Benzozepam^® (Tablets) Instructions for Use

Marketing Authorization Holder

Usolye-Sibirskiy Chemical and Pharmaceutical Plant, JSC (Russia)

ATC Code

N05BX (Other anxiolytics)

Active Substance

Bromdihydrochlorphenylbenzodiazepine (Grouping name)

Dosage Forms

	Benzozepam®	Tablets 0.5 mg: 10, 20, 30, 40 or 50 pcs.
		Tablets 1 mg: 10, 20, 30, 40 or 50 pcs.
		Tablets 2.5 mg: 10, 20, 30, 40 or 50 pcs.

Dosage Form, Packaging, and Composition

Tablets white, round, flat-cylindrical, with a bevel.

Excipients: lactose monohydrate – 81.5 mg, microcrystalline cellulose (MCC-101) – 15 mg, croscarmellose sodium – 2 mg, calcium stearate – 1 mg.

10 pcs. – contour cell packaging (1) – cardboard packs.
10 pcs. – contour cell packaging (2) – cardboard packs.
10 pcs. – contour cell packaging (3) – cardboard packs.
10 pcs. – contour cell packaging (4) – cardboard packs.
10 pcs. – contour cell packaging (5) – cardboard packs.

Tablets white, round, flat-cylindrical, with a bevel and a score on one side.

Excipients: lactose monohydrate – 122 mg, microcrystalline cellulose (MCC-101) – 22.5 mg, croscarmellose sodium – 3 mg, calcium stearate – 1.5 mg.

10 pcs. – contour cell packaging (1) – cardboard packs.
10 pcs. – contour cell packaging (2) – cardboard packs.
10 pcs. – contour cell packaging (3) – cardboard packs.
10 pcs. – contour cell packaging (4) – cardboard packs.
10 pcs. – contour cell packaging (5) – cardboard packs.

Tablets white, round, flat-cylindrical, with a bevel.

Excipients: lactose monohydrate – 161.5 mg, microcrystalline cellulose (MCC-101) – 30 mg, croscarmellose sodium – 4 mg, calcium stearate – 2 mg.

10 pcs. – contour cell packaging (1) – cardboard packs.
10 pcs. – contour cell packaging (2) – cardboard packs.
10 pcs. – contour cell packaging (3) – cardboard packs.
10 pcs. – contour cell packaging (4) – cardboard packs.
10 pcs. – contour cell packaging (5) – cardboard packs.

Clinical-Pharmacological Group

Anxiolytic (tranquilizer)

Pharmacotherapeutic Group

Anxiolytic agent (tranquilizer)

Pharmacological Action

Anxiolytic agent (tranquilizer) of the benzodiazepine series. It has anxiolytic, sedative-hypnotic, anticonvulsant and central muscle relaxant effects.

It enhances the inhibitory effect of GABA on the transmission of nerve impulses. It stimulates benzodiazepine receptors located in the allosteric center of postsynaptic GABA receptors of the ascending activating reticular formation of the brain stem and interneurons of the lateral horns of the spinal cord; reduces the excitability of subcortical structures of the brain (limbic system, thalamus, hypothalamus), inhibits polysynaptic spinal reflexes.

The anxiolytic effect is due to the effect on the amygdala complex of the limbic system and is manifested in a decrease in emotional stress, weakening of anxiety, fear, and restlessness.

The sedative effect is due to the effect on the reticular formation of the brain stem and nonspecific nuclei of the thalamus and is manifested by a reduction in symptoms of neurotic origin (anxiety, fear).

It has practically no effect on productive symptoms of psychotic origin (acute delusional, hallucinatory, affective disorders); a decrease in affective tension and delusional disorders is rarely observed.

The hypnotic effect is associated with inhibition of cells of the reticular formation of the brain stem. It reduces the impact of emotional, vegetative and motor stimuli that disrupt the mechanism of falling asleep.

The anticonvulsant effect is realized by enhancing presynaptic inhibition, suppresses the spread of the convulsive impulse, but does not relieve the excited state of the focus. The central muscle relaxant effect is due to inhibition of polysynaptic spinal afferent inhibitory pathways (and to a lesser extent, monosynaptic ones). Direct inhibition of motor nerves and muscle function is also possible.

Pharmacokinetics

After oral administration, it is well absorbed from the gastrointestinal tract, T_max – 1-2 hours. Metabolized in the liver. T_1/2 – 6-10-18 hours. It is excreted mainly by the kidneys in the form of metabolites.

Indications

Neurotic, neurosis-like, psychopathic and psychopath-like and other conditions (irritability, anxiety, nervous tension, emotional lability), reactive psychoses and senesthopathic-hypochondriacal disorders (including those resistant to the action of other anxiolytic agents (tranquilizers), obsessiveness, insomnia, withdrawal syndrome (alcoholism, substance abuse), status epilepticus, epileptic seizures (of various etiologies), temporal and myoclonic epilepsy.

In extreme conditions – as a means to facilitate overcoming feelings of fear and emotional tension.

As an antipsychotic agent – schizophrenia with increased sensitivity to antipsychotic drugs (including febrile form).

In neurological practice – muscle rigidity, athetosis, hyperkinesis, tic, autonomic lability (paroxysms of sympathoadrenal and mixed nature).

In anesthesiology – premedication (as a component of induction anesthesia).

ICD codes

Dosage Regimen

IM or IV (bolus or drip): for rapid relief of fear, anxiety, psychomotor agitation, as well as in vegetative paroxysms and psychotic conditions, initial dose – 0.5-1 mg, average daily dose – 3-5 mg, in severe cases – up to 7-9 mg.

Orally: for sleep disorders – 250-500 mcg 20-30 minutes before sleep. For the treatment of neurotic, psychopathic, neurosis-like and psychopath-like conditions, the initial dose is 0.5-1 mg 2-3 times a day. After 2-4 days, taking into account efficacy and tolerability, the dose can be increased to 4-6 mg/day. In cases of pronounced agitation, fear, anxiety, treatment is started with a dose of 3 mg/day, rapidly increasing the dose until a therapeutic effect is obtained. For the treatment of epilepsy – 2-10 mg/day.

For the treatment of alcohol withdrawal – orally, 2-5 mg/day or IM, 500 mcg 1-2 times/day, for vegetative paroxysms – IM, 0.5-1 mg. The average daily dose is 1.5-5 mg, it is divided into 2-3 doses, usually 0.5-1 mg in the morning and afternoon and up to 2.5 mg at night. In neurological practice for diseases with muscle hypertonus, 2-3 mg 1-2 times/day is prescribed. The maximum daily dose is 10 mg.

To avoid the development of drug dependence during course treatment, the duration of use is 2 weeks (in some cases, the duration of treatment can be extended to 2 months). When discontinuing this medicinal product, the dose should be reduced gradually.

Adverse Reactions

From the nervous system at the beginning of treatment (especially in elderly patients) – drowsiness, feeling of fatigue, dizziness, decreased ability to concentrate, ataxia, disorientation, unsteady gait, slowing of mental and motor reactions, confusion; rarely – headache, euphoria, depression, tremor, memory impairment, impaired coordination of movements (especially at high doses), depressed mood, dystonic extrapyramidal reactions (uncontrolled movements, including eyes), asthenia, myasthenia, dysarthria, epileptic seizures (in patients with epilepsy); extremely rarely – paradoxical reactions (aggressive outbursts, psychomotor agitation, fear, suicidal tendency, muscle spasm, hallucinations, agitation, irritability, anxiety, insomnia).

From the hematopoietic organs leukopenia, neutropenia, agranulocytosis (chills, hyperthermia, sore throat, excessive fatigue or weakness), anemia, thrombocytopenia.

From the digestive system dry mouth or salivation, heartburn, nausea, vomiting, decreased appetite, constipation or diarrhea; impaired liver function, increased activity of hepatic transaminases and alkaline phosphatase, jaundice.

From the genitourinary system: urinary incontinence, urinary retention, impaired renal function, decreased or increased libido, dysmenorrhea.

Allergic reactions skin rash, itching.

Local reactions phlebitis or venous thrombosis (redness, swelling or pain at the injection site).

Other habituation, drug dependence; decreased BP; rarely – visual impairment (diplopia), weight loss, tachycardia.

With a sharp dose reduction or discontinuation of use – withdrawal syndrome (irritability, nervousness, sleep disorders, dysphoria, spasm of smooth muscles of internal organs and skeletal muscles, depersonalization, increased sweating, depression, nausea, vomiting, tremor, perception disorders, including hyperacusis, paresthesia, photophobia; tachycardia, convulsions, rarely – acute psychosis).

Contraindications

Coma, shock, myasthenia, closed-angle glaucoma (acute attack or predisposition), acute alcohol poisoning (with weakening of vital functions), narcotic analgesics and hypnotics, severe COPD (possible increase in respiratory failure), acute respiratory failure, severe depression (suicidal tendencies may appear); first trimester of pregnancy, lactation period, children and adolescents under 18 years of age (safety and efficacy not established), hypersensitivity (including to other benzodiazepines).

Use in Pregnancy and Lactation

During pregnancy, use is possible only for vital indications. It has a toxic effect on the fetus and increases the risk of developing congenital malformations when used in the first trimester of pregnancy. Use in therapeutic doses at later stages of pregnancy may cause CNS depression in the newborn. Continuous use during pregnancy can lead to physical dependence with the development of withdrawal syndrome in the newborn. Children, especially young children, are very sensitive to the CNS depressant effect of benzodiazepines.

Use immediately before or during childbirth may cause respiratory depression, decreased muscle tone, hypotension, hypothermia and weak sucking reflex in the newborn (“floppy infant” syndrome).

Use in Hepatic Impairment

Use with caution in hepatic insufficiency.

Use in Renal Impairment

Use with caution in renal insufficiency.

Pediatric Use

Contraindicated in children and adolescents under 18 years of age (safety and efficacy not established).

Special Precautions

Use with caution in hepatic and/or renal insufficiency, cerebral and spinal ataxia, history of drug dependence, tendency to abuse psychoactive drugs, hyperkinesis, organic brain diseases, psychosis (paradoxical reactions are possible), hypoproteinemia, sleep apnea (established or suspected), in elderly patients.

In renal and/or hepatic insufficiency and during long-term treatment, it is necessary to monitor the peripheral blood picture and the activity of liver enzymes.

In patients who have not previously taken psychoactive drugs, a therapeutic response to the use of bromdihydrochlorphenylbenzodiazepine is observed at lower doses compared to patients taking antidepressants, anxiolytics or suffering from alcoholism.

Like other benzodiazepines, it has the ability to cause drug dependence with long-term use in high doses (more than 4 mg/day). With sudden discontinuation of use, withdrawal syndrome may occur (including depression, irritability, insomnia, increased sweating), especially with long-term use (more than 8-12 weeks). If patients develop such unusual reactions as increased aggressiveness, acute states of agitation, feelings of fear, thoughts of suicide, hallucinations, increased muscle cramps, difficulty falling asleep, shallow sleep, treatment should be discontinued.

During treatment, patients are strictly prohibited from consuming ethanol.

In case of overdose, pronounced drowsiness, prolonged confusion, decreased reflexes, prolonged dysarthria, nystagmus, tremor, bradycardia, shortness of breath or difficulty breathing, decreased BP, coma are possible. Gastric lavage, intake of activated charcoal are recommended; symptomatic therapy (maintenance of respiration and BP), administration of flumazenil (in a hospital setting); hemodialysis is not very effective.

Effect on the ability to drive vehicles and mechanisms

During the treatment period, caution must be exercised when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

With simultaneous use, Bromdihydrochlorphenylbenzodiazepine reduces the effectiveness of levodopa in patients with parkinsonism.

Bromdihydrochlorphenylbenzodiazepine may increase the toxicity of zidovudine.

Mutual enhancement of the effect is noted with simultaneous use of antipsychotic, antiepileptic or hypnotic agents, as well as central muscle relaxants, narcotic analgesics, ethanol.

Inhibitors of microsomal oxidation increase the risk of toxic effects. Inducers of liver microsomal enzymes reduce effectiveness.

Increases the concentration of imipramine in blood serum.

With simultaneous use with antihypertensive agents, an enhancement of the antihypertensive effect is possible. Against the background of simultaneous administration of clozapine, an increase in respiratory depression is possible.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.