Pheniron

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

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).

Pharmaceutical form. Hard capsules.

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

The contents of the capsules are powder ranging from white to white with a yellowish tint.

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 β-phenylethylamine. Phenibut possesses 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 action of hypnotics, narcotics, neuroleptics, and antiparkinsonian agents. It has no anticonvulsant effect. Phenibut prolongs the latent period of nystagmus and reduces its duration and manifestations. Phenibut significantly reduces asthenic symptoms and vasovegetative manifestations, including headache, sensation of heaviness in the head, sleep disturbances, irritability, emotional lability, and enhances mental performance. Phenibut improves psychological parameters—attention, memory, speed and accuracy of sensorimotor responses.

In asthenic and emotionally labile patients, already within the first days of treatment, well-being improves, interest and initiative increase, and motivation for active engagement rises, without sedative effects or excitation. In terms of anti-asthenic activity (fatigue, fatigability, hypodynamia, mental and physical asthenia), phenibut is more active than piracetam.

Pharmacokinetics

Absorption and Distribution

The drug is well absorbed after oral administration and readily penetrates into all tissues of the body, effectively crossing the blood-brain barrier (approximately 0.1% of the administered dose penetrates into brain tissue, and to a significantly greater extent in both young and elderly individuals). The highest binding of phenibut occurs in the liver (80%), and this binding is nonspecific. 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 250 mg oral dose 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; the 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 250 mg oral dose administered after food intake, and approximately 8 hours on day 4 after repeated oral doses of 250 mg administered three times daily.

Safety Preclinical Data

Preclinical data do not indicate a risk for humans based on pharmacological 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 phenibut dose of 7–14 g. Lower doses (50 and 100 mg/kg) did not affect the microstructure of the liver 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 and night restlessness in elderly people.

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

Meniere's disease, dizziness 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 during treatment of alcohol withdrawal syndrome.

Contraindications.

Hypersensitivity to the components of the medicinal product.

Pregnancy or breastfeeding period.

Interaction with other medicinal products and other types of interactions.

FENIRON can be combined with psychotropic medicinal products, reducing the doses of FENIRON and the concomitantly administered medicinal products.

FENIRON enhances and prolongs the effects 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 irritant effect of phenibut, lower doses should be prescribed for these patients.

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

Literature data indicate the development of dependence after using medicinal products containing phenibut in doses exceeding therapeutic ones.

Post-marketing experience with the use of phenibut 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 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; therefore, it 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

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 PHENIRON during pregnancy or breastfeeding is contraindicated.

Information regarding the effect of phenibut on fertility is lacking.

Ability to affect reaction speed when driving or operating machinery

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

Method of Administration and Dosage

Method of Administration

Take orally after meals, 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 treatment course may be extended to 4−6 weeks.

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

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

• 750 mg (3 capsules) three times daily for 5−7 days,
• after reduction 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 course, administer the medicinal product PHENIRON at a dose of 250 mg (1 capsule) twice daily for 5−7 days, then 250 mg (1 capsule) once daily for 7−10 days.

For relief of dizziness due to vestibular apparatus dysfunction of vascular or traumatic origin: administer the medicinal product PHENIRON at a dose of 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 the appearance of first symptoms.

If severe symptoms are present (e.g., vomiting), administration of the drug is likely to be ineffective.

For management of alcohol withdrawal syndrome: administer the medicinal product PHENIRON during the first days of treatment at a dose of 250−500 mg (1−2 capsules) three times daily and 750 mg (3 capsules) at bedtime, with gradual reduction of the daily dose.

Children aged 8 to 14 years

Stuttering, tics

Administer 250 mg (1 capsule) three times daily. Treatment duration is 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 effects of phenibut in patients with impaired kidney function when therapeutic doses are administered.

No drug dependence or withdrawal syndrome has been observed during use of this medicinal product. Literature contains reports of isolated cases of tolerance associated with 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 kidney function.

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

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 available data).

Reporting of suspected adverse reactions

Reporting of adverse reactions following the marketing authorization of a medicinal product is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, or their legal representatives, should report any suspected adverse reactions and lack of efficacy of the medicinal product via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Storage conditions. Store at a temperature 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, placed in a cardboard box.

Prescription status. Prescription only.

Manufacturer. Ukrainian-Spanish joint venture "Sperko Ukraine".

Manufacturer's address and location of its business operations.
21027, Ukraine, Vinnytsia, vul. 600-Richchia, 25.