Alfuzosin

Pharmacological properties

alfuzosin is an active derivative of quinazoline. in vitro pharmacological studies have shown the selectivity of alfuzosin on α1-adrenergic receptors located in the prostate gland, at the bottom of the bladder and in the prostate urethra.

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 the blockage is due to tension of the smooth muscles of the prostate gland, α is transmitted₁-adrenoreceptors. Activation α₁-adrenoreceptors stimulates smooth muscle contraction, thereby increasing the tone of the prostate gland, its membrane, prostate urethra and the bottom of the bladder, which leads to blockage of the outflow from the bladder and, possibly, secondary instability of the bladder.

Alpha blockade reduces intravesical obstruction by directly affecting the smooth muscles of the prostate gland.

Alfuzosin reduces the pressure in the urethra and thus reduces the resistance to urine outflow during urination. Alfuzosin suppresses the hypertonic reaction of the urethra before the vascular muscles.

Alfuzosin improves the parameters of the discharge, reducing the tone of the urethra and the resistance of the outflow from the bladder, facilitates the emptying of the bladder.

Pharmacokinetics Absorption. The average relative bioavailability is 104.4% compared with the immediate release form (2.5 mg 2 times a day) in healthy middle-aged volunteers, and C_max achieved 9 hours after taking the drug compared to 1 hour for the immediate release form.

Studies have shown that an appropriate pharmacokinetic profile is achieved when the drug is used after meals.

In the case of the use of the drug after eating, average C_max and C_trough are 13.6 (CO = 5.6) and 3.2 (CO = 1.6) ng / ml, respectively. Average AUC_0-24= 194 (SV = 75) ng • h / ml. A plateau of concentration is noted 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 a significant metabolism in the liver, only 11% of the starting compound appears unchanged in the urine. Most metabolites (not showing activity) are excreted in the feces (75–91%). T_½ 9.1 hours

Special Patient Groups

Renal failure. The average values ​​of concentration and AUC in patients with renal failure are moderately increased, without changing T_½. It is believed that this change in the pharmacokinetic profile of the drug has no clinical significance. Therefore, dose adjustment is not required.

Heart failure. The pharmacokinetic profile of alfuzosin does not change in chronic heart failure.

Elderly patients. In elderly patients, pharmacokinetic parameters (C_max and AUC) do not increase.

Indications

Symptomatic treatment of BPH.

Application

The drug is intended exclusively for men!

The recommended dose is 10 mg (1 tablet) once a day. Apply immediately after eating. Swallow the tablets whole. The patient should be warned that tablets should not be crushed, chewed, crushed, or ground into powder. Grinding tablets can lead to the 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.

Contraindications

Hypersensitivity to alfuzosin or any components of the drug.orthostatic hypotension; combination with other blockers of α-adrenergic receptors; liver failure, chronic renal failure (creatinine clearance 30 ml / min). childhood.

Side effects

Adverse reactions are listed by frequency: very often (1/10), often (1/100; 1/10), sometimes (1/1000; 1/100), rarely (1/10 000; 1/1000), very rarely (1/10 000). in each group, adverse reactions are listed in decreasing order of severity.

From the side of 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 relapse of angina pectoris in patients with a history of coronary artery disease.

From the digestive tract: often - nausea, abdominal pain; sometimes - diarrhea, dry mouth.

On the part of the skin and subcutaneous tissue: often - rash, itching; very rarely - urticaria, angioedema.

General disorders: often - asthenia; sometimes - flushing, swelling, chest pain; in isolated cases - priapism.

special instructions

As with all α1-adrenoreceptor blockers, some patients (especially those receiving antihypertensive treatment) may develop postural hypotension with or without symptoms (dizziness, fatigue, sweating) within a few hours after taking the drug. in such cases, the patient should lie until the symptoms disappear completely. these phenomena are usually temporary, noted at the beginning of treatment and do not require discontinuation of the drug. the patient must be warned about the possibility of such phenomena.

Patients Hypersensitive to α Blockers₁-adrenoreceptors begin treatment with low doses. It is necessary to regularly monitor blood pressure, especially at the beginning of treatment.

Patients with coronary insufficiency are not prescribed. It is necessary to continue the specific treatment of coronary insufficiency. If the course of angina resumes or worsens with conventional antianginal therapy, Alfirum should be discontinued.

In some patients who previously used tamsulosin, intraoperative atonic iris syndrome (ISAR, a variant of narrow pupil syndrome) was noted during cataract surgery. Separate messages were also received when other α blockers were used.₁-adrenoreceptors, therefore, the possibility of such an effect when using the drug Alfirum is not ruled out. Since ISAR can increase the severity of procedural complications during cataract surgery, an ophthalmologist must be warned in advance about existing or prior use of α blockers₁-adrenoreceptors.

The experience of using the drug in people with impaired renal function is limited, so 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 a vehicle or working with machinery. The drug can cause adverse reactions such as vertigo, dizziness and asthenia, so during treatment you should refrain from driving or working with machinery.

Interactions

Special care should be taken with the simultaneous use of alfuzosin and antihypertensive drugs, nitrates and potent cyp 3a4 inhibitors (ketoconazole, itraconazole and ritonavir).

The use of general anesthetics in patients taking alfuzosin can cause severe hypotension. It is recommended to stop using the drug 24 hours before surgery.

Overdose

With an overdose of the drug, hypotension is noted. it is necessary to hospitalize the patient, to treat arterial hypotension. the patient should be in a prone position.

The drug is poorly dialyzed due to the high degree of protein binding.

Storage conditions

At a temperature not exceeding 25 ° c.