Isorifam 150 mg+100 mg Capsule

Isorifam 150 mg+100 mg Capsule

Pharmacology

Rifampicin and isoniazid are active bactericidal anti-TB drugs which are particularly active against the rapidly growing extracellular organisms and also have bactericidal activity intracellularly. Rifampicin inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme. Cross-resistance to rifampicin has only been shown with other rifamycins. It has activity against slow-and intermittently-growing M. tuberculosis. Isoniazid acts against actively growing tubercle bacilli.

Dosage & Administration

Body weight <50 kg: 3 tab of 150/100 once daily or 1 tab of 450/300 once daily

Body weight >50 kg: 2 tab of 300/150 once daily.

Hepatic impairment: Max: 8 mg/kg daily.

Interaction

May reduce effectivity of hormonal contraceptives. Reduced absorption with antacids. May decrease plasma concentrations of antivirals (e.g. atazanavir, darunavir, fosamprenavir), atovaquone with rifampicin. Rifampicin may reduce serum levels of anticonvulsants (e.g. phenytoin), antiarrhythmics (e.g. disopyramide), oral anticoagulants, antifungals (e.g. ketoconazole), barbiturates, ?-blockers, Ca channel blockers (e.g. diltiazem), chloramphenicol, clarithromycin, corticosteroids, ciclosporin, cardiac glycosides, clofibrate, dapsone, diazepam, doxycycline, fluoroquinolones (e.g. ciprofloxacin), haloperidol, oral hypoglycemic agents (sulfonylureas), levothyroxine, methadone, narcotic analgesics, progestins, quinine, tacrolimus, theophylline, TCAs (e.g. amitriptyline, nortriptyline) and zidovudine. Increased risk of hepatotoxicity with halothane.

Isoniazid may inhibit the metabolism of anticonvulsants (e.g. carbamazepine, phenytoin), benzodiazepines (e.g. diazepam), haloperidol, ketoconazole, theophylline, and warfarin. May enhance the CNS effects of meperidine, cycloserine, and disulfiram with isoniazid. Loss of glucose control in patients on oral hypoglycaemics with isoniazid.

Contraindications

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

Side Effects

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 & Lactation

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

Precautions

Use of isoniazid should be carefully monitored in the following:

Daily users of alcohol. Daily ingestion of alcohol may be associated with a higher incidence of isoniazid hepatitis.

Patients with active chronic liver disease or severe renal dysfunction.

Age > 35.

Concurrent use of any chronically administered medication.

History of previous discontinuation of isoniazid.

Existence of peripheral neuropathy or conditions predisposing to neuropathy. Pregnancy.

Injection drug use.

Women belonging to minority groups, particularly in the post-partum period.

HIV seropositive patients.