Tamsulosin retard, 0.4 mg 30 pcs

Pharmacotherapeutic group:

an alpha1-adrenoblocker.

ATX code: G04CA02.

Pharmacological properties:

Pharmacodynamics

Tamsulosin is a specific blocker of postsynaptic alpha1-adrenoreceptors located in the smooth muscle of the prostate, bladder neck and prostatic urethra.

Blockade of alpha1-adrenoreceptors by tamsulosin leads to decrease of tone of the smooth muscles of the prostate, bladder neck and prostatic part of the urethra and improves outflow of urine. Simultaneously both symptoms of emptying and symptoms of filling caused by increased tone of smooth muscles and detrusor hyperactivity in benign prostatic hyperplasia (BPH) are reduced.

The ability of tamsulosin to affect alpha1A subtype of adrenoreceptors is 20 times greater than its ability to interact with alpha1B subtype of adrenoreceptors located in vascular smooth muscle.

Owing to its high selectivity, tamsulosin does not cause clinically significant reductions in systemic arterial blood pressure (BP) in both patients with arterial hypertension and patients with normal BP.

Pharmacokinetics

Absorption

Tamsulosin is well absorbed in the intestine and has almost 100% bioavailability. Absorption of tamsulosin slows down slightly after meals. The same level of absorption can be achieved if the patient takes the drug after the usual breakfast each time. Tamsulosin is characterized by linear kinetics. After a single oral dose of 0.4 mg of the drug, its maximum plasma concentration (Cmax) is reached after 6 hours. After multiple oral doses of 0.4 mg per day, the equilibrium concentration (Csс) is reached by day 5, and its value is approximately 2/3 that of a single dose.

Distribution

The binding to plasma proteins is 99%, the volume of distribution is small (about 0.2 L/kg).

Metabolism

Tamsulosin is slowly metabolized in the liver to form less active metabolites. Most of tamsulosin is present in plasma in unchanged form.

In the experiment the ability of tamsulosin to slightly induce the activity of microsomal liver enzymes was revealed. In mild to moderate hepatic insufficiency there is no need to adjust the dosing regimen.

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

The elimination half-life (T½) of the drug is 10 hours with a single dose of 0.4 mg after a meal, and 13 hours with multiple doses. There is no need to decrease the dose in renal failure, but in patients with severe renal insufficiency (creatinine clearance (CK) less than 10 ml/min) tamsulosin administration should be used with caution.

Indications

Treatment of dysuric disorders in benign prostatic hyperplasia.

Active ingredient

Composition

1 tablet contains:

the active ingredient:

Tamsulosin hydrochloride 0.4 mg;

excipients:

hypromellose (hydroxypropyl methylcellulose) 41.25 mg,

silica colloidal dioxide (aerosil) 0.625 mg,

p> microcrystalline cellulose 82.1 mg,

magnesium stearate 0.625 mg;

coating excipients:

Opadray II (series 85) 3 mg [polyvinyl alcohol, partially hydrolyzed, macrogol-3350, talc, titanium dioxide, iron oxide yellow dye, iron oxide red dye, iron oxide black dye].

How to take, the dosage

After breakfast, 1 film-coated sustained release tablet (0.4 mg) is taken orally with water once daily.

The tablet should not be chewed because this may affect the rate of release of the drug.

Interaction

When tamsulosin was administered together with atenololol, enalapril or nifedipine no interactions were found.

When tamsulosin is used concomitantly with cimetidine, a slight increase in plasma tamsulosin concentration has been observed and a decrease in concentration with furosemide, but this does not require changing the dose of Tamsulosin retard, because the drug concentration remains within the normal range.

Diazepam, propranololol, trichloromethiazide, chlormadinone, amitriptyline, diclofenac, glibenclamide, simvastatin and warfarin do not alter the free plasma fraction of tamsulosin in vitro. In turn, tamsulosin also does not alter the free fractions of diazepam, propranolol, trichloromethiazide and chlormadinone.

In in vitro studies, no interaction at the level of hepatic metabolism was found with amitriptyline, salbutamol, glibenclamide and finasteride. Diclofenac and warfarin may increase the excretion rate of tamsulosin.

The concomitant use of tamsulosin with strong CYP3A4 isoenzyme inhibitors may lead to increased tamsulosin concentrations. Concomitant use with ketoconazole (strong CYP3A4 isoenzyme inhibitor) led to the increase of area under pharmacokinetic curve “concentration-time” (AUC) and maximum concentration (Cmax) of tamsulosin by 2.8 and 2.2 times respectively.

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

The concomitant administration of tamsulosin and paroxetine, a strong CYP2D6 isoenzyme inhibitor, resulted in a 1.3-fold and 1.6-fold increase in Cmax and AUC of tamsulosin respectively, but this increase was not considered clinically significant.

The concomitant administration of other alpha1-adrenoreceptor antagonists may lead to a decrease in BP.

Special Instructions

As with other alpha1-adrenoblockers, treatment with Tamsulosin Retard may occasionally produce a decrease in BP, which may 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 the signs disappear.

In surgical interventions for cataract the drug may cause iris intraoperative instability syndrome (narrow pupil syndrome), which should be taken into account by the surgeon during the preoperative preparation of the patient and during the operation. The feasibility of cancelling tamsulosin therapy 1-2 weeks prior to cataract or glaucoma surgery has not yet been proven.

In cases of intraoperative iris instability have occurred in patients who discontinued the drug earlier before surgery. It is not recommended to start tamsulosin therapy in patients who are scheduled for cataract or glaucoma surgery.

There have been reports of cases of prolonged erections and priapism during therapy with alpha1-adrenoblockers. If an erection persists for more than 4 hours, immediate medical attention should be sought. If therapy of priapism was not carried out immediately, it may lead to penile tissue damage and permanent loss of potency.

Before starting therapy with Tamsulosin retard, the patient should be examined to rule out the presence of other diseases that may cause the same symptoms as BPH. A finger rectal examination and, if required, a prostate specific antigen determination should be performed before starting treatment and regularly during therapy.

Impact on driving and operating machinery

Perhaps caution should be exercised when driving motor vehicles and engaging in potentially hazardous activities requiring increased concentration and speed of psychomotor reactions due to the possible development of dizziness.

Contraindications

Hypersensitivity to tamsulosin or any other component of the drug,
orthostatic hypotension (including history), severe hepatic insufficiency, children under 18 years of age.

With caution

Chronic renal insufficiency (creatinine clearance (CK) below 10 ml/min).

Arterial hypotension.

Side effects

The incidence of adverse reactions is presented according to the WHO classification: very common (≥1/10 cases), common (≥1/100 and <1/10 cases), infrequent (≥1/1000 and <1/100 cases), rare (≥1/10000 and <1/1000 cases) and very rare (<1/10000 cases).

Cardiovascular system disorders:

Infrequent – sensation of palpitations, orthostatic hypotension.

Gastrointestinal tract disorders:

infrequent – constipation, diarrhea, nausea, vomiting.

Nervous system disorders:

often – dizziness;

infrequently – headache;

rarely – fainting.

Periodic system disorders:

infrequent – disorders of ejaculation;

very rare – priapism.

Respiratory, chest and mediastinum disorders:

infrequent – rhinitis.

Skin and subcutaneous tissue disorders

infrequent – rash, itching, urticaria;

rare – angioedema;

very rare – Stevens-Johnson syndrome;

frequency unknown – erythema multiforme exudative, exfoliative dermatitis.

Other:

infrequent – asthenia;

incidence unknown – nasal bleeding.

In cases of intraoperative iris instability (narrow pupil syndrome) during cataract and glaucoma surgery in patients taking tamsulosin have been described.

In addition to the side effects described above, atrial fibrillation, arrhythmias, tachycardia, and dyspnea have been observed with tamsulosin. Because the data were obtained by spontaneous post-registration reporting, determining the frequency and causality of these events with tamsulosin administration is difficult.

Overdose

There have been no reports of acute tamsulosin overdose.

However, theoretically, in case of overdose it is possible to develop an acute decrease in blood pressure (BP) and compensatory tachycardia, in which case symptomatic therapy is necessary. BP and heart rate may recover when the person takes a horizontal position.

If there is no effect, agents increasing circulating blood volume and, if necessary, vasoconstrictors may be used. Renal function should be monitored.

It is unlikely that dialysis will be effective because tamsulosin is strongly bound to plasma proteins.

In order to prevent further absorption of the drug, gastric lavage, administration of activated charcoal, or an osmotic laxative such as sodium sulfate are appropriate.

Pregnancy use

Tamsulosin retard is for use in males only.

Similarities