SR 5. W2364A_NT.XATRAL SR5 PAK/SA 5/12/05 9:47 Page 1

Transcription

1 W2364A_NT.XATRAL SR5 PAK/SA 5/12/05 9:47 Page 1 alfuzosin SR 5 mg (Alfuzosin HCI) COMPOSITION Each sustained-release, film-coated tablet contains: Alfuzosin hydrochloride mg Excipients... q.s. ad to one sustained-release, film-coated tablet CLINICAL PARTICULARS Therapeutic indications Treatment of the functional symptoms of benign prostatic hypertrophy. Dosage and method of administration The tablet should be swallowed whole, without chewing. - Adults: 1 tablet of XATRAL SR 5 mg, morning and evening. - Elderly subjects or hypertensive patients treated: as a systematic precaution, it is recommended to initiate treatment with one tablet of XATRAL SR 5 mg in the evening, and then increase the dosage depending on the patient s individual response, without exceeding the maximum dosage of 1 tablet of XATRAL SR 5 mg, morning and evening. - Patients with liver failure: it is recommended to initiate treatment with one tablet of XATRAL 2.5 mg per day, and then increase the dosage depending on the patient s individual response, without exceeding one tablet of XATRAL 2.5 mg, twice daily. Contra-indications This product must not be administered in the following cases: - hypersensitivity to alfuzosin, - orthostatic hypotension, - severe liver failure (class C in the CHILD-PUGH classification). Use of this product is generally inadvisable in combination with antihypertensive alpha-blockers (see Drug Interactions). Warnings and special precautions for use In certain subjects, and particularly those being treated with antihypertensive agents, orthostatic hypotension may occur during the hours following dosing, and may be accompanied by other symptoms (dizziness feeling, fatigue, sweating). Caution is recommended, particularly in elderly subjects. These symptoms are usually transient, occur at the beginning of treatment and generally do not prevent the pursuit of treatment. The patient should be informed as to the possible onset of these symptoms. Alfuzosin should not be prescribed as single-drug therapy in coronary patients. Specific treatment for coronary insufficiency should be pursued. If angina pectoris recurs or worsens, alfuzosin therapy should be discontinued. 1

2 W2364A_NT.XATRAL SR5 PAK/SA 5/12/05 9:47 Page 2 Interactions with other drugs and other forms of interaction Inadvisable combination +Antihypertensive alpha-blockers (prazosine, urapidil, minoxidil): Enhancement of the hypotensive effect. Risk of severe orthostatic hypotension. Combination to be taken into account + Antihypertensives Increased antihypertensive effect and risk of orthostatic hypotension (additive effect). Pregnancy and lactation The therapeutic indication does not concern women. The safety of alfuzosin during pregnancy and the passage of alfuzosin into breast milk are unknown. Effects on ability to drive and use machines Particular caution should be exercised by drivers and machine operators because of the risks of orthostatic hypotension, particularly at the beginning of treatment with alfuzosin. Undesirable effects The adverse effects most commonly observed in patients treated with alfuzosin are the following: - gastrointestinal disorders; nausea, gastric pain, diarrhoea; - giddiness, dizziness feeling, malaise; - headaches. The following have been reported in rare cases: - orthostatic hypotension, - syncope; - tachycardia; - palpitations; - chest pain (see Warnings and special precautions for use); - asthenia; - drowsiness; - oedema; - flushing; - dry mouth; - skin rashes; - pruritus. Overdose In the event of overdose, the patient should be hospitalized and kept in supine position. Standard treatment for hypotension should be implemented. Because of its high protein binding level, alfuzosin is difficult to dialyze. PHARMACOLOGICAL PROPERTIES Pharmacodynamic properties OTHER UROLOGICAL PRODUCTS/ALPHA-1 BLOCKER (G04BX02: genitourinary system and sex hormones). Alfuzosin is a quinazoline derivative, which is active when taken via the oral route. It is a selective antagonist of post-synaptic, alpha- 1 adrenergic receptors. In vitro pharmacology studies have confirmed the selectivity of alfuzosin for alpha- 1 adrenergic receptors situated in the prostate, the bladder trigone and the urethra. 2 W2364A

3 W2364A_NT.XATRAL SR5 PAK/SA 5/12/05 9:47 Page 3 Through direct action on the smooth muscle of prostate tissue, alpha blockers reduce obstruction downstream of the bladder. In vivo animal studies demonstrated that alfuzosin reduced urethral pressure and thus resistance to the urinary flow during micturition. A study in conscious rats demonstrates an effect on urethral pressure with a greater amplitude that the effect on blood pressure. During placebo-controlled studies in patients suffering from benign prostatic hypertrophy, alfuzosin: significantly increased the urinary flow rate by on average 30% in patients with rate of < 15 ml/second. This improvement was observed after the first dose; significantly reduced detrusor pressure and increased the volume, thus provoking the sensation of a need to urinate; significantly reduced the residual urine volume. These effects led to an improvement in irritative and obstructive urinary symptoms. They had no deleterious effect on sexual function. Pharmacokinetic properties - Peak plasma concentrations are reached approximately 3 hours after dosing. - The plasma elimination half-life is 8 hours. - Bioavailability is usually reduced by approximately 15%, when compared with that of the 2.5 mg, immediate-release formula. The pharmacokinetic profile is not modified by the concomitant consumption of food. Alfuzosin undergoes marked metabolism in the liver, with excretion in the urine of only 11% of the unchanged compound. Most of the metabolites (which are inactive) are excreted in the feces (75 to 90%). - In elderly subjects over the age of 75 years, alfuzosin is absorbed more rapidly and peak concentrations are higher. Bioavailability may be increased, and a reduction in the volume of distribution may be observed in certain patients. The elimination half-life remains unchanged. - The elimination half-life is prolonged in patients with severe liver failure. Bioavailability is increased when compared to that seen in healthy volunteers. - In patients with kidney failure who do or do not require dialysis, the volume of distribution and clearance of alfuzosin increase because of an elevation of the free fraction. Chronic or even severe kidney failure (creatinine clearance between 15 and 40 ml/min) are not aggravated by alfuzosin. - The pharmacokinetic profile of alfuzosin is not modified in the event of chronic heart failure. PHARMACEUTICAL PARTICULARS Shelf-life: 3 years. Special precautions for storage: Store below 40 C. Presentation: Boxes of 28 tablets Registration No Manufactured by: SANOFI WINTHROP INDUSTRIE 30-36, avenue Gustave Eiffel Tours - FRANCE For: Aventis Limited Plot 23 Sector 22, Korangi Industrial Area, Karachi Under Licence of Sanofi-Synthelabo, France 3

4 W2364A_NT.XATRAL SR5 PAK/SA 5/12/05 9:47 Page 4 *W2364A* 4 W2364A

5 W2364A_NT.XATRAL SR5 PAK/SA 5/12/05 9:47 Page 5 Approvals Technical Data For Sanofi-Aventis use only Code : Update : Local code : Current item code : Product/Item type : Country : Artwork by : Plant : Supplier code : W2364A V2-05/DEC/05 N.A. W2358B NOTICE XATRAL SR 5MG PAK Format : 157 x 135 mm - Rouleau Double Plant barcode : *W2364A* Colours : 1 - Noir PMS BLACK U Carine PHILIPPE TOURS N.A. Fonts : OceanSans AV - L39HrP24Dh Assembly Card : D-DPL2003-PLANTYPE Layout of Cutting : TN_LCG_NTRL_03/2 Technical Card : N.A. Technical Constraint : N.A.