Proptus

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT PROPTUS® (PROPTUS®)

Composition:

Active substance: levodropropizine;

5 ml of syrup contain levodropropizine 30 mg;

Excipients: sucrose; citric acid monohydrate; methylparahydroxybenzoate (E 218); propylparahydroxybenzoate (E 216); sodium hydroxide; cherry flavoring; purified water.

Pharmaceutical form. Syrup.

Main physico-chemical properties: clear, colorless to pale yellow liquid with a cherry odor.

Pharmacotherapeutic group

Antitussives, excluding combinations with expectorants. Other antitussive agents. Levodropropizine.

ATC code R05D B27.

Pharmacological Properties

Pharmacodynamics

Levodropropizine is an antitussive agent obtained by stereospecific synthesis and chemically corresponding to S(-)3-(4-phenyl-piperazin-1-yl)-propane-1,2-diol.

The antitussive activity of levodropropizine is mediated by several mechanisms, including peripheral action on the tracheobronchial tree, antiallergic and bronchodilating effects. In addition, local anesthetic activity has been demonstrated in preclinical studies.

The antitussive mechanism of levodropropizine involves slowing the transmission of nerve impulses through C-fibers and inhibition of neuropeptide release. The drug does not cause respiratory depression, significant cardiovascular effects, or constipation.

Levodropropizine suppresses bronchospasm induced by histamine, serotonin, and bradykinin, but does not affect bronchospasm induced by acetylcholine, demonstrating the absence of anticholinergic effects.

Levodropropizine is significantly less active than dropropizine in causing oxotremorine-induced tremor and pentamethylenetetrazole-induced convulsions, as well as in altering spontaneous motor activity in mice. Preclinical studies have shown that levodropropizine does not displace naloxone from opioid receptors and does not influence morphine withdrawal syndrome; discontinuation of treatment is not associated with the emergence of addictive behavior.

Clinically, the antitussive efficacy of levodropropizine has been demonstrated in cough associated with bronchopulmonary carcinoma, upper and lower respiratory tract infections, and pertussis.

The antitussive effect of levodropropizine is generally comparable to that of centrally acting antitussive agents; however, the drug has a better tolerability profile, primarily due to the absence of central sedative effects.

At therapeutic doses, levodropropizine does not alter electroencephalographic parameters and does not affect psychomotor performance in humans. Furthermore, no changes in cardiovascular parameters were observed in healthy volunteers receiving up to 240 mg of levodropropizine.

Levodropropizine does not suppress the respiratory center and does not affect mucociliary clearance in humans.

In patients with chronic respiratory insufficiency, levodropropizine does not exert a depressant effect on the respiratory system, either during spontaneous breathing or during hypercapnic ventilation.

Pharmacokinetics

After oral administration, levodropropizine is rapidly absorbed in the gastrointestinal tract and distributed throughout the human body. The bioavailability of levodropropizine after oral administration exceeds 75%. Recovery of radioactivity after oral administration of the drug reached 93%.

Plasma protein binding in humans is low (11–14%).

The elimination half-life is approximately 1–2 hours. The drug is primarily excreted in urine, both unchanged and as metabolites (conjugated levodropropizine, free and conjugated p-hydroxylevodropropizine). Within 48 hours, renal excretion of levodropropizine and the aforementioned metabolites amounts to approximately 35%. Repeated administration tests show that 8-day treatment (three times daily) does not alter the absorption and elimination profile of the drug, ruling out accumulation or metabolic autoinduction.

No significant changes in pharmacokinetic parameters are observed in children, elderly patients, or patients with mild to moderate renal impairment.

Clinical Characteristics

Indications

Symptomatic treatment of cough.

Contraindications

• Hypersensitivity to any component of the medicinal product.
• Excessive mucus production and impaired mucociliary function (Kartagener syndrome, ciliary dyskinesia).
• Pregnancy and breastfeeding period (see section "Use during pregnancy or breastfeeding").
• Children under 2 years of age (see section "Children").

Interaction with other medicinal products and other forms of interaction

Levodropropizine does not enhance the effects of centrally acting agents (e.g., benzodiazepines, alcohol, phenytoin, imipramine).

Preclinical data show that levodropropizine does not alter the activity of oral anticoagulants (such as warfarin) and does not affect the hypoglycemic action of insulin. Levodropropizine, when combined with benzodiazepines, does not change electroencephalographic parameters.

Patients with individual hypersensitivity should exercise caution when using sedative drugs concomitantly.

Clinical studies have not demonstrated any interactions with drugs used in the treatment of the bronchopulmonary system, such as β₂-adrenomimetics, methylxanthines and their derivatives, corticosteroids, antibiotics, mucoregulatory agents, and antihistamines.

Special precautions for use

Antitussive agents are symptomatic remedies and should be used only while awaiting diagnosis and/or treatment of the underlying condition.

Excipients

This medicinal product contains 5 g of sucrose per dose (10 ml). Use with caution in patients with diabetes mellitus.

This medicinal product may cause allergic reactions (possibly delayed), as it contains methylparahydroxybenzoate and propylparahydroxybenzoate.

This medicinal product contains sodium in the amount of 0.85 mmol per dose, i.e. it is practically sodium-free.

Use during pregnancy or breastfeeding

There are no data on the safety of levodropropizine use during pregnancy or breastfeeding; therefore, the medicinal product is contraindicated during these periods (see section "Contraindications").

Ability to affect reaction speed when driving or operating machinery

Caution should be exercised when driving or operating machinery, as dizziness, drowsiness, and reduced reaction time may occur.

Method of Administration and Dosage

This medicinal product is intended for oral use in adults and children aged 2 years and older. To ensure accurate dosing, the package contains a 5 ml dosing syringe.

It is recommended to take the medicinal product on an empty stomach.

Recommended doses

Adults: 10 ml of syrup up to 3 times daily, with at least a 6-hour interval between doses.

Children with body weight from 10 to 20 kg: 3 ml of syrup up to 3 times daily, with at least a 6-hour interval between doses.

Children with body weight from 20 to 30 kg: 5 ml of syrup up to 3 times daily, with at least a 6-hour interval between doses.

Elderly patients

Dose adjustment is not required. Use with caution, as sensitivity to certain drugs may be altered in elderly individuals.

Renal impairment

Dose adjustment is not required. Use with caution in patients with severe renal impairment (creatinine clearance <35 ml/min).

Treatment should be continued until cough resolves. If cough persists after 2 weeks of therapy, treatment should be discontinued and medical advice should be sought. Since cough is a symptom, the underlying cause should be identified and treated.

Children

The product is contraindicated in children under 2 years of age (see section "Contraindications").

Overdose

No significant adverse effects have been observed after single doses of levodropropizine up to 240 mg or after repeated administration of up to 120 mg three times daily for 8 days. Cases of overdose have been reported in children aged 2 to 4 years. All cases of accidental overdose resolved without consequences. In most cases, patients reported abdominal pain and vomiting; in one case, following ingestion of 600 mg of levodropropizine, excessive drowsiness and decreased blood oxygen saturation were observed.

In case of overdose with evident clinical symptoms, immediate symptomatic treatment should be initiated, including emergency measures such as gastric lavage, administration of activated charcoal, parenteral fluid replacement, etc.

Adverse Reactions

During treatment with levodropropizine, tachycardia, nausea, vomiting, diarrhea, and erythema may occur. Serious adverse reactions reported include urticaria and anaphylactoid reactions.

Most adverse reactions associated with levodropropizine are not severe and resolve after discontinuation of therapy, and in some cases, following appropriate medical treatment.

Adverse reactions observed (frequency unknown) during levodropropizine treatment are listed below.

Eye disorders: mydriasis, bilateral blindness.

Immune system disorders: allergic and anaphylactoid reactions, eyelid edema, angioneurotic edema, urticaria.

Psychiatric disorders: irritability, somnolence, personality change / disorder.

Nervous system disorders: syncope, dizziness, tremor, paresthesia, tonic-clonic seizures. In some cases, clonic-tonic seizures and petit mal epilepsy attacks (absences), as well as hypoglycemic coma, have been reported.

Cardiac disorders: tachycardia, atrial bigeminy.

Vascular disorders: arterial hypotension.

Respiratory, thoracic and mediastinal disorders: dyspnea, cough, swelling of the airways.

Gastrointestinal disorders: stomach pain, abdominal pain, nausea, vomiting, diarrhea.

Hepatobiliary disorders: cholestatic hepatitis.

Skin and subcutaneous tissue disorders: urticaria, erythema, exanthema, pruritus, Quincke's edema, skin reactions, glossitis and aphthous stomatitis, epidermolysis.

Musculoskeletal and connective tissue disorders: weakness in the lower limbs.

General disorders and administration site conditions: general weakness, generalized edema, asthenia.

Children

Cases of somnolence, hypotonia, and vomiting have been reported in breastfed infants whose mothers were taking levodropropizine. Symptoms appeared after feeding and resolved spontaneously after temporary interruption of breastfeeding for several feeds.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after drug authorization is important. It allows 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 through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life

2 years.

Storage conditions

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

Keep out of reach of children.

Packaging

100 ml or 200 ml in a glass bottle with a tamper-evident cap. Each bottle is packed in a cardboard package together with a 5 ml dosing syringe and a syringe adapter.

100 ml or 200 ml in a glass bottle with a child-resistant cap. Each bottle is packed in a cardboard package together with a 5 ml dosing syringe and a syringe adapter.

Prescription status

Prescription only.

Manufacturer

LLC "KUSUM PHARM".

Manufacturer's address and place of business

54 Skryabina Street, Sumy, Sumy region, 40020, Ukraine.