Cycloserine instructions for applying tablets. Cycloserin Antibiotic - Last Hope

each capsule contains:

Active substance: Cycloserine - 250 mg.

Excipients: Lactose - 57, 0 mg, corn starch - 33.0 mg, sodium Laurilsulfate - 2.0 mg, magnesium stearate - 8.0 mg.

The composition of solid gelatin capsules: Titanium dioxide (E 171) - 1.33 mg, iron oxide (III) - 0.155192 mg, gelatin - 63,152808 mg, water - 11.02 mg, sodium lauryl sulfate - 0.114 mg, bronopol - 0.076 mg, pose - 0.076 mg, methyl aprichedroxibenzoate - 0.057 mg, propyl aprichedroxybenzoate - 0.019 mg.

Capsules (No. 1) of a dark brown with a reddish color shade, the contents of the capsules - white or light yellow powder.

There is bacteriostatically or bactericidal depending on the concentration in the focus of inflammation and sensitivity of microorganisms.

Pharmacodynamics:

Mechanism of action. The antibiotic of a wide range of action, disrupts the synthesis of the cell wall, acting as a competitive D-Alanine antagonist, suppresses the enzymes responsible for the synthesis of the cell wall.

Active in terms of gram-negative microorganisms, at a concentration of 10-100 mg / l - Rickettsia SPP., Treponema SPP. The minimum overwhelming concentration in relation to Mycobacterium tuberculosis It is 3-25 mg / l on a liquid and 10-20 mg / l and more - on a dense nutrient medium. Drug stability arises slowly (after 6 months of treatment develops in 20-60% of cases).

Cycloserine is quickly absorbed from the gastrointestinal tract (gastrointestinal tract) after receiving inside. The time to achieve the maximum concentration in the blood plasma (TS MAX) - 3-4 hours. The drug is freely distributed through the liquids and tissues of the body.

Cycloserine penetrates through the hematorecephalic barrier (GEB), concentrations in the cerebrospinal fluid are approximately the same as in the plasma. In patients with tuberculosis, it was found in sputum, as well as in the pleural and ascitic fluids, in bile, amniotic fluid and in the blood of the fetus, in breast milk, lung tissues and in lymphoid tissue.

Cycloserine is excreted by kidneys by glomerular filtration unchanged (50% after 12 hours, 65-70% in the range of 24-72 h) and in a small number of intestinal.

In chronic renal failure after 2-3 days, cumulation phenomena may occur.

About 35% is metabolized, but the metabolites have not yet been identified. The semi-anniversary of the cycloserine varies within 8-12 hours.

Cycloserine is used both for the treatment of pulmonary tuberculosis in active form and for the treatment of an extreme tuberculosis (including kidney tuberculosis), subject to the sensitivity of microorganisms to this drug and after unsuccessful adequate treatment with basic drugs (rifampicin, isoniazide, streptomycin and etcutol). It should be used in combination with other anti-tuberculosis means. Effective with acute urinary tract infections caused by sensitive strains of gram-positive and gram-negative bacteria, especially Klebsiella SPP. Enterobacter SPP.andEscherichia coli. It should be used to treat these infections only after all conventional treatments are exhausted and when the sensitivity of microorganisms to this drug is determined.

Cycloserine is contraindicated in the following cases: increased sensitivity to cycloserine, organic diseases of the central nervous system (CNS), epilepsy, epileptic seizures (including a history), psyche disorders (anxiety, psychosis, depression, incl. In history ), severe renal failure (creatinine clearance less than 25 ml / min), alcohol abuse, lactation period, child age up to 3 years (for a given dosage form), heart failure, lactase deficiency, lactose intolerance, glucose-galactose malabsorption.

Children's age (from 3 to 18 years), chronic renal failure (creatinine clearance more than 25 ml / min).

The concentrations in the blood of the fetus are approaching concentrations that are found in the serum pregnant. A study on 2 generations of rats received doses up to 100 mg / kg body weight / day showed a lack of teratogenic effect in newborns. It does not establish damage to the fetus when prescribing pregnant women and does it have an impact on reproductive ability. It should be prescribed to pregnant women only in cases of extreme necessity.

Application during lactation. Concentrations in mother milk are approaching the concentrations detected in serum. The decision to cancel breastfeeding or discontinuation of treatment with the drug must be taken taking into account the treatment value for the drug for the mother.

Inside, immediately before taking food (when irritating the mucous membrane of the gastrointestinal tract - after eating).

The usual dose is from 500 mg to 1 g per day for several receptions under the control of the level of the drug in the blood. The initial dose for adults is most often 250 mg twice a day with a 12-hour interval during the first two weeks. Daily dose should not exceed 1 g.

Children (over 3 years old). The usual initial dose is from 10 mg / kg of body weight / day for several techniques, after which it varies depending on the concentration of the drug in the blood and therapeutic effect. The daily dose should not exceed 0.75 g.

Elderly. Patients over 60 years old, as well as with a mass of body less than 50 kg - 0.25 g 2 times a day.

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

Most side effects observed during cylosterine treatment were associated with a violation of the function of the central nervous system or was the manifestations of increased sensitivity to the drug. The following side effects were observed:

From the nervous system: cramps, drowsiness, headache, tremor, dysarthria, dizziness, confusion and violation of orientation, accompanied by loss of memory, psychosis, possibly with suicide attempts, character changes, increased irritability, aggressiveness, peripheral paresis, hyperreflexia, paresthesia, large and small attacks Clonic cramps and coma.

From the cardiovascular system and blood formation organs: exacerbation of heart failure (with doses of 1000-1500 mg / day), sideroblast and megaloblastic anemia.

From the digestive system, Nausea, heartburn, diarrhea, especially in elderly patients with previously existing liver diseases.

Allergic reactions:skin rash, itching.

Laboratory indicators: Improving the activity of "liver" aminotransferase.

Others: Cyanocobalamin and Folic Acid deficiency.

Signs and symptoms. Acute poisoning can be observed if an adult patient accepted inside more than 1 g. Chronic toxicity depends on the dose and may be observed if more than 500 mg of cycloserine is introduced daily into the body. When applied in patients with a disturbed kidney function, see "Contraindications" and "Special Instructions" sections. Usually, toxic effects are marked by the central nervous system. They may include headache, dizziness, confusion, increased irritability, paresthesia, dysarthria and psychosis. When using high doses, peripheral paresis, cramps and coma can be observed. It may increase the risk of developing epileptic seizures.

Treatment. It is recommended to conduct symptomatic and supportive treatment. It may be more efficient to reduce the absorption of the drug, rather than the calling of vomiting and washing the stomach. In the development of neurotoxic effects, the introduction of 200-300 mg of pyridoxine per day is shown. During hemodialysis is derived from the blood, but the development of the toxic effect of threatening life is not excluded.

It is reported that the simultaneous use of ethionamide enhances the neurotoxic effects of the drug. Alcohol is incompatible, especially when treating high doses of cycloserine. Alcohol increases the possibility and danger of epileptic seizures. Patients receiving and should be under the supervision of a doctor, since these combinations it is possible to strengthen the toxic effect on the CNS. A dose adjustment may be required. Increases the rate of removal of pyridoxine kidneys (can cause the development of anemia and peripheral neuritis, an increase in dose of pyridoxine is required).

Cycloserine treatment It is necessary to cancel or should be reduced by a dose if the patient develops allergic dermatitis or symptoms of the lesion of the central nervous system, such as convulsions, psychosis, drowsiness, confusion, hyperreflexia, headache, tremor, dizziness, peripheral paresis or dizard.

Inxication is usually observed at the concentration of the drug in the blood of more than 30 mg / l, which may be the result of an overdose or reduction of kidney clearance. The therapeutic cycloserine index is low. The risk of developing seizures increases in patients with chronic alcoholism.

When taking cycloserine, hematological indicators should be monitored, the excretory function of the kidneys, the concentration of the drug in the blood and the condition of the liver function.

Before the beginning of treatment, the cycloserine needs to highlight the cultures of microorganisms and determine the sensitivity of strains to this drug. In the case of tuberculosis infection, it is necessary to determine the sensitivity of the strain to other anti-tuberculosis drugs.

In the treatment of patients with a reduced kidney function, receiving a daily dose of more than 500 mg, in which signs and symptoms of overdose are allegedly detected, the concentration of the drug in the blood must be monitored at least once a week.

The dose must be corrected in such a way as to maintain the concentration of the drug in the blood below 30 mg / l.

Anticonvaluation or sedatives can be effective for the prevention of symptoms of the lesion of the central nervous system, for example, convulsion, the state of excitation or tremor.

It should be limited to the mental stress of patients and eliminate possible overheating factors (staying in the sun with a uncoated head, hot shower).

Patients receiving more than 500 mg of cycloserine per day should be under the direct supervision of the doctor due to the possible development of such symptoms. For the prevention of side neurotoxic effects, psychotropic drugs of benzodiazepine row (5 mg) or phenazepams (1 mg) per night are prescribed; Nootropic drugs - 800 mg 2 times a day, (vitamin B 6), glutamic acid 1 g 3 times a day.

In some cases, the use of cycloserine and other anti-tuberculosis drugs may cause the development of vitamin C 12 and / or folic acid in the body, megaloblastic and sideroblastic anemia. In the event of anemia during treatment, it is necessary to conduct an appropriate examination and treatment of the patient.

During the treatment period, caution must be taken care of potentially hazardous activities requiring increased concentrations of attention and speed of psychomotor reactions.

During the treatment period, caution must be taken when driven by vehicles and mechanisms.

250 mg capsules.

4 or 10 capsules in aluminum stripe.

1 Streap (4 capsules) along with instructions for use in a cardboard pack. 5 or 10 strippers (10 capsules) along with instructions for use in a cardboard pack.

When packing at the enterprise of OJSC "Pharmacezinz" (Russia):

Secondary Packaging of the Medicine Preparation.

1 or 10 strippers (4 capsules) together with the application instructions are placed in a pack of cardboard.

In case of packaging and packaging at the enterprise of OJSC "Pharmacezinz" (Russia).

Primary packaging of the medicinal preparation.

30, 50 or 100 capsules per bag of low-density polyethylene. The package sticks a label paper label or polymeric materials, self-adhesive.

Secondary Packaging of the Medicine Preparation.

One package along with the instructions for use is placed in a polymeric jar with a lid tensioned with the control of the first opening. On the banks stick labels from paper label or writing or polymeric materials, self-adhesive.

In a dry, light-protected place at a temperature not higher than 25 ° C.

Keep out of the reach of children.

2 years. Do not use after the period specified on the package.

Cycloserine - anti-tuberculosis drug of a wide spectrum of antibacterial action.

Release form and composition

Release cycloserine in the form of capsules:

• dosage 125 mg - No. 2, gelatin solid, opaque, with a lid and white body (5, 7 or 10 pcs. In the cell contour package; 10, 20, 30, 40, 50 or 100 pcs. in the polymer can, in a cardboard pack 1-6, 8, 10 packs or 1 bank);
• 250 mg dosage - gelatin solid; Depending on the manufacturer: №1, dark brown with a red tint of color, or with a red opaque cap and almost white or white case; No. 0, opaque white, or with a cap of a pale brown or orange color, and a white body (7 or 10 pcs. In the baking-free contour packaging, in a cardboard pack 1, 2, 3, 10, 50, 54, 60 packs ; 10 or 30 pcs. in the cell contour packaging, in a cardboard pack 1-6, 8, 10 packs; 100 pcs. in a polyethylene bottle, 10 pcs. in a blister, in a cardboard pack 1 vial or 1, 5, 10 Blisters; 4 or 10 pcs. in aluminum stripe, in a cardboard pack 1, 5, 10 stripters of 10 pcs., 1 or 10 strips of 4 pcs.; for 30, 50 or 100 pcs. in a low-density polyethylene package , in a polymer bank 1 package; 10, 20, 30, 40, 50 or 100 pcs. In a polymer can, in a cardboard pack 1 bank);
• dosage 500 mg - № 00, gelatin solid, opaque, with a lid and a yellow body (5, 7 or 10 pcs. In the cell contour package; 10, 20, 30, 40, 50, 100 pcs. in the polymer can In a cardboard pack 1-6, 8, 10 packs or 1 bank).

Content capsules: powder or mixture of granules and powder from almost white or white to pale yellow; Perhaps the presence of a seal of the contents of the capsule in its form, which when pressing disintegrates.

1 capsule contains:

• active substance: Cycloserine - 125, 250 or 500 mg;
• additional components: 125 and 500 mg - magnesium stearate, lactose, silicon colloidal dioxide; 250 mg - the composition depends on the manufacturer;
• capsule sheath; 125 mg - gelatin, titanium dioxide; 500 mg - gelatin, titanium dioxide, chinoline yellow dyes and solar sunset yellow; 250 mg - the composition depends on the manufacturer.

Pharmacological properties

Pharmacodynamics

Cycloserine belongs to the group of antibiotics of a wide range of action. Depending on the sensitivity of microorganisms and the concentration of the drug in the focus of inflammation, it exhibits bacteriostatic or bactericidal properties. Violating the synthesis of the cell shell, the active substance manifests itself as a competitive D-Alanine antagonist. The drug oppresses the activities of enzymes providing the synthesis of the cell wall.

Cycloserine shows an activity against gram-negative microorganisms, at a concentration of 10-100 mg / l to Treponema SPP. and rickettsia spp. The minimum overwhelming concentration (IPC) with respect to Mycobacterium tuberculosis is 10-20 mg / l and higher on dense, and 3-25 mg / l - on a liquid nutrient medium. The resistance of microorganisms is developing 6 months after the start of therapy in 20-80% of cases.

Pharmacokinetics

After oral administration, the absorption of cycloserine is 70-90%, it is almost not associated with plasma proteins. The maximum concentration of the drug (Cmax) in the blood plasma is proportional to the obtained dose 250, 500 and 1000 mg is 6, 24 and 30 μg / l, respectively. Its achievement time (T Cmax) - 3-4 hours. In the case of 250 mg cycloserine intake, every 12 hours Cmax may vary from 25 to 30 μg / ml.

The substance penetrates well in the tissue and fluid of the body, such as breast milk, spinal fluid, lymphatic tissue, wet, bile, light, pleural effusion, ascitic and synovial fluids. The placental barrier passes. In the pleural and abdominal cavity there may be 50-100% of the concentration of the means in serum.

The process of metabolic transformation is subject to no more than 35% of the adopted dose, the half-life on the background of the normal function of the kidneys is 10 hours. The means is excreted unchanged by the glomerular filtering: 50% after 12 hours, 65-70% in the range of 24-72 hours; An insignificant amount is excreted in feces.

In the presence of chronic renal failure (CPN), a cumulation may occur after 2-3 days.

Indications for use

• tuberculosis: chronic forms, active pulmonary tuberculosis, extrapulmonary tuberculosis (including kidney damage) - in the sensitivity of pathogens to the drug and after inefficient therapy with essential drugs (as part of combined treatment);
• infections of urinary tract due to sensitive strains of gram-negative and gram-positive bacteria (Escherichia coli, Enterobacter SPP.);
• atypical mycobacterial infections, including the MYCOBACERIUM AVIUM excited (as part of a combined treatment).

Contraindications

• chronic heart failure;
• epileptic seizures (including data as anamnesis);
• epilepsy;
• organic diseases of the central nervous system (CNS);
• CPN with creatinine clearance (CC) less than 25 or less than 50 ml / min (depending on the manufacturer);
• alcoholism;
• psyche disorders (anxiety, depression, psychosis, including in history);
• hypersensitivity to cycloserine components.

Additional contraindications depending on the manufacturer:

• porphyry;
• addiction;
• pregnancy and breastfeeding period;
• age up to 3 or up to 12 years;
• glucose-galactose malabsorption, lactose intolerance, lactase deficiency (if there is lactose capsules).

According to the instructions, cycloserine with extreme caution should be used in children.

Instructions for the use of cycloserine: method and dosage

Cycloserines are administered orally, immediately before meals, in the event of irritation of the mucous meadow of the digestive tract - after eating.

The initial dose for adults, as a rule, is 250 mg, taken 2 times a day (every 12 hours) during the first two weeks. In the future, if it is advisable, depending on tolerance, the dose is carefully raised to 250 mg 3-4 times a day (every 6-8 hours), while carrying out the control of the substance concentration in serum.

The maximum daily dose of cycloserine is 1000 mg, with functional disorders of the kidney, a dose decrease is required.

Patients with body weight less than 50 kg, as well as over 60 years old, must take the drug 2 times a day at 250 mg.

The duration of the treatment of infections of urinary tract - 7-10 days, mycobacterial infections - from 6 months or more.

Children after 3 years (or after 12 years - depending on the manufacturer) it is recommended to take the drug in a daily dose of 10-20 mg / kg of weight in 2-3 receptions, but not exceeding 750 mg per day. The reception of large doses of cycloserine is allowed only in the treatment of the acute phase of the tuberculosis process or with an insufficient effect of the above doses.

Side effects

• cardiovascular system and blood formation organs: occurrence of stagnant heart failure (when using daily doses of 1000-1500 mg);
• nervous System: dizziness, headache, nightmarish dreams, insomnia / drowsiness, increased irritability, anxiety, aggressiveness, memory deterioration, peripheral neuritis, tremor, paresthesia, muscular twitching, dysarthria, depression, euphoria, violation of orientation with memory loss, confusion of thoughts, Psychosis, confusion, a change in character, epileptiform convulsions, paresis, copor, suicidal mood, large and small attacks of clonic convulsions, hyperreflexia, suicidal attempts, coma;
• allergic reactions: itching, skin rash;
• digestive system: heartburn, nausea, diarrhea, increase in activity of hepatic aminotransferase (mainly in elderly patients with previously existing liver diseases);
• others: Cough enhancement, fever, megaloblastic / sideroblastic anemia, folic acid deficiency and cyanocobalamin.

Overdose

Overdose may be observed at a plasma concentration of cycloserine 25-30 mg / ml, resulting from a disruption of renal clearance or a reception of large doses of the drug. With oral use of the means in a daily dose of more than 1000 mg, the likelihood of acute poisoning increases. The symptoms of chronic intoxication against the background of a long-term intake of 500 mg per day are the following violations: dizziness, headache, increased irritability, confusion, psychosis, dysarthria, paresthesia, cramps, parires, coma.

At this state, it is recommended to conduct symptomatic and supporting therapy. Acceptance of activated carbon is more efficient to reduce suction than stomaching and vomiting induction. In convulsions, antiepileptic drugs are prescribed, in order to prevent neurotoxic reactions, pyridoxine is administered to 200-300 mg per day, as well as sedative and anticonvulsant drugs. The conduct of hemodialysis provides the conclusion of cycloserine from the blood, but cannot exclude the occurrence of the threatening life of intoxication.

special instructions

Before the start of therapy, the cultures of microorganisms are needed and the sensitivity of strains to the drug is required. In the case of the detection of tuberculosis infection, the strain's sensitivity should be determined to other anti-tuberculosis means.

If, on the background of therapy, the drug is noted the development of allergic dermatitis or symptoms of CNS intoxication (dizziness, tremor, headache, drowsiness, convulsions, depression / confusion, parires / dysarthria, hyperreflexia), its use is required to stop or reduce the dose. In patients with chronic alcoholism, due to the low therapeutic index of cycloserine, the risk of seizures is increasing.

During treatment, it is necessary to monitor the kidney function (the level of creatinine and nitrogen of urea in the blood), hematological indicators, liver activities and the concentration of the drug in the blood.

In order to prevent the development of symptoms of the TSNS defeat, in particular, the tremor, the state of initiation or convulsion can be used anticonvulsant or sedatives. Patients taking cycloserine in a daily dose of over 500 mg must be abused by direct control of the doctor due to the risk of such unwanted effects.

To reduce or prevent the toxic action of cycloserine, it is recommended during the course to take 3-4 times a day (before meals) glutamic acid at a dose of 500 mg and introducing an intramuscularly sodium salt of ATP (adenosine trifhosphate) 1 ml of 1% solution and pyridoxine to 200-300 mg in day.

For the prevention of the development of neurotoxic disorders, psychotropic drugs of benzodiazepine rows are used - phenazepam (at a dose of 1 mg) or diazepams (at a dose of 5 mg) for the night, as well as piracetam 2 times a day at a dose of 800 mg.

Sometimes the reception of cycloserine and other anti-tuberculosis drugs can lead to folic acid failure and cyanocobalamin (vitamin B 12) in the body, as well as to the development of sideroblastic and megaloblastic anemia. If on the background of therapy with the drug arises anemia, it is necessary to assign a corresponding examination and treatment.

Due to the rapid development of stability when using cycloserine in the form of a drug of monotherapy, it should be combined with other anti-tuberculosis drugs.

Impact on the ability to control vehicles and complex mechanisms

The influence of cycloserine on the ability to control the car and other complex equipment is not established, but due to the possible development of unwanted reactions from the central nervous system, patients should be abstained from potentially hazardous activities requiring the concentration of attention and speed of reactions.

Application during pregnancy and lactation

The concentrations of cycloserine in the blood of the fetus and in maternal milk are approaching concentrations detected in serum pregnant or nursing women (respectively). Information confirming the negative effect of the drug on the fetus at its reception during pregnancy is not available.

Application of cycloserine:

• pregnancy: It is allowed only in extremely rare cases, in vital necessity;
• lactation period: It is necessary to stop breastfeeding.

In some manufacturers, cycloserine pregnancy is indicated in the list of absolute contraindications to the drug reception, therefore it is necessary to carefully study the attached instructions.

Childcare

The drug is contraindicated to use children up to 3 or up to 12 years old (depending on the manufacturer). Take cycloserine in childhood is necessary with extreme caution.

With violations of the kidney function

In the presence of CPN (QC below 25 or 50 ml / min - depending on the manufacturer) therapy is contraindicated. In patients with reduced kidney function, receiving a drug in a daily dose of more than 500 mg, against the background of possible symptoms and signs of overdose, the level of cycloserine in the blood is required to be controlled at least 1 time per week. In this case, select the dose in this case so that the concentration of the drug in the blood was below 30 mg / l.

When violations of the liver function

Functional liver disorders do not affect cycloserine kinetics.

Application in old age

Elderly patients (over 60) the drug is recommended to receive 2 times a day at 250 mg.

Medicinal interaction

• pyridoxine: the rate of removal of this means by the kidneys increases (the development of peripheral neuritis and anemia is possible, a dose of pyridoxine should be increased);
• isoniazid: the frequency of sleepiness, dizziness (patients need careful observation increases);
• ethionamide: exacerbates the threat of the appearance of neurotoxic effects of the drug, the likelihood of convulsive syndrome increases;
• streptomycin, isoniazide, para iaxalcyl acid (PASK): Resistance to these funds is reduced;
• ethanol: the danger of epileptic seizures increases (especially in patients with chronic alcoholism).

Analogs

Analogues of cycloserine are: cansamine, cokesine, member, cycloin, cycloserin-Feren.

Terms and conditions of storage

Store in a place protected from moisture and light, inaccessible to children, at a temperature not exceeding 25 ° C.

Shelf life - 2 years.