Dalfaz retard - instructions for use, dose, side effects, contraindications

Excipients: microcrystalline cellulose - 42,00 mg; calcium hydrophosphate dihydrate - 65.00 mg; castor oil hydrogenated - 19.6 mg; povidone - 7.0 mg; magnesium stearate - 1.4 mg.

Film sheath

Hypromellose - 4,158 mg; propylene glycol 0.416 mg, titanium dioxide (E 171) 0.416 mg; ferric oxide red oxide (E 172) - 0.1765 μg; the colorant of iron oxide is yellow (E 172) - 9.8235 μg.

Description:Round, biconvex tablets, covered with a pale yellow coating.

Pharmacotherapeutic group:Alpha-1-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 alfaa₁adrenoreceptors 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, due to both anatomical (static) and functional (dynamic) factors.

The functional component of obstruction is due to the excitation of the alphaa₁-adrenoreceptors leading to a reduction in the smooth muscles of the prostate gland, its membrane, the triangle of the bladder and the prostatic part of the urethra, which leads to an increase in resistance to urine outflow from the bladder and, apparently, to secondary instability of the bladder.

Due to a direct effect on the smooth muscle tissue of the prostate gland associated with the blockade of alphaa₁β-adrenoreceptors, 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 symptoms of irritation of the urinary tract and symptoms,caused by violations of outflow of urine in patients with benign prostatic hyperplasia. In patients with a maximum rate of outflow of urine (Q_max) ≤15 ml / s alfuzosin, already starting with the first dose, significantly increases Q_max (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 connection with the selectivity of the action of alfuzosin, its effect on alphaa₁-adrenoceptors of blood vessels and, accordingly, on arterial pressure (BP), in case of its use in therapeutic doses, is practically absent.

Pharmacokinetics:

The maximum concentration of alfuzosin in plasma is achieved approximately 3 hours after ingestion.

The half-life (from the plasma) is 8 hours.

Bioavailability, compared with the immediate-release dosage form (alfuzosin 2.5 mg) is reduced by approximately 15%.

The intake of food does not affect the pharmacokinetic profile of the drug.

Binding to blood plasma proteins is about 90%.

Alfuzosin undergoes significant metabolism in the liver, mainly with the help of isoenzyme CYP3A4.

In urine, only 11% of unchanged alfuzosin is found.

Metabolites of alfuzosin do not have pharmacological activity. Most metabolites are excreted through the intestine (75-90%).

Pharmacokinetics in specific patient groups

Patients older than 75 years the absorption of the drug may be increased, and higher maximum plasma concentrations may be achieved. Some patients may increase the bioavailability of the drug and reduce the volume of distribution. The half-life does not change.

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

In patients with impaired renal function, requiring or not requiring hemodialysis, in connection with the increase in the free fraction of the drug, the volume of distribution and clearance of alfuzosin increase.

With 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 any of the excipients of the drug.

- Orthostatic hypotension.

- Severe hepatic impairment (class C according to classification Child-Pugh).

- Severe renal impairment (creatinine clearance <30 mL / min).

- Intestinal obstruction (due to the presence of castor oil in the formulation).

- Simultaneous reception of other alphasa₁adrenoblockers.

- Children under 18 years.

Carefully:

- In patients taking antihypertensive drugs or nitrates (possibly the development of orthostatic hypotension, both asymptomatic and symptomatic, accompanied by the appearance of dizziness, weakness, cold sweat).

- In elderly patients (over 75 years old).

- In patients with severe hypotensive reaction to other alphaa₁-adrenoconjunctors in the anamnesis.

- Patients with orthostatic hypotension with clinical manifestations.

- In patients with coronary artery disease, angina (the possibility of frequent and heavier attacks of angina pectoris).

- Patients with cerebral ischemia taking place with clinical symptoms or without clinical symptoms (in connection with the possibility of reducing blood pressure and strengthening cerebral ischemia).

- In patients with congenital or acquired lengthening of the interval QT or in patients taking medications that increase the duration of the interval QT.

- With isoenzyme inhibitors CYP3A4 (ketoconazole, itraconazole, ritonavir) (it is possible to increase the concentration of alfuzosin in blood plasma).

Pregnancy and lactation:Dalfaz® retard is not suitable for use in women.

Dosing and Administration:

The drug is intended for oral administration. Tablets should be taken whole and washed down with a glass of water. Tablets can not be crushed, chewed, grinded or ground to a powdered state, as a violation of the structure of the tablet can lead to an acceleration of the absorption of the active substance, which can contribute to the development of undesirable reactions.

Adults

The recommended dose is: 1 tablet of Dalfaz® retard, 5 mg twice daily (morning and evening).

Patients of advanced age and / or patients with hypertension who receive antihypertensive drugs

As a common precaution, when prescribing alfuzosin to these patient categories, it is recommended to start treatment with 1 tablet of Dalfaz® retard, 5 mg, in the evening, increasing the dose in accordance with the clinical response, but not exceeding the dose: 1 tablet twice a day.

Patients with renal insufficiency

With a creatinine clearance of more than 30 ml / min, no dosage adjustment is required.

Patients with hepatic insufficiency

It should take into account the elongation of the half-life of the drug and the possibility of increasing its bioavailability, so treatment should begin with 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.

Side effects:

The undesirable reactions listed below (HP) are given in accordance with the following gradations of the frequency of their occurrence: Often: (≥ 10%); often: (≥ 1% - <10%); infrequently: (≥ 0,1% - <1%); rarely: (≥ 0.01% - <0.1%); very rarely: (<0.01%) (including individual cases); unknown frequency: according to available data to establish the frequency of occurrence of HP is not possible.

Violations of the blood and lymphatic system

Unknown frequency: thrombocytopenia.

Heart Disease

Infrequently: tachycardia, palpitation.

Rarely: the possible increase or weighting of attacks of angina (see Fig. sections "With caution", "Special instructions").

Unknown frequency: atrial fibrillation.

Disturbances on the part of the organ of sight

Infrequently: visual impairment.

Unknown frequency: intraoperative syndrome of a flaccid iris (see section "Special instructions").

General disorders and disorders at the site of administration

Often: asthenia, malaise.

Infrequently: swelling, chest pain.

Disorders from the gastrointestinal tract

Often: nausea, abdominal pain, diarrhea, dryness of the oral mucosa.

Unknown frequency: vomiting.

Disturbances from the liver and bile ducts

Unknown frequency: hepatocellular jaundice, cholestasis and associated liver disease.

Disturbances from the nervous system

Often: feeling faint / dizzy, headache, vertigo.

Infrequently: syncope, drowsiness.

Unknown frequency: ischemic impairment of cerebral circulation in patients with already existing cerebrovascular pathology.

Violations of the genitals and mammary gland

Unknown frequency: priapism.

Disturbances from the respiratory system, chest and mediastinal organs

Infrequently: rhinitis.

Disturbances from the skin and subcutaneous tissues

Infrequently: rash, itching.

Rarely: urticaria, angioedema.

Vascular disorders

Often: decreased blood pressure, including orthostatic hypotension.

Infrequently: hyperemia of the skin.

Overdose:

Symptoms

Excessive decrease in blood pressure, reflex tachycardia.

Treatment

In case of an overdose, the patient is hospitalized. In case of an overdose, the patient should be in the "lying" position, and he needs constant monitoring of blood pressure. When blood pressure is lowered, the introduction of vasoconstrictors and plasma substitutes (to increase the volume of circulating blood) is recommended. After recovery of blood pressure, it is necessary to continue monitoring blood pressure for about another day.

Alfuzosin is poorly excreted by hemodialysis because of the high degree of binding to plasma proteins.

Interaction:

Contraindicated combinations

- With alpha blockersa₁-receptors (prazozin, urapidil) - the risk of severe orthostatic hypotension and increased hypotensive effect (see the section "Contraindications"),

Interactions that should be taken into account

- With antihypertensive drugs - Increased hypotensive effect and the risk of orthostatic hypotension (additive effect) (see section "Special instructions").

- With nitrates - increased risk of developing reflex tachycardia and lowering blood pressure.

- With funds for inhalation and non-inhaling general anesthesia - instability of blood pressure during general anesthesia is possible.

- With isoenzyme inhibitors CYP3A4 (ketoconazole, itraconazole and ritonavir) - an increase in the concentration of alfuzosin is possible. When a combination of alfuzosin at a dose of 10 mg per day with a course application of ketoconazole at a dose of 200 mg per day for 7 days FROM_max and 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 FROM_max and AUC of alfuzosin increased 2.3 times and 3.0 times, respectively (see the section "With caution").

Special instructions:

- Within hours after taking alfuzosin (as well as after taking any other alpha₁adrenoblockers) in some individuals, especially in patients taking antihypertensive drugs, may develop orthostatic hypotension with clinical symptoms (dizziness, severe weakness, cold sweat) or without it. With the development of these phenomena, the patient must be in a horizontal position until they disappear completely.

Orthostatic hypotension is usually transient and is observed, as a rule, at the beginning of the drug and usually does not require the withdrawal of treatment.

In post-marketing application of the drug in patients with risk factors for lowering blood pressure (such as heart disease or concomitant therapy antihypertensive drugs) reported a pronounced decrease in blood pressure. The risk of excessive blood pressure lowering and associated adverse reactions may be higher in elderly patients.

Before starting treatment, the patient should be warned about the possibility of described reactions.

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

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

- Patients with coronary deficiency in taking alfuzosin is necessary continue antianginal therapy. With the resumption or weighting of angina, treatment with alfuzosin should be discontinued.

- Care should be taken when using alfuzosin in patients with congenital or acquired lengthening interval QT or in patients taking medications that can lengthen the interval QT.

- Due to the fact that after the administration of alfuzosin, a decrease in blood pressure is possible, there is a risk of developing ischemic impairment cerebral circulation in predisposed patients (both having the corresponding symptoms, and those in whom the previous cerebrovascular disorders proceed asymptomatically).

- During the ophthalmic operations for cataracts in some patients who have taken or previously taken some alpha₁-adrenoconjunctive, there was a development intraoperative syndrome of flaccid iris (variant of narrow pupil syndrome). Although the risk of developing such a complication with the use of the drug Dalfaz® retard is very low, before performing an operation for 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 flaccid iris can increase the number of complications in this surgical intervention.

Ophthalmologists should be prepared for a possible change in the methodology of the operative interventions

- There are reports of cases of development in the background of therapy with alpha₁-adrenoblokatorami priapizma (prolonged painful erection of the penis, not related to sexual activity). 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. Patients should inform about the seriousness of this condition (seesection "Side effect") and the need to immediately seek medical help in case of maintaining an erection for more than 4 hours.

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

Care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased concentration and speed of psychomotor reactions, as the drug may cause dizziness and other side effects that may affect these abilities.

Form release / dosage:

The tablets of the prolonged action, covered with a cover, 5 mg.

Packaging:

For 14 tablets in a blister of aluminum foil and polyvinyl chloride film.

For 4 blisters together with instructions for use in a cardboard box.

Storage conditions:

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

Keep out of the reach of children.

Shelf life:

3 years.

Do not take the drug after the expiry date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N013809 / 01

Date of registration:19.11.2007 / 24.07.2014

Expiration Date:Unlimited

The owner of the registration certificate:Sanofi Winthrop IndustrySanofi Winthrop Industry France

Manufacturer: & nbsp

SANOFI WINTHROP INDUSTRIE France

Representation: & nbspSanofi Russia, JSCSanofi Russia, JSCRussia

Information update date: & nbsp21.04.2017

Illustrated instructions

Instructions

Dalfaz® retard (Dalfaz® retard)