Phezanef (Tablets) Instructions for Use

Marketing Authorization Holder

Akrikhin Chemical and Pharmaceutical Plant, JSC (Russia)

ATC Code

N05BX (Other anxiolytics)

Active Substance

Bromdihydrochlorphenylbenzodiazepine (Grouping name)

Dosage Form

Phezanef

Tablets 1 mg: 50 pcs.

Dosage Form, Packaging, and Composition

Tablets are white in color, flat-cylindrical in shape, with a bevel.

Excipients: milk sugar (lactose), potato starch, gelatin, calcium stearate, stearic acid.

10 pcs. – contour cell packs (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 brainstem and interneurons of the lateral horns of the spinal cord; reduces the excitability of subcortical brain structures (limbic system, thalamus, hypothalamus), inhibits polysynaptic spinal reflexes.

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

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

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

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

The anticonvulsant action 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 the 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, the time to reach C_max is 1-2 hours.

It is metabolized in the liver. T_1/2 is 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 anxiolytics (tranquilizers); autonomic dysfunctions and sleep disorders; prevention of states of fear and emotional tension; as an anticonvulsant agent: temporal and myoclonic epilepsy; in neurological practice: hyperkinesis, tics, muscle rigidity, autonomic lability.

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 states the initial dose is 0.5-1 mg (0.5-1 ml of 0.1% solution), the average daily dose is 3-5 mg, in severe cases – up to 7-9 mg.

Orally: for sleep disorders – 0.25-0.5 mg 20-30 minutes before sleep.

For the treatment of neurotic, psychopathic, neurosis-like and psychopath-like states 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 may be increased to 4-6 mg/day.

In cases of marked 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, 0.5 mg 1-2 times a 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 daytime and up to 2.5 mg at night. In neurological practice for diseases with muscular hypertonus, 2-3 mg 1 or 2 times a day is prescribed.

The maximum daily dose is 10 mg. To avoid the development of drug dependence during course treatment, the duration of use of bromdihydrochlorphenylbenzodiazepine, as well as other benzodiazepines, is 2 weeks (in some cases, the duration of treatment may be increased to 2 months). When discontinuing the drug, 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, slowed 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 eye movements), asthenia, muscle weakness, 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 system: leukopenia, neutropenia, agranulocytosis (chills, hyperthermia, sore throat, excessive fatigue or weakness), anemia, thrombocytopenia.

From the digestive system: dryness of the oral mucosa or salivation, heartburn, nausea, vomiting, decreased appetite, constipation or diarrhea; impaired liver function, increased activity of “liver” 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, skin itching.

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

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 abrupt dose reduction or discontinuation of administration – 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

Hypersensitivity (including to other benzodiazepines); coma, shock; myasthenia gravis; closed-angle glaucoma (acute attack or predisposition); acute alcohol poisoning (with weakening of vital functions), narcotic analgesics and hypnotic drugs; severe COPD (possible increase in respiratory failure); acute respiratory failure; severe depression (suicidal tendencies may manifest); pregnancy (especially the first trimester); lactation period; age under 18 years (safety and efficacy not established).

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

Use in Pregnancy and Lactation

Contraindicated during pregnancy (first trimester) and during lactation.

During pregnancy, use only for vital indications. It has a toxic effect on the fetus and increases the risk of congenital malformations when used in the first trimester of pregnancy. Administration of therapeutic doses in later stages of pregnancy may cause CNS depression in the newborn. Continuous use during pregnancy may lead to physical dependence with the development of withdrawal syndrome in the newborn.

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

Use in Hepatic Impairment

With caution: hepatic insufficiency.

Use in Renal Impairment

With caution: renal insufficiency.

Pediatric Use

Contraindicated: children under 18 years of age. Children, especially young children, are very sensitive to the CNS depressant effect of benzodiazepines.

Geriatric Use

With caution: elderly age.

Special Precautions

During treatment, patients are strictly prohibited from consuming ethanol.

The efficacy and safety of the drug in patients under 18 years of age have not been established.

In renal/hepatic insufficiency and during long-term treatment, monitoring of peripheral blood picture and liver enzyme activity is necessary.

Patients who have not previously taken psychoactive drugs respond to the drug at lower doses compared to patients who have taken antidepressants, anxiolytics, or patients with alcoholism.

Like other benzodiazepines, it has the ability to cause drug dependence when taken long-term in high doses (more than 4 mg/day).

Upon sudden discontinuation of administration, a withdrawal syndrome (depression, irritability, insomnia, increased sweating) may be noted, especially after long-term use (more than 8-12 weeks).

If patients develop such unusual reactions as increased aggressiveness, acute states of agitation, feelings of fear, suicidal thoughts, hallucinations, increased muscle cramps, difficulty falling asleep, shallow sleep, treatment should be discontinued.

Children, especially young children, are very sensitive to the CNS depressant effect of benzodiazepines.

Effect on the ability to drive vehicles and operate machinery

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

Reduces the effectiveness of levodopa in patients with parkinsonism.

May increase the toxicity of zidovudine.

Mutual enhancement of the effect is noted with simultaneous administration of antipsychotic (neuroleptic), anticonvulsant or hypnotic drugs, 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.

Hypotensive drugs may enhance the severity of BP reduction.

Against the background of simultaneous administration of clozapine, respiratory depression may be enhanced.

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.