Bifren®
Ukraine
Table of Contents
INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT BIFREN® (BIFREN)
Composition:
Active substance: phenibut;
1 capsule contains phenibut 250 mg;
Excipients: microcrystalline cellulose, sodium croscarmellose, colloidal anhydrous silicon dioxide, magnesium stearate, talc;
Capsule shell composition: gelatin, titanium dioxide (E 171).
Medicinal form. Capsules.
Main physicochemical properties: hard gelatin capsules with a white opaque cap and a white opaque body.
The capsule contents – a white or almost white powder.
The presence of compacted columns or lumps which disintegrate upon pressure is permissible.
Pharmacotherapeutic group.
Other psychostimulants and nootropic agents.
ATC code N06BX22.
Pharmacological Properties.
Pharmacodynamics.
Nootropics are also called psychometabolic stimulants because they favorably affect metabolic processes in the brain. Phenibut is a derivative of γ-aminobutyric acid (GABA) and beta-phenylethylamine. Phenibut exhibits both nootropic activity and anxiolytic (tranquilizing) activity typical of GABA derivatives. Phenibut does not affect cholinergic or adrenergic receptors. It reduces anxiety, 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, narcotic agents, neuroleptics, and antiparkinsonian drugs. It has no anticonvulsant effect. Phenibut prolongs the latent period of nystagmus and reduces its duration and intensity. Phenibut significantly reduces manifestations of asthenia 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 patients with asthenia and emotionally labile patients, improvement in general well-being, increased interest and initiative, and motivation for active engagement occur as early as the first days of treatment with the drug, without sedative effects or excitation. In terms of anti-asthenic activity (fatigue, tiredness, hypodynamia, mental and physical asthenia), phenibut is more active than piracetam.
Pharmacokinetics.
Absorption and Distribution
The drug is well absorbed from the gastrointestinal tract after oral administration and readily penetrates 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 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 250 mg oral dose 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 Elimination
80−95% of phenibut is metabolized in the liver; the metabolites are pharmacologically inactive.
Distribution in the liver and kidneys is close to uniform, while in the brain and blood it is lower than uniform. 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.
Clinical characteristics.
Indications.
- Asthenic and anxiety-neurotic conditions: restlessness, fear, anxiety; insomnia, nocturnal restlessness in elderly people; prevention of stress conditions prior to surgery.
- Meniere's disease and 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 during treatment of alcohol withdrawal syndrome.
Contraindications.
Hypersensitivity to the components of the drug.
Pregnancy and breastfeeding period.
Interaction with other medicinal products and other forms of interaction.
Bifren® can be combined with psychotropic medicinal agents, reducing the doses of Bifren® and concomitantly administered drugs.
Bifren® enhances and prolongs the effect of hypnotics, narcotics, neuroleptics, and antiparkinsonian agents.
Special precautions for use.
Caution should be exercised in patients with gastric or intestinal ulcers. To protect the mucosa from the irritating effect of phenibut, lower doses should be prescribed to these patients. With prolonged use, blood cell counts and liver function tests should be monitored.
Literature data indicate the development of dependence after taking medicinal products containing phenibut in doses exceeding the therapeutic dose.
Post-marketing experience with phenibut administered 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.
Use during pregnancy or breastfeeding.
Animal studies have not revealed mutagenic, teratogenic, or embryotoxic effects of phenibut. The use of the drug Bifren® during pregnancy or breastfeeding is contraindicated due to insufficient data on the use of the drug during these periods.
Information regarding the effect of phenibut on fertility is lacking.
Ability to influence reaction speed when driving or operating machinery.
Patients who experience drowsiness or other central nervous system disturbances during treatment with the drug 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 in adults
Administer 250–500 mg three times daily. The maximum single dose is 750 mg; for elderly patients, the maximum single dose is 500 mg. 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 dysfunction of various origins
For vestibular dysfunction of infectious origin and during exacerbations of Ménière’s disease:
- 750 mg three times daily for 5–7 days,
- after reduction of vestibular symptoms, continue treatment at a dose of 250–500 mg three times daily for 5–7 days, followed by 250 mg once daily for 5 days.
For milder disease courses, the medicinal product Bifren® should be administered at 250 mg twice daily for 5–7 days, followed by 250 mg once daily for 7–10 days.
For relief of dizziness in vestibular apparatus dysfunction of vascular and traumatic origin: administer the medicinal product Bifren® at 250 mg three times daily for 12 days.
For prevention of motion sickness (kinetosis): administer a single dose of 250–500 mg one hour before the expected onset of motion sickness, or upon the appearance of first symptoms.
If severe symptoms are present (e.g., vomiting), the drug is likely to be ineffective.
For management of alcohol withdrawal syndrome: during the first days of treatment, the medicinal product Bifren® is administered at 250–500 mg three times daily and 750 mg at night, with gradual reduction of the daily dose thereafter.
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 regarding adverse effects 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 contains reports of isolated cases of tolerance induced by phenibut therapy.
Children
Children aged 8 to 14 years: 250 mg three times daily; treatment duration ranges from 2 to 6 weeks. The medicinal product is not administered to children under 8 years of age.
Overdose
The drug is low-toxic at therapeutic doses.
Symptoms: drowsiness, nausea, vomiting, dizziness.
Prolonged use of high doses may lead to arterial hypotension, acute renal failure, eosinophilia, and fatty liver degeneration.
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), disturbances in thermoregulation, hypertension or hypotension, and tachycardia. Psychomotor agitation, hallucinations, seizures, and delirium have also been reported. Overdose cases were 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.
Classification of adverse reactions by frequency: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); frequency not known (cannot be estimated from the available data).
Immune system disorders: frequency not known – hypersensitivity reactions, including rash, pruritus, urticaria, erythema, angioneurotic edema, facial swelling, tongue swelling.
Nervous system disorders: frequency not known – drowsiness (at the beginning of treatment), headache and dizziness (at doses exceeding 2 g per day; the intensity of this adverse effect decreases when the dose is reduced).
Gastrointestinal disorders: frequency not known – nausea (at the beginning of treatment).
Hepatobiliary disorders: frequency not known – hepatotoxicity (with long-term use of high doses).
Skin and subcutaneous tissue disorders: rare – allergic reactions (rash, pruritus).
There is some evidence that incorrect use in children may lead to emotional lability and sleep disturbances.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continuous monitoring of the safety profile and assessment of the benefit-risk balance of the medicinal product.
Shelf life.
2 years.
Do not use after the expiry date stated on the packaging.
Storage conditions.
Store in the original packaging, out of reach of children, at a temperature not exceeding 25 °C.
Packaging.
10 capsules in a blister; 1, 2 or 6 blisters in a cardboard pack.
15 capsules in a blister; 2 or 4 blisters in a cardboard pack.
Prescription status.
Prescription only.
Manufacturer.
TOV "Pharma Start".
Manufacturer's address and place of business.
8 Vatslava Havela Boulevard, Kyiv, 03124, Ukraine.
In case of adverse reactions or questions regarding the safety and efficacy of the medicinal product, please contact the Pharmacovigilance Department of TOV "ASINO UKRAINA" at: 8 Vatslava Havela Boulevard, Kyiv, 03124, Tel/Fax: +380442812333.