Sonizin^® (Capsules) Instructions for Use

Marketing Authorization Holder

Gedeon Richter, Plc. (Hungary)

Manufactured By

Gedeon Richter-Rus, JSC (Russia)

Or

Gedeon Richter Romania, S.A. (Romania)

Quality Control Release

GEDEON RICHTER-RUS, JSC (Russia)

Or

GEDEON RICHTER ROMANIA, S.A. (Romania)

Contact Information

GEDEON RICHTER, PLC. (Hungary)

ATC Code

G04CA02 (Tamsulosin)

Active Substance

Tamsulosin (Rec.INN registered by WHO)

Dosage Form

Sonizin®

Modified-release capsules 0.4 mg: 10 or 30 pcs.

Dosage Form, Packaging, and Composition

Modified-release capsules hard gelatin, size No. 2; cap: opaque, brown in color; body: opaque, brownish-yellow in color; capsule contents – pellets white or almost white in color.

Excipients : capsule contents: calcium stearate, triethyl citrate, talc, methacrylic acid and ethyl acrylate copolymer (1:1), also containing polysorbate 80 and sodium lauryl sulfate, microcrystalline cellulose (E460); hard gelatin capsule: iron oxide red (E172), iron oxide black (E172), iron oxide yellow (E172), titanium dioxide (E171), gelatin.

10 pcs. – blisters (1) – carton packs.
10 pcs. – blisters (3) – carton packs.

Clinical-Pharmacological Group

Drug used for urination disorders associated with benign prostatic hyperplasia. Alpha₁-adrenergic blocker

Pharmacotherapeutic Group

Drugs used in urology; drugs for the treatment of benign prostatic hyperplasia; alpha-adrenergic blockers

Pharmacological Action

Tamsulosin is a specific blocker of postsynaptic α₁-adrenoceptors located in the smooth muscle of the prostate gland, bladder neck, and prostatic part of the urethra.

The blockade of α₁-adrenoceptors by tamsulosin leads to a decrease in the tone of the smooth muscle of the prostate gland, bladder neck, and prostatic part of the urethra and an improvement in urine outflow. Simultaneously, both voiding symptoms and filling symptoms caused by increased smooth muscle tone and detrusor hyperactivity in benign prostatic hyperplasia are reduced, namely – difficult urination (“weak stream”), urinary dribbling, urgent urge to urinate, frequent urination at night and during the day.

The ability of tamsulosin to act on α_1A-adrenoceptors is 20 times greater than its ability to interact with α_1B-adrenoceptors, which are located in the smooth muscles of blood vessels. Due to such high selectivity, the drug does not cause any clinically significant decrease in blood pressure, both in patients with arterial hypertension and in patients with normal baseline blood pressure.

Pharmacokinetics

Absorption

Tamsulosin is well absorbed in the intestine and has almost 100% bioavailability. The absorption of tamsulosin is somewhat slowed down after a meal.

A consistent level of absorption can be achieved if the patient always takes the drug after a regular breakfast. Tamsulosin is characterized by linear kinetics. After a single oral dose of 0.4 mg, its C_max in plasma is reached after 6 hours. After multiple oral doses of 0.4 mg/day, C_ss is reached by day 5, and its value is approximately two-thirds higher than the value of this parameter after a single dose.

Distribution

Plasma protein binding – 99%, V_d is small (about 0.2 l/kg).

Metabolism

Tamsulosin is slowly metabolized in the liver to form less active metabolites.

Most of the tamsulosin is present in the blood plasma in unchanged form.

Experiments have revealed the ability of tamsulosin to slightly induce the activity of liver microsomal enzymes.

In mild and moderate hepatic impairment, no dose adjustment is required.

Excretion

Tamsulosin and its metabolites are mainly excreted by the kidneys, with approximately about 9% of the drug excreted unchanged.

T_1/2 of the drug after a single dose of 0.4 mg after a meal is 10 hours, after multiple doses – 13 hours.

Special patient groups

No dose reduction is required in renal impairment; if the patient has severe renal impairment (creatinine clearance less than 10 ml/min), Tamsulosin should be used with caution.

Indications

• Treatment of dysuria in benign prostatic hyperplasia.

ICD codes

Dosage Regimen

Adults over 18 years of age, as well as elderly patients

Orally, after breakfast, with water, take 1 capsule (0.4 mg) once/day.

The capsule should not be chewed, as this may affect the release rate of the drug.

Do not take a double dose to make up for a missed dose. Resume taking the drug at 1 capsule/day.

The patient should not stop taking the drug without first consulting the attending physician.

Patients with impaired liver and kidney function

In renal impairment, as well as in mild and moderate hepatic impairment, no dose adjustment is required.

Adverse Reactions

* Post-marketing experience.

Cases of intraoperative floppy iris syndrome during cataract and glaucoma surgery in patients taking Tamsulosin have been described.

Post-marketing use of the drug

In addition to the adverse reactions described above, atrial fibrillation, arrhythmia, tachycardia, and dyspnea have been observed with the use of tamsulosin. Since these data were obtained by spontaneous reporting in the post-registration period, determining the frequency and causal relationship of these phenomena with tamsulosin intake is difficult.

Contraindications

• Hypersensitivity to tamsulosin or any other component of the drug;
• Orthostatic hypotension (including history);
• Severe hepatic impairment;
• Children under 18 years of age.

With caution

Severe renal impairment (creatinine clearance less than 10 ml/min).

Use in Pregnancy and Lactation

The drug Sonizin^® is intended for use only in males.

Use in Hepatic Impairment

Contraindication: severe hepatic impairment.

In mild and moderate hepatic impairment, no dose adjustment is required.

Use in Renal Impairment

With caution : severe renal impairment (creatinine clearance less than 10 ml/min).

In renal impairment, no dose adjustment is required.

Pediatric Use

Contraindicated in children and adolescents under 18 years of age.

Geriatric Use

When used in elderly patients, the risk of exacerbation of chronic diseases should be excluded.

Special Precautions

As with the use of other alpha₁-adrenergic blockers, in some cases, a decrease in blood pressure may be observed during treatment with the drug Sonizin^®, which can sometimes lead to fainting.

At the first signs of orthostatic hypotension (dizziness, weakness), the patient should sit or lie down and remain in this position until these symptoms disappear.

Before starting therapy with the drug Sonizin^®, the patient should be examined to exclude the presence of other diseases that may cause the same symptoms as benign prostatic hyperplasia. Before starting treatment and regularly during therapy, a digital rectal examination should be performed and, if required, determination of prostate-specific antigen (PSA).

Treatment with the drug Sonizin^® of patients with severe renal impairment (creatinine clearance <10 ml/min) requires caution, as studies in this category of patients have not been conducted.

Taking the drug Sonizin^® should be discontinued and immediate medical help should be sought if any of the following symptoms of angioedema occur: difficulty breathing with/without swelling of the face, lips, tongue and/or throat; swelling of the face, lips, tongue and/or throat, which may be accompanied by difficulty swallowing.

Taking the drug Sonizin^® should be discontinued and immediate medical help should be sought if any of the following symptoms of severe skin reactions occur, such as severe skin rash, skin redness, blistering, peeling and swelling of the skin, inflammation of the mucous membranes.

In some patients taking or having previously taken Tamsulosin, the development of intraoperative floppy iris syndrome was noted during surgery for cataract and glaucoma, which can lead to complications during surgery or in the postoperative period.

The advisability of discontinuing tamsulosin therapy 1-2 weeks before cataract or glaucoma surgery has not yet been proven. Cases of intraoperative floppy iris syndrome have occurred in patients who discontinued the drug earlier before surgery. It is not recommended to start tamsulosin therapy in patients scheduled for cataract or glaucoma surgery. During the preoperative examination of patients, the surgeon and ophthalmologist should take into account whether the patient is taking or has taken Tamsulosin. This is necessary to prepare for the possibility of developing intraoperative floppy iris syndrome during surgery.

There are reports of cases of prolonged erection and priapism during therapy with alpha₁-adrenergic blockers. If an erection persists for more than 4 hours, immediate medical attention should be sought. If therapy for priapism is not carried out immediately, this can lead to damage to the penile tissues and irreversible loss of potency.

Effect on ability to drive vehicles and operate machinery

The drug Sonizin^® may have a negative effect on the ability to drive a car and operate machinery. Patients should be aware that dizziness may occur when taking the drug.

Overdose

Symptoms: in high doses, Sonizin^® can cause a sharp decrease in blood pressure and an increase in heart rate followed by dizziness.

Treatment symptomatic therapy is necessary. To prevent further absorption of the drug, gastric lavage, intake of activated charcoal or an osmotic laxative, such as sodium sulfate, is advisable. Blood pressure and heart rate may recover when the person assumes a horizontal position. If there is no effect, agents that increase the volume of circulating blood and, if necessary, vasoconstrictors can be used. Kidney function should be monitored. Hemodialysis is unlikely to be effective, since Tamsulosin is tightly bound to plasma proteins.

Drug Interactions

No interaction was found when tamsulosin was used together with atenolol, enalapril, or theophylline.

With simultaneous use of tamsulosin with cimetidine, some increase in the concentration of tamsulosin in the blood plasma was noted, and with furosemide – a decrease in concentration, but this does not require a change in the dose of the drug Sonizin^®, since the concentration of the drug remains within the normal range.

Diazepam, propranolol, trichlormethiazide, chlormadinone, amitriptyline, diclofenac, glibenclamide, simvastatin and warfarin do not change the free fraction of tamsulosin in human plasma under in vitro conditions. In turn, Tamsulosin also does not change the free fractions of diazepam, propranolol, trichlormethiazide and chlormadinone.

Diclofenac and warfarin may increase the elimination rate of tamsulosin.

Concomitant administration of tamsulosin with strong inhibitors of the CYP3A4 isoenzyme may lead to an increase in the concentration of tamsulosin. Concomitant administration with ketoconazole (a strong inhibitor of the CYP3A4 isoenzyme) led to an increase in the AUC and C_max of tamsulosin by 2.8 and 2.2 times, respectively.

Tamsulosin hydrochloride should not be used in combination with strong inhibitors of the CYP3A4 isoenzyme in patients with impaired metabolism of the CYP2D6 isoenzyme. The drug should be used with caution in combination with strong and moderate inhibitors of the CYP3A4 isoenzyme.

Concomitant administration of tamsulosin and paroxetine, a strong CYP2D6 inhibitor, led to an increase in the C_max and AUC of tamsulosin by 1.3 and 1.6 times, respectively, but this increase was considered clinically insignificant.

Sonizin^® should not be taken simultaneously with other α₁-adrenoceptor antagonists, as this may cause a decrease in blood pressure.

Storage Conditions

The drug should be stored out of the reach of children, in the original packaging, at a temperature not exceeding 30°C (86°F).

Shelf Life

Shelf life – 3 years.

Dispensing Status

Dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.