Artesin, tablets 2 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 66-71% effective in 66-71% of patients; the beginning of the effect – after 1-2 weeks of treatment; maximum effect – after 14 weeks; the effect lasts for a long time.

The use of doxazosin in patients with arterial hypertension leads to a significant reduction of arterial pressure (BP) due to blockade of alpha 1-adrenoreceptors located in 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 uncommon during maintenance therapy.

Limits the risk of coronary heart disease. With 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, doxazosin has been found to increase insulin sensitivity in patients with impaired glucose tolerance.

During treatment with doxazosin 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.

The administration of doxazosin in patients with normal blood pressure is not accompanied by a decrease in BP. The development of orthostatic hypotension during treatment is uncharacteristic (it may develop only with prolonged use of high doses).

Doxazosin has no metabolic side effects and can be used in patients with bronchial asthma, diabetes, left ventricular insufficiency 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).

Binding with blood plasma proteins is about 98%. Excretion from blood plasma occurs in 2 phases with terminal elimination half-life – 19-22 hours, which allows to prescribe the preparation once a day.
It is quickly metabolized in liver by o-demethylation and hydroxylation.

Extracted through the intestine, mainly as metabolites up to 65%, only 5% is excreted unchanged by the kidneys.
Studies of pharmacokinetics of doxazosin in elderly patients and patients with kidney disease showed no significant pharmacokinetic differences.

Indications

Active ingredient

Composition

Active ingredient: doxazosinum mesylate 2.44 mg or 4.88 mg (in terms of doxazosin – 2.00 mg or 4.00 mg);
excipients: pregelatinized starch, lactose monohydrate, microcrystalline cellulose, sodium carboxymethyl starch, colloidal silicon dioxide (aerosil), magnesium stearate.

How to take, the dosage

Entreally once 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 increases the hypotensive effect/effect of hypotensive drugs (dosage adjustment is required when used in combination). It is not recommended to take doxazosin concomitantly with other alpha-adrenoreceptor blockers.
No adverse interaction has been noted with concomitant use of doxazosin and thiazide diuretics, furosemide, beta-adrenoblockers, “slow” calcium channel blockers, angiotensin-converting enzyme inhibitors, antibiotics, hypoglycemic agents for oral administration, indirect anticoagulants and uricosuric agents.
Doxazosin does not affect the degree of binding to plasma proteins of digoxin and phenytoin.
Concomitant use of doxazosin with inducers of microsomal oxidation in the liver may increase the effectiveness of doxazosin, with inhibitors – decrease.
Nonsteroidal anti-inflammatory drugs (especially indomethacin), estrogens and sympathomimetic agents may reduce the hypotensive effect/effect of doxazosin.
Cimetidine increases the bioavailability of doxazosin.
Co-use of doxazosin with FDE-5 inhibitors (udenafil, sildenafil, tadalafil, vardenafil) may lead to symptomatic hypotension.
Doxazosin, eliminating the alpha-adrenergic stimulating effects of epinephrine, may lead to tachycardia and hypotension.

Special Instructions

Before starting therapy of prostatic hyperplasia it is necessary to exclude cancerous rearrangement of the prostate.
The effect of “first” taking the drug is especially pronounced against the background of previous diuretic therapy and a sodium-restricted diet. It should be taken into account that the risk of orthostatic reactions also increases with alcohol consumption, hot weather, prolonged standing or physical exercise. In order to prevent orthostatic reactions, sudden and abrupt changes of body position (transition from lying to standing position) 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 any vasodilatory hypotensive agent, doxazosin should be used with caution in patients with heart disease requiring emergency care: pulmonary edema due to aortic or mitral stenosis, right ventricular failure due to pulmonary embolism or exudative pericarditis, left ventricular failure with low ventricular filling pressure; and in patients with severe myocardial ischemia, in whom too rapid or pronounced reduction in blood pressure may lead to increased angina symptoms.

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

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

There are reports of cases of prolonged erections and priapism on therapy with alpha1-adrenoblockers. In case of persistence of erection for more than 4 hours, it is necessary to seek medical attention 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

The frequency of side effects is categorized as follows: very frequent (>10%), frequent (>1% and < 10%), infrequent (>0.1% and < 1%), rare (>0.01% and < 0.1%), very rare (< 0.01%).

In patients with benign prostatic hyperplasia the same side effects as in patients with arterial hypertension occur, as well:
Cardiovascular system: infrequent – marked decrease of blood pressure, orthostatic hypotension, “flushes” of blood to the face.
Central and peripheral nervous system: frequent – paraesthesia, dry mouth, insomnia, increased excitability, infrequent – hypoesthesia, tremor, depression; very rare – priapism, impotence.
Endocrine system: very rare – gynecomastia.
Gastrointestinal tract: frequent – abdominal pain, diarrhea, dyspepsia, nausea; infrequent – flatulence, constipation, vomiting, loss of appetite.
Blood organs: very rare – leukopenia, thrombocytopenia.
Hepatobiliary system: very rare – increased activity of liver transaminases, cholestasis, hepatitis, jaundice.
Musculoskeletal system: infrequent – arthralgia, muscle cramps, muscle weakness, myalgia.
Respiratory system: frequent – shortness of breath, rhinitis, infrequent – cough, nasal bleeding, very rare – bronchospasm.
Skin: infrequent – alopecia, skin rash, itching, purpura, very rare – urticaria.
Senses: frequent – blurred vision, infrequent – tinnitus, atonic iris syndrome.
Urinary system: infrequent – urinary disorders, polyuria, urinary incontinence; very rare – dysuria, hematuria, nicturia.
Reproductive system: very rare – retrograde ejaculation.
Immune system: very rare – anaphylactic reactions.
Other: infrequent – weight gain, pain in various localizations.

Arterial hypertension
In clinical trials, especially at the beginning of treatment, orthostatic arterial hypotension has been observed most frequently, which in rare cases can lead to fainting.
Cardio-vascular system: frequent – peripheral edema.
Central and peripheral nervous system: very common – dizziness, headache; frequent – somnolence.
Gastrointestinal tract: frequent – nausea.
Respiratory system: frequent – rhinitis.
Other: frequent – asthenia, fatigue, malaise.
In patients with arterial hypertension the following adverse reactions were also observed (cause-effect relationship is not defined): frequent – tachycardia, palpitations, chest pain; infrequent – angina pectoris, myocardial infarction, arrhythmias; very rare – bradycardia, cerebrovascular disorders.

Overdose

Symptoms:

pronounced decrease in BP, sometimes accompanied by fainting.

Treatment:
the patient should be put in a horizontal position with elevated legs. Symptomatic therapy is administered. Hemodialysis is ineffective.

Pregnancy use

Similarities