Artesin, tablets 4 mg, 30 pcs.

In patients with benign prostatic hypertrophy doxazosin leads to significant improvement of urodynamic parameters and reduction of symptoms of the disease. The effect is associated with selective blockade by doxazosin of alpha1 – adrenoreceptors located in the muscular stroma and capsule of the prostate, in the bladder neck and in the proximal part of the urethra, which reduces resistance and pressure in the urethra, reduces resistance of the internal sphincter and facilitates urination. It is effective in 66-71 % of patients, the action beginning – after 1-2 weeks of the treatment, maximum action – after 14 weeks, the effect remains for a long time.
Application of doxazosin in patients with arterial hypertension leads to significant reduction of arterial pressure (AP) due to blockade of alpha1-adrenoreceptors located in the vascular network, reduction of vascular muscle tone and reduction of total peripheral vascular resistance. Doxazosin, among others, is effective in arterial hypertension accompanied by metabolic disorders (obesity, decreased glucose tolerance). After a single dose of doxazosin, the maximum hypotensive effect/effect is observed within 2 to 6 hours, and in general the hypotensive effect/effect lasts for 24 hours. During long-term use of doxazosin, no decrease in antihypertensive effect/effect is observed in patients. Increased plasma renin activity and tachycardia are infrequent during maintenance therapy.
It reduces the risk of coronary heart disease. During long-term treatment with doxazosin, regression of left ventricular hypertrophy, suppression of platelet aggregation and increased content of active plasminogen in tissues are observed. In addition, it is found that doxazosin increases insulin sensitivity in patients with impaired glucose tolerance.
During doxazosin treatment a decrease in plasma concentration of triglycerides, total cholesterol is observed. At the same time some increase of high density lipoprotein/total cholesterol ratio (by 4-13 %) is observed.
Taking doxazosin in patients with normal arterial pressure is not accompanied by BP reduction. The development of orthostatic hypotension during the treatment period is uncharacteristic (it may develop only with long-term administration of high doses).
Doxazosin has no metabolic side effects and may be used in patients with bronchial asthma, diabetes, left ventricular failure and gout.
After oral administration in therapeutic doses doxazosin is well absorbed in gastrointestinal tract, absorption – 80-90 % (simultaneous intake of food slows absorption by 1 hour), time to reach maximum concentration – 2-3 hours, in evening use – 5 hours. Bioavailability is 60-70 % (presystemic metabolism).
Blood plasma protein binding is about 98 %. Excretion from blood plasma occurs in two phases with terminal elimination half-life – 19-22 hours, which allows to prescribe the drug once a day.
It is quickly metabolized in liver by o-de-methylation and hydroxylation.
It is excreted intestinally, mainly as metabolites up to 65%, only 5% is excreted unchanged by kidneys.
Study of pharmacokinetics of doxazosin in elderly patients and patients with kidney disease showed no significant pharmacokinetic differences.

Indications

Active ingredient

Composition

1 tablet contains:

The active ingredient:

doxazosin mesylate (in terms of doxazosin) – 4 mg.

Auxiliary substances:

Potato starch – 20 mg;

Lactose monohydrate – 165.12 mg;

povidone – 2 mg;

Crosspovidone (Collidon CL) – 6 mg;

Magnesium stearate – 2 mg.

How to take, the dosage

One time a day (morning or evening), regardless of meals, without chewing and with plenty of water.
If the drug is missed at the usual time, you should take this dose as soon as possible. If it is time for the next dose, only that dose should be taken, without doubling the dose. If therapy with Artezin® was interrupted for several days, the drug should be restarted from the initial dose.
Dose adjustment of Artezin® preparation in elderly patients is not required.

Pharmacokinetics of doxazosin in patients with renal impairment are not altered, and doxazosin itself does not worsen the existing renal dysfunction, so in these patients Artesin® is used at normal doses.
In patients with hepatic impairment, Artesin® is used in lower doses (due to delayed metabolism of doxazosin).
In patients with benign prostatic hyperplasia the recommended initial dose in patients with normal blood pressure is 1 mg/day in order to minimize the possibility of postural hypotension and/or syncope (fainting). If necessary, depending on the urodynamic parameters and the presence of symptoms, the dose is increased (at intervals of 1-2 weeks) to 2-4 mg/day. The maximum daily dose is 8 mg. The recommended maintenance dose is 2-4 mg/day. The drug is used for a long time. The duration of treatment is determined by the doctor. In benign prostatic hyperplasia in patients with arterial hypertension the drug is prescribed in the same doses as in patients with arterial hypertension only.

In patients with arterial hypertension, the recommended starting dose is 1 mg/day in the evening before bedtime. After the first dose, the patient should stay in bed for 6-8 hours. This is required due to the possibility of orthostatic hypotension (first-dose phenomenon) after the first dose. In case of insufficient therapeutic effect, the daily dose may be increased to 2 mg/day after 1-2 weeks. Subsequently, the dose may be increased by 2 mg every 1-2 weeks to achieve the desired BP reduction. In most patients the optimal therapeutic effect is achieved at a daily dose of 8 mg. The maximum daily dose is 16 mg. After achieving a stable therapeutic effect, the dose is usually slightly reduced (the average therapeutic dose for maintenance therapy is usually 2-4 mg per day). If a diuretic or other hypotensive agent is added to therapy, the dose of Artezin® should be adjusted. In this case the dose of Artezin® preparation is decreased according to the patient’s state, and then it is gradually increased again, choosing the required dosage regimen.

Interaction

Doxazosin enhances the hypotensive effect of antihypertensive drugs.

No adverse interaction has been noted with concomitant use of doxazosin and thiazide diuretics, furosemide, β-adrenoblockers, BKK, ACE inhibitors, antibiotics, oral hypoglycemic agents, indirect anticoagulants and uricosuric agents.

It does not affect the degree of binding to plasma proteins of digoxin, phenytoin.

Concomitant use with inducers of microsomal oxidation in the liver may increase the effectiveness of doxazosin and decrease it with inhibitors.

NSAIDs (especially indomethacin), estrogens and sympathomimetic agents may decrease the hypotensive effect of doxazosin.

By eliminating α-adrenergic stimulating effects, it may lead to the development of tachycardia and arterial hypotension.

Cimetidine increases the bioavailability of doxazosin.

PDE inhibitors may increase the hypotensive effect (use caution).

Special Instructions

Before initiating therapy of prostatic hyperplasia, it is necessary to rule out cancerous rearrangement of the prostate gland. The effect of “first” taking the drug is especially pronounced at the background of previous diuretic therapy and diet with sodium restriction. It should be taken into account that the risk of orthostatic reactions also increases with alcohol consumption, hot weather, prolonged standing or physical exercises. In order to prevent orthostatic reactions, sudden and abrupt changes of body position (from lying down to standing up) should be avoided.

Doxazosin should be used with caution in elderly patients due to the possibility of orthostatic hypotension. The risk of dizziness, visual disturbances and fainting increases with age.

The patient should be informed about the increased risk of orthostatic hypotension with alcohol consumption, prolonged standing or exercise, and hot weather.

As with the use of other drugs that are fully biotransformed in the liver, caution should be exercised when prescribing doxazosin to patients with impaired liver function, especially in cases when simultaneously used drugs that may adversely affect liver function. In case of worsening of liver function parameters the drug should be withdrawn immediately.

Caution should be exercised when concomitant use of doxazosin with FDE-5 inhibitors, because this may lead to symptomatic hypotension in some patients. A 6-hour interval between the use of FDE-5 inhibitors and the use of doxazosin should be observed (to reduce the risk of BP decrease, treatment should be started with the use of FDE-5 inhibitors).

There have been reports of cases of prolonged erections and priapism on therapy with alpha1-adrenoblockers. In case of persistence of erection for more than 4 hours, medical attention should be sought immediately.

Synopsis

Contraindications

– hypersensitivity to quinazolines, doxazosin or to any of the drug excipients;
– lactose intolerance, lactase deficiency, glucose-galactose malabsorption;
– severe hepatic insufficiency;
– benign prostatic hyperplasia in combination with arterial hypotension or orthostatic hypotension in anamnesis;

Side effects

Arterial hypertension

In clinical studies, orthostatic hypotension, which in rare cases may lead to fainting, has been observed most frequently, especially at the beginning of treatment.

General reactions: asthenia, fatigue, malaise, allergic reactions, skin rash, urticaria.

Systemic reactions: peripheral edema, fainting.

CNS and peripheral nervous system disorders: dizziness, headache, drowsiness.

Gastrointestinal disorders: nausea.

Respiratory system: rhinitis.

And the following adverse reactions have also been noted in patients with arterial hypertension (causal relationship not established): bradycardia, tachycardia, palpitations, chest pain, angina pectoris, myocardial infarction, impaired cerebral circulation, and arrhythmias.

DHPS patients have the same side effects as patients with arterial hypertension, as well as:

General reactions: allergic reactions, skin rash, urticaria, back pain, sensation of heat (hot flashes), weight gain.

Systemic reactions: decreased BP, orthostatic hypotension.

CNS and peripheral nervous system: dry mouth, priapism, hypoesthesia, paresthesia, tremor, impotence, insomnia, increased excitability.

Endocrine system: gynecomastia.

Gastrointestinal disorders: abdominal pain, constipation, diarrhea, dyspepsia, flatulence, nausea, loss of appetite.

Hematopoietic disorders: leukopenia, purpura, thrombocytopenia.

Hepatobiliary system: increased liver transaminases activity, cholestasis, hepatitis, jaundice.

Skeletal and muscular system disorders: arthralgia, muscle cramps, muscle weakness, myalgia.

Respiratory system: bronchospasm, cough, shortness of breath, nasal bleeding.

Skin disorders: alopecia.

Sensory organs: blurred vision, tinnitus.

Urinary system disorders: dysuria, hematuria, urinary dysfunction, nycturia, polyuria, urinary incontinence.

Overdose

Symptoms: marked BP decrease, sometimes accompanied by fainting.

Treatment: transfer patient to supine position with lower extremities elevated above head level, symptomatic therapy; dialysis is ineffective.

Pregnancy use

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