Ethambutol-Akri^® (Tablets) Instructions for Use

Marketing Authorization Holder

Akrikhin Chemical and Pharmaceutical Plant, JSC (Russia)

Contact Information

AKRIKHIN JSC (Russia)

ATC Code

J04AK02 (Ethambutol)

Active Substance

Ethambutol (Rec.INN registered by WHO)

Dosage Form

Ethambutol-Akri®

Tablets 400 mg: 100 pcs.

Dosage Form, Packaging, and Composition

Tablets from white to white with a creamy or grayish tint, flat-cylindrical, with a bevel and a score line.

Excipients: calcium hydrogen phosphate dihydrate – 104.5 mg, sodium carboxymethyl starch – 5.5 mg, potato starch – 18.5 mg, magnesium stearate – 5.5 mg, povidone – 16 mg.

10 pcs. – contour cell packs (10) – cardboard packs.

Clinical-Pharmacological Group

Antituberculosis drug

Pharmacotherapeutic Group

Antitubercular agent

Pharmacological Action

Ethambutol is a chemotherapeutic agent that has a bacteriostatic effect on typical and atypical Mycobacterium tuberculosis.

The mechanism of action of the drug is associated with disruption of RNA synthesis in bacterial cells. It affects intracellular and extracellular types of bacteria. Primary resistance to the drug occurs in about 1% of patients.

Ethambutol is well absorbed in lung tissue and can reach a concentration 5-9 times higher than in blood serum, and penetrates well into many tissues and organs. The intracellular concentration in erythrocytes is twice as high as in blood serum.

Pharmacokinetics

Ethambutol is rapidly and 80% absorbed from the digestive tract. The MIC is 1 mg/ml.

After a single oral dose of 25 mg/kg body weight, C_max in serum of 25 µg/ml is reached after 2-4 hours; after 24 hours, the concentration is less than 1 µg/ml. It is 20-30% bound to plasma proteins.

Ethambutol is metabolized in the liver to dicarboxylic acid derivatives. T_1/2 is 3-4 hours, and in renal failure it is prolonged to 8 hours.

Within 24 hours, more than 50% of the drug dose is excreted in the urine unchanged, and 8-15% as inactive metabolites. About 20-22% of the initial dose of the drug is excreted in the feces unchanged.

Ethambutol crosses the placenta. The concentration of ethambutol in fetal blood is approximately 30% of the drug concentration in the mother’s blood.

Indications

• Pulmonary tuberculosis;
• Extrapulmonary tuberculosis.

ICD codes

Dosage Regimen

Orally, after meals, with plenty of fluid.

Adults – initial period of treatment: single dose – 15 mg/kg body weight/day; continuous treatment: usually 20 mg/kg body weight/day.

The dose can be increased to 30 mg/kg body weight per day (but not more than 2.0 g) in the initial period of treatment, in case of relapse of the disease, or in case of resistance of Koch’s bacilli to other anti-tuberculosis drugs.

Children from 13 years old are prescribed at the rate of 15-25 mg/kg body weight (but not more than 1.0 g). The full course of treatment lasts 9 months.

In renal diseases, the dosage of the drug depends on the degree of renal failure, the indicator of which is creatinine clearance (CC).

With CC over 100 ml/min, the daily dose is 20 mg/kg body weight/day; 70-100 ml/min – 15 mg/kg; below 70 ml/min – 10 mg/kg; during hemodialysis – 5 mg/kg; on the day of dialysis – 7 mg/kg.

In patients who have previously taken drugs with tuberculostatic action, bacterial resistance develops more often.

In such cases, Ethambutol-Akri^® should be taken with at least one or two anti-tuberculosis drugs that the patient has not taken before and to which no bacterial resistance has been noted.

Ethambutol-Akri^® is used in complex therapy with other anti-tuberculosis drugs: isoniazid, para-aminosalicylic acid, streptomycin, cycloserine, pyrazinamide, ethionamide and rifampicin.

Adverse Reactions

Retrobulbar inflammation of the optic nerve, unilateral or bilateral (decreased visual acuity, impaired color perception, presence of central or peripheral scotoma, limited visual field).

The occurrence of visual disturbances depends on the duration of treatment and existing diseases of the eyeball. If they appear, ethambutol treatment should be discontinued.

Visual changes are usually reversible and disappear a few weeks after discontinuation of treatment, in some cases after a few months. In exceptional cases, changes in the eyeball are irreversible due to optic nerve atrophy.

Allergic reactions: skin rash, skin itching, joint pain, increased body temperature, leukopenia.

Gastrointestinal disorders: metallic taste in the mouth, nausea and vomiting, abdominal pain, lack of appetite, increased activity of liver transaminases.

From the CNS: headaches and dizziness, confusion, disorientation, hallucinations, convulsions, depression, peripheral neuritis.

Increased level of uric acid in blood serum, manifestations of uric acid diathesis.

Contraindications

• Hypersensitivity to the drug;
• Inflammation of the optic nerve;
• Cataract;
• Diabetic retinopathy;
• Inflammatory eye diseases;
• Severe renal failure;
• Gout;
• Pregnancy;
• Lactation;
• Children under 13 years of age.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and lactation.

Use in Renal Impairment

The drug is contraindicated in severe renal failure.

Pediatric Use

The drug is contraindicated in children and adolescents under 13 years of age.

Special Precautions

In patients with renal failure, the dose of Ethambutol-Akri^® should be reduced due to the accumulation of the drug in the body.

Before starting treatment with Ethambutol-Akri^®, periodic ophthalmological monitoring should be performed: examination of the fundus, visual fields, visual acuity and color perception.

Periodic monitoring of liver and kidney function and a complete blood count is recommended.

Effect on ability to drive vehicles and operate machinery

Due to the possibility of visual impairment (decreased visual acuity, limited visual field, impaired color perception of green and red) during treatment with Ethambutol-Akri^®, one should not drive vehicles or operate moving mechanical equipment.

Overdose

Symptoms nausea, vomiting, hallucinations, polyneuritis.

Treatment symptomatic.

Drug Interactions

Enhances the effects of anti-tuberculosis drugs, the neurotoxicity of ciprofloxacin, aminoglycosides, asparaginase, carbamazepine, lithium salts, imipenem, methotrexate, quinine.

Ethambutol-Akri^® alters the metabolism of some trace elements, mainly zinc.

Aluminum hydroxide reduces the absorption of Ethambutol-Akri^® from the digestive tract.

Storage Conditions

List B. In a dry, light-protected place, at a temperature not exceeding 25°C (77°F). Keep out of reach of children.

Shelf Life

The shelf life is 3 years.

The drug should not be used after the expiration date.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.