Isoniazid - Darnitsa solution

General characteristics. Structure:

Dystvuyushchy substance: isoniazid;

1 ml of solution soderzhit100 isoniazid mg in terms of 100% dry matter;

excipient: water for injections.

Pharmacological properties:

Pharmacodynamics. The isoniazid 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. At parenteral administration quickly gets into body tissues, biological liquids. Passes through GEB, especially at an inflammation of a meninx. Gets into bones. It is metabolized in a liver, depending on genetic features of the person, with higher or lower speed. It is removed by kidneys. The elimination half-life at people with higher speed of metabolism of an isoniazid makes 0,5-1,5 hour, with lower – 4-6 hour. It is removed generally with bile, 30% of a dose are excreted with urine.

Pharmaceutical characteristics.

Main physical and chemical properties: the transparent colourless or slightly painted liquid.

Incompatibility. It is unknown.

Indications to use:

Treatment of all forms and localizations of active tuberculosis at adults and children (as means of the first row).

Route of administration and doses:

Izoniazid-Darnitsa apply intramusculary intravenously, in the form of inhalations, vnutrikavernozno.

Intravenously Izoniazid-Darnitsa enter for treatment of a widespread pulmonary tuberculosis, at a massive bakteriovydileniye, associated diseases of digestive tract, to patients who evade from administration of drug in inside, in case of inefficiency at a peroral way of introduction.

The intravenous daily dose makes: for adult 200-300 mg, for children – 100-300 mg (10-20 mg/kg of body weight), for newborn 3-5 mg/kg, but are no more than 10 mg/kg of body weight a day. Intravenously enter in the form of 2,5-10% of solution (if necessary drug is dissolved with water for injections or 0,9% chloride sodium solution) for 30-60 sec. of 1 times a day. The course of treatment depends on efficiency of therapy and portability of drug – 30-150 injections. For the purpose of prevention of by-effects at intravenous administration of Izoniazid-Darnitsa apply B6 vitamin (pyridoxine) and glutaminic acid. The pyridoxine is entered intramusculary (100-125 mg) in 30 min. the ambassador Izoniazida-Darnitsa or appointed in (60-100 mg) in each 2 h after intravenous administrations of Izoniazida-Darnitsa. Glutaminic acid accept from 1 to 1,5 g in a daily dose. At intravenous use of drug it is necessary to observe a bed rest for 1-1,5 h.

Intramusculary to adults and children enter in the form of ready not divorced 10% of Izoniazida-Darnitsa solution 5-12 mg/kg a day, 1 time a day, for 2-5 months. For weakening of side effect at this way of introduction inside along with Izoniazida-Darnitsa's introduction appoint a pyridoxine in a dose of 60-100 mg (it is also possible to enter intramusculary in 30 min. the ambassador Izoniazida-Darnitsa in a dose 100-125 mg/kg).

Izoniazid-Darnitsa is inhalation appoint in 1-2 receptions in the form of ready not divorced 10% of solution. A daily dose – 0,005-0,01 g (5-10 mg) on 1 kg of body weight. Inhalations carry out daily for 1-6 months.

The patient at fibrous and cavernous and cavernous forms of tuberculosis at a bakteriovydileniya and during the preoperative period appoint in the form of ready not divorced 10% of solution of the drug Izoniazid-Darnitsa in a daily dose 10-15 mg/kg,    1 time to days. Enter preferential vnutrikavernozno, by intratracheal injections.

The maximum daily and course dose of drug is established depending on character and a form of a disease, degree of an inactivation and individual portability of an isoniazid.

Features of use:

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 a pyridoxine to reduction of side effects (for example, Piridoksina gidrokhlorid-Darnitsa, intramusculary on 1 - 2 ml of 5% of solution a day), Thiamini chloridum (for example, Thiamine hlorid-Darnitsa, intramusculary 1 ml of 5% of solution a day) or Thiamini bromidum (intramusculary 1 ml of 6% of solution a day), 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 (for example, Darsil, Ursokhol).

During treatment it is desirable not to take some alcoholic drinks.

Administration of drug in a dose over 10 mg/kg at a pulmonary heart of the III degree, arterial hypertension of the II-III stages is not recommended, to 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, liver cirrhoses, a hypothyroidism, a myxedema.

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 inoziazidy appoint antibiotics of a broad spectrum of activity, a ftorkhinolona, streptocides, etc.

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, sleep disorders, 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: anorexia, nausea, vomiting.

From a liver and biliary tract: abnormal liver function, hepatitis, increase in level of serumal transaminases (SGOT, SGPT), bilirubinemia, bilirubinurea.

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, myocardium ischemia at elderly people.

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

From a reproductive system: gynecomastia and menorrhagias.

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

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

Interaction with other medicines:

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

Glucocorticosteroids – at simultaneous use metabolism and elimination of an isoniazid increases.

Phenytoinum, theophylline, carbamazepine – an isoniazid oppresses metabolism of the listed drugs that leads to increase in their concentration in a blood plasma and to possible strengthening of toxic action.

Dipheninum – an isoniazid strengthens antiarrhythmic action of dipheninum.

Potentially hepatotoxic and neurotoxic means (including alcohol, rifampicin) – are raised by probability of development of toxic hepatitis and neuropathy (with paracetamol the risk of development of a hepatotoxic action 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 kombintrovaniye 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, Rifampitsin-Darnitsa, Etambutol-Darnitsa, Pirazinamid-Darnitsa), and at multi-infection – along with antibiotics of a broad spectrum of activity: ftorkhinolonam (for example, Ofloksatsin-Darnitsa, Tsiprofloksatsin-Darnitsa), streptocides (for example, Biseptrim), macroleads (for example, Klamed, Azitsin, Roksilid), etc.

Contraindications:

Hypersensitivity to an isoniazid or excipients of drug.

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.

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

Use during pregnancy or feeding by a breast.

Use of drug at pregnancy in a dose higher than 10 mg/kg a day is contraindicated. 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, hemorrhages (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.

Drug is appointed to children since the neonatality period.

Overdose:

At overdose in 0,5-3 hours after use of drug there can be dysfunctions of a digestive tract, nausea, vomiting, neurotoxic manifestations, dizziness, deterioration in sight, the muffled speech and visual hallucinations. Heavy intoxication leads to respiratory depression and TsNS, emergence of spasms and a coma. Typical laboratory indicators of overdose by drug 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. 2 years. To Hanit in original packaging at a temperature from 2 °C to 8 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

On 5 ml in an ampoule; on 10 ampoules in a box; on 5 ampoules in a blister strip packaging; on the 2nd blister strip packagings in a pack.