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

Cap: dye red enchanting (E129) 0.102%, blue diamond dye (E133) 0.75%, titanium dioxide (E171) 1.0725%, gelatin 83.5%, water 14.5%, sodium lauryl sulfate 0.08%;

Housing: dye red enchanting (E129) 0.005%, dye quinoline yellow (E104) 0.5%, titanium dioxide (E171) 1.0999%, gelatin 83.82%, water 14.5%, sodium lauryl sulfate 0.08%.

Description:

Hard gelatin capsules. The size number 1.Color capsule: the lid is blue and the body is yellow. The cap is printed with the logo of the company Lupine Ltd., on the body there is an inscription "LUPIN".

The contents of the capsule are white to light yellow powder.

Pharmacotherapeutic group:Antibiotic

ATX: & nbsp

J.04.A.B Antibiotics

J.04.A.B.01 Cycloserine

Pharmacodynamics:

Cycloserine is a broad-spectrum antibiotic that is formed in the course of vital activity Streptomyces orchidaceus. Cycloserine acts bacteriostatically and bactericidal, depending on the concentration in the focus of infection and the sensitivity of microorganisms. Cycloserine violates 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 of sensitive strains of gram-positive and gram-negative bacteria. Delays the growth of mycobacterium tuberculosis Mycobacterium tuberculosis and Mycobacterium avium. Active against gram-negative microorganisms Rickettsia spp., Treponema spp., Klebsiella spp., Enterobacter spp., Escherichia coli in a concentration of 10-100 mg / l. The minimum inhibitory concentration for M. tuberculosis is 3-25 mg / L on a liquid medium 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:

Suction

After oral administration cycloserine quickly and almost completely (absorption 70-90%) is absorbed from the gastrointestinal tract (GIT), reaching a maximum concentration (C_mOh) in the blood plasma after 3-4 hours. The maximum concentration depends on the dose: when taking cycloserine at a dose of 0.25, 0.5 or 1 g, the maximum concentration in the blood plasma will be 6, 24 and 30 μg / ml, respectively. After taking 250 mg every 12 hours, the maximum concentration is 25-30 μg / ml.

Distribution and Metabolism

Cycloserin penetrates well into body fluids and tissues, including spinal fluid, breast milk, bile, sputum, lymphatic tissue, lungs, ascites and synovial fluid, pleural effusion, and also passes through the placenta. In the abdominal and pleural cavities contains 50% to 100% of the concentration of the drug in the blood serum. Partly (35%) is metabolized by the liver, metabolites are not identified.

Excretion

The half-life of cycloserine (T_1/2) with normal kidney function is 10 hours. In chronic renal failure, after 2-3 days of admission, cumulation phenomena may occur.It is excreted by glomerular filtration unchanged: 50% within 12 hours, 65-70% within 24-72 hours and small amounts through the intestine.

Indications:

As part of complex therapy:

- Tuberculosis of the lungs in active form, extrapulmonary tuberculosis (including kidney damage) under condition of microorganisms sensitivity to cyclosporine and after unsuccessful adequate treatment with the main anti-tuberculosis drugs (rifampicin, isoniazid, streptomycin, ethambutol);

- Atypical mycobacterial infections (including those caused by Mycobacterium avium);

- Acute urinary tract infections caused by sensitive strains of Gram-positive and Gram-negative bacteria, in particular Klebsiella spp., Enterobacter spp. and Escherichia coli. The drug should be used in these cases only after the ineffectiveness of essential drugs has been shown and the sensitivity of microorganisms to cycloserine has been determined.

Contraindications:

- Hypersensitivity to cycloserine or other components of the drug;

- organic diseases of the central nervous system;

- epilepsy, epileptic seizures (including in anamnesis);

- disturbances of the psyche (anxiety, marked state of arousal or psychosis, depression, including in anamnesis);

- acute and chronic heart failure;

- chronic renal failure (creatinine clearance less than 50 ml / min);

- alcoholism;

- lactation period;

- children under 3 years;

- porphyria.

Carefully:

- Children from 3 to 18 years of age (see section "Method of administration and dose");

- bVariability.

Pregnancy and lactation:

It is not established whether cycloserine damage to the fetus when used in pregnant women. Cycloserine should be prescribed to pregnant women only in case of emergency, if the benefit to the mother exceeds the potential risk to the fetus.

Concentrations of the drug in mother's milk are close to those in the mother's blood serum. The decision on the abolition of breastfeeding or the cessation of drug treatment should be taken taking into account the value of treatment with the drug for the mother.

Dosing and Administration:

Inside, immediately before meals (with irritation of the mucous membrane of the GIT, the drug should be taken after meals).

Adults: usually the dose ranges from 500 mg to 1000 mg per day. The initial dose for adults is 250 mg twice daily with a 12-hour interval during the first two weeks,then, if necessary, taking into account the tolerability dose carefully increased to 250 mg every 6-8 hours under the control of the concentration of the drug in the blood serum. The daily dose should not exceed 1000 mg.

Children from 3 to 18 years old: the initial dose is 10-20 mg / kg of body weight per day in 2-3 doses (not more than 750 mg per day, a large dose is given only in the acute phase of the tuberculosis process or with insufficient effectiveness of smaller doses).

Patients over 60 years of age, and also to patients with a body weight of less than 50 kg, the drug is prescribed in a dose of 250 mg twice a day.

The course of treatment with cycloserine in infections of the urinary tract is 7-10 days, with tuberculosis - 6 months or more.

Side effects:

Allergic reactions: skin rash, itching.

From the central nervous system: convulsions, drowsiness, insomnia, nightmares, headache, tremor, dysarthria, dizziness, confusion and impaired orientation, accompanied by loss of memory, anxiety, peripheral neuritis, psychosis, suicidal moods possibly with suicide attempts, euphoria, depression, increased irritability, aggressiveness , peripheral paresis,hyperreflexia, paresthesia, large and small seizures of clonic convulsions, coma, sopor, changes in character, muscle twitching.

From the digestive system: nausea, heartburn, diarrhea, especially in older people with previously existing liver disease.

From the side of the cardiovascular system: the development of congestive heart failure in patients taking from 1000 to 1500 mg of cycloserine per day, sideroblastic and megaloblastic anemia.

Laboratory indicators: increased activity of aminotransferases liver.

Other: deficiency of cyanocobalamin and folic acid, fever, increased cough.

Overdose:

Symptoms. Acute overdose can be observed with cycloserine at a dose of more than 1000 mg per day. Overdose phenomena can be observed at a plasma cycloserine concentration of 25-30 μg / ml (high-dose administration, impaired renal clearance).

Typically, toxic effects occur from the central nervous system and include headache, dizziness, confusion, increased irritability, paresthesia, dysarthria, psychosis, peripheral paresis, convulsions and coma.

Treatment. It is recommended that symptomatic and supportive treatment be provided. With convulsions - taking antiepileptic drugs. For the prevention of neurotoxic effects are introduced pyridoxine in a dose of 200-300 mg / day, preparations of benzodiazepine series (diazepam). Activated carbon may be more effective in reducing absorption than induction of vomiting and gastric lavage. Carrying out of a hemodialysis deduces cycloserine from the blood, but does not exclude the development of life-threatening intoxication.

Interaction:

- Cycloserin increases the rate of excretion of pyridoxine by the kidneys (can lead to the development of anemia and peripheral neuritis, which requires an increase in the dose of pyridoxine).

- Co-administration with ethionamide increases the risk of side effects from the central nervous system (CNS), especially convulsive syndrome.

- It is necessary to exclude the simultaneous administration of cycloserine and ethanol, especially when treated with high doses of cycloserine. Ethanol increases the possibility and danger of epileptic seizures.

- Patients receiving cycloserine and isoniazid, should be monitored for side effects from the CNS, for example, dizziness and drowsiness, because these drugs have a combined toxic effect on the central nervous system. A dose adjustment may be required.

- Cycloserine promotes a decrease in resistance to streptomycin, para-aminosalicylic acid (PASC) and isoniazid.

Special instructions:

Before starting treatment with cycloserine, isolate cultures of microorganisms and determine the sensitivity of strains to cycloserine. In the case of tuberculosis infection, it is necessary to determine the sensitivity of the mycobacterial strain to other antituberculosis drugs.

Patients taking more than 500 mg of cycloserine per day should be under the direct supervision of a doctor because of the possible development of side effects from the central nervous system. Treatment with cycloserine should be canceled or the dose should be reduced if the patient develops allergic dermatitis or symptoms of central nervous system intoxication (convulsions, psychosis, drowsiness, oppression or confusion, hyperreflexia, headache, tremor, dizziness, peripheral paresis or dysarthria).

The risk of developing convulsive syndrome increases in patients with chronic alcoholism, so the use of cycloserine by such patients is contraindicated.

Anticonvulsants or sedatives can be effective in preventing neurotoxic reactions (seizures, arousal or tremor).

When appointing and taking the drug, it is necessary to control hematological parameters, excretory function of the kidneys, the concentration of the drug in the blood plasma, the function of the liver and the parameters of electroencephalography. The concentration of cycloserine in blood plasma should not exceed 30 mcg / ml.

In the treatment of patients with reduced renal function taking a daily dose of more than 500 mg and who are suspected to have signs and symptoms of an overdose, the plasma level of the drug should be monitored at least once a week. The dose should be adjusted in such a way as to maintain the drug level in the blood plasma below 30 μg / ml. Control of kidney function (concentration of creatinine and urea nitrogen) should be done weekly. Patients with reduced renal function receiving cycloserine, should be under the direct supervision of a physician.

In some cases, the use of cycloserine and other anti-tuberculosis drugs can cause a deficiency of cyanocobalamin (vitamin B₁₂) and folic acid in the body, the development of megaloblastic anemia. In case of anemia during treatment with cycloserine, appropriate examination and treatment of the patient should be carried out.

The use of cycloserine can cause the development of sideroblastic anemia, exacerbation of porphyria.

It is possible to prevent or reduce the toxic effect of cycloserine by prescribing glutamic acid at a dose of 0.5 g 3-4 times a day (before meals) during the treatment period and pyridoxine in a dose of 200-300 mg per day.

It is necessary to limit the mental tension of patients and exclude possible factors of overheating (exposure to the sun, hot showers).

In connection with the rapid development of resistance with monotherapy with cycloserine it is necessary to combine it with other anti-tuberculosis drugs.

Effect on the ability to drive transp. cf. and fur:

During the treatment period it is necessary to refrain from engaging in potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Capsules, 250 mg.

Packaging:

6 capsules per strip of aluminum foil / polyethylene film and aluminum foil. On 10 strips in a cardboard pack together with the instruction on medical application.

40 capsules per bottle of high-density polyethylene. 1 bottle per cardboard pack together with instructions for medical use.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LP-004168

Date of registration:28.02.2017

Expiration Date:28.02.2022

The owner of the registration certificate:Lupine Co., Ltd.Lupine Co., Ltd. India

Manufacturer: & nbsp

LUPIN, Ltd. India

Representation: & nbspLUPIN LIMITEDLUPIN LIMITED

Information update date: & nbsp31.03.2017

Illustrated instructions

Instructions

Cyclorin (Cyclorin)