Instruction
APPROVED
Ministry of Health of the Republic of Azerbaijan
Chairman of the Expert Council of
Pharmacology and Pharmacopoeia
_____________ E.M. Aghayev
“6” November 2020
Patient Information Leaflet
TAMURIN® 0.4 mg extended-release capsules
TAMURİN®
International nonproprietary name: Tamsulosin
Composition
Active substance: Each capsule contains tamsulosin hydrochloride at an amount of 0.4 mg.
Excipients: HPMC sugar spheres, methacrylic acid copolymer dispersion (Eudragit L100), polyethylene glycol 6000 (PEG 6000), ethylcellulose N50, purified water.
Description
Hard gelatin capsules, no. 2 size. The body of the capsule is orange, the cap is green.
Pharmacotherapeutic group
α1-blocker.
АТC code: G04CA02.
Pharmacological properties
Pharmacodynamics
Mechanism of action
Tamsulosin is a selective and competitive blocker of post-synaptic α1-adrenoreceptors, prevailingly their subtypes designated α1 A and α1 D. It leads to a reduction of tone of smooth muscles of the prostate and prostatic part of the urethra.
Tamsulosin increases the maximum speed of urinary flow.
Administration of this drug reduces obstruction by reducing the tone of the smooth muscles of the prostate and urethra, which leads to alleviation of voiding symptoms.
Tamsulosin also alleviates the filling symptoms in the development of which detrusor overactivity plays an important role.
The effects on symptoms of filling and voiding persist for a long time. The necessity of surgical treatment or catheterization is delayed owing to these effects.
α1-blockers can reduce blood pressure by decreasing the tone of the smooth muscles of peripheral vessels. No reduction in systemic blood pressure of any significance was observed during studies with tamsulosin.
Children
A double-blind, randomized, dose-ranging study was performed in children with neuropathic bladder. A total of 161 children (with an age of 2 to 16 years) were involved and treated with 1 of 3 dose levels of tamsulosin (low [0.001 to 0.002 mg/kg], medium [0.002 to 0.004 mg/kg], and high [0.004 to 0.008 mg/kg]), or placebo. The primary endpoint was number of patients who decreased their detrusor leak point pressure to < 40 cm water based upon two evaluations on the same day. Secondary endpoints were: general and percent change from baseline in detrusor leak point pressure, improvement or stabilization of hydronephrosis and hydroureter and change in urine volumes and number of times wet at time of catheterization as recorded in catheterization diaries. No statistically significant difference was found between the placebo group and any of the 3 tamsulosin dose groups for either the primary or any secondary endpoints. Also, no dose-dependent effect was observed in any group of patients receiving different doses of tamsulosin.
Pharmacokinetics
Absorption
Tamsulosin is well absorbed from the intestinal tract and its bioavailability is almost complete. The absorption of tamsulosin decreases if the product is administered after the meal. The same absorption rate may be achieved via using the product every day at the same time after the standard breakfast. Kinetics of tamsulosin is linear. The maximum concentration in blood plasma is reached 6 hours after a single dose of 0.4 mg. The steady state concentration is reached by day five after multiple dosing of 0.4 mg, when Cmax is about two thirds higher than that reached after a single dose. Although this has been demonstrated only in the elderly, the same result would also be expected in younger patients. There is a significant individual difference in plasma levels of tamsulosin, both after single as well as multiple dosing.
Distribution
Approximately 99% of tamsulosin is bound to plasma proteins and its distribution volume is small (approximately 0.2 l/kg).
Metabolism
Tamsulosin is gradually metabolized in the liver with the formation of a small amount of active metabolites. The majority of tamsulosin is present in plasma in an unchanged form. In studies on rats, it was found that tamsulosin slightly increased the activity of microsomal enzymes of the liver. In vitro studies show that CYP3A4, as well as CYP2D6, which are involved in the metabolism of the drug, can lead to an increase in the concentration of tamsulosin. The metabolites are not as effective as the active substance itself.
Elimination
Tamsulosin and its metabolites are mainly excreted in the urine and approximately 9% of the dose given is released in an unchanged form.
The elimination half-life of tamsulosin is 10 hours (when taken after a meal at a dose of 0.4 mg) and 13 hours after multiple dosing.
Therapeutic indications
Treatment of dysuric disorders in benign prostatic hyperplasia.
Contraindications
Hypersensitivity to any component of the drug.
Orthostatic hypotension (including in the anamnesis).
Severe hepatic insufficiency.
Special warnings and precautions
As with other α1-blockers, a reduction in blood pressure can occur in individual cases during treatment with Tamurin as a result of which, rarely, syncope can occur. At the first signs of orthostatic hypotension (dizziness, weakness), the patient should sit or lie down until the symptoms have disappeared. Withdrawal syndrome does not occur.
The ‘Intraoperative Floppy Iris Syndrome’ (small pupil syndrome) has been observed during cataract or glaucoma surgery in some patients treated with tamsulosin; surgeon must take it into account when preparing the patient for surgery and during surgery.
Before therapy with Tamurin is initiated, the patient should be examined in order to exclude the presence of other conditions, which can cause the same symptoms as benign prostatic hyperplasia. Digital rectal examination and, when necessary, determination of prostate specific antigen (PSA) should be performed before treatment and at regular intervals during treatment.
The treatment of patients with severe renal impairment (CCl < 10 ml/min) should be approached with caution, as these patients have not been studied. The Intraoperative Floppy Iris Syndrome (small pupil syndrome) has been observed during cataract or glaucoma surgery in some patients on or previously treated with tamsulosin hydrochloride, which can lead to complications during or after surgery. The expediency of discontinuing therapy with tamsulosin hydrochloride 1-2 weeks before surgical intervention for cataract or glaucoma has not been proven. Intraoperative Floppy Iris Syndrome has also been reported in patients who had discontinued tamsulosin for a longer period prior to surgery. The initiation of therapy with tamsulosin hydrochloride in patients for whom cataract or glaucoma surgery is scheduled is not recommended. During pre-operative assessment, surgeon and ophthalmologist should take into account that he is taking tamsulosin currently and before. This is necessary in order to prepare for the possible development of Intraoperative Floppy Iris Syndrome.
Interaction with other medicinal products
No interactions have been observed when tamsulosin hydrochloride was given concomitantly with either atenolol, enalapril or theophylline. Concomitant use with cimetidine leads to a slight increase in the concentration of tamsulosin in the blood plasma, and when used with furosemide, a decrease was observed, but this does not require a decrease in the dose of Tamurin, as the concentration of the drug remains in the normal range. In vitro, neither diazepam nor propranolol, trichlormethiazide, chlormadinon, amitriptyline, diclofenac, glibenclamide, simvastatin and warfarin change the free fraction of tamsulosin in human plasma. In turn, neither does tamsulosin change the free fractions of diazepam, propranolol, trichlormethiazide and chlormadinon.
Diclofenac and warfarin may increase the elimination rate of tamsulosin.
Concomitant administration of tamsulosin hydrochloride with strong inhibitors of CYP3A4 may lead to an increase in concentration of tamsulosin.
Concomitant administration with ketoconazole (a strong CYP3A4 inhibitor) resulted in an increase in AUC and Cmax of tamsulosin by 2.8 and 2.2 fold, respectively.
Tamsulosin hydrochloride should not be given in combination with strong inhibitors of CYP3A4 in patients with impaired metabolism of CYP2D6 isoferment. Tamsulosin should be used with caution in combination with strong and moderate inhibitors of CYP3A4 (e.g. erythromycin).
Concomitant administration of tamsulosin hydrochloride with paroxetine, a strong inhibitor of CYP2D6 caused an increase in tamsulosin Cmax and AUC by 1.3 and 1.6 fold, respectively, but these increases are not considered clinically significant.
Concurrent administration of other α1-adrenoceptor antagonists could lead to hypotensive effects.
Pregnancy and lactation
Tamurin is intended for use only in men.
Effects on ability to drive and use machines
No studies on the effects on the ability to drive and use machines have been performed. Patients should be aware of the fact that dizziness can occur during the use of the drug.
Posology and method of administration
Adults over 18 years of age, as well as elderly patients.
One capsule (0.4 mg) daily after breakfast, with water. The capsule is swallowed without chewing, because otherwise the speed of release of the drug would be affected.
Patients with hepatic and renal impairment
No dose adjustment is required in patients with renal failure and mild to moderate hepatic insufficiency.
Side effects
Classification of incidence of side effects provided by the World Health Organization (WHO):
• common (> 1% <10%)
• uncommon (> 0.1% < 1%)
• rare (> 0.01% <0.1%)
• very rare (<0.1%)
• not known (cannot be estimated from the available data)
Cardiovascular system disorders: palpitation, postural hypotension (uncommon).
Eye disorders: visual impairment*, blurred vision* (not known).
Gastrointestinal disorders: constipation, diarrhea, nausea, vomiting (uncommon), dry mouth* (not known).
General disorders: asthenia (uncommon).
Nervous system disorders: dizziness (1.3%) (common), headache (uncommon), syncope (rare).
Reproductive system disorders: ejaculation disorder (including retrograde ejaculation and ejaculation failure) (common), priapism (very rare).
Respiratory, thoracic and mediastinal disorders: rhinitis (uncommon), epistaxis* (not known).
Skin and subcutaneous tissue disorders: rash, pruritus, urticaria (uncommon), angioedema (rare), Stevens-Johnson syndrome (very rare), erythema multiforme*, exfoliative dermatitis* (not known).
* Observed post-marketing.
During cataract or glaucoma surgery Intraoperative Floppy Iris Syndrome (small pupil syndrome) has been recorded in patients receiving tamsulosin.
In addition to the adverse events listed above, during postmarketing use of the drug, atrial fibrillation, arrhythmia, tachycardia and dyspnoea have been reported in patients receiving tamsulosin. Due to the fact that the data are received spontaneously after registration, it is difficult to determine the frequency and establish a causal relationship with tamsulosin intake.
Overdose
There is no data on tamsulosin overdose. However, theoretically, with an overdose, a sudden drop in blood pressure and the development of compensatory tachycardia are possible. In this case, symptomatic treatment is important. Blood pressure can be restored, and heart rate brought back to normal by lying the patient down. If this does not help then volume expanders and, when necessary, vasopressors could be employed. Renal function should be monitored. Dialysis is unlikely to be of help as tamsulosin is very highly bound to plasma proteins.
Gastric lavage can be applied, activated charcoal and an osmotic laxative, such as sodium sulphate, can be administered to prevent subsequent absorption of the medicinal product.
Presentation
0.4 mg prolonged-release capsules
10 capsules in blisters with PVC film and aluminum foil. 3 blisters are packed in a cardboard box with a package leaflet.
Storage conditions
Store below 25°C. Keep out of reach of children.
Shelf life
2 years.
Do not use after expiration date.
Terms of release from pharmacy
The drug is released by prescription.
Marketing authorization holder
PARLA PHARMACEUTICALS LLC
AZ1010, 16E, Kovkab Safaraliyeva str., Baku, Azerbaijan
Tel.: +994123105219.
Manufacturer
Dorsa Pharmaceutical Co., Iran.
4th Golfam, 3rd Golnoush, West Dr. Hesabi Blvd., Aboureyhan Blvd.,
Eshtehard Ind. Town, Eshtehard, Alborz, Iran (primary packaging).
Packed
AZERFARM LTD, 14, Bunyadov str., Bakikhanov UTS, Sabunchu district, Baku City.