Contents

Alfutor extended release tablets (10mg Alfuzosin Hydrochloride)

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.

Therapeutic indications

Treatment of the functional symptoms of benign prostatic hypertrophy (BPH).

Adjuvant treatment to a catheter in acute urinary retention related to benign prostatic hypertrophy

Posology and method of administration

The tablet should be swallowed whole

BPH: The recommended dose is one 10mg tablet to be taken once daily after a meal.

AUR: One 10 mg tablet daily after a meal to be taken from the first day of catheterization. The treatment should be administered for 3-4 days, 2-3 days during catheterization and 1 day after its removal.

Paediatric Population

Efficacy of Alfuzosin has not been demonstrated in children aged 2 to 16 years. Therefore Alfuzosin 10mg tablets is not indicated for use in the paediatric population.

Contraindications

Hypersensitivity to the active substance or to any of the excipients.
History of orthostatic hypotension.
Combination with other alpha-1 receptor blockers.
Hepatic insufficiency.

Special warnings and precautions for use

As with all alpha-1-blockers in some subjects, in particular patients receiving antihypertensive medications or nitrates, postural hypotension with or without symptoms (dizziness, fatigue, sweating) may develop within a few hours following administration. In such cases, the patient should lie down until the symptoms have completely disappeared.

These effects are transient, occur at the beginning of treatment and do not usually prevent the continuation of treatment. Pronounced drop in blood pressure has been reported in post-marketing surveillance in patient with pre-existing risk factors (such as underlying cardiac diseases and/or concomitant treatment with anti-hypertensive medication. The risk of developing hypotension and related adverse reactions may be greater in elderly patients. The patient should be warned of the possible occurrence of such events.

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

Care should be taken when Alfuzosin 10mg is administered to patients who have had a pronounced hypotensive response to another alpha-1-blocker.

Treatment should be initiated gradually in patients with hypersensitivity to alpha-1-blockers. Alfuzosin 10mg should be administered carefully to patients being treated with antihypertensive medication or nitrates. Blood pressure should be monitored regularly, especially at the beginning of 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.

Concomitant use of alfuzosin and potent CYP3A4 inhibitors (such as itraconazole, ketoconazole, protease inhibitors, clarithromycin, telithromycin and nefazodone) should be avoided. Alfuzosin should not be used concomitantly with CYP3A4 inhibitors that are known to increase the QTc interval (e.g. itraconazole and clarithromycin) and a temporary interruption of alfuzosin treatment is recommended if treatment with such medicinal products is initiated.

Prolonged erections and priapism have been reported with alpha-1 blockers including alfuzosin in post marketing experience. If priapism is not treated immediately, it could result in penile tissue damage and permanent loss of potency, therefore the patient should seek immediate medical assistance.

In coronary patients, the specific treatment for coronary insufficiency should be continued. If angina pectoris reappears or worsens Alfuzosin 10mg should be discontinued.

As there are no clinical safety data available in patients with severe renal impairment (creatinine clearance < 30ml/min), alfuzosin 10 mg prolonged released tablets should not be administered to this patient group.

Patients should be warned that the tablet should be swallowed whole. Any other mode of administration, such as crunching, crushing, chewing, grinding or pounding to powder should be prohibited. These actions may lead to inappropriate release and absorption of the drug and therefore possible early adverse reactions.

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 alpha-1-blockers. Although the risk of this event with alfuzosin appears very low, ophthalmic surgeons should be informed in advance of cataract surgery of current or past use of alpha-1-blockers, as IFIS may lead to increased procedural complications. The ophthalmologists should be prepared for possible modifications to their surgical technique.

Interaction with other medicinal products and other forms of interaction

Combinations contra-indicated:

Alpha-1-receptor blockers.

Concomitant use not recommended:

potent CYP3A4 inhibitors such as itraconazole, ketoconazole, protese inhibitors, clarithromycin, telithromycin and nefazodone since alfuzosin blood levels may be increased.

Combinations to be taken into account:

Antihypertensive drugs
Nitrates

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 10 mg 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 10 mg, 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.

The administration of general anaesthetics to patients receiving Alfuzosin could cause profound hypotension. It is recommended that the tablets be withdrawn 24 hours before surgery.

Pregnancy and lactation

Due to the type of indication this section is not applicable

Effects on ability to drive and use machines

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.

Overdose

In case of over dosage, the patient should be hospitalized, 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.

Alfutor extended release tablets (10mg Alfuzosin Hydrochloride)

Alfutor extended release tablets (10mg Alfuzosin Hydrochloride)