Tamfrex Xl 400 Microgram Capsules
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
TAMFREX XL 400 microgram capsules
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each prolonged-release capsule, hard contains 0.4 mg of tamsulosin hydrochloride.
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Prolonged-release capsule, hard
Olive green opaque/ Orange opaque size ‘0’ hard gelatin capsules imprinted with ‘D’ on cap and ‘53’ on body with black edible ink filled with white to off-white beadlets.
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.
Adults:
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.
Elderly persons:
Dose reduction is not necessary.
Patients with renal insufficiency:
In patients with creatinine clearance over 0.17 ml/sec. (10 ml/min) there is no need of dosage modification.
Patients with hepatic insufficiency:
In patients with mild to moderate liver dysfunction there is no need of dosage modification (see also 4.3, contraindications).
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 hydrochloride, including drug-induced angio-oedema, 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 a i-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.
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.
Angioedema has been rarely reported after the use of tamsulosin. Treatment should be discontinued immediately, the 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 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 seen 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.
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 a 1-adrenoceptor antagonists could lead to hypotensive effects.
4.6 Fertility, pregnancy and lactation
Tamsulosin Aurobindo 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 (>1/10 000 to <1/ 1 000) |
Very rare (<1/10 000) |
Not known (cannot be estimated from the available data) |
|
Nervous system disorders |
Dizziness (1.3%) |
Headache |
Syncope | ||
|
Eye disorders |
Vision blurred, visual impairment | ||||
|
Cardiac disorders |
Palpitations | ||||
|
Vascular disorders |
Orthostatic hypotension |
epistaxis | |||
|
Respiratory, thoracic and mediastinal disorders |
Rhinitis | ||||
|
Gastrointestinal disorders |
Constipation, diarrhoea, |
Dry mouth |
|
nausea, vomiting | |||||
|
Skin and subcutaneous tissue disorders |
Rash, pruritus, urticaria |
Angio- oedema |
Stevens- Johnson syndrome |
Erythema multiforme, Dermatitis exfoliative | |
|
Reproductive systems 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 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 overdosing.
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: Drugs used in benign prostatic hypertrophy, 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. Observational data indicate that use of tamsulosine may lead to a delay in the need for surgery or catheterization.
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.
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 Content
Cellulose, microcrystalline Talc
Methacrylic acid-ethyl acrylate copolymer
Sodium lauryl sulfate Polysorbate 80
Triacetin
Calcium stearate
Capsule shell
Indigo carmine (E132)
Iron oxide red (E172)
Iron oxide yellow (E172)
Titanium dioxide (E171) Gelatin
Sodium lauryl sulfate
Printing Ink
Shellac
Propylene glycol Black iron oxide (E172) Potassium hydroxide
6.2 Incompatibilities
Not applicable
6.3 Shelf life
2 years
6.4 Special precautions for storage
This medicinal product does not require any special temperature storage conditions
Store in the original package in order to protect from moisture.
6.5 Nature and contents of container
PVC/PE/PVDC/Aluminium blister packs
Blister: 1, 2, 4, 7, 10, 14, 15, 20, 28, 30, 50, 56, 60, 90, 98, 100 & 200 hard, capsules.
White opaque round HDPE bottle with white opaque polypropylene closure: 10 & 250 hard, capsules.
Not all pack sizes may be marketed
6.6 Special precautions for disposal
No special requirements.
7 MARKETING AUTHORISATION HOLDER
Milpharm Limited
Ares, Odyssey Business Park
West End Road
South Ruislip HA4 6QD
United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL 16363/0254
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
01/05/2012
10 DATE OF REVISION OF THE TEXT
21/05/2014