Tamurex 400 Mcg Prolonged Release Capsules
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Tamurex 400 micrograms prolonged-release capsules
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
One capsule contains 0.4 mg of tamsulosin hydrochloride.
For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Prolonged-release capsule, hard
Orange no 2 gelatin capsule which contains white or yellowish granules
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
One capsule daily, to be taken after breakfast or after the first meal of the day.
The capsule should be swallowed whole with a glass of water in sitting or in standing position (not in lying position). The capsule should not be broken or chewed as this will interfere with the modified release of the active ingredient. In cases when patients have difficulties swallowing (e. g. dysphagia), the capsule may be opened and the contents swallowed without chewing.
Paediatric population
The safety and efficacy of tamsulosine in children < 18 years have not been established. Currently available data are described in section 5.1
4.3 Contraindications
Hypersensitivity to tamsulosin including drug-induced angio-oedema, or to any of the excipients. A history of orthostatic hypotension. Severe hepatic insufficiency.
4.4 Special warnings and precautions for use
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.
Before therapy with tamsulosin 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 rarely reported after the use of tamsulosin. Treatment should be discontinued immediately, patient should be monitored until disappearance of the oedema, and tamsulosin 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. Isolated reports have also been received with other alpha-1 blockers and the possibility of a class effect cannot be excluded. As IFIS may lead to increased procedural complications during cataract operation current or past use of alpha-1 blockers should be made known to the ophthalmic surgeon in advance of surgery.
The benefit of stopping tamsulosin therapy prior to cataract surgery has not yet been established.
The initiation of tamsulosin therapy in patients awaiting cataract surgery is not recommended.
Interaction with other medicinal products and other forms of interaction
4.5
No interactions have been observed when tamsulosin was given concomitantly with either atenolol, enalapril, nifedipine or theophylline. Concomitant cimetidine raises, and concomitant furosemide lowers plasma concentrations of tamsulosin but, as the concentration of tamsulosin remains within the normal range, posology need to be altered.
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.
No interactions have been seen during in vitro studies with liver microsomal fractions (representative of the cytochrome P450-linked metabolizing enzyme system), involving amitriptyline, salbutamol, glibenclamide and finasteride. Diclofenac and warfarin may increase the elimination rate of tamsulosin. Concurrent administration of other a 1-adrenoceptor antagonists may lead to hypotensive effects.
4.6 Pregnancy and lactation
Tamsulosin is intended for males only.
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
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Nervous system disorders:
Common (>1/100, <1/10): Dizziness Uncommon (>1/1,000, <1/100): Headache Rare (>1/10,000, <1/1,000): Syncope
Eye disorders
Common (>1/100, <1/10):Floppy Iris Syndrome (IFIS, variant of small pupil syndromes during cataract surgery)
Cardiac disorders:
Uncommon (>1/1,000, <1/100): Tachycardia
Vascular disorders:
Uncommon (>1/1,000, <1/100): Orthostatic hypotension
Respiratory, thoracic and mediastinal disorders:
Uncommon (>1/1,000, <1/100): Rhinitis
Gastrointestinal disorders:
Uncommon (>1/1,000, <1/100): Constipation, diarrhoea, nausea, vomiting
Skin and subcutaneous tissue disorders:
Uncommon (>1/1,000, <1/100): rash, itching, urticaria Rare (>1/10,000, <1/1,000): Angiooedema
Reproductive system and breast disorders:
Uncommon (>1/1,000, <1/100): Abnormal ejaculation Very rare (<1/10,000): Priapism
General disorders and administration site conditions:
Uncommon (>1/1,000, <1/100): Asthenia
4.9 Overdose
No cases of acute overdosage have been reported. However, acute hypotension could theoretically occur after overdosage in which case 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.
If large quantities of the medicinal product are involved, gastric lavage may be performed and activated charcoal and an osmotic laxative, such as sodium sulphate, may be given.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: alpha-adrenoreceptor antagonists, 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 intestine 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.
Excretion
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.
5.3 Preclinical safety data
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
capsule contents: sodium alginate
methacrylic acid-ethyl acrylate copolymer 1:1
glycerol dibehenate
maltodextrin
sodium laurilsulphate
macrogol 6000
polysorbate 80
sodium hydroxide
simeticone emulsion (simeticone, methylcellulose, sorbic acid) silica, colloidal anhydrous
capsule shell: gelatin
red iron oxide (E172) titanium dioxide (E171) yellow iron oxide (E172)
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
2 years
6.4 Special precautions for storage
Store in the original container.
Do not store above 30°C.
6.5 Nature and contents of container
Blister: PVC/PVDC/Al-blister Blister are packed in cardboard cartons.
Capsule container: HDPE-container with PP-cap
Pack sizes: 30 capsules
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements.
7 MARKETING AUTHORISATION HOLDER
Strandhaven Limited T/A Somex Pharma
600 High Road
Seven Kings
Ilford Essex IG3 8BS
United Kingdom
tel: +44 20 8590 9399
fax: +44 20 8599 4437
e-Mail: info@somexpharma.com
8 MARKETING AUTHORISATION NUMBER(S)
PL 15764/0031
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
20/02/2007
10 DATE OF REVISION OF THE TEXT
17/09/2012