Pinexel PR 400 micrograms Prolonged-Release Hard Capsules – Summary of Product Characteristics (SmPC) for healthcare professionals

1 NAME OF THE MEDICINAL PRODUCT

Pinexel PR 400 micrograms Prolonged-Release Hard Capsules

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each capsule contains tamsulosin hydrochloride 400 microgram, equivalent to 367 microgram tamsulosin.

Also contains the excipient sunset yellow (E110) (see section 4.4).

For the full list of the excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Prolonged-release capsule, hard

Pinexel PR Capsules consist of a light green opaque cap and light yellow opaque body containing white to off white pellets, imprinted with ^W

₅₁₆ on the cap with black ink.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

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

4.2 Posology and method of administration

Posology

One capsule daily, to be taken after the same meal each day. The capsule should be swallowed whole and should not be crunched or chewed as this will interfere with the prolonged release of the active substance.

No dose adjustment is warranted in renal impairment.

No dose adjustment is warranted in patients with mild to moderate hepatic insuffiency (see also 4.3 Contraindications).

Paediatric Population

There is no relevant indication for use of Pinexel PR Capsules in children, The safety and efficacy of tamsulosin in children <18 years have not been established. Currently available data are described in section 5.1.

Method of administration

For oral use

4.3 Contraindications

Hypersensitivity to tamsulosin hydrochloride, including drug-induced angioedema or to any of the excipients listed in section 6.1; a history of orthostatic hypotension; severe hepatic insufficiency.

4.4 Special warnings and precautions for use

As with other α1-adrenocepto antagonists, a reduction in blood pressure can occur in individual cases during treatment with Pinexel PR, 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.

Before therapy with Pinexel PR 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 afterwards.

The treatment of patients with severe renal impairment (creatinine clearance of less than 10 ml/min) should be approached with caution as these patients have not been studied.

The ‘Intraoperative Floppy Iris Syndrome’ (IFIS, a variant of small pupil syndrome) has been observed during cataract and glaucoma surgery in some patients on or previously treated with tamsulosin hydrochloride. IFIS may increase the risk of eye complications during and after the

operation.Discontinuing tamsulosin hydrochloride 1 – 2 weeks prior to cataract and glaucoma surgery is anecdotally considered helpful, but the benefit of treatment discontinuation has not yet been established. IFIS has also been reported in patients who had discontinued tamsulosin for a longer period prior to the 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, surgeons and ophthalmic teams should consider whether patients scheduled for cataract or glaucoma surgery are being or have been treated with tamsulosin in order to ensure that appropriate measures will be in place to manage the IFIS during surgery.

Tamsulosin hydrochloride should not be given in combination with strong inhibitors of CYP3A4 in patients with poor metaboliser CYP2D6 phenotype.

Tamsulosin hydrochloride should be used with caution in combination with strong and moderate inhibitors of CYP3A4 (see section 4.5).

This medicine contains less than 1 mmol sodium (23 mg) per capsule, that is to say essentially ‘sodium-free’.

4.5 Interaction with other medicinal products and other forms of interaction

Interaction studies have only been performed in adults.

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4.6 Fertility, Pregnancy and lactation

Pinexel PR is not indicated for use in women.

Ejaculation disorders have been observed in short and long term clinical studies with tamsulosin. Events of ejaculation disorder, retrograde ejaculation and ejaculation failure have been reported in the post authorisation phase.

4.7 Effects on ability to drive and use machines

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

4.8 Undesirable effects

n

,

*observed post-marketing.

During cataract and glaucoma surgery a small pupil situation, known as Intraoperative Floppy Iris Syndrome (IFIS), has been associated with therapy of tamsulosin during post-marketing surveillance (see also section 4.4)

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 Yellow Card Scheme at www.mhra.gov.uk/yellowcard

4.9 Overdose

Symptoms:

Treatment:

In case of acute hypotension occurring after overdosage cardiovascular support should be given. 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 and general supportive measures applied. Dialysis is unlikely to be of help as tamsulosin is very highly bound to plasma proteins.

Measures, such as emesis, can be taken to impede absorption. When large quantities are involved, gastric lavage can be applied and activated charcoal and an osmotic laxative, such as sodium sulphate, can be administered

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Alpha1-adrenoceptor antagonist, ATC code: G04C A02

Preparations for the exclusive treatment of prostatic disease.

Mechanism of action

Tamsulosin binds selectively and competitively to postsynaptic alpha1-receptors, in particular to the subtype alpha1A and alpha1D. It brings about relaxation of prostatic and urethral smooth muscle.

Pharmacodynamic effects

Pinexel PR increases maximum urinary flow rate. It relieves obstruction by relaxing smooth muscle in prostate and urethra thereby improving voiding symptoms.

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

These effects on storage and voiding symptoms are maintained during long-term therapy. The need for surgery or catheterisation is significantly delayed.

Alpha1-blockers can reduce blood pressure by lowering peripheral resistance. No reduction in blood pressure of any clinical significance was observed during studies with Pinexel PR.

Paediatric Population

A double-blind, randomized, placebo-controlled, dose ranging study was performed in children with neuropathic bladder. A total of 161 children (with an age of 2 to 16 years) were randomized and treated at 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 (LPP) to <40 cm H2O based upon two evaluations on the same day. Secondary endpoints were: Actual and percent change from baseline in detrusor leak point pressure, improvement or stabilization of hydronephrosis and hydroureter and change in urine volumes obtained by catheterisation and number of times wet at time of catheterisation as recorded in catheterisation 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. No dose response was observed for any dose level.

5.2 Pharmacokinetic properties

Absorption:

Tamsulosin is absorbed from the intestine and is almost completely bioavailable.

Absorption of tamsulosin is reduced by a recent meal.

Uniformity of absorption can be promoted by the patient always taking Pinexel PR after the same meal each day.

Tamsulosin shows linear kinetics.

After a single dose of Pinexel PR in the fed state, plasma levels of tamsulosin peak at around 6 hours and, in the steady state, which is reached by day 5 of multiple dosing, C_max in patients is about two thirds higher than that reached after a single dose. Although this was seen in elderly patients, the same finding would also be expected in young ones.

There is a considerable inter-patient variation in plasma levels both after single and multiple dosing.

Distribution:

In man, tamsulosin is about 99% bound to plasma proteins and volume of distribution is small (about 0.2 l/kg).

Biotransformation:

Tamsulosin has a low first pass effect, being metabolised slowly. Most tamsulosin is present in plasma in the form of unchanged drug. It is metabolised in the liver.

In rats, hardly any induction of microsomal liver enzymes was seen to be caused by tamsulosin.

In vitro results suggest that CYP3A4 and also CYP2D6 are involved in metabolism, with possible minor contributions to tamsulosin hydrochloride metabolism by other CYP isozymes. Inhibition of CYP3A4 and CYP2D6 drug metabolizing enzymes may lead to increased exposure to tamsulosin hydrochloride (see section 4.4 and 4.5).

No dose adjustment is warranted in hepatic insufficiency.

None of the metabolites are more active than the original compound.

Elimination:

Tamsulosin and its metabolites are mainly excreted in the urine with about 9% of a dose being present in the form of unchanged drug.

After a single dose of Pinexel PR in the fed state, and in the steady state in patients, elimination half-lives of about 10 and 13 hours respectively have been measured.

The presence of renal impairment does not warrant lowering the dose.

5.3 Preclinical safety data

Single and repeat dose toxicity studies were performed in mice, rats and dogs. In addition reproduction toxicity studies were performed in rats, carcinogenicity in mice and rats and in vivo and in vitro genotoxicity were examined. The general toxicity profile as seen with high doses of tamsulosin is consistent with the known pharmacological actions of the alpha-adrenergic blocking agents. At very high dose levels the ECG was altered in dogs. This response is considered to be not clinically relevant. Tamsulosin showed no relevant genotoxic properties.

Increased incidences of proliferative changes of mammary glands of female rats and mice have been reported. These findings which are probably mediated by hyperprolactinaemia and only occurred at high dose levels are regarded as irrelevant.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Capsule contents:

Microcrystalline cellulose Methacrylic acid–ethyl acrylate copolymer (1:1) dispersion 30 per cent Talc

Purified water

Magnesium stearate

Triethyl citrate

Capsule shell contents:

Hard gelatin

Sodium laurilsulfate

Quinoline yellow E104

Titanium dioxide E171

Brilliant blue E133

Black imprinting ink (TekPrintTM SW-9008): Shellac

Black iron oxide E172

6.2 Incompatibilities

None known.

6.3 Shelf life

3 years.

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

Blister strips (PVC/PE/PVDC base, aluminium lid) containing 10 capsules contained in a cardboard box. Pack sizes of 30 capsules.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements.

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

7 MARKETING AUTHORISATION HOLDER

Austin McNeil Ltd.

772 Fulham Road,

London, England,

SW6 5SJ

8 MARKETING AUTHORISATION NUMBER(S)

PL 53797/0024

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

29/04/2025

10 DATE OF REVISION OF THE TEXT

29/04/2025