Omllos®

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

Composition:

Active substance: tamsulosin hydrochloride;

1 capsule contains 0.4 mg of tamsulosin hydrochloride;

Excipients:

Capsule contents: microcrystalline cellulose, methacrylic acid copolymer dispersion, polysorbate 80, sodium lauryl sulfate, triethyl citrate, talc;

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

Dosage form. Modified-release hard capsules.

Main physicochemical properties: hard gelatin capsules with an orange-colored body and an olive-colored cap. The capsule contents are granules of white to almost white color.

Pharmacotherapeutic group. Medicinal products 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 urethra, resulting in improved urinary flow. Concurrently, symptoms of obstruction and irritation associated with benign prostatic hyperplasia are reduced (difficulty initiating urination, weakened urinary stream, post-void dribbling, sensation of incomplete bladder emptying, frequent urges to urinate, nocturia, urgency).

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

α1-Adrenoceptor antagonists have the potential to lower blood pressure by reducing peripheral vascular resistance. However, during clinical trials with tamsulosin, 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 when taken after food intake. Consistent absorption is achieved when patients take tamsulosin modified-release capsules at the same time each day relative to food intake. The pharmacokinetics of tamsulosin are linear.

After a single oral dose of tamsulosin modified-release capsules taken after food, maximum plasma concentration (Cmax) is reached at approximately 6 hours. Steady-state plasma concentration is achieved by day 5 of daily dosing. At steady state, 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).

Metabolism

Tamsulosin hydrochloride does not undergo significant first-pass metabolism 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 the urine. Approximately 9% of the administered dose is excreted unchanged.

After a single oral dose of tamsulosin modified-release capsules taken after food, and at steady-state plasma concentrations, the elimination half-life is 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 of the medicinal product; history of orthostatic hypotension; severe hepatic impairment.

Interaction with other medicinal products and other forms of interaction.

Interaction studies have been performed only in adults.

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

Concomitant administration with cimetidine increases, while with furosemide decreases, plasma concentration of tamsulosin; however, since these levels remain within normal limits, 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. Co-administration with ketoconazole (a known strong CYP3A4 inhibitor) resulted in an increase in the area under the concentration-time curve (AUC) and Cmax by up to 2.8 and 2.2 times, 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 an increase in Cmax and AUC by up to 1.3 and 1.6 times, respectively, but this is not clinically significant.

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

Special precautions.

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

Prior to initiating tamsulosin therapy, a medical examination should be performed to identify other concomitant conditions that may cause symptoms similar to benign prostatic hyperplasia. Before starting treatment, a digital rectal examination of the prostate gland should be carried out, and if necessary, a test to determine the level of prostate-specific antigen (PSA) should be performed before treatment initiation and at regular intervals during therapy.

The drug should be administered with particular caution in patients with severe renal impairment (creatinine clearance <10 mL/min), as clinical studies with tamsulosin have not been conducted in such patients.

In some patients who were taking or had previously taken tamsulosin, intraoperative floppy iris syndrome (IFIS, a variant of intraoperative miosis) has been observed during cataract and glaucoma surgery, which may lead to an increased risk of complications during or after the procedure.

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

Initiation of tamsulosin hydrochloride therapy 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 to prevent potential complications associated with IFIS.

Tamsulosin hydrochloride should not be administered 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 (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 allergic reactions to sulfonamides.

Use during pregnancy or breastfeeding.

Tamsulosin is not indicated for use in women.

Fertility.

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

Dosage and Administration

The recommended dose for adults is 1 capsule daily, taken after breakfast or after the first meal of the day. The capsule should be swallowed whole and not crushed, chewed, or broken, as this would interfere with the modified release of the active ingredient.

Dose adjustment is not required in patients with renal impairment. Dose adjustment is also 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 reported at various overdose levels.

Treatment

In case of acute hypotension due to overdose, supportive therapy should be administered 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 vasopressors 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 beneficial.

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 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. Since these cases were reported spontaneously, the frequency of reporting and the role of tamsulosin in these events cannot be reliably determined.

Reporting of adverse reactions after drug registration is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmacy 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: http://aisf.dec.gov.ua.

Shelf life. 3 years.

Do not use after the expiry date stated on the packaging.

Storage conditions.

This medicinal product does not require special storage temperature conditions.

Keep out of reach and sight of children.

Packaging.

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

Prescription status.

Prescription only.

Manufacturer.

ALKALOID AD Skopje.

ALKALOID AD Skopje.

Manufacturer's address and place of business.

Boulevard Aleksandar Makedonski 12, Skopje, 1000, Republic of North Macedonia.

Boulevard Aleksandar Makedonski 12, Skopje, 1000, Republic of North Macedonia.