TAMSULOSINE VIATRIS SANTE LP 0,4 mg Cap LP Fl/30

Tamsulosin hydrochloride......................................................................................................................0,4 mg

For a prolonged-release capsule.

For the full list of excipients, see section Composition.

Lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH).

Dosage

One capsule per day, to be taken after breakfast or the first meal of the day.

No dose adjustment is necessary in cases of renal insufficiency.

No dose adjustment is necessary in patients with mild to moderate hepatic impairment (see section Contraindications).

Paediatric population

There is no justified use of TAMSULOSINE VIATRIS SANTE LP 0,4 mg, prolonged-release capsule in children.

The safety and efficacy of tamsulosine in children under 18 years of age have not been established. The data currently available are described in section Pharmacodynamics.

Method of administration

Oral use

The capsule must be swallowed whole and must not be chewed or crushed, as this interferes with the modified release of the active substance.

Hypersensitivity to tamsulosin hydrochloride, including history of angioedema with tamsulosin, or to any of the excipients.

History of orthostatic hypotension. Severe hepatic impairment.

As with other alpha-1-adrenoceptor antagonists, a fall in blood pressure may occur in some individuals during treatment with tamsulosin 0,4 mg, which in rare cases may lead to syncope. At the first signs of orthostatic hypotension (dizziness, weakness), the patient should sit or lie down until these symptoms have completely disappeared.

Before starting treatment with tamsulosin 0,4 mg, the patient should be examined in order to exclude the presence of other conditions that may cause the same symptoms as benign prostatic hyperplasia. A digital rectal examination and, if necessary, a prostate-specific antigen (PSA) test should be performed before starting treatment and thereafter at regular intervals.

Caution is required in patients with severe renal impairment (creatinine clearance < 10 ml/min) as these patients have not been studied.

Intra-operative floppy iris syndrome (IFIS, a variant of small pupil syndrome) has been observed during cataract surgery in some patients treated or previously treated with tamsulosin hydrochloride.

IFIS may increase the risk of ocular complications during and after the operation.

Interrupting tamsulosin hydrochloride 1 to 2 weeks before cataract surgery may be considered useful, but the benefit of interrupting treatment has not been established. IFIS has also been reported in patients who had discontinued tamsulosin for a longer period before cataract surgery.

Initiating treatment with tamsulosin hydrochloride in patients scheduled for cataract surgery is not recommended. During the preoperative consultation, surgeons and their ophthalmology team should check whether patients who are to undergo cataract surgery are or have been treated with tamsulosin, in order to ensure that appropriate measures will be in place to manage the occurrence of IFIS during surgery.

Tamsulosin hydrochloride should not be combined with potent CYP3A4 inhibitors in poor metabolisers with a CYP2D6 phenotype.

Caution is advised when administering tamsulosin hydrochloride in combination with potent or moderate CYP3A4 inhibitors (see section Interactions).

Interaction studies have only been performed in adults.

No interaction has been observed when tamsulosin hydrochloride was co-administered with atenolol, enalapril or theophylline.

Concomitant administration of cimetidine increases plasma concentrations of tamsulosin, whereas furosemide decreases them. However, as the concentrations remain within the normal range, no dose adjustment is necessary.

During tests in vitro, neither diazepam, propranolol, trichlormethiazide, chlormadinone, amitriptyline, diclofenac, glibenclamide, simvastatin nor warfarin alter the free fraction of tamsulosin in human plasma.

Likewise, tamsulosin does not modify the free fraction of diazepam, propranolol, trichlormethiazide and chlormadinone.

However, diclofenac and warfarin may increase the elimination rate of tamsulosin.

Concomitant administration of tamsulosine hydrochloride with strong CYP3A4 inhibitors may lead to an increase in exposure to tamsulosine hydrochloride. Concomitant administration with ketoconazole (known as a potent CYP3A4 inhibitor) resulted in an increase in the AUC and the Cmax of tamsulosin hydrochloride by a factor of 2,8 and 2,2 respectively. Tamsulosin hydrochloride must not be administered concomitantly with a potent CYP3A4 inhibitor in poor metabolisers with a CYP2D6 phenotype.

Tamsulosine hydrochloride should be used with caution in combination with moderate and potent CYP3A4 inhibitors.

Concomitant administration of tamsulosin hydrochloride with paroxetine, a potent inhibitor of CYP2D6, resulted in an increase in the Cmax and AUC of tamsulosin by a factor of 1,3 and 1,6 respectively, but these increases are not considered clinically relevant.

Concomitant administration with other alpha-1-adrenoceptor antagonists may lead to hypotensive effects.

The use of tamsulosin is not indicated in women.

Ejaculation disorders have been observed in short-term and long-term clinical studies with tamsulosine.

Cases of ejaculation disorders, retrograde ejaculation and anejaculation have been reported in the post-authorisation phase.

No studies have been performed on the effects on the ability to drive vehicles and use machines. However, patients should be aware that dizziness may occur.

* Observed after marketing

During cataract surgery, cases of narrow pupil, known as intraoperative floppy iris syndrome (IFIS), have been associated with tamsulosin treatment during post-marketing surveillance (see also section Warnings and precautions).

Post-marketing experience: in addition to the adverse events mentioned above, atrial fibrillation, arrhythmia, tachycardia and dyspnoea have been reported with the use of tamsulosin. As these spontaneously reported events come from worldwide post-marketing experience, their frequency and the role of tamsulosin in their occurrence cannot be determined.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system: National Agency for the Safety of Medicines and Health Products (ANSM) and the network of Regional Pharmacovigilance Centres - Website: https://signalement.social-sante.gouv.fr/.

Symptoms

An overdose of tamsulosin hydrochloride may potentially cause severe hypotensive effects. Severe hypotensive effects have been observed at various levels of overdose.

Treatment

In case of acute hypotension occurring after an overdose, appropriate cardiovascular measures should be taken. Blood pressure can be restored and heart rate normalised by placing the patient in a supine position. If this is not effective, plasma volume expanders and, if necessary, vasopressors may be used. Renal function should be monitored and general supportive measures should be implemented. Dialysis is unlikely to be useful since tamsulosin is highly protein bound.

Measures such as induced vomiting may be taken to prevent absorption. In the case of large quantities, gastric lavage may be performed and activated charcoal as well as an osmotic laxative, such as sodium sulfate, may be administered.

Pharmacotherapeutic class: alpha-1-adrenoceptor antagonists, ATC code: G04CA02. Medicinal products used exclusively in the treatment of prostate disorders.

Mechanism of action

Tamsulosin binds selectively and competitively to post-synaptic alpha-1-adrenoceptors, particularly the α 1A and α 1D, resulting in relaxation of the smooth muscle of the prostate and urethra.

Pharmacodynamic effects

Tamsulosin 0,4 mg increases maximum urinary flow rate. It improves obstructive syndromes through relaxation of prostatic and urethral smooth muscles, thereby relieving voiding symptoms.

It also improves storage symptoms in which bladder instability plays an important role.

These effects on storage and voiding are maintained during long-term treatment. The need for surgical intervention or catheterisation is significantly delayed.

Alpha-1-adrenoceptor antagonists may cause a decrease in blood pressure through a mechanism of decreased peripheral resistance. In studies with tamsulosin 0,4 mg, no clinically significant decrease in blood pressure was reported.

Paediatric population

A randomised, double-blind, placebo-controlled, dose-finding study was conducted in children with neurogenic bladder. A total of 161 children (aged 2 to 16 years) were randomised and treated with either one of the 3 doses 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 the number of patients who had a decrease in their "detrusor leak point pressure" (DLPP) to a value < 40 cm of water, at two assessments performed on the same day. Secondary endpoints were: the value and percentage change in detrusor leak point pressure from baseline, improvement or stabilisation of hydronephrosis and hydroureter, change in urinary volume measured by catheterisation, and the number of times protective pads were wet at the time of catheterisations, as reported in the catheterisation diary. No statistically significant difference was found between the placebo group and any of the 3 tamsulosin dose groups, either for the primary or the secondary endpoints. No response was observed regardless of the dose used.

Absorption

Tamsulosin hydrochloride is absorbed from the intestinal tract and its bioavailability is almost complete.

Absorption of tamsulosin hydrochloride is reduced by a recent meal but can be made uniform by regular intake of tamsulosin 0,4 mg after the same meal.

The pharmacokinetics of tamsulosin are linear. After administration of a single dose of tamsulosin 0,4 mg at the end of a meal, the peak plasma concentration of tamsulosin is reached approximately 6 hours after intake and, at steady state, which is reached by the 5e day of repeated administration, the Cmax of patients is approximately 2/3 higher than the concentration reached after a single dose. Although this result was observed in elderly patients, an identical result is expected in young patients.

There is considerable inter-individual variation in the plasma concentrations reached, whether after a single dose or repeated doses.

Distribution

In humans, tamsulosin is 99 % bound to plasma proteins. The volume of distribution is low (approximately 0,2 L/kg).

Biotransformation

The first-pass effect of tamsulosin is low, as it is metabolised slowly. The greater part of tamsulosin is found unchanged in plasma. It is metabolised in the liver.

In rats, practically no induction of hepatic microsomal enzymes related to tamsulosin was observed.

The results in vitro suggest that CYP3A4 and also CYP2D6 are involved in metabolism, with possible minor contributions to the metabolism of tamsulosin hydrochloride by other CYP isoenzymes. Inhibition of the CYP3A4 and CYP2D6 enzymes responsible for drug metabolism could result in an increase in exposure to tamsulosin hydrochloride (see sections Warnings and precautions and Interactions).

None of the metabolites obtained is more active than the parent molecule.

Elimination

Tamsulosin and its metabolites are mainly excreted in the urine, with approximately 9 % of the absorbed dose present unchanged.

In patients, after a single dose of tamsulosin 0,4 mg at the end of a meal, on the one hand, and at steady state, on the other hand, elimination half-lives of approximately 10 and 13 hours respectively were measured.

Single-dose and repeated-dose toxicity studies were carried out in mice, rats and dogs. In addition, reproductive toxicity in rats, carcinogenicity in mice and rats, and genotoxicity in vivo and in vitro were examined.

The general toxicity profile, as observed with high doses of tamsulosin, is consistent with the known pharmacological activity of alpha-1-adrenergic receptor antagonists.

Administration of very high doses resulted in an alteration of the ECG in dogs. This response is not considered clinically relevant. Tamsulosin showed no relevant genotoxic properties.

An increased incidence of proliferative changes of the mammary glands in female rats and mice has been reported. These findings, which are probably related to hyperprolactinaemia and occurred only at high doses, are not considered relevant.

2 years.

This medicine does not require any particular storage precautions.

No special requirements for disposal.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

• Indication(s) appearing in the MA at the date of publication of this order (30Plq/1, Fl/30)