| Drug | Common Side Effects | Serious Risks |
|---|---|---|
| Isoniazid | Transient nausea, headache, peripheral neuropathy | Hepatotoxicity, severe liver injury |
| Rifampin | Orange body fluids, mild GI upset | Hepatotoxicity, strong inducer of CYP450 |
| Ethambutol | Blurred vision, rash | Optic neuritis leading to permanent vision loss if untreated |
| Pyrazinamide | Gout flares, nausea | Severe hepatotoxicity, hyperuricemia |
| Bedaquiline | QT prolongation, nausea | Cardiac arrhythmia, hepatotoxicity |
| Delamanid | Headache, dizziness | QT prolongation, hepatic dysfunction |
When treating active tuberculosis, Isoniazid is a firstâline oral antibiotic that blocks mycolic acid synthesis in Mycobacterium tuberculosis. Itâs been a cornerstone of TB therapy since the 1950s, but clinicians often wonder whether another drug might work better for a particular patient. This article walks through the most common alternatives, points out where each shines, and helps you decide which regimen fits a given clinical picture.
Isoniazid (INH) is prized for three reasons:
Its downsides include liver toxicity, especially in older adults or those drinking alcohol, and a risk of peripheral neuropathy that can be mitigated with vitamin B6 supplementation.
Below are the main drugs youâll see paired with or swapped for Isoniazid in modern regimens.
Rifampin is a broadâspectrum antibiotic that inhibits RNA synthesis in Mycobacterium tuberculosis. Itâs usually given at 600mg daily for adults and is essential in both standard 6âmonth regimens and shorter 4âmonth protocols.
Ethambutol works by disrupting cellâwall formation and is given at 15mg/kg daily. Itâs added mainly to prevent resistance when susceptibility is unknown.
Pyrazinamide is a proâdrug that becomes active in acidic environments, targeting dormant bacilli. The typical adult dose is 20-25mg/kg daily for the first two months of treatment.
Streptomycin is an injectable aminoglycoside that interferes with protein synthesis. Itâs reserved for multiâdrugâresistant (MDR) cases or when oral options are limited.
Bedaquiline is a newer diarylquinoline that inhibits the ATP synthase of Mycobacterium tuberculosis. Approved for MDRâTB, itâs dosed 400mg daily for two weeks, then three times per week.
Delamanid is a nitroâimidazole that blocks mycolic acid synthesis, similar to Isoniazid but with a different enzymatic target. Used in MDRâTB, the adult dose is 100mg twice daily.
Each alternative brings its own sideâeffect profile, drugâinteraction concerns, and cost considerations.
| Drug | Typical Sideâeffects | Serious Risks |
|---|---|---|
| Isoniazid | Transient nausea, headache, peripheral neuropathy | Hepatotoxicity, severe liver injury |
| Rifampin | Orange body fluids, mild GI upset | Hepatotoxicity, strong inducer of CYP450 (affects many meds) |
| Ethambutol | Blurred vision, rash | Optic neuritis leading to permanent vision loss if untreated |
| Pyrazinamide | Gout flares, nausea | Severe hepatotoxicity, hyperuricemia |
| Streptomycin | Injection site pain | Ototoxicity, nephrotoxicity |
| Bedaquiline | QT prolongation, nausea | Cardiac arrhythmia, hepatotoxicity |
| Delamanid | Headache, dizziness | QT prolongation, hepatic dysfunction |
Understanding interactions helps avoid treatment failures. Isoniazid is a mild inhibitor of CYP2C19 and CYP3A4, meaning it can raise levels of certain antiretrovirals and anticonvulsants. Rifampin, on the other hand, is a potent CYP450 inducer, slashing concentrations of warfarin, oral contraceptives, and many HIV drugs. Bedaquiline and Delamanid share QTâprolonging potential, so they should never be combined with other QTâextending agents like fluoroquinolones without close ECG monitoring.
Hereâs a quick decision guide:
These scenarios illustrate that Isoniazid remains valuable, but the right choice balances resistance patterns, patient comorbidities, and drugâaccessibility.
For anyone on Isoniazid, baseline liver function tests (ALT/AST) are a must, with repeat testing at month 1 and month 2. Patients over 35years or those consuming alcohol regularly need more frequent checks. Vitamin B6 (pyridoxine) 25mg daily prevents neuropathy in highârisk groups. With Rifampin, monitor for drugâlevel drops of coâprescribed meds. Bedaquiline and Delamanid require baseline and monthly ECGs to watch QT intervals.
In the UK, Isoniazid and Rifampin are funded under the NHS TB program, making them essentially free for patients. Ethambutol and Pyrazinamide are similarly covered. Bedaquiline and Delamanid are newer and can be pricey (âÂŁ1,200âÂŁ1,500 for a full course), but theyâre available through specialty pharmacies for MDRâTB cases.
If youâre dealing with standard, drugâsusceptible TB, Isoniazid stays the cheapest, most effective backbone. When liver health is shaky, resistance looms, or the disease is multiâdrugâresistant, youâll need to lean on Rifampin, Ethambutol, or the newer agents. Always pair the drug choice with the right monitoring plan, and remember that drug interactions can make or break a regimen.
Occasional light drinking is generally tolerated, but heavy or chronic alcohol use dramatically raises the risk of liver injury. If you drink more than two units a day, discuss liverâfunction monitoring with your doctor.
Isoniazid can deplete pyridoxine, leading to peripheral neuropathy. A daily 25mg dose of pyridoxine prevents numbness and tingling, especially in diabetics and pregnant women.
Bedaquiline targets ATP synthase, a distinct bacterial enzyme, giving it activity against strains resistant to Isoniazid and Rifampin. Itâs reserved for MDRâTB and requires cardiac monitoring.
Yes, most guidelines list Isoniazid as safe in all trimesters, provided pyridoxine supplementation is given. It helps prevent congenital TB, which can be fatal.
For latent TB infection, a 6âmonth daily regimen (INH+pyridoxine) is common. For active disease, Isoniazid is part of a 6âmonth combination therapy, with the drug given throughout.
Andrea Dunn
October 5, 2025 AT 02:17They don't want you to know the real side effects đ
Sunthar Sinnathamby
October 8, 2025 AT 02:46Balancing the efficacy of isoniazid with its hepatotoxic risk is crucial. In standard TB cases, the drugâs early bactericidal activity saves lives. However, you must watch liver enzymes closely, especially in patients over 35 or with alcohol use. Adding pyridoxine can prevent peripheral neuropathy, a simple yet often overlooked step. The regimenâs low cost makes it unbeatable for most health systems. Stay vigilant, and youâll keep the cure effective.
Catherine Mihaljevic
October 11, 2025 AT 03:15Isoniazid works but itâs not a miracle drug it can wreck the liver if youâre not careful
Callum Smyth
October 14, 2025 AT 03:45Great rundown! đ Remember to schedule monthly liver function tests and keep pyridoxine handy â itâs a small step that prevents big problems. If a patient shows any jaundice, pause the therapy and reâevaluate. Keep the communication open with the care team and the patient â thatâs how you stay ahead of sideâeffects.