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

Active substanceDiazepamDiazepam

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Apaurin

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KRKA, dd, Novo mesto, AO

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Dosage form: & nbspcoated tablets

Composition:

1 tablet, coated, contains:

Core: 2 mg 5mg

Active substance:

Diazepam 2.00 mg 5.00 mg

Excipients:

Lactose Monohydrate 94.40 mg 91.40 mg

Corn starch 21.90 mg 21.90 mg

Povidone 6.00 mg 6.00 mg

Talc 5.00 mg 5.00 mg

Magnesium stearate 0.70 mg 0.70 mg

Sheath:

Sucrose 51.10 mg 50.30 mg

Acacia gum 0.90 mg 0.90 mg

Talc 28.00 mg 28.80 mg

* Dye sunset sunset yellow (E110) 0.0656 mg

* Dye quinoline yellow (E104) 0.0396 mg

* Indigocarmine (E132) 0.0059 mg

* Capol 600 Farma 0.60 mg 0.60 mg

* not included in the final mass of the tablet

Description:

Tablets 2 mg:

Round, biconvex tablets, covered with a shell of orange, with possible impregnations of white.

* Type of tablet on a cross-section: rough mass of white or almost white color with a cover of orange color.

Tablets 5 mg:

Round, biconvex tablets, covered with a shell of green color with possible impregnations of white.

* Type of tablet on a cross-section: rough mass of white or almost white color with a shell of green color.

Pharmacotherapeutic group:Anxiolytic agent (tranquilizer). List III of the list of narcotic drugs, psychotropic substances and their precursors subject to control in the Russian Federation

ATX: & nbsp

N.05.B.A.01 Diazepam

Pharmacodynamics:

Diazepam is a benzodiazepine derivative with a wide spectrum of action. Has an anxiolytic, hypnosedative, muscle-relaxing and anticonvulsant effect through specific benzodiazepine receptors, the largest number of which is located in the limbic system, hypothalamus, cerebellum and striatum.These receptors, along with GABA receptors (gamma-aminobutyric acid) form an anatomical and functional whole. After the binding of diazepam to the receptor, GABA-ergic transmission and inhibition of the central nervous system are enhanced. This leads to an anticonvulsant and muscular-relaxing effect. Due to the potentiation of GABA effects, the stimulating effect of such neurotransmitters as serotonin, noradrenaline or acetylcholine, which causes anxiolytic, hypnotic and sedative effects.

Pharmacokinetics:

Suction

Absorption of diazepam from the gastrointestinal tract (GIT) is rapid and complete. After ingestion, about 75% is absorbed: Bioavailability is 90%.

Food does not affect the absorption of diazepam.

Metabolism

Metabolized in the liver with the participation of isoenzymes CYP2C19, CYP3A4; CYP3A5 and CYP3A7 with the formation of three metabolites. The main metabolite - N-desmethyldiazepam, which has biological activity and a large T_1/2, than diazepam. The other two metabolites - oxazepam and temazepam, biologically active, but do not take significant part in the_; development of pharmacodynamic effects of diazepam at the expense of a shorter T_1/2 in comparison with the basic substance. Penetrates through the blood-brain and placental barrier, is found in breast milk in concentrations corresponding to 1/10 of the concentration in the blood plasma. The connection with plasma proteins is 98%.

Distribution and deduction

Diazepam - quickly distributed in the human body. The volume of distribution is approximately 1.1 l / kg, which indicates active binding to plasma proteins (98 - 99%). It is excreted by the kidneys - 70% (in the form of glucuronides), unchanged 1-2% and less than 10% - by the intestine. The excretion has a two-phase character: behind the initial phase of rapid and extensive distribution (T_1/2- 3 h) follows a prolonged phase (T_1/2- 20-70 hours). T_1/2desmethyldiazepam - 30-100 h, temazepam - 9.5-12.4 h and oxazepam - 5-15 h.

With repeated use, the accumulation of diazepam and its active metabolites is significant. Refers to benzodiazepines with long T_1/2, excretion after cessation of treatment is slow, because metabolites persist in the blood for several days or even weeks.

Indications:

Anxiety disorders.

Dysphoria (as part of combination therapy as an additional drug (LS)).

Insomnia (difficulty falling asleep).

Spasm of skeletal muscles with local trauma; spastic conditions associated with the defeat of the brain or spinal cord (cerebral palsy, athetosis, tetanus); myositis, bursitis, arthritis, spondylitis, rheumatoid arthritis; osteoarthritis, accompanied by a strain of skeletal muscles; vertebral syndrome, angina, tension headache.

An abstinent alcoholic syndrome: anxiety, tension, agitation, tremor, transient reactive states.

Premedication before surgical interventions and endoscopic manipulations, general anesthesia.

In the complex therapy: hypertension, peptic ulcer and duodenal ulcer; psychosomatic disorders in obstetrics and gynecology: menopausal and menstrual disorders, gestosis; eczema and other diseases, accompanied by itching, irritability.

Ménière's disease. Convulsive syndrome with drug poisoning.

Contraindications:

Hypersensitivity, coma, shock, acute alcohol intoxication with the weakening of vital functions, acute intoxication of drugs that have an inhibitory effect on the central nervous system (incl.narcotic analgesics and hypnotic drugs), myasthenia gravis, angle-closure glaucoma (acute attack or predisposition); severe chronic obstructive pulmonary disease (risk of progression of respiratory failure), acute respiratory failure, pregnancy, lactation period, children under 3 years of age, deficiency of lactase and / or sucrose / isomaltase, fructose or lactose intolerance, glucose-galactose malabsorption.

Carefully:Epilepsy or epileptic seizures in the anamnesis (initiation of diazepam treatment or its abrupt withdrawal can accelerate the development of seizures or epileptic status), hepatic and / or renal failure, cerebral and spinal ataxia, hyperkinesia, drug addiction in the anamnesis, propensity to abuse psychoactive drugs, organic diseases brain, hypoproteinemia, nocturnal apnea (established or presumed), advanced age.

Pregnancy and lactation:

The drug Apaurin is not recommended for pregnant women. Its use before delivery can cause a decrease in blood pressure, respiratory depression and cause the "cancellation" syndrome in a newborn.

The drug Apaurin is secreted into breast milk, so it can not be used, during the period breastfeeding. If it is necessary to use the drug, Apaurin breastfeeding should be discontinued.

Dosing and Administration:

The dose is always set by the doctor.

The dosage regimen depends on the severity of the symptoms, the patient's age and condition.

Anxiety disorders, dysphoria:

From 2 mg to 10 mg 2-3 times a day.

Insomnia (difficulty falling asleep):

From 4 mg to 10 mg in the evening, before bedtime.

Muscle spasms: 2-10 mg 3 times a day.

Spastic conditions of central origin in degenerative neurological diseases, Meniere's disease, convulsive syndrome: 5-10 mg 2-3 times a day.

Diseases of the musculoskeletal system: 5 mg 1-4 times a day.

Alcohol abstinence syndrome: 10 mg 3-4 times a day in the first 24 hours, followed by a decrease to 5 mg 3-4 times a day.

Premedication: on the eve of surgery, in the evening -10-20 mg.

Angina pectoris and hypertension, gastric ulcer and 12 pc, eczema and other diseases accompanied by itching and irritability: 2-5 mg 2-3 times a day.

Obstetrics and gynecology: psychosomatic disorders, climacteric and menstrual disorders, gestosis: 2-5 mg 2-3 times a day.

Older, weakened patients, as well as patients with atherosclerosis at the beginning of treatment: 2 mg 2 times a day, if necessary, increase the dose to obtain the optimal effect.

Working patient: 2 mg 1-2 times a day or 5 mg (the main dose) in the evening.

Syndrome of "lifting" diazepam: 2 tablets (5 each mg) 3 times in the first 24 hours, then 1 tablet (5 mg) 3 times a day.

Children over 3 years: 1 tablet (2 mg) 2-3 times a day.

Treatment begins with the recommended doses. After one or two weeks, the dose of the drug, if necessary, can be reduced so that the drug is taken 1 time per day, preferably in the evening.

Treatment usually lasts from several days to several weeks.

With prolonged use of benzodiazepines, the tolerability of these drugs varies; there may be signs of psychological and physical dependence. The risk of developing dependence is higher when using high doses and with long-term use.

With long-term use, the drug Apaurin should be canceled gradually, as a sharp cessation of therapy can cause symptoms of the "withdrawal" syndrome (tremor, abdominal and muscle spasms, vomiting, sweating).

Side effects:

Classification of the incidence of adverse events (WHO): very often> 1/10, often> 1/100 to <1/10, infrequently from> 1/1000 to <1/100, rarely> 1/10000 to <1 / 1000, very rarely from <1/10000, including individual messages.

On the part of the hematopoiesis system:

-very rare: neutropenia (with prolonged use, periodic monitoring of the blood composition is recommended), leukopenia, agranulocytosis, anemia, thrombocytopenia;

From the nervous system:

-frequently: weakness, drowsiness, ataxia,

-nonly: confusion, depression, dysarthria, incoherent speech, decreased activity, decreased libido, headache, dizziness, tremor, memory problems, insomnia, hallucinations, anxiety,

-only: headache, euphoria, depression, tremor, depression of mood, catalepsy, extrapyramidal reactions (uncontrolled body movements, including the eyes), hyporeflexia;

-very rare: paradoxical reactions (aggressive outbreaks, psychomotor agitation, fear, suicidal tendencies, muscle spasm, irritability, acute agitation);

From the cardiovascular system:

-nonly: heart palpitations, bradycardia, fainting, cardiovascular collapse;

From the sense organs:

-Often: blurred vision, diplopia, nystagmus;

From the digestive system:

-non-often: constipation, nausea, vomiting, dryness of the oral mucosa or hypersalivation, heartburn, hiccough, gastralgia, decreased appetite;

-very rare: jaundice (long-term use is recommended periodic monitoring of liver function), violations of liver function, increased activity of "liver" transaminases and alkaline phosphatase;

From the skin:

-only: urticaria, skin rash, itching;

From the musculoskeletal system:

-only: muscle weakness;

From the urinary system:

- Uncommon: urinary incontinence, urinary retention, impaired renal function;

On the part of the reproductive system:

-Often: violations of the menstrual cycle, increased or decreased libido.

Influence on the fetus: teratogenicity (especially I trimester), CNS depression, respiratory failure and suppression of sucking reflex in newborns whose mothers used the drug.

During and after therapy with diazepam, small, clinically insignificant changes in the electroencephalogram (most often, low-speed fast activity) are possible.

With prolonged use of benzodiazepines, the tolerability of these drugs varies; may develop signs of mental or physical dependence.The risk of developing dependence is higher when using high doses and long-term use of drugs.

With a sharp discontinuation of diazepam, the symptoms of the "withdrawal" syndrome (convulsions, tremors, abdominal and muscle cramps, vomiting, sweating) develop. Most often these symptoms develop after prolonged use of high doses. More mild symptoms (dysphoria, insomnia) are noted after a sudden withdrawal of benzodiazepines taken at therapeutic doses for several months.

Thus, rapid discontinuation of the drug should be avoided with its long-term use, and the daily dose should be reduced gradually.

With the development of severe adverse effects, treatment should be discontinued.

Overdose:

Symptoms: drowsiness, dizziness, weakness, dysarthria, respiratory failure; in more severe cases - loss of consciousness, hyporeflexia or areflexia, respiratory depression, especially when combined with alcohol or other substances that depress the central nervous system.

Treatment: gastric lavage, forced diuresis, activated charcoal. The patient needs active monitoring in an intensive care unit; in heavycases, especially with respiratory depression, a specific benzodiazepine receptor antagonist is prescribed - flumazenil. The half-life of flumazenil is approximately 1 hour, and it is shorter than the half-life of diazepam. Therefore, to maintain the desired level of consciousness, repeated administration of flumazenil is necessary, preferably in the form of infusions. The recommended initial dose of flumazenil is 0.3 mg intravenously. If the desired effect is not achieved within 60 seconds, you can reintroduce 0.1 mg until a total dose of 2 mg is reached or until the patient is conscious. If after restoration of consciousness of the patient it is broken. repeatedly, the same doses are usually administered. In such cases, intravenous flumazenil may be administered at a rate of 0.1 mg to 0.4 mg / hour, depending on the desired level of consciousness.

Although flumazenil is an effective antidote for benzodiazepine intoxications, it should not be administered with benzodiazepine intoxication in patients with epilepsy, since it can provoke the development of seizures.

Hemodialysis is ineffective.

Interaction:

During therapy, diazepam should avoid drinking alcohol because of the potential for potentiating its effects.

With the simultaneous use of diazepam with sedatives, antidepressants, antipsychotics, barbiturates, narcotic analgesics, anesthetics, monoamine oxidase (MAO) inhibitors, antiepileptic drugs and antihistamines, its suppressing effect on the central nervous system increases.

The combined use of erythromycin or rifampicin also enhances the effects of diazepam. Diazepam reduces the action of levodopa.

Cimetidine reduces the clearance of diazepam and enhances its effect.

Omeprazole slows the metabolism of diazepam and increases the time of its action and excretion. Simultaneous use of antifungal agents (itraconazole, fluconazole and ketoconazole) can increase plasma concentrations of diazepam and cause unwanted effects. Oral contraceptives can slow the metabolism of diazepam.

Rifampicin can increase the excretion of diazepam and lower its concentration in the blood plasma. Theophylline (used in low doses) can reduce or even distort the sedative effect of diazepam.

Special instructions:

In elderly patients,children and in patients with organic lesions of the central nervous system, treatment with Apaurin should be started cautiously and gradually, due to large differences in individual tolerability.

Caution is also necessary for chronic lung diseases, as possible the aggravation of respiratory failure.

Patients with severe kidney disease, expressed by cardiac insufficiency, with psychosis and a tendency to alcohol dependence, psychotropic drugs or prohibited psychotropic substances, should be carefully monitored. With prolonged use of benzodiazepines, the tolerability of these drugs varies.

Sometimes mental or physical drug dependence may develop, especially with prolonged use of high doses (more than 3 months). Therefore, individuals who are addicted to addiction, such as those suffering from alcoholism or dependence on other psychotropic substances, and patients with personality disorders, should be carefully monitored during treatment.

A sharp cessation of therapy can cause a transient increase in anxiety (anxiety of "withdrawal") or insomnia.

After long-term use, the drug Apaurin should be canceled gradually, as a sharp cessation of therapy can cause withdrawal symptoms (tremor, muscle and stomach cramps, vomiting, sweating).

Treatment usually lasts from several days to a maximum of 12 weeks, including a period of gradual dose reduction. Treatment can be continued only after a thorough reanalysis of the patient's condition.

When using any benzodiazepines in some cases, a paradoxical reaction may develop. It often develops in the elderly and in children. When there is excitement, aggressiveness, anxiety, confusion, increased muscle spasms or insomnia, treatment with Apaurin should be stopped.

Specific information on certain components of the drug

Sucrose can have a damaging effect on the teeth.

Azole dyes E110 (2 mg tablets) can cause allergic reactions.

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

The drug can affect psychophysical activities, especially when using alcohol or other drugs that depress the central nervous system.During the application of Apaureen it is necessary to refrain from managing motor transport and employment of other potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets coated with 2 mg and 5 mg.

Packaging:

For 15 tablets in a blister of PVC - aluminum foil.

2 blisters are placed in a pack of cardboard along with instructions for use.

Storage conditions:

The drug belongs to the list of No. 1 potent substances of the Standing Committee on Drug Control of the Ministry of Health and Social Development.

At a temperature of no higher than 25 ° C, in the original packaging.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N012412 / 01

Date of registration:23.02.2011

Expiration Date:Unlimited

Date of cancellation:2016-10-27

The owner of the registration certificate:KRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Manufacturer: & nbsp

KRKA, d.d. Slovenia

Representation: & nbspKRKA KRKA Slovenia

Information update date: & nbsp08.09.2017

Illustrated instructions

Instructions

Apaurin (Apaurin®)