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VASRAN XL 10 MG PROLONGED-RELEASE TABLETS

Active substance(s): 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: lactose
For a 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).

4.2

Posology and 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.

Adults:
The recommended dose is one 10 mg prolonged-release tablet daily.
Elderly patients (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.
Impaired renal function
Mild to moderate renal insufficiency (creatinine clearance > 30 ml/min):
Dose reduction is usually not necessary (see section 5.2).
Severe renal insufficiency
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.

4.3

Contraindications
-

Previous history of orthostatic hypotension

-

Hepatic insufficiency

-

4.4

Hypersensitivity to alfuzosin, other quinazolines (e.g. terazosine, doxazosine) or any
one of the excipients

Combination with other alpha 1 receptor blockers

Special warnings and precautions for use


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.



Care must be taken if are administered to
patients who are being treated with antihypertensives or nitrates. Blood pressure must be
regularly monitored, particularly at the start of the treatment.



In some patients orthostatic hypotension may develop within a few hours following
administration with or without symptoms (dizziness, tiredness, sweating).



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.
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, although the risk of this event with
alfuzosin appears very low.




Caution is urged if alfuzosin is administered to patients who have reacted to other alpha1-receptor blockers with severe hypotension.



The treatment should be started gradually in patients who are sensitive to other alpha-lreceptor blockers.



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



In the case of cardiac patients the treatment of coronary insufficiency 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 stopped.



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.



Patients should be instructed to take the tablet 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

Alfuzosin is not recommended for patients treated with other alpha-1 receptor blockers due
to increased hypotensive effect and risk of severe orthostatic hypotension.

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.

Interaction with other medicinal products and other forms of interaction

-

Combinations not recommended
Alpha-1 receptor blocking agents
Increased hypotensive effect. Risk of severe orthostatic hypotension.

-

-

Potent CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir, clarithromycin,
erythromycin)
Increase the plasma concentration of alfuzosin and increase the risk of undesirable
effects.
Combinations to be taken into account (see section 4.4)
Antihypertensive drugs
antihypertensive effect and risk of increased hypotension (cumulative effect).
Nitrate preparations.
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.

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, 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 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
Blood and
lymphatic
system
disorders
Nervous system
disorders

Eye disorders

Uncommon

Very rare

Not Known
Neutropenia

Dizziness/tiredness,
headache

Vertigo,
Drowsiness
Visual disturbances

Intraoperative
floppy iris
syndrome

Frequency
SOC
Common

Tachycardia,
palpitations,
syncope (in
particular at the
beginning of the
treatment),
Flushing

Cardiac disorders

Vascular
disorders

Respiratory,
thoracic and
mediastinal
disorders
Gastrointestinal
disorders

Uncommon

Very rare
New Onset,
Aggravation or
recurrence of
angina pectoris in
patient with precoronary artery
disorders (see
section 4.4)

Atrial
fibrillation

Postural hypotension
(initially, primarily
with too high a dose or
if treatment is resumed
after a short
interruption of
therapy)

Rhinitis
Nausea, abdominal
pain,

Diarrhoea, dry
mouth

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

Vomiting

Hepatotoxicity

Skin rashes,
pruritus,

Hepatocellular
injury,
cholestatic liver
disease.

Urticaria,
Angioneurotic
oedema

Urine incontinence
Oedema, chest
pains (see section
4.4), malaise

* Although only reported in isolated cases with alfuzosin, occurrence of priapism
cannot be excluded as it is generally accepted as being attributable to all other alpha
adrenoreceptor blockers.

4.9

Not Known

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.

Priapism *

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 Q m a x <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.
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.
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 (AUC ) was 145 ng x h/ml, the mean Cmax 10.6 ng/ml and Cmin was 3.23
ng/ml.

τ

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).
Elderly patients
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
Building 4, Chiswick Park
566 Chiswick High Road
London, W4 5YE
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
27/04/2012

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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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