Focusin®

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

Composition:

Active substance: tamsulosin;

1 capsule contains tamsulosin hydrochloride 0.4 mg;

Excipients: methacrylic acid copolymer dispersion, microcrystalline cellulose, dibutyl sebacate, polysorbate 80, colloidal hydrated silicon dioxide, calcium stearate;

capsule shell composition: gelatin, iron oxide red (E 172), iron oxide yellow (E 172), titanium dioxide (E 171), iron oxide black (E 172), indigotine (E 132).

Pharmaceutical form. Modified-release hard capsules.

Main physicochemical properties: hard gelatin capsules size № 3 with olive-colored cap and orange-colored body. Contents of the capsule: white or almost white pellets.

Pharmacotherapeutic group. Agents used in benign prostatic hyperplasia. α1-adrenergic receptor antagonists. ATC code G04C A02.

Pharmacological Properties.

Pharmacodynamics.

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

These effects are maintained over long-term treatment and significantly delay or prevent the need for surgical intervention or catheterization.

α1-Adrenoceptor antagonists have the potential to reduce blood pressure by decreasing peripheral vascular resistance. However, during clinical trials of the medicinal product, clinically significant reductions in blood pressure were not observed.

Pharmacokinetics.

Absorption: Tamsulosin is well absorbed from the gastrointestinal tract, with a bioavailability of nearly 100%. Absorption of tamsulosin is slightly slower when taken after food intake. Consistent absorption is achieved when the patient takes the medicinal product at the same time each day after meals. The pharmacokinetics of tamsulosin are linear.

After a single dose administered with food, peak plasma concentration of tamsulosin is reached approximately 6 hours later. Steady-state plasma concentration is achieved by the fifth day of daily dosing. The Cmax at steady state is approximately two-thirds higher than that observed 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).

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 α1-adrenoceptors. The majority of the active substance in the blood remains in unchanged form.

Elimination: Tamsulosin and its metabolites are primarily excreted from the body via urine. Approximately 9% of the administered dose is excreted as unchanged active substance.

After a single dose taken with food and at steady-state plasma concentrations, the elimination half-lives are approximately 10 and 13 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 types of interactions.

Interactions have been studied only in adults.

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

In in vitro studies, diazepam, propranolol, trichlormethiazide, chloromadinone, amitriptyline, diclofenac, glyburide, 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 chloromadinone 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 potent CYP3A4 inhibitor) resulted in increases in AUC and Cmax by up to 2.8- and 2.2-fold, 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 in combination with strong and moderate CYP3A4 inhibitors.

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

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

Special precautions for use.

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

Prior to initiating treatment with the drug, a medical examination should be performed to rule out other concomitant conditions that may cause similar symptoms to benign prostatic hyperplasia. Before starting treatment, a digital rectal examination of the prostate should be performed, and if necessary, a prostate-specific antigen (PSA) test should be conducted prior to 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 with the use of tamsulosin in such patients have not been conducted.

Rare cases of angioneurotic edema have been reported following tamsulosin administration. If angioneurotic edema occurs, the drug should be discontinued immediately and the patient should be monitored until the edema resolves. Re-administration of tamsulosin is not recommended.

In some patients receiving or who have received tamsulosin, intraoperative floppy iris syndrome (IFIS, a variant of the small pupil syndrome) has been observed 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 discontinuation has not yet been definitively established. Cases of floppy iris syndrome have also been reported in patients who had discontinued tamsulosin long before cataract surgery.

Initiation of tamsulosin hydrochloride treatment 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 potential complications associated with IFIS.

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

Tamsulosin hydrochloride should be used with caution in combination with strong and moderate inhibitors of CYP3A4 (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. Caution should be exercised when administering tamsulosin hydrochloride to patients who have previously experienced an allergic reaction to sulfonamides.

Use during pregnancy or breast-feeding.

The drug is not indicated for use in women.

Fertility

During short- and long-term clinical studies of tamsulosin, ejaculation disorders were observed. Cases of ejaculation disorder, retrograde ejaculation, and decreased ejaculation have also 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 or operate machinery have not been conducted. However, patients should be warned about the possibility of experiencing dizziness.

Method of administration and dosage.

The recommended dose for adults is 1 capsule daily, taken after breakfast or after the first meal. The capsule should be swallowed whole, without breaking or chewing, as this would interfere with the modified release of the active component.

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

Children.

The drug is not intended for use in children.

Safety and efficacy of tamsulosin in children under 18 years of age have not been evaluated.

Overdose.

Symptoms.

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

Treatment.

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

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

Adverse reactions.

*- reported during the post-marketing period.

During post-marketing surveillance, cases of intraoperative iris instability (floppy iris syndrome) during cataract and glaucoma surgery have been reported in patients receiving tamsulosin (see section "Special precautions for use").

Post-marketing experience: in addition to the adverse reactions listed above, cases of atrial fibrillation, arrhythmia, tachycardia, and dyspnea have been reported. Since these cases were reported spontaneously, the frequency of reporting and the role of tamsulosin in these cases cannot be reliably established.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after a medicinal product's registration is an important procedure for regulatory authorities. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are requested to report all suspected adverse reactions through the national adverse reaction reporting systems.

Shelf life. 3 years.

Storage conditions. Store at temperatures not exceeding 25 °C. Keep out of reach of children.

Packaging.

No. 90 (10x9): 10 capsules in a blister; 9 blisters in a cardboard box.

No. 90 (15x6): 15 capsules in a blister; 6 blisters in a cardboard box.

Prescription status. Prescription only.

Manufacturer.

Zentiva S.A.

Manufacturer's address and location of business activity.

Bd. Theodor Pallady 50, District 3, Bucharest, 032266, Romania.