Tamsulostad

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT TAMSULOSTAD (TAMSULOSTAD)

Composition:

Active substance: tamsulosin hydrochloride;

1 capsule contains tamsulosin hydrochloride 0.4 mg;

Excipients: microcrystalline cellulose, methacrylate copolymer (type A), polysorbate 80, sodium lauryl sulfate, triethyl citrate, talc; capsule shell: gelatin, indigocarmine (E 132), titanium dioxide (E 171), iron oxide red (E 172), iron oxide yellow (E 172), iron oxide black (E 172).

Medicinal form. Modified-release hard capsules.

Main physicochemical properties: hard gelatin capsules with an orange body and an olive-colored cap. The capsule is filled with pellets ranging from white to almost white.

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 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 portion of the urethra, resulting in improved urinary flow. At the same time, 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).

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

α1-Adrenoceptor antagonists may reduce arterial blood pressure due to decreased peripheral vascular tone. However, during clinical studies of the drug, no clinically significant reduction in arterial blood pressure was observed.

Pharmacokinetics.

Absorption. Tamsulosin is well absorbed from the gastrointestinal tract, with a bioavailability of nearly 100%. Absorption of tamsulosin is slightly slower following food intake. Consistent absorption is achieved when patients take Tamsulostad at the same time each day after eating. The pharmacokinetics of tamsulosin are linear.

After a single dose of Tamsulostad taken after food, peak plasma concentration of tamsulosin is reached approximately 6 hours later. Steady-state 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 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 is present in unchanged form.

Excretion. Tamsulosin hydrochloride is excreted by the kidneys, with 9% of the dose excreted unchanged. The elimination half-life after a single dose is 10 hours; the terminal half-life is 13 hours.

Clinical Characteristics.

Indications. Treatment of functional disorders of the lower urinary tract in benign prostatic hyperplasia.

Contraindications. Hypersensitivity reactions, including drug-induced angioneurotic Quincke's edema, to tamsulosin hydrochloride or to any other component of the medicinal product; orthostatic hypotension; severe hepatic impairment.

Interaction with other medicinal products and other forms of interaction.

Interaction studies have been conducted only in adults.

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

In vitro studies show that 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 administration of tamsulosin hydrochloride with strong CYP3A4 inhibitors may lead to increased effects of tamsulosin hydrochloride. Concomitant use with ketoconazole (a known potent CYP3A4 inhibitor) resulted in increases in Cmax and AUC by up to 2.2- and 2.8-fold, respectively.

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

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

Tamsulosin hydrochloride should be used with caution in combination with strong and moderate CYP3A4 inhibitors.

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

Special precautions for use

In some patients who were taking or had taken tamsulosin, intraoperative floppy iris syndrome (IFIS), a variant of iris flaccidity syndrome, has been observed during surgical procedures for cataract or glaucoma removal. This may lead to an increased risk of complications during or after such surgery.

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

Patients scheduled for elective cataract or glaucoma surgery should not initiate treatment with tamsulosin hydrochloride. 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.

As with other α1-adrenoblockers, use of Tamsulostad may in individual cases lead to a reduction in blood pressure, which may occasionally result in loss of consciousness. If early signs of orthostatic hypotension (dizziness, weakness) occur, the patient should immediately sit or lie down until symptoms resolve.

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

Tamsulosin hydrochloride should not be co-administered 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 (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 with a prior history of sulfonamide allergy.

Use during pregnancy or breastfeeding

Tamsulostad is indicated for use in males only.

Fertility

During short- and long-term clinical studies of tamsulosin, ejaculation disorders were observed. Cases of ejaculation disorder, 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 warned about the possible occurrence of dizziness.

Dosage and Administration.

The dosage and duration of treatment should be individually adjusted. The recommended dose for adults is 1 capsule per day. Take after breakfast or after the first meal of the day. The capsule should be swallowed whole with a sufficient amount of water, while standing or sitting. Do not chew or break the capsule, as this may interfere with the modified release of the active ingredient.

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

Children. The drug is not intended for use in children.

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

Overdose.

Symptoms.

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

Treatment.

In case of a sharp drop in blood pressure due to overdose, supportive therapy should be administered to restore normal cardiovascular function (e.g., the patient should assume a horizontal position). If this measure is ineffective, intravenous fluid 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 tamulosin, 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.

*- were observed during the post-marketing period.

Cases of intraoperative iris instability (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, cases of atrial fibrillation, arrhythmia, tachycardia, and dyspnea have been reported. These reports were spontaneous, and the frequency of reporting or the role of tamsulosin in these cases cannot be reliably established.

Shelf life. 3 years.

Storage conditions. Store in the original packaging, protected from light, at a temperature not exceeding 25 °C. Keep out of reach of children.

Packaging. 10 capsules in a blister; 3 blisters per cardboard box.

Prescription status. Prescription only.

Manufacturer: STADA Arzneimittel AG, Germany.

Address of the manufacturer’s place of business.
Stadastrasse 2–18, 61118 Bad Vilbel, Germany.