Alpha m

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT AlFA M

Composition:

Active substance: tamsulosin;

1 tablet contains tamsulosin hydrochloride 0.4 mg;

Excipients: sodium alginate, anhydrous citric acid, hypromellose, colloidal anhydrous silicon dioxide, magnesium stearate, hydroxypropylcellulose, polyethylene glycol 8000, iron oxide yellow pigment (E 172).

Pharmaceutical form. Film-coated modified-release tablets.

Main physicochemical properties: yellowish-brown, round, biconvex, film-coated tablets, engraved with «TA» above «0.4» on one side and engraved with «ARO» on the other side.

Pharmacotherapeutic group.

Agents used in benign prostatic hyperplasia. Alpha1-adrenoreceptor antagonists. ATC code G04C A02.

Pharmacological Properties

Pharmacodynamics

Tamsulosin selectively and competitively blocks postsynaptic α1-adrenoceptors, particularly α1A and α1D subtypes located in the smooth muscle of the prostate gland, bladder neck, and prostatic urethra. This leads to reduced smooth muscle tone in the prostate gland, bladder neck, and prostatic urethra, resulting in improved urinary flow.

Simultaneously, obstructive and irritative symptoms associated with benign prostatic hyperplasia are reduced (difficulty initiating micturition, weakened urinary stream, post-micturition dribbling, sensation of incomplete bladder emptying, frequent urges to urinate, nocturia, urinary urgency).

The ability of α1A-adrenoceptor blockers to reduce arterial pressure is related to decreased peripheral resistance. Tamsulosin at a daily dose of 0.4 mg does not cause clinically significant reduction in systemic arterial pressure (AP) in either patients with arterial hypertension or those with normal baseline AP.

Pharmacokinetics

Absorption. Alpha M is a prolonged-release tablet with controlled release based on a gel matrix system. This formulation ensures sustained and gradual release of tamsulosin, providing exposure with minimal fluctuations over 24 hours. After oral administration, 57% of tamsulosin is absorbed in the intestine. The rate and extent of absorption are not affected by food intake.

Tamsulosin exhibits linear pharmacokinetics. After single-dose administration on an empty stomach, maximum plasma concentration of the active substance is reached within 6 hours. At steady state, achieved by the fourth day of treatment, peak plasma concentration occurs within 4–6 hours regardless of food intake. Peak plasma concentration increases from 6 ng/mL after the first dose to 11 ng/mL at steady state.

As a result of prolonged release, the trough plasma concentration of tamsulosin amounts to 40% of the maximum concentration, independent of food intake.

Distribution. Plasma protein binding is 99%. The volume of distribution is low, up to 0.2 L/kg.

Metabolism. Tamsulosin hydrochloride does not undergo a significant first-pass effect and is slowly metabolized in the liver, forming pharmacologically active metabolites that retain high selectivity for α1A-adrenoceptors. The majority of the active substance in the blood is present in unchanged form.

Elimination. Tamsulosin hydrochloride is excreted by the kidneys, with 4–6% of the dose excreted unchanged. The elimination half-life of tamsulosin after single-dose administration and at steady state is 19 and 15 hours, respectively.

Clinical characteristics.

Indications.

Treatment of symptoms of the lower urinary tract in benign prostatic hyperplasia.

Contraindications.

Hypersensitivity reactions to tamsulosin hydrochloride or to any of the excipients, including drug-induced angioneurotic edema; history of orthostatic hypotension; severe hepatic impairment.

Interaction with other medicinal products and other forms of interaction.

Interaction studies have been conducted only in adults.

No drug interaction was observed when tamsulosin hydrochloride was administered concomitantly with atenolol, enalapril, or theophylline. Concomitant administration with cimetidine increases, while with furosemide decreases, plasma concentration of tamsulosin; however, since these levels remain within the normal range, dose adjustment of tamsulosin is not required.

In in vitro studies, diazepam, propranolol, trichlormethiazide, chlormadinone, amitriptyline, diclofenac, glyburide, simvastatin, and warfarin do not affect the free fraction of tamsulosin in human plasma. Similarly, tamsulosin does not alter the levels of free fractions of diazepam, propranolol, trichlormethiazide, and chlormadinone in human plasma. However, diclofenac and warfarin may increase the elimination rate of tamsulosin.

Concomitant administration of tamsulosin hydrochloride with strong CYP3A4 inhibitors may lead to increased effects of tamsulosin hydrochloride. Co-administration with ketoconazole (a known strong CYP3A4 inhibitor) resulted in increases in Cmax and AUC up to 2.2 and 2.8 times, respectively.

Concomitant use of tamsulosin hydrochloride and paroxetine (a strong CYP2D6 inhibitor) led to increases in Cmax and AUC by up to 1.3 and 1.6 times, respectively, but this is not considered clinically significant.

Tamsulosin hydrochloride should not be prescribed in combination with strong CYP3A4 inhibitors in patients with poor CYP2D6 metabolism.

Tamsulosin hydrochloride should be used with caution when co-administered with strong and moderate CYP3A4 inhibitors.

Concomitant use with other α1-adrenoblockers may enhance the hypotensive effect.

Special precautions for use.

As with other α1-adrenoblockers, administration of the drug Alfam (Alfa M) may in individual cases lead to a reduction in arterial pressure, which may occasionally result in loss of consciousness. If the first signs of orthostatic hypotension (dizziness, weakness) occur, the patient should immediately assume a horizontal position until the aforementioned symptoms disappear.

Before initiating treatment with this medicinal product, a medical examination should be performed to identify other concomitant diseases that may cause symptoms similar to those of benign prostatic hyperplasia. Prior to starting treatment, a digital rectal examination of the prostate gland should be performed, and, if necessary, a test to determine the level of prostate-specific antigen (PSA) should be conducted before treatment initiation and at regular intervals during treatment.

The drug should be administered with particular caution in patients with severe renal impairment (creatinine clearance <10 mL/min), as there are no data available on the use of the drug in this patient group.

In some patients receiving or who have previously received tamsulosin, the intraoperative floppy iris syndrome (IFIS, a variant of the floppy iris syndrome) has been reported during cataract or glaucoma surgery, which may lead to an increased risk of complications during or after such procedures.

Generally, it is recommended to discontinue tamsulosin treatment 1–2 weeks prior to cataract or glaucoma surgery; however, the benefit of such discontinuation has not yet been definitively established. Cases of IFIS have also been reported in patients who discontinued tamsulosin long before cataract surgery.

Initiation of tamsulosin hydrochloride therapy is not recommended in patients scheduled for cataract or glaucoma surgery. Ophthalmic surgeons should be informed whether the patient is currently taking or has previously taken tamsulosin to prevent potential complications associated with IFIS.

Tamsulosin hydrochloride should not be used in combination with strong CYP3A4 inhibitors (e.g., ketoconazole) in patients who are poor metabolizers of CYP2D6.

Tamsulosin hydrochloride should be used with caution in combination with strong (e.g., ketoconazole) and moderate CYP3A4 inhibitors (e.g., erythromycin) (see section "Interaction with other medicinal products and other forms of interaction").

Cases of allergic reactions to tamsulosin have been reported in patients with a history of allergy to sulfonamides. Occasionally, undissolved tablet remnants may be found in the feces. Caution should be exercised when administering tamsulosin hydrochloride to patients with a history of sulfonamide allergy.

Use during pregnancy or breastfeeding.

Alfam (Alfa M) is not indicated for use in women.

Fertility.
During short- and long-term clinical studies of tamsulosin, ejaculation disorders were observed. In the post-marketing period, cases of ejaculation disorders, retrograde ejaculation, and impaired ejaculation have been reported.

Ability to influence reaction rate when driving or operating machinery.

No studies on the effect of the drug on the ability to drive vehicles or operate machinery have been conducted. However, patients should be warned about the possibility of developing dizziness.

Method of Administration and Dosage

The recommended dose for adults is 1 tablet daily, taken after breakfast or after the first meal of the day. The tablet should be swallowed whole with milk or water; it must not be chewed or crushed, as this would interfere with the prolonged and controlled release of the active ingredient. The duration of treatment is determined individually.

Renal impairment does not require dose adjustment.

Patients with mild to moderate hepatic impairment also do not require dose reduction (see also "Contraindications").

Children

The drug is not intended for use in children.

The safety and efficacy of tamsulosin in children under 18 years of age have not been established.

Overdose

Symptoms

Overdose with tamsulosin hydrochloride may potentially cause severe hypotensive effects. Severe hypotension has been reported at various levels of overdose.

Treatment

In case of a significant drop in blood pressure due to overdose, supportive therapy should be initiated to restore normal cardiovascular function (e.g., placing the patient in a supine position). If this measure is ineffective, intravenous fluid therapy and vasopressor agents should be administered. Renal function should be monitored, and general supportive therapy provided. Due to the high degree of plasma protein binding of tamsulosin, hemodialysis is unlikely to be effective.

To prevent further absorption of the drug, induced vomiting may be considered. In cases of ingestion of a large amount of the drug, gastric lavage should be performed, followed by administration of activated charcoal and low-osmotic laxatives such as sodium sulfate.

Adverse reactions.

Nervous system disorders: dizziness, headache, fainting.

Eye disorders: blurred vision*, visual disturbances*.

Cardiac disorders: palpitations.

Vascular disorders: postural hypotension.

Respiratory, thoracic and mediastinal disorders: rhinitis, epistaxis*.

Gastrointestinal disorders: constipation, diarrhoea, nausea, vomiting, dry mouth*.

Skin and subcutaneous tissue disorders: rash, urticaria, pruritus, angioneurotic oedema, Stevens-Johnson syndrome, erythema multiforme*, exfoliative dermatitis*.

Reproductive system and breast disorders: ejaculation disorders, including retrograde ejaculation and ejaculation failure, priapism.

General disorders: asthenia.

*- reported during the post-marketing period.

In addition to the above-mentioned adverse reactions, there have been spontaneous reports of atrial fibrillation, arrhythmia, tachycardia, and dyspnoea during the post-marketing period; however, the frequency of reporting and the role of tamsulosin in these cases cannot be reliably established.

Cases of intraoperative iris instability (floppy iris syndrome) during cataract and glaucoma surgery have been reported in patients receiving long-term tamsulosin treatment (see section "Special precautions").

Reporting of suspected adverse reactions after medicine authorization is important. It allows continuous monitoring of the benefit-risk balance of the medicine. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, are encouraged to 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.

Keep out of the reach of children and store at a temperature not exceeding 25 °C.

Packaging. 10 tablets per blister, 3 or 6 blisters per cardboard box.

Prescription status. Prescription only.

Manufacturer.

Apothex Inc. /

Apotex Inc.

Manufacturer's address and place of business.

150 Signet Drive, Toronto, Ontario, Canada, M9L 1T9 /

150 Signet Drive, Toronto, Ontario, Canada, M9L 1T9.