In case of overdosage, the patient should be hospitalised, kept in the supine position, and conventional treatment of hypotension should take place.
In case of significant hypotension, the appropriate corrective treatment may be a vasoconstrictor that acts directly on vascular muscle fibres.
Alfuzosin is not dialysable because of its high degree of protein binding.
3 years.
None known.
Ethylcellulose
Hydrogenated Castor Oil
Hypromellose
Yellow Ferric Oxide (E172)
Magnesium Stearate
Microcrystalline Cellulose
Povidone
Silica Colloidal Hydrated
Mannitol.
Classification of expected frequencies:
Very common (>1/10), 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).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
- Nervous system disorders
Common: faintness/dizziness, headache
Uncommon: syncope, vertigo, malaise, drowsiness
- Eye disorders
Uncommon: vision abnormal
Not known: intraoperative floppy iris syndrome
- Cardiac disorders
Uncommon: tachycardia, palpitations, hypotension (postural),
Very rare: New onset, aggravation or recurrence of angina pectoris in patients with pre-existing coronary artery disease.
Not known: atrial fibrillation
- Vascular disorders
Uncommon: hypotension (postural), flushing
- Blood and lymphatic system disorders
Not known: neutropenia, thrombocytopenia
- Respiratory, thoracic and mediastinal disorders
Uncommon: rhinitis
- Gastro-intestinal disorders
Common: nausea, abdominal pain
Uncommon: diarrhoea, dry mouth, vomiting
Not known: vomiting
- Hepatobiliary disorders
Frequency unknown: hepatocellular injury, cholestatic liver disease.
- Skin and subcutaneous tissue disorders
Uncommon: rash, pruritus
Very rare: urticaria, angioedema
- Reproductive system and breast disorders
Frequency unknown: priapism
- General disorders and administration site conditions
Common: asthenia
Uncommon: flushes, oedema, chest pain
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 at: www.mhra.gov.uk/yellowcard
No data of therapeutic relevance.
Pharmacotherapeutic group: alpha-adrenoreceptor antagonists
ATC code: G04CA01
Alfuzosin is an orally active quinazoline derivative. It is a selective, peripherally acting antagonist of postsynaptic alpha-1-adrenoceptors.
In vitro pharmacological studies have documented the selectivity of alfuzosin for the alpha-1-adrenoreceptors located in the prostate, bladder base and prostatic urethra.
Clinical manifestations of Benign Prostatic Hypertrophy are associated with infra vesical obstruction which is triggered by both anatomical (static) and functional (dynamic) factors. The functional component of obstruction arises from the tension of prostatic smooth muscle which is mediated by alpha-adrenoceptors. Activation of alpha-1-adrenoceptors stimulates smooth muscle contraction, thereby increasing the tone of the prostate, prostatic capsule, prostatic urethra and bladder base, and, consequently, increasing the resistance to bladder outflow. This in turn leads to outflow obstruction and possible secondary bladder instability.
Alpha-blockade decreases infra vesical obstruction via a direct action on prostatic smooth muscle.
In vivo , animal studies have shown that alfuzosin decreases urethral pressure and therefore, resistance to urine flow during micturition. Moreover, alfuzosin inhibits the hypertonic response of the urethra more readily than that of vascular muscle and shows functional uroselectivity in conscious normotensive rats by decreasing urethral pressure at doses that do not affect blood pressure.
In man, alfuzosin improves voiding parameters by reducing urethral tone and bladder outlet resistance, and facilitates bladder emptying.
In placebo controlled studies in BPH patients, alfuzosin:
- significantly increases peak flow rate (Qmax) in patients with Qmax ≤ 15ml/s by a mean of 30%. This improvement is observed from the first dose,
- significantly reduces the detrusor pressure and increases the volume producing a strong desire to void,
- significantly reduces the residual urine volume.
These favourable urodynamic effects lead to an improvement of lower urinary tract symptoms ie. filling (irritative) as well as voiding (obstructive) symptoms.
Alfuzosin may cause moderate antihypertensive effects.
A lower frequency of acute urinary retention is observed in the alfuzosin treated patient than in the untreated patient.
AUR (related to BPH):
In the ALFAUR study, the effect of alfuzosin on the return of normal voiding was evaluated in 357 men over 50 years, presenting with a first episode of acute urinary retention (AUR), related to BPH. In this multicentre, randomised double blind parallel group study comparing alfuzosin 10mg/day and placebo, the evaluation of voiding was performed 24 hours after catheter removal, the morning after 2-3 days of treatment.
In men aged 65 years and over alfuzosin significantly increased the success rate of spontaneous voiding after catheter removal - see table. No benefit has been established in patients under 65 years of age or if treatment is extended beyond 4 days.
ALFAUR study: Percentage of patients (ITT population) successfully voiding post-catheter removal
|
Age |
Placebo N (%) |
Alfuzosin N (%) |
Relative difference vs placebo 95%CI |
p value |
|
65 years and above |
30 (35.7%) |
88 (56.1%) |
1.57 (1.14-2.16) |
0.003 |
|
Below 65 years |
28 (75.7%) |
58 (73.4%) |
0.97 (0.77-1.22) |
0.80 |
|
All patients (50 years and above) |
58 (47.8%) |
146 (61.9%) |
1.29 (1.04-1.60) |
0.012 |
Paediatric Population
Xatral XL is not indicated for use in the paediatric population.
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)
Prolonged-release formulation:
The mean value of the relative bioavailability is 104.4 % versus the immediate release formulation (2.5 mg tid) in middle-aged healthy volunteers and the maximum plasma concentration is being achieved 9 hours after administration compared to 1 hour for the immediate release formulation.
The apparent elimination half-life is 9.1 hours.
Studies have shown that consistent pharmacokinetic profiles are obtained when the product is administered after a meal.
Under fed conditions, mean Cmax and Ctrough values are 13.6 (SD=5.6) and 3.2 (SD=1.6) ng/ml respectively. Mean AUC0-24 is 194 (SD=75) ng.h/ml. A plateau of concentration is observed from 3 to 14 hours with concentrations above 8.1 ng/ml (Cav) for 11 hours.
Compared to healthy middle aged volunteers, the pharmacokinetic parameters (Cmax and AUC) are not increased in elderly patients.
Compared to subjects with normal renal function, mean Cmax and AUC values are moderately increased in patients with renal impairment, without modification of the apparent elimination half-life. This change in the pharmacokinetic profile is not considered clinically relevant. Therefore, this does not necessitate a dosing adjustment.
The binding of alfuzosin to plasma proteins is about 90%. Alfuzosin undergoes extensive metabolism by the liver, with only 11 % of the parent compound being excreted unchanged in the urine. The majority of the metabolites (which are inactive) are excreted in the faeces (75 to 91 %).
The pharmacokinetic profile of alfuzosin is not affected by chronic cardiac insufficiency.
Metabolic interactions: CYP3A4 is the main hepatic enzyme isoform involved in the metabolism of alfuzosin
16/06/2017
Aventis Pharma Limited
One Onslow Street
Guildford
Surrey
GU1 4YS
UK
or trading as:-
Sanofi-aventis or Sanofi
One Onslow Street
Guildford
Surrey
GU1 4YS
UK
No special precautions for storage.
Store in the original container.
PL 04425/0657
There are no data available on the effect on driving vehicles. Adverse reactions such as vertigo, dizziness and asthenia may occur essentially at the beginning of treatment. This has to be taken into account when driving vehicles and operating machinery.
No special requirements
02 April 2009
