Xatger 10 mg prolonged release tablets

6.5 Nature and contents of container
PVC/PVDC-aluminium blister.

10, 20, 30, 30x1, 50, 60, 60x1, 90, 100 tablets

Not all pack sizes may be marketed.

section 2:

Excipient with known effect:

Each tablet contains 7.6 mg lactose (as lactose monohydrate).

 

For the full list of excipients, see section 6.1.

section 4.1
Treatment of moderate to severe functional symptoms of benign prostatic hyperplasia (BPH).-

section 4.2

Posology

 

Adults

 One 10 mg prolonged-release tablet once daily. The first dose should be taken at bedtime. The tablet should be taken immediately after the same meal each day.

 

Paediatric population

The safety and efficacy of alfuzosin have not been demonstrated in children aged 2 to 16 years (see section 5.1). Therefore, alfuzosin is not indicated for use in paediatric population.

Patients with reduced renal function

Mild to moderate renal insufficiency

If a lower dose is not sufficient, therapy can be adjusted to one 10 mg prolonged-release tablet daily according to clinical response.

Patients with hepatic insufficiency

Method of administration

For oral use.

 

The prolonged-release tablet should be swallowed whole with a sufficient amount of fluid (see section 4.4).

section 4.4

Patients with severe renal impairment

Risk of hypotension

In coronary patients, the specific treatment for coronary insufficiency should be continued, taking into account that the concomitant administration of nitrates and alfuzosin may increase the risk of occurrence of hypotension. If angina pectoris reappears or worsens, alfuzosin should be discontinued.

Pronounced drop in blood pressure has been reported in post-marketing surveillance in patients with pre-existing risk factors (such as underlying cardiac disease and/or concomitant treatment with anti-hypertensive medication). The risk of developing hypotension and related adverse reactions may be greater in older people

There is a risk of cerebral ischaemic disorders in patients with symptomatic or asymptomatic pre-existing cerebral circulatory disturbances, due to the fact that hypotension may develop following alfuzosin administration (see section 4.8).

Previous history of hypersensitivity to other alpha₁-receptor blockers

Treatment should be initiated gradually in patients with hypersensitivity to other alpha₁-receptor blockers.

Cardiac failure

As with all alpha₁-receptor blockers, alfuzosin should be used with caution in patients with acute cardiac failure.

QTc prolongation

Intraoperative Floppy Iris Syndrome

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. Isolated reports have also been received with other alpha₁-receptor blockers and the possibility of a class effect cannot be excluded. As IFIS may lead to increased procedural complications during the operation, the surgeon should be informed of current or past alpha₁-receptor blocker use and prepare for possible modifications to their surgical technique.

 

Tablet administration

Lactose

This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

section 4.5

• protease inhibitors, clarithromycin, telithromycin and nefazodone since alfuzosin blood levels are increased (see section 5.2).
• Patients being treated with alfuzosin must be haemodynamically stable before treatment with a phosphodiesterase-5 inhibitor (sildenafil, tadalafil, vardenafil) is initiated.

 

Ketoconazole

Repeated 200 mg daily dosing of ketoconazole, for seven days resulted in a 2.1-fold increase in C_max and a 2.5-fold increase in exposure of xatger 10 mg prolonged-release tablets when administered under fed conditions. Other parameters such as t_max and t_1/2 were not modified.

 

The increase in alfuzosin C_max and AUC_(last) following repeated 400 mg daily administration of ketoconazole was 2.3-fold and 3.2-fold respectively (see section 5.2).

section 4.6

FertilityNo data are available.

section 4.8: table

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 HPRA Pharmacovigilance, Earlsfort Terrace, IRL – Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.

section 4.9

Symptoms

Hypotension, reflex tachycardia.

 

Management

section 5.1
Drugs used in benign prostatic hypertrophy, alpha-adrenoreceptor antagonists,

 

Mechanism of action

Pharmacodynamic effects

Clinical efficacy and safety

 

Benign Prostatic Hypertrophy (BPH)

Acute urinary retention (AUR) related to BPH

Alfuzosin has been shown to increase the chances of successful spontaneous urination at first episode of acute urinary retention (AUR) related to BPH and in the following six months after this episode, reducing the requirement for surgery.

 

In a double-blind placebo-controlled study including 357 patients, alfuzosin 10 mg daily increased the success rate of spontaneous urination after catheter removal in men over 65 years.

 

88 patients (56.1%) in alfuzosin group had successful urination, while 30 patients (35.7%) in the placebo treatment had successful urination (p = 0.003).

 

165 patients who achieved successful urination during the first phase were included in the second phase and were re-examined: alfuzosin reduced the risk of surgery (both emergency surgery due to recurrence of AUR or as non-emergency) compared to placebo with a risk reduction of respectively 61%, 52%, and 29% at 1, 3 and 6 months of treatment with alfuzosin.

section 5.2

Absorption

 The maximal plasma concentration is achieved 9 hours after administration.

 

Studies have shown that consistent pharmacokinetic profiles are obtained when the product is administered after a meal.

 

After the first dose (fed) the mean maximum plasma concentration was 7.72 ng/ml, AUC_inf was 127 ng x h/ml (fed), and t_max was 6.69 h (fed). Under steady state conditions (fed) the mean AUC over the dosing interval (AUC_τ) was 194 (SD = 75) ng x h/ml, mean C_max was 13.6 (SD = 5.6) ng/ml and C_min was 3.1 (SD = 1.6) ng/ml.

Biotransformation

Alfuzosin is extensively metabolised in the liver (through various routes). None of the metabolites are pharmacologically active.

 

Metabolic interactions: CYP3A4 isoform is the principal hepatic enzyme involved in the metabolism of alfuzosin (see section 4.5).

Alfuzosin metabolites are eliminated via renal excretion and probably also via biliary excretion.

Linearity/non-linearity

Alfuzosin has linear pharmacokinetic properties within the therapeutic dose range.

 

Renal or hepatic impairment

Compared to subjects with normal renal function, mean C_max 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 with creatinine clearance >30ml/min.

section 4.2 uopdated to include:

Paediatric population:

Efficacy of Xatger has not been demonstrated in children aged 2 to 16 years

(see section 5.1). Therefore, Xatger is not indicated for use in paediatric

population.

section 5.1 updated to include:

Paediatric population

Xatger 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.

section 4.4 Special warnings and precautions for use
added:

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 Xatger.

SPC uploaded on IPHA following approval of MR Renewal.

Section 5.2 Pharmacokinetic properties

Paragraph 'Alfuzosin has linear pharmacokinetic properties etc....' was repeated so removed one paragraph.

Section 9 Date of Authorisation/Renewal of the Authorisation

included date of last renewal: 5th September 2010

Section 10 Date of revision of the text

updated to April 2011

 Variations approved to update SPC section 4.2, 4.4 (include Intraoperative Floppy Iris Syndrome) 5.2 and 10 and consequential changes to the Package Leaflet.

 udpated SmPC in line with variation approval to increase shelf life to 4 years