Doksazozin

General characteristics. Structure:

Active ingredient: 1 mg, 2 mg or 4 mg of a doksazozin (in the form of a mezilat) in 1 tablet.

Excipients: [calcium stearate, hydrophosphate calcium dihydrate, lactoses monohydrate, kollidon-30 (povidone), sodium lauryl sulfate, talc].

Hypotensive, vasodilating, hypolipidemic, antispasmodic. It is applied to treatment of arterial hypertension, a symptomatic treatment of a benign hyperplasia of a prostate. Effectively reduces arterial pressure, facilitates the symptoms observed at prostate adenoma.

Pharmacological properties:

Pharmacodynamics. Doksazozin is the selection competitive blocker of postsynaptic alfa1-adrenoceptors (affinity to alfa1-adrenoceptors 600 times higher, than to alfa2-adrenoceptors), reduces the general peripheric vascular resistance (GPVR), warns the vasoconstriction caused by catecholamines that finally leads to a lowering of arterial pressure (ABP) without development of reflex tachycardia.

Reduces before - and an afterload on heart. After a single dose decrease in the ABP develops gradually, the maximum decrease is observed in 2-6 h and remains during 24 h.

After a single dose of drug the maximum of hypotensive action is observed during from 2 to 6 hours, and in general the hypotensive effect remains within 24 hours. During treatment doksazoziny patients with the arterial hypertension (AH) have no distinctions of sizes ABP in a standing position and "lying".

It is effective at AG, including, followed by metabolic disturbances (obesity, decrease in tolerance to glucose).

Reduces risk of development of the coronary heart disease (CHD). Administration of drug at patients with the normal ABP is not followed by decrease in the ABP. At prolonged use of a doksazozin at patients tolerance develops.

During treatment doksazoziny decrease in concentration in a blood plasma of triglycerides, the general cholesterol is observed. Some is at the same time noted (for 4-13%) growth of coefficient of lipoproteids of high density / the general cholesterol.

At prolonged treatment doksazoziny regression of a hypertrophy of the left ventricle (LV), suppression of aggregation of thrombocytes and increase in content in fabrics of active plasminogen is observed.

Because доксазозин blocks the alfa1-adrenoceptors located in a stroma and the capsule of a prostate and in a bladder neck there is a decrease in resistance and pressure in an urethra, reduction of resistance of an internal sphincter. Therefore purpose of a doksazozin the patient with symptoms of the benign hyperplasia of a prostate (BHP) leads to considerable improvement of indicators of urodynamic and reduction of manifestations of symptoms of a disease.

Renders effect at 66-71% of patients, the beginning of action – in 1-2 weeks of treatment, at most - after 14 weeks, the effect remains for a long time.

Pharmacokinetics. After intake in therapeutic doses доксазозин it is well soaked up, absorption – 80-90% (the concomitant use of food slows down absorption for 1 hour), time of achievement of the maximum concentration in a blood plasma (TCmax) makes 3 hours, at evening reception of TCmax is extended till 5 o'clock.

Bioavailability – 60-70%. Communication with proteins of a blood plasma – about 98%. Removal from a blood plasma happens in 2 phases, to a final elimination half-life (Т½) – 19-22 hours that allows to appoint drug of 1 times a day.

It is intensively metabolized in a liver by au demethylation and a hydroxylation. At patients with the broken function of a liver, and also at administration of drugs, capable to change "hepatic" metabolism, process of biotransformation of drug can be broken. The main removal - through intestines (63-65% in the form of metabolites and about 5% - in an invariable look). Kidneys remove about 10%. A research of pharmacokinetics of a doksazozin at elderly patients and patients with diseases of kidneys did not reveal essential pharmacokinetic distinctions.

Indications to use:

- Benign hyperplasia of a prostate: both in the presence of arterial hypertension, and at the normal level of arterial pressure.

- Arterial hypertension (as a part of a combination therapy).

Route of administration and doses:

Inside, once a day (in the morning or in the evening) irrespective of meal, without chewing and washing down with enough water.

Smaller doses owing to the slowed-down drug metabolism are required for patients with a liver failure.

If the patient forgot to accept drug in usual time, it should accept the corresponding dose of drug as soon as possible. If time is suitable for reception of the following dose, then it is necessary to accept only it (without doubling a drug dose). It is important to accept drug regularly. If the patient did not accept drug within several days, then the new therapeutic course should be begun with the smallest dose.

DGPZh: the initial dose makes 1 mg of a doksazozin a day. The patient should accept the first dose in the evening before going to bed. Depending on indicators of urodynamic and existence of symptoms of DGPZh the dose can be increased gradually bucketed in 1-2 weeks to 2 mg, 4 mg and 8 mg a day. The recommended maintenance dose of 2 - 4 mg a day. The maximum daily dose makes 8 mg.

After achievement of lasting therapeutic effect the dose is usually reduced (the average therapeutic dose at a maintenance therapy usually makes 2-4 mg a day).

AG: the initial dose of a doksazozin makes 1 mg a day before going to bed. After reception of the first dose the patient has to be in a bed within 6-8 hours. It is required in connection with a possibility of development of a phenomenon of the "first dose" which is especially expressed against the background of the previous reception of diuretics. At insufficiency of therapeutic effect of drug, the daily dose can be increased to 2 mg in 1-2 weeks. In the subsequent every 1-2 week the dose can be increased by 2 mg. At the vast majority of patients the optimum therapeutic effect is reached at a dose of 8 mg a day. The maximum daily dose makes 16 mg.

Features of use:

Use at pregnancy and during breastfeeding. Pregnant women can accept drug only when the advantage for mother exceeds potential risk for the fruit/child. There are no data on penetration of a doksazozin into breast milk therefore nursing mothers are recommended to stop feeding during treatment by drug Doksazozin.

Extra care should be shown at drug use Doksazozin by the patient with an abnormal liver function, especially when at the same time use the drugs capable to change "hepatic" metabolism (for example, ethanol, barbiturates, phenylbutazone, tricyclic antidepressants, Cimetidinum). In cases of deterioration in indicators of a functional condition of a liver drug is immediately cancelled.

For the purpose of prevention of orthostatic reactions patients have to avoid unexpected and sharp changes of position of a body (transition from situation "lying" in a standing position).

It is necessary to be careful at a concomitant use of inhibitors of phosphodiesterase-5 and a doksazozin since development of arterial hypotension is possible. For reduction of risk of development of arterial hypotension (including orthostatic) it is necessary to begin treatment with phosphodiesterase-5 inhibitors, only if the patient adapted to therapy doksazoziny, besides, between administration of drugs 6 hour period from reception of a doksazozin have to be observed.

At operative measures concerning a cataract against the background of administration of drug development of a syndrome of intraoperative instability of an iris of the eye of an eye (a syndrome of a narrow pupil) is possible that the surgeon needs to consider for preoperative training of the patient and when carrying out operation.

Alcohol intake is capable to strengthen undesirable reactions of a doksazozin.

The effect of "the first dose" of drug is especially expressed against the background of the previous diuretic therapy and a diet with sodium restriction.

Before therapy it is necessary to exclude cancer regeneration of a prostate.

Influence on ability to manage vehicles and other mechanisms. In case of administration of drug Doksazozin, it is necessary to be careful at control of vehicles or during the working, the demanding increased concentration of attention and speed of psychomotor reactions.

Side effects:

Frequency of side reactions at drug use Doksazozin is specified below according to the standard classification: very often (≥1/10); often (≥1/100, <1/10); infrequently (≥1/1000, <1/100); seldom (≥1/10000, <1/1000); very seldom (<1/10000).

From cardiovascular system: often – AG (including orthostatic), a heart consciousness, tachycardia; infrequently – stenocardia, a myocardial infarction; very seldom – bradycardia, disturbances of a rhythm, "inflows" of blood to face skin, peripheral hypostases.

From the central and peripheral nervous system: often – drowsiness, dizziness, a headache; infrequently – a stroke, hypesthesias, a faint, a tremor, agitation, a depression, alarm, sleeplessness, nervousness; very seldom – paresthesias, postural dizziness.

From sense bodys: often – вертиго; infrequently – a ring in ears; very seldom - an illegibility of visual perception, a syndrome of a narrow pupil.

From the alimentary system: often – an abdominal pain, dyspepsia, dryness of a mucous membrane of an oral cavity; infrequently - a lock, abdominal distention, vomiting, diarrhea, increase in activity of "hepatic" enzymes, appetite loss, anorexia; very seldom – hepatitis, a cholestasia, jaundice.

From respiratory system: often – bronchitis, cough, short wind, rhinitis, a xeromycteria; infrequently – nasal bleeding; very seldom bronchospasm.

From bodies of a hemopoiesis: leukopenia, thrombocytopenia.

From skeletal and muscular system: often – a dorsodynia, a mialgiya; not often – an arthralgia; seldom – spasms, weakness in muscles.

From integuments: often – an itch; infrequently – skin rash; very seldom small tortoiseshell, allopecia, purpura.

From urinogenital system: often cystitis, urine incontience; not often – a dysuria, increase in frequency of an urination, a hamaturia, impotence, gout; seldom - a polyuria; very seldom – increase in a diuresis, frustration of an urination, a nocturia, a gynecomastia, a priapism, a retrograde ejaculation.

General reactions: often - an adynamy, thorax pain, an indisposition; infrequently – pain, a face edema, weight reduction; very seldom – allergic reactions, fatigue.

Interaction with other medicines:

Doksazozin strengthens anti-hypertensive effect of antihypertensives (at use in a combination with them dose adjustment is required).

Adverse interaction at simultaneous use of a doksazozin and thiazide diuretics, furosemide, a beta - adrenoblockers, blockers of "slow" calcium channels, inhibitors of an angiotensin-converting enzyme, antibacterial agents, hypoglycemic means for intake, indirect anticoagulants and uricosuric means is noted.

Drug does not exert impact on extent of linkng with proteins of a blood plasma of digoxin, Phenytoinum.

At simultaneous use with inductors of enzymes of a microsomal oxidation in a liver (ethanol, barbiturates, phenylbutazone, tricyclic antidepressants) increase in efficiency of a doksazozin, with inhibitors (Cimetidinum) - decrease is possible.

Non-steroidal anti-inflammatory drugs (NPVP), especially indometacin, estrogen (liquid delay) and sympathomimetic means can reduce hypotensive action of a doksazozin.

Eliminating alpha адреностимулирующие effects of Epinephrinum, can lead to tachycardia and arterial hypotension.

The accompanying use with the selection inhibitors of phosphodiesterase-5 (sildenafit, tadalafit, vardenafit) can lead to development of arterial hypotension.

Contraindications:

- Hypersensitivity to a doksazozin and other derivatives of quinazoline (Prazozinum, теразозин) or to other components of drug;
- Tendency to orthostatic hypotension;
- AG (for patients with a benign hyperplasia of a prostate);
- Patients with DGPZh and the accompanying disturbance of outflow of urine from upper urinary tract, persistent infections of uric ways, stones in a bladder;
- Lactose intolerance, deficit of lactase or glyukozo-galaktozny malabsorption;
- Lactation period;
- Age up to 18 years (efficiency and safety are not established).

As monotherapy at patients or with the crowded bladder, or with an anury in a combination or without the progressing renal failure.

With care: a fluid lungs owing to an aortal or mitral stenosis; right-hand heart failure owing to a pulmonary embolism or exudative perikarditapravostoronnyaya serdechnaya nedostatochnost ʹ vsledstvie legochno ĭ embolii ili ekssudativny ĭ perikardit; left ventricular heart failure with low filling pressure; simultaneous use of inhibitors of phosphodiesterase-5 (sildenafit, vardenafit, trandalafit); syndrome of intraoperative instability of an iris of the eye of an eye (syndrome of a narrow pupil); abnormal liver function.

Overdose:

Symptoms: the expressed decrease in the ABP which sometimes is followed by a faint.

Treatment: gastric lavage, reception of absorbent carbon. The patient needs to be laid on a back and to raise legs. At the expressed decrease in the ABP hold antishock events – fill the volume of the circulating blood, if necessary appoint vazopressor.
The hemodialysis is inefficient.

Storage conditions:

In the dry place protected from light at a temperature not above 25 °C . To store in the place, unavailable to children. Period of validity: 2 years. Not to use after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets of 1 mg, 2 mg and 4 mg. On 7, 10, 15, 20 or 30 tablets in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished. On 1, 2, 3, 4 or 5 blister strip packagings with the application instruction in a pack from a cardboard.