Doxazosin Zentiva - instructions for use, dose, side effects, contraindications

Lactose 40,000 / 40,000 / 80,000 mg, microcrystalline granulated cellulose 31,267 / 45,000 / 90,000 mg, microcrystalline cellulose 45,000 / 30,055 / 60,110 mg, sodium carboxymethyl starch (type A) 1,200 / 1,200 / 2,400 mg, silicon dioxide colloidal anhydrous 0.120 / 0.120 / 0.240 mg , sodium lauryl sulfate 0.120 / 0.120 / 0.240 mg, magnesium stearate 1.080 / 1.080 / 2.160 mg

Description:

Tablets 1 mg: Round flat tablets white or almost white with engraved "ZX 1" on one side.

2 mg tablets: Prolonged, biconvex tablets white or almost white, engraved with "ZX 2" and risk for division on one side.

Tablets 4 mg: Oblong, biconvex tablets white or almost white, with engraved "ZX 4" and risk for division on one side.

Pharmacotherapeutic group:Alfa1 - adrenoblocker

ATX: & nbsp

C.02.C.A.04 Doxazosin

Pharmacodynamics:

Benign prostatic hyperplasia

The administration of doxazosin to patients with symptoms of benign hyperplasiaprostate gland (BPH) leads to a significant improvement in urodynamics and a decrease in symptoms of the disease. This action of the drug is associated with selective blockade of alpha1-adrenoreceptors located in the muscle stroma and capsule of the prostate gland, the neck of the bladder.

It is proved that doxazosin is an effective blocker of subtype-1A alpha1-adrenergic receptors, which constitute approximately 70% of all subtypes of alpha1-adrenergic receptors present in the prostate gland. This explains its effect in patients with BPH.

The effect of treatment with doxazosin and its safety have been proven with prolonged use of the drug (more than 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 the total peripheral vascular resistance. The appearance of this effect is associated with a selective blockade of alpha-adrenoreceptors located in blood vessels. When taking the drug 1 time per day, clinically significant antihypertensive effect persists for 24 hours, blood pressure decreases gradually; The maximum effect is usually observed 2-6 hours after ingestion.

Unlike nonselective alpha-blockers with prolonged treatment, addiction to the drug does not develop. When carrying out maintenance therapy, increased blood renin activity and tachycardia are rare. Doxazosin has a beneficial effect on the lipid profile of the blood, increasing the ratio of the concentration of high-density lipoproteins to total cholesterol (atherogenic index) and significantly reducing the concentration of triglycerides and total cholesterol.

Given the established relationship between arterial hypertension and the lipid profile of blood with coronary heart disease, the normalization of blood pressure and lipid concentration against the background of doxazosin administration lead to a reduction in the risk of developing ischemic heart disease.

It was observed that treatment with doxazosin led to regression of left ventricular hypertrophy, inhibition of platelet aggregation and increased activity of tissue plasminogen activator. In addition, it is established that doxazosin increases insulin sensitivity in patients with impaired glucose tolerance. Doxazosin does not have side effects on the metabolism and can be used in patients with bronchial asthma, diabetes, left ventricular failure and gout.

In controlled clinical trials conducted in patients with hypertension, treatment with doxazosin was associated with a lower incidence of erectile dysfunction.

Pharmacokinetics:

After ingestion doxazosin well absorbed in the gastrointestinal tract (80-90%). The maximum concentration in the blood plasma is achieved 1-2 hours after ingestion. Up to 98% binds to blood plasma proteins. Doxazosin undergoes significant biotransformation in the liver, metabolites have no pharmacological activity. Bioavailability - 69-70% (presystemic metabolism). In patients with impaired liver function, as well as when taking drugs that can alter hepatic metabolism, the biotransformation of the drug may be disrupted. The removal of the drug from the blood plasma is biphasic, with a finite half-life of 22 hours. Caution should be exercised when prescribing doxazosin, as well as with other drugs completely undergoing bistransformation in the liver, in patients with impaired hepatic function (see "With caution").Most of the ingested doxazosin is excreted as inactive metabolites through the intestine, less than 5% of the dose taken is excreted unchanged.

A study of pharmacokinetics in elderly patients and in patients with kidney disease did not reveal significant pharmacokinetic differences.

Indications:

benign prostatic hyperplasia;
arterial hypertension (as part of combination therapy).

Contraindications:

hypersensitivity to quinazoline derivatives (eg, to prazosin, terazosin, doxazosin) or to any of the auxiliary components of the preparation;
age to 18 years;
severe hepatic insufficiency (lack of experience in this category of patients);
anuria;
progressive renal failure;
arterial hypotension with orthostatic disorders (including in the anamnesis);
hypotension (refers only to the indication of pre-cancerous prostatic hyperplasia);
concomitant obstruction of the upper urinary tract;
chronic urinary tract infections
stones in the bladder
the period of breastfeeding (for the treatment of arterial hypertension)
lactose intolerance, lactase deficiency or glucose-galactose malabsorption due to the presence of lactose in the formulation);
obstructive disorders of the gastrointestinal tract;
esophageal obstruction;
reduction of the diameter of the lumen of the organs of the gastrointestinal tract of any stenya.

As a monotherapy:

patients with bladder overflow;

anuria with or without progressive renal failure.

Carefully:With pulmonary edema caused by stenosis of the mitral valve or aortic stenosis; heart failure with increased cardiac output; right ventricular failure due to pulmonary embolism or exudative pericarditis; left ventricular failure with low filling pressure; in elderly patients because of the risk of developing orthostatic symptoms (fainting, dizziness); when used simultaneously with phosphodiesterase type 5 inhibitors (PDE-5) (threat of symptomatic arterial hypotension); impaired liver function; during pregnancy; when performing surgery for cataracts.

Pregnancy and lactation:

Although in the experiments on animals the preparation did not have a teratogenic effect, but when applied in extremely high doses, the fetal survival was reduced. These doses are about 300 times greater than the maximum recommended dose for a person. Due to the lack of controlled clinical studies in pregnant women, the safety of the drug during pregnancy is not established. In this connection, during pregnancy, the drug can be prescribed

Only in those cases where the intended use for the mother exceeds the potential risk to the fetus.

Doxazosin is contraindicated in the period of breastfeeding, as studies in animals have shown that doxazosin accumulates in the milk of lactating rats, there is no information on the isolation of the drug into breast milk.

If necessary, use the drug should stop breastfeeding.

Dosing and Administration:

The drug Doxazosin Zentiva is administered orally regardless of food intake and is taken once a day. The tablet should be swallowed without chewing, squeezed with enough water.

Benign prostatic hyperplasia

The recommended initial dose of Doxazosin Zentiva is 1 mg 1 time per day in order to minimize the possibility of developing orthostatic hypotension and / or syncope (fainting) (see section "Special instructions"), Depending on the individual characteristics of the urodynamics and the presence of symptoms of BPH dose can be increased to 2 mg, then to 4 mg and up to a maximum daily dose of 8 mg per day. The recommended interval for increasing the dose is 1-2 weeks. Usually the recommended maintenance dose is 2-4 mg once a day. Arterial hypertension

It is recommended to start treatment with 1 mg once a day for 1 or 2 weeks in order to minimize the possibility of developing orthostatic hypotension and / or syncope (fainting) (the phenomenon of the "first dose") (see "Special instructions" ). After taking the first dose, the patient needs to monitor the blood pressure within 6-8 hours. This is required in connection with the possibility of developing the phenomenon of a "first dose", especially pronounced against the background of previous administration of diuretics.

For the next 1 or 2 weeks, the dose may be increased to 2 mg once a day, if necessary.To achieve the desired reduction in blood pressure, the daily dose should be increased gradually, keeping in regular intervals up to 4 mg, 8 mg and up to a maximum daily dose of 16 mg, depending on the severity of the patient's reaction to taking the drug. Usually the maintenance dose is 2-4 mg once a day.

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

If the therapy with Doxazosin Zentiva was interrupted for several days, the drug should be restarted from the initial dose.

Use in elderly patients.

No dose adjustment is required.

Application in renal failure.

The pharmacokinetics of doxazosin in patients with renal insufficiency does not change, and the drug itself does not worsen the existing renal dysfunction, so in such patients it is used in usual doses.

Use in patients with impaired liver function.

Use with caution (see section "Special instructions").

Use in children

Doxazosin Zentiva is contraindicated in children under 18 years of age due to a lack of sufficient data on efficacy and safety.

Side effects:

Adverse reactions are divided into system-organ classes according to the classification of the Medical Dictionary of Regulatory Activities (MedDRA).

The WHO classification was used to indicate the incidence of adverse events:

very often (> 10%);

often (> 1% and <10%);

infrequently (> 0.1% and <1%);

rarely (> 0.01% and <0.1%);

very rarely (<0.01%);

unknown frequency (according to available data, it is not possible to determine the frequency of occurrence of a side effect).

Infectious and parasitic diseases:

often - respiratory infections, urinary tract infections.

Violations from the blood and lymphatic system:

very rarely - thrombocytopenia, leukopenia.

Immune system disorders:

infrequently - allergic reactions; very rarely - anaphylactic reactions.

Disorders from the metabolism and nutrition:

infrequently - anorexia, increased appetite, weight gain, gout.

Disorders of the psyche: infrequent - agitation, anxiety, insomnia, anxiety, depression.

Impaired nervous system:

often - drowsiness, headache, dizziness; infrequently - hypoesthesia, tremor, fainting, impaired cerebral circulation; very rarely - paresthesia, orthostatic dizziness.

Disorders from the side of the organ of vision:

very rarely - blurred vision; unknown frequency - intraoperative syndrome of atonic iris (variant of "narrow pupil" syndrome).

Hearing disorders and labyrinthine disturbances:

often - vertigo; infrequently, noise in the ears.

Heart Disease:

often - palpitation, tachycardia; infrequently - angina, myocardial infarction; very rarely - a bradycardia, an arrhythmia.

Vascular disorders:

often - marked decrease in blood pressure, orthostatic hypotension; very rarely - "tides" of blood to the skin of the face.

Disturbances from the respiratory system, chest and mediastinal organs:

often - shortness of breath, rhinitis, cough, bronchitis; infrequently - epistaxis; very rarely - bronchospasm.

Disorders from the gastrointestinal tract:

often - abdominal pain, indigestion, dryness of the oral mucosa, nausea; infrequently - flatulence, diarrhea, constipation, vomiting, gastroenteritis.

Disorders from the liver and bile ducts:

very rarely - cholestasis, hepatitis, jaundice.

Laboratory and instrumental data:

rarely - increased activity of "liver" transaminases.

Disturbances from the skin and subcutaneous tissues:

often - itchy skin; infrequent skin rash; very rarely - purpura, alopecia, urticaria.

Disorders from the musculoskeletal and connective tissue: often - back pain, myalgia; infrequently - arthralgia; rarely - muscle spasms, muscle weakness.

Disorders from the kidneys and urinary tract:

often - cystitis, urinary incontinence; infrequent - increased frequency of urination, dysuria, hematuria; rarely - polyuria; very rarely - nocturia, an increase in daily diuresis.

Violations of the genitals and breast:

infrequently - erectile dysfunction; very rarely - gynecomastia, priapism; unknown frequency - retrograde ejaculation.

General disorders and disorders at the site of administration:

often - asthenia, peripheral edema, chest pain, flu-like syndrome; infrequently - edema of the face, pain of different localization; very rarely - fatigue, malaise.

Overdose:

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

Treatment: when signs of an overdose appear, it is necessary to rinse the stomach and prescribe Activated carbon, the patient must be placed in a horizontal position, with his head down, raise his legs. It is urgent to see a doctor. Symptomatic therapy is performed.

If these measures are not sufficient, the patient should first be taken out of shock by transfusion of plasma-substituting solutions. If necessary, vasopressor agents are administered. It should be monitored and, if necessary, maintained kidney function.

As doxazosin is highly associated with plasma proteins, hemodialysis is ineffective.

Interaction:

Joint use of the drug Doxazosin Zentiva with phosphodiesterase-5 inhibitors (PDE-5) (sildenafil, tadalafil, tardenafil, vardenafil, udenafil) in some patients can lead to symptomatic arterial hypotension (see section "Special instructions").

It is not recommended to take DOXASOZINE ZENTIVA at the same time as other α1-adrenoreceptor blockers.

The drug Doxazozin Zentiva enhances the antihypertensive effect of other antihypertensive drugs.

Doxazosin binds to a high degree of blood plasma proteins (98%). In vitro studies have shown that doxazosin does not affect the binding of proteins to the following drugs: digoxin, phenytoin, warfarin or indomethacin.

Undesirable drug interactions were not observed in clinical trials with thiazide diuretics, furosemide, beta-blockers, nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics, hypoglycemic agents for oral administration, with funds for uric acid and anticoagulants. However, official studies of the interaction of these drugs have not been conducted.

There was no adverse interaction with simultaneous use of doxazosin with "slow" calcium channel blockers and angiotensin-converting enzyme (ACE) inhibitors.

With simultaneous use with induction of microsomal oxidation in the liver, it is possible to increase the effectiveness of doxazosin, with inhibitors - decrease.

Estrogens and sympathomimetic agents can reduce the hypotensive effect of doxazosin. Eliminating alpha-adrenostimulating effects of epinephrine (epinephrine), doxazosin can lead to tachycardia and arterial hypotension.

In an open, randomized, placebo-controlled study in 22 healthy male volunteers, taking a single doxazosin dose of 1 mg per day on the first day of a four-day regimen of cimetidine (400 mg orally twice daily) resulted in an increase of 10% in the mean area under the concentration- time "(AUC) of doxazosin without statistically significant changes in mean values of maximum concentration (Cbax) and half-life (T_1/2) of doxazosin. A 10% increase in the mean AUC for doxazosin with cimetidine is within the inter-individual variability (27%) of the mean AUC for doxazosin with placebo. (T_1/2)

Special instructions:

Initiation of therapy:

As with any alpha 1-blockers, especially at the beginning of therapy, when treated with Doxazosin Zentiva, a very small number of patients may experience orthostatic hypotension, manifested by dizziness and weakness or loss of consciousness (syncope) (see section "Dosage and Administration" ").In this regard, it is necessary to monitor blood pressure at the beginning of therapy in order to minimize the likelihood of development of orthostatic effects. Before starting treatment with Doxazosin Zentiva, the patient should be warned how to avoid the symptoms of orthostatic hypotension, in particular, it is necessary to refrain from sudden changes in body position. At the beginning of treatment with Doxazosin Zentiva, patients should be advised that care should be taken in case of weakness or dizziness.

The drug Doxazosin Zentiva should be used with caution in elderly patients due to the possibility of developing orthostatic hypotension. With age, the risk of dizziness, visual impairment and fainting increases. The patient should be informed of the increased risk of developing orthostatic hypotension with alcohol, prolonged standing or exercise, and in hot weather.

Benign prostatic hyperplasia (BPH).

Before starting BPH therapy, it is necessary to exclude her cancer degeneration.In patients with BPH, the drug can be administered both in the presence of arterial

hypertension, and with normal blood pressure. When using the drug in patients with BPH with normal BP, the change in the latter is not significant. In this case, the use of Doxazosin Zentiva in patients with a combination of arterial hypertension and BPH is possible in monotherapy.

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

Intraoperative syndrome of atonic iris

The intraoperative syndrome of atonic iris (variant of the "narrow pupil" syndrome) was observed in some patients during a cataract operation that received or received treatment with alpha 1-adrenergic blockers. Since the intraoperative syndrome of atonic iris can lead to more complications during surgical interventions, it is necessary to alert the ophthalmic surgeon that alpha1-adrenoblockers are being taken at the moment or taken before surgery.

Co-administration with PDE-5 inhibitors

With simultaneous use of doxazosin with PDE-5 inhibitors (for example, with sildenafil, tadalafil, vardenafil,udenafil) should be careful, since both drugs have vasodilator effects and can lead to the development of symptomatic arterial hypotension in some patients. To reduce the risk of orthostatic hypotension, treatment with PDE5 inhibitors is recommended to start only if the patient's hemodynamic parameters stabilized against the background of the use of alpha-adrenoblockers. In addition, treatment with PDE5 inhibitors is recommended starting at the lowest possible dose and maintaining a 6-hour interval from taking doxazosin. Studies of drugs with prolonged release of doxazosin have not been conducted.

Impaired liver function

Caution should be exercised when prescribing Doxazosin Zentiva, as well as other drugs completely exposed to biotransformation in the liver, to patients with impaired hepatic function (see section "Pharmacokinetics"), avoiding the appointment of maximum doses. It is not recommended to use Doxazosin Zentiva in patients with severe hepatic insufficiency due to a lack of sufficient experience of use.

Lactose intolerance

The preparation contains lactose.Patients with hereditary lactose intolerance, lactase deficiency or glucose-galactose malabsorption drug is contraindicated.

Application in patients with acute cardiac pathology

As with any other vasodilatory and antihypertensive agents, caution should be exercised when administering the drug doxazosin ZENTIVA patients with the following acute cardiac pathology:

pulmonary edema caused by stenosis of the mitral valve or aortic stenosis; heart failure with increased cardiac output; right ventricular failure due to pulmonary embolism or exudative pericarditis; left ventricular failure with low filling pressure.

Effect on the ability to drive transp. cf. and fur:Since the period of treatment with doxazosin ZENTIVA may experience drowsiness, dizziness, and syncope, especially early in treatment, care should be taken when driving and while busy with other potentially hazardous activities that require high concentration and psychomotor speed reactions.

Form release / dosage:

Tablets, 1 mg, 2 mg, 4 mg.

Packaging:

Tablets 1 mg: For 15 tablets in a blister of A1 / PVC / PVDC. For 1 or 2 blisters in a cardboard pack together with instructions for use.

Tablets 2 mg: 10 tablets in a blister of A1 / PVC / PVDC. For 1, 3, 6 or 9 blisters in a cardboard pack together with instructions for use.

Tablets 4 mg: 10 tablets in a blister of A1 / PVC / PVDC. By 3, 6.9 or 10 blisters in a cardboard pack together with instructions for use.

Storage conditions:

Store at a temperature of 10-25 ° C, in a place protected from light.

Keep out of the reach of children.

Shelf life:

3 years.

The drug should not be used after the expiry date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N014395 / 01

Date of registration:07.09.2007 / 25.06.2014

The owner of the registration certificate:Zentiva c.s.Zentiva c.s. Czech Republic

Manufacturer: & nbsp

ZENTIVA, k.s. Czech Republic

Information update date: & nbsp01.02.2016

Illustrated instructions

Instructions

Doxazosin Zentiva (Doxazosin Zentiva)