The antibiotic Cycloserine is the last hope. Instructions for use

Cycloserine is a drug belonging to the group of anti-tuberculosis drugs.

What is the composition and form of release of the drug Cycloserine?

The drug is supplied to the pharmaceutical market in gelatin capsules, they are hard, size No. 1, the body is almost white, the cap is red in color, there is a light yellowish powder inside. Active substance anti-tuberculosis drug is cycloserine at a dosage of 250 milligrams.

Auxiliary capsule compounds are represented by such compounds: magnesium stearate, added calcium phosphate, silicon dioxide, talc. shell dosage form formed by the following ingredients: titanium dioxide, gelatin, crimson dye and quinoline yellow, in addition, water.

Cycloserine capsules are placed in blisters. Anti-tuberculosis medication for sale by prescription. The implementation of the drug is designed for two years from the date of pharmaceutical release of the drug.

What is the action of Cycloserine capsules?

The drug Cycloserine acts bacteriostatically and bactericidal, which is determined by the dosage of the anti-tuberculosis agent. The drug disrupts the biosynthesis of the bacterial cell wall, inhibits the activity of enzymes, acts on the following pathogens: Rickettsia spp., in addition, Treponema spp., and Mycobacterium tuberculosis.

After using the capsules, the absorption of the drug reaches 90 percent. The anti-tuberculosis drug practically does not bind to proteins circulating in the plasma. The maximum concentration is noted in three, four hours.

Penetrates into body fluids, as well as into tissues quite well, including lymph, breast milk, bile, as well as phlegm, and so on. Metabolized up to 35 percent of the dose taken. The half-life lasts up to ten hours with normal kidney function. Excreted by the kidneys and slightly through the intestines.

What are the indications for the use of Cycloserine?

The drug Cycloserine (capsules) instructions for use allows the use in the following cases: with tuberculosis, with mycobacterial infection that occurs atypically, as well as with infection urinary tract.

What are the contraindications for Cycloserine?

I will list when Cycloserine instructions for use do not allow the use:

At hypersensitivity to the medication;
At ;
In the presence of organic diseases of the central nervous system;
With epileptic seizures;
;
Do not use the remedy for;
With mental disorders, for example, with a depressive state, with identified anxiety, with a history of psychosis.

With caution, the drug Cycloserine should be used in pediatrics.

What is the use and dosage of the medicine Cycloserine?

The drug Cycloserine is prescribed orally, capsules are taken at 0.25 grams twice a day for the first 12 hours, and then the frequency of the drug is increased to four times a day, while it is important to control the concentration of the drug in the blood. The maximum daily dosage should not exceed one gram. Before starting therapy, it is important to consult a doctor.

Overdose from Cycloserine

An overdose of Cycloserine will cause a number of the following symptoms: convulsions, headache, paresis, dizziness, coma, possible paresthesia, confusion, psychosis, irritability. Treatment is symptomatic with preliminary gastric lavage.

What are the side effects of Cycloserine?

The use of Cycloserine, which we continue to talk about on this page www.site, provokes the development of the following negative reactions, I will list these symptoms: exacerbation of heart failure, headache, convulsions join, dizziness is possible, heartburn is observed, insomnia or the development of drowsiness is characteristic, loose stools are not excluded.

In addition, the drug Cycloserine can provoke the following side effects: nightmares are observed, nausea joins, anxiety is characteristic, irritability is noted, vomiting is not excluded, in addition, memory loss, psychosis, paresthesia, increased coughing are possible, and the patient also has a suicidal mood.

Other side effects will be expressed following symptoms: the patient has peripheral neuritis, fever joins, characteristically depression, tremor is possible, euphoria is not excluded, some allergic reactions, megaloblastic anemia joins, in addition, an increase in liver aminotransferases.

When side effects for application medication Cycloserine, the patient needs to consult a doctor in a timely manner to prevent the development of any complications.

special instructions

To prevent damage to the nervous system, in particular, the appearance of seizures, tremors, you can prescribe anticonvulsant medications to the patient or sedatives together with the drug Cycloserine.

It is important to store Cycloserine capsules in a dry place and avoid over-moisturizing the dosage form, otherwise the therapeutic effect of the subsequent use of the drug will be lost.

How to replace Cycloserine, what analogs to use?

The drug Kokserin, Cycloserin-Ferein, Kansamine, in addition, D-cycloserine, as well. All of the listed drugs belong to the analogues of Cycloserine.

Conclusion

Before using the drug Cycloserine, it is important to contact your doctor to select the appropriate dosage of the drug.

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Cyclocarine, Cyclovalidine, Closin, Farmiserina, Novoserine, Orientomycin, Oxamycin, Serocycline, Seromycin, Tebemycin, Tizomycin

Recipe

Rep.: Tab. Cycloserine 0.25
No. 40
D.S. 1 tablet 3 times a day (before meals)

pharmachologic effect

The drug has a wide spectrum antibacterial action: inhibits gram-positive and gram-negative bacteria. The most valuable property is its ability to retard the growth of Mycobacterium tuberculosis (tuberculosis pathogens). In activity it is inferior to streptomycin, isoniazid and ftivazid, but it acts on Mycobacterium tuberculosis resistant to these drugs and para-aminosalicylic acid.

Mode of application

Inside, immediately before a meal (in case of irritation of the gastrointestinal mucosa - after eating), adults - 0.25 g of Cycloserine every 12 hours for the first 12 hours, then, if necessary, taking into account tolerance, the dose is carefully increased to 250 mg every 6-8 hours under monitoring the concentration of the drug in the blood serum.

The maximum daily dose is 1 g. Patients over 60 years of age, as well as those weighing less than 50 kg - 0.25 g 2 times a day. Daily dose Cycloserine for children - 0.01-0.02 g / kg (not higher than 0.75 g / day).

Indications

Cycloserine is considered as a “reserve” anti-tuberculosis drug, i.e. prescribed to patients with chronic forms of tuberculosis, in whom the previously used main drugs have ceased to have an effect
.
Cycloserine can also be combined with basic drugs to prevent the development of resistance (drug resistance) of mycobacteria. It is also possible the combined use of cycloserine with other second-line drugs, ethionamide, pyrazinamide, etc.

Contraindications

Hypersensitivity, epilepsy, depression, severe agitation, psychosis, severe kidney failure, alcoholism.

Side effects

From the nervous system: headache, dizziness, insomnia or drowsiness, "nightmarish" dreams, anxiety, irritability, memory loss, paresthesia, peripheral neuritis, tremor, euphoria, depression, suicidal mood, psychosis, epileptiform convulsions.

From the side digestive system: nausea, heartburn, diarrhea.

Other: fever, increased cough.

Overdose.

An overdose is observed at a concentration of Cycloserine in plasma of 25-30 mg / ml - taking high doses, impaired renal clearance; acute poisoning can occur if more than 1 g / day is ingested.

Symptoms chronic intoxication with prolonged use at a dose of more than 500 mg / day: headache, dizziness, confusion, irritability, paresthesia, psychosis, dysarthria, paresis, convulsions, coma.
Treatment of overdose with Cycloserine: symptomatic, activated charcoal, antiepileptic drugs. To prevent neurotoxic effects, pyridoxine is administered at a dose of 200-300 mg / day, anticonvulsant and sedative drugs.

Release form

Tablets or capsules of 0.25 g.

ATTENTION!

The information on the page you are viewing was created for informational purposes only and does not promote self-treatment in any way. The resource is designed to familiarize healthcare professionals with additional information about certain medicines, thereby increasing their level of professionalism. The use of the drug "" in without fail provides a consultation with a specialist, as well as his recommendations on the method of application and dosage of the medicine you have chosen.

Cycloserine: instructions for use and reviews

Latin name: Cycloserine

ATX code: J04AB01

Active substance: cycloserine (cycloserinum)

Producer: Biocom CJSC (Russia), Valenta Pharmaceutical JSC (Russia), Promed Exports Pvt.Ltd (India), Dong-A Pharmaceutical Co. Ltd ( South Korea) and etc.

Description and photo update: 10.07.2018

Cycloserine is an anti-tuberculosis drug. a wide range antibacterial action.

Release form and composition

Cycloserine is produced in the form of capsules:

  • dosage 125 mg - No. 2, gelatinous solid, opaque, with cap and body white color(5, 7 or 10 pieces in a blister pack; 10, 20, 30, 40, 50 or 100 pieces in a polymer can, in a cardboard bundle 1-6, 8, 10 packs or 1 can);
  • dosage 250 mg - gelatin solid; depending on the manufacturer: No. 1, dark brown with a red tint, or with a red opaque cap and an almost white or white body; No. 0, opaque white, or with a lid in pale brown or orange color, and a white body (7 or 10 pcs. in a blister strip pack, in a carton pack 1, 2, 3, 10, 50, 54, 60 packs; 10 or 30 pcs. in a blister strip pack, in a carton pack 1 –6, 8, 10 packs, 100 pcs in a polyethylene bottle, 10 pcs in a blister, in a carton pack 1 bottle or 1, 5, 10 blisters, 4 or 10 pcs in an aluminum strip, in a carton pack 1 , 5, 10 strips of 10 pcs, 1 or 10 strips of 4 pcs, 30, 50 or 100 pcs in a bag of low density polyethylene, in a polymer can 1 bag, 10, 20, 30, 40, 50 or 100 pieces in a polymer can, in a cardboard bundle 1 can);
  • dosage 500 mg - No. 00, gelatinous solid, opaque, with cap and body yellow color(5, 7 or 10 pieces in a blister strip pack; 10, 20, 30, 40, 50, 100 pieces in a polymer can, in a cardboard bundle 1-6, 8, 10 packs or 1 can).

Capsule contents: powder or mixture of granules and powder from almost white or white to pale yellow; there may be a seal of the contents of the capsule in its shape, which breaks up when pressed.

1 capsule contains:

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

Pharmacological properties

Pharmacodynamics

Cycloserine belongs to the group of broad-spectrum antibiotics. 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 membrane, the active substance manifests itself as a competitive antagonist of D-alanine. The drug inhibits the activity of enzymes that ensure the synthesis of the cell wall.

Cycloserine is active against gram-negative microorganisms, at a concentration of 10-100 mg / l - to Treponema spp. and Rickettsia spp. The minimum inhibitory concentration (MIC) in relation to Mycobacterium tuberculosis is 10–20 mg/l and higher on solid, and 3–25 mg/l on liquid nutrient medium. Resistance of microorganisms develops 6 months after the start of therapy in 20-80% of cases.

Pharmacokinetics

After oral administration, the absorption of cycloserine is 70-90%, it almost does not bind to plasma proteins. The maximum concentration of the drug (Cmax) in blood plasma in proportion to the received dose of 250, 500 and 1000 mg is 6, 24 and 30 μg / l, respectively. The time to reach it (T Cmax) is 3–4 hours. In the case of taking cycloserine 250 mg every 12 hours, Cmax can vary from 25 to 30 mcg / ml.

The substance penetrates well into tissues and body fluids, such as breast milk, cerebrospinal fluid, lymphatic tissue, sputum, bile, lungs, pleural effusion, ascitic and synovial fluid. Crosses the placental barrier. in the pleural and abdominal cavity may contain 50-100% of the serum concentration of the agent.

The process of metabolic transformation undergoes no more than 35% of the dose taken, the elimination half-life against the background normal function kidney is 10 hours. The agent is excreted unchanged through glomerular filtration: 50% - after 12 hours, 65-70% within 24-72 hours; a small amount is excreted in the faeces.

In the presence of chronic renal failure (CRF), cumulation may occur after 2–3 days.

Indications for use

  • tuberculosis: chronic forms, active pulmonary tuberculosis, extrapulmonary tuberculosis(including kidney damage) - with the sensitivity of pathogens to the drug and after ineffective therapy with basic drugs (as part of combined treatment);
  • urinary tract infections caused by susceptible strains of gram-negative and gram-positive bacteria (Escherichia coli, Enterobacter spp.);
  • atypical mycobacterial infections, including those caused by Mycobacterium avium (as part of a combination treatment).

Contraindications

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

Additional contraindications depending on the manufacturer:

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

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

Instructions for use Cycloserine: method and dosage

Cycloserine is taken orally, immediately before meals, in case of irritation of the mucous digestive tract- after meal.

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

The maximum daily dose of Cycloserine is 1000 mg, with functional disorders kidney requires a dose reduction.

Patients with a body weight of less than 50 kg, and over 60 years of age, should take the drug 250 mg twice a day.

Duration of therapy for urinary tract infections - 7-10 days, mycobacterial infections - from 6 months or more.

Children after 3 years (or after 12 years - depending on the manufacturer) are recommended to take the drug at a daily dose of 10-20 mg / kg of body weight in 2-3 doses, but not exceeding 750 mg per day. Taking large doses of Cycloserine is allowed only in the treatment of the acute phase of the tuberculous process or with insufficient effect of the above doses.

Side effects

  • cardiovascular system and hematopoietic organs: the occurrence of congestive heart failure (when using daily doses of 1000-1500 mg);
  • nervous system: dizziness, headache, nightmares, insomnia / drowsiness, irritability, anxiety, aggressiveness, memory impairment, peripheral neuritis, tremor, paresthesia, muscle twitching, dysarthria, depression, euphoria, disorientation with memory loss, confusion, psychosis, confusion, change in character, epileptiform convulsions, paresis, stupor, suicidal mood, large and small attacks of clonic convulsions, hyperreflexia, suicidal attempts, coma;
  • allergic reactions: itching, skin rash;
  • digestive system: heartburn, nausea, diarrhea, increased activity of hepatic aminotransferases (mainly in elderly patients with pre-existing liver disease);
  • other: increased cough, fever, megaloblastic / sideroblastic anemia, folic acid and cyanocobalamin deficiency.

Overdose

Overdose may occur at plasma concentrations of cycloserine 25-30 mg / ml, resulting from impaired renal clearance or taking large doses of the drug. At oral use funds in a daily dose of more than 1000 mg increases the likelihood of acute poisoning. Symptoms of chronic intoxication against the background of long-term use of the drug at 500 mg per day include the following disorders: dizziness, headache, irritability, confusion, psychosis, dysarthria, paresthesia, convulsions, paresis, coma.

At given state recommend symptomatic and supportive therapy. Reception activated carbon is more effective in reducing absorption than gastric lavage and induction of vomiting. For convulsions, antiepileptic drugs are prescribed, in order to prevent neurotoxic reactions, pyridoxine is administered at a dose of 200–300 mg per day, as well as sedative and anticonvulsant drugs. medicines. Carrying out hemodialysis ensures the removal of cycloserine from the blood, but cannot exclude the occurrence of life-threatening intoxication.

special instructions

Before starting therapy, it is required to isolate cultures of microorganisms and establish the sensitivity of strains to the drug. If tuberculosis infection is detected, the sensitivity of the strain to other anti-tuberculosis drugs should be determined.

If, during drug therapy, the development of allergic dermatitis or symptoms of CNS intoxication (dizziness, tremor, headache, drowsiness, convulsions, depression / confusion, paresis / dysarthria, hyperreflexia) is noted, its use must be discontinued or the dose reduced. In patients with chronic alcoholism due to the low therapeutic index of cycloserine, the risk of seizures increases.

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

Anticonvulsants or sedatives may be used to prevent the development of CNS symptoms such as tremors, agitation, or seizures. Patients taking cycloserine in a daily dose of more than 500 mg should be under the direct supervision of a physician due to the risk of such undesirable effects.

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

To prevent the development of neurotoxic disorders, psychotropic drugs of the benzodiazepine series are used - phenazepam (at a dose of 1 mg) or diazepam (at a dose of 5 mg) at night, as well as piracetam 2 times a day at a dose of 800 mg.

Sometimes taking cycloserine and other anti-tuberculosis drugs can lead to a deficiency of folic acid and cyanocobalamin (vitamin B 12) in the body, as well as to the development of sideroblastic and megaloblastic anemia. If anemia occurs during drug therapy, it is necessary to prescribe an appropriate examination and treatment.

Due to the rapid development of resistance when using cycloserine as a monotherapy drug, it should be combined with other anti-TB drugs.

Influence on the ability to drive vehicles and complex mechanisms

The effect of cycloserine on the ability to drive a car and other complex machinery has not been established, but due to possible development adverse reactions from the side of the central nervous system, patients should refrain from potentially dangerous species activities that require concentration and quick reactions.

Use during pregnancy and lactation

The concentration of cycloserine in the blood of the fetus and in mother's milk approach the concentrations found in the serum of a pregnant or breastfeeding woman (respectively). There are no data confirming the negative effect of the drug on the fetus when taken during pregnancy.

Application of Cycloserine:

  • pregnancy: allowed only in extremely rare cases, with a vital need;
  • lactation period: stop breastfeeding.

Some manufacturers of Cycloserine indicate pregnancy in the list absolute contraindications before taking the drug, so you should carefully study the attached instructions.

Application in childhood

The drug is contraindicated for children under 3 or under 12 years of age (depending on the manufacturer). Take cycloserine at childhood necessary with extreme caution.

For impaired renal function

In the presence of chronic renal failure (CC below 25 or 50 ml / min - depending on the manufacturer), therapy is contraindicated. In patients with reduced renal function, receiving the 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 must be monitored at least 1 time per week. In this case, the dose should be selected in such a way that the concentration of the drug in the blood is below 30 mg / l.

For impaired liver function

Functional disorders of the liver do not affect the kinetics of cycloserine.

Use in the elderly

Elderly patients (over 60 years old) are recommended to take the drug 2 times a day, 250 mg.

drug interaction

  • pyridoxine: increased excretion rate this tool kidneys (the development of peripheral neuritis and anemia is possible, the dose of pyridoxine should be increased);
  • isoniazid: increased incidence of drowsiness, dizziness (patients require careful monitoring);
  • ethionamide: the threat of the appearance of neurotoxic effects of the drug is aggravated, the likelihood of occurrence increases convulsive syndrome;
  • streptomycin, isoniazid, para-aminosalicylic acid (PAS): reduced resistance to these drugs;
  • ethanol: increased risk of development epileptic seizures(especially in patients with chronic alcoholism).

Analogues

Analogues of Cycloserine are: Kansamine, Kokserin, Maiser, Cyclorin, Cycloserin-Ferein.

Terms and conditions of storage

Store in a place protected from moisture and light, out of the reach of children, at a temperature not exceeding 25 °C.

Shelf life - 2 years.

Cycloserine is formed during the vital activity of Streptomyces orchidaceus and other microorganisms or is formed synthetically. Cycloserine disrupts cell wall synthesis. Cycloserine is a competitive antagonist and analogue of D-alanine. Cycloserine inhibits the activity of two enzymes that are involved in the formation of the bacterial cell wall at the early stages: D-alanyl-D-alanine synthetase (ensures the inclusion of D-alanine in the pentapeptide, which is necessary for the formation of peptidoglycans) and L-alanine racemase (turns L-alanyl into D -alanine). Cycloserine is effective against Mycobacterium tuberculosis, gram-negative, gram-positive bacteria, and other microorganisms. Cycloserine exhibits a bactericidal or bacteriostatic effect, depending on the sensitivity of microorganisms and concentration in the focus of infection. Cycloserine is active against gram-negative microorganisms at a concentration of 10-100 mg/l - Rickettsia spp., Treponema spp., the minimum inhibitory concentration against Mycobacterium tuberculosis is 3-25 mg/l in liquid and 10-20 mg/l and more on solid nutrient medium. Cycloserine is active against Klebsiella spp., Enterobacter spp., Eschevichia coli. The resistance of Mycobacterium tuberculosis to cycloserine develops rarely and slowly, after six months of treatment, up to 20-30% of strains resistant to the drug are isolated. Cycloserine did not show cross-resistance with other anti-tuberculosis drugs. The effectiveness of cycloserine in chronic forms of tuberculosis, which are caused by mycobacteria that are resistant to other anti-tuberculosis drugs, atypical mycobacterioses, which are caused by the Mycobacterium xenopi complex, Mycobacterium avium-intracellulare and others, has been shown.
When administered orally, cycloserine is rapidly and almost completely (70-90%) absorbed from the gastrointestinal tract. The maximum concentration of cycloserine in the blood is reached after 3 to 8 hours. When taken at a dose of 250 mg every 12 hours, the maximum concentration of cycloserine in the blood is 25-30 mcg / ml. Cycloserine almost does not bind to plasma proteins. Cycloserine is well distributed in body fluids and tissues, including spinal, synovial, ascitic and pleural fluids, sputum, bile, lungs, lymphoid tissue. Cycloserine crosses the blood-brain and placental barrier and is excreted in breast milk. The concentration of cycloserine in the pleural, cerebrospinal fluid, breast milk and fetal blood approaches the plasma concentration. Cycloserine is partially (35%) biotransformed in the liver to unidentified metabolites. The half-life of cycloserine is 8-12 hours. Cycloserine is excreted mainly by the kidneys (by glomerular filtration) unchanged (66% during the day and another 10% is excreted over the next 2 days) and in small amounts with faeces. Repeated receptions cycloserine may be accompanied by cumulation. In renal insufficiency, the half-life of cycloserine increases.
Studies evaluating the carcinogenicity of cycloserine have not been performed.
In the test of non-reparative synthesis of deoxyribonucleic acid and the Ames test, negative results were obtained.
Studies on two generations of rats showed no impairment of fertility during the first mating and some decrease in fertility during the second mating. Studies on two generations of rats that received doses up to 100 mg / kg per day did not reveal a teratogenic effect of cycloserine. The ability of cycloserine to cause damage to the fetus when the drug is taken by pregnant women has not been established.

Indications

Active form of pulmonary tuberculosis, extrapulmonary tuberculosis (including kidney damage) with the sensitivity of microorganisms to cycloserine and after unsuccessful adequate therapy essential anti-tuberculosis drugs (isoniazid, streptomycin, ethambutol, rifampicin) only in combination with other anti-tuberculosis drugs medicines; chronic forms of tuberculosis; combination of tuberculosis acute infections urinary tract, which are caused by susceptible strains of gram-negative and gram-positive microorganisms, especially Enterobacter spp., Klebsiella spp., Eschevichia coli with the ineffectiveness of essential drugs (using cycloserine for the treatment of these infections is necessary only when all conventional drugs for treatment and the sensitivity of microorganisms to it was determined); atypical mycobacterial infections (including those caused by Mycobacterium avium); urinary tract infections.

Route of administration of cycloserine and dose

Cycloserine is taken orally immediately before meals, with irritation of the mucous membrane gastrointestinal tract the drug is taken after meals.
Adults, the initial dose is 250 mg 2 times a day with an interval of 12 hours during the first two weeks, then, if necessary, taking into account tolerance, the dose is carefully increased to 250 mg every 6 to 8 hours under the control of the concentration of cycloserine in the blood, the maximum daily dose is 1 d. For children (over 3 years old) usual dose ranges from 10 mg / kg per day in 2 to 3 doses, then the dose varies depending on the concentration of cycloserine in the blood and therapeutic effect; a large dose is given only with insufficient effectiveness of smaller doses or in the acute phase of the tuberculous process; the daily dose for children should not exceed 750 mg. Patients over 60 years of age, as well as patients weighing less than 50 kg, cycloserine is prescribed 250 mg twice a day.
Before starting therapy, it is necessary to isolate cultures of microorganisms and determine the sensitivity of strains of microorganisms to cycloserine and other anti-tuberculosis drugs.
During therapy, you can not drink alcohol.
Elderly patients with impaired functional state kidneys are prescribed smaller doses of cycloserine.
During therapy, it is necessary to control the concentration of cycloserine in the blood (the concentration of cycloserine in the blood should not exceed 30 mg / l, at concentrations above 30 mg / ml, toxicity is likely), kidney and liver function, and hematological parameters.
Sedative or anticonvulsant drugs may be used to prevent symptoms of neurotoxicity (including convulsions, tremors, agitation).
Careful monitoring of patients who receive cycloserine at a dose of more than 500 mg per day is necessary to identify signs of toxic effects of the drug on the central nervous system.
Cycloserine should be discontinued or the dose reduced if the patient develops allergic dermatitis or symptoms of intoxication from the central nervous system: convulsions, drowsiness, psychosis, confusion, depression of consciousness, headache, hyperreflexia, tremor, paresis, dizziness, dysarthria.
The risk of developing convulsive syndrome increases in patients with chronic alcoholism, so the use of cycloserine in this condition is contraindicated.
When treating patients with reduced renal function who take a daily dose of more than 500 mg and who are likely to have signs and symptoms of an overdose, the concentration of cycloserine in the blood should be determined at least once a week. The dose of cycloserine should be adjusted to maintain the drug concentration in the blood below 30 mg/L. Such patients should be under the direct supervision of a physician due to the possible development of symptoms of toxicity.
In some cases, the use of cycloserine and other anti-tuberculosis drugs can cause a deficiency of folic acid and cyanocobalamin (vitamin B12) in the body, the development of megaloblastic anemia. With the development of anemia during therapy, it is necessary to conduct an appropriate examination and treatment of the patient.
It is possible to reduce or prevent the toxic effects of cycloserine by prescribing glutamic acid 500 mg 3 to 4 times a day (before meals) during the period of therapy, and daily intramuscular injection sodium salt adenosine triphosphoric acid (1 ml of 1% solution), pyridoxine 200-300 mg per day.
During treatment with cycloserine, it is necessary to limit mental stress patients and exclude possible factors of overheating (hot showers, exposure to the sun).
During treatment with cycloserine, it is necessary to refuse to perform potentially hazardous activities that require the speed of psychomotor reactions and increased concentration attention (including transport management, work with mechanisms).

Contraindications for use

Hypersensitivity, depression, epilepsy, severe agitation, chronic renal failure (creatinine clearance less than 25 ml / min), psychosis, alcoholism, mental disorders (psychosis, anxiety, depression, including history), organic diseases of the central nervous system, chronic heart failure, seizures(including history), age up to 3 years, pregnancy, breastfeeding.

Application restrictions

Chronic renal failure (creatinine clearance more than 25 ml / min), age up to 18 years.

Use during pregnancy and lactation

The use of cycloserine is contraindicated in pregnancy. It has not been established whether cycloserine causes fetal harm when used in pregnant women. Cycloserine should only be given to pregnant women when absolutely necessary. During lactation for the duration of cycloserine therapy, it is necessary to stop breastfeeding or stop taking cycloserine for the duration of breastfeeding, taking into account the importance of treatment with the drug for the mother.

Side effects of cycloserine

Nervous system and sense organs: tremor, headache, dysarthria, convulsions, epileptic convulsions, dizziness, drowsiness, semiconscious state, disorientation, confusion, memory loss, psychosis, anxiety, insomnia, stupor, suicidal behavior, peripheral neuritis, euphoria, suicidal attempts, change in character, aggressiveness, irritability, paresis, paresthesia, depression, attacks of clonic convulsions, hyperreflexia, coma .
Digestive system: nausea, heartburn, increased serum aminotransferase levels (especially in elderly patients with liver disease).
Cardiovascular system and blood (hematopoiesis, hemostasis): congestive heart failure, exacerbation of chronic heart failure, megaloblastic anemia, sideroblastic anemia.
Allergic reactions: skin rash, itching.
Others: fever, increased cough.

Interaction of cycloserine with other substances

Cycloserine helps to reduce resistance to streptomycin, isoniazid, para-aminosalicylic acid.
Isoniazid and ethionamide (including combined drugs) at joint application cycloserine with mutually increase neurotoxicity.
Cycloserine is incompatible with alcohol (the risk of developing epileptic seizures increases).
Azithromycin slows down excretion, increases the concentration of cycloserine in the blood and increases the risk of toxicity.
Cycloserine enhances the mutual effect of the combined drugs amoxicillin + clavulanic acid, amoxicillin + sulbactam.
in a placebo controlled clinical trial in patients with multidrug-resistant tuberculosis, no significant pharmacokinetic interaction of bedaquiline and cycloserine was observed.
Possible interaction of cycloserine and a combination of benfotiamine + pyridoxine.
Stability was observed BCG vaccines to cycloserine.
Cycloserine weakens the effect of pyridoxine (including the composition of various combinations) by increasing the rate of excretion of pyridoxine by the kidneys (may cause the development of anemia, peripheral neuritis, an increase in the dose of pyridoxine is necessary).
In the combined treatment of tuberculosis, it is necessary to take into account the additive effect on the central nervous system of protionamide (as part of a combination of pyrazinamide + prothionamide + rifabutin + [pyridoxine]) and cycloserine.
Prothionamide (as part of combinations of lomefloxacin + pyrazinamide + prothionamide + ethambutol, lomefloxacin + pyrazinamide + prothionamide + ethambutol + pyridoxine) is compatible with cycloserine.
Cycloserine reduces the effect of pyridoxal phosphate.
Possible interaction of the combination of pyridoxine + thiamine + cyanocobalamin + [lidocaine] with cycloserine.
The combined use of pyridoxine with cycloserine can cause neuropathy and anemia.
With the combined use of protionamide and cycloserine, convulsions become more frequent.
When sharing folic acid reduces the effects of cycloserine.

Overdose

Acute overdose can occur when using cycloserine in a dose of more than 1 g. Signs of overdose can be observed when the content of cycloserine in the blood serum is 25-30 mg / ml (high doses, if more than 500 mg of cycloserine is administered daily to the body, impaired renal clearance). With an overdose of cycloserine, headache, irritability, dizziness, paresthesia, paresis, dysarthria, convulsions, semi-consciousness, psychosis, confusion, coma develop.
taking activated charcoal (may be more effective than inducing vomiting and gastric lavage); symptomatic and supportive treatment; with convulsions, the use of antiepileptic drugs; to prevent neurotoxic effects, pyridoxine (200-300 mg per day), nootropic drugs (piracetam, glutamic acid), benzodiazepine drugs (diazepam) are used. Carrying out hemodialysis removes cycloserine from the blood, but does not exclude the development of life-threatening intoxication.

Trade names of drugs with the active substance cycloserine

Combined drugs:
Cycloserine + Pyridoxine: Kokserin Plus, Cyclo plus, Cyclomycin® plus.

bactericidal antibiotic, violates the synthesis of the cell wall. Active against gram-negative microorganisms, at a concentration of 10-100 mg / l - against Rickettsia spp., Treponema spp.. Currently used only for the treatment of patients with tuberculosis. IPC in relation to Mycobacterium tuberculosis is 3-25 mg/l on liquid and 5-40 mg/l on solid nutrient medium. Resistance of mycobacteria to cycloserine develops slowly (after 6 months of treatment - in 20-60% of cases). Does not cause the development of cross-drug resistance. In activity inferior to streptomycin and ftivazid, but active against Mycobacterium tuberculosis resistant to these drugs and PAS.
After oral administration, it is rapidly and almost completely absorbed from the gastrointestinal tract (70-90%). The time to reach the maximum concentration is 3-4 hours. It does not bind to plasma proteins. It penetrates well into body fluids and tissues, including CSF, breast milk, bile, sputum, lymphatic tissue, lungs, ascitic and synovial fluid, pleural effusion, crosses the placenta. in the abdomen and pleural cavity contains 50-100% concentration of the drug in the blood serum. Up to 35% of the drug is metabolized. The half-life with normal kidney function is 10 hours. It is excreted by glomerular filtration in active form(after 6 hours - 20%, after 12 hours - 30%, after 24 hours - 50%, after 2-3 days - up to 70%), small amounts - with feces.

Indications for the use of the drug Cycloserine

Chronic forms of tuberculosis (as a reserve drug).

The use of the drug Cycloserine

Inside, immediately before meals (in case of irritation of the gastrointestinal mucosa - after eating), adults - 0.25 g every 12 hours for the first 12 hours, then, if necessary, taking into account tolerance, the dose is gradually increased to 250 mg every 6-8 hours under the control of the concentration of cycloserine in the blood serum. The maximum daily dose is 1 g. Patients over the age of 60, as well as those weighing less than 50 kg - 0.25 g 2 times a day. The daily dose for children is 0.01-0.02 g / kg (not higher than 0.75 g / day).

Contraindications to the use of the drug Cycloserine

Hypersensitivity to the drug, organic diseases of the central nervous system, epilepsy, seizures (including history), mental disorders(anxiety, psychosis, depression, including history), heart failure, renal failure, alcoholism, pregnancy and lactation. Use with caution in children.

Side effects of cycloserine

headache, dizziness, insomnia or drowsiness, anxiety, irritability, memory loss, paresthesia, peripheral neuritis, tremor, euphoria, depression, suicidal ideation, psychosis, epileptiform convulsions; nausea, heartburn; fever, increased cough.

Special instructions for the use of the drug Cycloserine

Caution should be used in children. prevent or reduce toxic effect cycloserine can be prescribed during treatment with glutamic acid 0.5 g 3-4 times a day (before meals), and daily intramuscular injection of ATP sodium salt (1 ml of 1% solution). During the period of treatment, it is necessary to monitor kidney function (the level of creatinine and urea nitrogen in the blood serum), the concentration of cycloserine in the blood serum (should not exceed 30 mcg / ml). In connection with rapid development resistance in monotherapy with cycloserine, its combination with other anti-tuberculosis drugs is recommended.

Interactions of the drug Cycloserine

Ethionamide, pyrazinamide, sodium paraaminosalicylate, rifampicin, isoniazid increase the antituberculous effect of cycloserine, increase the frequency of reactions from the central nervous system (convulsive seizures, dizziness, drowsiness). Ethanol increases the risk of developing epileptic seizures. Cycloserine increases the excretion of pyridoxine by the kidneys (may induce anemia and peripheral neuritis, an increase in the dose of pyridoxine is required).

Overdose of the drug Cycloserine, symptoms and treatment

overdose phenomena are observed at a concentration of cycloserine in the blood plasma of 30 mg / ml and above (taking high doses, impaired renal clearance). Acute poisoning may occur when ingested more than 1 g / day.
Symptoms: headache, dizziness, confusion, irritability, paresthesia, psychosis, dysarthria, paresis, convulsions, coma. Treatment is symptomatic. To prevent neurotoxic effects, pyridoxine is administered at a dose of 200-300 mg/day. Hemodialysis is not effective.

List of pharmacies where you can buy Cycloserine:

  • St. Petersburg