Isoniazid is a first-line antituberculosis medication that represents the cornerstone of modern TB therapy worldwide. As a highly specific bactericidal agent against Mycobacterium tuberculosis, it has demonstrated unparalleled efficacy in both active disease treatment and latent infection prevention. This synthetic hydrazide derivative of isonicotinic acid works by inhibiting the synthesis of mycolic acids, essential components of the mycobacterial cell wall. Its exceptional tissue penetration, including cerebrospinal fluid and caseous lesions, makes it particularly valuable in diverse clinical presentations of tuberculosis.

Features

• Chemical name: isonicotinic acid hydrazide
• Molecular formula: C₆H₇N₃O
• Mechanism: Inhibition of mycolic acid synthesis through enoyl-acyl carrier protein reductase (InhA) inhibition
• Bioavailability: Nearly 90% following oral administration
• Protein binding: Approximately 10-15%
• Metabolism: Hepatic, primarily via N-acetyltransferase 2 (NAT2)
• Elimination half-life: Fast acetylators: 0.5-1.6 hours; Slow acetylators: 2-5 hours
• Excretion: Primarily renal (75-95%)
• Pregnancy category: Category C (risk not ruled out)

Benefits

• Superior bactericidal activity against actively dividing tubercle bacilli
• Effective prevention of tuberculosis in latent infection, reducing progression risk by up to 90%
• Excellent tissue penetration including lungs, cerebrospinal fluid, and caseous material
• Oral administration convenience with once-daily dosing in most regimens
• Proven synergy with other antituberculosis drugs, enabling shorter treatment durations
• Cost-effective therapy with decades of clinical validation and established safety profile

Common use

Isoniazid is primarily indicated for the treatment of all forms of active tuberculosis caused by susceptible strains of Mycobacterium tuberculosis. It is routinely administered as part of combination therapy to prevent the emergence of drug resistance. Additionally, it serves as monotherapy for the treatment of latent tuberculosis infection in appropriate candidates. The medication finds particular utility in preventing TB reactivation in immunocompromised patients, including those with HIV infection, and individuals with recent exposure to infectious tuberculosis cases. Isoniazid is also used in chemoprophylaxis for children under five years of age who have positive tuberculin skin tests without evidence of active disease.

Dosage and direction

Active tuberculosis treatment (always in combination therapy):

• Adults: 5 mg/kg (maximum 300 mg) daily or 15 mg/kg (maximum 900 mg) 2-3 times weekly
• Children: 10-15 mg/kg (maximum 300 mg) daily or 20-40 mg/kg (maximum 900 mg) 2-3 times weekly

Latent tuberculosis treatment:

• Adults: 300 mg daily for 6-9 months or 900 mg twice weekly for 9 months
• Children: 10-20 mg/kg (maximum 300 mg) daily for 9 months

Administration should occur on an empty stomach, preferably one hour before or two hours after meals, to maximize absorption. For patients experiencing gastrointestinal upset, administration with food may be considered, though this may reduce bioavailability by approximately 20%. Dosage adjustments are necessary in patients with severe hepatic impairment, and therapeutic drug monitoring may be indicated in special populations.

Precautions

Baseline assessment should include complete blood count, liver function tests, and renal function evaluation. Monthly monitoring of liver enzymes is recommended during treatment, with more frequent monitoring in patients with pre-existing liver disease, chronic alcohol use, or concurrent hepatotoxic medications. Patients should be educated to report immediately any symptoms of hepatitis, including fatigue, weakness, nausea, vomiting, dark urine, or jaundice. Peripheral neuropathy risk necessitates pyridoxine (vitamin B6) supplementation at 25-50 mg daily in malnourished patients, pregnant women, diabetics, alcoholics, and those with HIV infection. Regular ophthalmological examinations are advised as isoniazid may rarely cause optic neuritis.

Contraindications

Isoniazid is contraindicated in patients with a history of severe hypersensitivity reactions to the drug, including drug-induced hepatitis. Previous isoniazid-associated hepatic injury represents an absolute contraindication to rechallenge. Acute liver disease of any etiology, severe renal impairment without dialysis, and history of isoniazid-induced fever, chills, or arthritis also preclude its use. The medication should not be administered during acute gout attacks due to potential effects on uric acid metabolism. Concomitant use with carbamazepine or phenytoin requires extreme caution due to mutually inhibitory metabolism.

Possible side effect

Common (≥1%): Peripheral neuropathy, elevated liver enzymes, nausea, vomiting, epigastric discomfort, dizziness, headache, dry mouth Uncommon (0.1-1%): Drug-induced hepatitis, fever, skin rash, arthralgia, paresthesia, optic neuritis, tinnitus Rare (<0.1%): Lupus-like syndrome, hematologic abnormalities (agranulocytosis, eosinophilia, thrombocytopenia), psychosis, seizures, gynecomastia Very rare: Hypersensitivity vasculitis, metabolic acidosis, rheumatic syndrome, pellegra

Hepatotoxicity represents the most serious adverse effect, typically occurring within the first three months of therapy but potentially developing at any time during treatment. Risk factors include advanced age, concurrent alcohol use, pre-existing liver disease, and slow acetylator status.

Drug interaction

Isoniazid inhibits several cytochrome P450 enzymes, particularly CYP2C19 and CYP3A4, leading to numerous clinically significant interactions:

• Anticonvulsants: Increases phenytoin and carbamazepine levels (monitor levels and reduce dose)
• Benzodiazepines: Potentiates effects of diazepam and triazolam
• Theophylline: Increases serum concentrations (monitor levels)
• Warfarin: Enhances anticoagulant effect (monitor INR closely)
• Ketoconazole: May decrease ketoconazole levels
• Disulfiram: Increased risk of neurotoxic effects
• Rifampin: Concomitant use increases hepatotoxicity risk
• Acetaminophen: Enhanced hepatotoxicity potential
• Antacids: Aluminum-containing antacids may decrease absorption

Missed dose

If a dose is missed, it should be taken as soon as remembered unless it is almost time for the next scheduled dose. In that case, the missed dose should be skipped and the regular dosing schedule resumed. Doubling of doses is not recommended. For patients on twice-weekly regimens, if a dose is missed, the schedule should be adjusted to maintain the appropriate interval between doses. Consistent adherence is critical to prevent development of drug resistance. Patients should be educated about the importance of compliance and provided with strategies to maintain regular dosing.

Overdose

Acute isoniazid overdose represents a medical emergency requiring immediate intervention. Symptoms typically develop within 30 minutes to 3 hours and may include nausea, vomiting, slurred speech, dizziness, visual disturbances, and seizures. Severe overdose can lead to metabolic acidosis, coma, respiratory depression, and death. The antidote is pyridoxine (vitamin B6), administered intravenously in gram-for-gram equivalence to the amount of isoniazid ingested. If the ingested amount is unknown, 5 grams of pyridoxine should be given initially, repeated as necessary. Supportive care including airway management, benzodiazepines for seizures, and sodium bicarbonate for acidosis is essential. Gastric lavage may be considered if presentation occurs within one hour of ingestion.

Storage

Store at controlled room temperature (20-25°C or 68-77°F) in a tight, light-resistant container. Keep away from excessive moisture and heat. Do not freeze. Keep out of reach of children and pets. Discard any medication that has expired or shows signs of deterioration. Tablets should be kept in their original packaging until use to protect from light and moisture. Do not transfer to other containers unless specifically designed for medication storage.

Disclaimer

This information is provided 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 made based on individual patient characteristics, drug susceptibility testing, and local treatment guidelines. Healthcare providers should consult full prescribing information and current clinical guidelines before initiating therapy. Patients should not adjust their dosage or discontinue medication without consulting their healthcare provider.

Reviews

“Isoniazid remains the backbone of tuberculosis therapy after decades of use. Its efficacy in both active disease and latent infection is well-established, though hepatotoxicity requires vigilant monitoring. The addition of pyridoxine has significantly reduced neurological adverse effects.” - Infectious Disease Specialist, 15 years experience

“While newer agents have emerged, isoniazid’s cost-effectiveness and proven track record maintain its position as first-line therapy. The twice-weekly directly observed therapy option has been invaluable in ensuring adherence in resource-limited settings.” - Public Health Physician

“Managing isoniazid therapy requires careful patient selection and monitoring, but the benefits in appropriate candidates are substantial. The drug interactions necessitate thorough medication reconciliation, particularly in elderly patients with polypharmacy.” - Clinical Pharmacist