EMB-Fatol 400

Uses

EMB-Fatol 400 is used for the treatment of pulmonary tuberculosis. It should not be used as the sole antituberculous drug, but should be used in conjunction with at least one other antituberculous drug. Selection of the companion drug should be based on clinical experience, considerations of comparative safety, and appropriate in vitro susceptibility studies. In patients who have not received previous antituberculous therapy, ie, initial treatment, the most frequently used regimens have been the following:

• EMB-Fatol 400 plus isoniazid
• EMB-Fatol 400 plus isoniazid plus streptomycin.

In patients who have received previous antituberculous therapy, mycobacterial resistance to other drugs used in initial therapy is frequent. Consequently, in such retreatment patients, EMB-Fatol 400 should be combined with at least one of the second line drugs not previously administered to the patient and to which bacterial susceptibility has been used by appropriate in vitro studies. Antituberculous drugs used with EMB-Fatol 400 have included cycloserine, ethionamide, pyrazinamide, viomycin and other drugs. Isoniazid, aminosalicylic acid, and streptomycin have also been used in multiple drug regimens. Alternating drug regimens have also been utilized.

EMB-Fatol 400 is also used to associated treatment for these conditions: Mycobacterium Infections, Mycobacterium avium complex infection, Pulmonary Tuberculosis (TB)

How EMB-Fatol 400 works

EMB-Fatol 400 diffuses into Mycobacterium cells. Once inside the cell, ethambutol inhibits the arabinosyltransferases (embA, embB, and embC), preventing formation of the cell wall components arabinogalactan and lipoarabinomannan, and preventing cell division. Decreased concentrations of arabinogalactan in the cell wall reduces the number of binding sites for mycolic acid, leading to the accumulation of mycolic acid, trehalose monomycolate, and trehalose dimycolate. Lipoarabinomannan is a component of a cell surface molecule involved in the interaction with host cells. Reduced levels of lipoarabinomannan may interfere with mycobacterial interaction with host cells.

Dosage

EMB-Fatol 400 dosage

EMB-Fatol 400 should not be used alone, in initial treatment or in retreatment. EMB-Fatol 400 should be administered on a once every 24-hour basis only.Absorptionis not significantly altered by administration with food. Therapy, in general, should be continued until bacteriological conversion has become permanent and maximal clinical improvement has occurred.

EMB-Fatol 400 is not recommended for use in pediatric patients under thirteen years of age since safe conditions for use have not been established.

Initial Treatment:In patients who have not received previous antituberculous therapy, administer EMB-Fatol 400 15 mg/kg of body weight, as a single oral dose once every 24 hours. In the more recent studies, isoniazid has been administered concurrently in a single, daily, oral dose.

Retreatment:In patients who have received previous antituberculous therapy, administer EMB-Fatol 400 25 mg/kg of body weight, as a single oral dose once every 24 hours. Concurrently administer at least one other antituberculous drug to which the organisms have been demonstrated to be susceptible by appropriatein vitrotests. Suitable drugs usually consist of those not previously used in the treatment of the patient. After 60 days of EMB-Fatol 400 administration, decrease the dose to 15 mg/kg of body weight, and administer as a single oral dose once every 24 hours.

During the period when a patient is on a daily dose of 25 mg/kg, monthly eye examinations are advised.

Renal Impairment: Dose adjustment may be needed as determined by blood levels of ethambutol.

Should be taken with food.

Side Effects

Retrobulbar neuritis with reduction in visual acuity, constriction of visual field, central or peripheral scotoma and green-red colour blindness of 1 or both eyes. Reduced renal clearance of urate and may precipitate acute gout. Confusion, disorientation, hallucinations, headache, dizziness, malaise, jaundice or transient liver dysfunction, peripheral neuropathy, thrombocytopenia, pulmonary infiltrates, eosinophilia and GI disturbances (e.g. nausea, vomiting, anorexia, abdominal pain). Rarely, retinal haemorrhage, hypersensitivity reactions including rashes, pruritus, leucopenia, fever, and joint pains.

Toxicity

Patients experiencing a chronic overdose of ethambutol may present with disturbances in colour vision and reduced visual acuity as symptoms of optic neuropathy. In these cases, ethambutol should be stopped. Data regarding acute overdose of ethambutol are not readily available. Patients experiencing an acute overdose of ethambutol may be experience an increased risk and severity of adverse effects such as pruritus, joint pain, gastrointestinal upset, abdominal pain, malaise, headache, dizziness, mental confusion, disorientation, and possible hallucinations. Patients should be treated with symptomatic and supportive measures.

Precaution

Patient with ocular defects (e.g. cataracts, recurrent ocular inflammatory conditions, diabetic neuropathy). Renal impairment. Pregnancy and lactation.

Interaction

Delayed or reduced absorption with aluminium hydroxide.

Food Interaction

• Take separate from antacids. Do not take aluminum hydroxide containing antacids for at least 4 hours after ethambutol administration.
• Take with food. Food reduces irritation.

EMB-Fatol 400 Drug Interaction

Unknown: fluticasone / salmeterol, fluticasone / salmeterol, acetaminophen, acetaminophen, montelukast, montelukast, tiotropium, tiotropium, acetaminophen, acetaminophen, multivitamin, multivitamin, cyanocobalamin, cyanocobalamin, pyridoxine, pyridoxine, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol

EMB-Fatol 400 Disease Interaction

Major: optic neuritisModerate: hepatic impairment, hyperuricemia, renal dysfunction

Volume of Distribution

Patients coinfected with tuberculosis and HIV have an estimated ethambutol volume of distribution of 76.2 L.

Elimination Route

Oral ethambutol is approximately 75-80% orally bioavailable. A 25 mg/kg oral dose of ethambutol reaches a C_max of 2-5 µg/mL, with a T_max of 2-4 hours. In a separate study, the AUC_0-8 varied from 6.3 ± 5.5 h*mg/L to 10.8 ± 7.6 h*mg/L depending on CYP1A2 genetic polymorphisms.

Half Life

EMB-Fatol 400 has a half life of 3.3 hours in patients with normal renal function. In patients with renal failure, the half life could be 7 hours or longer.

Clearance

Patients coinfected with tuberculosis and HIV have an estimated ethambutol oral clearance of 77.4 L/h.

Elimination Route

EMB-Fatol 400 is 50% eliminated in the urine as the unmetabolized parent compound and 8-15% as inactive metabolites. 20-22% of a dose is eliminated unchanged in the feces.

Pregnancy & Breastfeeding use

Category C: Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Contraindication

EMB-Fatol 400 is contraindicated in patients who are known to be hypersensitive to this drug. It is also contraindicated in patients with known optic neuritis unless clinical judgment determines that it may be used. EMB-Fatol 400 is contraindicated in patients who are unable to appreciate and report visual side effects or changes in vision.

Storage Condition

Store between 20-25°C. Protect from light, moisture and excessive heat.

Innovators Monograph

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