Tranquilar® ic

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT TRANQUILAR® IS

Composition:

Active substance: temgicoluril;

1 tablet contains temgicoluril 300 mg (0.3 g);

Excipients: methylcellulose, calcium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: white-colored tablets, flat cylindrical shape, with bevelled edges; the company trademark is imprinted on one surface of the tablet, and a score line is present on the other surface.

Pharmacotherapeutic group.

Psychostimulants, drugs used in attention deficit hyperactivity disorder (ADHD), and nootropic agents. Other psychostimulant and nootropic agents. Temgicoluril.

ATC code N06BX21.

Pharmacological Properties

Pharmacodynamics

The active ingredient of the medicinal product, temgicoluril, is chemically similar to natural metabolites of the body: the temgicoluril molecule consists of two methylated fragments of urea incorporated into a bicyclic structure.

Tranquil® IS affects the activity of the limbic-reticular complex, particularly the emotiogenic zones of the hypothalamus, and also influences all four major neurotransmitter systems—GABAergic, cholinergic, serotonergic, and adrenergic—promoting their balance and integration, but does not exert peripheral adrenolytic effects. Tranquil® IS exhibits antagonistic activity against excitation of the adrenergic and glutamatergic systems and enhances the inhibitory serotonergic and GABAergic mechanisms in the brain. The neurotransmitter profile of the drug includes a dopamine-positive component.

The medicinal product has normothymic properties.

Tranquil® IS has moderate tranquilizing (anxiolytic) activity, relieving or reducing feelings of uneasiness, anxiety, fear, inner emotional tension, and irritability. The anxiolytic effect of the drug is not accompanied by myorelaxation or impaired motor coordination. The drug does not reduce mental or physical activity; therefore, it can be used during working hours or while studying. For this reason, Tranquil® IS is classified as a daytime tranquilizer. The drug does not exhibit hypnotic effects but enhances the action of hypnotics and improves sleep when disturbed.

In addition to its anxiolytic effect, the drug exerts nootropic action. Tranquil® IS improves cognitive functions, increases attention and mental performance, without stimulating symptoms of productive psychopathological disorders such as delusions or pathological emotional activity.

The drug reduces the severity of adverse effects (emotional blunting, oversedation, muscle weakness) caused by neuroleptics and benzodiazepine tranquilizers.

The drug has anti-alcohol effects. In patients with alcoholism, one of the reasons for increased craving for alcohol is a reduced level of endogenous ethanol in blood plasma. Tranquil® IS, by increasing the level of endogenous ethanol (to a greater extent than other tranquilizers), reduces the craving for alcohol.

Tranquil® IS alleviates nicotine withdrawal.

The drug does not produce elevated mood or feelings of euphoria.

Pharmacokinetics

After oral administration, bioavailability is 77–80%; up to 40% of temgicoluril binds to erythrocytes; the remaining 60% is not bound to blood proteins and remains free in blood plasma, allowing temgicoluril to distribute freely throughout the body and pass unimpeded through membranes. The volume of distribution is 0.9 L/kg. Maximum concentration of temgicoluril in blood plasma is reached within 30 minutes; a high level persists for 3–4 hours, then gradually declines. Temgicoluril is completely eliminated from the body: 55–70% of the administered dose is excreted in urine, the remainder in feces, unchanged, within 24 hours. Temgicoluril does not accumulate in the body and is not subject to biochemical transformation.

Clinical characteristics.

Indications.

The medicinal product is intended for use in adults.

Neuroses and neurosis-like conditions accompanied by feelings of anxiety and fear, emotional lability, and restlessness.

Cardialgia of various origins (not related to ischemic heart disease).

For improving tolerance of neuroleptics and tranquilizers.

Used as part of combination therapy for nicotine dependence as an agent that reduces craving for smoking.

Contraindications.

Hypersensitivity to temgicoluril or to any of the excipients of the medicinal product.

Interaction with other medicinal products and other types of interactions.

Trankvilar® IS can be combined with neuroleptics, tranquilizers (benzodiazepines), hypnotics, antidepressants, and psychostimulants.

Special precautions.

Physical dependence, development of dependence, and withdrawal syndrome have not been established with the use of temgicoluril.

The drug should be used with caution in patients with arterial hypotension, and in those with impaired liver or kidney function.

There have been isolated reports of acute hypersensitivity reactions.

Use during pregnancy or breastfeeding.

Temgicoluril penetrates well into all tissues and body fluids.

There is insufficient data on the safety of temgicoluril use during pregnancy and breastfeeding; therefore, the drug is not recommended for administration to pregnant women or women who are breastfeeding.

Ability to affect reaction rate while driving or operating machinery.

Caution should be exercised when driving or operating machinery, since the use of temgicoluril may cause decreased arterial pressure and weakness.

Dosage and Administration

The medicinal product should be taken orally, regardless of food intake. Dosage depends on individual patient characteristics and the therapeutic goal of treatment.

The usual adult dose is 300–600 mg 2–3 times daily. The dose may be increased if necessary. The maximum single dose is 3 g; the maximum daily dose is 10 g. The duration of treatment ranges from several days to 2–3 months.

In the complex treatment of nicotine dependence, the medicinal product should be administered at a dose of 600–900 mg daily for 5–6 weeks.

For elderly patients and patients with hepatic insufficiency, dose adjustment is not required.

In patients with renal insufficiency, dose adjustment has not been studied. The medicinal product should be administered with caution in such patients.

If one or several doses have been missed, treatment should be continued according to the previously prescribed regimen.

Children.

The medicinal product is not intended for use in children.

Overdose.

The medicinal product has low toxicity. In cases of significant overdose, adverse effects may be intensified (including allergic reactions, dyspeptic disorders, weakness, temporary reduction in arterial blood pressure and body temperature).

Treatment: gastric lavage should be performed, along with standard detoxification procedures and symptomatic therapy.

No specific antidote is known.

Side effects

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

Adverse reactions associated with the use of the medicinal product are classified by organ systems and frequency. Frequency is defined as follows: 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).

Nervous system disorders: rare – dizziness.

Cardiovascular system disorders: rare – decreased blood pressure.

Gastrointestinal disorders: rare – dyspeptic disorders (including nausea, vomiting, diarrhea). In such cases, the dose of the medicinal product should be reduced.

Respiratory system disorders: rare – bronchospasm.

Skin and subcutaneous tissue disorders: rare – allergic reactions (including skin rash, itching, urticaria, angioedema). If an allergic reaction occurs, administration of the medicinal product should be discontinued.

General disorders: rare – decreased body temperature, weakness. When blood pressure and/or body temperature decreases (body temperature may decrease by 1–1.5 °C), there is no need to discontinue the medicinal product. Blood pressure and body temperature will normalize after completion of the treatment course.

Reporting of suspected adverse reactions

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

Shelf life. 4 years.

Storage conditions.

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

Keep out of reach of children.

Packaging.

10 tablets per blister pack; 2 blisters per carton.

Prescription status. Prescription only.

Manufacturer.

Interkhim Limited Liability Company.

Manufacturer's address and location of business activity.

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