Alfuzosin hydrochloride..... 10 mg
For one Modified -release tablet
Drugs used in benign prostatic hypertrophy/alpha-Blockers
Alfuzosin is a quinazoline derivative, active by the oral route. It is a selective antagonist of post-synaptic alpha-1 adrenergic receptors. Pharmacological studies conducted in vitro have confirmed the selectivity of Alfuzosin for alpha-1 adrenergic receptors located in the prostate, the trigone of the bladder and the urethra.
Due to a direct action on the smooth muscle of the prostatic tissue, alpha-blockers reduce lower urinary tract obstruction. In vivo studies in animals have shown that Alfuzosin reduces urethral pressure and hence resistance to urinary flow during voiding. A study on awake rats reveals an effect on urethral pressure greater than that on blood pressure.
In placebo-controlled studies in patients with benign prostatic hypertrophy, Alfuzosin:
- Significantly increased urinary flow rate by a mean of 30% in patients with a flow rate ≤15 ml/s. This improvement is observed from the first dose,
- Significantly reduced the detrusor pressure and increased the volume, producing a strong need to void.
- Significantly reduced the residual urine volume.
These effects lead to an improvement in irritative and obstructive urinary symptoms. They have no detrimental effect on sexual function.
In the ALFAUR study, the effect of Alfuzosin on return to voiding was assessed in 357 men over the age of 50 presenting a first painful episode of acute urinary retention (AUR) related to benign prostatic hypertrophy (BPH) with a residual urine volume of between 500 and 1500 ml following insertion of a catheter and for the first hour after catheterisation. In this multi-centered, randomised, double-blind study in two parallel groups comparing 10 mg/day Alfuzosin LP with placebo, evaluation of return to voiding was conducted 24 hours after removal of the catheter, in the morning, after at least two days of Alfuzosin treatment.
Treatment with Alfuzosin significantly increased (p = 0.012) the rate of return to voiding after catheter removal in patients having suffered a first episode of AUR, i.e. 146 returns to voiding (61.9%) in the Alfuzosin group versus 58 (47.9%) in the placebo group.
Plasma protein binding of Alfuzosin hydrochloride is approximately 90%. Alfuzosin undergoes marked metabolisation by the liver with excretion in the urine of only 11% of unchanged substance.
Most of the metabolites (which are inactive) are excreted in the faeces (75 to 90%).
The pharmacokinetic profile of Alfuzosin is not modified in the event of chronic heart failure.
The mean value for relative bioavailability is 104.4% after administration of the 10-mg dose, in comparison with that for the immediate-release formulation at a dosage of 7.5 mg (2.5 mg t.i.d.), in middle-aged healthy volunteers. The peak plasma concentration is reached 9 hours after administration as compared to 1 hour for the immediate formulation.
The apparent elimination half-life is 9.1 hours.
Studies have shown that the bioavailability is increased when the drug is administered after a meal (Cf. Posology and method of administration).
The pharmacokinetic parameters (Cmax and AUC) are not increased in the elderly as compared to middle-aged healthy volunteers.
The mean Cmax and AUC values are moderately increased in patients with moderately impaired kidney function (creatinine clearance > 30 ml/min), without any modification in elimination half-life, as compared to patients with normal kidney function.
Dosage adjustment is not, therefore, necessary in patients with impaired kidney function with a creatinine clearance > 30 ml/min.
- Treatment of certain functional symptoms of benign prostatic hypertrophy, particularly if surgery has to be delayed for some reason.
- Adjuvant treatment to a catheter in acute urinary retention related to benign prostatic hypertrophy.
This drug must not be administered in the following situations:
- Hypersensitivity to Alfuzosin.
- Orthostatic hypotension,impaired liver function.
- Severely impaired kidney function (creatinine clearance < 30 ml/min).
This drug not generally advised in combination with antihypertensive alpha-blockers (Cf. Interactions with other medicinal products).
The most commonly reported undesirable effects in patients treated with Alfuzosin have been as follows:
- Gastrointestinal disturbances: nausea, gastric pain, diarrhea , Light-headedness, dizziness, feeling faint, Headaches.
The following have been reported more
- Orthostatic hypotension, Syncope, Tachycardia, Palpitations, Chest pain (Cf. Special warnings and special precautions for use), Asthenia , Drowsiness, oedema, Hot flushes, Dryness of the mouth, Skin rashes and pruritus.
In the event of overdose, the patient should be hospitalised and. kept lying down. Standard treatment for hypotension should be instigated. Due to its high degree of protein binding, Alfuzosin is not easily dialysable.
The recommended dosage is one 10-mg tablet per day, to be taken immediately after the evening meal.
Adjuvant treatment to a catheter in acute urinary retention related to benign prostatic hypertrophy:
The recommended dosage is one 10-mg tablet per day, to be taken after a meal, from the first day of catheterisation onwards.
The treatment is administered for 3 to 4 days, i.e. 2 to 3 days while the catheter is in place and 1 day after it is removed.
The tablet must be swallowed whole.
Interactions with other medicinal products and other forms of interaction:
- Antihypertensive alpha-blockers (Prazosin, Urapidil, Minoxidil):
Increase in the hypotensive effect. Risk of severe orthostatic hypotension.
Combination to be taken into account
- Antihypertensive drugs:
Antihypertensive effect and risk of orthostatic hypotension increased (additive effect).
The administration of general anaesthetics to patients receiving Alfuzosin could cause profound hypotension.
It is recommended that Alfuzosin be withdrawn 24 hours before surgery.
Special warnings and special precautions for use
In some subjects, particularly those treated with antihypertensive medication, orthostatic hypotension may after taking the drug, possibly accompanied by symptoms (dizziness, fatigue, sweating). Caution is recommended, particularly in the elderly.
These effects are usually transient, occur at the beginning of treatment and do not usually prevent the continuation of treatment. The patient must be informed of the possible occurrence of such incidents.
In coronary patients, Alfuzosin should not be prescribed alone. Specific medication for coronary insufficiency should be continued. In the event of the recurrence or exacerbation of angina, treatment with Alfuzosin should be stopped.
Treatment should be initiated gradually in patients with hypersensitivity to alpha-1 blockers. Alfuzosin should be administered carefully to patients being treated with antihypertensives. Blood pressure should be monitored regularly, especially at the beginning of the treatment.
Pregnancy and lactation
The therapeutic indication does not apply to women.
The safety of Alfuzosin during pregnancy and its passage into breast milk are unknown.
Effects on ability to drive and use machines
Particular caution is required when driving vehicles or using machines due to the risks of orthostatic hypotension, especially at the start of treatment with Alfuzosin.
Keep in a dry place, at a temperature not exceeding 30 °C.
Pack of 1, 2 or 3 AL/PVC/PVDC blisters each of 10 tablets.