Cycloserin-Ferein - instructions for use, dose, side effects, contraindications

Case: titanium dioxide - 0.8000%, dyes: azorubin - 0.6843%, ponso 4R - 0,0> 36%, yellow quinoline - 0,1912%, blue patented - 0,0088%, diamond black PN-0 , 0192%, gelatin - up to 100%.

Cap: titanium dioxide - 0.8000%, dyes: azorubin - 0.6843%, ponso 4R - 0.0336%, yellow quinoline - 0.1912%, blue patented - 0.0088%, diamond black PN - 0.0192 %, gelatin - up to 100%.

Description:

Hard gelatin capsules number 0. Body and cap capsule burgundy. The contents of the capsules are white or white with a yellowish tinge powder.

Pharmacotherapeutic group:Antibiotic.

ATX: & nbsp

J.04.A.B Antibiotics

J.04.A.B.01 Cycloserine

Pharmacodynamics:

Cycloserine, a broad-spectrum antibiotic, disrupts the synthesis of the cell wall, acting as a competitive antagonist of D-alanine, suppresses the enzymes responsible for the synthesis of the cell wall. Active against gram-negative microorganisms, in a concentration of 10-100 mg / l - Rickettsia spp., Treponema spp, Klebsiella spp., Enterobacter spp., Escherichia coli. Retards the growth of mycobacterium tuberculosis (active against Mycobacterium tuberculosis, Mycobacterium avium). The minimum inhibitory concentration (MIC) in relation to Mycobaelerium tuberculosis is 3-25 mg / l on liquid and 10-20 mg / l and more - on a dense nutrient medium. Drug resistance appears slowly (after 6 months of treatment it develops in 20-60% of cases).

Pharmacokinetics:

After oral administration, quickly and almost completely (70-90%) is absorbed from the gastrointestinal tract. Virtually does not bind to blood plasma proteins. Time to reach the maximum concentration in the blood plasma (TC_max) 3-4 hours, in proportion to the dose of 0.25, 0.5 and 1 g, the maximum concentration in the blood plasma (C_max) is 6, 24 and 30 μg / ml, respectively.After taking 250 mg every 12 hours C_max is 25-30 μg / ml.

It penetrates well into body fluids and tissues, including cerebrospinal fluid, breast milk, bile, sputum, lymphatic tissue, lungs, ascites and synovial fluid, pleural effusion, passes through the placenta. In the abdominal and pleural cavities contains 50-100% of the concentration of the drug in the blood serum.

Partially (35%) is biotransformed in the liver to unidentified metabolites. The half-life (T1 / 2) with normal kidney function is 10 hours.

It is excreted by glomerular filtration unchanged: 50% after 12 hours, 65-70% within 24-72 hours, small amounts through the gastrointestinal tract. With chronic renal failure, after 2-3 days, cumulation phenomena may occur.

Indications:

In the combination therapy:

Tuberculosis: active pulmonary tuberculosis, extrapulmonary tuberculosis (including kidney damage) in case of sensitivity of microorganisms to the drug and after unsuccessful adequate treatment with essential drugs, chronic forms of tuberculosis and atypical bacterial infections (including those caused by Mycobacterium avium).
Cycloserin is effective in the treatment of acute urinary tract infections caused by sensitive strains of gram-positive and gram-negative bacteria, especially species Klebsiella spp., Enterobacter spp. and Escherichia coli. In the treatment of urinary tract infections caused by bacteria other than mycobacteria, cycloserine should only after all the usual means of treatment have been exhausted and when the sensitivity of microorganisms to a given drug has been determined.

Contraindications:

Hypersensitivity to the components that make up the drug, epilepsy, epileptic seizures (including in the anamnesis), mental disorders (anxiety, depression, expressed state of arousal or psychosis, including in the anamnesis), organic diseases of the central nervous system (CNS), chronic renal failure (creatinine clearance less than 50 ml / min), heart failure, alcoholism, children under 3 years old.

Pregnancy and lactation:

The use of the drug during pregnancy is possible only in exceptional cases, when the expected benefit to the mother exceeds the potential risk to the fetus.If you need to use the drug during lactation, breastfeeding should be discontinued.

Dosing and Administration:

Inside, immediately before meals (with irritation of the mucous membrane of the gastrointestinal tract - after eating).

Adults the drug is prescribed at 500-750 mg / day in 2-3 doses (250 mg 2 times a day at 12 hour intervals for the first 2 weeks, then, if necessary, taking into account the tolerability dose is carefully increased to 250 mg every 6- 8 h) under the control of the concentration of cycloserine in the blood. The highest single dose for adults is 250 mg; the maximum daily dose is 1 g.

Patients older than 60 years, and also with a body weight of less than 50 kg, the drug is prescribed 250 mg twice a day.

Children over 3 years old prescribe 10-20 mg / kg of body weight per day in 2-3 doses (not higher than 750 mg / day, a large dose is prescribed only in the acute phase of the tuberculosis process or with insufficient effectiveness of smaller doses).

Side effects:

In the treatment with cycloserine, side effects can occur, mainly due to the toxic effect of the drug on the nervous system. These phenomena usually occur when the dose is reduced or the drug is withdrawn.

From the central nervous system and the peripheral nervous system: headache, dizziness, insomnia or drowsiness, nightmarish dreams, anxiety, increased irritability, aggressiveness, memory loss, paresthesia, peripheral neuritis, muscle twitching, tremor, dysarthria, euphoria, depression, suicidal mood, confusion of thoughts, impaired orientation, accompanied by loss of memory, psychosis, epileptiform convulsions, coma, confusion, paresis, sopor, character change, hyperreflexia, large and small seizures of clonic convulsions, suicidal attempts.

From the digestive system: increased activity of "hepatic" aminotransferases, deficiency of cyanocobalamin and folic acid, nausea, heartburn, diarrhea, especially in elderly patients with pre-existing liver diseases.

From the cardiovascular system and hematopoiesis system: megaloblastic or sideroblastic anemia, exacerbation of chronic heart failure was noted when applied at a dose of 1000-1500 mg / day.

Allergic reactions: skin rash, itching.

Other: fever, coughing.

Overdose:

Overdose is observed at a plasma cycloserine concentration of 25-30 μg / ml - high doses, impaired renal clearance; Acute poisoning can occur if ingested more than 1 g / day.

Symptoms: headache, dizziness, confusion, increased irritability, paresthesia, psychosis, dysarthria, paresis, convulsions, coma.

Treatment: symptomatic, Activated carbon, antiepileptic drugs. For the prevention of neurotoxic effects are introduced pyridoxine in a dose of 200-300 mg / day, preparations of benzodiazepine series (diazepam).

Interaction:

Reduces resistance to isoniazid, streptomycin and paraaminosalicylic acid (PASK).

Enhances the neurotoxic effect of ethionamide.

Ethanol increases the risk of epileptic seizures.

Isoniazid enhances the toxic effect of the drug on the central nervous system. Patients receiving cycloserine and isoniazid, should be under the control of the doctor regarding signs of toxic effects on the central nervous system (for example: drowsiness, dizziness). Increases the rate of excretion of pyridoxine by the kidneys (may cause the development of anemia and peripheral neuritis, an increase in the dose of pyridoxine is required).

Special instructions:

Before the beginning of treatment it is necessary to determine the sensitivity of strains of microorganisms to cycloserine and other anti-tuberculosis drugs. During the treatment period, the concentration of cycloserine in the blood should be monitored (at concentrations above 30 μg / ml, toxicity is likely), hematologic parameters, kidney and liver function. In the treatment of patients with reduced renal function, taking a daily dose of more than 500 mg, it is necessary to monitor urinalysis weekly. In case of development against the background of treatment of allergic dermatitis or symptoms of the central nervous system (convulsions, psychosis, drowsiness, confusion, hyperreflexia, headache, dizziness, tremor, peripheral paresis, dysarthria), drug treatment should be discontinued.

It is possible to prevent or reduce the toxic effect of cycloserine by prescribing glutamic acid 500 mg 3-4 times daily (before meals) during the treatment period, and daily intramuscular injection of sodium salt ATP (1 ml of 1% solution), pyridoxine 200-300 mg / day . Therapy with cycloserine should be carried out in combination with other anti-TB drugs.

Anticonvulsants or sedatives can be effective in preventing the symptoms of central nervous system damage.

It is necessary to limit the psychoemotional burden of patients and exclude possible factors of overheating (exposure to the sun with uncovered head, hot shower).

Effect on the ability to drive transp. cf. and fur:In the period of treatment, it is recommended to abandon the management of vehicles, mechanisms.

Form release / dosage:

Capsules 250 mg.

Packaging:

10 capsules per circuit cell packaging made of polyvinylchloride film and flexible packaging on the basis of aluminum foil.

For 10, 20, 50, 100 capsules in cans of polymeric with screw caps.

The bank, 1, 2, 5, 10 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

Packing for hospitals

For 50, 100, 200, 300, 500 contour mesh packages together with an equal number of instructions for use are placed in a box of corrugated cardboard.

For 10, 20, 50, 100 capsules are placed in cans of polymer with lids.

For 150, 250, 500 cans, together with an equal number of instructions for use, are placed in a box of corrugated cardboard.

For 500, 1000 capsules are placed in polymer cans with lids.

For 4, 6, 10, 12 cans, together with an equal number of instructions for use, are placed in a box of corrugated cardboard.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:2 years. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002859

Date of registration:13.02.2015

The owner of the registration certificate:BRYNTSALOV-A, CJSC BRYNTSALOV-A, CJSC Russia

Manufacturer: & nbsp

BRYNTSALOV-A, CJSC Russia

Information update date: & nbsp09.10.2015

Illustrated instructions

Instructions

Cycloserine-Ferein® (Cycloserine-Ferein®)