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

Excipients: cellulose microcrystalline (avicel PH 101 - 45,000 / 90,00 mg, emcocele 90 M - 30,055 / 60,1 1 mg) - 75,055 / 150,1 1 mg, lactose - 40/80 mg, sodium carboxymethyl starch - 1.20 / 2 , 40 mg, magnesium stearate -1,08/2,16 mg, silicon dioxide colloid - 0.12 / 0.24 mg, sodium lauryl sulfate - 0.12 / 0.24 mg.

Description:

2 mg: Oblong white tablets with a risk and impression D and 2 on both sides of the risks on one side of the pill.

4 mg: Oblong white tablets with a risk and impression D and 4 on both sides of the risks on one side of the pill.

Pharmacotherapeutic group:alpha1-blocker

ATX: & nbsp

C.02.C.A.04 Doxazosin

Pharmacodynamics:

Doxazosin is a selective competitive blocker of postsynaptic alpha₁-adrenergic receptors (affinity for alpha₁-receptors are 600 times higher than to alpha₂), an antihypertensive drug and a drug for the treatment of benign prostatic hyperplasia (BPH).

Reduces the overall peripheral vascular resistance (OPSS), prevents vasoconstriction caused by catecholamines, which ultimately leads to a decrease in blood pressure without the development of reflex tachycardia. Reduces pre- and afterload.The use of the drug once a day leads to a clinically significant decrease in blood pressure (BP), the antihypertensive effect persists for 24 hours. After taking the drug, the decrease in blood pressure occurs gradually, the maximum effect is observed after 2-6 hours. In patients with arterial hypertension (AH) During treatment with doxazosin, blood pressure in a supine and sitting position will be the same.

Unlike non-selective alpha blockers₁-adrenoceptors with long-term treatment with doxazosin, the development of tolerance to the drug was not observed. With prolonged treatment, an increase in renin plasma activity and tachycardia is rarely observed.

Clinical studies have shown that doxazosin contributes to an increase in the ratio of high-density lipoprotein (HDL) / total cholesterol (about 4-13% of the initial value), reduces the total concentration of triglycerides (TG) and cholesterol in the blood plasma.

Effective with AH, including those accompanied by metabolic disorders (obesity, hyperlipidemia, decreased glucose tolerance).

With long-term treatment, regression of left ventricular hypertrophy, suppression of platelet aggregation,an increase in activity in the tissues of the activator of profibrinolysin (plasminogen) and a decrease in the formation of collagen in the walls of the arteries.

Reduces the risk of coronary heart disease (CHD).

Increases the content of angiotensin-converting enzyme (ACE), uncharacteristic development of orthostatic hypotension in response to the first dose (can develop only with prolonged use of high doses). The intake of the drug in normotonics is not accompanied by a decrease in blood pressure.

The use of doxazosin in patients with BPH leads to a significant improvement in urodynamic parameters and a reduction in the symptoms of the disease. The effect is associated with a selective alpha blockade₁-adrenoceptors of subtype Ia (70% of all subtypes present in the prostate), which are localized in the muscle stroma, prostatic capsule, in the neck of the bladder and in the proximal part of the urethra, which reduces the muscle tone of the prostate and facilitates urination. The effect in 66-71% of patients, the onset of action - after 1-2 weeks of treatment, maximum - after 14 weeks, persists for a long time.

Pharmacokinetics:

After oral administration doxazosin well absorbed in the digestive tract (about 80-90%), simultaneous intake of food slows down absorption for 1 hour. The maximum concentration in the blood plasma is reached approximately 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 is 69-70% (presystemic metabolism). Metabolized mainly in the liver by o-demethylation and hydroxylation. 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.

Excretion from the blood plasma is biphasic, with a finite half-life of 22 hours, which allows the drug to be used once a day.

It is excreted through the intestine, mainly in the form of inactive metabolites (63-65%), less than 5% - unchanged; about 10% through the kidneys.

Pharmacokinetic studies in elderly patients and patients with kidney disease did not reveal significant pharmacokinetic differences.

Indications:

- Arterial hypertension (as part of combination therapy);

- benign prostatic hyperplasia (BPH).

Contraindications:

- Hypersensitivity to quinazoline derivatives (eg, Prazonin, terazonin, doxazosin) or to any of the auxiliary components of the preparation;

- use in patients who have an orthostatic hypotension in an anamnesis;

- BPH combined with arterial hypotension;

- BPH combined with a violation of patency of the upper urinary tract, chronic infections of the urinary tract or stones in the bladder;

- progressive renal failure;

- the period of breastfeeding (for the treatment of hypertension);

- lactose intolerance, lactase deficiency or glucose-galactose malabsorption (due to the presence of lactose in the formulation);

- severe hepatic insufficiency (experience is insufficient);

- age under 18 years (effectiveness and safety not established);

- in monotherapy in the treatment of patients with urinary incontinence due to overflow of the bladder or anuria.

Carefully:

With pulmonary edema,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 (dizziness, fainting); when used simultaneously with phosphodiesterase type 5 inhibitors (PDE-5) because of the risk of symptomatic arterial hypotension; when liver function is impaired; when performing a cataract operation; during pregnancy.

Pregnancy and lactation:

In animal studies, teratogenic effects of doxazosin were not identified. The safety of doxazosin during pregnancy has not been established, since no adequate or well-controlled studies of the use of the drug in pregnant women have been conducted. In connection with this, during pregnancy, the drug Doxazosin Belupo can be prescribed only if the intended benefit to the mother exceeds the potential risk to the fetus.

Studies in animals have shown that doxazosin accumulates in milk, so the use of the drug Doxazosin Belupo during breastfeeding is contraindicated. If necessary, use the drug should stop breastfeeding.

Dosing and Administration:

Inside, once a day, regardless of meal time. The tablet should be swallowed without chewing, squeezed with enough liquid.

Drug Doxazosin Belupo can be used both in the morning and in the evening. The first method is preferably performed before bedtime to prevent the possible development of orthostatic hypotension.

Arterial hypertension

The recommended initial dose is 1 mg (1/2 tablets 2 mg) once a day for 1-2 weeks to minimize the possibility of developing orthostatic hypotension and / or syncope (fainting) phenomenon (the "first dose" phenomenon). For the next 1-2 weeks, if necessary, the dose may be increased to 2 mg once daily. To achieve the desired reduction in blood pressure, the daily dose should be increased gradually at regular intervals to 4 mg, 8 mg and 16 mg once a day, depending on the severity of the hypotensive effect of the drug. The usual maintenance dose is 2-4 mg once daily.

If the antihypertensive effect is insufficient, it is possible to add a diuretic or other antihypertensive agent to therapy. In this case, you need to adjust the dose of Doxazosin Belupo depending on the condition of the patient with further titration under the supervision of the doctor.

Benign prostatic hyperplasia (BPH)

The recommended initial dose is 1 mg (1/2 tablets of 2 mg) once a day to minimize the possibility of developing orthostatic hypotension and / or syncope (fainting) (the phenomenon of the "first dose"), depending on the individual characteristics of the indicators urodynamics and the presence of symptoms of BPH, the dose can be increased at intervals of 1 to 2 weeks to 2 mg, then to 4 mg and to a maximum daily dose of 8 mg. The usual maintenance dose is 2-4 mg once daily.

In the event of discontinuation of therapy with Doxazosin Belupo for several days, the use of the drug should be resumed from the initial dose.

Use in elderly patients

No dose adjustment is required.

Use in patients with renal insufficiency

Since the pharmacokinetics of doxazosin in patients with renal insufficiency does not change, and the drug itself does not worsen the existing renal dysfunction, a usual dose of the drug is recommended for such patients.

Use in patients with impaired hepatic function

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

Side effects:

The incidence of adverse reactions is classified according to the recommendations of the World Health Organization: very often (≥10%); often (≥1% and <10%); infrequently (≥0.1%, <1%); rarely (≥0.01%, <0.1%); very rarely (<0.01%); an 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: rarely - thrombocytopenia, and leukopenia.

Immune system disorders: infrequently - allergic reactions: very rarely - anaphylactic reactions.

Metabolic disorders: infrequently - anorexia, increased appetite, weight gain, gout.

Disturbances from the nervous system: often - drowsiness, dizziness, headache; infrequently - hypoesthesia, tremor, fainting, impaired cerebral circulation; very rarely - paresthesia, orthostatic dizziness.

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

Disturbances on the part of the organ of sight: very rarely - blurred vision: unknown frequency - intraoperative syndrome of atonic iris (variant of "narrow pupil" syndrome).

Hearing disorders and labyrinthine disorders: often - vertigo; infrequently, noise in the ears.

Disorders from the cardiovascular system: often - palpitations, tachycardia, marked decrease in blood pressure, orthostatic hypotension; infrequently - angina, myocardial infarction; very rarely - a bradycardia, an arrhythmia, "tides" of a blood to a 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 - constipation, flatulence, vomiting, diarrhea, gastroenteritis.

Disturbances from the liver and bile ducts: infrequently - violations of the liver function; very rarely - cholestasis. hepatitis, jaundice.

Disturbances from the skin and subcutaneous tissues: often - itchy skin; infrequent skin rash; very rarely - purpura, alopecia, urticaria.

Disturbances from 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; infrequently - dysuria, increased frequency of urination, hematuria; rarely - polyuria; very rarely - nocturia, an increase in daily diuresis, violation of urination.

Violations of the genitals and mammary gland: infrequently - erectile dysfunction; very rarely - gynecomastia, priapism; unknown frequency - retrograde ejaculation.

Laboratory and instrumental data: rarely - increased activity "hepatic" transaminases.

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

Overdose:

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

Treatment: the patient should be placed in a horizontal position on the back, with his head down, and raise his legs, rinse the stomach and appoint Activated carbon. If necessary, apply symptomatic therapy. If these measures are insufficient, the patient should be removed from shock by transfusion of plasma-substituting solutions, if necessary, vasopressor agents are administered. It should be monitored and, if necessary, maintained kidney function.

Hemodialysis is ineffective because doxazosin binds to blood plasma proteins.

Interaction:

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

Doxazosin Belupo enhances the antihypertensive effect of other antihypertensive drugs.

It is not recommended to take Doxazosin Belupo simultaneously with other alpha blockers₁adrenoreceptors.

Doxazosin binds to a high degree of blood plasma proteins (98%). Doxazosin does not affect the degree of binding to blood proteins of digoxin, warfarin, phenytoin, indomethacin.

There were no adverse interaction in clinical trials of thiazide diuretics, furosemide, beta-blockers, nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics, hypoglycemic agents for oral administration, with means for uricosuric and anticoagulants. However, official studies of the interaction of these drugs have not been conducted.

At simultaneous application with inductors of microsomal oxidation in the liver, it is possible to increase the efficiency of doxazosin, while simultaneous use with inhibitors - its reduction.

There was no adverse interaction with simultaneous use of doxazosin with blockers of "slow" calcium channels and ACE inhibitors.

Cimetidine increases the area under the concentration-time curve (AUC) of doxazosin.

Estrogens and sympathomimetic drugs can reduce the hypotensive effect of doxazosin.

Eliminating the alpha-adrenostimulating effects of epinephrine, doxazosin can lead to the development of tachycardia and arterial hypotension.

Special instructions:

In the treatment with the drug Doxazosin Belupo, as in the treatment of any alpha₁-adrenoconvertors, an insignificant number of patients may have orthostatic hypotension, manifested by weakness, dizziness or loss of consciousness, especially at the beginning of therapy (see section "Dosing and Administration"). In this regard, it is necessary to monitor BP at the beginning of therapy in order to minimize the likelihood of development of orthostatic effects. Before starting treatment with Doxazosin Belupo, the patient should be warned how to avoid the appearance of symptoms of orthostatic hypotension, in particular, the need to refrain from sudden changes in body position, as well as the need to be careful in case of weakness or dizziness.

Drug Doxazosin Belupo should be used with caution in elderly patients in connection with the possibility of developing orthostatic hypotension.With age, the risk of dizziness, visual impairment and fainting increases. The patient should be informed of the increase in the development of orthostatic hypotension with alcohol, prolonged standing, exercise and in hot weather.

Use in patients with acute heart failure

Just as with the use of other vasodilators and hypotensive drugs, care must be taken when prescribing the drug to patients in the presence of the following diseases:

- 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

Use in patients with impaired hepatic function

Like other drugs, the metabolism of which occurs in the liver, doxazosin should be used with caution in the treatment of patients with impaired liver function. It is not recommended to take this medication for patients with severe hepatic impairment because oflack of clinical experience. Simultaneous use with PDE-5 inhibitors

With simultaneous use of the drug Doxazosin Belupo with PDE-5 inhibitors (sildenafil, tardenafil, tadalafil, vardenafil, udenafil) should be careful, since both drugs have a vasodilating effect and can lead to the development of symptomatic arterial hypotension in some patients. To reduce the risk of orthostatic hypotension, treatment with PDE-5 inhibitors is recommended to start only if the patient has stable hemodynamics against the background of the use of alpha-blockers. To begin treatment with inhibitors of PDE-5 is recommended from the lowest possible dose in 6 hours after doxazosin administration.

Intraoperative syndrome of atonic iris

Intraoperative syndrome of atonic iris (variant of "narrow pupil" syndrome) was observed in some patients during cataract surgery, undergoing or undergoing alpha treatment₁adrenoblockers. Since the intraoperative syndrome of atonic iris can lead to an increase in complications during surgical interventions,It is necessary to inform the ophthalmologist about the current or previous treatment of alpha₁adrenoblockers.

Benign prostatic hyperplasia (BPH)

Before starting BPH therapy, it is necessary to exclude her cancer degeneration. In patients with BPH, the drug can be prescribed both in the presence of arterial hypertension, and with normal BP. When using the drug in patients with BPH with normal BP, the change in the latter is not significant. The use of Doxazosin Belupo in patients with a combination of arterial hypertension and BPH is possible in monotherapy.

Doxazosin does not affect the concentration of prostate-specific antigen (G1CA) in the blood plasma.

Lactose intolerance

The drug contains lactose, so the drug is contraindicated for patients with hereditary lactose intolerance, lactase deficiency or glucose-galactose malabsorption.

Priapism

During post-registration studies, cases of development of prolonged erection and priapism were reported against the background of alpha therapy₁adrenoblockers, including doxazosin. If you have an erection for more than 4 hours, you should immediately seek medical help.If priapism therapy has not been performed immediately, it can lead to damage to the penile tissue and an irreversible loss of potency.

Effect on the ability to drive transp. cf. and fur:

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

Form release / dosage:

Tablets, 2 mg and 4 mg.

Packaging:

For 20 tablets in PVC / PVDC / / Al blister.

One blister, along with instructions for use, is placed in a cardboard box.

Storage conditions:

At a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-000340

Date of registration:22.02.2011 / 12.04.2016

Expiration Date:Unlimited

The owner of the registration certificate:Beluga, medicines and cosmetics.Beluga, medicines and cosmetics. Croatia

Manufacturer: & nbsp

BELUPO, Pharmaceuticals & Cosmetics, d.d. Croatia

Representation: & nbspBeluga, medicines and cosmetics. Beluga, medicines and cosmetics. Croatia

Information update date: & nbsp11.11.2016

Illustrated instructions

Instructions

Doxazosin Belupo (Doxazosin Belupo)