Rifampicin + Isoniazid + Ethambutol

Indications

Rifampicin + Isoniazid + Ethambutol is used for: Indicated in the initial and continuation phase of pulmonary and extra-pulmonary tuberculosis.

Adult Dose

Adult The recommended dosage and treatment regimen for tuberculosis is dependent on the patient's medical history, response to treatment, and the sensitivity of the isolate. Ethambutol : 15 mg – 25 mg / kg Rifampicin : 10 mg / kg up to 600 mg Isoniazid : 5 mg – 10 mg / kg up to 300 mg During initial phase which usually lasts 3 months, Ethambutol HCl / Rifampicin / Isoniazid is usually administered on a daily continuous basis. When indicated, other antituberculosis drug such as Pyrazinamide, Streptomycin may be added. Following the intensive phase, treatment should be continued with Ethambutol HCL / Rifampicin / Isoniazid to complete 6 months. Hepatic Failure: Dose adjustment may be necessary in patients with hepatic insufficiency.

Child Dose

This drug is not recommended for use in children under 13 years of age since safe conditions of use have not been established.

Renal Dose

Ethambutol accumulates in patients with renal insufficiency. If renal impairment is severe or if patients are slow acetylators, a reduction in dosage may be required.

Administration

Contra Indications

This should not be used in patients with a known hypersensitivity to ethambutol, isoniazid or rifampicin or to any of the excipients in this product. Also contraindicated in the presence of alcoholism, optic neuritis, impaired hepatic function and severe renal insufficiency, hyperuricemia and/or gouty arthritis, in the presence of jaundice, or in patients with known retrobulbar neuritis unless the doctor determines that it may be used.

Precautions

Ethambutol has a unique effect on the eye. It is, therefore, recommended that all patients taking Ethambutol HCl / Rifampicin / Isoniazid should undergo a full ophthalmic examination before starting treatment and periodically during drug administration. This examination should include visual acuity, colour vision, perimetry, and ophthalmoscopy. In patients with visual defects such as cataract, recurrent inflammatory conditions of the eye, optic neuritis, and diabetic retinopathy, the evaluation of changes in visual acuity is more difficult. In such patients consideration should be given to the relationship between benefits expected from Ethambutol HCl / Rifampicin / Isoniazid administration and possible visual deterioration. Patients at risk for peripheral neuropathy as a result of malnutrition, chronic alcohol dependence, or diabetes should additionally receive pyridoxine, 10 mg daily. Ethambutol is excreted into breast milk. Rifampicin and isoniazid are excreted in breast milk. Therefore, infants should not be breast fed by patients receiving Ethambutol HCl / Rifampicin / Isoniazid.

Pregnancy-Lactation

Interactions

May reduce effectivity of hormonal contraceptives. Reduced absorption w/ antacids. May decrease plasma concentrations of antivirals (e.g. atazanavir, darunavir, fosamprenavir), atovaquone w/ rifampicin. Rifampicin may reduce serum levels of anticonvulsants (e.g. phenytoin), antiarrhythmics (e.g. disopyramide), oral anticoagulants, antifungals (e.g. ketoconazole), barbiturates, β-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 w/ 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 w/ isoniazid. Loss of glucose control in patients on oral hypoglycaemics w/ isoniazid. Potentially Fatal: Concurrent treatment w/ saquinavir/ritonavir combination may result to severe hepatoxicity.

Adverse Effects

Side effects of Rifampicin + Isoniazid + Ethambutol : GI symptoms (e.g. anorexia, nausea, vomiting, constipation, diarrhoea), alterations in liver function, peripheral neuritis, optic neuritis, headache, drowsiness, convulsions, vertigo, blood disorders (e.g. leucopenia, haemolytic anaemia, aplastic anaemia, eosinophilia), dry mouth, itching w/ or w/o rash, flushing, urticaria, rash, purpura, pancreatitis, oedema, interstitial pneumonitis, hyperreflexia, hyperglycaemia, adrenal insufficiency, gynaecomastia, menstrual disturbances, difficulty in micturition, muscular weakness, myopathy, SLE-like syndrome, pellagra, exfoliative dermatitis, pemphigus, toxic epidermal necrolysis, pemphigoid reactions, orange-red discolouration of urine, saliva and other body secretions; hearing loss and tinnitus, influenza-like symptoms, resp symptoms, collapse and shock, thrombocytopenic purpura, disseminated intravascular coagulation, acute renal failure. Rarely, psychoses, pemphigoid reaction, erythema multiforme, Lyells syndrome and vasculitis. Potentially Fatal: Severe/fatal hepatitis (e.g. jaundice).

Mechanism of Action

The mechanism of action of ethambutol is not fully known. It diffuses into mycobacteria and appears to suppress multiplication by interfering with RNA synthesis. It is effective only against mycobacteria that are actively dividing. Rifampicin inhibits bacterial RNA synthesis by bonding strongly to the beta subunit of DNAdependent RNA polymerase, preventing the attachment of the enzyme to DNA and thus blocking initiation of RNA transcription. Isoniazid is a bactericidal antitubercular agent, which is active against actively dividing mycobacteria, and its mode of action may relate to inhibition of mycolic acid synthesis and the disruption of the cell wall in susceptible organisms.