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VASRAN XL 10 MG PROLONGED-RELEASE TABLETS

Active substance(s): ALFUZOSIN HYDROCHLORIDE / ALFUZOSIN HYDROCHLORIDE / ALFUZOSIN HYDROCHLORIDE

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Vasran XL 10 mg prolonged-release tablets.

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 10 mg alfuzosin hydrochloride.
Excipients with known effect: lactose
For the full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Prolonged-release tablet.
White to off-white, round, uncoated, biconvex tablets with flattened edges, debossed
with ‘RY 10’ on one side.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications

Treatment of moderate to severe functional symptoms of benign prostate hyperplasia
(BPH).
As an adjunct therapy in connection with catheterisation in acute urinary retention
(AUR) related to BPH.

4.2

Posology and method of administration

Posology:
Adults:
BPH: The recommended dose is one 10 mg prolonged-release tablet daily.
AUR: One 10 mg prolonged-release tablet daily after a meal to be taken from the first
day of catheterisation. Efficacy in the long-term treatment of AUR has not been
established.

Older people (over the age of 65 years)
The recommended dose is the same as that for adults. Pharmacokinetic and clinical
safety studies have shown that dose adjustment is not necessary in the case of elderly
patients.
Patients with renal impairment
Based on pharmacokinetic and clinical safety data, patients with renal insufficiency
(creatinine clearance ≥30 ml/min) can be treated with the usual dose.
Alfuzosin 10 mg should not be given to patients with severely impaired renal function
(creatinine clearance < 30 ml/min) as there are no clinical safety data available for this
patient group (see section 4.4).
Hepatic insufficiency:
Alfuzosin, given as 10 mg prolonged-release tablets are contraindicated in patients
with hepatic insufficiency. Preparations containing a low dose of alfuzosin
hydrochloride might be used in patients with mild to moderate hepatic insufficiency
as instructed in the corresponding product information.
Paediatric population:
Efficacy of Alfuzosin has not been demonstrated in children aged 2 to 16 years (see
section 5.1).Therefore, Alfuzosin is not indicated for use in paediatric population.
Method of administration
Oral use.
The prolonged-release tablet should be taken whole with sufficient amount of fluid
(e.g. a glass of water). The prolonged-release tablets must not be crushed, chewed or
divided (see section 4.4).
The first dose should be taken at bedtime. The prolonged-release tablet 10 mg should
be taken immediately after the same meal each day.
4.3

4.4


Contraindications
-

Hypersensitivity to alfuzosin, other quinazolines (e.g. terazosine, doxazosine) or any
one of the excipients as listed in section 6.1

-

History of orthostatic hypotension

-

Hepatic insufficiency

-

Combination with other alpha 1 receptor blockers

Special warnings and precautions for use
As there are no clinical safety data available in patients with severe renal impairment
(creatinine clearance < 30ml/min), Alfuzosin 10 mg prolonged-release tablets should not
be administered to this patient group.



The patient should be examined before commencement of therapy with alfuzosin to
exclude the presence of other conditions that can produce similar symptoms to those of
BPH.



Alfuzosin 10 mg Prolonged-release tablets should be given with caution to patients who
are being treated with antihypertensives or nitrates. In some subjects orthostatic
hypotension with or without symptoms (dizziness, tiredness, sweating) may develop
within a few hours following administration



These effects are transient, occur at the start of the treatment and usually do not require
the treatment to be stopped. The patient should be warned that these symptoms may
possibly occur. In such cases the patient should rest lying down until the symptoms have
completely disappeared.



Pronounced drop in blood pressure has been reported in post-marketing surveillance in
patients with pre-existing risk factors (such as underlying cardiac diseases and/or
concomitant treatment with anti-hypertensive medication).



Caution should be taken if alfuzosin is administered to patients who have had a
pronounced response to another alpha-1-receptor blockers.



In coronary patients the specific treatment should be continued, taking into account the
fact that concomitant administration of nitrates and alfuzosin can increase the risk of
hypotension occurring. If angina pectoris recurs the treatment with alfuzosin should be
discontinued.



As with all alpha-1-receptor blockers alfuzosin should be used with caution in patients
with acute cardiac failure.



Alfuzosin should be administered carefully to patients being treated with
antihypertensives. The treatment should be started gradually in patients with
hipersensitivity to other alpha-l-receptor blockers. Blood pressure must be regularly
monitored, particularly at the start of the treatment.



Patients with congenital QTc prolongation, with a known history of acquired QTc
prolongation or who are taking drugs known to increase the QTc interval should be
evaluated before and during the administration of alfuzosin



The ’Interoperative 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 the cataract operation, current or past use of alpha-1 blockers should
be made known to the opthalmic surgeon in advance of surgery.



Patients should be warned that the tablet should be swallowed whole. Other methods of
administration such as crushing, pulverising or chewing the tablets must be prohibited.

Incorrect administration can lead to inappropriate release and absorption of the active
substance with the risk of early side effects.


This product contains lactose. Patients with rare hereditary conditions such as galactose
intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not use
this medicinal product.

4.5

Interaction with other medicinal products and other forms of interaction

-

Combinations not recommended
Alpha-1 receptor blockers (see section 4.3)

-

Combinations to be taken into account (see section 4.4)
Antihypertensive drugs (See section 4.4)

-

Nitrate preparations. (See section 4.4)
Potent CYP3A4 inhibitors (ketoconazole, itraconazole, protease inhibitor (ritonavir),
clarithromycin, erythromycin) telithromycin and nefazodone:
Increase the plasma concentration of alfuzosin and increase the risk of undesirable
effects. (see section 5.2)

-

Ketoconazole: Repeated 200 mg daily dosing of ketoconazole, for seven days
resulted in a 2.1-fold increase in Cmax and a 2.5-fold increase in exposure of
alfuzosin when administered as a single dose under fed conditions (high fat meal).
Other parameters such as tmax and t1/2 were not modified.
Cmax and AUC of alfuzosin when administered as a single dose under fed
conditions, increased 2.3- fold and 3.0- fold, respectively following 8-day repeated
400 mg ketoconazole daily dosing (see Section 5.2 Pharmacokinetic properties).

-

Administration of general anaesthetics to a patient being treated with alfuzosin may
lead to profound hypotension. It is recommended that the tablets be withdrawn 24
hours before surgery.
Other forms of interaction
No pharmacodynamic or pharmacokinetic interaction has been observed in healthy
volunteers between alfuzosin and the following drugs: warfarin, digoxin,
hydrochlorothiazide and atenolol.

4.6

Fertility, Pregnancy and lactation
In view of the area of indication this section is not applicable.

4.7

Effects on ability to drive and use machines
There are no data available on the effect on driving vehicles.

Undesirable effects such as vertigo, weakness, dizziness and asthenia can occur particularly at
the start of the treatment. This should be taken into account when driving vehicles or using
machines.

4.8

Undesirable effects
The most commonly reported event is dizziness, which occurs in approximately 5 %
of treated patients.
The adverse reactions considered at least possibly related to treatment are listed
below by body system organ class and absolute frequency. Frequencies are defined as
very common (≥1/10); common (>1/100 to <1/10); uncommon (>1/1000 to <1/100);
rare (>1/10 000 to <1/1000); very rare (<1/10 000), not known (cannot be estimated
from the available data)

Frequency
SOC
Common

Uncommon

Very rare

Blood and
lymphatic
system
disorders

Neutropenia
Thrombocytop
enia

Immune
system
disorder
Nervous
system
disorders

Not Known

Angioneurotic
oedema
Faintness/Dizzine
ss, headache

Vertigo, Drowsiness

Eye disorders

Vision abnormal

Cardiac
disorders

Tachycardia,
palpitations, Chest
pains

Angina pectoris in
patient with precoronary artery
disorders (see section
4.4)

Intraoperative
floppy iris
syndrome (See
section 4.4)
Atrial
fibrillation

Frequency
SOC
Common

Vascular
disorders

Respiratory,
thoracic and
mediastinal
disorders
Nausea,
Gastrointestinal
abdominal pain,
disorders
dyspepsia

Uncommon

Not Known

Hepatotoxicity

Hepatocellular
injury,
cholestatic
liver disease.

Postural hypotension
(See section 4.4)
(initially, primarily
with too high a dose
or if treatment is
started again after a
short interruption of
therapy),
Syncope (initially
above all with too
high a dose or if
treatment is started
again after a short
interruption of
therapy)

Rhinitis
Vomiting Diarrhoea,
dry mouth

Hepatobiliary
disorders
Skin and
subcutaneous
tissue disorders
Renal and
urinary
disorders
Reproductive
system and
breast disorders
General
disorders and
Asthenia,
administration
site conditions

Very rare

Skin rashes, pruritus,
exanthema, urticaria
Urine incontinence
Priapism

Oedema, (see section
4.4), malaise, hot
flushes

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 the Yellow Card Scheme
at: www.mhra.gov.uk/yellowcard.

4.9

Overdose
In case of overdose, the patient should be admitted to hospital, kept in supine position, and
given normal support therapy for hypotension. The appropriate antidote is a vasoconstrictor
that acts directly on the smooth muscle in the blood vessels such as noradrenaline.
Gastric flushing and/or the administration of medicinal charcoal should be considered.
Alfuzosin is not easily dialysed due to the strong degree of protein binding.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic category: alpha-adrenoreceptor antagonists. ATC code: G04C A01
Alfuzosin
Alfuzosin, a racemic compound, is an orally active quinazoline derivative that selectively
blocks post-synaptic alpha-l-receptors. In vitro studies have shown that the substance acts
selectively on alpha-1-receptors in the trigone of the urine bladder, the urethra and the prostate
gland. The clinical symptoms of benign prostate hyperplasia are not only related to the size of
the prostate but also to the sympathicomimetic nerve impulses which through stimulation of
the postsynaptic alpha-receptors increase the tension of the smooth muscles of the lower
urinary tract. Through treatment with alfuzosin the smooth muscles relax as a result of which
the urine flow improves.
The clinical evidence of the selective effect on the urinary tract is shown by the clinical
efficacy and the good safety profile in men treated with alfuzosin, including elderly patients
and patients with hypertension. Alfuzosin can result in moderate antihypertensive effects.
In men, alfuzosin improves the voiding of water by reducing urethral muscle tone and bladder
outlet resistance, thereby facilitating bladder emptying.
In patients treated with alfuzosin a lower frequency of acute urine retention was observed than
in untreated patients.




In placebo-controlled studies in patients with benign prostate hyperplasia alfuzosin:
significantly increased maximum urine flow (Qmax) in patients with Qmax<15 ml/sec
by an average of 30%. This improvement was observed from the first dose;
a significantly reduced detrusor pressure and an increased volume, producing a strong
desire to void,
a significantly reduced the residual urine volume.

The efficacy on peak flow rate is observed up to 24 hours after intake.
These urodynamic effects result in an improvement in lower urinary tract symptoms (LUTS),
i.e. symptoms relating to retention (irritating) and urine discharge (obstructive) which is
clearly demonstrated.

A lower frequency of acute urinary retention is observed in the alfuzosin treated patient than
in the untreated patient. Alfuzosin 10 mg has been shown to increase the probability of
successful spontaneous voiding in patients presenting with a first episode of acute urinary
retention related to BPH. In a double-blind placebo-controlled clinical study in 357 patients,
the success rate of spontaneous voiding after catheter removal was 61.9% in the alfuzosin
group and 47.9% in the placebo group (p=0.012). This relative increase of 29% in the success
rate of spontaneous voiding is clinically significant, since a higher percentage of patients may
be discharged without a catheter. In the high risk group (quantity of removed urine > 1,000
ml) the relative increase in the success rate of spontaneous voiding in the alfuzosin group
compared with the placebo group was even greater than the clinically significant change in
the overall data set.
Paediatric population
Alfuzosin is not indicated for use in the paediatric population (see section 4.2).
Efficacy of alfuzosin hydrochloride was not demonstrated in the two studies conducted in 197
patients 2 to 16 years of age with elevated detrusor leak point pressure (LPP≥40 cm H2O) of
neurologic origin. Patients were treated with alfuzosin hydrochloride 0.1 mg/kg/day or 0.2
mg/kg/day using adapted paediatric formulations.
5.2

Pharmacokinetic properties
Alfuzosin has linear pharmacokinetics in the therapeutic dosage range. The kinetic
profile is characterised by large inter-individual fluctuations in the plasma
concentration. The kinetic profile is characterised by large inter-individual
fluctuations in plasma concentrations. Absorption is increased when the medication is
administered after a meal.
Absorption
After the first dose (following a meal) the mean maximum plasma concentration was
7.72 ng/ml and the AUCinf 127 ng x h/ml (after a meal) and the tmax was 6.69 hours
(after a meal). In steady state conditions (after a meal) the mean AUC over the dosage
interval (AUCτ) was 145 ng x h/ml, the mean Cmax 10.6 ng/ml and Cmin was 3.23
ng/ml.
Distribution
Plasma protein binding is approx. 90%. The distribution volume of alfuzosin in
healthy test subjects is 2.5 l/kg. It has been shown that the substance is distributed
more in the prostate than in the plasma.
Elimination
The apparent elimination half-life is approximately 8 hours. Alfuzosin is largely
metabolised in the liver (various routes), the metabolites are eliminated by the
kidneys and probably also via the bile, 75-91% of an oral dose is eliminated in the
faeces, 35% in unmodified form and the rest as metabolites, which indicates that
some excretion via the bile takes place. Around 10% of the dose is eliminated in
unmodified form in the urine. None of the metabolites are pharmacologically active.

Renal or hepatic impairment
The volume of distribution and clearance increases with reduced renal function,
possibly owing to a decreased degree of protein binding. The half-life, however, is
unchanged. This change in the pharmacokinetic profile is not considered clinically
relevant. Therefore, this does not necessitate a dosing adjustment in patients with
mild to moderate renal insufficiency (see sections 4.2 and 4.4).
The half-life is prolonged in patients with severe hepatic insufficiency. The peak
plasma concentration is doubled and the bioavailability increases in relation to that in
young, healthy volunteers. Alfuzosin 10 mg prolonged release tablets are
contraindicated in hepatic insufficiency (see section 4.3).
Older people
Compared to healthy middle-aged volunteers, the peak plasma concentration (Cmax)
and bioavailability (AUC) are not increased in elderly patients. The elimination halflife (t½) remains unchanged.

5.3

Preclinical safety data
Pre-clinical data reveal no special hazard for humans based on conventional studies of
genotoxicity, carcinogenic potential or reproductive toxicity for males. In vitro,
alfuzosin prolonged the action potential duration and QT interval duration at a
clinically relevant concentration.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Lactose anhydrous
Colloidal anhydrous silica
Povidone
Talc
Magnesium stearate
Hypromellose
Hydroxypropyl cellulose

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 storage conditions.

6.5

Nature and contents of container
PVC-aluminium blister.
Pack sizes: 10, 30 and 90 tablets.
Not all pack sizes may be marketed.

6.6

Special precautions for disposal
No special requirements.

7

MARKETING AUTHORISATION HOLDER
Ranbaxy (UK) Limited
5th floor, Hyde Park, Hayes 3
11 Millington Road
Hayes, UB3 4AZ
United Kingdom

8

MARKETING AUTHORISATION NUMBER(S)
PL 14894/0567

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
05/11/2008

10

DATE OF REVISION OF THE TEXT
18/09/2016

Expand Transcript

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.

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