Tanez eras®

INSTRUCTIONS for medical use of the medicinal product Tanyz Eras® (Tanyz Eras®)

Composition:

Active ingredient: tamsulosin hydrochloride;

1 prolonged-release tablet contains tamsulosin hydrochloride 0.4 mg;

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

Pharmaceutical form. Prolonged-release tablets.

Main physicochemical properties: round, white, scored tablets with "T9SL" engraved on one side and "0.4" on the other.

Pharmacotherapeutic group. Drugs used in benign prostatic hyperplasia. Alpha-adrenoreceptor antagonists.

ATC code G04C A02.

Pharmacological properties.

Pharmacodynamics.

Mechanism of action

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.

Pharmacodynamic effects

Tamsulosin increases the maximum urinary flow rate. Concurrently, symptoms of obstruction and irritation associated with benign prostatic hyperplasia are reduced (difficulty initiating urination, weakened urinary stream, dribbling after urination, sensation of incomplete bladder emptying, frequent urination, nocturia, urinary urgency).

The drug also improves storage symptoms, in which bladder instability plays an important role. This effect on storage and voiding symptoms is maintained during long-term therapy. The need for surgical intervention or catheterization is significantly delayed.

The ability of α1A-adrenergic blockers to reduce blood pressure is related to a decrease in 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 patients with normal initial AP.

Pharmacokinetics.

Absorption

Tamsulosin hydrochloride, administered as extended-release tablets, is absorbed in the intestine. Approximately 57% of the dose taken on an empty stomach is absorbed.

The rate and extent of absorption of tamsulosin administered as extended-release tablets are not altered by food intake with low fat content.

Tamsulosin exhibits linear pharmacokinetics.

After single-dose administration on an empty stomach, maximum plasma concentration of the active substance is observed approximately 6 hours later. At steady state, achieved by the 4th day of drug administration, peak concentration occurs 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.

Due to the extended-release formulation, the trough plasma concentration of tamsulosin reaches approximately 40% of the maximum concentration, independent of food intake. There is considerable inter-patient variability in plasma tamsulosin levels following both single and multiple dosing.

Distribution

Plasma protein binding is approximately 99%. The volume of distribution is low (approximately 0.2 L/kg).

Biotransformation

Tamsulosin hydrochloride has a low first-pass effect and is slowly metabolized. The majority of tamsulosin in plasma remains unchanged. It is metabolized in the liver.

In rats, no induction of hepatic microsomal enzymes related to tamsulosin administration was observed.

In vitro results indicate that CYP3A4 and CYP2D6 are involved in metabolism; other CYP isoenzymes have minimal effects on tamsulosin. Inhibition of CYP3A4 and CYP2D6 enzymes, which metabolize medicinal products, 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 by the kidneys. Approximately 4–6% of the dose is excreted unchanged.

The elimination half-life of tamsulosin is approximately 19 hours after single dose administration and 15 hours at steady state.

Clinical characteristics.

Indications.

Treatment of functional disorders of the lower urinary tract due to benign prostatic hyperplasia.

Contraindications.

• Hypersensitivity to tamsulosin hydrochloride (including angioedema caused by the drug) 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 were conducted only in adults.

No drug interactions were observed when tamsulosin was administered concomitantly with atenolol, enalapril, nifedipine, or theophylline. Concomitant administration with cimetidine increases, while with furosemide decreases, the plasma concentration of tamsulosin; however, since these levels remain within normal limits, 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 from plasma.

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

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

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

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

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

Special precautions for use

As with other α1-adrenoblockers, administration of tamsulosin may in individual cases lead to a decrease in blood pressure, which may occasionally result in loss of consciousness. If the first signs of orthostatic hypotension (dizziness, weakness) occur, the patient should sit down or assume a horizontal position until the aforementioned symptoms disappear.

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

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

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

Patients scheduled for elective cataract or glaucoma surgery should not initiate treatment with tamsulosin hydrochloride. To prevent potential complications associated with IFIS, surgeons and ophthalmologists should be informed whether the patient is currently taking or has previously taken tamsulosin.

Tamsulosin hydrochloride should not be co-administered with strong inhibitors of CYP3A4 in 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").

Undissolved tablet residues may occasionally be observed in the 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 experienced an allergic reaction to sulfonamides.

Use during pregnancy or breastfeeding

Taniz Eras® is not intended for use in women.

Fertility

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

Effect on ability to drive and operate 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 possible occurrence of dizziness.

Dosage and Administration

Dosage

The recommended dose is 1 tablet daily, independent of food intake. The duration of treatment should be determined individually.

Dose adjustment is not required in patients with renal impairment.

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

Administration

Oral use.

The tablet should be swallowed whole, without breaking or chewing, as this may interfere with the prolonged and controlled release of the active ingredient.

Children

This medicinal product is not intended for use in children.

The safety and efficacy of tamsulosin in children 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 acute hypotension 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, intravenous fluid therapy and vasopressor agents should be administered. Renal function should be monitored, and general supportive treatment 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 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.

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

Post-marketing experience.

In addition to the adverse reactions listed above, cases of atrial fibrillation, arrhythmia, tachycardia, and dyspnea have been reported. These cases were reported spontaneously, and therefore the frequency of reporting and the role of tamsulosin in their occurrence cannot be reliably determined.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after medicinal product authorization is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy through the Automated Information System for Pharmacovigilance at the following link: https://aisf.dec.gov.ua.

Shelf life. 3 years.

Storage conditions.

Keep in the original packaging to protect from light.

Keep out of reach of children.

Packaging.

10 tablets per blister, 3 or 9 blisters per cardboard box.

Prescription category. Prescription only.

Manufacturer.

KRKA, d.d., Novo mesto, Slovenia.

TAD Pharma GmbH, Germany.

Manufacturer's address and place of business.

Šmarješka cesta 6, 8501 Novo mesto, Slovenia.

Heinz-Lohmann-Strasse 5, 27472 Cuxhaven, Germany.