Pinexel Pr 400 Micrograms Prolonged-Release Hard Capsules
SUMMARY OF PRODUCT CHARACTERISTICS
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 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 5I[6 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
For oral use.
One capsule a day after breakfast or the first meal of the day. The capsule is swallowed whole with a glass of water while standing or sitting (not lying down). The capsule should not be broken or pulled apart as this may have an effect on the release of the long-acting active ingredient.
Paediatric Population
The safety and efficacy of tamsulosin in children <18 years have not been established. Currently available data are described in section 5.1.
4.3 Contraindications
Hypersensitivity to tamsulosin hydrochloride, including drug-induced angio-oedema, or to any other component of the product; a history of orthostatic hypotension; severe hepatic insufficiency.
4.4. Special warnings and precautions for use
As with other alpha1 blockers, 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 severely renally impaired patients (creatinine clearance of less than 10 ml/min) should be approached with caution as these patients have not been studied.
Angio-oedema has been reported rarely after the use of tamsulosin. Treatment should be discontinued immediately, the patient should be monitored until the disappearance of the oedema, and tamsulosin should not be readministered.
The ‘Intraoperative Floppy Iris Syndrome’ (IFIS, a variant of small pupil syndrome) has been observed during cataract surgery in some patients on or previously treated with tamsulosin. IFIS may lead to increased procedural complications during the operation. The initiation of therapy with tamsulosin in patients for whom cataract surgery is scheduled is not recommended.
Discontinuing tamsulosin 1 - 2 weeks prior to cataract surgery is anecdotally considered helpful, but the benefit and duration of stopping of theapy prior to cataract surgery has not yet been established.
During pre-operative assessment, cataract surgeons and ophthalmic teams should consider whether patients scheduled for cataract 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.
Concomitant use of phosphodiesterase-5-inhibitors (e.g. sildenafil, tadalafil, vardenafil) and tamsulosin may lead to symptomatic hypotension in some patients. In order to minimise the risk for developing postural hypotension the patient should be stable on the alpha-blocker therapy before initiating use of phospodiesterase-5-inhibitors.
4.5 Interaction with other medicinal products and other forms of interaction
No interactions have been seen when Pinexel PR was given concomitantly with either atenolol, enalapril , nifedipine or theophylline. Concomitant cimetidine brings about a rise in plasma levels of tamsulosin, and furosemide a fall, but as levels remain within the normal range posology need not be changed.
In vitro neither diazepam nor propranolol, trichlormethiazide, chlormadinon, amitryptyline, diclofenac, glibenclamide, simvastatin, and warfarin change the free fraction of tamsulosin in human plasma. Neither does tamsulosin change the free fractions of diazepam, propranolol, trichlormethiazide, and chlormadinon.
No interactions at the level of hepatic metabolism have been seen during in vitro studies with liver microsomal fractions (representative of the cytochrome P450-linked drug metabolising enzyme system), involving amitriptyline, salbutamol, glibenclamide and finasteride. Diclofenac and warfarin, however, may increase the elimination rate of tamsulosin.
There is a theoretical risk of enhanced hypotensive effect when given concurrently with drugs which may reduce blood pressure, including anaesthetic agents and other ^-adrenoceptor antagonists. Concomitant use of phosphodiesterase-5-inhibitors (e.g. sildenafil, tadalafil, vardenafil) and tamsulosin may lead to symptomatic hypotension in some patients (see section 4.4).
4.6 Pregnancy and lactation
Not applicable as Pinexel PR is intended for male patients only.
4.7 Effects on ability to drive and use machines
No data is available on whether Pinexel PR adversely affects the ability to drive or operate machines. However, in this respect patients should be aware of the fact that drowsiness, blurred vision, dizziness and syncope can occur.
4.8 Undesirable effects
The assessment of side effects is based on the following frequencies: Very common (> 1/10)
Common (> 1/100, < 1/10)
Uncommon (> 1/1,000, < 1/100)
Rare (> 1/10,000, < 1/1000)
Very rare (< 1/10, 000)
Not well known (frequency on the basis of the available data, not assessable).
|
Common |
Uncommon |
Rare |
Very rare |
Unknown | |
|
(>1/100, <1/10) |
(>1/1 000, <1/100) |
(>1/10 000, <1/1 000) |
(<1/10 000) | ||
|
Nervous system disorders |
Dizziness |
Headache |
Syncope | ||
|
Cardiac disorders |
Palpitations | ||||
|
Vascular disorders |
Postural hypotension | ||||
|
Respiratory, thoracic and mediastinum-related disorders |
Rhinitis | ||||
|
Gastrointestinal disorders |
Constipation, diarrhoea, nausea, vomiting |
Dry mouth | |||
|
Skin and subcutaneous tissue disorders |
Rash, pruritus, urticaria |
Angio- oedema | |||
|
Reproductive systems and breast disorders |
Abnormal ejaculation |
Priapism | |||
|
General disorders and administration site conditions |
Asthenia |
During cataract 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
Acute overdose with 5 mg tamsulosin hydrochloride has been reported. Acute hypotension (systolic blood pressure 70 mm Hg), vomiting and diarrhoea were observed, which were treated with fluid replacement and the patient could be discharged the same day. 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
5.1. Pharmacodynamic properties
Pharmacotherapeutic group:
ATC Code G04C A02 Alpha1-adrenoceptor antagonist.
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, which bring about relaxation of the smooth muscle of the prostate, whereby tension is reduced.
Pharmacodynamic effects:
Pinexel PR increases maximum urinary flow rate by reducing smooth muscle tension in prostate and urethra and thereby relieving obstruction.
It also improves the complex of irritative and obstructive symptoms in which bladder instability and tension of the smooth muscles of the lower urinary tract play an important role.
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, Cmax 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.
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.
6.6 Special precautions for disposal
No special instructions.
Any unused product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
Wockhardt UK Ltd Ash Road North Wrexham
LL13 9UF UK
8 MARKETING AUTHORISATION NUMBER(S)
PL 29831/0366
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
04/05/2010
10 DATE OF REVISION OF THE TEXT
21/08/2015