Efina

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT EFINA (EFINA)

Composition:

Active substances: triprolidine hydrochloride, pseudoephedrine hydrochloride;

One tablet contains triprolidine hydrochloride 2.5 mg, pseudoephedrine hydrochloride 60.0 mg;

Excipients: lactose monohydrate; microcrystalline cellulose; maize starch; povidone; magnesium stearate; talc; colloidal anhydrous silicon dioxide; sodium croscarmellose.

Pharmaceutical form. Tablets.

Main physicochemical properties: white or almost white, round, biconvex tablets.

Pharmacotherapeutic group. Systemic anti-edema agents used in nasal pathology. ATC code R01B A52.

Pharmacological properties.

Pharmacodynamics.

Efina is a combination of a nasal decongestant – pseudoephedrine – and an H1-histamine receptor antagonist – triprolidine.

Triprolidine is a potent H1-histamine receptor antagonist of the alkylamine class with minimal anticholinergic activity. Triprolidine provides symptomatic relief in conditions that are wholly or partially mediated by the release of histamine.

Pseudoephedrine is a sympathomimetic agent that effectively reduces mucosal edema of the upper respiratory tract, particularly the nasal mucosa and paranasal sinuses, as it acts both directly and indirectly as a sympathomimetic. Compared to ephedrine, it has considerably less central nervous system (CNS) stimulation, causes less tachycardia, and produces a smaller increase in arterial pressure.

Pharmacokinetics.

Both pseudoephedrine and triprolidine are well absorbed from the gastrointestinal tract following oral administration. After administration of 1 tablet, the maximum plasma concentration (Cmax) of triprolidine is 5.5–6.0 ng/mL, reached at approximately 2 hours (Tmax) after intake. The elimination half-life of triprolidine from plasma is approximately 3.2 hours. Only about 1% of the administered dose of triprolidine is excreted unchanged.

The Cmax of pseudoephedrine in plasma is approximately 180 ng/mL, reached at approximately 2 hours (Tmax) after intake. The elimination half-life from plasma is 5.5 hours.

Pseudoephedrine is partially metabolized in the liver to inactive metabolites. Pseudoephedrine and its metabolites are excreted by the kidneys, with 55–75% of the dose excreted unchanged. The excretion rate of pseudoephedrine increases with urine acidification and correspondingly decreases with increasing urine pH.

Clinical characteristics.

Indications. Symptomatic treatment of upper respiratory tract diseases, such as allergic rhinitis, vasomotor rhinitis, and also during common cold.

Contraindications. Hypersensitivity to pseudoephedrine hydrochloride, triprolidine hydrochloride, acrivastine, or to any of the excipients of the medicinal product.

Severe arterial hypertension, severe ischemic heart disease; severe renal impairment, severe hepatic and renal disorders, bronchial asthma, bronchitis and bronchiectasis accompanied by excessive secretion, pheochromocytoma.

Do not administer to patients receiving other sympathomimetics (decongestants, appetite suppressants, and amphetamine-like psychostimulants).

Do not administer to patients receiving monoamine oxidase inhibitors (MAOIs), or who have received them within the preceding two weeks (including the antibacterial agent furazolidone); patients receiving other symptomatic treatments containing pseudoephedrine or triprolidine; severe hepatic impairment; children, pregnancy, breastfeeding.

Interaction with other medicinal products and other types of interactions.

Concomitant use of Efyn and tricyclic antidepressants, other sympathomimetics, or MAO inhibitors, or furazolidone may lead to increased arterial pressure (see section "Contraindications").

Concomitant use of the medicinal product with antihypertensive agents (e.g. beta-blockers, methyldopa, reserpine, debrecin, guanethidine) reduces the effectiveness of the latter.

Use of the medicinal product in patients receiving cardiac glycosides, quinidine, or tricyclic antidepressants may increase the risk of arrhythmias.

Concomitant use with sympathomimetics (decongestants, appetite suppressants, amphetamine-like psychostimulants) affecting the catabolism of sympathomimetic amines may lead to increased blood pressure.

Concomitant use with hypnotics, sedatives, or tranquilizers may enhance drowsiness. A similar effect is observed with concomitant alcohol consumption.

Special precautions.

The recommended dosage must not be exceeded. The drug should not be taken concurrently with other medications containing pseudoephedrine or triprolidine.

Use with caution and under medical supervision:

§ in patients with impaired liver or kidney function, urinary retention, prostatic hyperplasia, gastrointestinal disorders, hyperthyroidism, cardiovascular diseases (coronary heart disease, arrhythmias, tachycardia), arterial hypertension, occlusive vascular diseases, including atherosclerosis, aneurysm, in patients with diabetes mellitus, glaucoma, increased intraocular pressure, in elderly patients, in patients with epilepsy, bronchial asthma, bronchitis, and bronchiectasis.

Concomitant use of this drug with furazolidone is not recommended, as it may lead to an increase in arterial pressure (AP).

The drug should be used cautiously in patients receiving beta-blockers and other antihypertensive agents.

The use of the drug may cause drowsiness, dizziness, blurred vision, and impaired psychomotor performance, which may seriously affect a patient's ability to drive or operate machinery. If such symptoms occur, patients should avoid driving or operating machinery.

Avoid concomitant use with other medications containing antihistamine components, including cold and cough remedies.

When used in children and elderly patients, neurological and anticholinergic adverse effects and paradoxical excitation are more likely to occur.

The drug contains lactose and therefore should not be administered to patients with rare hereditary forms of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome.

Concomitant use with anticholinergic agents such as atropine, and certain psychotropic drugs, may result in tachycardia, dry mouth, urinary retention, and gastrointestinal disturbances (spasmodic abdominal pain).

Since the drug may suppress allergic skin test reactions, its administration should be discontinued several days prior to performing such tests.

Alcohol or CNS depressant drugs must not be taken concurrently with Efina.

Use during pregnancy or breastfeeding.

The drug is contraindicated during pregnancy and breastfeeding.

Effect on the ability to drive or operate machinery.

The anticholinergic properties of triprolidine may cause drowsiness, dizziness, blurred vision, and altered psychomotor performance in some patients, which may seriously impair their ability to drive or operate machinery. Patients experiencing these effects should refrain from driving or operating machinery (see section "Special precautions").

Dosage and Administration

Patients should be advised to consult a physician if symptoms of the illness do not resolve within 7 days. Recommended doses and frequency of administration should not be exceeded. Avoid concomitant use with other agents containing antihistamines, including medications for cold and cough (see section "Special Warnings and Precautions for Use").

Tablets should be taken orally.

Adults and children aged 16 years and older – 1 tablet 3–4 times daily (with intervals of 4–6 hours between doses).

The maximum daily dose is 4 tablets.

The duration of treatment should be determined individually by a physician.

Special patient groups.

Elderly patients.

Specific studies evaluating the effects of pseudoephedrine or triprolidine in elderly patients have not been conducted. Elderly patients are more susceptible to neurological anticholinergic effects caused by triprolidine, including confusion and paradoxical excitation (see section "Special Warnings and Precautions for Use").

Dosing in renal impairment.

Pseudoephedrine is primarily excreted by the kidneys. Renal impairment increases plasma levels of pseudoephedrine. Pseudoephedrine should not be used in patients with severe renal impairment (see section "Contraindications") and should be used with caution in patients with moderate renal impairment (see section "Special Warnings and Precautions for Use").

Dosing in hepatic impairment.

Triprolidine is primarily eliminated via hepatic metabolism; therefore, dose reduction should be considered in patients with severe liver disease (see section "Special Warnings and Precautions for Use").

Children. The drug is contraindicated in children under 16 years of age.

Overdose.

Overdose may lead to an intensification of the drug's adverse effects.

Symptoms.

Pseudoephedrine overdose may result in symptoms related to stimulation of the central nervous and cardiovascular systems (e.g., excitement, restlessness, hallucinations, arterial hypertension and arrhythmias, palpitations, urinary retention, nausea, vomiting, thirst). In severe cases, psychosis, seizures, coma, and hypertensive crisis may occur.

Serum potassium levels may decrease due to intracellular shift from the extracellular space.

Overdose of triprolidine is likely to cause reactions similar to those described in the section "Adverse Reactions." Additional symptoms may include ataxia, weakness, respiratory depression, dryness of the skin and mucous membranes, hyperpyrexia, tremor, psychosis, seizures, tachycardia, and arrhythmia.

Treatment: symptomatic and supportive therapy.

In acute poisoning, gastric lavage via a tube and administration of activated charcoal (within 3 hours of tablet ingestion) are required. Special attention should be given to restoring proper respiratory gas exchange by ensuring airway patency and instituting assisted or artificial ventilation if necessary. Catheterization of the urinary bladder may be required. Forced acid diuresis or dialysis enhances the elimination of pseudoephedrine. Seizures and associated central nervous system stimulation should be treated with parenteral diazepam.

Adverse Reactions

Adverse effects are classified according to frequency of occurrence:

Very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10,000 to < 1/1000); very rare (< 1/10,000); frequency not known (cannot be estimated from available data).

Pseudoephedrine

Psychiatric disorders

Common: nervousness, insomnia.
Uncommon: agitation, restlessness, tremor.
Rare: hallucinations (especially in children).

Nervous system disorders

Common: dizziness.
Uncommon: headache.

Cardiovascular disorders

Rare: tachycardia, palpitations, increased blood pressure, arrhythmia.
An increase in systolic blood pressure has been observed; however, in therapeutic doses, the effect of pseudoephedrine on blood pressure is not considered clinically significant.

Gastrointestinal disorders

Common: dry mouth, nausea, vomiting.
Uncommon: decreased appetite.

Skin and subcutaneous tissue disorders

Rare: rash, allergic dermatitis, increased sweating.
Various skin allergic reactions, with or without systemic signs such as bronchospasm and angioedema, have been reported following pseudoephedrine use.

Renal and urinary disorders

Uncommon: dysuria, urinary retention.
Urinary retention is mainly observed in patients with urinary outflow obstruction, such as prostatic hyperplasia.

Triprolidine

Psychiatric disorders

Frequency not known: paradoxical excitation (most susceptible are children and elderly patients: increased energy, restlessness, nervousness), confusion (most susceptible are elderly patients), nocturnal delirium, hallucinations (mainly in children).

Nervous system disorders

Very common: sedative effect, drowsiness.
Common: inattention, coordination disturbances, dizziness.
Uncommon: headache.

Cardiovascular disorders

Uncommon: orthostatic hypotension, palpitations, tachycardia, weakness.

Eye disorders

Frequency not known: blurred vision.

Respiratory, thoracic and mediastinal disorders

Frequency not known: thickening of bronchial secretions, nasal congestion.

Gastrointestinal disorders

Common: dryness of mouth, nose, and throat.
Frequency not known: gastrointestinal discomfort including nausea and vomiting, anorexia, diarrhea, constipation, increased appetite, heartburn, weight gain.

Skin and subcutaneous tissue disorders

Frequency not known: rash and urticaria, photosensitivity reactions.

Renal and urinary disorders

Frequency not known: urinary retention, dysuria, polyuria.

Shelf life.
3 years.

Storage conditions.
Store in a place protected from light and moisture at a temperature not exceeding 25°C.
Keep out of reach of children.

Packaging.
4 tablets in a blister, 1 blister in a cardboard package (package No. 4);
10 tablets in a blister, 2 blisters in a cardboard package (package No. 20 (10x2));
10 tablets in a blister, 10 blisters in a cardboard package (package No. 100 (10x10)).

Prescription category.
Prescription-only medicine.

Manufacturer.
Bausch & Lomb (Bafna) Pharmaceuticals Ltd., India.

Manufacturer's address.
147, Madhavaram Red Hills Road, Grantlion, Village Vadakarai, Chennai, Tamil Nadu IN 600052, India.