hepatitis (age-related risk), rash, fever, arthralgias, lupus-like syndrome. Rare but serious: Optic neuritis, seizures, psychosis, agranulocytosis, hemolytic anemia, hypersensitivity reactions including Stevens-Johnson syndrome. Peripheral neuropathy typically presents as symmetric numbness, tingling, or burning sensations in extremities. Hepatotoxicity may range from asymptomatic transaminase elevation to fulminant hepatic failure.

Drug interaction

Significant interactions occur with: Anticonvulsants (phenytoin, carbamazepine) - increased levels requiring monitoring; Benzodiazepines - reduced clearance; Ketoconazole - decreased absorption; Warfarin - enhanced anticoagulant effect; Disulfiram - increased neurotoxicity risk; Rifampin - increased risk of hepatotoxicity; Aluminum-containing antacids - decreased isoniazid absorption. Concurrent use with other hepatotoxic drugs (e.g., acetaminophen, statins) requires careful monitoring. Isoniazid inhibits several cytochrome P450 enzymes, particularly CYP2C19 and CYP3A4.

Missed dose

If a dose is missed, it should be taken as soon as remembered unless it is nearly time for the next scheduled dose. Do not double the dose to make up for a missed one. For twice-weekly regimens, if a dose is missed, resume the schedule as soon as possible and continue with the original dosing day schedule. Consistent adherence is critical for treatment success and prevention of resistance. Patients should contact their healthcare provider if multiple doses are missed to discuss potential adjustments to the treatment plan.

Overdose

Symptoms of overdose typically appear within 30 minutes to 3 hours and may include nausea, vomiting, dizziness, slurred speech, blurred vision, visual hallucinations, seizures, metabolic acidosis, and coma. Massive overdose may cause severe metabolic acidosis, hyperglycemia, and respiratory distress. Treatment is supportive and symptomatic: gastric lavage if presented early, activated charcoal, intravenous pyridoxine (gram-for-gram equivalent to ingested isoniazid), and control of seizures with benzodiazepines. Hemodialysis may be effective in severe cases. Immediate medical attention is required.

Storage

Store at controlled room temperature (20-25°C or 68-77°F) in a tight, light-resistant container. Keep away from moisture and excessive heat. Do not freeze the oral solution. Keep out of reach of children and pets. Do not use beyond the expiration date printed on the packaging. Proper disposal of unused medication through take-back programs is recommended to prevent environmental contamination and accidental ingestion.

Disclaimer

This information is for educational purposes only and does not constitute medical advice. Isoniazid is a prescription medication that should only be used under the supervision of a qualified healthcare professional. Treatment decisions should be based on individual patient characteristics, drug susceptibility testing, and local treatment guidelines. Patients should not initiate, adjust, or discontinue therapy without consulting their physician. Healthcare providers should reference official prescribing information and current clinical guidelines for complete dosing, safety, and monitoring recommendations.

Reviews

“Isoniazid remains the backbone of our TB control program. Its efficacy in combination therapy is well-established, though we maintain vigilant monitoring for hepatotoxicity, particularly in older patients.” - Infectious Disease Specialist, 15 years experience

“After implementing routine pyridoxine supplementation, we’ve significantly reduced neuropathy cases in our TB clinic. The drug’s effectiveness in latent TB prevention is particularly valuable in high-risk populations.” - TB Program Director, urban health department

“While isoniazid is essential, the rising rates of mono-resistance require careful susceptibility testing before initiation. Our program uses molecular testing to guide therapy decisions.” - Microbiology Laboratory Director

“Patient education about adherence and side effect recognition is crucial. We’ve developed visual aids to help patients understand the importance of completing therapy despite initial symptom resolution.” - TB Nurse Educator