Фтизоактив

General characteristics. Structure:

Active ingredients: 100 mg of an isoniazid and 5 mg of a pyridoxine; 150 mg of an isoniazid and 7,5 mg of a pyridoxine; 200 mg of an isoniazid and 10 mg of a pyridoxine; 300 mg of an isoniazid and 15 mg of a pyridoxine; 300 mg of an isoniazid and 60 mg of a pyridoxine.

Excipients: starch potato grade "Extra", povidone, magnesium stearate, silicon dioxide colloid, talc.

The combined means against tuberculosis, especially active concerning the fast-breeding microorganisms (including located intracellularly).

Pharmacological properties:

Pharmacodynamics. The isoniazid has bactericidal effect on actively sharing Mycobacterium tuberculosis cells. The mechanism of its action consists in oppression of synthesis of the mikoliyevy acids which are a component of a cell wall of mycobacteria. For tuberculosis mycobacteria the minimum overwhelming concentration of drug makes 0,025-0,05 mg/l. The isoniazid possesses moderate action on slow and fast-growing atypical mycobacteria.

Pyridoxine (B6 vitamin). Participates in a metabolism. It is necessary for normal functioning of the central and peripheral nervous system. At a tuberculosis infection there comes deficit of a pyridoxine. In this regard the daily dose of vitamin raises to 60 mg. At a concomitant use of a pyridoxine inside with an isoniazid, lomefloksatsiny, Pyrazinamidum and Ethambutolum do not observe interaction of these drugs at the pharmacokinetic and microbiological levels. Reduces a neurotoxicity of antitubercular medicines.

Pharmacokinetics. Isoniazid. Reception of the isoniazid inside together with a pyridoxine which is a part of "Ftizoaktiv" does not influence the speed of its absorption from digestive tract. The isoniazid gets into many fabrics and liquids, including cerebrospinal fluid. Time of achievement of the maximum concentration of drug in blood (TCmax) - 2 hours, the size Cmax is-6,6 mg/l, an elimination half-life (T1/2) - 5,8 hours. The isoniazid practically does not contact proteins of plasma. The isoniazid to 80-90% is excreted with urine and 10% with a stake within a day. Key products of metabolism of an isoniazid - N-atsetilizoniazid and isonicotinic acid.

The pyridoxine is soaked up quickly throughout a small intestine, the bigger quantity is absorbed in a jejunum. It is metabolized in a liver with formation pharmacological of active metabolites (пиридоксаль phosphate and пиридоксаминофосфат). Piridoksal phosphate contacts proteins of plasma for 90%. Well gets into all fabrics; collects preferential in a liver, it is less - in muscles and the central nervous system. Gets through a placenta, cosecretes with breast milk. An elimination half-life - 15-20 days. It is removed by kidneys.

Indications to use:

Tuberculosis (any localization, at adults and children, treatment and prevention, including as a part of a combination therapy).

Route of administration and doses:

Inside, after food, on 600-900 mg/days of an isoniazid in 1-3 receptions, the maximum single dose - 600 mg of an isoniazid, daily - 900 mg of an isoniazid; to children is more senior 3 – x years - on 5-15 mg/kg/days of an isoniazid, frequency rate of reception - 1 - 2 time a day, the maximum dose - 500 mg/days of an isoniazid.

For the purpose of prevention by the adult and to children is more senior 3-x years - inside, on 5-10 mg/kg/days of an isoniazid in two steps in days, within 2 months. During pregnancy and at a severe form of a pulmonary heart, the expressed atherosclerosis, coronary heart disease and arterial hypertension should not appoint more than 10 mg/kg of an isoniazid in doses.

Features of use:

For delay of development of microbic stability appoint together with other antitubercular drugs.

In certain cases during treatment fatal medicinal hepatitis which can arise even after several months of the end of use develops.

The risk increases with age (the largest frequency in an age group of 35-64 years), especially at the daily use of ethanol. Therefore it is monthly necessary to control function of a liver, to persons 35 years function of a liver in addition are more senior investigate before an initiation of treatment. Except the ethanol use accessory factors of risk are chronic diseases of a liver, parenteral use of any medicines and the puerperal period; under these circumstances control of function of a liver (laboratory and clinical) should be carried out more often.

Patients have to be informed on need to report about any manifestations of damage of a liver (inexplicable anorexia, nausea, vomiting, urine darkening, jaundice, rash, paresthesias of brushes and feet, weakness, fatigue or fever lasting more than 3 days, abdominal pains, especially in right hypochondrium). In these cases drug is immediately cancelled.

To the patients who earlier had izoniazidny hepatitis appoint alternative antitubercular medicines. In need of therapy resuming, it is begun after full permission of clinical and laboratory signs of hepatitis with the subsequent constant control of function of a liver. At any signs of a recurrence drug is immediately cancelled.

At patients with acute diseases of a liver preventive reception Ftizoaktiva should be postponed. Due to the different speed of metabolism before use Ftizoaktiva it is reasonable to determine isoniazid inactivation speed by its content in blood and urine. At a bystry inactivation drug is used in higher doses.

During treatment it is necessary to avoid the use of cheese (especially Swiss or Cheshire), fishes (especially a tuna, a sardinella, a skipdzhek) as at their simultaneous use with an isoniazid emergence of the reactions (a dermahemia, an itch, feeling of heat or cold, heartbeat, the increased sweating, a fever, a headache, dizziness) connected with suppression of activity of a monoaminooxidase (MAO) and diaminoxidase and leading to disturbance of metabolism of tyramine and the histamine which are contained in fish and cheese is possible.

It must be kept in mind that the isoniazid can cause a hyperglycemia with a secondary glucosuria; tests with recovery of ions of copper can be false positive, and drug does not influence fermental glucose tests. Simultaneous alcohol intake promotes strengthening of hepatotoxic reactions. Laboratory indicators of alaninaminotranspherase and aspartate aminotransferase, concentration of bilirubin in blood serum can tranzitorno raise without clinical manifestations.

At severe damages of a liver the pyridoxine in high doses can cause deterioration in its function. When determining urobilinigen by means of Ehrlich's reagent can distort results. During treatment it is necessary to be careful during the driving of motor transport and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions

Side effects:

Connected with an isoniazid. From a nervous system: headache, dizziness, paresthesias, numbness of extremities, peripheral neuropathy; seldom - excessive fatigue or weakness, irritability, euphoria, sleeplessness, an optic neuritis, a polyneuritis, toxic psychosis, emotional lability, a depression, spasms, toxic neuropathy, memory disturbance.

From cardiovascular system: heart consciousness, stenocardia, increase in arterial pressure.

From the alimentary system: nausea, vomiting, gastralgia; increase in activity of alaninaminotranspherase and aspartate aminotransferase, hyperbilirubinemia, bilirubinurea, jaundice; seldom - toxic hepatitis, including with a lethal outcome.

From bodies of a hemopoiesis: agranulocytosis, hemolitic, sideroblastny or aplastic anemia, thrombocytopenia, eosinophilia.

Allergic reactions: skin rash (korevidny, makulopapulezny, exfoliative, purpura), itch, fever, arthralgia, lymphadenopathy, vasculitis.

From a metabolism: pyridoxine hypovitaminosis (B6 vitamin), pellagra, hyperglycemia, metabolic acidosis, gynecomastia.

Others: very seldom - a menorrhagia, tendency to bleedings and hemorrhages.

Connected with a pyridoxine. Allergic reactions, hypersecretion of hydrochloric acid, numbness, emergence of feeling of a prelum in extremities - a symptom of "stockings" and "gloves", it is rare - skin rash, a skin itch.

Interaction with other medicines:

Isoniazid. At a combination with paracetamol also nephrotoxicity increases gepatoto-; the isoniazid induces system of P450 cytochrome therefore metabolism of paracetamol increases up to toxic products.

Ethanol raises a hepatotoxic of an isoniazid and accelerates his metabolism.

Reduces theophylline metabolism that can lead to increase in its concentration in blood.

Reduces metabolic transformations and increases concentration in alfentanil blood. Cycloserinum and Disulfiramum strengthen adverse central effects of an isoniazid.

Raises a rifampicin hepatotoxic. The combination to a pyridoxine reduces danger of development of peripheral neuritis.

With care it is necessary to combine with potentially neuro, gepato-and nefrotoksichny medicines because of danger of strengthening of side effect. Strengthens action of derivatives of coumarin and an indandion, benzodiazepines, carbamazepine, theophylline as reduces their metabolism due to activation of isoenzymes of P450 cytochrome. Glucocorticosteroids accelerate metabolism in a liver and reduce active concentration in blood.

Suppresses metabolism of Phenytoinum that leads to increase in its concentration in blood and to strengthening of toxic effect (correction of the mode of dosing of Phenytoinum, especially at patients with slow acetylation of an isoniazid can be required); it is necessary to consider at appointment as an anticonvulsant at overdose as an isoniazid. Antiacid medicines (especially aluminum-bearing) slow down absorption and reduce concentration of an isoniazid in blood (antacids should be accepted not earlier than in 1 h after reception of an isoniazid).

At simultaneous use with enflurany the isoniazid can increase formation of the inorganic fluoric metabolite possessing nefrotoksichny action.

At joint reception with rifampicin reduces concentration of a ketokonazol in blood. Increases concentration of valproic acid in blood (control of concentration of valproic acid is necessary; correction of the mode of dosing can be required).

The pyridoxine weakens action of a levodopa at their combined use. The pyridoxine reduces risk of development of toxic effect of antitubercular drugs on the central and peripheral nervous system.

Contraindications:

Hypersensitivity to any component of drug. Medicinal hepatitis and a liver failure (against the background of the previous treatment of an isoniazid), liver diseases in aggravation stages, a convulsive syndrome, children's age up to 3 years. With care: the peptic ulcer of a stomach and a 12-perstny gut, coronary heart disease, alcoholism, a liver failure, a renal failure, convulsive attacks, age is more senior than 35 years, the exhausted patients, therapy cancellation with an isoniazid in the anamnesis, peripheral neuropathy, HIV infection, dekompensirovanny diseases of warmly vascular system (stenocardia, arterial hypertension), a hypothyroidism. - not to appoint use at a lactation and pregnancy in a dose it is higher than 10 mg/kg on an isoniazid.

Overdose:

Isoniazid. Symptoms are shown during 0.5-3 h after introduction: nausea, vomiting, dizziness, the greased speech, a vision disorder, visual hallucinations.

At the expressed overdose: a respiratory distress syndrome, the oppression of the central nervous system which is quickly passing from a stupor into a coma, the heavy not stopped spasms, a heavy metabolic acidosis, acetonuria, a hyperglycemia.

Treatment: at the expressed overdose (80-150 mg/kg) insufficient therapy leads to a neurotoxicity with a lethal outcome. At adequate therapy the forecast favorable.

At asymptomatic overdose: absorbent carbon, gastric lavage. At reception in a dose more than 80 mg/kg in the same dose intravenously enter a pyridoxine if the dose of the accepted isoniazid is unknown, then the adult intravenously enter 5 g of a pyridoxine, to children - 80 mg/kg within 30-60 min. At clinical manifestations: adequate ventilation, maintenance of activity it is warm – vascular system, prevention of aspiration of gastric contents.

If the dose of the accepted isoniazid is known, intravenously bolyusno enter the same quantity of a pyridoxine within 3-5 min. If the dose of the accepted isoniazid is unknown, then the adult intravenously enter 5 g of a pyridoxine, to children - 80 mg/kg. If spasms do not stop, the dose can be repeated. Seldom it is necessary to appoint a dose more than 10 g.

The maximum safe dose of a pyridoxine at overdose by an isoniazid is unknown. At inefficiency of a pyridoxine appoint diazepam. It is necessary to control the content of electrolytes, urea, glucose and the partial pressure of gases in blood. At development of a metabolic acidosis Natrii hydrocarbonas can strengthen a hypercapnia (continuous monitoring is necessary). Dialysis is appointed if spasms and acidosis were not stopped by a pyridoxine, diazepam and Natrii hydrocarbonas.

Storage conditions:

In the dry, protected from light place at a temperature not over 25 ºС.

Issue conditions:

According to the recipe

Packaging:

On 100, 500 or 1000 tablets (for hospitals) in bank of polymeric.