Stronazon 400 Micrograms Mr Capsules
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Stronazon 400 micrograms MR Capsules
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
One capsule contains 0.4 mg of tamsulosin hydrochloride.
For the full list of excipients, see section 6.1
3 PHARMACEUTICAL FORM
Modified-release capsule, hard
Hard gelatin capsules with orange coloured body and olive coloured cap. The capsule is filled with white to off-white pellets.
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 a day after breakfast or the first meal of the day. Method of administration
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.
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 the active substance or to any of the excipients listed in section 6.1. History of orthostatic hypotension.
Severe hepatic insufficiency.
4.4 Special warnings and precautions for use
As with other a 1-adrenoceptors antagonists, a reduction in blood pressure can occur in individual cases during treatment with tamsulosin, 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.
The patient should be examined before commencement of therapy with tamsulosin to exclude the presence of other conditions that can produce similar symptoms to those of benign prostatic hyperplasia. The prostate should be examined via the rectum and, if necessary, the prostate specific antigen (PSA) count determined prior to commencement of treatment and again later at regular intervals.
The treatment of patients with severe renal impairment (creatinine clearance of < 10 ml/min) should be approached with caution as these patients have not been studied.
Angioedema has been rarely reported after the use of tamsulosin hydrochloride. Treatment should be discontinued immediately, the patient should be monitored until disappearance of the oedema, and tamsulosin hydrochloride should not be re-administered.
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 hydrochloride. IFIS may increase the risk of eye complications during and after the operation.
Discontinuing tamsulosin hydrochloride 1-2 weeks prior to cataract 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 cataract surgery.
The initiation of therapy with tamsulosin hydrochloride in patients for whom cataract surgery is scheduled is not recommended. 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.
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).
4.5 Interaction with other medicinal products and other forms of interaction
Interaction studies have only been performed in adults.
No interactions have been observed when tamsulosin hydrochloride was given concomitantly with either atenolol, enalapril or theophylline. Concomitant cimetidine brings about a rise in plasma levels of tamsulosin, whereas furosemide a fall, but as levels remain within the normal range posology need not be adjusted.
In vitro, neither diazepam nor propranolol, trichlormethiazide, chlormadinon, amitriptyline, 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.
Tamsulosin has not been found to interact at the level of hepatic metabolism with amitriptyline, salbutamol, glibenclamide or finasteride during in vitro studies with liver microsomal fractions (representing the cytochrome P450-linked metabolizing enzyme system).
Diclofenac and warfarin may increase the elimination rate of tamsulosin.
Concomitant administration of tamsulosin hydrochloride with strong inhibitors of CYP3A4 may lead to increased exposure to tamsulosin hydrochloride. Concomitant administration with ketoconazole (a known strong CYP3A4 inhibitor) resulted in an increase in AUC and Cmax of tamsulosin hydrochloride by a factor of 2.8 and 2.2, respectively.
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.
Concomitant administration of tamsulosin hydrochloride with paroxetine, a strong inhibitor of CYP2D6, resulted in a Cmax and AUC of tamsulosin that
had increased by a factor of 1.3 and 1.6, respectively, but these increases are not considered clinically relevant. Concurrent administration with another a1-adrenoreceptor antagonist may lower blood pressure.
4.6 Fertility, pregnancy and lactation
Tamsulosin 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 authorization 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
|
System Organ Class |
Common (>1/100, <1/10) |
Uncommon (>1/1 000, <1/100) |
Rare (>1/10 000, <1/1 000) |
Very rare (<1/10 000) |
Not known |
|
Nervous system disorders |
Dizziness (1.3%) |
Headache |
Syncope | ||
|
Eye disorders |
Vision blurred, visual impairment | ||||
|
Cardiac disorders |
Palpitations | ||||
|
Vascular disorders |
Orthostatic hypotension | ||||
|
Respiratory, thoracic and mediastinum-related disorders |
Rhinitis |
Epistaxis | |||
|
Gastrointesti nal disorders |
Constipation, diarrhoea, nausea, vomiting |
Dry mouth |
|
Skin and subcutaneous tissue disorders |
Rash, pruritus, urticaria |
Angio- oedema |
Stevens- Johnson syndrome |
Erythema multiforme, dermatitis exfoliative | |
|
Reproductive systems and breast disorders |
Ejaculation disorders including retrograde ejaculation, ejaculation failure |
Priapism | |||
|
General disorders and administratio n 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).
Post-marketing experience: In addition to the adverse events listed above, atrial fibrillation, arrhythmia, tachycardia and dyspnoea have been reported in association with tamsulosin use. Because these spontaneously reported events are from the worldwide post marketing experience, the frequency of events and the role of tamsulosin in their causation cannot be reliably 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 Yellow Card Scheme: www.mhra.gov.uk/yellowcard
4.9 Overdose
Symptoms
Overdosage with tamsulosin hydrochloride can potentially result in severe hypotensive effects. Severe hypotensive effects have been observed at different levels of overdosingTreatment
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 may 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
Tamsulosin is an a1A adrenoreceptor antagonist. The medicinal product is only used for the treatment of prostatic conditions.
ATC code: G04CA02
Mechanism of action
Tamsulosin binds selectively and competitively to postsynaptic a1A adrenoreceptors, which convey smooth muscle contraction, thereby relaxing prostatic and urethral smooth muscle.
Pharmacodynamic effects
Tamsulosin increases the maximum urinary flow rate by relaxing prostatic and urethral smooth muscle, thus relieving obstruction.
The medicinal product also improves the irritative and obstructive symptoms in which the contraction of smooth muscle in the lower urinary tract plays an important role.
Alpha-blockers can reduce blood pressure by lowering peripheral resistance. No reduction in blood pressure of any clinical significance was observed during studies with tamsulosin in normotensive patients.
The medicinal product’s effect on storage and voiding symptoms are also maintained during long-term therapy, as a result of which the need for surgical treatment is significantly postponed.
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 rapidly absorbed from the intestines and its bioavailability is almost complete. Absorption is slowed down if a meal has been eaten before taking the medicinal product. Uniformity of absorption can be assured by always taking tamsulosin after breakfast.
Tamsulosin shows linear kinetics.
Peak plasma levels are achieved at approximately six hours after a single dose of tamsulosin taken after a full meal. The steady state is reached by day five of multiple dosing, when Cmax in patients 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 are huge inter-patient variations in plasma levels of tamsulosin, both after single as well as multiple dosing.
Distribution
In humans, tamsulosin is more than 99% bound to plasma proteins and the volume of distribution is small (about 0.2 l/kg).
Biotransformation
Tamsulosin has a low first pass metabolic effect. Most tamsulosin is found unaltered in plasma. The substance is metabolised in the liver.
In studies on rats, tamsulosin was found to cause only a slight induction of microsomal liver enzymes.
The metabolites are not as effective and toxic as the active medicinal product itself.
Elimination
Tamsulosin and its metabolites are mainly excreted in the urine with about 9% of the dose being present in unchanged form.
The elimination half-life of tamsulosin in patients is approximately 10 hours (when taken after a meal) and 13 hours in the steady state.
Preclinical safety data
5.3
Toxicity after a single dose and multiple dosing has been investigated in mice, rats and dogs. Reproductive toxicity has also been investigated in rats, carcinogenicity in mice and rats, and genotoxicity in vivo and in vitro.
The common toxicity profile found with large doses of tamsulosin is equivalent to the pharmacological effect associated with alpha adrenergic antagonists.
Changes in ECG readings were found with very large doses in dogs. This is not, however, assumed to be of any clinical significance. Tamsulosin has not been found to have any significant genotoxic properties.
Greater proliferative changes in the mammary glands of female rats and mice have been discovered on exposure to tamsulosin. These findings, which are probably indirectly linked to hyperprolactinaemia and only occur as a result of large doses having been taken, are considered clinically insignificant.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Content of capsule
Microcrystalline cellulose
Methacrylic acid-ethyl acrylate copolymer
Polysorbate 80
Sodium laurilsulfate
Triethyl citrate
Talc
Capsule body
Gelatine
Indigotine (E 132)
Titanium dioxide (E 171)
Yellow iron oxide (E 172)
Red iron oxide (E 172)
Black iron oxide (E 172)
6.2 Incompatibilities
Not applicable.
Shelf life
6.3
3 years.
6.4 Special precautions for storage
Blister packs: Store in the original package.
Tablet containers: Keep the container tightly closed.
6.5 Nature and contents of container
PVC/PE/PVDC/Aluminium blister packs in cardboard boxes and HDPE tablet containers with PP child-resistant closures containing 10, 14, 20, 28, 30, 50, 56, 60, 90, 100 or 200 modified-release capsules.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
No special requirements.
7 MARKETING AUTHORISATION HOLDER
Actavis UK Limited (Trading style: Actavis)
Whiddon Valley BARNSTAPLE N Devon EX32 8NS
8 MARKETING AUTHORISATION NUMBER(S)
PL 0142/0639
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
23/03/2010
10 DATE OF REVISION OF THE TEXT
15/10/2014