Galebon 0.4mg Prolonged-Release Capsules
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Galebon 0.4 mg prolonged-release capsules, hard
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each prolonged-release capsule, hard contains 0.4 mg tamsulosin hydrochloride.
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Prolonged-release capsule, hard.
330 mg white or off-white film-coated pellets are filled in the size No. 2 capsules which upper part is brown opaque, lower part is buff opaque.
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 breakfast or the first meal of the day.
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
Use in renal impairment
No dose adjustment is warranted in renal impairment.
Use in hepatic impairment
No dose adjustment is warranted in patients with mild to moderate hepatic insufficiency (see also section 4.3 Contraindications).
Method of administration
For oral use. The capsule must be swallowed whole and must not be crunched or chewed as this interferes with the prolonged release of the active substance.
4.3 Contraindications
- Hypersensitivity to the active substance, including drug-induced angioedema, 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 ai-adrenoceptor 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.
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 patients with severe renal impairment (creatinine clearance of < 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. IFIS may increase the risk of eye complications during and after 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 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.
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 seen when tamsulosin was given concomitantly with either atenolol, enalapril, nifedipine 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, chlormadinone, 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 chlormadinone.
Diclofenac and warfarin, however, 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 of other a1-adrenoceptor antagonists could lead to hypotensive effects.
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 to <1/10) |
Uncommon 1/1,000 to <1/100) |
Rare fc1/10,000 to <1/1,000) |
Very rare (<1/10,00 0) |
Not known (cannot be stimated rom the available lata) |
|
Nervous system disorders |
Dizziness (1.3%) |
Headache |
Syncope | ||
|
Eye disorders |
Vision blurred, Visual impairment | ||||
|
Cardiac disorders |
Palpitations |
|
System Organ Class |
Common 1/100 to <1/10) |
Uncommon 1/1,000 to <1/100) |
Rare 1/10,000 to <1/1,000) |
Very rare (<1/10,00 0) |
Not known (cannot be stimated rom the available lata) |
|
Vascular disorders |
Orthostatic hypotension | ||||
|
Respiratory, thoracic and mediastinal disorders |
Rhinitis |
Epistaxis | |||
|
Gastrointestinal disorders |
Constipation, Diarrhoea, Nausea, Vomiting |
Dry mouth | |||
|
Skin and subcutaneous tissue disorders |
Rash, Pruritus, Urticaria |
Angioedema |
Stevens- Johnson syndrome |
Erythema multiforme, Dermatitis exfoliative | |
|
Reproductive system and breast disorders |
Ejaculation disorders, Retrograde ejaculation, Ejaculation failure |
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 postmarketing 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 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 overdosing.
Acute overdose with 5 mg of tamsulosin has been reported. Acute hypotension (systolic blood pressure 70 mmHg), vomiting and diarrhoea were observed, which were treated with fluid replacement and the patient could be discharged the same day.
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: Urologicals, Alpha-adrenoreceptor antagonists, ATC code: G04CA02
Mechanism of action
Tamsulosin binds selectively and competitively to the postsynaptic a1-adrenoceptors, in particular to subtypes a1A and a1D. It brings about relaxation of prostatic and urethral smooth muscle.
Pharmacodynamic effects
Tamsulosin increases the 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.
a1-adrenoceptor antagonists can reduce blood pressure by lowering peripheral resistance. No reduction in blood pressure of any clinical significance was observed during studies with tamsulosin.
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 tamsulosin after breakfast or the first meal of the day. Tamsulosin shows linear kinetics.
After a single dose of tamsulosin 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 active substance. It is metabolised in the
liver. In rats, hardly any induction of microsomal liver enzymes was seen to be caused by tamsulosin. None of the metabolites are more active than the original compound.
No dose adjustment is warranted in patients with mild to moderate hepatic insufficiency (see section 4.3).
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 tamsulosin in the fed state, and in the steady state in patients, elimination half-lives of about 10 and 13 hours, respectively, have been measured.
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 a 1-adrenoreceptor antagonists. 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 content:
Microcrystalline cellulose (E460),
Methacrylic acid - ethyl acrylate copolymer 1:1 (including: polysorbate 80, sodium laurylsulfate),
Talc,
Triethyl citrate,
Calcium stearate.
Capsule shell:
Yellow iron oxide (E172), Black iron oxide (E172), Red iron oxide (E172),
Titanium dioxide (E171), Gelatine.
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
3 years.
6.4. Special precautions for storage
Store in the original package in order to protect from light.
6.5 Nature and contents of container
30, 90 or 100 capsules are packed into colourless, transparent PVC/PVDC/Al blisters.
Not all pack sizes may be marketed 6.6. Special precautions for disposal and handling
No special requirements.
Any unused product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
Consilient Health Ltd.
5th floor, Beaux Lane House, Mercer Street Lower,
Dublin 2, Ireland.
MARKETING AUTHORISATION NUMBER(S)
PL 24837/0010
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DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date of first authorisation: 29/10/2007 Date of latest renewal: 19/01/2010
DATE OF REVISION OF THE TEXT
11/12/2013