Alfuzosin - instructions for use, dose, side effects, contraindications

Excipients: kollidone SR [polyvinyl acetate 80%, povidone 19%, sodium lauryl sulfate 0.8%, silicon dioxide 0.2%] - 58.8 mg; lactose monohydrate 74.1 mg; silicon dioxide colloidal - 1.4 mg; magnesium stearate - 0.7 mg.

Dosage of 10 mg

active substance: alfuzosin hydrochloride - 10.0 mg;

Excipients: hypromellose (Methocel K 4M) - 100.0 mg; starch corn pregelatinization (starch 1500) - 136.2 mg; silicon dioxide colloidal - 1.3 mg; magnesium stearate - 2.5 mg.

Description:

Round flat cylindrical tablets white or white with a yellowish tint of color with a facet (5 mg dose) or with a facet and a risk (dosage of 10 mg).

Pharmacotherapeutic group:Alpha-blocker

ATX: & nbsp

G.04.C Drugs for the treatment of benign prostatic hyperplasia

Pharmacodynamics:

Alfuzosin is a quinazoline derivative that is active in oral use. He is a selective antagonist of postsynaptic alpha₁- adrenoreceptors located in the prostate gland, the triangle of the bladder and the urethra.

Clinical manifestations of benign prostatic hypertrophy are expressed in the infravesical obstruction of the urinary tract, caused by both anatomical (static) and functional (dynamic) factors. The functional component of obstruction is due to the excitation of alpha₁-adrenoreceptors, leading to a contraction of smooth muscles prostate gland, ce of the membrane, triangle of the bladder and the prostatic part of the urethra, which leads to an increase in the resistance of the urine incontinence from the bladder and, apparently, to the secondary instability of the bladder.

Due to a direct effect on the smooth muscles of the prostate gland associated with blockade alpha₁-adrenoceptor, alfuzosin reduces infravesical obstruction, pressure in the urethra and resistance to urine outflow during urination. Thereby alfuzosin improves the flow of urine and facilitates the emptying of the bladder. These beneficial effects on urodynamics lead to a reduction in urinary tract irritation symptoms and symptoms due to impairment of urinary outflow in patients with benign prostatic hyperplasia. In patients with maximum speed, the incontinence of urine (Q_m_Oh) ≤ 15 ml / s alfuzosin, already starting with the first dose, significantly increases Q_m_Oh (an average of 30%). In addition, in patients with benign prostatic hypertrophy alfuzosin significantly reduces the pressure in the detrusor of the bladder and increases the amount of urine causing a urge to urinate, and also significantly reduces the amount of residual urine. These effects lead to a decrease in obstructive and irritative symptoms of benign prostatic hypertrophy. The drug has no adverse effect on sexual function. In view of the selectivity of the action of alfuzosin, its effect on alpha₁-adrenoceptors vessels and, accordingly, the arterial pressure (BP) in case of its use in therapeutic doses is practically absent.

Pharmacokinetics:

Suction

After ingestion of 5 mg of alfuzosin, the maximum concentration in the blood plasma (C_m_Oh) - 10.3 ng / ml - is achieved after 3 hours. Eating does not affect the absorption of the active substance.

Distribution

The half-life of plasma is 8 hours. Bioavailability is 45-53%. Binding to blood plasma proteins is about 90%.

Metabolism

Alfuzosin undergoes significant metabolism in the liver, mainly by using the isoenzyme CYP3A4. In urine, only 11% of unchanged alfuzosin is found. Metabolites do not have pharmacological activity.

Excretion

In urine, only 11% of unchanged alfuzosin is found. Most metabolites are excreted through the intestine (75-90%).

Pharmacokinetics in specific patient groups

Elderly patients

In patients older than 75 years, absorption of the drug may be increased, and higher C_m_Oh. Some patients may increase the bioavailability of the drug and reduce the volume of distribution. In this case, the period of semivariety does not change.

Patients with hepatic impairment

In patients with severe impairment of liver function, the elimination half-life increases and, in comparison with healthy volunteers, the bioavailability of the drug increases.

Patients with impaired renal function

In patients with impaired renal function (creatinine clearance less than 50 ml / min) requiring or not requiring hemodialysis, due to the increase in the free drug fraction, the volume of distribution and clearance of alfuzosin are increasing.

Patients with chronic heart failure

In chronic heart failure, the pharmacokinetic profile of alfuzosin does not change.

Indications:

Functional disorders of urination with benign prostatic hyperplasia.

Contraindications:

- Hypersensitivity to alfuzosin and / or other components of the drug;

- orthostatic hypotension;

- severe violations of liver function (class C on the Child-Pyo scale);

- severe renal dysfunction (CC less than 30 ml / min);

- simultaneous reception of other alpha₁- adrenoblockers;

- deficiency of lactase, lactose intolerance, glucose-galactose malabsorption;

- children's age till 18 years.

Carefully:

- Ischemia of the brain (in connection with the possibility of lowering blood pressure and strengthening cerebral ischemia);

- ischemic heart disease, angina (there may be an increase and a weighting of attacks with angina pectoris);

- impaired renal function (QC more than 30 ml / min);

- orthostatic hypotension (in anamnesis);

- pronounced hypotensive reaction to other alpha₁-adrenoconstructors in history;

- congenital or acquired interval elongation (QT or simultaneous reception of drugs that increase the duration of the interval QT;

- concomitant therapy with antihypertensive drugs or nitrates (orthostatic hypotension is possible, as it proceeds asymptomatically, and accompanied by such clinical manifestations as dizziness, weakness, cold sweat);

- concomitant therapy with inhibitors of isoenzyme CYP4A3 (ketoconazole, itraconazole, rigonavir);

- Older age (over 75 years).

Pregnancy and lactation:

The drug is not intended for use in women.

Dosing and Administration:

Inside, without chewing, drinking 1/2 cup of water.

It is forbidden to crush, crush, grind the tablet into powder. These actions can lead to inappropriate release of alfuzosin from the tablet and its rapid absorption, which increases the risk of developing unwanted reactions.

Adults

The recommended dose is 5 mg 2 times a day (morning and evening).

Elderly patients and / or patients with hypertension receiving antihypertensive drugs

As a precaution when applying the drug Alfuzosin In such categories of patients it is recommended to start treatment with 5 mg once a day in the evening, increasing the dose in accordance with the clinical response, but not exceeding doses of 10 mg per day (5 mg twice a day).

Patients with renal insufficiency

With QC more than 30 ml / min, correction of the dosing regimen is not required.

Patients with hepatic insufficiency

It should be taken into account the lengthening of the half-life of alfuzosin and the possibility increasing its bioavailability, so treatment should begin at a dose of 2.5 mg 1 time per day, which may increase depending on the clinical response, but should not exceed 2.5 mg 2 times a day (to ensure this dosing regimen should be used alfuzosin in another dosage form: 2.5 mg tablets).

Side effects:

Classification of the incidence of adverse events according to recommendations World Health Organization (WHO):

Often ≥1/10;

often from ≥1/100 to <1/10;

infrequently from ≥1/1000 to <1/100;

rarely from ≥1/10000 to <1/1000;

very rarely <1/10000, including individual messages;

the frequency is unknown - it is not possible to establish the frequency of occurrence from the available data.

Violations from the blood and lymphatic system:

frequency unknown - thrombocytopenia.

Heart Disease:

infrequently - tachycardia, palpitation;

very rarely - the possible increase or weighting of angina attacks (see sections "With caution" and "Special instructions"); frequency is unknown - atrial fibrillation.

Disorders from the side of the organ of vision:

infrequently: visual impairment;

frequency unknown - intraoperative syndrome of a flaccid iris (see section "Special instructions").

General disorders:

often - asthenia, malaise;

rarely - swelling, pain in the chest.

Disorders from the gastrointestinal tract:

often - nausea, abdominal pain, diarrhea, dryness of the oral mucosa;

frequency is unknown - vomiting.

Disorders from the liver and bile ducts:

the frequency is unknown - hepatocellular jaundice, cholestasis and associated liver disease.

Impaired nervous system:

often - a feeling of faintness / dizziness, headache, vertigo; infrequently - syncopal condition, drowsiness;

frequency unknown - ischemic impairment of cerebral circulation in patients with already existing cerebrovascular pathology.

Violations of the genitals and breast:

frequency is unknown - priapism.

Disturbances from the respiratory system, chest and mediastinal organs:

infrequently - rhinitis.

Disturbances from the skin and subcutaneous tissues:

infrequent - rash, itching;

very rarely - hives, angioedema.

Vascular disorders:

infrequently - a decrease in blood pressure, including orthostatic hypotension; hyperemia of the skin.

Overdose:

Symptoms

Significant decrease in blood pressure, reflex tachycardia.

Treatment

In case of an overdose, the patient must be hospitalized. The patient should be in the "lying" position, constant monitoring of blood pressure is necessary. Traditional treatment of hypotension (administration of vasoconstrictors, plasma substitutes (to increase the volume of circulating blood) should be performed.) After restoration of blood pressure (elimination of hypotension), it is necessary to continue blood pressure control for approximately 24 hours.

Dialysis is ineffective because of the high degree of binding of alfuzosin to plasma proteins.

Interaction:

Contraindicated combinations

Other alpha blockers₁β-adrenoreceptors (praozosin, urapidil)

Strengthening the hypotensive effect and the risk of severe orthostatic hypotension (see the section "Contraindications"),

Interactions that should be taken into account

Hypotensive drugs

Strengthening the hypotensive effect and the risk of developing orthostatic hypotension (additive effect).

Nitrates

Increased risk of developing reflex tachycardia and lowering blood pressure.

Means for inhalation and non-inhaling general anesthesia

Possible instability of blood pressure during general anesthesia.

Inhibitor inhibitors CYP3A4 (ketoconazole, itraconazole, ritonavir)

It is possible to increase the concentration of alfuzosin in the blood plasma. When a combination of alfuzosin at a dose of 10 mg per day with a course of ketoconazole at a dose of 200 mg per day for 7 days C_max and the area under the "concentration-time" curve (AUC) of alfuzosin increased 2.1 times and 2.46 times, respectively, and when combined with a course application of ketoconazole at a dose of 400 mg per day for 8 days C_max and AUC of alfuzosin increased 2.3 times and 3 times, respectively (see the section "With caution").

Special instructions:

Within hours after taking alfuzosin (as well as after taking any other alpha₁adrenoblockers) in some patients (especially when taking antihypertensive drugs at the same time) may develop orthostatic hypotension with clinical symptoms (dizziness, severe weakness, cold sweat) or without it. At occurrence of these phenomena the patient should be in horizontal position before their full disappearance. Orthostatic hypotension is usually transient, it is observed, as a rule, at the beginning of treatment with the drug Alfuzosin and usually does not require withdrawal of the drug.

In the postmarketing use of alfuzosin in patients with risk factors for lowering blood pressure (such as heart disease or concomitant therapy with antihypertensive drugs), a pronounced decrease in blood pressure was reported. The risk of excessive blood pressure lowering and associated adverse reactions may be higher in elderly patients.

Before starting treatment, the patient should be alerted to the possibility of the reactions described above.

Caution should be exercised when using alfuzosin in patients with orthostatic hypotension with clinicalsymptomatology or in patients taking antihypertensive drugs or nitrates: more careful monitoring of blood pressure is necessary, including when moving from horizontal to vertical position, especially at the beginning of treatment.

Caution should be exercised when using alfuzosin in patients with severe hypotensive response to the administration of other alpha blockers₁-adrenoceptors in the anamnesis.

Patients with coronary insufficiency with alfuzosin should continue antianginal therapy. With the resumption or weighting of angina, treatment with alfuzosin should be discontinued.

Caution should be exercised when using alfuzosin in patients with congenital or acquired lengthening of the interval QT or in patients taking medications that can lengthen the interval QT.

Due to the possible decrease in blood pressure after administration of alfuzosin, there is a risk of development of ischemic impairment of cerebral circulation in patients predisposed to it (both having the corresponding symptoms and those whose previous cerebrovascular disorders are asymptomatic).

During ophthalmic operations for cataracts in some patients who have taken or used to take some alpha₁-adrenoconvertors, development of intraoperative syndrome of flaccid iris was observed (variant of narrow pupil syndrome). Although the risk of developing such a complication when taking the drug Alfuzosin it seems very low, before the operation on cataracts, the ophthalmic surgeon should be informed that the patient is taking alpha₁- adrenoblockers or took them earlier, since the development of intraoperative syndrome of a flaccid iris can increase the number of complications in this surgical intervention. Ophthalmologists should be prepared for a possible change in the methods of surgical intervention.

There are reports of cases of development of prolonged erection and priapism against the background of alpha therapy₁adrenoblockers. If the erection persists for more than 4 hours, you should immediately seek medical help. If priapism therapy has not been carried out immediately, it can lead to damage to the tissues of the penis and an irreversible loss of potency.

Effect on the ability to drive transp. cf. and fur:

It should be borne in mind that at the beginning of treatment there may be dizziness and other side effects that can affect the concentration of attention and the speed of psychomotor reactions, so care should be taken when driving vehicles and mechanisms.

Form release / dosage:Long-acting tablets 5 mg and 10 mg.

Packaging:

10 or 14 tablets in a planar cell packaging made of a polyvinylchloride film and aluminum foil.

60 tablets in a can of high-density polyethylene.

1, 3, 5 or 6 contiguous cell packs of 10 tablets, 1, 2 or 4 contour packs of 14 tablets or one pot together with instructions for use in a pack of cardboard.

Storage conditions:

Store in a dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LP-000665

Date of registration:28.09.2011 / 29.09.2016

Expiration Date:Unlimited

The owner of the registration certificate:VERTEKS, AO VERTEKS, AO Russia

Manufacturer: & nbsp

VERTEKS, AO Russia

Information update date: & nbsp13.07.2017

Illustrated instructions

Instructions

Alfuzosin (Alfuzosin)