Dalfaz SR

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

Dalfaz SR HCl 2.5 mg film-coated tablets should be swallowed whole. The first dose should be given just before bedtime.

Adults

The usual dose is one tablet three times daily. The dose may be increased to a maximum of 4 tablets (10 mg) per day depending on the clinical response.

Elderly and treated hypertensive patients

As a routine precaution when prescribing Dalfaz SR to elderly patients (aged over 65 years) and the treated hypertensive patient, the initial dose should be 1 tablet in the morning and 1 tablet in the evening.

Renal insufficiency

In patients with renal insufficiency, as a precaution, it is recommended that the dosing be started at Dalfaz SR HCl 2.5mg twice daily adjusted according to clinical response.

Hepatic insufficiency

In patients with mild to moderate hepatic insufficiency, it is recommended that therapy should commence with a single dose of Dalfaz SR HCl 2.5 mg Tablets/day to be increased to Dalfaz SR HCl 2.5 mg Tablets twice daily according to clinical response.

Dalfaz SR HCl 2.5 mg tablets are contraindicated in patients with severe hepatic insufficiency.

Paediatric population:

Efficacy of Dalfaz SR has not been demonstrated in children aged 2 to 16 years. Therefore, Dalfaz SR is not indicated for use in paediatric population.

- Hypersensitivity to the active substance Dalfaz SR, another quinazolines (eg: terazosine, doxazosine) or to any of the excipients.

- History of orthostatic hypotension.

- Combination with other alfa1-blockers and / or dopamine receptor agonists.

- Severe hepatic insufficiency

Blood pressure should be monitored at the start of treatment. A reduction in blood pressure may arise in individual cases.

Dalfaz SR HCl should be given with caution to patients who are on antihypertensive medication or nitrates.

In some subjects postural hypotension may develop, with or without symptom (dizziness, fatigue, sweating) within a few hours following administration. These effects are transient, occur in the beginning of treatment and do not usually prevent the continuation of treatment.

In cases of orthostatic hypotension the patient should lie or sit down until the symptoms have disappeared.

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

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

As with all alpha-1-blockers, Dalfaz SR should be used with caution in patients with acute cardiac failure.

- lung oedema due to mitral or tricuspidal stenosis,

- high output cardiac failure,

- cardiac failure due to pulmonary embolism or pericardial effusion

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 Dalfaz SR

The patient should be examined prior to treatment with Dalfaz SR to exclude other conditions, which may cause the same symptoms as benign prostatic hyperplasia. A digital rectal examination should be performed prior to treatment and regularly during treatment. A prostate specific antigen (PSA) test should also be carried out if required.

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 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 ophthalmic surgeon in advance of surgery.

Dalfaz SR should not be used in patients suffering from incontinence due to overflow, anuria or prolonged renal insufficiency.

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.

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.

No data are available concerning the effect on ability to drive or use machines. Side-effects such as, vertigo, dizziness or asthenia may occur, in particular, at the start of treatment. This should be taken into consideration when driving vehicles or using machines.

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 (>1/10000 to ≤1/1000); very rare (≤1/10000), not known (cannot be estimated from the available data).

In case of overdosage, the patient should be hospitalised, kept in the supine position, and conventional treatment of hypotension should take place. Dalfaz SR is not easily dialysable because of its high degree of protein binding. Gastric lavage is a possibility followed by administration of activated carbon and a laxative.

Pharmacotherapeutic group: alpha adrenoreceptor antagonists

ATC code: G04CA01

Dalfaz SR is an orally active quinazoline derivative. It is a selective, peripherally acting antagonist of post synaptic alfa1-adrenoceptors.

In vitro pharmacological studies have documented the selectivity of Dalfaz SR for the alpha1-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 α-adrenoceptors. Activation of alfa1-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 Dalfaz SR decreases urethral pressure and therefore, resistance to urine flow during micturition. Moreover, Dalfaz SR 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, Dalfaz SR improves voiding parameters by reducing urethral tone and bladder outlet resistance, and facilitates bladder emptying.

In placebo controlled studies in BPH patients, Dalfaz SR significantly increases peak flow rate (Q_max) in patients with Q_max ≤ 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.

Paediatric population

Dalfaz SR is not indicated for use in the paediatric population.

Efficacy of Dalfaz SR 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 Dalfaz SR hydrochloride 0.1 mg/kg/day or 0.2 mg/kg/day using adapted paediatric formulations.

Dalfaz SR HCl 2.5mg Tablets are well absorbed with a mean bioavailability of 64%, peak plasma levels are generally reached in 0.5-6 hours. The kinetics are linear within the therapeutic dosage. The kinetic profile is characterised by large inter-individual variations in plasma concentrations. The half-life is 3 - 5 hours. The plasma-protein binding of Dalfaz SR is approximately 90%. Dalfaz SR is metabolised by the liver and is primarily excreted in urine and faeces. None of the metabolites found in humans has a pharmacodynamic action. Theharmacokinetic profile is not influenced by concurrent ingestion of food.

Absorption in patients older than 75 years is more rapid and plasma levels are higher. Biological availability may be higher, while for some patients the distribution volume is reduced. The elimination half-life remains unchanged.

The distribution volume and metabolic clearance of Dalfaz SR is increased with renal insufficiency through an increase of the free fraction. Chronic renal insufficiency, even where this is severe (creatinine clearance between 15 and 40 ml/minute) is not negatively influenced by Dalfaz SR.

A twofold increase of C_max levels and a threefold increase in the AUC have been observed in patients with severe hepatic insufficiency. The biological availability is increased in comparison with healthy volunteers. The pharmacokinetic profile of Dalfaz SR is not influenced by chronic cardiac insufficiency.

Metabolic interactions: CYP3A4 is the principal hepatic enzyme isoform involved in the metabolism of Dalfaz SR

In vitro, Dalfaz SR prolonged the action potential duration and QT interval duration at a clinically relevant concentration.

No other data of therapeutic relevance.

Not applicable.

Any unused product or waste material should be disposed of in accordance with local requirements.