Flosin

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

Composition:

Active substance: tamsulosin hydrochloride;

1 capsule contains tamsulosin hydrochloride 0.400 mg;

Excipients:

Granule core: microcrystalline cellulose, methacrylate copolymer (type A) dispersion 30% (containing polysorbate 80 and sodium lauryl sulfate), triethyl citrate, talc;

Granule coating: methacrylate copolymer (type A) dispersion 30% (containing polysorbate 80 and sodium lauryl sulfate), triethyl citrate, talc;

Capsule (body composition): iron oxide red (E 172), titanium dioxide (E 171), iron oxide yellow (E 172), gelatin;

Capsule (cap composition): indigocarmine – FD&C Blue No. 2 (E 132), iron oxide black (E 172), titanium dioxide (E 171), iron oxide yellow (E 172), gelatin.

Pharmaceutical form.

Modified-release hard capsules.

Main physicochemical properties: hard gelatin capsule with an orange-colored body and olive-colored cap; the capsule is filled with white or almost white granules.

Pharmacotherapeutic group.

Agents used in the treatment of benign prostatic hyperplasia. α1-adrenoreceptor antagonists. ATC code G04C A02.

Pharmacological properties.

Pharmacodynamics.

Mechanism of action

Tamsulosin selectively and competitively binds to postsynaptic α1A-adrenoceptors, particularly adrenoceptors of the α1A and α1D subtypes. This leads to reduced tone of the smooth muscle of the prostate gland and urethra.

Pharmacodynamic effects

Tamsulosin increases the maximum urinary flow rate. By relaxing the smooth muscles of the prostate gland and urethra, it reduces obstruction of the urinary tract and thereby facilitates micturition.

It also improves the reservoir function, which is often impaired due to bladder instability.

These effects on reservoir function and micturition are maintained during long-term treatment. Thus, tamsulosin significantly reduces the need for surgical intervention or catheterization.

α1-adrenoceptor antagonists may reduce blood pressure by decreasing peripheral vascular resistance. However, clinically significant reductions in blood pressure have not been observed in studies with tamsulosin.

Pharmacokinetics.

Absorption.

Tamsulosin is absorbed in the intestine and is almost completely bioavailable. When tamsulosin is administered immediately after food intake, its absorption is reduced. To ensure consistent absorption, tamsulosin should be taken at the same time each day relative to food intake. Tamsulosin exhibits linear kinetics.

After a single dose administered with food, maximum plasma concentration is reached after approximately 6 hours. At steady state, which is achieved by the 5th day of treatment, the Cmax is approximately two-thirds higher than after a single dose.

Distribution.

In men, tamsulosin is approximately 99% bound to plasma proteins. The volume of distribution is low (approximately 0.2 L/kg).

Biotransformation.

During first-pass metabolism in the liver, tamsulosin is slowly metabolized. In plasma, tamsulosin is present mainly as unchanged active substance. Tamsulosin is metabolized in the liver.

In rats, tamsulosin caused almost no induction of hepatic microsomal enzymes.

None of the metabolites of tamsulosin has higher activity than the parent compound.

Elimination.

Tamsulosin and its metabolites are primarily excreted in urine, with approximately 9% of the administered dose excreted as unchanged active substance. After a single dose administered with food, the elimination half-life is approximately 10 hours; after reaching steady state, it is approximately 13 hours.

Clinical characteristics.

Indications.

Treatment of functional disorders of the lower urinary tract in benign prostatic hyperplasia (BPH).

Contraindications.

Hypersensitivity to the active substance, including drug-induced angioedema, or to any of the excipients of the medicinal product; history of orthostatic hypotension; severe hepatic impairment.

Interaction with other medicinal products and other forms of interactions.

Children

Studies on the interaction of tamsulosin with other medicinal products have been conducted only in adults.

No drug interactions were observed when tamsulosin hydrochloride was administered concomitantly with atenolol, enalapril, or theophylline.

Concomitant administration with cimetidine increases, while 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 free fractions of diazepam, propranolol, trichlormethiazide, and chlormadinone in human plasma. However, diclofenac and warfarin may increase the elimination rate of tamsulosin.

Concomitant use with strong CYP3A4 inhibitors may lead to an increased effect of tamsulosin hydrochloride. When co-administered with ketoconazole (a known strong CYP3A4 inhibitor), AUC and Cmax values of tamsulosin hydrochloride increase by factors of 2.8 and 2.2, respectively.

Tamsulosin hydrochloride should not be used in combination with strong CYP3A4 inhibitors in patients with a phenotype characterized by low CYP2D6 metabolic activity.

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

When administered concomitantly with paroxetine, a strong CYP2D6 inhibitor, Cmax and AUC values of tamsulosin increase by 1.3 and 1.6 times, respectively; however, this increase is not considered clinically significant.

Concomitant use of tamsulosin with other α1-adrenergic blockers may result in a hypotensive effect.

Special precautions for use

Like other α1-adrenoceptor antagonists, tamsulosin may in some cases cause a reduction in blood pressure, which may occasionally lead to loss of consciousness. If early signs of orthostatic hypotension (dizziness, weakness) occur, the patient should sit or lie down until symptoms resolve.

Before initiating tamsulosin treatment, patients should undergo evaluation to exclude any other diseases presenting with symptoms similar to those of benign prostatic hyperplasia. Digital rectal examination of the prostate and, if necessary, measurement of prostate-specific antigen (PSA) levels should be performed prior to treatment and at regular intervals during treatment.

Particular caution is required when treating patients with severe renal impairment (creatinine clearance < 10 mL/min), as studies in such patients have not been conducted.

During cataract and glaucoma surgery, intraoperative floppy iris syndrome (IFIS), a variant of the small pupil syndrome, has been observed in some patients receiving or previously treated with tamsulosin. IFIS may increase procedural complications during and after surgery.

In some cases, tamsulosin should be discontinued 1–2 weeks prior to cataract and glaucoma surgery; however, the benefit of discontinuing tamsulosin treatment has not yet been fully established. IFIS has also been reported in patients who discontinued tamsulosin long before cataract surgery.

Initiating tamsulosin therapy in patients scheduled for cataract and glaucoma surgery is not recommended.

To avoid IFIS that may occur during cataract and glaucoma surgery, surgeons and ophthalmologists should determine during preoperative assessment whether the patient has been treated with tamsulosin before or is currently receiving this medicinal product.

Tamsulosin should not be used in combination with strong CYP3A4 inhibitors in patients with a phenotype characterized by poor CYP2D6 metabolism.

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

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 experienced allergic reactions to sulfonamides.

Excipients

This medicinal product contains less than 1 mmol (23 mg)/capsule of sodium, i.e. essentially "sodium-free".

Use during pregnancy or breast-feeding

Tamsulosin is not indicated for use in women.

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

Effect on ability to drive and use machines

Studies on the effect of tamsulosin on the ability to drive or operate machinery have not been conducted. However, patients should be aware that dizziness may occur during treatment with this medicinal product.

Method of Administration and Dosage

One capsule daily, taken after breakfast or the first meal of the day.

The capsule should be swallowed whole and must not be crushed or chewed, as this would interfere with the modified release of the active substance.

No dose adjustment is required in patients with impaired renal function. Dose adjustment is not necessary in patients with mild to moderate hepatic impairment (see also section "Contraindications").

Children

There are no relevant indications for the use of tamsulosin in children.

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 observed at various overdose levels.

Treatment

In case of acute drop in blood pressure due to overdose, supportive therapy should be initiated to restore normal cardiovascular function. To normalize blood pressure and heart rate, the patient should be placed in a supine position. If this measure is ineffective, plasma expanders should be administered and, if necessary, vasoconstrictive agents. Renal function should be monitored and supportive treatment provided. Hemodialysis is unlikely to be effective, as tamsulosin is highly bound to plasma proteins.

Measures aimed at preventing absorption, such as inducing vomiting, may be helpful. In cases of significant overdose, gastric lavage should be performed, along with administration of activated charcoal and an osmotic laxative, such as sodium sulfate.

Adverse reactions.

*- reported during the post-marketing period.

Cases of intraoperative floppy iris syndrome (IFIS) during cataract and glaucoma surgery have been described in patients receiving tamsulosin (see section "Special precautions").

Post-marketing experience. In addition to the above-mentioned adverse reactions, cases of atrial fibrillation, arrhythmia, tachycardia, and dyspnea have been reported with the use of tamsulosin. Since the worldwide post-marketing experience is the source of the above-mentioned spontaneous reports, the frequency of reporting and the role of tamsulosin in these cases cannot be reliably determined.

Reporting of suspected adverse reactions

It is important to report suspected adverse reactions after marketing authorization of a medicinal product. This allows ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions.

Shelf life. 3 years.

Do not use the medicinal product after the expiry date.

Storage conditions.

No special storage conditions required. Store in the original packaging.

Packaging.

10 capsules in a blister; 3 or 10 blisters in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

Menarini-Von Heyden GmbH

Menarini-Von Heyden GmbH

Manufacturer's address and place of business.

Leipziger Strasse 7-13, 01097 Dresden, Germany.

Leipziger Strasse 7-13, 01097 Dresden, Germany.

Marketing Authorization Holder.

Menarini International Operations Luxembourg S.A.

Menarini International Operations Luxembourg S.A.

Address of the Marketing Authorization Holder and place of business.

1, Avenue de la Gare, L-1611 Luxembourg, Luxembourg.

1, Avenue de la Gare, L-1611 Luxembourg, Luxembourg.