Rimcure 3-FDC Tablet

Rifampin, isoniazid, and pyrazinamide is indicated in the initial phase of the short-course treatment of pulmonary tuberculosis. During this phase, which should last 2 months, this drug should be administered on a daily, continuous basis. 
 
Following the initial phase and treatment with this drug, treatment should be continued with rifampin and isoniazid for at least 4 months. Treatment should be continued for a longer period of time if the patient is still sputum or culture positive, if resistant organisms are present, or if the patient is HIV positive.

In the treatment of tuberculosis, the small number of resistant cells present within large populations of susceptible cells can rapidly become the predominant type. Since resistance can emerge rapidly, susceptibility tests should be performed in the event of persistent positive cultures during the course of treatment. Bacteriologic smears or cultures should be obtained before the start of therapy to confirm the susceptibility of the organism to rifampin, isoniazid, and pyrazinamide and they should be repeated throughout therapy to monitor response to the treatment. If test results show resistance to any of the components of this drug and the patient is not responding to therapy, the drug regimen should be modified.

Rifampicin, isoniazid and pyrazinamide are all active bactericidal antituberculosis drugs. Rifampicin and isoniazid are particularly active against the rapidly growing extracellular organisms and have an intracellular bactericidal activity. Rifampicin also inhibits DNA-dependent RNA polymerase activity in susceptible cells and it has activity against slow and intermittently-growing M tuberculosis. Pyrazinamide, particularly in the acid pH environment of macrophages is active against intracellular organisms. Combination of these agents covers activity against the 3 different bacterial populations.

Total Dosage Requirement:

• Rifampicin: 10 (8-12) mg/kg body mass/day.
• Isoniazid: 5 (4-6) mg/kg body mass/day.
• Pyrazinamide: 25 (20-30) mg/kg body mass/day.

Pediatric Patients: The ratio of the drugs may not be appropriate in pediatric patients under the age of 15 (e.g., higher mg/kg doses of isoniazid are usually given in pediatric patients than adults).

The tablets should be given as a single dose, preferably on an empty stomach, at least 30 min before breakfast to ensure a high peak serum concentration.

Tablets are recommended in the initial intensive phase of the short course treatment of tuberculosis. During this phase which lasts for 2 months

Rifampicin may reduce effectivity of hormonal contraceptives, ACE inhibitors (e.g. enalapril, imidapril), antiemetics (e.g. aprepitant), antineoplastics (e.g. imatinib), diuretics (e.g. eplerenone), drugs for erectile dysfunction (e.g. tadalafil), oral hypoglycaemics (e.g. nateglinide, repaglinide), NSAIDs (e.g. etoricoxib). Rifampicin may reduce serum levels of atovaquone, ketoconazole. Antacids may reduce absorption of rifampicin. Anaesthetics and halothane may increase risk for hepatotoxicity with rifampicin and isoniazid.

Isoniazid may increase serum levels of phenytoin and theophylline; and may decrease carbamazepine metabolism. Stavudine may increase risk of distal sensory neuropathy with isoniazid. Antacids may reduce isoniazid absorption. May increase plasma levels of isoniazid with para-aminosalicylic acid. Increased risk of CNS toxicity when isoniazid is used concomitantly with cycloserine.

Pyrazinamide antagonizes the effects of probenecid and sulfinpyrazone.

Potentially Fatal: Concominant use with saquinavir/ritonavir may increase risk of severe hepatotoxicity. May reduce antiviral efficacy of atazanavir, darunavir, fosamprenavir, saquinavir, or tipranavir.

Known or suspected hypersensitivity to rifamycins and/or to isoniazid and to pyrazinamide and/or to any of the excipients including a history of drug-induced hepatitis, acute liver diseases regardless of their origin, and peripheral neuritis.

Unwanted effects which may occur during continuous daily or intermittent therapy: Rifampicin: Rifampicin may cause reddish discolouration of body fluids and occasionally other body secretions eg, urine, sputum, lacrimal fluid, faeces, saliva and sweat. It may permanently discolour soft contact lenses.

Hepatic Effects: Very common (>10%) is an asymptomatic increase in liver enzymes; severe life-threatening hepatic reactions eg, hepatic failure and acute fulminant hepatitis are uncommon (>0.1% and <1%). In isolated cases (<0.01 %), a fatal outcome was observed.

Renal Effects: Elevations of BUN and serum uric acid, haemolysis, haematuria, interstitial nephritis, renal insufficiency.

Gastrointestinal Effects: Nausea, abdominal pains, vomiting or diarrhoea, pseudomembranous colitis.

Central and Peripheral Nervous System Effects: Tiredness, drowsiness, headache, dizziness, ataxia, mental confusion, muscular weakness, visual disturbances.

Haematological Changes: Leucopenia, eosinophilia, thrombocytopenia and thrombocytopenic purpura.

Effects on Skin and Appendages: Flushing, itching with or without skin rash, urticaria, reddening of the eyes, exudative conjunctivitis or generalised hypersensitivity reactions involving the skin eg, exfoliative dermatitis, Lyell's syndrome and pemphigoid reactions.

Endocrine Effects: Disturbances in the menstrual cycle, induction of crisis in Addison patients.

Unwanted effects chiefly occurring during intermittent therapy or upon resumption of treatment after temporary interruption

Pregnancy Category C. Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks

Caution is advised in patients with impaired renal or liver function, diabetes mellitus, chronic alcoholism and undernourished patients, patients with a history of gout and patients suffering from convulsive disorders and acute porphyria. Precautions need to be taken: Blood counts and liver function tests (SGPT, SGOT) should be performed periodically (especially in prolonged treatment) and at baseline, if possible.

Patients with current chronic liver disease or impaired liver function should be treated with caution and under strict medical supervision. Careful monitoring of liver function should be carried out and attention should be paid to possible prodromal symptoms of hepatitis eg, fatigue, weakness, malaise, anorexia, nausea or vomiting. If these symptoms appear or if signs suggestive of hepatic damage are detected, treatment should be discontinued promptly. The occurrence of severe and sometimes fatal hepatitis associated may develop even after many months of treatment.

Combined anti- Tubercular Preparations.

Should be stored in cool and dry place.