Tamsin forte

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT TAMSIN FORTE (TAMSIN FORTE)

Composition:

Active substance: tamsulosin hydrochloride;

1 prolonged-release tablet contains 0.4 mg of tamsulosin hydrochloride;

Excipients: hypromellose (hydroxypropylmethylcellulose), microcrystalline cellulose, carbomer, colloidal silicon dioxide anhydrous, iron(III) oxide red (E 172), magnesium stearate.

Pharmaceutical form.

Prolonged-release tablets.

Main physicochemical properties: white, smooth-surfaced, round, biconvex tablets with the engraving "T9SL" on one side and "0.4" on the other side.

Pharmacotherapeutic group.

Agents used in benign prostatic hyperplasia. α1-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, thereby improving urine flow.

Concurrently, obstructive and irritative symptoms associated with benign prostatic hyperplasia are alleviated (difficulty initiating urination, weakened urinary stream, post-void dribbling, sensation of incomplete bladder emptying, frequent nocturnal urges to urinate, urinary urgency).

The ability of α1A-adrenergic blockers to reduce arterial blood 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), both in patients with arterial hypertension and in those with normal baseline AP.

Pharmacokinetics

Absorption. Tamsin Forte is a prolonged-release tablet with controlled release, providing sustained and gradual release of tamsulosin, resulting in exposure with minimal fluctuations over 24 hours.

After oral administration on an empty stomach, 57% of tamsulosin is absorbed in the intestine. The rate and extent of absorption of the prolonged-release tablets are not altered when taken with a low-fat meal. The extent of absorption increases by 64% and 149% (AUC and Cmax, respectively) when administered with a high-fat meal compared to administration on an empty stomach.

Tamsulosin exhibits linear pharmacokinetics.

After a single dose of Tamsin Forte administered on an empty stomach, the Cmax of the active substance in plasma is observed after 6 hours. At steady state, achieved by the fourth day of treatment, peak concentrations occur within 4–6 hours, regardless of food intake. Peak plasma concentration increases from approximately 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 (approximately 0.2 L/kg).

Metabolism. Tamsulosin hydrochloride has a low first-pass effect and is slowly metabolized. The majority of the active substance circulates in the bloodstream unchanged. It is metabolized in the liver. In vitro studies indicate that CYP3A4 and CYP2D6 are involved in its metabolism, while other CYP isoenzymes have minimal effect on tamsulosin. Inhibition of metabolizing enzymes CYP3A4 and CYP2D6 may lead to increased exposure to tamsulosin hydrochloride (see sections "Interaction with other medicinal products and other forms of interaction" and "Special precautions for use"). None of the metabolites are more active than the parent compound.

Elimination. Tamsulosin and its metabolites are primarily excreted via 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 functional disorders of the lower urinary tract due to benign prostatic hyperplasia.

Contraindications.

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

Interaction with other medicinal products and other forms of interaction.

Interaction studies have been performed only in adults.

No drug interactions were observed when tamsulosin hydrochloride was administered concomitantly with atenolol, enalapril, or theophylline. Concomitant administration with cimetidine increases, and with furosemide decreases, the plasma concentration of tamsulosin; however, since these levels remain within the normal range, no special dose adjustment of tamsulosin is required.

In in vitro studies, diazepam, propranolol, trichlormethiazide, chlormadinone, amitriptyline, diclofenac, glibenclamide, 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. Concomitant use with ketoconazole (a known strong CYP3A4 inhibitor) resulted in increases in AUC and Cmax by up to 2.8 and 2.2 times, respectively.

Tamsulosin hydrochloride should not be prescribed in combination with strong CYP3A4 inhibitors in patients who are poor metabolizers of CYP2D6.

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

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

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

Special precautions.

As with other α1-adrenergic blockers, administration of the drug may in individual cases lead to a reduction in arterial pressure, which rarely may result in loss of consciousness. If early signs of orthostatic hypotension (dizziness, weakness) occur, the patient should sit down or lie down until the aforementioned symptoms subside.

Before initiating treatment with Tamsin Forte, a medical examination should be performed to rule out other concomitant conditions that may cause symptoms similar to benign prostatic hyperplasia. Prior to starting treatment, a digital rectal examination of the prostate gland should be carried out, and if necessary, a test to determine the level of prostate-specific antigen (PSA) should be performed before treatment initiation and at regular intervals during treatment.

The drug should be administered with particular caution to patients with severe renal impairment (creatinine clearance <10 mL/min), as clinical studies have not been conducted in such patients.

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

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

Initiation of tamsulosin hydrochloride is not recommended in patients scheduled for cataract or glaucoma surgery. Surgeons and ophthalmologists should be informed whether the patient is currently taking or has previously taken tamsulosin in order to prevent possible complications associated with IFIS.

Tamsulosin hydrochloride should not be administered in combination with strong CYP3A4 inhibitors to patients who are poor metabolizers of CYP2D6.

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

Undissolved tablet residues may occasionally be found in feces.

Allergic reactions to tamsulosin have been reported in patients with a history of allergy to sulfonamides. Caution should be exercised when administering tamsulosin hydrochloride to patients who have previously exhibited allergic reactions to sulfonamides.

Use during pregnancy or breastfeeding.

Tamsin Forte is not indicated for use in women.

Fertility

During both short- and long-term clinical studies of tamsulosin, ejaculation disorders were observed. Cases of ejaculation disorders, retrograde ejaculation, and insufficient ejaculation have been reported in the post-marketing period.

Ability to affect reaction speed when driving or operating machinery.

Studies on the effect of the drug on the ability to drive vehicles or operate machinery have not been conducted. However, patients should be informed about the possible occurrence of dizziness.

Dosage and Administration.

For oral use.

The recommended dose is one tablet daily, regardless of food intake. The tablet should be swallowed whole, without chewing or breaking, as this may interfere with the prolonged release of the active substance.

The duration of treatment is determined individually.

Dose adjustment is not required in patients with renal impairment. Dose adjustment is not required in patients with mild to moderate hepatic impairment (see also section "Contraindications").

Children.

The drug is not indicated for use in children.

Safety and efficacy of tamulosin in children have not been established.

Overdose.

Symptoms.

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

Treatment.

In case of acute drop in blood pressure due to overdose, supportive therapy should be initiated to restore normal cardiovascular function (e.g., the patient should be placed in a supine position). If this measure is ineffective, infusion therapy and administration of vasopressor agents should be considered. Renal function should be monitored, and general supportive treatment provided. Due to the high degree of tamulosin binding to plasma proteins, hemodialysis is unlikely to be effective.

To prevent further absorption of the drug, induced vomiting may be considered. In cases of significant overdose, gastric lavage with activated charcoal and low-osmotic laxatives such as sodium sulfate should be performed.

Adverse reactions.

*- reported during the post-marketing period.

During post-marketing surveillance, cases of intraoperative iris instability of the eye (intraoperative floppy iris syndrome) during cataract and glaucoma surgery have been reported in patients receiving tamsulosin (see section "Dosage and Administration").

Post-marketing experience: in addition to the above-mentioned adverse reactions, spontaneous reports of atrial fibrillation, arrhythmia, tachycardia, and dyspnea have been received. These reports were spontaneous, and therefore the frequency of reporting and the role of tamsulosin in these cases cannot be reliably established.

Shelf life.

3 years.

Storage conditions.

Keep out of reach and sight of children.

Protect from light and moisture.

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

Packaging.

10 tablets per blister pack; 3 blisters per cardboard box.

Prescription status.

Prescription only.

Manufacturer.

Sínton Hispania, S.L./Synthon Hispania, S.L.

Manufacturer's address and place of business.

C/ Castelló, n°1, Sant Boi de Llobregat, Barcelona, 08830, Spain /
C/ Castelló, n°1, Sant Boi de Llobregat, Barcelona, 08830, Spain.