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

shell: Opadrai II 85F18422 - 10.00 mg: partially hydrolyzed polyvinyl alcohol - 40.00%, Macrogol-3350 - 20.20%, talcum - 14.80%, titanium dioxide E171 - 25.00%.

Description:Round, biconvex tablets, covered with a film shell of white or almost white color. On the cross section, the nucleus is white or almost white in color.

Pharmacotherapeutic group:Alpha-blocker

ATX: & nbsp

C.02.C.A.04 Doxazosin

Pharmacodynamics:

Doxazosin is a selective alpha blocker₁adrenoreceptors.

It prevents the smooth muscle of the peripheral vascular wall, reduces the overall peripheral vascular resistance, lowers blood pressure (BP).

Doxazosin has an antihypertensive effect that does not depend on the age and position of the patient's body.

Reduces pre- and postnagruzku on the myocardium.

After a single administration, the decrease in blood pressure develops gradually, the maximum decrease is observed after 2-6 hours, the antihypertensive effect persists for 24 hours.

Helps normalize the ratio of high-density lipoproteins and total cholesterol, reduces the total concentration of triglycerides and cholesterol.

Effective in hypertension, including those accompanied by metabolic disorders (obesity, dyslipidemia, decreased glucose tolerance).

With long-term use, regression of left ventricular hypertrophy, suppression of platelet aggregation, increased activity in the tissues of the activator of the profibrinolysin (plasminogen) and a decrease in the formation of collagen in the walls of the arteries are noted.

In response to the first dose, the development of orthostatic hypotension is characteristic. The use of doxazosin in patients with normal blood pressure is not accompanied by a decrease.

In patients with benign prostatic hyperplasia, the use of doxazosin leads to an improvement in urodynamic parameters and a reduction in the symptoms of the disease. The effect is associated with a selective alpha blockade₁-adrenoceptor subtype A (70% of all subtypes present in the prostate gland) that are localized in the muscular stroma, prostatic capsule,the neck of the bladder and in the proximal part of the urethra, which reduces the muscle tone of the prostate and makes it easier to urinate. The effect in 66-71% of patients, the beginning of therapeutic effect - after 1-2 weeks of treatment.

Pharmacokinetics:

Doxazosin is well absorbed in the gastrointestinal tract. The connection with blood plasma proteins is about 98%.

The maximum concentration (C_mOh) in plasma 10.1 ± 5.6 ng / ml is determined after 8.0 ± 3.7 h.

Effect of food

FROM_max and the area under the "concentration-time" curve (AUC) of doxazosin is higher after eating, compared with fasting. To prevent sudden changes in the concentration of doxazosin in blood plasma, the drug should be taken during breakfast.

The effect of passage time on the intestine

A significantly shorter passage time of the drug (eg, a syndrome of the small intestine) can affect the pharmacokinetics of doxazosin, reducing its concentration in the blood plasma. On the other hand, increasing the passage time in the gut (for example, chronic constipation) can increase the exposure of doxazosin, which leads to an increased risk of unwanted reactions.

Metabolism

Metabolised in the liver. The main way of elimination of doxazosin is due to the isoenzyme CYP3A4. To a much lesser extent it is possible to participate in isoenzymes CYP2D6 and CYP2C19.

Excretion

Doxazosin is excreted through the intestine, mainly in the form of metabolites (up to 65%), 5% - unchanged; through the kidneys is about 10%.

The half-life of doxazosin is about 15-19 hours.

The influence of age

In the equilibrium state C_mOh and AUC doxazosin in elderly patients over the age of 65 is on average 27% and 34% higher, respectively, compared with younger patients.

Impaired liver function

The use of doxazosin in patients with mild hepatic insufficiency (from 5 to 6 on the Child-Pugh scale) increases the exposure of the drug by 40% compared with patients without hepatic insufficiency.

Indications:

- Dprosthetic hyperplasia of the prostate, both in the presence of arterial hypertension, and with normal blood pressure;

- arterial hypertension (as part of combination therapy).

Contraindications:

- Hypersensitivity to doxazosin, to any other of the drug components or to other quinazoline derivatives;

- benign prostatic hyperplasia with concurrent impairment of urinary outflow from the upper parts of the urinary tract, chronic infections of the urinary tract, stones in the bladder;

- lactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome; intestinal obstruction, obstruction of the esophagus;

- severe violations of the liver (more than 9 points on the scale Child-Pugh);

- the period of breastfeeding,

- age under 18 years (efficiency and safety not established).

Carefully:

Aortic and / or mitral stenosis, right-sided heart failure due to pulmonary embolism or exudative pericarditis, left ventricular heart failure with low filling pressure, simultaneous use of phosphodiesterase-5 inhibitorssildenafil, vardenafil, tadalafil, udenafil), intraoperative irrosis of the iris, mild to moderate hepatic insufficiency (from 5 to 9 on the Child-Pugh scale), propensity to arterial hypotension (orthostatic disorders of blood circulation regulation), pregnancy.

Pregnancy and lactation:

In animal studies, it has been shown that doxazosin does not have teratogenic and embryotoxic effects.

The use of the drug during pregnancy is possible only when the benefit to the mother exceeds the potential risk to the fetus.

Data on the penetration of doxazosin into breast milk are not available, however, during lactation, if the drug is needed, breastfeeding should be discontinued.

Dosing and Administration:

Inside, entirely, not liquid, squeezed a small amount of liquid, during breakfast.

If the drug intake is missed, the missed dose is not taken in addition and the drug is continued according to the established schedule.

Benign prostatic hyperplasia, both in the presence of arterial hypertension, and with normal blood pressure

The recommended dose is 1 tablet (4 mg) once a day. The maximum daily dose is 2 tablets (8 mg) once a day.

Arterial hypertension (as part of combination therapy)

The recommended initial dose is 1 tablet (4 mg) once a day. After taking the first dose, the patient should be in bed for 6 to 8 hours. This is required in connection with the possible development of the phenomenon of the "first dose", especially against the background of previous use of diuretics.The maximum therapeutic effect is achieved after 4 weeks of therapy. If after 4 weeks of therapy the effect is insufficient and the patient tolerates the drug well, its dose can be increased. The maximum daily dose is 2 tablets (8 mg) once a day.

Elderly patients: correction of the dose is not required.

Impaired renal function: correction of the dose is not required.

Side effects:

Classification of the frequency of development of side effects of the World Health Organization: very often - more than 1/10; often from more than 1/100 to less than 1/10; infrequently - from more than 1/1000 to less than 1/100; rarely from more than 1/10000 to less than 1/1000; very rarely - less than 1/10000.

From the side of the cardiovascular system:

often: marked decrease in blood pressure, palpitations, tachycardia;

infrequently: angina pectoris, myocardial infarction;

very rarely: a bradycardia, violation of the heart rhythm, "tides" of blood to the skin of the face, peripheral edema.

From the nervous system:

often: sleep disturbance, dizziness, headache;

infrequently: stroke, hypesis, syncope, tremor, agitation, depression, anxiety, nervousness, dysphonia, memory impairment, convulsions;

very rarely: paresthesia, postural dizziness.

From the sense organs:

often: disruption of accommodation, photophobia, tearing, tasting;

infrequently: ringing in the ears; rarely: conjunctivitis;

very rarely: blurred vision, miosis.

From the digestive system:

often: abdominal pain, indigestion, dryness of the oral mucosa;

infrequently: constipation, bloating, vomiting, diarrhea, increased appetite, anorexia;

very rarely: hepatitis, cholestatic jaundice.

From the respiratory system:

often: bronchitis, cough, shortness of breath, rhinitis, dryness of the nasal mucosa;

infrequently: epistaxis;

very rarely: bronchospasm.

From the side of the musculoskeletal system:

often: back pain, myalgia;

infrequently: arthralgia; rarely: cramps, muscle weakness.

From the skin:

often: itching;

infrequently: skin rash;

very rarely: urticaria, alopecia.

From the genitourinary system:

often: cystitis, urinary incontinence;

infrequently: dysuria, hematuria, impotence;

rarely: polyuria;

very rarely: frustration of urination, nocturia, gynecomastia, priapism, retrograde ejaculation.

From the side of metabolism:

infrequent: exacerbation of gout.

On the part of the hematopoiesis system:

very rarely: thrombocytopenic purpura.

Laboratory indicators:

infrequently: hypokalemia, increased activity of "liver" transaminases;

rarely: hypoglycemia, leukopenia, thrombocytopenia;

Very rarely: erythrocytopenia, uremia, creatinineemia.

General reactions:

often: asthenia, pain in the chest;

infrequently: angioedema, weight loss;

very rarely: allergic reactions, increased fatigue.

Overdose:

Symptoms: marked decrease in blood pressure, headache, loss of consciousness, shortness of breath, palpitations, tachycardia, heart rhythm disturbances, nausea, vomiting, hypoglycemia and hypokalemia are possible.

Treatment: gastric lavage, reception of activated charcoal; the patient must be placed in the "lying" position on his back and raised his legs. With a marked decrease in blood pressure, take measures to replenish the volume of circulating blood, if necessary, apply vasopressors. Hemodialysis is ineffective, since doxazosin almost completely binds to blood plasma proteins.

Interaction:

Doxazosin enhances the antihypertensive effect of other antihypertensive drugs (with simultaneous use with them, correction of the dose of antihypertensive drugs is required).

There was no adverse interaction with simultaneous use of doxazosin and thiazide diuretics, furosemide, beta-adrenoblockers, slow calcium channel blockers, angiotensin converting enzyme inhibitors, antibacterial agents, hypoglycemic agents for oral administration, indirect anticoagulants and uricosuric agents.

Doxazosin does not affect the degree of binding to proteins of the blood plasma digoxin, phenytoin, indomethacin.

With simultaneous use with inductors of microsomal liver enzymes, it is possible to increase the effectiveness of doxazosin, with inhibitors - a decrease.

Cimetidine increases AUC doxazosin.

Non-steroidal anti-inflammatory drugs, especially indomethacin, estrogens (fluid retention) and sympathomimetic agents can reduce the antihypertensive effect of doxazosin.

Eliminating the alpha-adrenomimetic effects of epinephrine, the use of doxazosin can lead to the development of tachycardia and lowering blood pressure.

The simultaneous use of doxazosin with phosphodiesterase-5 inhibitors (including sildenafil, tadalafil, vardenafil, udenafil) can lead to a decrease in blood pressure

Special instructions:

Particular care should be taken when using Artesin® retard in patients with impaired hepatic function, especially in those cases when drugs that can alter hepatic metabolism are used simultaneously. In cases of changes in "hepatic" transaminases, Artesin® retard should be discontinued as soon as possible.

In order to prevent orthostatic reactions, patients should avoid sudden and abrupt changes in body position (transition from the "lying" position to the "standing" position).

Caution should be exercised while using phosphodiesterase-5 inhibitors and Artesin® retard drugs, since a decrease in blood pressure is possible.

It is necessary to observe a 6-hour interval between the use of phosphodiesterase-5 inhibitors and the use of Artesin® retard (to reduce the risk of lowering blood pressure, treatment is started with the use of phosphodiesterase-5 inhibitors).

When surgical interventions for cataracts against the background of the use of Artesin® retard, the development of the syndrome of intraoperative instability of the iris can be considered, which must be taken into account in the preoperative preparation of the patient and the surgicalinterference.

Taking alcohol can increase the side effect of Artesin® retard.

The effect of the "first" dose of Artesin® retard is especially pronounced against the background of previous therapy with diuretics and a diet with restriction of consumption of table salt.

Before starting therapy, prostate cancer should be excluded.

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

During the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:

Tablets of prolonged action, film-coated, 4 mg.

Packaging:

For 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

By 3 contour mesh packages together with the instruction for use are placed in a cardboard pack.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002654

Date of registration:09.10.2014

Expiration Date:09.10.2019

The owner of the registration certificate:VALENTA PHARM, PAO VALENTA PHARM, PAO Russia

Manufacturer: & nbsp

VALENTA PHARMACEUTICS, JSC Russia

Representation: & nbspVALENTA PHARM, PAO VALENTA PHARM, PAO Russia

Information update date: & nbsp25.09.2017

Illustrated instructions

Instructions

Artesin® retard (Artezin® retard)