Tuspan

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT TUSPAN® (TUSPAN®)

Composition:

Active ingredient: butamirate citrate;

1 ml of syrup contains 1.5 mg of butamirate citrate;

Excipients: sorbitol solution, non-crystallizing (E 420); glycerol; sodium saccharin; benzoic acid (E 210); vanillin; ethyl alcohol (96%) rectified; sodium hydroxide; purified water.

Pharmaceutical form. Syrup.

Main physicochemical properties: clear solution ranging from colorless to slightly brownish-yellow.

Pharmacotherapeutic group. Cough and cold preparations. Antitussives. ATC code: R05DB13.

Pharmacological properties.

Pharmacodynamics.

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

The active ingredient of the medicinal product is butamirate citrate, which suppresses cough and differs in structure and pharmacological action from opium alkaloids. It is believed that this substance acts on the central nervous system. Butamirate citrate produces a non-specific anticholinergic and bronchospasmolytic effect, which improves respiratory function. Butamirate citrate does not cause habituation or dependence.

Butamirate citrate has a wide therapeutic range, is well tolerated at therapeutic doses, and is therefore suitable as an antitussive agent for children.

Pharmacokinetics.

Butamirate is rapidly absorbed, distributed throughout the body, and then predominantly hydrolyzed to 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 highly protein-bound in the body.

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

Measurable concentrations of butamirate appear in the blood within 5–10 minutes after administration of 22.5 mg, 45 mg, 67.5 mg, and 90 mg. Maximum plasma concentrations are reached within 1 hour for all four doses, with a mean maximum plasma concentration of 16.1 ng/mL after a 90 mg dose.

The mean maximum plasma concentration of 2-phenylbutyric acid is achieved within 1.5 hours, with the highest exposure observed after the 90 mg dose (3052 ng/mL).

The mean maximum plasma concentration of diethylaminoethoxyethanol is achieved within 0.67 hours, with the highest exposure observed after the 90 mg dose (160 ng/mL).

Metabolites are primarily excreted by the kidneys. Butamirate is detectable in urine for 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 impact of hepatic or renal impairment on the pharmacokinetic parameters of butamirate.

Clinical characteristics.

Indications.

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

Contraindications.

Hypersensitivity to the active substance or to any of the excipients of the medicinal product.

Interaction with other medicinal products and other forms of interaction.

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

Special precautions for use

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

The syrup contains sweeteners — sodium saccharin and sorbitol, therefore it can be prescribed to patients with diabetes mellitus. Sorbitol is a source of fructose, so Tusspan® should not be used in patients with fructose intolerance.

If a patient has known intolerance to certain sugars, medical advice should be sought before taking this medicinal product.

Tusspan® contains a small amount of ethanol (alcohol), less than 100 mg per dose. The medicinal product contains less than 1 mmol of sodium (23 mg) per dose, i.e. it is practically sodium-free.

If cough persists for more than 7 days, a doctor should be consulted.

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

Keep the medicinal product out of reach and sight of children.

Use during pregnancy or breastfeeding.

The safety of Tusspan® during pregnancy or breastfeeding has not been evaluated in specific studies. Animal studies have not indicated any direct or indirect harmful effects on pregnancy or fetal health.

During pregnancy, Tusspan® should be used only on a physician's prescription and only when there are clear clinical indications for such treatment. If the expected benefit to the pregnant woman outweighs the potential risk to the fetus, the lowest effective dose and shortest possible duration of treatment should be prescribed.

It is unknown whether the active substance or its metabolites are excreted in breast milk.

For safety reasons, the benefits and risks of using Tusspan® during breastfeeding must be carefully weighed. The use of this medicinal product during lactation is possible only upon medical advice, if, in the physician’s opinion, the expected benefit to the mother outweighs the potential risk to the infant. In such cases, the lowest effective dose and shortest possible duration of treatment should be prescribed.

Effect on ability to drive and use machines.

The medicinal product may cause fatigue and affect the ability to drive or operate machinery.

Dosage and Administration.

For oral use only.

Children aged 3 to 6 years: 5 ml (7.5 mg) three times daily; maximum daily dose — 15 ml (22.5 mg).

Children aged 6 to 12 years: 10 ml (15 mg) three times daily; maximum daily dose — 30 ml (45 mg).

Adolescents aged 12 years and older: 15 ml (22.5 mg) three times daily; maximum daily dose — 45 ml (67.5 mg).

Adults: 15 ml (22.5 mg) four times daily; maximum daily dose — 60 ml (90 mg).

The measuring cup should be washed and dried after each use and after use by another person.

The maximum treatment duration without a doctor's prescription should not exceed 1 week.

The medication should preferably be taken before meals.

The lowest effective dose for the shortest duration necessary to achieve the desired effect should be used.

Do not exceed the recommended dose.

Children.

The drug in this pharmaceutical form is not intended for children under 3 years of age.

Overdose.

Tusspan® overdose may cause symptoms such as drowsiness, nausea, vomiting, diarrhea, dizziness, and arterial 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.

Side effects.

From the nervous system (rare: ≥ 1/10,000, < 1/1,000): dizziness, somnolence.

From the gastrointestinal tract (rare: ≥ 1/10,000, < 1/1,000): nausea, diarrhea.

From the immune system (rare: ≥ 1/10,000, < 1/1,000): anaphylactic shock.

From the skin and subcutaneous tissue (rare: ≥ 1/10,000, < 1/1,000): angioneurotic edema, skin rashes, urticaria, pruritus.

Reporting of adverse reactions after drug registration is of great importance. It enables continuous monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should 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. 3 years.

Shelf life after opening the bottle — 1 month.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C, in a place inaccessible to children.

Packaging. 100 ml or 200 ml of syrup in polymer bottles, closed with polymer caps, 1 bottle with a measuring cup in a carton.

Dispensing category. Over-the-counter.

Manufacturer.

JSC "VITAMINS".

Address of the manufacturer and location of business activity.

31 Uspenska Street, Uman, Cherkasy region, 20300, Ukraine.