Drug reference

Isoniazid + Rifampicin

Antimycobacterial · Antitubercular

Also known as Rifinah, R-Cinex, Akurit-4 FDC (contains more drugs, but RIF+INH is a common component), Rimactazid

AntimycobacterialAntitubercularATC J04AM02

CDSCO approvedSchedule HATC J04AM02

EXCRETION

—

not curated

INTERACTIONS

—

none in our sources

PREGNANCY

Category C (Isoniazid, Rifampicin). Both drugs are considered essential for treating active tuberculosis during pregnancy due to the significant risks of untreated maternal TB to both mother and fetus. Pyridoxine supplementation is recommended with isoniazid to prevent maternal and fetal neuropathy. The benefits of treatment generally outweigh the potential risks.

FDA category + note

Mechanism

Rifampicin inhibits bacterial DNA-dependent RNA polymerase, thereby suppressing RNA synthesis and causing bactericidal action against Mycobacterium tuberculosis. Isoniazid inhibits mycolic acid synthesis, an essential component of the mycobacterial cell wall, leading to cell wall disruption and bactericidal activity. The combination provides synergistic action, enhancing efficacy and reducing the risk of resistance development. Combination rationale: This fixed-dose combination is a cornerstone of tuberculosis treatment. It significantly improves patient adherence by reducing the pill burden, which is crucial for the long duration of TB therapy. The combination also provides synergistic bactericidal action against Mycobacterium tuberculosis, enhancing efficacy and, importantly, minimizing the development of drug resistance, a major challenge in TB management.

Indications

Treatment of all forms of pulmonary and extrapulmonary tuberculosis caused by susceptible strains of Mycobacterium tuberculosis

Dosing

Adult: Standard daily oral dose for new smear-positive pulmonary TB patients, based on Revised National Tuberculosis Control Programme (RNTCP) guidelines in India (e.g., for body weight 30-39 kg: Rifampicin 450 mg + Isoniazid 300 mg daily; for 40-49 kg: Rifampicin 600 mg + Isoniazid 300 mg daily; for 50-60 kg: Rifampicin 600 mg + Isoniazid 300 mg daily; for >60 kg: Rifampicin 600 mg + Isoniazid 300 mg da…
Pediatric: Weight-band based dosing: e.g., for 10-15 kg: Rifampicin 150 mg + Isoniazid 75 mg; for 16-24 kg: Rifampicin 225 mg + Isoniazid 150 mg; for 25-30 kg: Rifampicin 300 mg + Isoniazid 150 mg. Doses are administered once daily. Pediatric formulations and strengths may vary.
Renal adjustment: Isoniazid and Rifampicin are largely metabolized by the liver. In severe renal impairment (CrCl <25 mL/min), accumulation of isoniazid metabolites can occur; dose adjustment or monitoring may be needed, typically by reducing the frequency to 3 times weekly.…

Pharmacokinetics

Onset

Onset of antibacterial effect occurs within hours to days, but clinical improvement in tuberculosis takes weeks to months.

Peak effect

Isoniazid: 1-2 hours; Rifampicin: 2-4 hours.

Duration

Not typically applicable for chronic antitubercular therapy; efficacy is maintained through continuous daily dosing.

Half-life

Isoniazid: 0.5-1.6 hours in rapid acetylators, 2-5 hours in slow acetylators; Rifampicin: 2-5 hours (decreases with repeated dosing due to autoinduction).

Bioavailability

Isoniazid: 90% (oral); Rifampicin: 90-95% (oral)

Protein binding

Isoniazid: 0-10%; Rifampicin: 80% (primarily to albumin). Protein binding can be reduced in patients with hepatic impairment.

Metabolism

Isoniazid: Primarily hepatic via N-acetylation and hydrolysis; Rifampicin: Primarily hepatic via deacetylation (active metabolite) and glucuronidation. Rifampicin is a potent inducer of cytochrome P450 enzymes (e.g., CYP3A4, CYP2C9, CYP2C19), leading to autoinduction of its own metabolism and increased metabolism of other co-administered drugs.

Excretion

Isoniazid: Primarily renal (75-95% as metabolites within 24 hours); Rifampicin: Primarily biliary/fecal (60-65%), with minor renal excretion (15-30% as parent drug or active metabolites).

Contraindications

Hypersensitivity to isoniazid, rifampicin, or any component of the formulation
Acute hepatic disease or drug-induced hepatitis
Severe renal impairment (use with extreme caution or adjust dose)
History of peripheral neuropathy (for isoniazid component)

Side effects

Common

Hepatotoxicity (elevated liver enzymes, jaundice)Gastrointestinal disturbances (nausea, vomiting, abdominal pain)Orange-red discoloration of urine, sweat, saliva, tears, and other body fluids (rifampicin)Rash, pruritusHeadache, dizzinessPeripheral neuropathy (isoniazid, dose-related and more common in slow acetylators, often prevented with pyridoxine co-administration)

Serious

Severe hepatotoxicity (fulminant hepatitis, hepatic failure)
Drug-induced lupus erythematosus
Thrombocytopenia, leukopenia, hemolytic anemia
Stevens-Johnson syndrome, toxic epidermal necrolysis
Renal failure (acute interstitial nephritis)
Optic neuritis, psychosis (isoniazid)
Flu-like syndrome (rifampicin, especially with intermittent dosing)

Pregnancy & lactation

Pregnancy

Lactation

Both isoniazid and rifampicin are excreted in breast milk in concentrations sufficient to be detected. However, the amounts are typically small, and the drugs are generally considered compatible with breastfeeding by WHO and many clinical guidelines, especially given the importance of treating active maternal TB. Monitor breastfed infants for potential side effects, though serious adverse effects are rare.