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

active substance: cycloserine 250 mg; Excipients: calcium hydrophosphate - 122.4 mg, silicon dioxide colloid (aerosil) - 3.8 mg, calcium stearate - 3.8 mg; hard gelatine capsules: titanium dioxide E 171 - 2.0%, gelatin - up to 100%.

Description:

capsules № 0 of white color. The contents of capsules - powder - white or light yellow color.

Pharmacotherapeutic group:Antibiotic.

ATX: & nbsp

J.04.A.B Antibiotics

J.04.A.B.01 Cycloserine

Pharmacodynamics:

Cycloserin is a bactericidal broad-spectrum antibiotic that breaks the synthesis of the cell wall, acting as a competitive antagonist of D-alanine, inhibits enzymes,responsible for the synthesis of the cell wall. It is active against gram-negative microorganisms, in a concentration of 10-100 mg / l - Rickettsia spp., Treponema spp.

The minimum inhibitory concentration (MPC) in relation to Mycobacterium 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 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, proportional to the accepted dose of 0.25, 0.5 and 1 g maximum: the 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, phlegm, lymphatic tissue: light, ascitic 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.

The combination of tuberculosis with acute infections of the urinary tract caused by sensitive strains of gram-positive and gram-negative bacteria, especially Klebsiella spp.,. Enterobacter spp., Escherichia Coli with ineffectiveness of essential drugs.

Atypical mycobacterial infections (including those caused by Mycobacterium avium), urinary tract infections.

Contraindications:

Hypersensitivity to the components of the drug, epilepsy, depression, severe exertion, psychosis, severe chronic renal failure (creatinine clearance less than 50 ml / min), acute and chronic heart failure, alcoholism, drug addiction,pregnancy, lactation, children under 12 years (for this dosage form).

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 or 12.5 mg / kg of body weight (250 mg for the first 12 hours, then if necessary taking into account the tolerability dose is carefully increased to 250 mg every 6-8 hours) under the control of the level of the drug in the blood. The highest single. dose for adults - 250 mg; the maximum daily dose is 1g.

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 12 years of age the initial dose of cycloserine is 10-20 mg / kg of body weight per day in 2-3 doses (no higher than 750 mg / day, a high dose is given only in the acute phase of the tuberculosis process or with insufficient effectiveness of smaller doses).

The dose varies depending on the therapeutic effect and the level of cycloserine in the blood.

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 with a reduced dose or drug withdrawal;

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 neuropathy, muscle twitching, tremor, dysarthria, euphoria, depression, suicidal mood, confusion of thoughts, impaired orientation, accompanied by loss of memory, psychosis, epileptiform spasm, coma.

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

From the cardiovascular system and hematopoiesis system: megaloblastic or sideroblastic anemia.

Allergic and other reactions: skin rash, itching, fever, increased cough.

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 chronic intoxication with long-term admission in a dose of more than 0.5 g / day: 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), nootropic drugs (piracetam, glutamic acid).

Interaction:

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

Enhances the neurotoxic effect of ethionamide.

Ethanol increases the risk of seizures.

Isoniazid enhances the toxic effect of the drug on the central nervous system.

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 level of cycloserine in the blood should be monitored (at concentrations above 30 μg / ml, toxicity is likely), hematological parameters, kidney and liver function.In the treatment of patients with reduced renal function, taking a daily dose of more than 0.5 g, a weekly urine test should be monitored.

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 0.5 g 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 .

Anticonvulsant or sedative, drugs can be effective in preventing 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).

Form release / dosage:

Capsules 250 mg.

Packaging:

10 capsules per circuit cell packaging made of polyvinylchloride or polyvinylchloride / polyvinylidene chloride film and aluminum foil printed lacquer.

3 or 10 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Storage conditions:

In dry the dark place; at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:P N001664 / 01

Date of registration:14.07.2009

The owner of the registration certificate:VALENTA PHARM, PAO VALENTA PHARM, PAO Russia

Manufacturer: & nbsp

VALENTA PHARMACEUTICS, JSC Russia

Information update date: & nbsp09.10.2015

Illustrated instructions

Instructions

Cycloserine (Cycloserine)