Urimac

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT URIMAC

Composition:

Active substance: tamsulosin hydrochloride;

1 capsule contains tamsulosin hydrochloride 0.4 mg;

Excipients: polysorbate 80, triacetin, methacrylic acid copolymer dispersion, sodium lauryl sulfate, microcrystalline cellulose, calcium stearate, gelatin capsule: gelatin, indigocarmine (E 132), black iron oxide (E 172), red iron oxide (E 172), yellow iron oxide (E 172), titanium dioxide (E 171), sodium lauryl sulfate.

Pharmaceutical form. Prolonged-release hard capsules.

Main physicochemical properties: hard gelatin capsules No. 2 with an opaque brown-green cap and an opaque orange body, marked with: "CL 23" on the cap and "0.4" on the body, containing white to almost white free-flowing spherical granules.

Pharmacotherapeutic group.

Agents used in urology. Agents used in benign prostatic hyperplasia. Alpha1-adrenergic receptor antagonists.

ATC code: G04CA02.

Pharmacological Properties

Pharmacodynamics

Tamsulosin hydrochloride 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 reduces the tone of the smooth muscle in the prostate, bladder neck, and prostatic urethra, thereby improving urinary flow. Simultaneously, symptoms of obstruction and irritation 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).

Therapeutic effect typically develops within 2 weeks after initiation of treatment. These effects are maintained over long-term therapy and significantly reduce the need for surgical intervention or catheterization.

α1-Adrenoceptor antagonists can lower arterial blood pressure by reducing peripheral vascular resistance. However, during clinical trials, tamsulosin hydrochloride did not show clinically significant reductions in blood pressure.

Pharmacokinetics

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

After a single oral dose of tamsulosin hydrochloride taken after food, peak plasma concentration of tamsulosin is reached in approximately 6 hours. Steady-state plasma concentration is achieved by day 5 of daily dosing. At steady state, maximum concentration 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 remains in unchanged form.

Elimination. Tamsulosin and its metabolites are primarily excreted via urine. Approximately 9% of the administered dose is excreted unchanged.

After a single dose of tamsulosin hydrochloride taken after food, and at steady-state plasma concentrations, 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 forms of interaction.

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

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. Combined use with ketoconazole (a known potent CYP3A4 inhibitor) resulted in increases in maximum concentration (Cmax) and area under the concentration-time curve (AUC) by up to 2.2 and 2.8 times, 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 times, respectively, but this is not considered clinically significant.

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 in combination with strong and moderate CYP3A4 inhibitors.

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

Special precautions for use.

As with other α1-adrenoblockers, administration of the drug may in individual cases lead to a reduction in arterial pressure, which may sometimes result in loss of consciousness. If the first signs of orthostatic hypotension (dizziness, weakness) occur, the patient should immediately lie down until the aforementioned symptoms disappear.

Before initiating treatment with the drug, a medical examination should be performed to identify other concomitant diseases that may cause similar symptoms to benign prostatic hyperplasia. Prior to starting therapy, a digital rectal examination of the prostate gland should be conducted. If necessary, a test to determine the level of prostate-specific antigen (PSA) should also be performed 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 tamoxifen hydrochloride have not been conducted in such patients.

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

In some patients taking tamoxifen, intraoperative floppy iris syndrome (IFIS, a variant of intraoperative miosis) has been observed during surgical procedures for cataract removal and glaucoma, which may lead to increased complications during such surgery.

Generally, it is recommended to discontinue tamoxifen treatment 1–2 weeks before cataract or glaucoma surgery. However, the optimal timing and necessity of discontinuation have not yet been definitively established.

Cases of floppy iris syndrome have also been reported in patients who had discontinued tamoxifen long before cataract surgery.

Patients scheduled for elective cataract or glaucoma surgery should not initiate treatment with tamoxifen hydrochloride. Ophthalmic surgeons should be informed whether the patient is currently taking (or has previously taken) tamoxifen to prevent possible complications associated with IFIS.

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

Tamoxifen should be used with caution in combination with strong and moderate inhibitors of CYP3A4.

Undissolved tablet residues may occasionally be observed in feces.

Cases of allergic reactions to tamoxifen have been reported in patients with a history of allergy to sulfonamides. Caution should be exercised when administering tamoxifen to patients with a previous history of sulfonamide allergy.

Use during pregnancy or breastfeeding.

The drug is not intended for use in women.

Fertility.

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

Ability to affect reaction rate while driving or operating machinery.

The effect of the drug on the ability to drive or operate machinery has not been studied. However, patients should be warned about the possible occurrence of dizziness and fainting.

Dosage and Administration.

The recommended dose for adults is 1 capsule daily, taken after breakfast; the capsule should be swallowed whole, without chewing, as chewing would interfere with the modified release of the active ingredient, and taken with milk or water (approximately 150 ml) while standing or sitting.

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 moderate to severe hepatic impairment (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 established.

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 a sharp drop in blood pressure due to overdose, supportive therapy should be administered to restore normal cardiovascular function. To normalize blood pressure and heart rate, the patient should be placed in a horizontal position. If this measure is ineffective, plasma expanders should be used, and, if necessary, vasoconstrictor agents. Kidney function should be monitored and supportive therapy 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 help. In cases of significant overdose, gastric lavage should be performed, along with administration of activated charcoal and an osmotic laxative, such as sodium sulfate.

Side effects.

From the central nervous system: dizziness, headache, fainting.

From the cardiovascular system: palpitations, postural hypotension.

From the respiratory system: rhinitis, epistaxis.

From the gastrointestinal tract: constipation, diarrhea, nausea, vomiting, dry mouth.

From the skin: rash, urticaria, pruritus, angioneurotic edema (Quincke's edema), Stevens-Johnson syndrome, erythema multiforme, exfoliative dermatitis, photosensitivity reaction.

From the genitourinary system: priapism; ejaculation disorders, including retrograde ejaculation and ejaculatory insufficiency.

From the visual system: blurred vision, visual disturbances.

General disorders: asthenia.

Cases of intraoperative iris flaccidity (floppy iris syndrome) have been reported during cataract and glaucoma surgery in patients who had been taking tamsulosin for a prolonged period (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. Since the worldwide post-marketing experience is the source of the above spontaneous reports, the reporting frequency and the role of tamsulosin in these cases cannot be reliably established.

Shelf life. 2 years.

Storage conditions.

Store at a temperature not exceeding 30 °C in the original packaging.

Keep out of reach and sight of children.

Packaging.

10 capsules in a blister pack, 3 blisters in a cardboard box.

Prescription status. Prescription only.

Manufacturer.

MACLEODS PHARMACEUTICALS LIMITED.

Manufacturer's address and location of business activity.

Village Theda, P.O. Lodhiamaira, Tehsil Baddi, District Solan, Himachal Pradesh, 174101, India.