Od-tam

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT OD-TAM (OD-TAM)

Composition:

Active substance: tamsulosin / tamsulosine;

1 capsule contains 0.4 mg of tamsulosin hydrochloride;

Excipients:

Granule core: microcrystalline cellulose (PH-101), talc, methacrylic acid copolymer dispersion 30% Eudragit L 30 D 55 (containing polysorbate 80 and sodium lauryl sulfate), triacetin;

Granule coating: methacrylic acid copolymer dispersion 30% Eudragit L 30 D 55 (containing polysorbate 80 and sodium lauryl sulfate), triacetin, talc;

Extra-granular filler: talc, calcium stearate;

Capsule cap: FD & C Blue No. 2 indigocarmine (E 132), iron oxide red (E 172), iron oxide yellow (E 172), titanium dioxide (E 171), gelatin, purified water, sodium lauryl sulfate;

Capsule body: iron oxide red (E 172), iron oxide yellow (E 172), titanium dioxide (E 171), gelatin, purified water, sodium lauryl sulfate;

Printing ink: TEK Print SW-9008 Black (shellac, iron oxide black (E 172)).

Pharmaceutical form. Prolonged-release capsules.

Main physicochemical properties: hard gelatin capsules of size "1 EL", opaque, olive-green / opaque, orange-colored, printed with food-grade black ink with the characters "D" on the cap and "53" on the body, containing pellets ranging from white to almost white in color.

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 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).

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

α1-adrenoceptor antagonists may reduce arterial pressure due to decreased peripheral vascular tone. However, during clinical studies of 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 after food intake. Consistent absorption is achieved when the patient takes tamsulosin at the same time each day after meals. The pharmacokinetics of tamsulosin are linear.

After a single dose of tamsulosin taken after food, peak plasma concentration is reached approximately 6 hours later. Steady-state concentration is achieved by the fifth day of daily dosing. At steady state, Cmax 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 is not subject to 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 is present in unchanged form.

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

After a single dose of tamsulosin 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 in 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 interactions

Interaction studies were 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, whereas with furosemide decreases, tamsulosin plasma concentration; 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 levels of 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. Concomitant use with ketoconazole (a known strong CYP3A4 inhibitor) resulted in increases in 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 with low CYP2D6 metabolism.

Tamsulosin hydrochloride should be used with caution when administered concomitantly 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 times, 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-adrenoblockers, administration of tamsulosin may in individual cases lead to a reduction in blood pressure, which might occasionally result in loss of consciousness. If the first signs of orthostatic hypotension (dizziness, weakness) occur, the patient should assume a sitting or lying position until the aforementioned symptoms subside.

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

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

In some patients who were taking or had taken tamsulosin, intraoperative floppy iris syndrome (IFIS, a variant of the floppy iris syndrome) has been observed during cataract or glaucoma surgery, which may increase the 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.

Patients scheduled for 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.

Tamsulosin hydrochloride should not be administered 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 (see "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 previous history of sulfonamide allergy.

Use during pregnancy or breastfeeding

Tamsulosin 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 impaired 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.

Method of Administration and Dosage

The recommended dose for adults is 1 capsule daily after breakfast or after the first meal of the day. The capsule should be swallowed whole, without breaking or chewing, 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.

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 levels of overdose.

Treatment

In case of a significant drop in blood pressure 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 should be initiated and vasopressor agents administered. Renal function should be monitored, and general supportive therapy 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 case of ingestion of a large amount of the drug, gastric lavage should be performed using activated charcoal and low-osmotic laxatives such as sodium sulfate.

Adverse reactions

*Occurred during the post-marketing period

Cases of intraoperative iris instability of the eye (floppy iris syndrome) during cataract and glaucoma surgery have been reported in patients taking tamsulosin during the post-marketing surveillance 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 these cases were reported spontaneously, the frequency of reporting and the causal relationship with tamsulosin use cannot be reliably established.

Suspected adverse reactions reporting

Reporting of suspected adverse reactions after medicinal product registration is of great importance. It enables ongoing 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 pharmacovigilance information system at the following link: https://aisf.dec.gov.ua.

Shelf life

2 years.

Storage conditions

Store at a temperature not exceeding 25 °C in the original packaging. Keep out of reach of children.

Packaging

10 capsules in a blister; 3 blisters in a cardboard box together with the instructions for medical use.

Prescription status

Prescription only.

Manufacturer

Aurobindo Pharma Limited - Unit VII / Aurobindo Pharma Limited - Unit VII.

Manufacturer's address and location of its business activities

Special Economic Zone, TSIIC, Plot No. S1, Sy. Nos. 411/P, 425/P, 434/P, 435/P and 458/P, Green Industrial Park, Polepally Village, Jedcherla Mandal, Mahabubnagar District, Telangana State, 509302, India / Special Economic Zone, TSIIC, Plot No. S1, Sy. Nos. 411/P, 425/P, 434/P, 435/P and 458/P, Green Industrial Park, Polepally Village, Jedcherla Mandal, Mahabubnagar District, Telangana State, 509302, India.