Composition, form of production and packaging
Tablets of white color, round, biconcave, with engraving "CN 1" on one side and engraving of the Pfizer logo on the other.
1 tab.
Doxazosin mesylate 1.213 mg,
which corresponds to the content of doxazosin 1 mg
Excipients: sodium carboxymethyl starch - 1.2 mg, lactose monohydrate - 40 mg, microcrystalline cellulose - 76,382 mg, magnesium stearate - 1.08 mg, sodium lauryl sulfate - 120 Ојg.
7 pcs. - blisters (2) - packs of cardboard.
10 pieces. - blisters (3) - packs of cardboard.
14 pcs. - blisters (1) - packs of cardboard.
Tablets of white color, oval, biconcave, with engraving "CN 2" and risk on one side and engraving of the Pfizer logo - on the other.
1 tab.
doxazosin mesylate 2.43 mg,
which corresponds to the content of doxazosin 2 mg
Excipients: sodium carboxymethyl starch - 1.2 mg, lactose monohydrate - 40 mg, microcrystalline cellulose - 75.17 mg, magnesium stearate - 1.08 mg, sodium lauryl sulfate - 120 Ојg.
7 pcs. - blisters (2) - packs of cardboard.
10 pieces. - blisters (3) - packs of cardboard.
14 pcs. - blisters (1) - packs of cardboard.
Tablets of white color, diamond-shaped, biconcave, with engraving "CN 4" and risk on one side and engraving of the Pfizer logo - on the other.
1 tab.
doxazosin mesylate 4.85 mg,
which corresponds to the content of doxazosin 4 mg
Excipients: sodium carboxymethyl starch - 2.4 mg, lactose monohydrate - 80 mg, microcrystalline cellulose - 150.35 mg, magnesium stearate - 2.16 mg, sodium lauryl sulfate - 240 Ојg.
7 pcs. - blisters (2) - packs of cardboard.
10 pieces. - blisters (3) - packs of cardboard.
14 pcs. - blisters (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2013.
PHARMACHOLOGIC EFFECT
Alpha 1- adrenoblocker.
Benign prostatic hyperplasia
The appointment 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 a selective blockade of ОІ-adrenoreceptors located in the stroma and capsule of the prostate and the neck of the bladder.
Is it proven that doxazosin is a blocker? 1- adrenoreceptors of subtype 1A, which constitute approximately 70% of all subtypes? 1- adrenoreceptors, represented in the prostate gland. This explains its effect in patients with BPH.
The supportive effect of Cardura treatment and its safety is proved with long-term use of the drug (for example, up to 48 months).
Arterial hypertension
The use of Cardura in patients with arterial hypertension leads to a significant reduction in blood pressure as a result of a decrease in OPSS. The appearance of this effect is associated with a selective blockade? 1- adrenoreceptors located in the vascular network. When taking the drug 1 time / day clinically significant hypotensive effect persists for 24 hours. BP decreases gradually, the maximum effect is usually observed in 2-6 hours after taking the drug. In patients with hypertension, blood pressure in treatment with doxazosin was the same in the prone and standing position.
Unlike nonselective alpha-blockers with prolonged treatment with doxazosin, tolerance to the drug did not develop. When carrying out maintenance therapy, increased plasma renin activity and tachycardia are rare.
Doxazosin has a beneficial effect on the lipid profile of blood, significantly increasing the ratio of HDL cholesterol to total cholesterol and significantly reducing the content of total triglycerides and total cholesterol. In this regard, it has an advantage over diuretics and beta-blockers, which do not affect favorably on these parameters. Given the established association of arterial hypertension and lipid profile of blood with IHD, the beneficial effect of doxazosin simultaneously on blood pressure and lipid levels leads to a reduction in the risk of developing coronary heart disease.
Treatment with doxazosin 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 does not have side effects of metabolic effects and can be used in patients with bronchial asthma, diabetes, with left ventricular failure and gout.
In vitro studies have shown the antioxidant properties of doxazosin 6 'and 7'-hydroxymetabolites at a concentration of 5 Ојmol.
In controlled clinical trials conducted in patients with hypertension, treatment with doxazosin was accompanied by an improvement in erectile function. In addition, in patients receiving doxazosin, the newly emerging erectile dysfunction was less common than in patients receiving antihypertensive drugs.
PHARMACOKINETICS
Suction and distribution
After oral administration at therapeutic doses, doxazosin is well absorbed; C max 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 ways of metabolizing doxazosin are O-demethylation and hydroxylation.
Excretion from the blood plasma is biphasic with a finite T 1/2 of 22 h, which allows prescribing the drug 1 time / day.
Pharmacokinetics in special clinical cases
According to pharmacokinetic studies in elderly patients 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 capable of altering hepatic metabolism (eg, cimetidine). In a clinical study in 12 patients with moderate impairment of liver function, single administration of doxazosin was accompanied by an increase in AUC by 43% and a decrease in true oral clearance by 40%. Caution should be exercised when prescribing doxazosin, as well as other drugs completely exposed to biotransformation in the liver, to patients with impaired liver function.
INDICATIONS
- benign prostatic hyperplasia (BPH);
- to treat delayed outflow of urine and other symptoms associated with BPH;
- arterial hypertension (as part of combination therapy).
DOSING MODE
The drug can be prescribed for reception in the morning and in the evening.
In benign prostatic hyperplasia, the initial dose of Cardura 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 symptoms of BPH, the dose can be increased to 2 mg, then to 4 mg and to the maximum recommended dose of 8 mg. The recommended interval for increasing the dose 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. Treatment is recommended to start with 1 mg 1 time / day for 1 or 2 weeks in order to minimize the possibility of postural hypotension and / or syncope (fainting) phenomenon (the "first dose" phenomenon). 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 intake of diuretics.
For the next 1 or 2 weeks, the dose may be increased to 2 mg 1 time / day. To achieve the desired reduction in blood pressure, if necessary, the daily dose should be increased gradually, at regular intervals, up to 4 mg, 8 mg and up to a maximum of 16 mg, depending on the severity of the patient's reaction. The average dose is 2-4 mg 1 time / day.
If a diuretic or other antihypertensive drug is added to the therapy, the dose of Cardura must be adjusted depending on the patient's condition with further titration under the supervision of the doctor.
If the drug Kardura was interrupted for several days, the drug should be restarted from the initial dose.
The pharmacokinetics of doxazosin in patients with renal insufficiency does not change, and the drug itself does not exacerbate existing renal dysfunction, therefore in patients of this group Cardura is used in usual doses.
With caution should prescribe the drug for liver failure .
When the drug is prescribed for elderly patients, correction of the dosing regimen is not required.
The experience of using Cardura in children is absent.
SIDE EFFECT
The incidence of adverse reactions is represented by 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 controlled clinical trials in patients with benign prostatic hyperplasia, the same side effects were observed as in patients with hypertension.
During post-marketing use of the drug, the following adverse reactions were reported.
On the part of the hematopoiesis system: very rare - leukopenia, thrombocytopenia.
From the side of the organ of hearing and the vestibular apparatus: infrequent - noise in the ears.
From the side of the organ of vision: frequent - violation of color perception; infrequent - a syndrome of an atonic iris.
From the digestive system: frequent - abdominal pain, diarrhea, indigestion, dryness of the oral mucosa; infrequent - flatulence, constipation, vomiting; very rare - cholestasis, hepatitis, jaundice, increased activity of hepatic transaminases.
From the side of 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 central and peripheral nervous system: frequent - paresthesia; infrequent - hypesthesia, tremor.
From the side of the psyche: frequent - agitation, anxiety, insomnia; infrequent - depression.
From the side of the urinary tract: infrequent - increased frequency of urination, polyuria, urinary incontinence; very rare - dysuria, hematuria, nocturia.
From the side of the reproductive system: 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.
On the part of the skin: infrequent - alopecia, skin itch, skin rash, purpura; very rare - hives.
From the cardiovascular system: infrequent - flushes of blood to the skin of the face, marked decrease in blood pressure, postural hypotension.
Other: infrequent - pains of different localization.
Arterial hypertension
In controlled clinical trials of the drug Kardura, the most frequent adverse reactions that can be attributed to the type of postural (occasionally associated with syncope) or nonspecific, which included:
From the side of the organ of hearing and the vestibular apparatus: frequent - vertigo.
From the side of the digestive system: frequent - nausea.
From the central and peripheral nervous system: very frequent - dizziness, headache; frequent - postural dizziness (after the first dose, a pronounced decrease in blood pressure may develop, which can lead to orthostatic dizziness, in severe cases, especially with a rapid transition from a prone position to a standing position or a sitting position - to fainting), drowsiness.
On the part of the respiratory system: frequent - rhinitis.
Other: frequent - asthenia, swelling of the lower extremities, fatigue, weakness.
The following adverse reactions were noted during the marketing use of Cardura in patients with hypertension, although in general such symptoms could be observed in the absence of treatment with this drug: frequent - tachycardia, palpitation, chest pain; infrequent - angina pectoris, myocardial infarction and arrhythmia, very rare - bradycardia, cerebral circulation disorders.
CONTRAINDICATIONS
- severe hepatic insufficiency (due to lack of experience in this category of patients);
- urinary tract infections;
anuria;
progressive renal failure;
- hypotension and propensity to orthostatic disorders (including in anamnesis);
- concomitant obstruction of the upper urinary tract;
- stones in the bladder;
- Lactase deficiency, lactose intolerance, glucose-galactose malabsorption;
- age up to 18 years;
- Hypersensitivity to quinazolines, doxazosin or to the auxiliary components of the drug.
Precautions: mitral and aortic stenosis, cardiac insufficiency with an increase in the minute release, right ventricular failure due to pulmonary embolism or exudative pericarditis, left ventricular failure with low filling pressure, cerebral circulation disorders, elderly age, concomitant use with PDE5 inhibitors. Symptomatic hypotension, hepatic failure may occur.
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 decreased.These doses are about 300 times greater than the maximum recommended dose for a person. Because of the lack of adequate, well-controlled studies in pregnant or lactating women, the safety of using Cardura during pregnancy or during lactation has not yet been established. In connection with this, during pregnancy or lactation, Cardura can be used only when, in the opinion of the doctor, the potential benefit to the mother exceeds the potential risk to the fetus or the baby.
APPLICATION FOR FUNCTIONS OF THE LIVER
The pharmacokinetics of doxazosin in patients with renal insufficiency does not change, and the drug itself does not exacerbate existing renal dysfunction, therefore in patients of this group Cardura is used in usual doses.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Care should be taken when prescribing Cardura, as well as other drugs completely exposed to biotransformation in the liver, to patients with impaired liver function, avoiding the appointment of maximum doses.
APPLICATION FOR CHILDREN
Contraindicated in children and adolescents under 18 years.
APPLICATION IN ELDERLY PATIENTS
With caution: the elderly.
SPECIAL INSTRUCTIONS
Postural hypotension / syncope
As with any alpha-blockers, especially at the beginning of therapy, a very small percentage of patients had postural hypotension, manifested by dizziness and weakness or by loss of consciousness (fainting). Before starting any alpha-blocker, the patient should 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 Cardura, the patient should be advised that care should be taken in case of weakness or dizziness.
Cardura 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
In patients with BPH, the drug can be prescribed both in the presence of arterial hypertension, and with normal blood pressure. When the drug is used in patients with BPH with normal BP, the change in the latter is not significant. In patients with a combination of arterial hypertension and BPH, it is possible to use monotherapy.Before starting treatment for prostatic hyperplasia, it is necessary to exclude her cancerous degeneration.
Doxazosin does not affect the concentration of prostate-specific antigen (PSA) in the blood plasma.
Intraoperative syndrome of atonic iris
Intraoperative syndrome of atonic iris (variant of narrow pupil syndrome) was observed in some patients during a cataract operation, who received or received treatment with alpha 1- adrenoblockers. Since the intraoperative syndrome of atonic iris can lead to more complications during surgical interventions, it is necessary to alert the operating surgeon that alpha 1- adrenoblockers are being taken at this time or taken before surgery.
Combined use with PDE5 inhibitors
Caution should be exercised when using Cardura together with PDE5 inhibitors, as this may lead to symptomatic hypotension in some patients.
Impaired liver function
Care should be taken when prescribing Cardura, as well as other drugs completely exposed to biotransformation in the liver, to patients with impaired liver function, avoiding the appointment of maximum doses.
Impact on the ability to drive vehicles and manage mechanisms
During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.
OVERDOSE
Symptoms: marked decrease in blood pressure, sometimes accompanied by fainting.
Treatment: it is necessary to immediately put the patient on his back and raise his legs, if necessary, conduct symptomatic therapy. The binding of doxazosin to plasma proteins is high, so dialysis is not effective.
DRUG INTERACTION
The combined use of Cardura with PDE5 inhibitors in some patients can lead to symptomatic hypotension.
The large (98%) part of doxazosin in the blood plasma is associated with proteins. The results of a human blood plasma study in vitro indicate that doxazosin does not affect the binding to proteins of digoxin, warfarin, phenytoin, or indomethacin. In clinical practice cardura preparation was used without any indication of interaction with thiazide diuretics, furosemide, beta-blockers, antibiotics, hypoglycemic agents for oral administration, uricosuric agents and anticoagulants.
NSAIDs (especially indomethacin), estrogens and sympathomimetic drugs can reduce the antihypertensive effect of doxazosin.
Doxazosin, eliminating the effects of alpha-adrenostimuliruyuschee epinephrine may lead to the development of hypotension and tachycardia.
When concomitantly with sildenafil for treating pulmonary hypertension increases the risk of orthostatic hypotension.
For a single application of the drug cardura 1 mg / day for 4 days while taking 400 mg of cimetidine 2 times / day, there was a 10% increase in mean AUC values and statistically significant increase in mean C max and average T 1/2 doxazosin. This 10% increase in mean AUC values doxazosin in patients receiving cimetidine is within the variability of the oscillations (27%) average AUC values for doxazosin in comparison with placebo.
When applied simultaneously with other antihypertensives increases the severity of their action (dose required correction).
Do not take simultaneously with other blockers? -adrenoceptor.
While the use of inducers of microsomal oxidation in the liver may increase the efficiency of doxazosin and inhibitors - decrease.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The preparation should be stored in a dry place, protected from light and the reach of children at a temperature not higher than 30 В° C. Shelf life - 5 years.
