Universal reference book for medicines

Active substance: ethambutol, isoniazid

Type: Anti-TB drug

Manufacturer: FARMASINTEZ (Russia)
Composition, form of production and packaging
1 tab.

isoniazid 150 mg

ethambutol hydrochloride 400 mg

500 pcs.
- polymer cans.
500 pcs.
- polypropylene cans.
100 pieces.
- polypropylene cans.
1000 pcs.
- polypropylene cans.
Tablets 1 tab.

isoniazid 300 mg

ethambutol hydrochloride 800 mg

500 pcs.
- polymer cans.
500 pcs.
- polypropylene cans.
100 pieces.
- polypropylene cans.
1000 pcs.
- polypropylene cans.

Description of the drug approved by the manufacturer for the printed edition of 2010.


Protubetam contains a combination of two anti-tuberculosis drugs.

has a bactericidal effect on the actively dividing cells of Mycobacterium tuberculosis. The mechanism of its action is the inhibition of the synthesis of mycolic acids, which are a component of the cell wall of mycobacteria. For mycobacteria tuberculosis, the minimum inhibitory concentration of the drug is 0.025-0.05 mg / l. Isoniazid has a moderate effect on slow and fast-growing atypical mycobacteria.
Bacteriostatic drug, effective against typical and atypical mycobacteria tuberculosis. The mechanism of action of the drug is associated with a violation of the synthesis of RNA in bacterial cells, it suppresses the synthesis of the cell wall, blocking the inclusion of mycolic acids in it. Etambutol is active against rapidly and slowly growing atypical, mycobacteria. The minimum inhibitory concentration of ethambutol is - 0.78-2.0 mg / l. Ethambutol does not act on nontuberculous pathogenic microorganisms.


Isoniazid quickly and completely absorbed when ingested, eating reduces absorption and bioavailability.
The effect of "first passage" through the liver has a great influence on the bioavailability index. TC max - 1-2 hours, C max after oral intake of a single dose of 300 mg - 3-7 Ојg / ml. The connection with proteins is insignificant - up to 10%. The volume of distribution is 0.57-0.76 l / kg. Well distributed throughout the body, penetrating all tissues and fluids, including cerebrospinal, pleural, ascites; high concentrations are created in the lung tissue, kidneys, liver, muscles, saliva and sputum. Penetrates through the placental barrier and into breast milk.
It is metabolized in the liver by acetylation with the formation of inactive products.
The liver is acetylated with N-acetyltransferase to form N-acetylisoaniazide, which is then converted to isonicotinic acid and monoacetylhydrazine, which has a hepatotoxic effect by forming a mixed oxidase system of cytochrome P450 during the N-hydroxylation of the active intermediate metabolite. The rate of acetylation is genetically determined; in people with "slow" acetylation, there is little N-acetyltransferase. It is an inhibitor of CYP2C9 and CYP2E1 isoenzymes in the liver. T 1/2 for "fast acetylators" - 0.5-1.6 hours; for "slow" - 2-5 hours. In case of renal insufficiency T 1/2 can increase up to 6.7 hours T 1/2 for children aged 1.5 to 15 years - 2.3-4.9 h, and in newborns - 7.8-19.8 h (which is explained by the imperfection of the processes of acetylation in newborns). Despite the fact that the index T 1/2 significantly varies depending on the individual intensity of the acetylation processes, the average value of T 1/2 is 3 hours (ingestion 600 mg) and 5.1 h (900 mg). With repeated appointments, T 1/2 is shortened to 2-3 hours.
It is excreted mainly by the kidneys: 75-95% of the drug is excreted within 24 hours, mainly in the form of inactive metabolites - N-acetylisiniazide and isonicotinic acid.
At the same time, "fast acetylators" contain N - acetylisiniazide content of 93%, and "slow" - not more than 63%. Small amounts are excreted with feces. The drug is removed from the blood during hemodialysis; 5 h hemodialysis allows you to remove from the blood to 73% of the drug.

Absorption is high;
bioavailability - 75-80%. After oral administration of a dose of 25 mg, the time to reach the maximum concentration of the drug in the blood TCmax is 2-4 hours, the maximum concentration of the drug in the blood C max is 1-5 Ојg / ml. Connection with plasma proteins - 20-30%.
It penetrates well into tissues and organs, as well as into biological fluids, except for ascitic and pleural (in spinal fluid only with meningitis).
The greatest concentrations are created in the kidneys, lungs, saliva, urine. Penetrates into breast milk. Do not pass through the intact blood-brain barrier.
Partially metabolic is expressed in the liver (15%) with the formation of inactive metabolites.
T 1/2 - 3-4 hours, with renal dysfunction -8 hours. It is excreted by the kidneys - 80-90% (50% - unchanged, 15% - in the form of inactive metabolites) through the gastrointestinal tract - 10-20% (in unchanged form). It is excreted in hemodialysis and peritoneal dialysis.

- treatment of all forms and localizations of tuberculosis caused by sensitive mycobacteria to isoniazid and ethambutol;

- can be used for chemoprophylaxis of tuberculosis and conducting anti-relapse therapy.


The drug Protubetam is administered orally 1 to 3 times a day, after a meal (at the rate of 5-15 mg / kg / day isoniazid, the maximum dose is 900 mg / day).
The drug is used daily in the intensive care period (3-4 months), in the subsequent time - every other day. The total course dose of Protubetam for each individual and depends on the nature of the disease, the effectiveness of treatment and tolerability.


From the side of the central nervous system: headache, dizziness, rarely - unusual fatigue or weakness, irritability, euphoria, insomnia, paresthesia, numbness of limbs, peripheral neuropathy, optic neuritis, polyneuritis, psychosis, mood change, depression.
Seizures can occur in patients with epilepsy.
From the cardiovascular system: palpitation, angina, increased blood pressure.

On the part of the digestive system: nausea, vomiting, gastralgia, toxic hepatitis.

Allergic reactions: skin rash, itching, hyperthermia, arthralgia.

Other: very rarely - gynecomastia, menorrhagia, tendency to bleeding and hemorrhage.


From the side of the nervous system and sensory organs: weakness, headache, dizziness, impaired consciousness, disorientation, hallucinations, depression, peripheral neuritis (paresthesia in the extremities, numbness, paresis, itching), optic neuritis (decreased visual acuity, mostly green and red flowers, color blindness, scotoma).

On the part of the digestive system: decreased appetite, nausea, vomiting, gastralgia, impaired liver function - increased activity of "liver" transaminases (ALT, ACT, alkaline phosphatase).

Allergic reactions: dermatitis, skin rash, itching, arthralgia, fever, anaphylaxis.

Other: hyperuricemia, exacerbation of gout.


- epilepsy and other diseases, accompanied by a tendency to convulsions;

- arterial hypertension II-III
- cardiac ischemia;

- cirrhosis of the liver;

acute hepatitis;

- myxedema;

- optic neuritis;

- cataract;

- diabetic retinopathy;

- Children's age (up to 13 years);

- Pregnancy;

- lactation period;

- hypersensitivity to isoniazid and ethambutol.

With caution, prescribe the drug to people with chronic kidney failure.


Contraindicated during pregnancy and lactation.


With caution, prescribe the drug to people with chronic kidney failure.


Contraindicated in cirrhosis of the liver, acute hepatitis.


Contraindicated in children under 13 years.


During treatment it is necessary to refrain from taking ethanol.
Protubetam may have a hepatotoxic effect, so use with caution in patients with impaired liver function in individuals with chronic alcoholism a.
For the prevention and treatment of peripheral neuropathy, additional administration of pyridoxine (vitamin B 6 ) is recommended.
In some cases, especially in patients with a history of gout, it is recommended to periodically monitor the level of uric acid in the serum. It is necessary to check the visual acuity of each eye individually and both eyes together. Visual acuity is checked before treatment and periodically during treatment. With any change in visual acuity, patients should immediately consult a doctor. If there is a decrease in visual acuity, the drug is canceled. Vision usually normalizes after a timely withdrawal.
Impact on the ability to drive vehicles and manage mechanisms

When taking in high doses, it is possible to develop adverse reactions from the nervous system, for example, peripheral neuropathy, which affects the ability to drive and work with complex equipment.



Symptoms: dizziness, dysarthria, lethargy, disorientation, hyperreflexia, peripheral polyneuropathy, abnormal liver function, metabolic acidosis, hyperglycemia, glucosuria, ketonuria, convulsions (1-3 hours after drug administration), coma.

Treatment: peripheral polyneuropathy (vitamins: pyridoxine, thiamine, glutamic acid, nicotinamide, massage, physiotherapeutic procedures);
seizures (in / m pyridoxine hydrochloride - 200-250 mg, in / m 25% solution of magnesium sulfate - 10 ml, diazepam); a violation of liver function (methionine, thioctic acid, cyanocobalamin).

Symptoms: nausea, vomiting, hallucinations, polyneuritis.

Treatment: symptomatic.



When combined with paracetamol, hepato- and nephrotoxicity increases;
isoniazid induces a cytochrome P450 system, which increases the metabolism of paracetamol to toxic products.
Ethanol increases the hepatotoxicity of isoniazid and speeds up its metabolism.

Reduces the metabolism of theophylline, which can lead to an increase in its concentration in the blood.

Cycloserine and disulfiram increases the adverse central effects of isoniazid.

Combination with pyridoxine reduces the risk of peripheral neuritis.

Caution should be combined with potentially neuro-, hepato- and nephrotoxic drugs because of the risk of side effects.

Strengthens the action of coumarin and indanedione derivatives, benzodiazepines, carbamazepine, as it reduces their metabolism by activating the cytochrome P450 system.

Glucocorticosteroids accelerate metabolism in the liver and reduce active concentrations in the blood.

It suppresses the metabolism of phenytoin, which leads to an increase in its concentration in the blood and an increase in the toxic effect (correction of the dosing regimen of phenytoin may be necessary, especially in patients with slow acetylation of isoniazid).


Aluminum hydroxide reduces the absorption of ethambutol.

The use of ethambutol with aminoglycosides, ciprofloxesin, imipenem, carbamazepine, lithium salts, quinine increases the risk of neurotoxic action of the drug.

Etambutol enhances the antimicrobial activity of other antituberculosis drugs.


For hospitals.


List B. In a dry, the dark place at a temperature of no higher than 25 В° C.
Keep away from children. Shelf life - 2 years.
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