Repin B6 (Tablets) Instructions for Use

Marketing Authorization Holder

M.J. Biopharm Pvt. Ltd. (India)

ATC Code

J04AM06 (Rifampicin, Pyrazinamide, Ethambutol and Isoniazid)

Dosage Form

Repin B6

Film-coated tablets: 500 or 1000 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets, dark brown in color, oval in shape, biconvex; on the cross-section, the tablet is reddish-brown in color with white specks.

Excipients: corn starch, microcrystalline cellulose, croscarmellose sodium, colloidal silicon dioxide, sodium starch glycolate, talc, magnesium stearate, opadry brown 04B56935.

500 pcs. – polyethylene bags (1) – plastic jars.
1000 pcs. – polyethylene bags (1) – plastic jars.

Clinical-Pharmacological Group

Antituberculosis drug

Pharmacotherapeutic Group

Combined antitubercular agent

Pharmacological Action

Combined antituberculosis agent.

Isoniazid exerts a bactericidal effect on actively dividing cells of Mycobacterium tuberculosis, inhibits the synthesis of mycolic acids, which are a component of the cell wall, and has a moderate effect on slowly and rapidly growing atypical mycobacteria. The MIC for Mycobacterium tuberculosis is 0.025-0.05 mg/L.

Rifampicin exerts a bactericidal effect on intracellularly and extracellularly located microorganisms, inhibits DNA-dependent RNA polymerase of microorganisms. The MIC for Mycobacterium tuberculosis is 2 mg/L.

Pyrazinamide possesses bactericidal activity, initially converting into an active form – pyrazinoic acid. The target of pyrazinamide is the mycobacterial fatty acid synthase I gene, involved in the biosynthesis of mycolic acid. It acts on intracellularly located mycobacteria and penetrates well into tuberculosis foci. In an acidic environment, the MIC is 20 mg/L.

Ethambutol is a bacteriostatic drug effective against typical and atypical Mycobacterium tuberculosis. It inhibits the synthesis of the cell wall by blocking the incorporation of mycolic acids into it. The MIC is 0.78-2 mg/L.

Pyridoxine is a vitamin agent; it is involved in metabolism. It is necessary for the normal functioning of the central and peripheral nervous system. Antituberculosis drugs can reduce the concentration of pyridoxine, therefore the daily requirement for the vitamin increases to 60 mg.

Indications

Tuberculosis (newly diagnosed, any forms).

ICD codes

Dosage Regimen

Administer orally, as a single daily dose in the morning, on an empty stomach at least 30-40 minutes before a meal.

Calculate the dose based on the patient’s body weight and the rifampicin component at 10 mg/kg.

The standard adult dosage is 4 tablets for patients weighing 33-50 kg and 5 tablets for patients weighing over 50 kg.

Do not exceed the maximum daily dose of 5 tablets.

Swallow the tablets whole with a full glass of water; do not crush or chew.

The typical course of treatment for the initial phase of tuberculosis is 2 months, with a possible extension to 4 months based on clinical assessment.

Adhere strictly to the prescribed regimen to prevent the development of drug resistance.

Monitor liver function tests and visual acuity regularly throughout therapy.

Adverse Reactions

Isoniazid

Nervous system disorders: headache, dizziness, rarely – fatigue, weakness, irritability, euphoria, insomnia, paresthesia, numbness of extremities, peripheral neuropathy, optic neuritis, polyneuritis, psychoses, emotional lability, depression, increased frequency of seizures in patients with epilepsy.

Cardiovascular system disorders: palpitations, angina pectoris, increased blood pressure.

Digestive system disorders: nausea, vomiting, gastralgia, toxic hepatitis.

Allergic reactions: skin rash, itching, hyperthermia, arthralgia.

Other: very rarely – gynecomastia, menorrhagia, tendency to bleeding and hemorrhage.

Rifampicin

Digestive system disorders: nausea, vomiting, diarrhea, decreased appetite, erosive gastritis, pseudomembranous enterocolitis, increased activity of liver transaminases in blood serum, hyperbilirubinemia, hepatitis.

Allergic reactions: urticaria, eosinophilia, angioedema, bronchospasm, arthralgia, fever.

Nervous system disorders: headache, decreased visual acuity, ataxia, disorientation.

Urinary system disorders: nephronecrosis, interstitial nephritis, acute renal failure.

Other: leukopenia, dysmenorrhea, induction of porphyria, myasthenia, hyperuricemia, exacerbation of gout, flu-like syndrome, skin reactions, hemolytic anemia, thrombocytopenic purpura.

Pyrazinamide

Digestive system disorders: nausea, vomiting, diarrhea, metallic taste in the mouth, impaired liver function (decreased appetite, liver tenderness, hepatomegaly, jaundice, yellow atrophy of the liver), exacerbation of peptic ulcer.

Nervous system disorders: dizziness, headache, sleep disturbances, increased excitability, depression, in some cases – hallucinations, convulsions, confusion.

Hematopoietic system disorders: thrombocytopenia, sideroblastic anemia, vacuolization of erythrocytes, porphyria, hypercoagulation, splenomegaly.

Musculoskeletal system disorders: arthralgia, myalgia.

Urinary system disorders: dysuria, interstitial nephritis.

Allergic reactions: skin rash, urticaria.

Other: hyperthermia, acne, hyperuricemia, exacerbation of gout, photosensitization, increased serum iron concentration.

Ethambutol

Nervous system disorders: weakness, headache, dizziness, impaired consciousness, disorientation, hallucinations, depression, peripheral neuritis (paresthesia in the extremities, numbness, paresis, itching).

Sensory organ disorders: optic neuritis (decreased visual acuity, impaired color perception, mainly of green and red colors, color blindness, scotoma).

Digestive system disorders: decreased appetite, nausea, vomiting, gastralgia, increased activity of liver transaminases.

Allergic reactions: dermatitis, skin rash, itching, arthralgia, fever, anaphylaxis.

Other: hyperuricemia, exacerbation of gout.

Pyridoxine

Allergic reactions, hypersecretion of hydrochloric acid, numbness, appearance of a feeling of compression in the extremities – “stocking” and “glove” symptom, rarely – rash, skin itching.

Contraindications

Hypersensitivity to the components of the combination; liver and gastrointestinal diseases in the acute phase; diseases of the central nervous system (including epilepsy, other diseases with a tendency to convulsive seizures); diseases of the visual organs (optic neuritis, cataract, diabetic retinopathy, inflammatory eye diseases); acute renal failure; children under 13 years of age; pregnancy; breastfeeding period.

With caution

Hypothyroidism, hyperuricemia, gout.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and lactation.

Use in Hepatic Impairment

Contraindication — liver diseases in the acute stage.

Use in Renal Impairment

Contraindicated for use in acute renal failure.

Pediatric Use

Contraindication — children under 13 years of age.

Geriatric Use

Use with caution in elderly patients to avoid the risk of exacerbation of chronic diseases.

Special Precautions

Dosing and administration regimen are determined taking into account the patient’s body weight.

Drug Interactions

Administration of isoniazid, rifampicin, ethambutol and, especially, pyrazinamide in a combined dosage form significantly increases antimicrobial activity against Mycobacterium tuberculosis.

Rifampicin induces some cytochrome P450 system enzymes, accelerating the metabolism of prednisolone, phenytoin, quinidine, oral anticoagulants, hormonal contraceptives, antifungal drugs, cimetidine, cyclosporine.

Isoniazid reduces the binding of rifampicin to plasma proteins, Pyrazinamide slows down the excretion of rifampicin.

PAS (para-aminosalicylic acid) impairs the absorption of rifampicin.

Concomitant use of rifampicin with lomefloxacin and ofloxacin leads to a decrease in the antimicrobial activity of these combinations against Mycobacterium tuberculosis.

Antacids, opioid analgesics reduce the bioavailability of rifampicin.

Isoniazid: MAO inhibitors increase the risk of adverse effects from the central nervous system and cardiovascular system.

Pyridoxine, glutamic acid reduce the risk of adverse effects of isoniazid.

Concomitant use of isoniazid and cycloserine increases the risk of neurotoxic adverse effects.

Pyrazinamide increases the serum concentration of isoniazid and rifampicin by slowing their excretion. When rifampicin is taken concomitantly with pyrazinamide, hepatotoxicity increases.

Aluminum hydroxide reduces the absorption of ethambutol.

Concomitant use of ethambutol with aminoglycosides, ciprofloxacin, imipenem, carbamazepine, lithium salts, quinine increases the risk of neurotoxic effects of drugs.

Ethambutol enhances the antimicrobial activity of other antituberculosis agents.

Pyridoxine weakens the effect of levodopa when used concomitantly, reduces the risk of toxic effects of antituberculosis drugs on the central and peripheral nervous system.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.