Pharmacological properties
Pharmacodynamics. Alfuzosin is an active quinazoline derivative. In vitro pharmacological studies have shown the selectivity of alfuzosin's action on α1-adrenoreceptors located in the prostate gland, at the bottom of the bladder and in the prostatic urethra.
The clinical manifestations of benign prostatic hypertrophy (BPH) are associated with intravesical obstruction, the mechanism of which includes both anatomical (static) and functional (dynamic) factors. The functional component of obstruction occurs due to the tension of the smooth muscles of the prostate gland, transmitted by α 1 -adrenoreceptors. Activation of α 1 -adrenoreceptors stimulates smooth muscle contraction, thereby increasing the tone of the prostate gland, its membrane, the prostatic part of the urethra and the fundus of the bladder, which leads to obstruction of the outflow from the bladder and, possibly, secondary bladder instability.
Alpha blockade reduces intravesical obstruction by directly affecting the smooth muscle of the prostate.
Alfuzosin reduces the pressure in the urethra and thus reduces the resistance to urine outflow during urination. Alfuzosin inhibits the hypertensive response of the urethra to the vascular muscles.
Alfuzosin improves excretion parameters by reducing urethral tone and bladder outflow resistance, facilitating bladder emptying.
Pharmacokinetics. Absorption. The mean relative bioavailability is 104.4% compared to the immediate-release form (2.5 mg twice daily) in healthy middle-aged volunteers, and Cmax is achieved 9 hours after administration compared to 1 hour for the immediate-release form.
Studies have shown that an appropriate pharmacokinetic profile is achieved when the drug is administered after a meal.
When the drug is administered after a meal, the average values of C max and C trough are 13.6 (CO = 5.6) and 3.2 (CO = 1.6) ng / ml, respectively. The average value of AUC 0-24 = 194 (CV = 75) ng • h / ml. The concentration plateau is observed after 3-14 hours, the concentration exceeds 8.1 ng / ml (C mav) for 11 hours.
Distribution: The binding of alfuzosin to plasma proteins is ≈90%.
Metabolism and excretion. Alfuzosin undergoes extensive metabolism in the liver, only 11% of the parent compound is found unchanged in the urine. Most of the metabolites (which do not show activity) are excreted in the feces (75-91%). T ½ is 9.1 hours.
Special patient groups
Renal impairment. Mean concentrations and AUC values in patients with renal impairment are moderately increased, without change in T½. This change in the pharmacokinetic profile of the drug is considered to be of no clinical significance. Therefore, dose adjustment is not required.
Heart failure: The pharmacokinetic profile of alfuzosin is not altered in chronic heart failure.
Elderly patients: Pharmacokinetic parameters (C max and AUC) are not increased in elderly patients.
Indication
Symptomatic treatment of BPH.
Application
The drug is intended exclusively for men!
The recommended dose is 10 mg (1 tablet) once a day. It is used immediately after a meal. The tablets should be swallowed whole. The patient should be warned that the tablets should not be bitten, chewed, crushed or ground into powder. Crushing the tablets may lead to rapid release and absorption of the active substance of the drug and, as a result, to the rapid appearance of side effects of the drug.
Contraindication
Hypersensitivity to Alfuzosin or any of the components of the drug. Orthostatic hypotension; combination with other α-adrenoceptor blockers; Liver failure, chronic renal failure (creatinine clearance 30 ml/min). Children.
Side effects
Adverse reactions are listed by frequency: very common (1/10), common (1/100; 1/10), uncommon (1/1000; 1/100), rare (1/10,000; 1/1000), very rare (1/10,000). Within each group, adverse reactions are presented in order of decreasing seriousness.
From the nervous system: often - fainting / dizziness, headache; sometimes - vertigo, malaise, drowsiness.
From the cardiovascular system: rarely - tachycardia, palpitations, arterial hypotension (orthostatic), syncope; very rarely - the occurrence, worsening or recurrence of angina pectoris in patients with a history of coronary artery disease.
From the gastrointestinal tract: often - nausea, abdominal pain; sometimes - diarrhea, dry mouth.
Skin and subcutaneous tissue disorders: often - rash, itching; very rarely - urticaria, angioedema.
General disorders: often - asthenia; sometimes - hot flashes, edema, chest pain; in isolated cases - priapism.
Special instructions
As with all α1-blockers, some patients (especially those receiving antihypertensive treatment) may develop postural hypotension with or without symptoms (dizziness, fatigue, increased sweating) within a few hours after taking the drug. In such cases, the patient should lie down until the symptoms disappear completely. These phenomena are usually temporary, occur at the beginning of treatment and do not require discontinuation of the drug. The patient should be warned about the possibility of such phenomena.
The drug is not prescribed to patients with coronary insufficiency. It is necessary to continue specific treatment of coronary insufficiency. If angina pectoris recurs or worsens with conventional antianginal therapy, Alfirum should be canceled.
In some patients who previously used tamsulosin, intraoperative atonic iris syndrome (ISAR, a variant of narrow pupil syndrome) was noted during cataract surgery. Isolated reports have also been received with the use of other α 1 -adrenoceptor blockers, so the possibility of such an effect with the use of Alfirum cannot be excluded. Since ISAR may increase the severity of procedural complications during cataract surgery, the ophthalmologist should be warned in advance about the existing or previous use of α 1 -adrenoceptor blockers.
Experience with the drug in people with impaired renal function is limited, therefore it is recommended to use the drug with caution in such patients.
The drug is used in patients with creatinine clearance of 30 ml/min.
The ability to influence the reaction rate when driving or working with complex mechanisms. The drug can cause side effects such as vertigo, dizziness and asthenia, so during treatment you should refrain from driving or working with mechanisms.
Interactions
Particular caution should be exercised when using alfuzosin concomitantly with antihypertensive drugs, nitrates and strong CYP 3A4 inhibitors (ketoconazole, itraconazole and ritonavir).
The use of general anesthetics in patients taking alfuzosin may cause severe hypotension. It is recommended that the drug be discontinued 24 hours before surgery.
Overdose
In case of overdose of the drug, arterial hypotension is observed. It is necessary to hospitalize the patient, treat arterial hypotension. The patient should be in a supine position.
The drug is poorly dialyzed due to the high degree of protein binding.
Storage conditions
At a temperature not exceeding 25 °C.
