SINTUS

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT SINTUS

Composition:

Active substance: butamirate citrate;

1 ml of solution contains 5 mg of butamirate citrate;

Excipients: sorbitol solution, non-crystallizing (E 420); glycerol; sodium saccharin; benzoic acid; natural raspberry flavoring; sodium hydroxide; ethanol 96%; purified water.

Pharmaceutical form. Oral drops, solution.

Main physicochemical properties: clear, colorless solution with a raspberry odor.

Pharmacotherapeutic group. Medicinal products used for cough and colds. Antitussives. ATC code R05DB13.

Pharmacological Properties

Pharmacodynamics

A non-opioid antitussive agent with central action. However, the exact mechanism of action is unknown.

The active ingredient of Synthuss is butamirate citrate, which suppresses cough and structurally and pharmacologically differs from opium alkaloids. The substance is believed to act on the central nervous system. Butamirate citrate exhibits a non-specific anticholinergic and bronchospasmolytic effect, thereby improving respiratory function. Synthuss does not cause habituation or dependence.

Butamirate citrate has a wide therapeutic range; therefore, Synthuss is well tolerated at therapeutic doses and is well suited as a cough suppressant for children.

Pharmacokinetics

Butamirate is rapidly absorbed, distributed throughout the body, and subsequently hydrolyzed mainly into 2-phenylbutyric acid and diethylaminoethoxyethanol, both of which also possess antitussive activity. 2-Phenylbutyric acid is further partially metabolized via hydroxylation. Butamirate and 2-phenylbutyric acid are extensively bound to plasma proteins in the body.

The effect of food on bioavailability has not been confirmed. The metabolism of butamirate into 2-phenylbutyric acid and diethylaminoethoxyethanol is completely proportional within the dose range of 22.5 mg – 90 mg.

Metabolites are primarily excreted by the kidneys. Butamirate is detectable in urine up to 48 hours after administration. According to measurement results, the elimination half-life is 1.48–1.93 hours for butamirate, 23.26–24.42 hours for 2-phenylbutyric acid, and 2.72–2.90 hours for diethylaminoethoxyethanol.

There is no evidence of the influence of hepatic or renal impairment on the pharmacokinetic parameters of butamirate.

Clinical characteristics.

Indications.

Symptomatic treatment of cough (including dry cough) of various origins in children.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients of the medicinal product, hereditary fructose intolerance, due to the presence of sorbitol in the medicinal product.

Interaction with other medicinal products and other forms of interaction.

Concomitant use of expectorants and mucolytics should be avoided. The exact mechanism of interaction with other medicinal products has not been studied, but the central cough-suppressant mechanism of action of the medicinal product may be enhanced by the effects of strong depressants, including alcohol.

Special precautions.

Since butamirate suppresses the cough reflex, concomitant use of expectorants should be avoided, as this may lead to mucus stagnation in the airways, increasing the risk of bronchospasm and respiratory tract infection.

Before initiating treatment with this medicinal product, it should be clarified whether etiological treatment of cough is required.

If cough persists after treatment according to the recommended therapeutic regimen, the dose of the medicinal product should not be increased; instead, the patient's clinical condition should be re-evaluated.

When administering the drug to patients with kidney and/or liver disease, increased risk of adverse reactions due to possible accumulation of the active substance should be taken into account.

The medicinal product contains the sweetener sorbitol, which may be used in patients with diabetes mellitus (1 g of sorbitol corresponds to approximately 17 kJ or 4 kcal).

The medicinal product contains sorbitol. Sorbitol is a source of fructose. It should not be administered to patients with rare hereditary fructose intolerance. If intolerance to certain sugars is suspected, consult a physician before taking this medicinal product. Synthuss contains a small amount of ethanol (2.81 mg/mL), which amounts to less than 100 mg per dose.

If cough persists for more than 7 days, or if fever, dyspnea, or chest tightness develops, medical advice should be sought.

In patients whose symptoms worsen or do not improve within 7 days and/or are accompanied by fever, rash, or persistent headache, additional investigations should be performed to identify the underlying cause.

This medicinal product should be administered to children under 2 years of age only under medical supervision.

Keep out of reach and sight of children.

Use during pregnancy or breastfeeding.

The product is intended for use in children.

Pregnancy

Animal studies have not indicated direct or indirect harmful effects on pregnancy or fetal health. The safety of using the drug during pregnancy has not been evaluated in specific clinical studies involving pregnant women. Therefore, use during pregnancy is not recommended, except when considered necessary and specifically advised by a physician.

Breastfeeding

It is unknown whether the active substance and/or its metabolites pass into breast milk; therefore, this medicinal product is not recommended during breastfeeding.

Fertility

There are no data on the adverse effects of the medicinal product on fertility.

Ability to affect reaction speed when driving or operating machinery.

The product is intended for use in children.

Rarely, Synthuss may cause somnolence and/or dizziness, which may have a minor influence on the ability to drive or operate machinery. Caution should be exercised when driving a vehicle or performing other tasks requiring alertness (e.g., operating mechanical equipment).

It may cause fatigue and affect reaction ability when driving vehicles or operating machinery.

Dosage and Administration.

The medicinal product is intended for use in children.

The single dose depends on the child's age and is as follows:

The maximum treatment duration without a doctor's prescription should not exceed 7 days (see section "Special Instructions").

The lowest dose required to achieve efficacy should be used for the shortest duration of treatment.

Do not exceed the recommended dose.

Method of administration

Synthuss, drops, is intended for oral administration. The medicinal product can be mixed with a small amount of water prior to use.

Patients with renal and/or hepatic impairment

There are no data on the use of this medicinal product in this patient group.

Children.

Not recommended for children under 2 months of age.

For children under 2 years of age, use only under medical supervision.

For children aged 3 years and older, another dosage form—Synthuss syrup—may be used.

Overdose.

Overdose may cause the following symptoms: drowsiness, nausea, vomiting, diarrhea, dizziness, and hypotension.

Further treatment should be based on clinical indications.

There is no specific antidote for butamirate overdose. In case of overdose, symptomatic treatment and monitoring of vital functions are required.

Adverse reactions.

From the nervous system: (rare: ≥ 1/10000, < 1/1000) – drowsiness, dizziness.

From the gastrointestinal tract: (rare: ≥ 1/10000, < 1/1000) – nausea, diarrhea.

From the immune system: (rare: ≥ 1/10000, < 1/1000) – anaphylactic shock.

From the skin and subcutaneous tissue: (rare: ≥ 1/10000, < 1/1000) – angioneurotic edema, skin rashes, urticaria, pruritus.

Reporting suspected adverse reactions.

Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continuous monitoring of the benefit-risk balance of the product. Healthcare professionals and patients, as well as their legal representatives, are encouraged to report any suspected adverse reactions and lack of efficacy of the medicinal product via the Automated Information System for Pharmacovigilance at the following link: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Shelf life after first opening of the container: 4 months.

Storage conditions.

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

Keep out of reach and sight of children.

Packaging.

20 ml in a bottle with dropper cap and lid; 1 bottle in a cardboard box.

Availability.

Over-the-counter (without prescription).

Manufacturer.

VETPROM AD, production site Vpharma / VETPROM AD, the Vpharma site.

Manufacturer's address and address of the place of business activity.

26 Otec Paisiy Str., Radomir 2400, Bulgaria.