Phenazepam® ic

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT PHENAZEPAM® IS (PHENAZEPAM IS)

Composition:

Active substance: phenazepam;

One tablet contains 0.5 mg (0.0005 g), 1 mg (0.001 g), or 2.5 mg (0.0025 g) of phenazepam;

Excipients: lactose monohydrate, potato starch, calcium stearate, gelatin.

Pharmaceutical form. Tablets.

Main physicochemical properties: white-colored, flat cylindrical tablets with beveled edges; the company trademark is imprinted on one surface of the tablet.

Pharmacotherapeutic group.
Anxiolytics. Benzodiazepine derivatives. ATC code N05BA.

Pharmacological properties.

Pharmacodynamics.

Phenazepam® IS is a tranquilizer belonging to the benzodiazepine derivatives group. It exerts anxiolytic, anticonvulsant, muscle relaxant, and sedative effects.

Phenazepam is an exogenous ligand of specific benzodiazepine receptors in the central nervous system (CNS). Its mechanism of action is associated with reducing excitability of subcortical brain centers and inhibition of their interaction with the cerebral cortex.

Pharmacokinetics.

After oral administration, phenazepam is well absorbed from the gastrointestinal tract. Time to reach maximum plasma concentration of phenazepam – from 1 to 2 hours. Elimination half-life – from 6 to 18 hours. Metabolized in the liver. Excretion of phenazepam occurs mainly via the kidneys.

Clinical characteristics.

Indications.

Neurotic, neurosis-like, psychopathic, and psychopathy-like states; hypochondriacal-asthenic syndrome; autonomic dysfunctions accompanied by increased irritability, anxiety, fear, psychomotor agitation, emotional lability, sleep disturbances, and other manifestations.

As an anxiolytic agent in the complex therapy of withdrawal syndrome, tics, and hyperkineses.

Contraindications.

Hypersensitivity to benzodiazepines or to any component of the medicinal product; severe respiratory disorders (respiratory insufficiency, acute pulmonary failure, severe chronic obstructive pulmonary disease, bronchial asthma); nocturnal apnea syndrome; myasthenia gravis; acute angle-closure glaucoma or predisposition to its development; severe hepatic and/or renal function impairment; asthenia; cachexia; severe depression; shock state; acute poisoning with alcohol, other tranquilizers, neuroleptics, hypnotics, or narcotics. Pregnancy or breastfeeding period. Pediatric age (under 18 years). Alcohol consumption during treatment.

Interaction with other medicinal products and other forms of interactions.

Mutual enhancement of effects may occur when phenazepam is used concomitantly with other central nervous system depressants, such as neuroleptics (including phenothiazine derivatives), antiepileptic agents, hypnotics (including barbiturates), central muscle relaxants, narcotic analgesics, and alcohol. Concomitant use of phenazepam and clozapine may enhance respiratory depression. Inhibitors of hepatic microsomal enzymes (e.g., cimetidine) increase the risk of phenazepam-induced toxic effects. Inducers of hepatic microsomal enzymes (e.g., rifampicin) reduce phenazepam's efficacy. Phenazepam decreases the effectiveness of levodopa in patients with Parkinsonism. Concurrent administration of phenazepam with zidovudine increases zidovudine toxicity. Phenazepam should not be used concomitantly with monoamine oxidase inhibitors (MAOIs). Phenazepam increases plasma concentration of imipramine and enhances its sedative effect. Concomitant use of phenazepam with antihypertensive agents may enhance antihypertensive action.

Special precautions for use.

The duration of treatment with phenazepam should be as short as possible, depending on the indication.

Concomitant use of phenazepam with central nervous system depressants may enhance the clinical effects of phenazepam, including profound sedative effect, clinically significant respiratory and/or cardiovascular depression. Therefore, concomitant use of phenazepam with central nervous system depressants, including alcohol, is contraindicated (see sections "Contraindications", "Interaction with other medicinal products and other forms of interaction").

Tolerance

Patients who have not previously taken psychotropic medicinal products may require lower doses of phenazepam than patients previously treated with antidepressants, anxiolytics, or patients with alcohol dependence.

Prolonged use of phenazepam leads to diminished therapeutic effect, which may lead to patients self-increasing the dose of phenazepam in order to achieve the desired therapeutic effect.

Dependence

Use of phenazepam for several weeks at doses exceeding 4 mg/day may lead to the development of psychological and physical dependence. Patients with alcohol dependence or dependence on other medicinal products have an increased risk of developing dependence on phenazepam.

Sudden discontinuation of phenazepam may cause withdrawal syndrome (including irritability, anxiety, sleep disturbances, increased sweating, depression), especially after long-term use (more than 8–12 weeks). In some patients, withdrawal symptoms may occur even after short-term treatment with phenazepam, particularly when high doses are used. To avoid the development of withdrawal symptoms, discontinuation of phenazepam therapy should be carried out by gradual dose reduction.

Paradoxical reactions

Phenazepam, like all benzodiazepines, may cause paradoxical reactions such as anxiety, fear, anger, aggressive outbursts, irritability, hallucinations, nightmares, insomnia, light sleep, increased muscle spasms, suicidal thoughts, inappropriate behavior, and other behavioral disorders. Such reactions are most commonly observed in elderly patients and patients with psychiatric disorders, as well as when phenazepam is used concomitantly with other medicinal products or alcohol. If paradoxical reactions occur, phenazepam treatment should be discontinued.

Special patient groups

Phenazepam should be used with caution in patients with cerebral or spinal ataxia, history of alcohol, drug, or substance dependence, tendency to abuse psychoactive medicinal products, and in patients with hypoproteinemia.

Patients with psychiatric disorders or organic brain lesions may experience paradoxical reactions when treated with phenazepam. Monotherapy with phenazepam increases the risk of suicidal thoughts in these patients.

In patients with bronchial asthma and elderly patients, use of phenazepam may worsen airway patency.

In patients with hepatic and/or renal insufficiency, phenazepam may accumulate in the body, enhancing the effects of other medicinal products and increasing the severity of adverse reactions.

Elderly patients, debilitated patients, and patients with hepatic and/or renal insufficiency (see section "Contraindications") require dose reduction due to increased risk of adverse reactions. Impaired balance, coordination of movements, and muscle weakness may lead to falls and injuries.

During prolonged therapy with phenazepam, peripheral blood count and hepatic enzyme activity should be monitored.

The medicinal product contains lactose and therefore should not be administered to patients with rare hereditary forms of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome.

Use during pregnancy or breastfeeding.

Do not use the medicinal product during pregnancy or breastfeeding.

Data on the safety of benzodiazepine use in pregnant women are limited. Phenazepam has a toxic effect on the fetus. Use of phenazepam during the first trimester of pregnancy increases the risk of congenital malformations. Use of benzodiazepines during the last trimester of pregnancy or during labor at high doses may cause hypothermia, hypotonia ("floppy infant syndrome"), cardiac arrhythmias, moderate respiratory depression, and weak sucking reflex in the newborn. In infants whose mothers have taken benzodiazepines long-term during late pregnancy, physical dependence may develop after birth, and there may be a risk of withdrawal syndrome.

Benzodiazepines pass into breast milk; therefore, the medicinal product should not be used in breastfeeding women.

Women of reproductive age who are taking phenazepam and who are planning to become pregnant or suspect they are pregnant should consult their physician regarding the need to discontinue treatment.

Ability to affect reaction speed when driving or operating machinery.

During treatment with phenazepam, patients should refrain from driving or operating machinery.

Dosage and Administration

Phenazepam® IS tablets should be administered orally, without chewing. The dosage regimen should be individually determined based on the indication, course of the disease, and the patient's sensitivity to the drug.

To achieve the required dose, tablets with the appropriate content of active substance should be used.

The lowest effective doses should be used. If necessary, the dose should be gradually increased.

For the treatment of neurotic, neurosis-like, psychopathic, and psychopathy-like conditions, hypochondriacal-sensitization syndrome, and autonomic dysfunctions accompanied by increased irritability, anxiety, fear, psychomotor agitation, and emotional lability, the usual dose of the drug is typically 0.5–1 mg 2–3 times daily. After 2–4 days, depending on efficacy and tolerability, the dose may be increased, if necessary, to 4–6 mg daily. The morning and daytime doses are 0.5–1 mg, and the remaining portion of the total daily dose should be taken at bedtime. In cases of pronounced agitation, fear, or anxiety, treatment should be initiated at a dose of 3 mg daily, rapidly increasing to 4–6 mg daily until the desired therapeutic effect is achieved.

For sleep disorders, the dose is 0.5 mg taken 20–30 minutes before bedtime.

In combination therapy for tics and hyperkinesias, the dose is 0.5–3 mg once or twice daily; for alcohol withdrawal syndrome – 2.5–5 mg daily.

The maximum daily dose of the drug is 10 mg and may be used exclusively under inpatient conditions and under medical supervision.

The duration of treatment—up to 2 months—is individually determined by the physician depending on the patient's condition and disease course. Prolonged use of the drug is not recommended. Discontinuation of the drug should be carried out by gradual dose reduction. Patients who have used phenazepam for a prolonged period may require a longer tapering period.

Children.

Due to insufficient data on the efficacy and safety of phenazepam in children (under 18 years of age), the drug is not administered to patients in this age group.

Overdose.

Symptoms: coma, profound depression of consciousness, cardiac and respiratory functions, reduced reflexes, prolonged confusion, bradycardia, arterial hypotension, dizziness, dyspnea or labored breathing, pronounced drowsiness, nystagmus, visual and speech disturbances, marked impairment of balance and motor coordination, tremor, and possible allergic reactions.

Treatment.

Gastric lavage and administration of activated charcoal (within 1 hour after overdose ingestion) are recommended. Hemodialysis is poorly effective. Monitoring of vital functions is essential. Symptomatic therapy aimed at supporting cardiovascular, respiratory, and central nervous system functions: maintenance of adequate hemodynamics and airway patency (if necessary, mechanical ventilation). In case of respiratory depression, administration of flumazenil—an antagonist of benzodiazepines—should be performed under inpatient conditions (intravenously, 0.2 mg, repeated if necessary up to 1 mg, in 5% glucose solution or 0.9% sodium chloride solution). Flumazenil has a short elimination half-life (approximately 1 hour). Close monitoring of the patient is required during and after flumazenil administration.

Adverse Reactions

Adverse reactions associated with the use of phenazepam depend on individual patient sensitivity, duration of treatment, dosage, and the rate of dose escalation. When the dose is gradually increased by no more than 1.5–2.5 mg/day, adverse reactions are generally not observed. However, with rapid dose escalation of more than 5–7 mg/day, the frequency of adverse reactions increases. The severity of adverse reactions can be reduced or eliminated by lowering the dose of phenazepam.

Adverse reactions are classified by organ systems and frequency of occurrence: very common (≥ 1/10), common (≥ 1/100 – < 1/10), uncommon (≥ 1/1000 – < 1/100), rare (≥ 1/10,000 – < 1/1000), very rare (< 1/10,000).

Psychiatric disorders: At the beginning of treatment (especially in elderly patients) – reduced ability to concentrate attention, disorientation in time and space, confusion; uncommon – memory impairment; rare – euphoria, depression, emotional blunting, low mood; very rare – paradoxical reactions such as feelings of restlessness, fear, anxiety, anger, emotional excitement, psychomotor agitation, aggression, irritability, delirium, hallucinations, psychosis, memory loss, insomnia, nightmares, behavioral disturbances, muscle spasms, suicidal thoughts.

Nervous system disorders: At the beginning of treatment (especially in elderly patients) – drowsiness, increased fatigue, dizziness, ataxia, unsteady gait, slowed mental and motor reactions; common – mild headache, muscle weakness, impaired balance and gait (especially in elderly patients); uncommon – speech disorders; rare – headache, tremor, impaired coordination (especially with high-dose use), dystonic extrapyramidal reactions (involuntary movements, including of the eyes), asthenia, dysarthria, epileptic seizures (in patients with epilepsy).

Eye disorders: Rare – visual disturbances (mydriasis, diplopia, blurred vision).

Cardiac and vascular disorders: Rare – slight arterial hypotension, tachycardia.

Blood and lymphatic system disorders: Rare – leukopenia, neutropenia, agranulocytosis (chills, hyperthermia, sore throat, increased fatigue or weakness), anemia, thrombocytopenia.

Gastrointestinal disorders: Decreased appetite, dry mouth or hypersalivation, heartburn, nausea, vomiting, constipation, diarrhea.

Hepatobiliary disorders: Rare – liver function abnormalities, increased activity of liver transaminases and alkaline phosphatase, jaundice.

Renal and urinary disorders: Renal function impairment; common – urinary dysfunction (urinary incontinence, urinary retention).

Reproductive system disorders: Dysmenorrhea; uncommon – menstrual cycle disturbances, decreased or increased libido.

Immune system disorders: Allergic reactions, including skin rash, itching, skin hyperemia, angioneurotic edema.

Other: Rare – weight loss.

When phenazepam is used in elderly patients, there is an increased risk of falls and fractures.

During phenazepam treatment, pre-depressive states may develop but remain undiagnosed.

Phenazepam use may lead to the development of tolerance and psychological and physical dependence (see section "Special precautions"). Patients with alcohol dependence or dependence on other medicinal products have an increased risk of developing dependence on phenazepam. Sudden discontinuation of phenazepam may cause withdrawal syndrome. Symptoms of withdrawal syndrome include: headache, muscle pain, nausea, vomiting, excessive sweating, restlessness, irritability, nervousness, increased anxiety, emotional tension, dysphoria, depression, sleep disturbances, spasms of smooth muscles of internal organs and skeletal muscles, tremor, tachycardia, seizures, confusion, depersonalization, perceptual disturbances including hyperacusis, photophobia, paresthesia; rare – acute psychosis.

Shelf life. 4 years.

Storage conditions.

Store in original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

10 tablets per blister; 5 blisters (for 0.5 mg dosage), 2 or 5 blisters (for 1 mg dosage), 2 blisters (for 2.5 mg dosage) per cardboard box.

Prescription status. Prescription only.

Manufacturer.

Limited liability company "INTERSIM".

Manufacturer's address and place of business.

Ukraine, 65025, Odessa, 21st km of Starokyivska Road, 40-A.