Cardura tablets 4mg, No. 30

benign prostatic hyperplasia (BPH);

for the treatment of urinary retention and other symptoms associated with BPH;

arterial hypertension (as part of combination therapy).

The drug can be prescribed for taking both in the morning and in the evening.

In benign prostatic hyperplasia, the initial dose of Kardura is 1 mg 1 time / day in order to minimize the possibility of postural hypotension and / or syncope (syncope). Depending on the individual characteristics of urodynamics and the presence of BPH symptoms, the dose can be increased to 2 mg, and then to 4 mg and up to the maximum recommended dose of 8 mg. The recommended interval for dose escalation is 1-2 weeks. The average recommended dose is 2-4 mg 1 time / day.

With arterial hypertension, the dose of the drug varies from 1 to 16 mg / day. It is recommended to start treatment with 1 mg once a day for 1 or 2 weeks in order to minimize the possibility of postural hypotension and / or syncope (syncope) ('first dose' phenomenon). After taking the first dose, the patient needs to monitor blood pressure for 6-8 hours. This is required due to the possibility of the development of the 'first dose' phenomenon, especially pronounced against the background of previous diuretic use.

Over the next 1 or 2 weeks, the dose may be increased to 2 mg 1 time / day. To achieve the desired decrease in blood pressure, if necessary, the daily dose should be increased gradually, observing uniform intervals, up to 4 mg, 8 mg and up to a maximum of 16 mg, depending on the severity of the patient's response. The average dose is 2-4 mg 1 time / day.

If a diuretic or other antihypertensive agent is added to the therapy, it is necessary to adjust the dose of Kardura, depending on the patient's condition, with its further titration under the supervision of a physician.

If therapy with Kardura was interrupted for several days, the drug should be resumed from the initial dose.

The pharmacokinetics of doxazosin in patients with renal insufficiency does not change, and the drug itself does not aggravate existing renal dysfunction, therefore, in patients of this group, Kardura is used in normal doses.

The drug should be prescribed with caution in liver failure.

When prescribing the drug to elderly patients, correction of the dosage regimen is not required.

There is no experience with the use of Kardura in children.

White tablets

1 tab.

doxazosin

Excipients: sodium carboxymethyl starch, lactose monohydrate, microcrystalline cellulose, magnesium stearate, sodium lauryl sulfate.

• severe hepatic impairment (due to lack of experience in this category of patients);

• urinary tract infections;

• anuria;

• progressive renal failure;

• hypotension and a tendency to orthostatic disorders (including a history);

• concomitant obstruction of the upper urinary tract;

• stones in the bladder;

• lactase deficiency, lactose intolerance, glucose-galactose malabsorption;

• age under 18;

• hypersensitivity to quinazolines, doxazosin or to auxiliary components of the drug.

With care: mitral and aortic stenosis, heart failure with increased minute output, right ventricular failure due to pulmonary embolism or pericardial effusion, left ventricular failure with low filling pressure, cerebrovascular accident, old age, simultaneous use with PDE5 inhibitors, because symptomatic hypotension, hepatic failure may occur.

pharmachologic effect

Alpha1-blocker.

Benign prostatic hyperplasia

The administration of doxazosin to patients with symptoms of benign prostatic hyperplasia (BPH) leads to a significant improvement in urodynamics and a decrease in the manifestation of symptoms of the disease. This action of the drug is associated with the selective blockade of ?-adrenergic receptors located in the stroma and capsule of the prostate gland and the bladder neck.

It has been proven that doxazosin is a blocker of ?1-adrenergic receptors of subtype 1A, which make up approximately 70% of all ?1-adrenergic receptor subtypes present in the prostate gland. This explains its effect in patients with BPH.

The supportive effect of Kardura treatment and its safety have been proven with prolonged use of the drug (for example, up to 48 months).

Arterial hypertension

The use of Kardura in patients with arterial hypertension leads to a significant decrease in blood pressure as a result of a decrease in systemic vascular resistance. The appearance of this effect is associated with the selective blockade of ? 1-adrenergic receptors located in the vascular network. When the drug is taken 1 time / day, a clinically significant hypotensive effect persists for 24 hours. Blood pressure decreases gradually, the maximum effect is usually observed 2-6 hours after taking the drug. In patients with arterial hypertension, blood pressure during treatment with doxazosin was the same in the supine and standing positions.

Unlike nonselective alpha-blockers, long-term treatment with doxazosin did not develop tolerance to the drug. Increased plasma renin activity and tachycardia are uncommon during maintenance therapy.

Doxazosin has a beneficial effect on the lipid profile of the blood, significantly increasing the ratio of HDL to total cholesterol and significantly reducing total triglycerides and total cholesterol. In this regard, it has an advantage over diuretics and beta-blockers, which do not favorably affect these parameters. Taking into account the established relationship between arterial hypertension and blood lipid profile with ischemic heart disease, the beneficial effect of doxazosin on blood pressure and lipid levels simultaneously leads to a decrease in the risk of developing coronary heart disease.

Doxazosin treatment led to regression of left ventricular hypertrophy, inhibition of platelet aggregation, and increased activity of tissue plasminogen activator. In addition, doxazosin improves insulin sensitivity in patients with impaired glucose tolerance.

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

In vitro studies have shown the antioxidant properties of the 6 'and 7'-hydroxy metabolites of doxazosin at a concentration of 5 ?mol.

In controlled clinical trials conducted in patients with arterial hypertension, doxazosin treatment was accompanied by an improvement in erectile function. In addition, in patients treated with doxazosin, newly emerging erectile dysfunction was noted less frequently than in patients treated with antihypertensive drugs.

Pharmacokinetics

Absorption and distribution

After oral administration in therapeutic doses, doxazosin is well absorbed; Cmax is reached after about 2 hours. It binds to plasma proteins by 98%.

Metabolism and excretion

Doxazosin undergoes active biotransformation in the liver; less than 5% of the dose is excreted unchanged. The primary pathways of doxazosin metabolism are O-demethylation and hydroxylation.

Excretion from blood plasma is biphasic with a final T1 / 2 of 22 hours, which allows prescribing the drug 1 time / day.

Pharmacokinetics in special clinical situations

According to pharmacokinetic studies in the elderly and patients with renal insufficiency, the pharmacokinetics of doxazosin does not differ significantly from that in younger patients with normal renal function.

There are only limited data on pharmacokinetics obtained in patients with impaired liver function, and on the effect of drugs that can alter hepatic metabolism (for example, cimetidine). In a clinical study in 12 patients with moderate hepatic impairment, a single use of doxazosin was accompanied by an increase in AUC by 43% and a decrease in true oral clearance by 40%. Care must be taken when prescribing doxazosin, as well as other drugs that are completely biotransformed in the liver, to patients with impaired liver function.

Side effect

The frequency of adverse reactions is presented according to 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 prostatic hyperplasia

According to data from controlled clinical trials, patients with benign prostatic hyperplasia experienced the same side effects as patients with arterial hypertension.

With the post-marketing use of the drug, the following adverse reactions have been reported.

From the hematopoietic system: very rare - leukopenia, thrombocytopenia.

On the part of the organ of hearing and vestibular apparatus: infrequent - tinnitus.

From the side of the organ of vision: frequent - violation of color perception; infrequent - atonic iris syndrome.

From the digestive system: frequent - abdominal pain, diarrhea, dyspepsia, dryness of the oral mucosa; infrequent - flatulence, constipation, vomiting; very rare - cholestasis, hepatitis, jaundice, increased activity of hepatic transaminases.

From the immune system: very rare - anaphylactic reactions.

Laboratory indicators: infrequent - weight gain.

From the side of metabolism: infrequent - anorexia.

From the musculoskeletal system: infrequent - arthralgia, back pain, muscle spasms, muscle weakness, myalgia.

From the side of the central and peripheral nervous system: frequent - paresthesias; infrequent - hypesthesia, tremor.

From the side of the psyche: frequent - agitation, anxiety, insomnia; infrequent - depression.

From the urinary tract: infrequent - increased urination, polyuria, urinary incontinence; very rare - dysuria, hematuria, nocturia.

Reproductive system disorders: very rare - gynecomastia, impotence, priapism; very rarely - retrograde ejaculation.

From the respiratory system: frequent - shortness of breath, rhinitis; infrequent - cough, nosebleeds; very rare - exacerbation of existing bronchospasm.

From the side of the skin: infrequent - alopecia, itching, skin rash, purpura; very rare - urticaria.

From the side of the cardiovascular system: infrequent - flushes of blood to the skin of the face, a marked decrease in blood pressure, postural hypotension.

Others: infrequent - pains of different localization.

Arterial hypertension

In controlled clinical trials of the drug Kardura, the most common adverse reactions that can be attributed to the type of postural (occasionally associated with syncope) or nonspecific, which included:

On the part of the organ of hearing and vestibular apparatus: frequent - vertigo.

From the digestive system: frequent - nausea.

From the side of the central and peripheral nervous system: very frequent - dizziness, headache; frequent - postural dizziness (after taking the first dose, a pronounced decrease in blood pressure may develop, which can lead to orthostatic dizziness, in severe cases, especially with a quick transition from a prone position to a standing position or to a sitting position - to fainting), drowsiness.

Respiratory system: frequent - rhinitis.

Others: frequent - asthenia, edema of the lower extremities, fatigue, weakness.

The following adverse reactions were observed in the process of marketing the drug Kardura in patients with arterial hypertension, although in general, such symptoms could be observed in the absence of treatment with this drug: frequent - tachycardia, palpitations, chest pain; infrequent - angina pectoris, myocardial infarction and arrhythmias, very rare - bradycardia, cerebrovascular accident.

Application during pregnancy and lactation

Although in experiments on animals the drug did not have a teratogenic effect, when it was used in extremely high doses, a decrease in fetal survival was observed. These doses were approximately 300 times the maximum recommended human dose. Due to the lack of adequate well-controlled studies in pregnant or lactating women, the safety of using Kardura during pregnancy or lactation has not yet been established. In this regard, during pregnancy or lactation, Kardura can be used only when, in the opinion of the doctor, the potential benefit to the mother outweighs the potential risk to the fetus or child.

Application for violations of liver function

Care must be taken when prescribing the drug Kardura, as well as other drugs that are completely biotransformed in the liver, to patients with impaired liver function, avoiding the appointment of maximum doses.

Application for impaired renal function

The pharmacokinetics of doxazosin in patients with renal insufficiency does not change, and the drug itself does not aggravate existing renal dysfunction, therefore, in patients of this group, Kardura is used in normal doses.

Application in children

Contraindicated in children and adolescents under 18 years of age.

Use in elderly patients

With care: old age.

special instructions

Postural hypotension / syncope

As with treatment with any alpha-blockers, especially at the beginning of therapy, a very small percentage of patients experienced postural hypotension, manifested by dizziness and weakness or loss of consciousness (fainting). Before starting the appointment of any alpha-blocker, the patient must be warned how to avoid symptoms of postural hypotension, in particular, it is necessary to refrain from rapid changes in body position. At the beginning of treatment with Kardura, the patient should be advised to exercise caution in the event of weakness or dizziness.

The drug Kardura should be used with caution in elderly patients due to the possibility of orthostatic hypotension. The risk of dizziness, visual impairment 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 in hot weather.

Benign prostatic hyperplasia

In patients with BPH, the drug can be prescribed both in the presence of arterial hypertension and in normal blood pressure. When using the drug in patients with BPH with normal blood pressure, the change in the latter is insignificant. Moreover, in patients with a combination of arterial hypertension and BPH, it is possible to use it in monotherapy. Before starting therapy for prostatic hyperplasia, it is necessary to exclude its cancerous degeneration.

Doxazosin does not affect the concentration of prostate-specific antigen (PSA) in blood plasma.

Intraoperative atonic iris syndrome

Intraoperative atonic iris syndrome (a variant of narrow pupil syndrome) has been observed in some patients undergoing cataract surgery who are receiving or receiving treatment with alpha-1 blockers. Since intraoperative atonic iris syndrome can lead to an increase in complications during surgical interventions, it is necessary to warn the operating surgeon that alpha1-blockers are currently being taken or taken earlier before surgery.

Combined use with PDE5 inhibitors

Caution should be exercised when using the drug Kardura together with PDE5 inhibitors, since in some patients this can lead to symptomatic hypotension.

Liver dysfunction

Care must be taken when prescribing the drug Kardura, as well as other drugs that are completely biotransformed in the liver, to patients with impaired liver function, avoiding the appointment of maximum doses.

Influence on the ability to drive vehicles and use mechanisms

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

Overdose

Symptoms: a pronounced decrease in blood pressure, sometimes accompanied by fainting.

Treatment: it is necessary to immediately lay the patient on his back and raise his legs, if necessary, carry out symptomatic therapy. Plasma protein binding of doxazosin is high, so dialysis is ineffective.

Ћекарственное взаимодействие

—овместное применение препарата  ардура с ингибиторами ‘?Ё5 у некоторых пациентов может привести к симптоматической гипотензии.

Ѕольша¤ (98%) часть доксазозина в плазме крови св¤зана с белками. –езультаты исследовани¤ плазмы крови человека in vitro свидетельствуют о том, что доксазозин не вли¤ет на св¤зывание с белками дигоксина, варфарина, фенитоина или индометацина. ¬ клинической практике препарат  ардура примен¤лс¤ без каких-либо признаков взаимодействи¤ с тиазидными диуретиками, фуросемидом, бета-адреноблокаторами, антибиотиками, гипогликемическими средствами дл¤ приема внутрь, урикозурическими средствами и антикоагул¤нтами.

Ќѕ¬ѕ (особенно индометацин), эстрогены и симпатомиметические средства могут снижать антигипертензивное действие доксазозина.

?оксазозин, устран¤¤ альфа-адреностимулирующие эффекты эпинефрина, может приводить к развитию тахикардии и артериальной гипотензии.

ѕри одновременном приеме с силденафилом дл¤ лечени¤ легочной гипертензии повышаетс¤ риск ортостатической гипотензии.

ѕри однократном применении препарата  ардура по 1 мг/сут в течение 4-х дней при одновременном приеме 400 мг циметидина 2 раза/сут, наблюдалось 10% повышение средних значений AUC и статистически незначимое увеличение среднего уровн¤ Cmax и среднего T1/2 доксазозина. ѕодобное 10% повышение средних значений AUC доксазозина на фоне приема циметидина находитс¤ в рамках колебаний вариабельности (27%) средних значений AUC дл¤ доксазозина в сравнении с плацебо.

ѕри одновременном применении с другими гипотензивными средствами усиливает выраженность их действи¤ (необходима коррекци¤ дозы).

It is not recommended to take it concurrently with other? -Adrenoreceptor blockers.

With simultaneous use with inducers of microsomal oxidation in the liver, an increase in the effectiveness of doxazosin is possible, and with inhibitors, a decrease.