Cardura

General characteristics. Structure:

International unlicensed name: доксазозин
Active agent: doksazozina мезилат 1,213 mg / 2,430 mg / 4,850 mg (ekvivalentno1 mg, 2 mg, 4 mg of a doksazozin).
Auxiliary monohydrate of 40,000 mg, cellulose of microcrystallic 76,382 mg / 75,170 mg, magnesium stearate of 1,080 mg, sodium lauryl sulfate of 0,120 mg veshchestva:karboksimetilkrakhmat sodium of 1,200 mg, lactoses.

Tablets of 4 mg
Karboksimetilkrakhmal of sodium of 2,400 mg, lactoses monohydrate of 80,000 mg, cellulose of microcrystallic 150,350 mg, magnesium stearate of 2,160 mg, sodium lauryl sulfate of 0,240 mg.

Description: Tablets of 1 mg - white, round, biconvex, on one party - CN 1 engraving, on other party - Pfizer log engraving.

Tablets of 2 mg - white, oval, biconvex, on one party - an engraving of CN 2 and risk, on other party - Pfizer log engraving.

Tablets of 4 mg - white, rhomboid, biconvex, on one party - an engraving of CN 4 and risk, on other party - Pfizer lotto engraving.

Pharmacological properties:

Pharmacodynamics. Benign hyperplasia of a prostate. 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. This effect of drug is connected with the selection blockade of the alfa1-adrenoceptors located in a stroma and the capsule of a prostate gland, a bladder neck.

It is proved what доксазозин is an effective blocker of a subtype 1A of alfa1-adrenoceptors which make about 70% of all subtypes, alfa1-adrenoceptors which are in a prostate. Its action at patients has also a talk with DGPZh it.

The supporting effect of treatment doksazoziny and its safety are proved at prolonged use of drug (e.g. up to 48 months).

Arterial hypertension

Use of a doksazozin for patients with arterial hypertension leads to a significant lowering of arterial pressure (ABP) as a result of reduction of the general peripheric vascular resistance. Emergence of this effect is connected with the selection blockade of the alfa1-adrenoceptors located in network of vessels. At administration of drug of 1 times a day clinically significant anti-hypertensive effect remains during 24 h, the ABP decreases gradually; the maximum effect is observed usually in 2-6 h after administration of drug inside. At patients with arterial hypertension of the ABP at treatment doksazoziny was identical in the family way "lying" and "standing".

It is noted that unlike non-selective alfa1-adrenoblockers at prolonged treatment doksazoziny tolerance to drug did not develop. When carrying out a maintenance therapy increase in activity of a renin of a blood plasma and tachycardia meet infrequently.

Doksazozin exerts beneficial effect on a blood lipid profile, considerably raising a ratio of content of lipoproteids of high density to the general cholesterol and considerably reducing the content of the general triglycerides and the general cholesterol. In this regard it has advantage before diuretics and
beta adrenoblockers which do not influence favorably the specified parameters. Considering the established connection of arterial hypertension and a blood lipid profile with coronary heart disease, normalization of the ABP and concentration of lipids against the background of reception of a doksazozin lead to decrease in risk of development of coronary heart disease.

It was observed that treatment doksazoziny led to regression of a hypertrophy of a left ventricle, oppression of aggregation of thrombocytes and strengthening of activity of a fabric plasminogen activator. Besides, it is established what доксазозин increases sensitivity to insulin at patients with the broken tolerance to glucose.

Doksazozin has no side metabolic effects and can be applied at patients with bronchial asthma, a diabetes mellitus, left ventricular failure and gout.

The researches in vitro showed antioxidant properties 6’ and 7’ - hydroxymetabolites of a doksazozin in concentration of 5 micromol.

In the controlled clinical trials conducted at patients with arterial hypertension treatment doksazoziny was followed by improvement of erectile function. Besides, at the patients receiving доксазозин again arisen disturbances of erectile function were noted less often, than at the patients receiving angigipertenzivny means.

Pharmacokinetics. After intake in therapeutic doses доксазозин it is well soaked up; concentration it in blood reaches a maximum approximately in 2 h.

Doksazozin approximately for 98% contacts proteins of a blood plasma.

Primary ways of metabolism of a doksazozin are O-demethylation and a hydroxylation.

Removal from a blood plasma is two-phase with a final elimination half-life of 22 h that allows to appoint drug of 1 times a day. Doksazozin is exposed to active biotransformation; only less than 5% of a dose are removed in not changed look.

Use for special groups of patients

According to pharmacokinetic researches at elderly patients and patients with a renal failure the drug pharmacokinetics significantly does not differ from that at patients, younger age with normal function of kidneys.

There are only limited data obtained at patients with the broken function of a liver and on influence of the drugs capable to change hepatic metabolism (for example, Cimetidinum). In clinical trial at 12 patients with a moderate abnormal liver function single use of a doksazozin was followed by increase in the area under a curve "concentration time" (AUC) for 43% and decrease in true peroral clearance by 40%. It is necessary to be careful at purpose of a doksazozin, as well as other medicines which are completely exposed to a bistransformation in a liver, to patients with abnormal liver functions (see the section "Special Instructions").

Indications to use:

- benign hyperplasia of a prostate;
- for the treatment of a delay of outflow of urine and symptoms connected with DGPZh;
- arterial hypertension (as a part of a combination therapy).

Route of administration and doses:

The drug Cardura can be appointed both in the morning, and in the evening, and is intended for intake.

Benign hyperplasia of a prostate

The recommended initial dose of the drug Cardura makes 1 mg of 1 times a day to minimize a possibility of development of postural hypotension and/or a syncopal state (syncope) (see the section "Special Instructions"). Depending on specific features of indicators of urodynamic and existence of symptoms of DGPZh it is possible to increase a dose to 2 mg, and then to 4 mg and to the maximum recommended dose of 8 mg. The recommended interval for increase in a dose makes 1-2 weeks. Usually recommended dose is equal to 2-4 mg of 1 times a day.

Arterial hypertension

The dosage varies from 1 to 16 mg/days. Treatment is recommended to be begun with 1 mg of 1 times a day within 1 or 2 weeks to minimize a possibility of development of postural hypotension and/or a syncopal state (syncope) (a phenomenon of "the first dose") (see the section "Special Instructions"). After reception of the first dose the patient needs monitoring of the ABP 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.

Within the next 1 or 2 weeks the dose can be increased to 2 mg of 1 times a day. For achievement of desirable decrease in the ABP if it is necessary, the daily dose should be increased gradually, observing uniform intervals to 4 mg, 8 mg and to maximum - 16 mg depending on expressiveness of reaction of the patient to administration of drug. Usually the dose makes 2-4 mg of 1 times a day.

If diuretic or other antihypertensive is added to therapy it is necessary to adjust a drug Cardura dose depending on a condition of the patient with its further titration under control of the doctor.

If therapy by the drug Cardura was interrupted for several days, it is necessary to resume drug use from an initial dose.

Use for patients of advanced age

Correction of a dose is not required.

Use at a renal failure

The pharmacokinetics of a doksazozin at patients with a renal failure does not change, and drug does not worsen the available renal dysfunction therefore at such patients it is applied in usual doses.

Use at a liver failure

It is necessary to be careful (see the section "Special Instructions").

Use for children

Experience of use of the drug Cardura for children is absent.

Features of use:

Postural hypotension / syncope

As well as at treatment any alpha adrenoblockers, in particular at the beginning of therapy, at very insignificant percent of patients observed the postural hypotension shown by dizziness and weakness or a loss of consciousness (faint) (see the section "Route of Administration and Doses"). Before purpose of any alpha adrenoblocker, the patient it is necessary to warn how it is necessary to avoid symptoms of development of postural hypotension, in particular it is necessary to abstain from bystry postural changes of a body. In an initiation of treatment the drug Cardura the patient should make recommendations of need to be careful in case of weakness or dizziness.

The drug Cardura should be used with care at elderly patients in connection with a possibility of development of orthostatic hypotension. With age the risk of developing of dizziness, a vision disorder and a faint increases.

The patient needs to be informed on increase in risk of development of orthostatic hypotension at alcohol intake, long standing or performance of physical exercises, and also at hot weather.

Benign hyperplasia of a prostate

At sick DGPZh it is possible to appoint drug both in the presence of arterial hypertension, and at the normal ABP. At use of drug for patients with DGPZh with the normal ABP change of the last is insignificant. At the same time at patients with a combination of arterial hypertension and DGPZh use in monotherapy is possible.

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

Doksazozin does not influence concentration of prostatspetsifichesky antigen (DOG) in a blood plasma.

Intraoperative syndrome of an atonichny iris

The intraoperative syndrome of an atonichny iris (option of a syndrome of a narrow pupil) was observed at some patients when carrying out operation on a cataract who receive or received treatment by alfa1-adrenoblockers. As the intraoperative syndrome of an atonichny iris can lead to increase of complications during surgical interventions, it is necessary to warn the operating surgeon that alfa1-adrenoblockers are accepted at the moment or were accepted before operation earlier.

Combined use with FDE-5 inhibitors

It is necessary to be careful at combined use of the drug Cardura with FDE-5 inhibitors as at some patients it can lead to symptomatic hypotension.

Abnormal liver function

It is necessary to be careful at purpose of the drug Cardura, as well as other medicines which are completely exposed to biotransformation in a liver, to patients with an abnormal liver function (see the section "Pharmacokinetics"), avoiding purpose of the maximum doses.

Influence on ability of driving and use of the equipment

During treatment it is necessary to be careful at control of vehicles and occupations other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Incompatibility

It is not known.

Side effects:

Frequency of undesirable reactions is presented on the following classification:

Very frequent:
≥10%

Frequent:
≥1% and <10%

Infrequent:
≥0,1% and <1%

Rare:
≥0,01% and <0,1%

Very rare:
<0,01%


Benign hyperplasia of a prostate

According to controlled clinical trials, at sick DGPZh the same side reactions, as occurred at patients with arterial hypertension.

At post-marketing use of drug it was reported about the following undesirable reactions:

From hemopoietic and lymphatic system: very rare - a leukopenia, thrombocytopenia.

From an acoustic organ and vestibular mechanism: infrequent - a sonitus.

From an organ of sight: frequent - disturbance of color perception, infrequent – a syndrome of an atonichny iris.

From digestive tract: frequent - an abdominal pain, diarrhea, dyspepsia, dryness of a mucous membrane of an oral cavity; infrequent - a meteorism, a lock, vomiting.

From a liver: very rare - a cholestasia, hepatitis, jaundice.

From immune system: very rare - anaphylactic reactions.

Laboratory indicators: infrequent - increase in body weight; very rare - increase in activity of "hepatic" transaminases.

From a metabolism: infrequent - anorexia.

From a musculoskeletal system: infrequent - an arthralgia, a dorsodynia, muscular spasms, muscular weakness, a mialgiya.

From the central and peripheral nervous system: frequent – paresthesias; infrequent - hypesthesias, a tremor.

From mentality: frequent - excitement, concern, sleeplessness; infrequent - a depression.

From urinary tract: infrequent - increase of an urination, a polyuria, an urine incontience; very rare - a dysuria, a hamaturia, a nocturia.

From reproductive system: very rare - a gynecomastia, impotence, a priapism; very seldom - a retrograde ejaculation.

From respiratory system: frequent - short wind, rhinitis; infrequent - cough, nasal bleeding; very rare - an aggravation of the available bronchospasm.

From integuments: infrequent - an alopecia, a skin itch, skin rash, a purpura; very rare - a small tortoiseshell.

From cardiovascular system: infrequent - "inflows" of blood to face skin, the expressed decrease in the ABP, postural hypotension.

Others: infrequent - pains of various localization.

Arterial hypertension

In controlled clinical trials of the drug Cardura side reactions which can be referred to type postural (occasionally connected with a faint) or nonspecific which included most often met:

From an acoustic organ and vestibular mechanism: frequent - вертиго.

From digestive tract: frequent - nausea.

From the central and peripheral nervous system: very frequent - dizziness, a headache; frequent - postural dizziness (after reception of the first dose the expressed decrease in the ABP which can lead to orthostatic dizziness, in hard cases can develop, especially upon bystry transition from situation "lying" in a standing position or in situation "sitting" - to a faint), drowsiness.

From respiratory system: frequent - rhinitis.

Others: frequent - an adynamy, hypostases of the lower extremities, fatigue, weakness.

It was noted the following side reactions in the course of marketing use of the drug Cardura for patients with arterial hypertension though in general such symptoms could be observed also in the absence of treatment by this drug: frequent - tachycardia, a heart consciousness, thorax pain; infrequent - stenocardia, a myocardial infarction and arrhythmias, very rare – bradycardia, disturbances of cerebral circulation.

Interaction with other medicines:

Combined use of the drug Cardura with FDE-5 inhibitors at some patients can lead to symptomatic hypotension (see the section "Special Instructions").

Big (98%) a part of a doksazozin in a blood plasma is connected with proteins. Results of a research of a blood plasma of the person of in vitro demonstrate to what доксазозин does not influence linkng with proteins of digoxin, warfarin, Phenytoinum or indometacin. In clinical practice the drug Cardura was used without any signs of interaction with thiazide diuretics, furosemide, beta adrenoblockers, antibiotics, hypoglycemic means for intake, uricosuric means and anticoagulants.

Non-steroidal anti-inflammatory drugs (especially indometacin), are oestrogenic and sympathomimetic means can reduce anti-hypertensive action of a doksazozin.

Doksazozin, eliminating alpha адреностимулирующие effects of Epinephrinum, can lead to development of tachycardia and arterial hypotension.

At a concomitant use with sildenafily for treatment of pulmonary hypertensia the risk of orthostatic hypotension increases.

At single use of the drug Cardura on 1 mg a day within 4 days at a concomitant use of 400 mg of Cimetidinum 2 times a day, were observed by 10% increase in average AUC values and statistically insignificant increase in the average level of Cmax (the maximum concentration in a blood plasma) and an average elimination half-life of a doksazozin. The similar 10% increase in average AUC values of a doksazozin against the background of reception of Cimetidinum are within variability fluctuations (27%) of average AUC values for a doksazozin in comparison with placebo.

At simultaneous use with other antihypertensives increases expressiveness of their action (dose adjustment is necessary).

It is not recommended to accept along with other blockers of alpha adrenoceptors.

At simultaneous use with inductors of a microsomal oxidation in a liver increase in efficiency of a doksazozin, and with inhibitors – decrease is possible.

Contraindications:

- hypersensitivity to quinazolines, a doksazozin or to any of auxiliary components of drug;
- deficit of lactase, lactose intolerance, glyukozo-galaktozny malabsorption;
- age up to 18 years;
- a heavy liver failure due to the lack of experience of use for this category of patients;
- infections of urinary tract;
- anury;
- the progressing renal failure;
- hypotension and tendency to orthostatic disturbances (including in the anamnesis);
- the accompanying obstruction of upper urinary tract;
- stones in a bladder.

With care. A mitral and aortal stenosis, heart failure with increase in minute emission, the right ventricular insufficiency caused by an embolism of a pulmonary artery or an exudative pericardis, a left ventricular failure with low filling pressure, disturbances of cerebral circulation, advanced age, simultaneous use with inhibitors of phosphodiesterase of the 5th type (FDE-5) since there can be symptomatic hypotension, a liver failure.

Use at pregnancy and during breastfeeding

Though in experiments drug had no teratogenic effect on animals, but at its use in exclusively high doses decrease in survival of a fruit was observed. The specified doses approximately by 300 times surpassed the maximum recommended doses for the person. Due to the lack of adequate well controlled researches at pregnant women or the feeding women, safety of use of the drug Cardura during pregnancy or during feeding by a breast is not established yet. In this regard during pregnancy or in the period of a lactation the drug Cardura can be used only then when, according to the doctor, the potential advantage for mother exceeds potential risk for a fruit or the child.

Overdose:

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

Treatment: it is necessary to lay immediately the patient on a back and to raise legs, if necessary to carry out symptomatic therapy. Linkng of a doksazozin with proteins of a blood plasma high therefore dialysis is not effective.

Storage conditions:

In the dry, protected from light place, at a temperature not above 30 °C. To store in the place, unavailable to children. A period of validity - 5 years.

Issue conditions:

According to the recipe

Packaging:

Tablets on 1, 2, 4 mg. On 7, 10 or 14 tablets in the blister from Al/PVC. On 2 blisters on 7 tablets, on 1 blister on 14 tablets or on 3 blisters on 10 tablets together with the application instruction in a cardboard pack.