Cycloserinum

General characteristics. Structure:

Active agent: Cycloserinum - 250,0 mg.

Excipients: lactose - 162,0 mg, silicon dioxide colloid - 3,0 mg, magnesium stearate - 5,0 mg.

Structure of the case of the capsule: titanium dioxide - 2%, gelatin - to 100%.

Structure of a lid of the capsule: dye ferrous oxide black - 0,1%, dye ferrous oxide red - 0,12%, dye ferrous oxide of yellow-0,3%, titanium dioxide - 2%, gelatin - to 100.

Pharmacological properties:

Pharmacodynamics. Cycloserinum - the antibiotic of a broad spectrum of activity which is formed in the course of Streptomyces orchidaceus zhiznideyatel-nost. Cycloserinum works bacteriostatically or bakteritsidno depending on concentration in the center of an infection and sensitivity of microorganisms. Cycloserinum breaks synthesis of a cell wall, working as the competitive antagonist of D-alanine, suppresses the enzymes responsible for synthesis of a cell wall of sensitive strains of gram-positive and gram-negative bacteria. Growth of mycobacteria of tuberculosis detains (Mycobacterium avium is active concerning Mycobacterium tuberculosis). The minimum overwhelming concentration in relation to M. tuberculosis makes 3-25 mg/l on liquid and 10-20 mg/l and more - on a dense medium. It is active concerning Rickettsia spp., Treponema spp. in concentration of 10100 mg/l.
Medicinal stability arises slowly (after 6 months of treatment develops in 20-60% of cases).

Pharmacokinetics. After intake quickly and almost completely (70-90%) it is soaked up from digestive tract. Time of achievement of the maximum concentration in a blood plasma - 3-4 h. In proportion to the accepted dose 0,25, 0,5, 1 g the maximum concentration in a blood plasma makes 6,24 and 30 mkg/ml respectively. After reception of 250 mg each 12 h the maximum concentration makes 25-30 mkg/ml. Well breast milk, bile, a phlegm, lymphatic fabric, lungs, ascitic and synovial liquids, a pleural exudate gets into liquids and body tissues, including cerebrospinal fluid, passes through a placenta. The abdominal and pleural cavity contains 50-100% of concentration of drug in blood serum.
Elimination half-life at normal function of kidneys - 10 h. It is removed by glomerular filtering in not changed look: 50% in 12 h, 65-70% within 24-72 h, small amounts - through digestive tract. At a chronic renal failure in 2-3 days there can be cumulation phenomena.

Indications to use:

As a part of complex therapy: - An active pulmonary tuberculosis, extra pulmonary tuberculosis (including damage of kidneys) in case of sensitivity of microorganisms to drug and after unsuccessful adequate treatment by the main medicines, chronic forms of tuberculosis;
- A tuberculosis combination to acute infections of the urinary tract caused by sensitive strains of gram-positive and gram-negative bacteria, in particular Klebsiella spp., Enterobacter coli at inefficiency of the main medicines;
- Atypical mikobakterialny infections (including the caused Mycobacterium avium), infections of urinary tract.

Route of administration and doses:

Inside, just before meal (at irritation of a mucous membrane of digestive tract - after food). Adults: the usual dose makes from 500 mg to 1 g a day. The initial dose for adults most often makes 250 mg 2 times a day from 12 an hour interval within the first two weeks, then if necessary taking into account portability the dose is carefully increased to 250 mg by each 6-8 h under control of concentration of drug in blood serum. The daily dose should not exceed 1 g.
To patients 60 years, and also with body weight less than 50 kg are more senior, drug 2 times a day appoint in a dose 250 mg.
At children 3 years an initial dose of Cycloserinum are more senior makes 10-20 mg/kg of body weight a day in 2-3 receptions (not higher than 750 mg/days; the high dose is given only in an acute phase of tubercular process or at insufficient efficiency of smaller doses).

Features of use:

Before an initiation of treatment Cycloserinum it is necessary to mark out cultures of microorganisms and to define sensitivity of strains to Cycloserinum. The patients receiving more than 500 mg of Cycloserinum a day have to be under direct observation of the doctor because of possible development of side effects from the central nervous system.
Treatment by Cycloserinum needs to be cancelled or it is necessary to reduce a dose if at the patient allergic dermatitis or symptoms of intoxication of the central nervous system develop, for example: spasms, psychosis, drowsiness, oppression or confusion of consciousness, hyperreflexia, headache, tremor, dizziness, paresis or dysarthtia.
The risk of development of a convulsive syndrome increases at patients with an alcoholism therefore use of Cycloserinum at this state is contraindicated.
Anticonvulsant or sedative drugs can be effective for prevention of neurotoxic reactions, for example: spasms, condition of excitement or tremor. At administration of drug it is necessary to control hematologic indicators, secretory function of kidneys, concentration of Cycloserinum in blood and a condition of function of a liver. Concentration of Cycloserinum in blood should not exceed 30 mg/ml. At treatment of patients with reduced function of the kidneys accepting a daily dose more than 500 mg and in which presumably signs and symptoms of overdose are found drug level in blood needs to be controlled, at least, once a week. The dose needs to be adjusted so that to support drug level in blood lower than 30 mg/l. Such patients have to be under direct observation of the doctor because of possible development of symptoms of toxicity. In certain cases use of Cycloserinum and other antitubercular drugs can cause insufficiency of cyanocobalamine (B12 vitamin) and folic acid in an organism, development of megaloblastny anemia. In case of developing of anemia during treatment it is necessary to conduct the corresponding examination and treatment of the patient.
It is possible to warn or reduce toxic action of Cycloserinum, appointing during treatment glutaminic acid on 0,5 g 3 - 4 times a day (to food), and daily intramuscular administration of sodium salt of adenosine triphosphoric acid (1 ml of 1% of solution), a pyridoxine of 200-300 mg/days.
It is necessary to limit the mental tension of patients and to exclude possible factors of an overheat (stay to the bare-headed sun, a hot shower).

INFLUENCE ON ABILITY TO DRIVE THE CAR AND TO BE ENGAGED IN OTHER POTENTIALLY DANGEROUS TYPES OF ACTIVITY
During treatment it is necessary to refrain from occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

The majority of the side effects which are observed during treatment by Cycloserinum is connected with dysfunction of the central nervous system, use of high doses of drug (more than 500 mg/days) or is manifestation of hypersensitivity to drug.
- From a nervous system: epileptic spasms, drowsiness, sleeplessness, a sopor, a headache, a tremor, a dysarthtia, dizziness, confusion of consciousness and the disturbance of orientation which is followed by memory loss; uneasiness, peripheral neuritis, psychosis perhaps with attempts of suicide, character change, euphoria, a depression, an acrimony, aggression, paresis, a hyperreflexia, paresthesia, big and small attacks of clonic spasms and a lump.
- From the alimentary system: nausea, heartburn, diarrhea, especially at elderly people with earlier existing liver diseases.
- From cardiovascular system: development of congestive heart failure in the patients accepting from 1 to 1,5 g of Cycloserinum a day was noted.
- Treat other established side effects: allergic reactions, itch, megaloblastny and sideroblastny anemia and increase in activity of aminotransferases of a liver, fever, strengthening of cough.

Interaction with other medicines:

Cycloserinum promotes decrease in resistance to an isoniazid, streptomycin and p-aminosalicylic acid (PASK). The patients receiving Cycloserinum and an isoniazid have to be under control as these drugs have the combined toxic effect on the central nervous system.
- Increases the speed of removal of a pyridoxine kidneys (can cause development of anemia and peripheral neuritis, increase in a dose of a piidoksin is required).
- Simultaneous introduction of Etioniamidum exponentiates neurotoxic side effects, increases risk of emergence of side effects from the central nervous system, especially convulsive syndrome.
- Ethanol increases risk of development of epileptic seizures.

Contraindications:

Hypersensitivity to Cycloserinum and other components of drug, organic diseases of the central nervous system, epilepsy, epileptic seizures (including in the anamnesis), disturbances of mentality (uneasiness, psychosis, a depression, including in the anamnesis), chronic heart failure, a chronic renal failure (clearance of creatinine less than 50 ml/min.), alcoholism, the lactation period, children's age up to 3 years.
Due to the existence in composition of lactose drug is not recommended to be used at patients with hereditary deficit of lactase, a lactose intolerance and a sprue of glucose galactose.

C CARE Pregnancy.

USE DURING PREGNANCY AND DURING BREASTFEEDING
Use during pregnancy: it is not established whether damage of a fruit at use for pregnant women causes Cycloserinum. Pregnant women should appoint Cycloserinum only in emergency cases. Use during breastfeeding: concentration in maternal milk approach the concentration found in blood serum of mother. The decision on feeding cancellation by a breast or the treatment terminations by drug needs to be accepted taking into account value of treatment by drug for mother.

Overdose:

Symptoms. The acute overdose can be observed at use of Cycloserinum in a dose more than 1 g. The phenomena of overdose can be observed at concentration of Cycloserinum in a blood plasma of 25-30 mg/ml (reception of high doses, disturbance of renal clearance).
Usually toxic effects meet from the central nervous system. They can include a headache, dizziness, confusion of consciousness, an acrimony, paresthesia, a dysarthtia and psychosis. At use of high doses paresis, spasms and a coma can be observed. Ethanol can increase risk of development of epileptic seizures.

Treatment. Performing the symptomatic and supporting treatment is recommended. At spasms - antiepileptic means. For prevention of neurotoxic effects enter a pyridoxine in a dose of 200-300 mg/days, drugs of a benzodiazepine row (diazepam), nootropic medicines (piracetam, glutaminic acid). Absorbent carbon can be more effective for absorption reduction, than induction of vomiting and a gastric lavage. Carrying out a hemodialysis brings Cycloserinum out of blood, but does not exclude development of life-threatening intoxication.

Storage conditions:

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:

Capsules of 250 mg.
On 10, 30 capsules in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished. On 10, 20, 30, 40, 50 or 100 capsules in banks polymeric for medicines. To one bank or 1, 2, 3, 4, 5, 6, 8 or 10 blister strip packagings together with the application instruction place in cardboard packaging (pack).