Isorifam300 mg+150 mg

Isorifam is a fixed-dose combination of two first-line antitubercular agents used, as part of a physician-directed multi-drug regimen, in the treatment of tuberculosis (TB).

Established / Guideline-Supported Uses

• Continuation-phase treatment of active pulmonary and extrapulmonary tuberculosis: after an initial intensive phase that includes additional agents (e.g., pyrazinamide and ethambutol), Isorifam is used for the continuation phase (commonly at least 4 months, per WHO/national tuberculosis treatment guidelines) to complete eradication of Mycobacterium tuberculosis.
• Standard component of first-line anti-TB regimens (e.g., the WHO-recommended 2HRZE/4HR regimen), where Isorifam supplies the rifampicin and isoniazid components of the regimen.

Use Requiring Combination Therapy

Isorifam must never be used as monotherapy for active tuberculosis. It is appropriate only as part of a complete, physician-supervised multi-drug antitubercular regimen, because single-agent use rapidly selects for drug-resistant M. tuberculosis, including multidrug-resistant TB (MDR-TB).

Rifampicin + Isoniazid tablets contain a fixed-dose combination of Rifampicin and Isoniazid. Common strength ratios marketed include 150 mg + 75 mg, 300 mg + 150 mg, and 450 mg + 300 mg (Rifampicin + Isoniazid respectively), selected according to the patient's body-weight band, for oral administration as part of antitubercular therapy.

Isorifam combines two bactericidal antitubercular agents with complementary mechanisms of action against Mycobacterium tuberculosis. Rifampicin is a rifamycin-class antibiotic that inhibits bacterial RNA synthesis, while isoniazid is a synthetic hydrazide that blocks synthesis of mycolic acids essential to the mycobacterial cell wall.

Combining the two agents in a single fixed-dose tablet is standard practice in tuberculosis control programs, as it simplifies dosing, may improve adherence, and reduces the risk that patients will inadvertently take one component without the other (a practice associated with development of drug resistance).

Isorifam imparts a harmless orange-red discoloration to urine, tears, sweat, and saliva due to the rifampicin component; patients should be counselled about this and advised that soft contact lenses may become permanently stained.

Isorifam belongs to the therapeutic class of Antitubercular Agents (Fixed-Dose Combination), pairing a rifamycin antibiotic (rifampicin) with an antimycobacterial isonicotinic acid hydrazide (isoniazid).

Mechanism of Action

Rifampicin binds the beta-subunit of bacterial DNA-dependent RNA polymerase, blocking RNA chain initiation and inhibiting bacterial RNA synthesis; this activity is bactericidal against actively dividing and slowly metabolizing M. tuberculosis.

Isoniazid is a prodrug activated by the mycobacterial catalase-peroxidase enzyme (KatG) into a reactive intermediate that inhibits InhA, an enzyme required for synthesis of mycolic acids in the mycobacterial cell wall. This action is bactericidal against rapidly dividing organisms.

Pharmacokinetics

Both components are well absorbed orally, with absorption reduced by food (best taken on an empty stomach). Rifampicin undergoes hepatic deacetylation and is excreted mainly in bile with enterohepatic recirculation; it is a potent inducer of hepatic cytochrome P450 enzymes. Isoniazid is metabolized in the liver primarily by N-acetyltransferase 2 (NAT2); acetylator status ("fast" vs "slow" acetylators), which varies genetically, influences plasma levels, half-life, and risk of certain adverse effects (e.g., peripheral neuropathy, hepatotoxicity). Rifampicin + Isoniazid components are eliminated via renal and biliary/fecal routes.

• Take Isorifam by mouth, preferably on an empty stomach — at least 1 hour before or 2 hours after a meal — with a full glass of water, as food can reduce absorption of the rifampicin component.
• Swallow tablets whole; do not crush or chew unless your physician/pharmacist advises otherwise.
• Take the dose at the same time each day to maintain steady blood levels and support adherence.
• Complete the full course of Isorifam exactly as prescribed, even if you feel better before the course ends.
• If a dose is missed, take it as soon as remembered unless it is close to the next dose; do not double the dose. Contact your physician for guidance if you miss multiple doses.

The rifampicin component of Isorifam is a potent inducer of hepatic cytochrome P450 enzymes (including CYP3A4), which can significantly reduce the blood levels and effectiveness of many co-administered drugs. The isoniazid component can inhibit metabolism of certain other drugs. Clinically important interactions include:

• Hormonal contraceptives: rifampicin markedly reduces contraceptive efficacy; women of reproductive potential should be advised to use an alternative or additional non-hormonal method of contraception during and after treatment.
• Oral anticoagulants (e.g., warfarin): rifampicin reduces anticoagulant effect (may need dose increase), while isoniazid can increase warfarin levels; close INR monitoring is required.
• Antiretroviral drugs (protease inhibitors, some NNRTIs): rifampicin substantially lowers levels of many antiretrovirals; certain combinations (e.g., with ritonavir-boosted protease inhibitors) should be avoided — HIV-TB co-treatment requires specialist guidance.
• Azole antifungals, corticosteroids, oral hypoglycemics, anticonvulsants (e.g., phenytoin), theophylline, and cyclosporine: rifampicin can markedly lower their effectiveness through enzyme induction; isoniazid can raise phenytoin and carbamazepine levels through enzyme inhibition — dose adjustment and monitoring are often needed.
• Alcohol: increases the risk of hepatotoxicity with both components (see Precautions and Warnings) and should be avoided during treatment.
• Aluminum-containing antacids: can reduce isoniazid absorption; separate dosing by at least 1 hour.

Inform your physician and pharmacist of all other medicines you are taking before starting Isorifam.

As with any medicine, Isorifam can cause side effects. Report any of the following to your physician.

Common

• Nausea, vomiting, abdominal discomfort, loss of appetite, diarrhea
• Harmless orange-red discoloration of urine, tears, sweat, and saliva (rifampicin component); may stain soft contact lenses
• Headache, dizziness, drowsiness, or tiredness

Less Common / Serious (seek medical attention)

• Signs of liver injury: yellowing of skin/eyes, dark urine, unusual fatigue, loss of appetite, right upper abdominal pain (see Precautions and Warnings for hepatotoxicity monitoring)
• Numbness, tingling, or burning sensation in the hands or feet (peripheral neuropathy, mainly with isoniazid)
• Skin rash, itching, hives, or flu-like reactions (fever, chills, muscle pain) — occasionally with intermittent dosing
• Easy bruising or bleeding (thrombocytopenia), unusual paleness or fatigue (hemolytic anemia), sore throat/fever (leukopenia)
• Reduced urine output or blood in urine (rare interstitial nephritis)

Seek urgent medical care for signs of a severe allergic reaction (swelling of the face/throat, difficulty breathing) or severe skin reactions (blistering, peeling skin).

Pregnancy: Active tuberculosis in pregnancy carries significant risk to both mother and fetus if untreated, and Isorifam is generally used to treat TB during pregnancy when clearly needed, as the potential benefit is considered to outweigh potential risk; however, it should be used only under close physician supervision, with consideration of pyridoxine (vitamin B6) supplementation to reduce the risk of isoniazid-associated peripheral neuropathy. Consult your physician before use in pregnancy — do not start or stop treatment without medical advice.

Lactation: Small amounts of rifampicin and isoniazid pass into breast milk. Breastfeeding is generally considered compatible with maternal treatment for tuberculosis, as amounts in milk are low and untreated maternal TB poses a greater risk to the infant; the breastfed infant should be monitored, and pyridoxine supplementation for the infant may be advised by the physician. Discuss the benefits and risks with your physician before breastfeeding while using Isorifam.

Hepatotoxicity (Important Warning)

Both components of Isorifam can cause liver injury, and the risk is additive when used together; fatal hepatitis has been reported, particularly in patients with pre-existing liver disease, regular alcohol use, older age, malnutrition, or concurrent use of other hepatotoxic drugs. Baseline liver function tests are recommended before starting treatment, with periodic monitoring during treatment, especially in higher-risk patients. Stop treatment and contact your physician immediately if you develop signs of liver injury (yellowing of skin/eyes, dark urine, persistent nausea, unusual fatigue, abdominal pain).

Peripheral Neuropathy

Isoniazid can cause peripheral neuropathy (numbness, tingling, or burning in hands/feet), more likely in patients with diabetes, malnutrition, alcohol use disorder, HIV infection, renal failure, or slow-acetylator status. Pyridoxine (vitamin B6) supplementation is often prescribed alongside Isorifam to reduce this risk.

Treatment Adherence (Antitubercular Stewardship)

Take Isorifam exactly as prescribed by your physician for the full duration of treatment (often 6 months or more as part of a complete regimen); do not stop, extend, skip doses, or share this medicine with others without medical advice. Irregular dosing or premature discontinuation is a leading cause of treatment failure and multidrug-resistant tuberculosis (MDR-TB).

Other Precautions

• Avoid alcohol during treatment because of the additive risk of liver toxicity.
• Isorifam causes harmless orange-red discoloration of body fluids and may permanently stain soft contact lenses.
• Use with caution in patients over 35 years of age, those with HIV infection, and those on other chronic hepatotoxic medications — closer monitoring is warranted (see Use in Special Populations).
• Rifampicin markedly reduces the effectiveness of hormonal contraceptives (see Interactions) — advise an alternative method of contraception.

Overdose of Isorifam is a medical emergency. Isoniazid overdose in particular can cause severe, potentially life-threatening effects, including refractory seizures, severe metabolic (lactic) acidosis, and coma, which may appear within 30 minutes to a few hours of ingestion; rifampicin overdose can cause nausea, vomiting, loss of consciousness, an exaggerated brownish-red to orange discoloration of skin and body fluids, and liver dysfunction.

If overdose is suspected, seek immediate medical attention or contact emergency services/a poison control center right away — do not wait for symptoms to appear. Take the medication container with you. Management is supportive and must be provided in a medical facility (e.g., airway support, seizure control, and — for isoniazid overdose — prompt intravenous pyridoxine (vitamin B6) as part of emergency treatment, along with gastric decontamination and, in severe cases, hemodialysis); do not attempt to treat an overdose at home.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Hepatic Impairment

Use with caution and consider a reduced total dose in mild-to-moderate hepatic impairment, with close monitoring of liver function; Isorifam is contraindicated in severe/active liver disease (see Contraindications).

Renal Impairment

Rifampicin dose adjustment is generally not required in renal impairment, as it is mainly eliminated via the biliary route; isoniazid dose may need adjustment in severe renal failure, particularly in slow acetylators, due to reduced clearance.

Elderly

Patients over 35 years of age are at increased risk of hepatotoxicity and should be monitored more closely for signs of liver injury and peripheral neuropathy during treatment with Isorifam.

HIV Co-infection

Patients with HIV co-infection are at increased risk of hepatotoxicity and require careful management of drug interactions between Isorifam and antiretroviral therapy (see Interactions); specialist input is recommended.

Diabetes / Alcohol Use / Malnutrition

These patients have an increased risk of isoniazid-associated peripheral neuropathy; pyridoxine (vitamin B6) supplementation is commonly recommended.

The duration of Isorifam therapy is determined by the physician based on the overall tuberculosis treatment regimen and the patient's response. In a typical first-line regimen, Isorifam is used for the continuation phase, generally at least 4 months, following an initial intensive phase with additional antitubercular agents — giving a total standard treatment duration of 6 months or more for drug-susceptible TB (longer for certain forms of extrapulmonary TB, treatment interruption, or drug resistance). The full prescribed duration must be completed exactly as directed, even if symptoms resolve earlier, to prevent relapse and drug resistance.

Antitubercular agents (fixed-dose combination): Rifamycin antibiotic (rifampicin) + Isonicotinic acid hydrazide / antimycobacterial agent (isoniazid)

In Rifampicin + Isoniazid, rifampicin inhibits bacterial DNA-dependent RNA polymerase, blocking transcription and RNA synthesis in Mycobacterium tuberculosis. Isoniazid is a prodrug activated within the mycobacterium by catalase-peroxidase (KatG) to a reactive species that inhibits InhA, disrupting mycolic acid synthesis essential for the mycobacterial cell wall. Together these complementary, bactericidal mechanisms target both actively dividing and slower-metabolizing bacilli, reducing the likelihood of resistance emerging compared with either drug alone.

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Isorifam is used in children as part of standard multi-drug tuberculosis treatment regimens, following WHO and national pediatric TB dosing guidance, with dosing calculated by body weight (approximately rifampicin 10–20 mg/kg/day and isoniazid 7–15 mg/kg/day, within recommended maximums) and appropriate weight-band formulations. Use should be supervised by a physician experienced in pediatric TB management, with monitoring for hepatotoxicity and, where indicated, pyridoxine (vitamin B6) co-supplementation to reduce the risk of peripheral neuropathy, particularly in malnourished or breastfed infants. Safety and efficacy of specific fixed-dose tablet strengths in very young infants should be confirmed with the prescribing physician, as formulation availability varies.