Clonazepam - instructions for use, doses, side effects, contraindications

Active substanceClonazepamClonazepam

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Clonazepam

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Remedika Co., Ltd. Cyprus

Clonazepam

pills inwards

MOSCOW ENDOCRINE FACTORY, FSUE Russia

Dosage form: & nbsppills

Composition:

Composition per tablet for a dosage of 0.5 mg.

Active substance:

clonazepam - 0.5 mg

Excipients:

potato starch - 30.0 mg,

Mannitol (mannitol) - 51.5 mg,

lactose monohydrate - 50.0 mg,

crospovidone XL-10), 9.0 mg,

povidone type K-25 (polyvinylpyrrolidone medium-molecular medical) - 4.5 mg,

silicon dioxide colloid (aerosil) - 3.0 mg, magnesium stearate - 1.5 mg.

Composition per tablet for a dosage of 2.0 mg.

Active substance:

clonazepam 2.0 mg

Excipients:

potato starch - 30.0 mg,

Mannitol (mannitol) - 50.0 mg,

lactose monohydrate - 50.0 mg,

crospovidone XL-10), 9.0 mg,

povidone type K-25 (polyvinylpyrrolidone medium-molecular medical) - 4.5 mg,

silicon dioxide colloid (aerosil) - 3.0 mg, magnesium stearate - 1.5 mg.

Description:Round flat-cylindrical tablets of white or almost white color with a facet and a cross-shaped risk.

Pharmacotherapeutic group:Antiepileptic agent. Psychotropic substance listed in List III of the "List of narcotic drugs, psychotropic substances and their precursors subject to control in the Russian Federation"

ATX: & nbsp

N.03.A.E.01 Clonazepam

Pharmacodynamics:

Clonazepam belongs to the benzodiazepine group. Has anticonvulsant, sedative, central muscle relaxant and anxiolytic effect. Enhances the inhibitory effect of gamma-aminobutyric acid (a mediator of pre- and postsynaptic inhibition in all parts of the central nervous system (CNS)) on the transmission of nerve impulses. Electroencephalographic studies have shown that clonazepam quickly suppresses paroxysmal activity of various types, including complexes "spike-wave" with absences (petit mal), slow and generalized complexes "spike-wave", "soldering" of temporal and other localizations, as well as irregular "spikes" and "waves." Effective in focal and generalized forms of epilepsy. Anxiolytic action is due to the influence on the amygdala complex of the limbic system and is manifested in a decrease in emotional tension, easing anxiety, fear, anxiety. The sedative effect is due to the influence on the reticular formation of the brainstem and the nonspecific nuclei of the thalamus and is manifested by a decrease in the symptomatology of neurotic origin (anxiety, fear).

Pharmacokinetics:

- Suction: when administered orally clonazepam well absorbed from the gastrointestinal tract (GIT), reaching a maximum concentration of C_m_Oh in the blood plasma 1-4 hours after taking. Bioavailability is about 90%.

- distribution: 85% of clonazepam binds to plasma proteins. The average volume of distribution is 3 l / kg. It is assumed that clonazepam penetrates through blood-brain and placental barriers, penetrates into breast milk.

- metabolism: biotransformation of clonazepam includes oxidative hydroxylation and reduction of the 7-nitro group in the liver to form 7-amino or 7-acetylamino compounds with an insignificant amount of 3-hydroxy derivatives of all three compounds and their glucuronide and sulfate conjugates. Nitro compounds have pharmacological activity, and amino compounds - no. The equilibrium concentration in the blood is reached after 4-6 days.

- excretion: is excreted in the form of metabolites with urine (50-70%) and through the gastrointestinal tract (10-30%). About 0.5% of the dose taken is excreted by the kidneys unchanged. Half-life T_1/2 is 20-60 hours.

Indications:All clinical forms of epilepsy and seizures in children and adults, including absences (small epileptic seizure),including atypical absence; primary or secondary generalized clonic-tonic (major epileptic seizure), tonic or clonic convulsions; simple or complex partial (focal) convulsions; various forms of myoclonic seizures, myoclonus and associated pathological movements.

Contraindications:

- Hypersensitivity to any of the components of the drug or to other benzodiazepines;

- Acute pulmonary insufficiency;

- Severe respiratory failure;

- Sleep apnea syndrome;

- Myasthenia gravis;

- Severe hepatic impairment;

- Oppression of consciousness;

- Hereditary lactose intolerance, lactase deficiency, glucose-galactose malabsorption;

- Children under 3 years.

Carefully:

Cerebrospinal or spinal ataxia, hepatic insufficiency, impaired renal and hepatic function, cirrhosis of the liver, chronic diseases of the respiratory system, heart failure, depression, suicidal thoughts and attempts in history, psychoses, chronic alcoholism, drug addiction in the anamnesis (including narcotic), porphyria, elderly age, with acute intoxication with alcohol or narcotic substances.

Pregnancy and lactation:

Fertility

According to available data on pre-clinical studies, clonazepam has a toxic effect on reproductive function. Epidemiological assessments prove the teratogenic effect of anticonvulsants. In the course of preclinical studies, there was a twofold increase in the incidence of birth defects, with doses exceeding the therapeutic doses for humans in 3, 9 and 18 times, compared with the control groups. Due to the teratogenic properties of clonazepam, patients with childbearing potential need to use effective contraceptive methods throughout the treatment period and two weeks after the end of treatment.

Pregnancy

Clonazepam has an adverse pharmacological effect on pregnancy and fetus / newborn baby. The introduction of high doses in the last trimester of pregnancy or during labor can cause disturbances in the heart rhythm in the fetus and hypothermia, hypotension, mild respiratory depression, and a weak sucking reflex in the newborn. In children whose mothers constantly took benzodiazepines in the late stages of pregnancy, it is possible to develop physical dependence,also such children may be at some risk of development of the syndrome of "cancellation" in the postnatal period. Therefore, clonazepam can be used during pregnancy only if the benefits for the mother clearly exceed the risk to the fetus.

Breast-feeding

Determined that clonazepam penetrates into the mother's milk in small amounts. therefore clonazepam can be used in breast-feeding mothers only if the benefit to the mother clearly exceeds the risk for the child.

Dosing and Administration:

Inside.

Recommended dose

Dividable tablets of 0.5 mg provide the possibility of introducing lower daily doses at the initial stages of treatment (if necessary).

The dose and duration of therapy is determined individually by the doctor.

Treatment should be started with low doses, increasing them gradually to obtain the optimal therapeutic effect.

Adults

The initial dose should not be more than 1 mg / day. The maintenance dose for adults is usually 4 to 8 mg.

Elderly patients

In view of the fact that elderly patients are particularly sensitive to the action of antidepressants,and also due to confusion in the use of the drug, the initial dose of clonazepam in this category is recommended as no more than 0.5 mg / day.

This is the total daily dose, which should be divided into 3 or 4 doses at intervals throughout the day. If necessary, higher doses may be administered as prescribed by the physician, up to a maximum of 20 mg per day. The maintenance dose should be administered 2-4 weeks after the start of treatment.

Children

To ensure optimal dosage in children, 0.5 mg tablets should be used.

Children from 3 to 5 years old

The initial dose should be no more than 0.25 mg / day.

The maintenance dose is 1-3 mg.

Children from 6 to 12 years old

The initial dose should not be more than 0.5 mg / day. The maintenance dose is usually in the range of 3-6 mg.

In some patients, some forms of epilepsy may cease to be adequately controlled by clonazepam. Control can again be established by increasing the dose or interrupting the treatment with clonazepam for 2 or 3 weeks. During a break in therapy, you may need to carefully monitor and use other medications.

Treatment should begin with low doses.The dose can be increased to achieve a maintenance dose, established as providing the optimal therapeutic effect in a particular patient.

The dose of clonazepam should be adjusted according to the needs of each patient and depends on the individual response to therapy. The maintenance dose should be determined in accordance with the clinical response and tolerance. The daily dose should be divided into 3 equal parts. If you divide the dose into three equal parts is impossible, the largest of them must be taken before bedtime. Once the maintenance dose level is reached, the daily dose can be taken in the evening once.

Simultaneous use of more than one antiepileptic drug is a common practice in the treatment of epilepsy and can be used with the use of clonazepam. The dose of each drug should be selected to achieve the optimal effect. It is necessary to analyze the dosing regimen and the rationality of the selected therapy in case of epileptic status in the patient receiving clonazepam orally.Before the addition of clonazepam to existing anticonvulsant therapy, it should be borne in mind that the use of several anticonvulsant drugs may lead to an increase in undesirable effects.

Side effects:

Clonazepam is well tolerated. Undesirable reactions, usually light and reversible.

Classification of WHO adverse adverse reactions according to the frequency of development:

Often - >1/10; often - from 1/100 to 1/10; infrequently - from 1/1000 to 1/100; rarely - from 1/10000 to 1/1000; rarely - <1/10000, including individual messages.

Disturbances from the blood system and lymphatic system: Rarely, as in the case of other benzodiazepines, single cases of blood dyscrasia have been reported.

Mental disorders: often - reduced concentration, anxiety, confusion and disorientation. Anterograde amnesia can occur with the use of benzodiazepines at a therapeutic dose, the risk increases with higher doses. The development of amnesia can be determined by the unusual behavior of the patient.

Infrequently, the use of benzodiazepines may lead to the development of physical and mental drug dependence.The risk of dependence increases with the increase in the dose of the drug and the duration of its use, as well as in patients with alcoholism and / or having a history of drug dependence.

Rarely - depression (can also be associated with the underlying disease).

Impaired nervous system: often - dizziness, ataxia, drowsiness and impaired coordination; rarely - (especially with prolonged use or with high-dose treatment) the development of reversible disorders, such as speech slowing or indistinctness (dysarthria), impaired coordination of movement and gait (ataxia). In predisposed patients, it is possible to develop convulsive seizures (see "Special instructions").

Disorders from the side of the organ of vision: often - nystagmus; rarely - diplopia.

Heart Disease: rarely - heart failure, including cardiac arrest.

Disturbances from the respiratory system, chest and mediastinal organs: rarely - respiratory depression (may occur with intravenous administration of clonazepam, this effect may be aggravated by previous obstruction of the respiratory tract or brain damage or when combined with other respiratory depression drugs).As a rule, this violation can be avoided by selecting the dose to obtain the optimal therapeutic effect.

Gastrointestinal disorders: rarely - symptoms of gastrointestinal disorders, including nausea.

Disorders from the liver and bile ducts: rarely - a change in the indices of functional hepatic tests.

Disturbances from the skin and subcutaneous tissues: rarely - hives, itching, temporary hair loss and changes in pigmentation. It was reported that allergic reactions, including very rare cases of anaphylaxis and angioedema, can occur with the use of benzodiazepines.

Disturbances from muscular, skeletal and connective tissue: often - muscle weakness and muscle hypotension.

Disorders from the kidneys and urinary tract: rarely - urinary incontinence.

Disorders from the reproductive system and mammary glands: rarely - decreased sexual desire (loss of libido) and impotence, reversible premature appearance of secondary sexual characteristics in children (incomplete premature puberty).

Overdose:

Symptoms: Symptoms of overdose or intoxication are very different in different people depending on age, body weight and individual reaction to the drug. Benzodiazepines usually cause drowsiness, ataxia, dysarthria and nystagmus. An overdose of clonazepam rarely presents a danger to life if the drug is taken as monotherapy, but can lead to coma, aflexia, apnea, hypotension and cardiorespiratory depression. The coma usually lasts only a few hours, but in older people it can be longer and more cyclical. Effects of respiratory depression in the use of benzodiazepines are more serious in patients with severe chronic obstructive airway disease.

Benzodiazepines potentiate the effects of other agents that depress the central nervous system, including alcohol.

Treatment: Maintain airway patency and adequate ventilation, if indicated.

- The benefit of washing the stomach is not established. It is appropriate to use activated carbon (50 g for an adult, 10-15 g for a child) in adults or children who took more than 0.4 mg / kg for 1 hour, in the absence of severe drowsiness.

- Gastric lavage is not necessary if only these drugs have been taken.

- In patients without symptoms within 4 hours, the manifestation of symptoms is further unlikely.

- Supportive measures are used, due to the clinical condition of the patient. In particular, patients may need symptomatic treatment of cardiorespiratory reactions or CNS reactions.

- Flumazenil, which is a benzodiazepine antagonist, is rarely used because it has a short half-life (about 1 hour). Flumazenil It is not used in case of overdose of several drugs simultaneously, and also as a "diagnostic test".

Interaction:

Since alcohol can provoke epileptic seizures, regardless of the therapy, patients should under no circumstances drink alcohol during treatment with clonazepam. In combination with clonazepam, alcohol can affect the effects of the drug, adversely affect the success of therapy or cause unpredictable side effects.

When using clonazepam in combination with other antiepileptic drugs, side effects such as sedation and apathy, toxicity may be more pronounced, especially when combined with hydantoins, phenobarbital and their combinations.This requires special care when adjusting the dose in the initial stages of treatment. The combination of clonazepam and valproate sodium was occasionally associated with the development of epileptic status of small seizures. Although some patients are tolerant and tolerant of this combination of drugs, this potential hazard should be considered when deciding whether to use it.

Antiepileptic drugs, such as phenytoin, phenobarbital, carbamazepine and valproate can induce clonazepam metabolism, providing higher clearance and lower plasma clonazepam concentrations in combination therapy.

Selective serotonin reuptake inhibitors, such as sertraline and fluoxetine, do not affect the pharmacokinetics of clonazepam when combined.

Known inhibitors of hepatic enzymes, for example, cimetidine, as shown, reduce the clearance of benzodiazepines and can enhance their action, and the known inducers of hepatic enzymes, for example, rifampicin, can increase the clearance of benzodiazepines.

With simultaneous treatment with phenytoin or primidone, from time to time there is a change, usually an increase in the concentration of these two substances in the serum.

Simultaneous use of clonazepam and other central-action drugs, for example, other anticonvulsant (antiepileptic) drugs, anesthetics, hypnotics, psychotropic drugs and some analgesics, and muscle relaxants can lead to mutual potentiation of drug effects. This is especially true in the presence of alcohol. When combined therapy with drugs of central action, the dose of each drug should be adjusted to achieve the optimal effect.

Special instructions:

- Suicidal thoughts and behavior were recorded in patients who received antiepileptic drugs for several indications. A meta-analysis of randomized placebo-controlled trials of antiepileptic drugs also showed a slight increase in risk occurrence of suicidal thoughts and behavior. The mechanism of development of this risk is unknown, however, the available data do not exclude the possibility of an increased risk in the application of clonazepam.

Therefore, patients should be monitored for suicidal thoughts and behavior, and appropriate treatment should be considered.Patients (and caregivers) should seek medical help if signs of suicidal thoughts or behavior appear.

- Patients with depression and / or attempted suicide in anamnesis should be closely monitored.

- In certain forms of epilepsy, it is possible to increase the frequency of attacks with prolonged treatment. Clonazepam usually has a beneficial effect on behavioral disorders in patients with epilepsy. In some cases, paradoxical effects may arise, such as aggressiveness, excitability, nervousness, hostility, anxiety, sleep disorders, nightmares, realistic dreams, irritability, agitation, psychotic disorders and the activation of new types of seizures. If this occurs, the benefit of continuing the use of this drug should be assessed in comparison with the undesirable effect. It may be necessary to add another suitable medication to the treatment regimen, or, in some cases, it may be advisable to discontinue clonazepam therapy.

- Clonazepam should be used with caution in patients with chronic pulmonary insufficiency or with impaired renal or hepatic function, as well as in elderly or debilitated patients.In these cases, the dose, as a rule, should be reduced.

- As with the use of other antiepileptic drugs, clonazepam therapy, even if it is short-term, should not be abruptly interrupted, but should be abolished by gradually reducing the dose, taking into account the risk of developing epileptic status. In these cases, a combination with other antiepileptic drugs is indicated. This precautionary measure also should be considered when canceling another drug, while the patient is still receiving clonazepam therapy.

- Prolonged use of benzodiazepines may lead to the development of dependence with the syndrome of "withdrawal" when discontinuing use.

- Clonazepam can be used only with extreme caution in patients with spinal or cerebellar ataxia, with acute intoxication with alcohol or drugs and in patients with severe liver damage (eg, cirrhosis of the liver).

- Clonazepam should be avoided with alcohol and / or drugs depressing the central nervous system. Such combined use may potentially enhance the clinical effects of clonazepam, including severe sedation, clinically significant respiratory and / or cardiovascular depression.

- Benzodiazepines should be used with extreme caution in patients with alcohol or drug dependence.

- Children and young children clonazepam can lead to increased production of saliva and bronchial secretion. Therefore, special attention should be paid to maintaining airway patency.

Exposure to the respiratory system may be aggravated by previous airway obstruction or brain damage or when combined with other drugs that depress respiration. Typically, this effect can be avoided by carefully adjusting the dose to meet individual needs.

The dosage of clonazepam should be carefully adjusted to the individual needs of patients with pre-existing respiratory system diseases (eg, chronic obstructive pulmonary disease) or liver and in patients receiving treatment with other central-action drugs or anticonvulsants (antiepileptic drugs).

- There are conflicting data on the effect or absence of clonazepam in patients with porphyria. Therefore, in this group of patients clonazepam should be used with caution.

"Like all preparations of a similar action, clonazepam, can influence the patient's reactions (for example, the ability to drive a vehicle, driving behavior) (see "Impact on the ability to drive vehicles and mechanisms").

- In patients with uncomplicated loss reactions, the use of benzodiazepines may slow psychological adaptation.

- Dependence and withdrawal syndrome. The use of benzodiazepines may lead to the development of physical and mental drug dependence. In particular, prolonged or high-dose therapy can lead to reversible disorders such as dysarthria, decreased coordination of movements and gait disturbances (ataxia), nystagmus and dyspnea.

Moreover, the risk of anterograde amnesia, which can occur with the use of benzodiazepines at therapeutic doses, increases with higher doses. Amnestic effects can be associated with improper behavior. In certain forms of epilepsy, an increase in the frequency of attacks with prolonged treatment is possible.The risk of dependence increases with increasing dose and duration of treatment; it is also higher in patients with alcohol and / or drug addiction in the anamnesis.

As soon as physical dependence develops, the sudden cessation of treatment is accompanied by the emergence of the "withdrawal" syndrome. With prolonged treatment, the "cancellation" syndrome can develop after a long period of use, especially at high doses, or if the daily dose decreases rapidly or the drug suddenly stops. Symptoms include tremors, sweating, agitation, sleep disorders and anxiety, headaches, muscle pain, extreme anxiety, tension, confusion, irritability and epileptic seizures that may be associated with the underlying disease. In severe cases, the following symptoms can occur: derealization, depersonalization, hyperacusia, numbness and tingling of the limbs, hypersensitivity to light, noise and physical contacts or hallucinations. Since the risk of developing the "withdrawal" syndrome is higher when the treatment is discontinued sharply, the drug should be abruptly discontinued and treatment, even if it bears a short-term character, should be discontinued, gradually reducing the daily dose. The risk of developing the "withdrawal" syndrome is increased if benzodiazepines are used in conjunction with daytime sedatives (cross tolerance).

- In patients receiving benzodiazepines, there is an increased risk of falls and fractures. Risk increases in those who receive both sedatives (including alcoholic beverages) and in the elderly.

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

Patients with epilepsy are not allowed to drive a car. Even with adequate control of epilepsy with clonazepam, it should be remembered that any increase in dosage or a change in the dose of the drug may alter the reactions of patients depending on individual susceptibility. Even if you take clonazepam on purpose, it can slow down the reaction so that the ability to drive a vehicle or control machinery is impaired. This effect is enhanced by drinking alcohol. Therefore, driving, steering mechanisms and other hazardous activities should be avoided.

Form release / dosage:Tablets 0.5 mg and 2.0 mg.

Packaging:

10 tablets per contour cell packaging made of polyvinylchloride film and foil of aluminum printed lacquered or flexible packaging on the basis of aluminum foil.

By 3 contour mesh packages together with instructions for use in a pack of cardboard.

Storage conditions:

In accordance with the rules for the storage of psychotropic substances on the list III "List of narcotic drugs, psychotropic substances and their precursors subject to control in the Russian Federation".

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

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date, indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-004450

Date of registration:11.09.2017

Expiration Date:11.09.2022

The owner of the registration certificate:MOSCOW ENDOCRINE FACTORY, FSUE MOSCOW ENDOCRINE FACTORY, FSUE Russia

Manufacturer: & nbsp

MOSCOW ENDOCRINE FACTORY, FSUE Russia

Information update date: & nbsp28.09.2017

Illustrated instructions

Instructions

Clonazepam (Clonazepam)