Befin

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT BEFIN (BEFIN)

Composition:

active substance: phenibut;

1 hard capsule contains phenibut 250 mg;

excipients: lactose monohydrate; potato starch; calcium stearate;

capsule shell composition: gelatin, titanium dioxide (E 171).

Dosage form. Hard capsules.

Basic physico-chemical properties: white to off-white hard gelatin capsules.

The contents of the capsules – powder from white to white with a yellowish tinge.

Pharmacotherapeutic group. Other psychostimulants and nootropic agents.

ATC code N06B X22.

Pharmacological Properties

Pharmacodynamics

Phenibut favorably affects metabolic processes in nerve cells of the brain. Phenibut is a derivative of γ-aminobutyric acid (GABA) and beta-phenylethylamine. Phenibut exhibits both nootropic and anxiolytic (tranquilizing) activity typical of GABA derivatives. Phenibut does not affect cholinergic or adrenergic receptors. It reduces anxiety, apprehension, fear, and improves sleep; therefore, the drug can be used for the treatment of neuroses and also preoperatively. Phenibut prolongs and enhances the effects of hypnotics, narcotics, neuroleptics, and antiparkinsonian agents. It does not exert anticonvulsant effects. Phenibut prolongs the latent period of nystagmus and reduces its duration and manifestations. Phenibut significantly reduces asthenic symptoms and vasovegetative symptoms, including headache, sensation of heaviness in the head, sleep disturbances, irritability, emotional lability, and increases mental performance. Phenibut improves psychological parameters—attention, memory, speed, and accuracy of sensorimotor responses.

In asthenic and emotionally labile patients, improvement in well-being, increased interest and initiative, and motivation for active engagement are observed from the first days of treatment with the drug, without sedative or stimulating effects. Phenibut is more active than piracetam regarding antiasthenic activity (fatigue, fatigability, hypodynamia, mental and physical asthenia).

Pharmacokinetics

Absorption and Distribution

The drug is well absorbed after oral administration and penetrates well into all body tissues, crossing the blood-brain barrier effectively (approximately 0.1% of the administered dose penetrates into brain tissue, and this is significantly greater in both young and elderly individuals). The highest binding of phenibut occurs in the liver (80%), and it is not specific. In healthy volunteers, maximum plasma concentration (Cmax) of the active substance after a single oral dose of 250 mg taken with food is reached approximately within 3 hours. Cmax after a single oral dose of 250 mg is approximately 2593 ng/mL, and steady-state Cmax on day 4 after repeated oral administration of 250 mg three times daily is approximately 4057 ng/mL.

Biotransformation and Excretion

80–95% of phenibut is metabolized in the liver; metabolites are pharmacologically inactive. Approximately 5% of the dose is excreted unchanged in urine. No accumulation is observed upon repeated administration.

The elimination half-life in healthy volunteers is approximately 7 hours after a single oral dose of 250 mg administered with food, and approximately 8 hours on day 4 after repeated oral doses of 250 mg administered three times daily.

Non-clinical Safety Data

Non-clinical data do not indicate a risk for humans based on pharmacology studies, repeated-dose toxicity studies, and genotoxicity studies. In a 6-month study in rats, administration of the active substance orally at doses of 50, 100, and 200 mg/kg body weight per day did not result in changes in general condition or body weight of animals, or in morphological composition and biochemical blood parameters. Only after administration of high doses of phenibut in male rats during weeks 19–23 was eosinophilia observed. After prolonged administration of the active substance at doses of 100 to 200 mg/kg body weight per day, fatty liver degeneration was observed in 20% of rats. When extrapolated to humans with a body weight of 70 kg, this corresponds to a daily dose of phenibut of 7–14 g. Lower doses (50 and 100 mg/kg) did not affect the liver microstructure in rodents. These data suggest that intake of very high doses may cause hepatotoxicity.

Clinical characteristics.

Indications.

Asthenic and anxiety-neurotic states: restlessness, fear, anxiety.

Insomnia, nocturnal restlessness in elderly people.

Prevention of stress conditions prior to surgical interventions or painful diagnostic procedures.

Meniere's disease, vertigo associated with vestibular analyzer dysfunction of various origins.

Prevention of kinetosis (a specific condition characterized by nausea, vomiting, prostration, and vestibular dysfunction caused by being in a moving object such as a ship or airplane).

Stuttering, tics in children aged 8 to 14 years.

As an adjunctive agent in the treatment of alcohol withdrawal syndrome.

Contraindications.

Hypersensitivity to the components of the medicinal product.

Pregnancy and breastfeeding period.

Interaction with other medicinal products and other forms of interaction.

The medicinal product Bephin may be combined with psychotropic medicinal products, reducing the doses of Bephin and the medicinal products used with it.

Bephin enhances and prolongs the effect of hypnotics, narcotics, neuroleptics, and antiparkinsonian medicinal products.

Special precautions for use

The medicinal product should be used with caution in patients with gastric or intestinal pathology. To protect the mucosa from the irritating effect of phenibut, lower doses should be administered to these patients.

In case of prolonged treatment, blood cell counts and liver function test parameters should be monitored.

Literature data indicate the development of dependence following the use of medicinal products containing phenibut at doses exceeding the therapeutic dose.

Post-marketing experience with phenibut use at therapeutic doses does not indicate the development of withdrawal syndrome. However, literature data suggest that abrupt discontinuation of phenibut administered at doses higher than therapeutic may lead to withdrawal syndrome, which can be severe and may require hospitalization. In some cases, insomnia, psychomotor agitation, psychosis, auditory and visual hallucinations, anxiety, depression, dizziness, seizures, nausea, vomiting, palpitations, and tachycardia have been reported.

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

Use during pregnancy or breastfeeding

Animal studies have not revealed mutagenic, teratogenic, or embryotoxic effects of phenibut. There are insufficient and well-controlled studies on the safety of phenibut use in pregnant women. Therefore, the use of Befin during pregnancy or breastfeeding is contraindicated.

There is no information available regarding the effect of phenibut on fertility.

Ability to influence reaction rate while driving or operating machinery

Patients who experience somnolence, dizziness, or other central nervous system disturbances during treatment with the medicinal product Befin should refrain from driving or operating machinery.

Method of Administration and Dosage

Method of Administration

Take orally after meals, swallowing with sufficient amount of water.

Adults

For asthenic and anxiety-neurotic conditions

Administer 250−500 mg (1−2 capsules) three times daily. The maximum single dose is 750 mg (3 capsules); for elderly patients, the maximum single dose is 500 mg (2 capsules). The treatment course lasts 2−3 weeks. If necessary, the course may be extended up to 4−6 weeks.

For Ménière’s disease and vertigo associated with vestibular dysfunction of various origins

For vestibular dysfunction of infectious origin and during exacerbations of Ménière’s disease:

• 750 mg (3 capsules) three times daily for 5−7 days;
• after reduction in severity of vestibular symptoms, continue treatment at a dose of 250−500 mg (1−2 capsules) three times daily for 5−7 days, followed by 250 mg (1 capsule) once daily for 5 days.

For relatively mild disease courses, the medicinal product Bephin should be administered at 250 mg (1 capsule) twice daily for 5−7 days, followed by 250 mg (1 capsule) once daily for 7−10 days.

For relief of vertigo due to vestibular apparatus dysfunction of vascular or traumatic origin: administer the medicinal product Bephin at 250 mg (1 capsule) three times daily for 12 days.

For prevention of motion sickness (kinetosis): administer a single dose of 250−500 mg (1−2 capsules) one hour before the expected onset of motion sickness or upon appearance of the first symptoms.

If severe symptoms are present (e.g., vomiting), administration of the drug is minimally effective.

For management of alcohol withdrawal syndrome: during the initial days of treatment, administer Bephin at 250−500 mg (1−2 capsules) three times daily and 750 mg (3 capsules) at bedtime, gradually reducing the daily dose.

Children aged 8 to 14 years

Stuttering, tics

Administer 250 mg (1 capsule) three times daily. Treatment duration ranges from 2 to 6 weeks.

Patients with hepatic impairment

High doses of the drug may cause hepatotoxicity in patients with hepatic impairment. Lower doses should be prescribed for this patient group.

Patients with renal impairment

There are no data on adverse reactions of phenibut in patients with impaired renal function when administered at therapeutic doses.

No drug dependence or withdrawal syndrome has been observed during use of this medicinal product. Literature reports isolated cases of tolerance induced by phenibut therapy.

Children

The medicinal product may be used in children aged 8 years and older.

Overdose

The drug is low in toxicity at therapeutic doses.

Symptoms: drowsiness, nausea, vomiting, dizziness.

Prolonged use of high doses may lead to eosinophilia, arterial hypotension, fatty liver degeneration, and impaired renal function.

Post-marketing data indicate serious cases of phenibut overdose, presenting with symptoms such as depression (including decreased level of consciousness, reduced muscle tone, stupor, respiratory depression), impaired thermoregulation, arterial hypertension or hypotension, and tachycardia. Psychomotor agitation, hallucinations, seizures, and delirium have also been reported. Overdose has been associated with use of phenibut-containing medicinal products at doses exceeding the therapeutic range.

Treatment: symptomatic therapy.

There is no specific antidote.

Adverse reactions.

Phenibut, like other medicinal products, may cause adverse reactions, although they do not occur in all patients.

The frequency of adverse reactions is classified as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10000 to < 1/1000); very rare (< 1/10000); frequency not known (cannot be estimated from the available data).

Reporting of suspected adverse reactions

Reporting of adverse reactions following the registration of a medicinal product is of great importance. It enables continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, as well as their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy via the Automated Information System for Pharmacovigilance at the following link: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Storage conditions. Store at temperatures not exceeding 25 °C. Keep out of reach and sight of children.

Packaging. 20 hard capsules in a polyethylene container, sealed with a polyethylene cap with a tamper-evident seal, in a cardboard box.

Prescription status. Prescription only.

Manufacturer. Joint Ukrainian-Spanish enterprise "Sperko Ukraine".

Manufacturer's address and location of its business activities

21027, Ukraine, Vinnytsia, vul. 600-richchia, 25.