Skip to Content

UK Edition. Click here for US version.

MORVESIN 400 MICROGRAM SR CAPSULES

Active substance(s): TAMSULOSIN HYDROCHLORIDE / TAMSULOSIN HYDROCHLORIDE

View full screen / Print PDF » Download PDF ⇩
Transcript
SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Morvesin 400 microgram SR Capsules

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each capsule contains tamsulosin hydrochloride 0.4 mg.
For the full list of excipients, see 6.1.

3

PHARMACEUTICAL FORM
Modified-release capsule, hard.
Light green/yellow capsule. The capsules contain white to slightly yellowish 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
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.
No dose adjustment is warranted in renal impairment. No dose adjustment is
warranted in patients with mild to moderate hepatic insufficiency (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, including drug-induced angio-oedema, or to any of
the excipients.
Orthostatic hypotension observed earlier (history of orthostatic hypotension).
Severe hepatic insufficiency.

4.4

Special warnings and precautions for use
The use of tamsulosin may lower blood pressure, which in rare cases may
cause fainting. If initial symptoms of orthostatic hypotension start to appear
(dizziness, weakness), then the patient should sit or lie down until the
symptoms have gone.
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 BPH. The prostate should be examined via the rectum
and, if necessary, the PSA count determined prior to commencement of
treatment and again later at regular intervals.
The treatment of severely renally impaired patients (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, 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 and glaucoma surgery in some
patients on or previously treated with tamsulosin. IFIS may increase the risk of
eye complications during and after the operation. Discontinuing tamsulosin 12 weeks prior to cataract or glaucoma surgery is anecdotally considered
helpful, but the benefit and duration of requirement of stopping the therapy
prior to cataract surgery has not yet been established. IFIS has also been
reported in patients who had discontinued tamsulosin for a longer period prior
to the surgery.
The initiation of therapy with tamsulosin in patients for whom cataract or
glaucoma surgery is scheduled is not recommended. During pre-operative
assessment, surgeons and ophthalmic teams should consider whether patients

scheduled for cataract or glaucoma 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 has been given
concomitantly with atenolol, enalapril, 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 not 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.
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 α1-adrenoreceptor antagonist may
lower blood pressure.
4.6

Fertility, pregnancy and lactation

Tamsulosin hydrochloride 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

Nervous system
disorders

Common

Uncommon Rare

Very rare

(>1/100,
<1/10)

(>1/1 000,
<1/100)

(>1/10 000, (<1/10 000)
<1/1 000)

Dizziness

Headache

Syncope

Not known

Vision
blurred,
visual
impairment

Eye disorders

Cardiac disorders

palpitations

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

Reproductive
systems and breast
disorders

ejaculation
disorders,
including
retrograde
ejaculation
and

Angiooedema

StevensJohnson
syndrome
Priapism

erythema
multiforme,
dermatitis
exfoliative

ejaculation
failure
General disorders
and administration
site conditions

Asthenia

During cataract and glaucoma 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.
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. 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:
α1A adrenoreceptor antagonist, ATC code: G04CA02.
The medicinal product is only used for the treatment of prostatic conditions.

Mechanism of action

Tamsulosin binds selectively and competitively to postsynaptic α1A
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 about 99% bound to plasma proteins and 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.
In vitro results suggest that CYP3A4 and also CYP2D6 are involved in
metabolism, with possible minor contributions to tamsulosin hydrochloride
metabolism by other CYP isozymes. Inhibition of CYP3A4 and CYP2D6 drug
metabolizing enzymes may lead to
increased exposure to tamsulosin hydrochloride (see section 4.4 and 4.5).
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 active substance.
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
Content of capsule
Microcrystalline cellulose (E460)
Polyacrylate
Metacrylic acid-ethyl acrylate copolymer (1:1)
Polysorbate 80 (E433)
Sodium laurilsulfate
Talc (E553b)
Colloidal anhydrous silica (E551)
Capsule shell
Gelatine (E441)
Patent Blue V (E131)
Titanium dioxide (E171)
Yellow iron oxide (E172)
Red iron oxide (E172)
Black iron oxide (E172)

6.2

Incompatibilities
Not applicable.

6.3

Shelf life
2 Years.

6.4

Special precautions for storage
Store below 30 º C.

6.5

Nature and contents of container
PVDC/TE/PVC//Al blister
Pack sizes:
NL/H/0789/001/DC: 10, 20, 28, 30, 50, 56, 60, 90 and 100 capsules;
Not all pack sizes may be marketed.

6.6

Special precautions for disposal
No special requirements.

7

MARKETING AUTHORISATION HOLDER
Sandoz Limited
Frimley Business Park,
Frimley,
Camberley,
Surrey,
GU16 7SR.
United Kingdom

8

MARKETING AUTHORISATION NUMBER(S)
PL 04416/0695

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
24/07/2007

10

DATE OF REVISION OF THE TEXT
01/05/2014

Expand view ⇕

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

Hide