Isoniazid - Darnitsa

General characteristics. Structure:

Active ingredient: isoniazid, hydrazide of isonicotinic acid;

1 tablet contains 300 mg of an isoniazid (in terms of 100% dry matter);

excipients: cellulose microcrystallic, methyl cellulose, sodium of a kroskarmeloz, calcium stearate.

Pharmacological properties:

Pharmacodynamics. Izoniazid-Darnitsa inhibits a DNA-dependent RNA polymerase and slows down synthesis of mikolevy acids of a cell wall of mycobacteria of tuberculosis. Drug has high bacteriostatic activity in relation to tuberculosis mycobacteria, detaining them growth in concentration of 0,03 mkg/ml. It is especially active concerning quickly breeding microorganisms. Poorly influences on causative agents of other infectious diseases.

Pharmacokinetics. It is well soaked up from digestive tract, easily gets through a blood-brain barrier. Time of achievement of the maximum concentration in blood (Tmax) makes 1-4 hours. Linkng with proteins of plasma makes up to 10%. Distribution volume – 0,56-0,76 l/kg. Tuberculostatic concentration after reception in a single dose remains within 6-24 hours. It is widely distributed in fabrics and liquids of an organism, including cerebrospinal fluid, a pleural exudate, ascitic liquid, skin, lungs, a phlegm, saliva, caseous masses. Gets through a placenta and it is excreted in breast milk.

It is metabolized in a liver by acetylation. Speed of acetylation is genetically determined and caused by the level of activity N-acetyltransferase. Depending on the speed of acetylation of patients subdivide on "bystry" and "slow" inactivators. At "bystry" inactivators the elimination half-life of an isoniazid makes 0,5-1,6 hours, and amount of the not changed substance emitted with kidneys – less than 10% a day. At "slow" inactivators – respectively 2-5 hours and more than 10% a day.

Pharmaceutical characteristics.

Main physical and chemical properties: tablets of color, white or white with a cream shade, a round form, with a flat surface, risky and a facet. On a surface of tablets the mramornost is allowed.

Indications to use:

• In a combination with 3-4 other protituberkulyozny drugs – for treatment of active tuberculosis of all forms and localizations;

• as monotherapy – for treatment of a latent tuberculosis infection and prevention of tuberculosis at persons who were or is in close contact with TB patients.

Route of administration and doses:

Daily and course doses are established individually, depending on a current and a form of a disease, degree of an inactivation of an isoniazid, efficiency of therapy and portability of drug.

The isoniazid is applied inside to food or in 30-40 minutes after meal.

To adults and children 4 years are more senior it is appointed in a daily dose of 5 mg/kg of 1 times a day at daily use or 10 mg/kg at intermittent reception (3 times a week).

The maximum daily dose for adults – 600 mg, for children – 500 mg.

Treatment of active tuberculosis lasts 6-8 months, for the purpose of prevention accept 2-3 months.

Features of use:

Considering that at monotherapy by an isoniazid to it stability of activators quickly develops (in 70% of cases), for delay of this process drug is appointed only together with other antitubercular drugs. At multi-infection along with an isoniazid appoint antibiotics of a broad spectrum of activity, a ftorkhinolona, streptocides, etc.

During treatment medical control, regular conducting functional hepatic trials and ophthalmologic inspection is necessary. In the first month it is necessary to conduct examination at least 2 times, then – 1 time a month.

In case of their emergence apply to reduction of side effects intramusculary a pyridoxine, Thiamini chloridum or Thiamini bromidum, glutaminic acid, the ATP sodium salt.

For the prevention of possible toxic influence of an isoniazid on a liver it is appointed in combination with gepatoprotektor.

During treatment it is undesirable to take alcoholic drinks.

Over 10 mg/kg at a pulmonary heart of the III degree, arterial hypertension of the II-III degree, coronary heart disease, diseases of a nervous system, bronchial asthma, psoriasis, eczema in a phase of an aggravation, a chronic renal failure, hepatitis in an aggravation phase, cirrhosis, a hypothyroidism, a myxedema are not recommended to use drug in a dose.

At patients with a diabetes mellitus the positive take of the glyukozurichesky test is possible.

Ability to influence speed of response at control of motor transport or work with other mechanisms.

Drivers and operators of difficult mechanisms need to consider probability of development of side effects from a nervous system which can affect ability to concentrate attention and speed of response.

Side effects:

From the central and peripheral nervous system: dizziness, a headache, irritability, euphoria, a sleep disorder, paresthesias, peripheral neuritis, psychoses, increase of attacks at patients with epilepsy, spasms, toxic encephalopathy, dysmnesias.

From sense bodys: optic neuritis, atrophy of an optic nerve.

From digestive tract: a sensation of discomfort in a stomach, anorexia, nausea, vomiting.

From gepatobiliarny system: abnormal liver function, hepatitis, increase in level of serumal transaminases (SGOT, SGPT), bilirubinemia, bilirubinurea, jaundice.

From endocrine system and a metabolism: deficit of a pyridoxine, pellagra, hyperglycemia, metabolic acidosis.

From cardiovascular system: a heart consciousness, pain behind a breast and in heart, arterial hypertension.

From system of blood: agranulocytosis, hemolitic anemia, sideroblastichesky anemia, aplastic anemia, thrombocytopenia, eosinophilia.

From a musculoskeletal system: rhematoid syndrome.

From a reproductive system: gynecomastia and menorrhagias.

Allergic reactions: skin itch, dermatitis, fervescence, lymphadenopathy, vasculitis, enanthesis (exfoliative, makulopapulezny, purpura), lupoid syndrome.

From an organism in general: indisposition, weakness.

Usually side effects pass at reduction of a dose or a temporary break in drug use.

Interaction with other medicines:

Antiacid means – reduction of absorption of an isoniazid (the interval between their reception has to make not less than 1 hour).

Indirect anticoagulants, benzodiazepines, Phenytoinum, carbamazepine, theophylline, MAO inhibitors – the isoniazid exponentiates effects of these drugs (including toxic).

Potentially hepatotoxic and neurotoxic means (including alcohol, rifampicin) – the probability of development of toxic hepatitis and neuropathy (with paracetamol the risk of development of a hepatotoxic action increases) increases.

Valproatum – at simultaneous use raises concentration of Valproatum in a blood plasma.

Stavudin – raises risk of development of distal touch neuropathy.

B6 vitamin and glutaminic acid – at a combination decreases probability of side effects of an isoniazid.

Apply to strengthening of efficiency of Izoniazid-Darnitsa in a combination with other antitubercular drugs (for example, rifampicin, Ethambutolum, Pyrazinamidum), and at multi-infection – along with antibiotics of a broad spectrum of activity: ftorkhinologam (for example, ofloxacin, ciprofloxacin), streptocides (for example, co-trimoxazole), macroleads (for example, кларитромицин, azithromycin, рокситромицин), etc.

Izoniazid-Darnitsa it is not necessary to accept during food. Researches showed that bioavailability of an isoniazid considerably decreases if it is applied together with food.

Increases antiarrhythmic properties of dipheninum.

Contraindications:

Hypersensitivity to an isoniazid or excipients of drug.

The epilepsy and other diseases which are followed by tendency to convulsive attacks, heavy psychoses, poliomyelitis (including in the anamnesis), toxic hepatitis in the anamnesis owing to use of derivatives of hydrazide of isonicotinic acid (Ftivazidum, etc.), the expressed atherosclerosis, an acute liver and/or renal failure.

Use of an isoniazid in a dose higher than 10 mg/kg of body weight a day is contraindicated during pregnancy. Feeding period breast.

Use during pregnancy or feeding by a breast.

During pregnancy use of drug in a dose higher than 10 mg/kg a day is contraindicated. In a dose to 10 mg/kg of body weight a day use of an isoniazid is possible taking into account a ratio advantage/risk. At use of Izoniazida-Darnitsa pregnant women (in a daily dose to 10 mg/kg of body weight) need to consider that the isoniazid gets through a placenta and can cause development of a myelomeningocele and hypospadias, hemorrhage (owing to a hypovitaminosis To), and also a delay of psychomotor fetation.

The isoniazid gets to breast milk therefore, considering probability of development of hepatitis and peripheral neuritis at the child, it is necessary to resolve an issue of the feeding termination by a breast or to stop drug use.

Children.
In this dosage form the Isoniazid is appointed to children 4 years are more senior.

Overdose:

At overdose in 0,5-3 hours after administration of drug nausea, vomiting, dizziness, deterioration in sight, the confused speech and visual hallucinations can develop. Heavy intoxication leads to respiratory depression and TsNS, spasms and a coma. Typical laboratory indicators of overdose by an isoniazid are the metabolic acidosis, acetonuria, a hyperglycemia.

Treatment. A gastric lavage, absorbent carbon, intravenously – high doses of a pyridoxine. The hemodialysis is effective.

Storage conditions:

Period of validity. 5 years. In the place protected from light at a temperature not above 25 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in a blister strip packaging, on 5 blister strip packagings in a pack. On 1000, 1500, 2500 tablets in containers.