Isoniazid vs Other TB Drugs: Detailed Comparison of Alternatives

Quick Takeaways

• Isoniazid remains the backbone of first‑line TB therapy but has notable neuro‑toxic and hepatotoxic risks.
• Rifampicin offers the strongest bactericidal power but induces many drug interactions.
• Ethambutol and Pyrazinamide are useful for shortening treatment duration, yet each brings distinct side‑effect profiles.
• Newer agents like Bedaquiline and Delamanid are reserved for multi‑drug‑resistant TB (MDR‑TB) and require careful cardiac monitoring.
• Choosing a regimen hinges on disease severity, resistance patterns, comorbidities, and patient adherence potential.

What is Isoniazid?

When doctors talk about standard tuberculosis (TB) therapy, Isoniazid is a first‑line antimicrobial that specifically targets Mycobacterium tuberculosis. First approved in the 1950s, it’s taken daily for six months in most uncomplicated cases. Its popularity stems from low cost, oral dosing, and proven efficacy against drug‑susceptible TB.

How Isoniazid Works: Mechanism of Action

Isoniazid inhibits the synthesis of mycolic acids, essential lipids that form the bacterial cell wall. Without a sturdy wall, the tubercle bacillus cannot survive. This mechanism is bactericidal against actively replicating bacteria but less effective on dormant loads, which is why it’s paired with other drugs that hit different bacterial targets.

Key Clinical Attributes of Isoniazid

• Typical adult dose: 5mg/kg (max 300mg) once daily.
• Side‑effects: peripheral neuropathy, hepatitis, rash, and rare sideroblastic anemia.
• Resistance: Mutations in thekatGgene or inhA promoter region can render the drug ineffective.
• Drug interactions: Minimal, but pyridoxine (vitaminB6) supplementation is recommended to prevent neuropathy, especially in diabetics or alcohol users.
• Cost (2025, US): Approximately $0.05 per tablet, making it one of the cheapest anti‑TB drugs worldwide.

First‑Line Alternatives: Rifampicin, Ethambutol, Pyrazinamide, and Streptomycin

These four agents are the classic companions in the “RIPE” regimen (Rifampicin, Isoniazid, Pyrazinamide, Ethambutol). Below is a side‑by‑side look at how each stacks up against Isoniazid.

Newer Options for Drug‑Resistant TB: Bedaquiline and Delamanid

When Mycobacterium tuberculosis becomes resistant to at least isoniazid and rifampicin (MDR‑TB), clinicians turn to newer, pricier agents.

• Bedaquiline: Targets ATP synthase, leading to bacterial energy collapse. Usually given for 6months at 400mg daily (first 2weeks) then 200mg three times weekly.
• Delamanid: Inhibits mycolic‑acid synthesis via a different pathway than isoniazid. Dosage is 100mg twice daily for 6months.

Both drugs can prolong the QT interval, so baseline ECG and regular monitoring are mandatory. Their annual cost exceeds $10,000 per patient, limiting use to high‑risk cases or where WHO‑endorsed regimens demand them.

How to Choose the Right Regimen

Clinicians weigh several factors:

1. Resistance profile: Drug‑susceptible TB follows the standard 6‑month RIPE course. Any resistance to isoniazid (e.g., INH‑resistant TB) often prompts substitution with fluoroquinolones or higher‑dose rifampicin.
2. Patient comorbidities: Liver disease steers doctors away from isoniazid and pyrazinamide; visual impairment limits ethambutol.
3. Drug interactions: Rifampicin induces CYP450 enzymes, reducing levels of antiretrovirals, oral contraceptives, and some anticoagulants.
4. Adherence potential: Fixed‑dose combination tablets (RIPE) simplify regimens, reducing missed doses.
5. Cost & accessibility: In low‑resource settings, affordability of isoniazid and rifampicin makes them the default.

Based on these variables, a typical decision tree looks like this: start with susceptibility testing → if both isoniazid and rifampicin are sensitive, use standard RIPE → if isoniazid resistant, replace it with a fluoroquinolone (e.g., levofloxacin) → if MDR‑TB confirmed, add bedaquiline or delamanid under specialist supervision.

Monitoring and Pitfalls

Even the best‑chosen regimen can go awry without proper follow‑up.

• Liver function: Check ALT/AST at baseline and monthly for the first two months; pause isoniazid if transaminases exceed three times the upper limit of normal.
• Neuropathy prevention: Give 25mg pyridoxine daily to anyone at risk (diabetics, pregnant women, alcohol users).
• Vision screening: Perform a red‑green color test monthly when ethambutol is part of the regimen.
• QT monitoring: For bedaquiline or delamanid, obtain an ECG before starting and then every two weeks.

Missing any of these checkpoints can lead to severe adverse events that force treatment interruption-often the biggest cause of treatment failure.

Frequently Asked Questions