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Active ingredients
Doxazosin
Release form
Pills
Composition
Active ingredient: Doxazosin (Doxazosin) Active ingredient concentration (mg): 4
Pharmacological effect
Alpha1-adrenergic blocker. Benign prostatic hyperplasia Assignment of doxazosin to patients with symptoms of benign prostatic hyperplasia (BPH) leads to a significant improvement in urodynamics and reduction of symptoms of the disease. This action of the drug is associated with selective blockade of α-adrenergic receptors located in the stroma and capsule of the prostate gland and bladder neck. gland. This explains its effect in patients with BPH. The supportive effect of treatment with Cardura and its safety has been proven with prolonged use of the drug (for example, up to 48 months). The appearance of this effect is associated with selective blockade of α1-adrenergic receptors located in the vascular network. When taking the drug 1 time / day, the clinically significant hypotensive effect lasts for 24 hours. The BP decreases gradually, the maximum effect is usually observed 2-6 hours after taking the drug. In patients with arterial hypertension, blood pressure in doxazosin treatment was the same when lying and standing. In contrast to non-selective alpha-blockers, long-term treatment with doxazosin did not develop tolerance to the drug. During maintenance therapy, increased plasma renin and tachycardia occur infrequently. Doxazosin has a beneficial effect on blood lipid profile, significantly increasing the ratio of HDL to total cholesterol and significantly reducing total triglycerides and total cholesterol. In this regard, it has the advantage over diuretics and beta-blockers, which do not affect favorably on these parameters. Considering the established connection of arterial hypertension and lipid profile of the blood with IHD,The beneficial effect of doxazosin on blood pressure and lipid levels simultaneously reduces the risk of developing IBS. 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 does not have adverse metabolic effects and can be used in patients with bronchial asthma, diabetes mellitus, left ventricular failure and gout. In vitro studies have shown antioxidant properties of 6 'and 7' -hydroxymetabolites of doxazosin at a concentration of 5 μmol. In controlled clinical studies conducted in patients with arterial hypertension, treatment with doxazosin was accompanied by ulu sheniem erectile function. In addition, in patients treated with doxazosin, recurring erectile dysfunction was less common than in patients who received antihypertensive drugs.
Pharmacokinetics
Absorption and distribution After oral administration in therapeutic doses, doxazosin is well absorbed; Сmax is reached in approximately 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 you to prescribe the drug 1 time / day. Pharmacokinetics in special clinical situations The pharmacokinetics of doxazosin do not significantly differ from those in younger patients with normal renal function. There are only limited data on pharmacokinetics; nye in patients with impaired liver function, and the effect of drugs that can alter hepatic metabolism (eg cimetidine). In a clinical study in 12 patients with moderately impaired liver function, a single dose 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. The indications are benign prostatic hyperplasia (BPH); - for the treatment of delayed outflow of urine and other symptoms associated with BPH; - arterial hypertension (in combination therapy).
Indications
Hypertension, urinary tract obstruction and symptoms due to benign prostatic hyperplasia.
Contraindications
Hypersensitivity (including other quinazolines).
Precautionary measures
Do not exceed the recommended doses. With caution: mitral and aortic stenosis, heart failure with increased minute release, right ventricular failure due to pulmonary embolism or pericardial effusion, left ventricular failure with low filling pressure, cerebral circulation, elderly, simultaneous use of inhibitors with low blood pressure inhibitors, cerebral circulation, elderly, simultaneous use of inhibitors with low blood pressure inhibitors, cerebrovascular circulation, elderly patients, simultaneous use of inhibitors with low blood pressure inhibitors, cerebral blood circulation, elderly, simultaneous use of inhibitors with low blood pressure inhibitors, cerebral circulation, inhibition, simultaneous use of inhibitors with inhibitors of low blood pressure, cerebral circulation, elderly, simultaneous use of inhibitors with F inhibitors; because symptomatic hypotension, liver failure may occur.
Use during pregnancy and lactation
Although in animal experiments the drug did not have a teratogenic effect, but when used in extremely high doses, a decrease in fetal survival was observed. These doses are approximately 300 times higher than the maximum recommended doses for humans. Due to the lack of adequate well-controlled studies in pregnant or lactating women, the safety of using the drug Cardura during pregnancy or during breastfeeding has not yet been established. In this regard, during pregnancy or lactation, the drug Cardura can be used only when, according to the doctor, the potential benefit to the mother outweighs the potential risk to the fetus or child.
Dosage and administration
Cardura is taken orally (in the morning or in the evening). Arterial hypertension. The dosage ranges from 1 to 16 mg / day. The initial dose of Cardura is 1 mg once a day for 1 or 2 weeks. Over the next 1 or 2 weeks, it is possible to increase the dose to 2 mg once a day. To achieve the desired reduction in blood pressure, if necessary, the daily dose should be increased gradually, observing uniform intervals up to 4, 8 and 16 mg, depending on the severity of the patient's response. The usual recommended dose is 2-4 mg 1 time per day. Benign prostatic hyperplasia. The initial dose of Cardura is 1 mg once a day.Depending on the individual characteristics of urodynamics and the presence of symptoms of the disease, the dose can be increased to 2 mg, and then to 4 mg and up to a maximum recommended dose of 8 mg. The recommended interval for increasing the dose is 1-2 weeks. The usual recommended dose is 2-4 mg 1 time per day. The experience with doxazosin in children is absent.
Side effects
BPHP According to controlled clinical studies, the same adverse reactions as in hypertensive patients were encountered in patients with BPH. The following adverse reactions were reported during postmarketing use of the drug. From the hematopoietic and lymphatic systems: very rarely - leukopenia, thrombocytopenia. and vestibular apparatus: rarely - tinnitus. On the part of the organ of vision: often - a violation of color perception; infrequently - atonic iris syndrome. From the gastrointestinal tract: often - abdominal pain, diarrhea, dyspepsia, dryness of the oral mucosa; infrequently - flatulence, constipation, vomiting. From the liver: very rarely - cholestasis, hepatitis, jaundice. From the immune system: very rarely - anaphylactic reactions. Laboratory values: rarely - an increase in body weight; very rarely - increased activity of liver transaminases. From the side of metabolism: infrequently - anorexia. From the side of the musculoskeletal system: rarely - arthralgia, back pain, muscle spasms, muscle weakness, myalgia. From the side of the central nervous system and peripheral nervous system: often - paresthesias; infrequently - hypesthesia, tremor. On the mental side: often - agitation, anxiety, insomnia; infrequently - depression. From the urinary tract: infrequently - increased urination, polyuria, urinary incontinence; very rarely - dysuria, hematuria, nocturia. For the reproductive system: very rarely - gynecomastia, impotence, priapism; very rarely - retrograde ejaculation. On the part of the respiratory system: often - shortness of breath, rhinitis; infrequently - cough, nosebleeds; very rarely - exacerbation of existing bronchospasm. On the skin side: infrequently - alopecia, pruritus, skin rash, purpura; very rarely - urticaria. From the CVS: infrequently - flushing to the skin of the face, pronounced decrease in blood pressure, postural hypotension. Other: infrequently - pain of different localization. Arterial hypertension In controlled clinical studies of the drug Kardur, the most frequent adverse reactions that can be attributed to the type postural (occasionally associated with syncope) or non-specific,which included the following reactions. From the organ of hearing and vestibular apparatus: often - vertigo. From the gastrointestinal tract: often - nausea. From the CNS and peripheral nervous system: very often - dizziness, headache; often - 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 rapid transition from a prone position to a standing position or to a sitting position - to faint), drowsiness. Systems: often - rhinitis. Other: often - asthenia, edema of the lower limbs, fatigue, weakness.
Overdose
Symptoms: marked reduction in blood pressure, sometimes accompanied by fainting. Treatment: it is necessary to immediately lay the patient on his back and lift his legs, if necessary, to carry out symptomatic therapy. Doxazosin binding to plasma proteins is high, so dialysis is not effective.
Interaction with other drugs
The combined use of the drug Cardura with PDE5 inhibitors in some patients can lead to symptomatic hypotension. A large (98%) part of doxazosin in the blood plasma is associated with proteins. The results of an in vitro study of human blood plasma indicate that doxazosin does not affect the binding of digoxin, warfarin, phenytoin or indomethacin proteins. In clinical practice, the drug Cardura was used without any signs of interaction with thiazide diuretics, furosemide, beta-adrenergic blockers, antibiotics, hypoglycemic oral preparations, uricosuric drugs and anticoagulants. Doxazosin, by eliminating the alpha-adrenostimulating effects of epinephrine, can lead to the development of tachycardia and arterial hypotension. At the same time With sildenafil for the treatment of pulmonary hypertension, the risk of orthostatic hypotension increases. With a single use 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 average AUC values and statistically insignificant increase in average Cmax and average T1 / 2 doxazosin.A similar 10% increase in the mean AUC of doxazosin while taking cimetidine is within the limits of variability in variability (27%) of the mean AUC for doxazosin compared with placebo. When used simultaneously with other antihypertensives, it increases their severity (dose adjustment is necessary). Not recommended taken simultaneously with other α-adrenoreceptor blockers. When used simultaneously with microsomal oxidation in the liver, it is possible to increase the effectiveness of doxazosin, and with inhibitors - reduction.
special instructions
Postural hypotension / Fainting As with the 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 should be warned how to avoid the symptoms of postural hypotension, in particular, to refrain from rapid changes in body position. At the beginning of treatment with Kardur, the patient should be advised about the need to be careful in case of weakness or dizziness. The drug of Cardur should be used with caution in elderly patients due to the possibility of orthostatic hypotension. With age, the risk of dizziness, visual impairment and fainting increases. The patient should be informed about the increased risk of orthostatic hypotension with alcohol, prolonged standing or exercise, as well as during hot weather. Benign prostatic hyperplasia In patients with BPH, the drug can be prescribed as if there is hypertension, and with normal blood pressure. When using the drug in patients with BPH with normal blood pressure, the change in the latter is not significant. At the same time, it is possible to use monotherapy in patients with a combination of arterial hypertension and BPH. Doxazosin does not affect plasma concentration of prostate-specific antigen (PSA) before initiating prostatic hyperplasia therapy. Doxazosin has been diagnosed in some patients during cataract surgery. receive or receive treatment with alpha1-blockers.Since the intraoperative syndrome of atonic iris can lead to an increase in complications during surgical interventions, it is necessary to warn the operating surgeon that alpha1-adrenergic blockers are taken at the moment or were taken earlier before the operation. Combined use with PDE5 inhibitors PDE5 inhibitors, as in some patients this can lead to symptomatic hypotension. Liver dysfunction caution when prescribing Cardura, as well as other drugs that are completely biotransformed in the liver, to patients with impaired liver function, avoiding the appointment of maximum doses. Impact on the ability to drive vehicles and control mechanisms. During the period of treatment, care must be taken when driving and exercising other potentially hazardous activities that require increased concentration of attention and quickness of psychomotor reactions.