Дальфаз® ретард

General characteristics. Structure:

Active agent: alfuzozina hydrochloride of 5 mg
excipients: MKTs — 42 mg; calcium hydrophosphate a dihydrate — 65 mg; the castor oil hydrogenated — 19,6 mg; povidone — 7 mg; magnesium stearate — 1,4 mg  
On a tablet without cover weight — 140 mg  
film cover: a gipromelloza — 4,158 mg; propylene glycol — 0,416 mg; titanium dioxide (E171) — 0,416 mg; dye ferrous oxide red (E172) — 0,1765 mkg and dye ferrous oxide yellow (E172) — 9,8235 mkg (in the form of suspension)  
On a tablet, coated, weight — 145 mg

Description. Round biconvex tablets, coated pale yellow color.

Pharmacological properties:

Pharmacodynamics. Alfuzozin is derivative quinazoline, active at oral administration. He is the selection antagonist of the postsynaptic alfa1-adrenoceptors located in a prostate, a triangle of a bladder and an urethra.
Clinical manifestations of a high-quality prostatauxe are expressed in the infravezikalny obstruction of urinary tract caused both anatomic (static) and functional (dynamic) factors. The functional component of obstruction is caused by excitement alfa1kadrenoretseptorov, leading to reduction of smooth muscles of a prostate, its cover, triangle of a bladder and a prostatic part of an urethra that leads to increase in resistance to outflow of urine from a bladder and, apparently, to secondary instability of a bladder.
Owing to the direct impact on smooth muscles of tissue of prostate gland connected with blockade альфа^адренорецепторов альфузозин reduces infravezikalny obstruction, pressure in an urethra and resistance to outflow of urine during an urination. At the expense of it альфузозин improves outflow of urine and facilitates bladder emptying. These favorable effects on urodynamic lead to reduction of symptoms of irritation of the urinary tract and symptoms caused by disturbances of outflow of urine at patients with a benign hyperplasia of a prostate. At patients with the maximum speed of outflow of urine is (Qmax) ^ 15 ml/sec. альфузозин, already since the first dose, considerably increases Qmax (on average by 30%). Besides, at patients with a high-quality prostatauxe альфузозин considerably reduces pressure in a detruzor of a bladder and increases the urine volume causing a desire to an urination and also considerably reduces the volume of a residual urine. These effects bring at improvement of obstructive and irritativny symptoms of a high-quality prostatauxe. Drug has no adverse effect on sexual function.
Due to the selectivity of action of an alfuzozin its influence on alfa1-adrenoceptors of vessels and, respectively, on arterial pressure, in case of its use in therapeutic doses, is practically absent.

Pharmacokinetics. The maximum concentration in plasma is reached approximately in 3 hours after administration of drug inside.
The elimination half-life makes 8 hours (of plasma).
Bioavailability in comparison with a dosage form of immediate release,
альфузозин 2,5 mg, it is lowered approximately by 15%.
Meal does not influence a fakokinetichesky profile of drug.
Linkng with proteins of plasma about 90%.
Alfuzozin is exposed to considerable metabolism in a liver, generally by means of SUR3A4. In urine only 11% of not changed drug are found. Metabolites have no pharmacological activity. The majority of metabolites is removed with a stake (75-90%). Pharmacokinetics at special groups of patients
At persons 75 years can be more senior drug absorption is increased, and higher maximum plasma concentration can be reached. At some patients increase in bioavailability of drug and reduction of volume of distribution is possible. At the same time the elimination half-life does not change.
At patients with heavy abnormal liver functions the eliminative elimination half-life increases and, in comparison with healthy volunteers, bioavailability of drug increases.
At patients with the renal failures which are demanding or not demanding carrying out a hemodialysis in connection with increase in free fraction of drug the volume of distribution and clearance of an alfuzozin increase.
At chronic heart failure the pharmacokinetic profile of an alfuzozin does not change.

Indications to use:

Functional disturbances of an urination at a benign hyperplasia of a prostate.

Route of administration and doses:

Drug is intended for intake. A pill has to be taken entirely and be washed down with 1 glass of water. Tablets cannot be crushed, chewed, ground or crushed to a powder state as disturbance of structure of a tablet can lead to acceleration of absorption of active ingredient that can promote development of side effects. Adults
The recommended dose makes: on 1 tablet Dalfaz ретард, 5 mg - twice a day (in the morning and in the evening).
The patients of an elderly vozrastk and/or patients with arterial hypertension receiving antihypertensives
As a usual precautionary measure, at purpose of an alfuzozin these categories of patients are recommended to begin treatment with 1 tablet Dalfaz ретард, 5 mg, in the evening, raising a dose according to the clinical answer, but not to exceed a dose: 1 tablet twice a day. Patients with pocheny insufficiency
At clearance of creatinine more than 30 ml/min. of correction of the mode of dosing are not required.
Patients with a liver failure
It is necessary to consider lengthening of an elimination half-life of drug and a possibility of increase in its bioavailability therefore treatment has to begin with a dose of 2,5 mg
1 time a day which can increase depending on the clinical answer, but should not exceed 2,5 mg 2 times a day.

Features of use:

• At some persons, in particular, at the patients receiving hypotensive drugs within several hours after reception of an alfuzozin (as well as after reception of any other alfa1-adrenoblockers) orthostatic hypotension with clinical symptomatology (dizziness, sharp weakness, cold sweat) or without it can develop. Orthostatic hypotension usually happens passing and is observed, as a rule, at the beginning of administration of drug and usually does not demand treatment cancellation. At emergence of these phenomena of the patient has to be before their total disappearance in horizontal position. Before an initiation of treatment of the patient it has to be warned about possibility of such phenomena.
• It is necessary to be careful at purpose of an alfuzozin to patients with orthostatic hypotonia with clinical symptomatology, to patients with indications of the anamnesis on the expressed hypotensive reaction in response to reception of other blockers of alfa1-adrenoceptors: more careful control of arterial pressure is necessary, including, upon transition from horizontal position in vertical, especially in an initiation of treatment.
• Patients with coronary insufficiency at reception of an alfuzozin need to continue anti-anginal therapy. When resuming or weighting stenocardia treatment alfuzoziny should be stopped.
• It is necessary to be careful at purpose of an alfuzozin to patsitseta with the inborn or acquired lengthening of an interval of QT or receiving medicines capable to extend QT interval.
• Because after reception of an alfuzozin the lowering of arterial pressure is possible, there is a risk of development of ischemic disturbance of cerebral circulation in the patients predisposed to it (as having the corresponding symptoms, and for at what the previous cerebrovascular frustration proceed asymptomatically).
• During ophthalmologic operations for a cataract at some patients accepting at this time or accepting earlier some alfa1-adrenoblockers development of an intraoperative syndrome of a sluggish iris (option of a syndrome of a narrow pupil) was observed. Though the risk of development of such complication at a prema of the drug Dalfaz®retard is represented very low, before carrying out operation for a cataract the surgeon-ophthalmologist has to be informed that the patient accepts alfa1-adrenoblockers or accepted them earlier as development of an intraoperative syndrome of a sluggish iris can increase quantity of complications at this operational vmeshatelst. Ophthalmologists have to be ready to possible change of a technique of an operative measure.

Influence on ability to manage vehicles and to be engaged in other potentially dangerous types of activity
There are no data on influence of drug on control of vehicles. It is necessary to take into account a possibility of development вертиго, dizziness and an adynamy, especially in an initiation of treatment that can affect ability to manage vehicles and to be engaged in other potentially dangerous types of activity, in particular to work with mechanisms.

Side effects:

The undesirable effects provided below are given in a soovetstviye with the following
gradation of frequency of their emergence:
Very often: (> 10%);
Often: (> 1% - <10%);
Infrequently: (> 0,1% - <1%);
Seldom: (0,01% - 0,1%);
Very seldom: (<0,01%) (including separate cases). Unknown frequency: according to the available data it is not possible to establish the frequency of emergence of side effect.

Disturbances from heart
Infrequently: tachycardia, heartbeat.
Very seldom: stenocardia at patients from  earlier existing coronary
insufficiency (see the section "With Care", "Special Instructions").
Unknown frequency: fibrillation of auricles.
Disturbances from an organ of sight
Infrequently: vision disorders.
Unknown frequency: an intraoperative syndrome of a sluggish iris (see the section "Special Instructions").
The general frustration and disturbances in an injection site
Often: adynamy, indisposition.
Infrequently: hypostases, stethalgias.
Disturbances from digestive tract
Often: nausea, abdominal pains, diarrhea, dryness of a mucous membrane of an oral cavity. Disturbances from a liver and biliary tract
Unknown frequency: hepatocellular jaundice, cholestasia and related diseases of a liver.
Disturbances from a nervous system
Often: feeling faintness/dizziness, headache, вертиго.
Infrequently: syncope, drowsiness.
Unknown frequency: ischemic disturbances of cerebral circulation at patients with already available cerebrovascular pathology. Disturbances from generative organs and a mammary gland Unknown frequency: priapism.
Disturbances from respiratory system, bodies of a thorax and a mediastinum Infrequently: rhinitis.
Disturbances from skin and hypodermic fabrics Infrequently: rash, itch.
Very seldom: small tortoiseshell, Quincke's disease. Disturbances from vessels Often: orthostatic hypotension. Infrequently: hyperemia of integuments.

Interaction with other medicines:

• hypotensive drugs, including blockers of slow calcium channels - strengthening of hypotensive effect and risk of development of orthostatic hypotonia (the additive action) (see. "Special instructions").
• nitrates - increases in risk of development of reflex tachycardia and a lowering of arterial pressure.
• the general anesthetics - instability of the ABP is possible during an anesthesia.
• CYP4A3 inhibitors (кетоконазол, интраконазол and ритонавир) - increase in concentration of an alfuzozin (at a combination with ketokonazoly Smakh of an alfuzozin increases by 2,1-2,3 times) is possible.

Contraindications:

•   Hypersensitivity  to  an alfuzozin  and/or other  igrediyenta of drug.
• Orthostatic hypotension.
• Heavy abnormal liver functions (a class C on Child-Pugh classification).
• Heavy renal failures (clearance of creatinine <30 ml/min.).
• Intestinal impassability (in connection with existence in composition of drug of castor oil).
• Concomitant use of others альфа^адреноблокаторов. With care

• At the patients receiving hypotensive drugs (development of the orthostatic hypotonia which is followed by symptoms, such as dizziness, weakness, cold sweat or proceeding asymptomatically is possible).
• At patients of advanced age (75 years are more senior).
• At patients with indications of the anamnesis on the expressed hypotonic reaction to other alfagadrenoblokator.
• At patients with orthostatic hypotonia with clinical manifestations.
• At patients with coronary heart disease, stenocardia (a possibility of increase and weighting of attacks of stenocardia).
• At patients with the available symptomatic and symptomless ischemic disease of a brain (in connection with a possibility of a lowering of arterial pressure and strengthening of ischemia of a brain).
• Patients with the inborn or acquired lengthening of an interval have QT or at the patients accepting the medicines extending QT interval.

Overdose:

Symptoms
Arterial hypotension, reflex tachycardia. Treatment
In case of overdose of the patient is subject to hospitalization. At overdose of the patient has to is in situation "lying" and it needs continuous monitoring of arterial pressure. At a lowering of arterial pressure introduction of vasoconstrictors and plasma substitutes is recommended (for increase in volume of the circulating blood). After recovery of arterial pressure (elimination of hypotonia) it is necessary to continue control of arterial pressure still approximately within a day.
Alfuzozin is badly brought by means of a hemodialysis because of high extent of linkng with proteins of plasma.

Storage conditions:

To store in the dry place at a temperature not above 25 °C. To store in the place, unavailable to children. List B. Period of validity 3 years. Not to accept drug after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets of the prolonged action, coated, 5 mg. On 14 tablets in the blister from aluminum foil and a film polyvinyl chloride. On 4 blisters together with the application instruction in a cardboard pack.