Isoniazid: The Gold Standard in Tuberculosis Treatment
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Synonyms
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Isoniazid is a first-line antituberculosis medication that has remained the cornerstone of TB therapy for decades. As a highly specific bactericidal agent, it targets Mycobacterium tuberculosis with exceptional efficacy, particularly against actively dividing bacilli. Its role extends beyond active disease treatment to crucial prophylactic use in latent tuberculosis infection, preventing progression to active disease. This medication continues to be an essential component of global TB control programs due to its proven effectiveness and generally favorable safety profile when properly monitored.
Features
- Chemical name: isonicotinic acid hydrazide
- Molecular formula: C₆H₇N₃O
- Available as 100 mg and 300 mg oral tablets
- Also available as syrup formulation (50 mg/5 mL)
- Requires prescription in all jurisdictions
- Typically administered as part of combination therapy
- Stable at room temperature when properly stored
- Rapid oral absorption with peak serum concentrations within 1-2 hours
Benefits
- Highly effective bactericidal action against Mycobacterium tuberculosis, rapidly reducing bacterial load and infectivity
- Critical component of combination therapy that prevents development of drug resistance when used appropriately
- Proven efficacy in latent TB infection with up to 90% risk reduction for progression to active disease
- Well-established safety profile when monitoring protocols are followed, allowing for long-term administration
- Cost-effective treatment option that remains accessible in resource-limited settings
- Flexible dosing regimens that can be adapted to various patient populations and clinical scenarios
Common use
Isoniazid is primarily indicated for the treatment of all forms of active tuberculosis caused by susceptible strains of Mycobacterium tuberculosis. It must always be administered in combination with other antituberculosis drugs to prevent the development of drug resistance. The medication is equally crucial for the treatment of latent tuberculosis infection in appropriate candidates, significantly reducing the risk of progression to active disease. Special populations including children, HIV-positive individuals, and contacts of active TB cases often benefit from isoniazid prophylaxis according to established guidelines.
Dosage and direction
Active tuberculosis treatment: 5 mg/kg (up to 300 mg) daily or 15 mg/kg (up to 900 mg) twice weekly as part of combination therapy. Treatment duration typically ranges from 6 to 9 months depending on regimen and disease characteristics.
Latent tuberculosis treatment: 300 mg daily or 900 mg twice weekly for 6-9 months. Alternative regimens may be considered based on patient factors and local guidelines.
Pediatric dosing: 10-15 mg/kg daily (up to 300 mg) or 20-40 mg/kg twice weekly (up to 900 mg).
Administration should occur on an empty stomach, preferably one hour before or two hours after meals, to maximize absorption. However, if gastrointestinal upset occurs, administration with a small amount of food may be acceptable despite slightly reduced bioavailability.
Precautions
Baseline assessment should include complete blood count, liver function tests, and renal function assessment. Regular monitoring of liver enzymes is mandatory during treatment, with increased frequency in patients with pre-existing liver disease, chronic alcohol use, or during the postpartum period. Patients should be educated to report immediately any symptoms suggesting hepatitis, including unexplained anorexia, nausea, vomiting, dark urine, or jaundice. Peripheral neuropathy risk necessitates pyridoxine supplementation in malnourished patients, those with alcohol dependence, pregnant women, and individuals with diabetes or HIV. Visual acuity should be monitored as isoniazid may cause optic neuritis.
Contraindications
Isoniazid is contraindicated in patients with previous severe hypersensitivity reactions to the drug. Acute liver disease of any etiology represents a relative contraindication, requiring careful risk-benefit assessment. Previous isoniazid-associated liver injury necessitates extreme caution if re-challenge is considered. The medication should not be administered to patients with severe peripheral neuropathy unless no alternative exists and appropriate mitigation strategies are implemented. Concurrent use with carbamazepine, phenytoin, or disulfiram requires careful monitoring due to potentially serious interactions.
Possible side effect
Common reactions (≥1%): peripheral neuropathy (preventable with pyridoxine), asymptomatic transaminase elevation, nausea, vomiting, epigastric discomfort, dizziness.
Serious reactions (<1%): drug-induced hepatitis (age-dependent risk), optic neuritis with blurred vision and color vision disturbances, agranulocytosis, hemolytic anemia, lupus-like syndrome, seizures in overdose, hypersensitivity reactions including rash and fever.
Rare events: psychiatric symptoms including psychosis, arthralgia, gynecomastia, pellagra-like syndrome, metabolic acidosis.
Drug interaction
Isoniazid inhibits several cytochrome P450 enzymes, notably CYP2C19 and CYP3A4, leading to numerous clinically significant interactions. Concurrent administration with phenytoin or carbamazepine may increase levels of these anticonvulsants, necessitating dose reduction and therapeutic drug monitoring. Benzodiazepines, particularly triazolam, may have enhanced effects. Theophylline levels may increase requiring dosage adjustment. Alcohol consumption may increase the risk of hepatitis. Rifampin coadministration may increase isoniazid’s hepatotoxicity potential while decreasing its serum levels through induction of metabolism. Antacids containing aluminum may decrease isoniazid absorption.
Missed dose
If a dose is missed, it should be taken as soon as possible on the same day. If remembered the next day, the missed dose should be skipped and the regular schedule resumed. Doubling of doses is not recommended. For twice-weekly regimens, if a dose is missed, the scheduling should be adjusted to maintain the appropriate interval between doses. Consistent adherence is critical to treatment success and resistance prevention. Patients should be counseled on the importance of adherence and provided with strategies to maintain their dosing schedule.
Overdose
Acute isoniazid overdose represents a medical emergency requiring immediate intervention. Symptoms typically appear 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, and respiratory depression. Treatment involves immediate gastric lavage if presentation is early, activated charcoal administration, and aggressive supportive care. Pyridoxine (vitamin B6) is the specific antidote and should be administered intravenously in gram quantities equivalent to the amount of isoniazid ingested. Seizures should be controlled with benzodiazepines, with pyridoxine being the primary anticonvulsant in this context.
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 liquid formulations. Keep out of reach of children and pets. Do not use beyond the expiration date printed on packaging. Proper disposal of unused medication is recommended through drug take-back programs rather than flushing or household trash disposal.
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 familiar with tuberculosis management. Treatment decisions must be individualized based on specific patient circumstances, drug susceptibility testing, and current treatment guidelines. Healthcare providers should consult full prescribing information and current guidelines before initiating therapy. Patients should not adjust their dosage or discontinue medication without consulting their healthcare provider.
Reviews
Clinical experience with isoniazid spans over six decades, establishing it as one of the most thoroughly studied antimicrobial agents. The medical literature consistently demonstrates its efficacy in both active tuberculosis treatment and latent infection prevention when used appropriately. Systematic reviews confirm that isoniazid-containing regimens achieve cure rates exceeding 95% in drug-susceptible tuberculosis with adequate adherence. The preventive therapy efficacy is well-documented across diverse populations, though careful patient selection and monitoring remain essential. While hepatotoxicity concerns are valid, the risk-benefit ratio strongly favors appropriate use in indicated patients with proper monitoring protocols. Ongoing research continues to refine its role in various clinical scenarios and special populations.