Artezin

General characteristics. Structure:

Active agent: a doksazozina мезилат (in terms of доксазозин) 4 mg

Excipients: potato starch — 20 mg; lactoses monohydrate — 165,12 mg; povidone — 2 mg; кросповидон (Kollidon CL) — 6 mg; magnesium stearate — 2 mg.

Pharmacological properties:

Pharmacodynamics. Doksazozin is the selection competitive blocker postsynaptic α1-адренорецепторов. Due to decrease in a tone of muscles of vessels доксазозин reduces OPSS that leads to decrease in the ABP.
After a single dose of drug the maximum of hypotensive action is observed during from 2 to 6 h, and in general the hypotensive effect remains during 24 h. During treatment doksazoziny patients with arterial hypertension have no distinctions of sizes ABP in a standing position and lying.
It is effective at arterial hypertension, including followed by metabolic disturbances (obesity, decrease in tolerance to glucose).
Reduces risk of development of an ischemic heart disease.
Administration of drug at normotonik is not followed by decrease in the ABP.
At prolonged use of a doksazozin at patients decrease in anti-hypertensive effect is not observed.
During treatment doksazoziny decrease in level of concentration in a blood plasma of triglycerides, the general cholesterol (GC) is observed. Some is at the same time noted (for 4–13%) growth of coefficient of LPVP/OH.
At prolonged treatment drug observes regression of a hypertrophy of a left ventricle, suppression of aggregation of thrombocytes and increase in content in fabrics of active plasminogen.
Because доксазозин blocks α1-адренорецепторы, 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 drug the patient with symptoms of a benign hyperplasia of a prostate 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 absorption — 80–90% (the concomitant use of food slows down absorption on 1 h), Tmax — 3 h is well soaked up in a GIT, at evening reception — 5 h. Bioavailability — 60–70% (presistemny metabolism).
Linkng with proteins of a blood plasma — about 98%. Removal from a blood plasma happens in 2 phases, to final T1/2 — 19–22 h that allows to appoint drug of 1 times a day.
It is quickly metabolized in a liver by au demethylation and a hydroxylation.
It is removed through intestines, it is preferential in the form of metabolites (to 65%), only 5% are removed by kidneys in not changed look.
Researches of pharmacokinetics of a doksazozin at elderly patients and at patients with diseases of kidneys did not reveal essential distinctions.

Indications to use:

Arterial hypertension (in a combination with other anti-hypertensive drugs, including thiazide diuretics, β-adrenoblockers, BKK, APF inhibitors);

Benign hyperplasia of a prostate, both in the presence of arterial hypertension, and at the normal ABP.

Route of administration and doses:

Inside.

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

For providing the below-mentioned mode of dosing use of the drug Artezin® in a dosage form is possible: tablets on 1 and 2 mg.

At arterial hypertension the initial dose makes 1 mg/days before going to bed. After reception of the first dose of the patient has to be in a bed during 6–8 h. It is required in connection with a possibility of development of a phenomenon of the first dose, especially expressed against the background of the previous reception of diuretics.

At insufficiency of therapeutic effect the daily dose can be increased to 2 mg in 1–2 weeks. In the subsequent in each 1–2 weeks 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/days. The maximum dose — 16 mg/days (it is impossible to exceed).

After achievement of lasting therapeutic effect the dose is usually a little reduced (the average therapeutic dose at a maintenance therapy is usually equal to 2-4 mg/days).

At treatment of patients with the benign hyperplasia of a prostate (BHP) an initial dose — 1 mg/days to minimize a possibility of development of orthostatic hypotension and/or faint. If necessary, depending on indicators of urodynamic and existence of symptoms of DGPZh, the dose is increased (with an interval of 1-2 weeks) to 2–4 mg/days.

The most admissible dose — 8 mg/days. The recommended maintenance dose — 2–4 mg/days.

Drug is used it is long. Duration of treatment is determined by the doctor.

Features of use:

Extra care needs to be observed at an abnormal liver function, especially at simultaneous use of HP with a hepatotoxic action. In case 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 a prone position to a standing position).

It is necessary to be careful at combined use with FDE inhibitors (means for treatment of erectile dysfunction) as at some patients it can lead to symptomatic hypotension.

Alcohol intake is capable to strengthen undesirable reactions.

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

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

Influence on ability to manage vehicles and to work with mechanisms. Because Artezin® is capable to cause orthostatic reactions, in an initiation of treatment or during increase in dosages, it is reasonable to patient to abstain from all potentially dangerous types of activity, in particular from control of motor transport and other vehicles and mechanisms.

Side effects:

Arterial hypertension

In clinical trials were most often observed, especially in an initiation of treatment, orthostatic hypotension which in rare instances can lead to a faint.
General reactions: adynamy, fatigue, indisposition, allergic reactions, skin rash, small tortoiseshell.
- From CCC: peripheral hypostases, faint.
- From TsNS and a peripheral nervous system: dizziness, headache, drowsiness.
- From a GIT: nausea.
- From respiratory system: rhinitis.
- And also the following side reactions at patients with arterial hypertension were noted (relationship of cause and effect is not established): bradycardia, tachycardia, heartbeat, stethalgia, stenocardia, myocardial infarction, disturbance of cerebral circulation and arrhythmia.

DGPZH
At sick DGPZh the same side effects, as occur at patients with arterial hypertension, and also:
- General reactions: allergic reactions, skin rash, small tortoiseshell, dorsodynia, feeling of heat (inflows), increase in body weight.
- From CCC: decrease in the ABP, orthostatic hypotension.
- From TsNS and a peripheral nervous system: dryness in a mouth, a priapism, a hypesthesia, paresthesias, a tremor, impotence, sleeplessness, a hyperexcitability.
- From endocrine system: gynecomastia.
- From a GIT: abdominal pain, lock, diarrhea, dyspepsia, meteorism, nausea, appetite loss.
- From bodies of a hemopoiesis: leukopenia, purpura, thrombocytopenia.
- From gepatobiliarny system: increase in activity of hepatic transaminases, cholestasia, hepatitis, jaundice.
- From skeletal and muscular system: an arthralgia, muscular spasms, weakness in muscles, a mialgiya.
- From respiratory system: bronchospasm, cough, short wind, nasal bleeding.
- From sense bodys: illegibility of visual perception, sonitus.
- From an urinary system: dysuria, hamaturia, disturbance of an urination, nocturia, polyuria, urine incontience.

Interaction with other medicines:

Doksazozin strengthens hypotensive effect of anti-hypertensive HP.
Adverse interaction at simultaneous use of a doksazozin and thiazide diuretics, furosemide, β-adrenoblockers, BKK, APF inhibitors, antibiotics, peroral hypoglycemic means, indirect anticoagulants and uricosuric means is noted.
Does not influence extent of linkng with proteins of a blood plasma of digoxin, Phenytoinum.
At simultaneous use with inductors of a microsomal oxidation in a liver increase in efficiency of a doksazozin, with inhibitors — decrease is possible.
NPVS (especially indometacin), are oestrogenic and sympathomimetic means can reduce hypotensive action of a doksazozin.
Eliminating α-adrenostimuliruyushchy effects, can lead to development of tachycardia and arterial hypotension.
Cimetidinum increases bioavailability of a doksazozin.
FDE inhibitors can strengthen hypotensive action (to be careful).

Contraindications:

- hypersensitivity, including to other derivatives of quinazoline or any of auxiliary components of drug;
- age up to 18 years (efficiency and safety are not established).

With care: abnormal liver function; aortal and mitral stenosis; orthostatic hypotension.

Use at pregnancy and feeding by a breast
So far experience of use of the drug Artezin® for patients with arterial hypertension during pregnancy and during breastfeeding is insufficient. Therefore, despite the lack of teratogenic and embriotoksichesky action (according to pilot studies), Artezin® can be appointed at pregnancy and during breastfeeding only after careful weighing by the attending physician of a ratio advantage/risk.

Overdose:

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

Treatment: transfer of the patient in a prone position with the lower extremities raised higher than the level of the head, symptomatic therapy; dialysis is inefficient.

Storage conditions:

In the dry, protected from light place, at a temperature not above 25 °C.
To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets, 4 mg, 2 mg, 1 mg. In packagings of planimetric PVC, cell from a film, and the printing aluminum foil varnished on 10 pieces. In a pack cardboard 3 packagings.