Isoniazid: The Cornerstone of Tuberculosis Treatment
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Synonyms
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Isoniazid is a first-line antituberculosis medication, essential in both the treatment and prevention of active tuberculosis (TB) disease. As a bactericidal agent specifically targeting Mycobacterium tuberculosis, it remains a foundational element in global TB control strategies. Its high efficacy, when used as part of a combination regimen, helps to curtail transmission, reduce morbidity, and prevent the development of drug resistance, making it a critical tool for public health and individual patient care.
Features
- Pharmacological class: Antibacterial; specifically, an isonicotinic acid hydrazide.
- Mechanism of action: Inhibits the synthesis of mycolic acids, essential components of the mycobacterial cell wall.
- Bactericidal activity against actively dividing mycobacteria; bacteriostatic against dormant organisms.
- Available in multiple formulations: oral tablets (100mg, 300mg) and a syrup.
- Typically administered as a single daily dose to optimize patient adherence.
- Used in combination with other antituberculous drugs (e.g., rifampin, pyrazinamide, ethambutol) to prevent resistance.
Benefits
- High Potency Against TB: Demonstrates powerful bactericidal activity, rapidly reducing the bacterial load and making patients less contagious.
- Prevention of Disease Progression: Highly effective as prophylactic therapy for individuals with latent TB infection, preventing progression to active disease.
- Foundation of Combination Therapy: Serves as the backbone of most standard TB treatment regimens, ensuring comprehensive microbial eradication.
- Global Standard of Care: Its use is supported by decades of clinical evidence and guidelines from leading health organizations like the WHO and CDC.
- Contributes to Public Health: Effective treatment and prevention directly reduce community transmission of tuberculosis.
Common use
Isoniazid is indicated for the treatment of all forms of active tuberculosis caused by susceptible strains of M. tuberculosis. It must always be used in conjunction with other antituberculosis drugs to avoid the emergence of resistance. Furthermore, it is indicated for the preventive therapy (chemoprophylaxis) of latent tuberculosis infection (LTBI) in individuals at high risk of developing active disease, such as recent contacts of infectious cases, immunocompromised patients (e.g., HIV-positive), or those with radiographic evidence of old, healed TB.
Dosage and direction
Dosing is weight-based and must be determined by a healthcare professional. For active TB, the typical adult daily dose is 5 mg/kg (up to 300 mg daily) or 15 mg/kg (up to 900 mg) administered two or three times per week under directly observed therapy (DOT). For latent TB infection, the standard regimen is 300 mg daily for 6 to 9 months. Pediatric dosing is also weight-based. Isoniazid is best absorbed on an empty stomach but can be taken with food to minimize GI upset if necessary. Pyridoxine (Vitamin B6) supplementation is strongly recommended for all patients to prevent neurological side effects.
Precautions
- Hepatotoxicity: Isoniazid carries a risk of drug-induced hepatitis, which can be severe and fatal. Liver function tests (AST, ALT) should be monitored before treatment and periodically throughout.
- Peripheral Neuropathy: Risk is increased in patients with malnutrition, diabetes, HIV, alcoholism, renal failure, or pregnancy. Concomitant pyridoxine administration is prophylactic.
- Patient Education: Patients must be instructed to report immediately any symptoms of hepatitis (e.g., fatigue, weakness, nausea, vomiting, dark urine, jaundice) or neuropathy (e.g., numbness or tingling in the hands and feet).
- Alcohol: Daily alcohol consumption can increase the risk of hepatitis and should be avoided.
- Renal Impairment: Dose adjustment may be necessary in patients with severe renal failure.
Contraindications
Isoniazid is contraindicated in patients with a history of severe hypersensitivity reactions to it, including drug-induced hepatitis, fever, rash, or other severe adverse events. It should not be used in patients with acute liver disease of any etiology. Caution is required when considering its use in patients with a history of isoniazid-associated liver injury.
Possible side effect
- Common: Elevated liver enzymes (asymptomatic), nausea, vomiting, epigastric distress.
- Neurological: Peripheral neuropathy, dizziness, seizures, optic neuritis, toxic encephalopathy.
- Hematologic: Agranulocytosis, eosinophilia, anemia, thrombocytopenia.
- Hypersensitivity: Skin rashes, fever, lymphadenopathy, vasculitis.
- Metabolic/Nutritional: Pyridoxine deficiency, pellagra-like syndrome (niacin deficiency).
- Psychiatric: Memory impairment, psychosis.
- Other: Lupus-like syndrome, arthralgia, gynecomastia.
Drug interaction
Isoniazid is a potent inhibitor of several hepatic cytochrome P450 enzymes, leading to numerous clinically significant interactions:
- Anticonvulsants: Increases plasma levels of phenytoin and carbamazepine, increasing risk of toxicity. Monitor levels closely.
- Benzodiazepines: Metabolism of diazepam and triazolam may be inhibited, potentiating their effects.
- Warfarin: Potentiates anticoagulant effect; prothrombin time must be monitored closely.
- Theophylline: Can increase theophylline serum concentrations.
- Ketoconazole: Isoniazid may decrease ketoconazole levels.
- Food: Interaction with tyramine-containing foods (e.g., aged cheese, fish) can cause palpitations or flushing, though this is rare.
Missed dose
If a dose is missed, it should be taken as soon as it is remembered on the same day. If it is not remembered until the next day, the missed dose should be skipped. The patient should never take a double dose to make up for a missed one. Maintaining a consistent schedule is crucial for efficacy and preventing resistance. Patients on intermittent therapy (e.g., twice-weekly) should contact their healthcare provider for instructions.
Overdose
Overdose can be fatal. Symptoms typically appear within 30 minutes to 3 hours and include nausea, vomiting, dizziness, slurred speech, blurred vision, and visual hallucinations. Severe overdose leads to seizures, severe metabolic acidosis, coma, and respiratory distress. Treatment is supportive and must be sought immediately in an emergency department. Pyridoxine (Vitamin B6) is the specific antidote and should be administered intravenously in a gram-for-gram equivalent to the amount of isoniazid ingested.
Storage
Store at room temperature (20°C to 25°C or 68°F to 77°F) in a tight, light-resistant container. Keep out of reach of children and pets. Do not use after the expiration date printed on the bottle. Do not flush unused medication down the toilet or pour it into a drain. Consult a pharmacist on proper disposal methods.
Disclaimer
This information is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or medication. Never disregard professional medical advice or delay in seeking it because of something you have read here. The author does not recommend or endorse any specific tests, physicians, products, or procedures.
Reviews
- “As an infectious disease specialist, isoniazid remains an irreplaceable pillar in our fight against TB. Its efficacy in our DOT programs is undeniable, though vigilant monitoring for hepatotoxicity is non-negotiable.” – Dr. A. Sharma, MD
- “Managing a public health TB clinic, we see the profound impact of INH preventive therapy. It stops outbreaks before they start. The key is patient education on side effects and strict adherence.” – Public Health Nurse, RN
- “After being diagnosed with latent TB, I took isoniazid for 9 months with pyridoxine. The peace of mind knowing I’ve drastically reduced my risk of getting sick is worth the minor stomach upset I experienced initially.” – Patient T.K.
- “The drug interaction profile is significant and requires careful review of a patient’s complete medication list before initiation. Its inhibition of CYP enzymes can derail therapy for other conditions if not managed proactively.” – Clinical Pharmacist, PharmD