rifampicin + isoniazid




Full Prescribing Info
Rifampicin, isoniazid.
Each film-coated tablet contains rifampicin 150 mg and isoniazid 75 mg.
Duomax is a fixed-dose combination of rifampicin and isoniazid used in the treatment of tuberculosis. It has been developed for improving patient compliance.
Pharmacology: Rifampicin: The oral administration of rifampicin produces peak plasma concentrations in 2-4 hrs. The t½ of rifampicin varies from 1.5-5 hrs and is increased in the presence of hepatic dysfunction; it may be decreased in patients receiving isoniazid concurrently who are slow inactivators of Duomax. Up to 30% of a dose of rifampicin is excreted in the urine; less than half of this may be unaltered antibiotic. Adjustment of dosage is not necessary in patients with impaired renal function.
Isoniazid: Peak plasma concentrations of 3-5 mcg/mL develop 1-2 hrs after oral ingestion of usual doses. From 75-95% of a dose of isoniazid is excreted in the urine within 24 hrs, as metabolites. The main excretory products in man are the result of enzymatic acetylation (acetylisoniazid) and enzymatic hydrolysis (isonicotinic acid). The rate of acetylation significantly alters the concentrations of Duomax that are achieved in plasma and its t½ in the circulation. The t½ of Duomax may be prolonged in the presence of hepatic insufficiency.
Microbiology: Rifampicin and isoniazid at therapeutic levels have demonstrated bactericidal activity against both intra- and extracellular Mycobacterium tuberculosis. Rifampicin inhibits DNA-dependent RNA polymerase activity in susceptible Mycobacterium tuberculosis and is bactericidal against slow and intermittently growing organisms. Isoniazid kills actively growing tubercle bacilli by inhibiting the biosynthesis of mycolic acids present in the cell wall of M. tuberculosis.
Continuation phase of short course treatment of patients with pulmonary or extrapulmonary tuberculosis. During this phase, Duomax should be administered on a daily continuous basis.
Dosage/Direction for Use
Duomax is administered to patients on the basis of body weight.
Adults >70 kg: 5 tablets; 55-70 kg: 4 tablets; 38-54 kg: 3 tablets; 30-37 kg: 2 tablets.
Rifampicin: Nausea, vomiting and increasing lethargy appears within a short time after ingestion, unconsciousness may occur when there is severe hepatic disease. Brownish-red or orange discoloration of the skin, urine, sweat, saliva, tears and feces will occur and its intensity is proportional to the amout ingested. Liver enlargement, possibly with tenderness, may develop within a few hours after severe overdosage, jaundice may develop rapidly. Other physical findings remain essentially normal. Bilirubin levels may increase rapidly with severe overdosage. The treatment is supportive.
Isoniazid: Nausea, vomiting, dizziness, slurring of speech, blurring of vision and visual hallucinations are early manifestations of overdosage. Respiratory distress and central nervous system depression progressing to coma with or without seizures, may occur with marked overdosage. Severe metabolic acidosis, acetonuria and hyperglycemia are typical laboratory findings. Treatment consists of gastric lavage following intubation and the control of convulsions by diazepam IV. Large doses of pyridoxine may have to be given IV. Metabolic acidosis can be corrected by sodium bicarbonate.
History of hypersensitivity to rifampicin, isoniazid or to any of the excipients of Duomax.
Patients with severe hepatic damage; patients who develop severe adverse reactions to isoniazid like drug fever, chills and arthritis; acute liver disease with any etiology and patients suffering from acute gout.
Special Precautions
Duomax is not recommended for initial therapy of tuberculosis or for prevention therapy.
Duomax should be used with caution in patients of diabetes mellitus, since diabetes management may be more difficult.
Rifampicin: Intermittent administration (once or twice weekly) of rifampicin may cause flu-like syndrome with fever, chills and malaise, hematologic reactions (leukopenia, thrombocytopenia or acute hemolytic anemia), cutaneous and hepatic reactions more frequently. Duomax due to its rifampicin content, may produce a reddish coloration of the urine, sweat, sputum and tears about which the patient should be cautioned.
Isoniazid: Patients who consume alcohol daily should be carefully monitored for hepatitis.
Adverse Reactions
Adverse reactions reported for individual components are as follows.
Rifampicin: Gastrointestinal: Heartburn, epigastric distress, anorexia, nausea, vomiting, jaundice, flatulence, cramps and diarrhea have been reported.
Hematological: Thrombocytopenia, transient leukopenia, hemolytic anemia and decreased hemoglobin have been observed.
Central Nervous System: Headache, fever, drowsiness, fatigue, ataxia, dizziness, mental confusion, behavioral changes and rarely, myopathy have been reported.
Ocular: Visual disturbances.
Renal: Elevations in blood urea nitrogen and serum uric acid have been reported. On rare occasions, hemolysis, hemoglobinuria, hematuria, interstitial nephritis, renal insufficiency and acute renal failure have been observed.
Cutaneous: These are mild and self-limiting but are not hypersensitivity reactions. They occur in the form of flushing and itching with or without rash.
Hypersensitivity Reactions: These are seen occasionally as pruritus, urticaria, rash, pemphigoid reaction, eosinophilia and conjunctivitis.
Isoniazid: Hepatitis: Severe hepatitis may occur due to isoniazid, which may sometimes be fatal. The risk of developing hepatitis is age-related and increases after the age of 20 years and is maximum at 65 years. This risk is also increased with daily consumption of alcohol. Patients given isoniazid are therefore required to be monitored at regular intervals for serum transaminase levels and for any prodromal symptoms of hepatitis eg, fatigue, weakness, malaise, anorexia, nausea or vomiting.
Peripheral Neuropathy: This is the most common side effect, which is dose related. Occurs more commonly in the patients susceptible to neuropathy eg, malnourished, alcoholics, diabetics.
Gastrointestinal: Nausea, vomiting and epigastric distress.
Hematologic: Agranulocytosis, hemolytic, sideroblastic or aplastic anemia, thrombocytopenia and eosinophilia.
Hypersensitivity Reactions: Fever, skin eruptions, lymphadenopathy and vasculitis.
Metabolic: Pyridoxine deficiency, pellagra, hyperglycemia, metabolic acidosis and gynecomastia.
Miscellaneous: Rheumatic syndrome and systemic lupus erythematosus-like syndrome.
Drug Interactions
Rifampicin: Being an inducer of cytochrome P-450 enzymes, rifampicin may accelerate elimination of certain drugs using this metabolic pathway. These include phenytoin, antiarrhythmics (disopyramide, mexiletine, quinidine), anticoagulants, antifungals (fluconazole, itraconazole, ketoconazole), barbiturates, β-blockers, calcium-channel blockers (diltiazem, nifedipine, verapamil), chloramphenicol, ciprofloxacin, corticosteroids, cyclosporine, cardiac glycosides, oral contraceptives, clofibrate, dapsone, diazepam, haloperidol, oral hypoglycemic agents, narcotic analgesics, progestins and theophylline. It may be necessary to adjust the dosage of these drugs if they are given concurrently with Duomax.
Isoniazid: Isoniazid inhibits the metabolism of anticonvulsants, benzodiazepines, haloperidol, ketoconazole, theophylline and warfarin. It may be necessary to adjust the dosage of these drugs if they are given concurrently with Duomax.
Store at temperatures not exceeding 30°C.
MIMS Class
ATC Classification
J04AM02 - rifampicin and isoniazid ; Belongs to the class of combination drugs used in the systemic treatment of tuberculosis.
FC tab 80's.
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