Doxazosin-Teva, tablets 4 mg 30 pcs

Indications

Benign prostatic hyperplasia (BPH): both in the presence of arterial hypertension and normal blood pressure.

Arterial hypertension: in combination with other antihypertensive agents such as thiazide diuretics, beta-blockers, slow calcium channel blockers or angiotensin-converting enzyme inhibitors.

Pharmacological effect

Pharmacotherapeutic group: α1-blocker

ATX code: C02CA04

Pharmacological properties

Pharmacodynamics

Doxazosin is a selective competitive blocker of postsynaptic alpha1-adrenergic receptors.

Benign prostatic hyperplasia

Administration of doxazosin to patients with symptoms of benign prostatic hyperplasia (BPH) leads to significant improvement in indicators

urodynamics and reduction of symptoms of the disease. This effect of the drug is associated with the selective blockade of alpha1-adrenergic receptors located in the stroma and capsule of the prostate gland, and the neck of the bladder.

Doxazosin has been shown to be an effective blocker of alpha1-adrenergic receptor subtype 1A, which constitutes approximately 70% of all alpha1-adrenergic receptor subtypes found in the prostate gland. This explains its effect in patients with BPH.

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

Arterial hypertension

The use of doxazosin in patients with arterial hypertension leads to a significant decrease in blood pressure (BP) as a result of a decrease in total peripheral

vascular resistance. The appearance of this effect is associated with selective blockade of alpha1-adrenergic receptors located in the vascular wall. When taking the drug 1 time per

day, a clinically significant antihypertensive effect persists for 24 hours, blood pressure decreases gradually; the maximum effect is usually observed 2-6 hours after taking the drug orally. In patients with arterial hypertension, blood pressure during treatment with doxazosin was the same in the “lying” and “standing” positions.

It was noted that, in contrast to non-selective alpha1-blockers, tolerance to the drug did not develop during long-term treatment with doxazosin. During maintenance therapy, increased plasma renin activity and tachycardia are uncommon. Doxazosin has a beneficial effect on the blood lipid profile, significantly

increasing the ratio of high-density lipoprotein to total cholesterol and significantly reducing triglycerides and total cholesterol. In this regard, it has an advantage over diuretics and beta-blockers, which do not have a beneficial effect on these parameters.

Considering the established connection between arterial hypertension and blood lipid profile and coronary heart disease, normalization of blood pressure and lipid concentrations while taking doxazosin leads to a reduction in the risk of developing coronary heart disease.

It was found that treatment with doxazosin led to regression of left ventricular hypertrophy, inhibition of platelet aggregation and increased tissue activator activity

plasminogen. In addition, doxazosin has been found to improve 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′ hydroxymetabolites of doxazosin at a concentration of 5 micromolar.

In controlled clinical studies conducted in patients with arterial hypertension, treatment with doxazosin was associated with improvement in erectile function.

In addition, in patients receiving doxazosin, new-onset erectile dysfunction was observed less frequently than in patients receiving antihypertensive drugs.

Pharmacokinetics

After oral administration in therapeutic doses, doxazosin is well absorbed; Its concentration in the blood reaches a maximum after approximately 2 hours.

The binding of doxazosin to blood proteins reaches approximately 98%.

The primary metabolic pathways of doxazosin are O-demethylation and hydroxylation.

Elimination from blood plasma is biphasic with a final half-life of 22 hours.

which allows you to prescribe the drug once a day.

Doxazosin undergoes active biotransformation in the liver.

In vitro studies have shown that the main route of elimination of doxazosin is through the CYP3A4 isoenzyme; however, the elimination pathways through the CYP2D6 and CYP2C9 isoenzymes are also involved in the process, but to a lesser extent.

Only less than 5% of the dose is excreted unchanged.

Use in special patient groups

According to pharmacokinetic studies in elderly patients and patients with

renal failure, the pharmacokinetics of the drug do not differ significantly from that in younger patients with normal renal function.

There are only limited data from patients with impaired function

liver, and the effects of drugs that can alter hepatic metabolism (for example,

cimetidine). In a clinical study in 12 patients with moderate hepatic impairment, a single dose of doxazosin was associated with a 43% increase in area under the concentration-time curve (AUC) and a 40% decrease in true oral clearance.

Caution must be exercised when prescribing doxazosin, as well as other drugs that are completely biotransformed in the liver, to patients with impaired liver function.

Special instructions

Orthostatic hypotension/syncope

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

Doxazosin should be used with caution in elderly patients due to the possibility of orthostatic hypotension. As you age, your risk of dizziness, blurred vision and fainting increases.

The patient should be informed about the increased risk of orthostatic hypotension when drinking alcohol, standing or exercising for long periods of time, or in hot weather.

Benign prostatic hyperplasia

In patients with BPH, doxazosin can be prescribed both in the presence of arterial hypertension and in normal blood pressure. When used in patients with BPH with normal blood pressure, the change in the latter is not significant. Moreover, in patients with a combination of arterial hypertension and BPH, it can be used in monotherapy. Doxazosin does not affect the concentration of prostate-specific antigen (PSA) in blood plasma.

Prostate carcinoma (cancer) causes many of the symptoms that occur with BPH, and both conditions can coexist in the same patient. Therefore, before using doxazosin for the treatment of BPH, it is necessary to exclude prostate carcinoma.

Use in patients with acute cardiovascular diseases

As with the use of any other vasodilators and antihypertensive drugs, caution must be exercised when using doxazosin preparations in patients with

the following acute cardiovascular diseases:

– pulmonary edema caused by mitral valve stenosis or aortic stenosis;

– heart failure with increased cardiac output;

– right ventricular heart failure caused by pulmonary embolism

or exudative pericarditis;

– left ventricular failure with low filling pressure.

Intraoperative atonic iris syndrome

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

Combined use with PDE-5 inhibitors

When using doxazosin concomitantly with PDE5 inhibitors (for example, sildenafil, tadalafil, vardenafil, udenafil), caution should be exercised.

since both drugs have vasodilatory effects, which can lead to

development of symptomatic arterial hypotension in some patients. To reduce the risk of orthostatic hypotension, treatment with PDE5 inhibitors

It is recommended to start only if the patient’s hemodynamic parameters have stabilized while using alpha-blockers. In addition, treatment with PDE5 inhibitors is recommended to begin with the lowest possible dose and maintain a 6-hour interval from taking doxazosin. Concomitant studies of PDE5 inhibitors and extended-release doxazosin have not been conducted.

Liver dysfunction

Caution must be exercised when prescribing doxazosin drugs, as well as other drugs that are completely biotransformed in the liver, to patients with impaired liver function, avoiding prescribing maximum doses. The use of Doxazosin-Teva in patients with severe liver failure is not recommended due to the lack of sufficient experience with use.

Priapism

During post-marketing studies, cases of prolonged erection and priapism have been reported during therapy with alpha1-adrenergic receptors, including doxazosin. If an erection persists for more than 4 hours, you should immediately seek medical help. If treatment for priapism is not carried out immediately, it can lead to damage to the tissue of the penis and irreversible loss of potency.

Impact on the ability to drive vehicles and machinery

During treatment with Doxazosin-Teva, especially at the beginning of treatment or when the dose is increased, dizziness and weakness may occur. In this regard, caution should be exercised when driving vehicles and while engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Active ingredient

Doxazosin

Composition

1 tablet contains:

active ingredient:

doxazosin mesylate (in terms of doxazosin) 4.85 mg (4.00 mg);

excipients:

microcrystalline cellulose 150.11 mg,

lactose (anhydrous) 80.00 mg,

sodium carboxymethyl starch (type A) 2.40 mg,

colloidal silicon dioxide 0.24 mg,

sodium lauryl sulfate 0.24 mg,

magnesium stearate 2.16 mg.

Pregnancy

Pregnancy

Although doxazosin was not teratogenic in animal experiments, decreased survival was observed when administered in extremely high doses.

fetus These doses were approximately 300 times higher than the maximum recommended doses for humans.

Due to the lack of adequate well-controlled studies in pregnant or breastfeeding women, the safety of doxazosin during pregnancy or breastfeeding has not yet been established. In this regard, during pregnancy, Doxazosin-Teva can be prescribed only when, in the opinion of the doctor, the potential benefit to the mother outweighs the potential risk to the fetus or child.

Breastfeeding period

There has been a documented case of doxazosin passing into human breast milk. Studies in laboratory animals have shown that doxazosin accumulates in milk. If it is necessary to use the drug Doxazosin-Teva during lactation, breastfeeding should be stopped.

Contraindications

– hypersensitivity to doxazosin, quinazoline derivatives (for example, to

prazosin, terazosin) or any of the auxiliary components of the drug;

– orthostatic hypotension and a tendency to orthostatic disorders (including

medical history);

– severe liver failure (there is no experience in this category

patients);

– urinary tract infections;

– anuria;

– progressive renal failure;

– concomitant obstruction of the upper urinary tract;

– stones in the bladder;

– patients with urinary incontinence due to bladder overflow (paradoxical

ishuria);

– arterial hypotension (only when used according to the indication “Benign

prostatic hyperplasia”);

– period of breastfeeding (only when used according to the indication “Arterial

hypertension”);

– children under 18 years of age;

– rare hereditary galactose intolerance, lactase deficiency, glucose syndrome

galactose malabsorption.

With caution

– pulmonary edema caused by mitral valve stenosis or aortic stenosis;

– heart failure with increased cardiac output;

– right ventricular heart failure caused by pulmonary embolism

or exudative pericarditis;

– left ventricular heart failure with low filling pressure; 5

– cerebrovascular accidents;

– in patients over 65 years of age due to the risk of developing orthostatic symptoms (fainting,

dizziness);

– simultaneous use with phosphodiesterase type 5 inhibitors (PDE-5) (threat

occurrence of symptomatic arterial hypotension);

– liver dysfunction;

– pregnancy;

– during cataract surgery.

Side Effects

The incidence of side effects is classified according to recommendations

World Health Organization: very often – at least 10%; often – at least 1%,

but less than 10%; infrequently – not less than 0.1%, but less than 1%; rarely – not less than 0.01%, but less than 0.1%;

very rare, including individual messages – less than 0.01%.

Benign prostatic hyperplasia7

According to controlled clinical studies, patients with BPH experienced those

the same adverse reactions as in patients with arterial hypertension.

The following have been reported during post-marketing use of doxazosin preparations:

adverse reactions:

Blood and lymphatic system disorders

very rarely: leukopenia, thrombocytopenia.

Immune system disorders

very rare: anaphylactic reactions.

Metabolic and nutritional disorders

uncommon: anorexia;

rarely: gout, increased appetite.

Mental disorders

often: agitation, anxiety, insomnia;

uncommon: depression.

Nervous system disorders

very often: dizziness, headache;

often: paresthesia;

uncommon: hypoesthesia, fainting, tremor.

Visual disorders

often: impaired color perception;

uncommon: atonic iris syndrome.

Hearing and labyrinth disorders

uncommon: tinnitus.

Heart disorders

often: tachycardia;

rarely: angina pectoris, myocardial infarction, heart rhythm disturbances;

very rarely: bradycardia.

Vascular disorders

infrequently: “flushes” of blood to the skin of the face, marked decrease in blood pressure, orthostatic

hypotension.

Respiratory, thoracic and mediastinal disorders

often: shortness of breath, rhinitis;

uncommon: cough, nosebleeds; 8

very rarely: exacerbation of existing bronchospasm.

Gastrointestinal disorders

often: abdominal pain, diarrhea, dyspepsia, dry oral mucosa;

uncommon: flatulence, constipation, gastroenteritis, vomiting;

unknown: taste disturbance.

Disorders of the liver and biliary tract

very rarely: cholestasis, hepatitis, jaundice.

Skin and subcutaneous tissue disorders

uncommon: alopecia, itching, skin rash, purpura;

very rare: urticaria.

Musculoskeletal and connective tissue disorders

uncommon: arthralgia, back pain, muscle spasms, muscle weakness, myalgia.

Renal and urinary tract disorders

often: cystitis, urinary incontinence;

infrequently: increased frequency of urination, polyuria;

very rarely: dysuria, hematuria, nocturia.

Disorders of the genital organs and mammary glands

uncommon: impotence;

very rare: gynecomastia, priapism, retrograde ejaculation.

General and administration site disorders

uncommon: pain of various localizations.

Influence on the results of laboratory and instrumental studies

uncommon: weight gain;

very rarely: increased activity of liver transaminases.

Arterial hypertension

In controlled clinical trials of doxazosin, the most common

adverse reactions that can be classified as postural (rarely associated with

fainting) or nonspecific, which included:

Infectious and parasitic diseases

often: respiratory tract infections, urinary tract infections.

Nervous system disorders

very often: dizziness, headache;9

often: postural dizziness (may develop after taking the first dose

a pronounced decrease in blood pressure, which can lead to orthostatic dizziness, in

severe cases, especially when quickly moving from a lying position to a standing position

or in the “sitting” position – to fainting), drowsiness.

Hearing and labyrinth disorders

often: vertigo.

Respiratory, thoracic and mediastinal disorders

often: rhinitis.

Gastrointestinal disorders

often: nausea.

General and administration site disorders

often: asthenia, swelling of the lower extremities, fatigue, weakness.

The following adverse reactions have been reported during marketing use:

doxazosin in patients with hypertension, although in general such symptoms may

observed even in the absence of treatment with this drug:

often: tachycardia, palpitations, chest pain;

uncommon: angina pectoris, myocardial infarction and arrhythmias;

very rare: bradycardia, cerebrovascular accident.

Interaction

Concomitant use of doxazosin with phosphodiesterase type 5 (PDE5) inhibitors may lead to symptomatic hypotension in some patients.

In vitro studies have shown that doscazosin is a substrate of the CYP3A4 isoenzyme. Caution should be exercised when using doxazosin and

strong CYP3A4 inhibitors such as clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin or voriconazole.

The majority (98%) of doxazosin in plasma is protein bound.

In vitro studies of human plasma indicate that doxazosin does not affect the protein binding of digoxin, warfarin, phenytoin or indomethacin. In clinical practice, doxazosin has been used without any evidence of interaction with thiazide diuretics, furosemide, beta-blockers, antibiotics, oral hypoglycemic agents, uricosurics and anticoagulants.

Nonsteroidal anti-inflammatory drugs (especially indomethacin), estrogens and sympathomimetic agents may reduce the antihypertensive effect of doxazosin.

Doxazosin, eliminating the alpha-adrenergic stimulating effects of epinephrine (adrenaline), can lead to the development of tachycardia and arterial hypotension.

When taken concomitantly with sildenafil for the treatment of pulmonary hypertension, the risk of orthostatic hypotension increases.

With a single dose of doxazosin 1 mg per day for 4 days, while taking cimetidine 400 mg 2 times a day, a 10% increase in mean AUC values ​​and a statistically insignificant increase in the mean Cmax level (maximum plasma concentration) and the mean half-life of doxazosin were observed. Similar 10% increase in mean doxazosin AUC values ​​during dosing

cimetidine is within the variability (27%) of mean AUC values ​​for doxazosin compared with placebo.

When used simultaneously with other antihypertensive drugs, the severity of their action increases (dose adjustment is necessary). It is not recommended to take simultaneously with other alpha-adrenergic blockers.

When used simultaneously with inducers of microsomal oxidation in the liver, the effectiveness of doxazosin may increase, and when used simultaneously with inhibitors, it may decrease.

Overdose

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

Treatment: the patient must immediately be placed in a lying position, legs raised and measures taken to replenish the volume of circulating blood. Symptomatic therapy. Hemodialysis is ineffective.

Storage conditions

Store at a temperature not exceeding 25°C.

Keep out of the reach of children!

Shelf life

5 years. Do not use after expiration date.

Manufacturer

Teva Pharmaceutical Works Private Limited Company, Hungary