Pharmacological properties of the drug Cardura
Doxazosin (1-(4-amino-6,7-dimethoxy-2-quinazoline)-4-(1,4-benzodioxan-2-ylcarbonyl)piperazine monomethanesulfonate) is a selective α1-adrenergic receptor blocker, an antihypertensive agent and a drug for the treatment of benign prostatic hyperplasia (BPH). AH (arterial hypertension) Doxazosin dilates blood vessels due to selective competitive blockade of postsynaptic α1-adrenergic receptors of blood vessels. The use of doxazosin in patients with hypertension (arterial hypertension) leads to a clinically significant decrease in blood pressure due to a decrease in peripheral vascular resistance. When using the drug once a day, a clinically significant hypotensive effect persists for 24 hours. Blood pressure decreases gradually: the maximum effect develops, as a rule, 2-6 hours after using the drug. In patients with hypertension (arterial hypertension) during treatment with doxazosin, blood pressure is the same in the supine and standing positions. In contrast to non-selective α1-adrenergic receptor blockers, long-term treatment with doxazosin does not develop tolerance to the drug. During therapy, increased plasma renin activity and tachycardia are rarely observed. Doxazosin has a positive effect on the blood lipid profile, significantly reduces the atherogenic index, the content of total TG and total cholesterol. Considering the established connection between hypertension (arterial hypertension) and lipid metabolism disorders and coronary heart disease, the beneficial effect of doxazosin on blood pressure and the level of atherogenic lipids simultaneously helps reduce the risk of developing coronary artery disease. Treatment with doxazosin leads to regression of left ventricular myocardial hypertrophy and inhibition of platelet aggregation. In addition, doxazosin increases the sensitivity of peripheral tissues to insulin in those patients in whom it is impaired. In controlled clinical studies in patients with hypertension (arterial hypertension), the use of doxazosin did not affect erectile function. In addition, patients who received doxazosin were less likely to complain of erectile dysfunction compared to patients who took other antihypertensive drugs. Doxazosin does not have a negative effect on metabolism; it can be used in patients with asthma, diabetes mellitus, gout, the elderly, and also in patients with heart failure. in vitro study revealed the antioxidant properties of 6'- and 7'-hydroxy metabolites of doxazosin at a concentration of 5 μmol. BPH Prescribing doxazosin to patients with symptoms of BPH helps to significantly improve urodynamics and reduce the severity of symptoms of the disease. The mechanism of action of the drug is due to the selective blockade of α1-adrenergic receptors, which are located in the stroma and capsule of the prostate gland and in the neck of the bladder. It has been established that doxazosin is a strong blocker of subtype IA α1-adrenergic receptors, which make up about 70% of all prostate receptor subtypes. This explains its effectiveness in patients with BPH. The effectiveness of maintenance treatment and the safety of doxazosin were established through long-term use of the drug (more than 48 months) in patients with BPH. After oral administration in therapeutic doses, doxazosin is well absorbed from the digestive tract; its concentration in the blood plasma reaches its maximum level after approximately 2 hours. Elimination from the blood plasma is biphasic, with a half-life of 22 hours, which allows the drug to be administered once a day. Doxazosin undergoes active biotransformation; less than 5% of the dose taken is excreted unchanged in the urine. In patients with renal failure, the pharmacokinetics of the drug do not differ significantly from that in patients with unchanged renal function. There is insufficient data regarding the use of the drug in patients with impaired liver function, so caution must be exercised when prescribing doxazosin to such patients. About 98% of doxazosin is bound to plasma proteins.
Cardura
Alpha1-adrenergic blocker.
Benign prostatic hyperplasia
Prescribing doxazosin to patients with symptoms of benign prostatic hyperplasia (BPH) leads to a significant improvement in urodynamics and a decrease in the manifestations of symptoms of the disease. This effect of the drug is associated with the selective blockade of α-adrenergic receptors located in the stroma and capsule of the prostate gland and the bladder neck.
It has been proven that doxazosin is a blocker of α1-adrenergic receptors of subtype 1A, which constitute approximately 70% of all α1-adrenergic receptor subtypes present in the prostate gland. This explains its effect in patients with BPH.
The supporting effect of treatment with Cardura and its safety have been proven 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 decrease in blood pressure as a result of a decrease in peripheral vascular resistance. The appearance of this effect is associated with selective blockade of α1-adrenergic receptors located in the vascular network. When taking the drug once a day, a clinically significant hypotensive effect persists for 24 hours. Blood pressure decreases gradually, the maximum effect is usually observed 2-6 hours after taking the drug. In patients with arterial hypertension, blood pressure during treatment with doxazosin was the same in the supine and standing positions.
In contrast to non-selective alpha-blockers, tolerance to the drug did not develop during long-term treatment with doxazosin. During maintenance therapy, increases in plasma renin activity and tachycardia are uncommon.
Doxazosin has a beneficial effect on the 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 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, the beneficial effect of doxazosin on blood pressure and lipid levels simultaneously leads to a reduction in the risk of developing coronary artery 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 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 6′ and 7′-hydroxy metabolites of doxazosin at a concentration of 5 μmol.
In controlled clinical studies conducted in patients with arterial hypertension, treatment with doxazosin was accompanied by an 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
Suction and distribution
After oral administration in therapeutic doses, doxazosin is well absorbed; Cmax is reached in approximately 2 hours. It is 98% bound to plasma proteins.
Metabolism and excretion
Doxazosin undergoes active biotransformation in the liver; less than 5% of the dose is excreted unchanged. The primary metabolic pathways of doxazosin are O-demethylation and hydroxylation.
Elimination from blood plasma is biphasic with a final T1/2 of 22 hours, which allows the drug to be administered once a day.
Pharmacokinetics in special clinical situations
According to pharmacokinetic studies in elderly people and patients with renal failure, the pharmacokinetics of doxazosin do not differ significantly from that in younger patients with normal renal function.
There are only limited pharmacokinetic data obtained in patients with impaired liver function and on the effect 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 an increase in AUC by 43% and a decrease in true oral clearance by 40%. 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.
Indications for use of the drug Cardura
AH (arterial hypertension) The drug is indicated for the treatment of patients with AH (arterial hypertension) as a first-line agent for blood pressure control. If monotherapy is ineffective, the drug can be prescribed in combination with other antihypertensive drugs (thiazide diuretics, β-adrenergic receptor blockers, calcium ion antagonists, ACE inhibitors). BPH The drug is prescribed to patients with delayed urinary outflow and in the presence of symptoms caused by BPH. Patients with BPH can be prescribed Cardura both for hypertension (arterial hypertension) and for normal blood pressure. When using the drug in patients with BPH and normal blood pressure, changes in the latter are insignificant. In patients with hypertension (arterial hypertension) and BPH, Cardura monotherapy may be effective.
Use of the drug Cardura
Prescribed internally. The drug can be taken both in the morning and in the evening. It is advisable to take the first dose of the drug before bedtime to prevent the possible development of orthostatic hypotension. AH (arterial hypertension) Prescribed in a dose of 1 to 16 mg/day. It is recommended to begin treatment with a dose of 1 mg once a day for 1–2 weeks. Over the next 1–2 weeks, the dose can be increased to 2 mg once a day. If necessary, the daily dose is gradually increased to 4 at regular intervals; 8 and 16 mg depending on the severity of the hypotensive effect of the drug. Typically, the effective dose is 2–4 mg once daily. BPH The initial dose of Cardura is 1 mg once a day. Depending on the individual characteristics of urodynamics and the presence of symptoms of BPH, the dose can be increased at intervals of 1–2 weeks to 2 mg, then to 4 mg and then to the maximum recommended dose of 8 mg/day. Typically, the effective dose is 2–4 mg once daily.
Side effects of the drug Cardura
When used in patients with hypertension (arterial hypertension) In controlled clinical studies during the treatment of hypertension (arterial hypertension), orthostatic reactions (rarely loss of consciousness) or nonspecific side effects, which are listed below, were most often observed. Body as a whole: asthenia, fatigue, malaise. Central nervous system and peripheral nervous system: dizziness, headache, drowsiness. Gastrointestinal tract: nausea. Respiratory system: rhinitis. Benign prostatic hyperplasia : According to controlled clinical trials, patients with BPH experienced the same adverse events as patients with hypertension (arterial hypertension). After the widespread introduction of the drug into practice, the following adverse events were reported: Autonomic nervous system: dry mouth, priapism. Body as a whole: allergic reactions, hot flashes, pain, weight gain. Cardiovascular system: hypotension, postural hypotension. Central nervous system and peripheral nervous system: hypoesthesia, paresthesia, tremor. Endocrine system: gynecomastia. Gastrointestinal tract: abdominal pain, constipation, diarrhea, dyspepsia, flatulence, vomiting. Hematopoiesis: leukopenia, thrombocytopenic purpura. Liver: changes in liver function tests, cholestasis, hepatitis, jaundice. Musculoskeletal system: arthralgia, muscle contractions, muscle weakness, myalgia. Mental disorders: agitation, anorexia, insomnia, increased excitability, anxiety, depression, impotence. Respiratory system: bronchospasm, cough, breathing problems, nosebleeds. Skin and its appendages: alopecia, itching, rash. Sense organs: visual disturbances, tinnitus. Genitourinary system: dysuria, hematuria, urinary disorders, frequent urination, nocturia, urinary incontinence. The following are other adverse reactions that occurred during post-registration studies of the drug in patients with hypertension (arterial hypertension) (such symptoms were also observed in the absence of treatment with Cardura): tachycardia, bradycardia, palpitations, chest pain, angina pectoris, myocardial infarction and cerebral disorders blood circulation
Cardura, 30 pcs., 2 mg, tablets
The frequency of adverse reactions is presented according to the following classification: very often - ≥10%; often - ≥1% and <10%; uncommon - ≥0.1% and <1%; rarely - ≥0.01% and <0.1%; very rare - <0.01%.
BPH
According to controlled clinical studies, patients with BPH experienced the same adverse reactions as patients with arterial hypertension.
The following adverse reactions have been reported during post-marketing use of the drug.
From the hematopoietic and lymphatic system:
very rarely - leukopenia, thrombocytopenia.
From the organ of hearing and vestibular apparatus:
infrequently - tinnitus.
From the side of the organ of vision:
often - impaired 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 indicators:
infrequently - weight gain; very rarely - increased activity of liver transaminases.
From the side of metabolism:
infrequently - anorexia.
From the musculoskeletal system:
uncommon - arthralgia, back pain, muscle spasms, muscle weakness, myalgia.
From the central nervous system and peripheral nervous system:
often - paresthesia; infrequently - hypoesthesia, tremor.
From the mental side:
often - agitation, anxiety, insomnia; infrequently - depression.
From the urinary tract:
infrequently - increased frequency of urination, polyuria, urinary incontinence; very rarely - dysuria, hematuria, nocturia.
From the reproductive system:
very rarely - gynecomastia, impotence, priapism; very rarely - retrograde ejaculation.
From the respiratory system:
often - shortness of breath, rhinitis; infrequently - cough, nosebleeds; very rarely - exacerbation of existing bronchospasm.
From the skin:
uncommon - alopecia, itching, skin rash, purpura; very rarely - urticaria.
From the SSS side:
uncommon - flushing of the face, marked decrease in blood pressure, postural hypotension.
Other:
infrequently - pain of various localizations.
Arterial hypertension
In controlled clinical trials of Cardura, the most common adverse reactions were classified as postural (rarely 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 central nervous system 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 when quickly moving from a lying position to a standing position or to a sitting position - to fainting), drowsiness.
From the respiratory system:
often - rhinitis.
Other:
often - asthenia, swelling of the lower extremities, fatigue, weakness.
The following adverse reactions were noted during the marketing use of the drug Cardura in patients with arterial hypertension, although in general such symptoms could be observed in the absence of treatment with this drug: often - tachycardia, palpitations, chest pain; infrequently - angina pectoris, myocardial infarction and arrhythmias; very rarely - bradycardia, cerebrovascular accident.
Special instructions for the use of Cardura
When prescribing antihypertensive therapy, the doctor should give the patient recommendations on measures to prevent and eliminate the symptoms of postural hypotension. The patient should be warned that dizziness and weakness may occur when starting doxazosin treatment. There is no experience of use in children. Caution should be exercised when prescribing the drug (as well as other drugs that are completely biotransformed in the liver) to patients with impaired liver function. The pharmacokinetics of Cardura in patients with renal failure does not change, and the use of the drug does not worsen the condition of renal failure, therefore, for the treatment of such patients it is prescribed in normal doses. Due to the lack of results from well-controlled clinical studies, the safety of Cardura during pregnancy and lactation has not been established, so the drug can be used only if the potential benefit outweighs the possible risk. It should also be taken into account that while taking the drug (especially at the beginning of treatment), the ability to drive vehicles and work with potentially dangerous mechanisms may decrease.
Cardura®
The frequency of adverse reactions is presented according to the following classification:
Very common: ≥10%
Frequent: ≥1% and <10%
Uncommon: ≥0.1% and <1%
Rare: ≥0.01% and <0.1%
Very rare: <0.01%
Benign prostatic hyperplasia
According to controlled clinical studies, patients with BPH experienced the same adverse reactions as patients with arterial hypertension.
The following adverse reactions have been reported during post-marketing use of the drug:
From the hematopoietic and lymphatic system:
very rare - leukopenia, thrombocytopenia.
From the organ of hearing and vestibular apparatus:
Uncommon: tinnitus.
From the side of the organ of vision
: frequent - impaired color perception, infrequent - atonic iris syndrome.
From the gastrointestinal tract:
frequent - abdominal pain, diarrhea, dyspepsia, dryness of the oral mucosa; infrequent - flatulence, constipation, vomiting.
From the liver:
very rare - cholestasis, hepatitis, jaundice.
From the immune system:
very rare - anaphylactic reactions.
Laboratory indicators
: uncommon - weight gain; very rare - increased activity of “liver” transaminases.
From the side of metabolism:
uncommon - anorexia.
From the musculoskeletal system
: uncommon - arthralgia, back pain, muscle spasms, muscle weakness, myalgia.
From the central and peripheral nervous system:
frequent - paresthesia; infrequent - hypoesthesia, tremor.
From the mental side:
frequent - agitation, anxiety, insomnia; infrequently - depression.
From the urinary tract:
infrequent - increased frequency of urination, polyuria, urinary incontinence; very rare - dysuria, hematuria, nocturia.
From the reproductive system:
very rare - gynecomastia, impotence, priapism; very rarely - retrograde ejaculation.
From the respiratory system
: frequent - shortness of breath, rhinitis; uncommon - cough, nosebleeds; very rare - exacerbation of existing bronchospasm.
From the skin:
uncommon - alopecia, itching, skin rash, purpura; very rare - urticaria.
From the cardiovascular system
: infrequent - “flushes” of blood to the skin of the face, marked decrease in blood pressure, postural hypotension.
Others
: infrequent - pain of various localizations.
Arterial hypertension
In controlled clinical trials of Cardura, the most common adverse reactions were classified as postural (occasionally associated with syncope) or nonspecific, which included:
From the organ of hearing and vestibular apparatus:
frequent - vertigo.
From the gastrointestinal tract:
frequent - nausea.
From the central and peripheral nervous system:
very common - dizziness, headache; frequent - 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 when quickly moving from a lying position to a standing position or to a sitting position - to fainting) , drowsiness.
From the respiratory system:
frequent - rhinitis.
Others
: frequent - asthenia, swelling of the lower extremities, fatigue, weakness.
The following adverse reactions were noted during the marketing use of the drug Cardura in patients with arterial hypertension, although in general such symptoms could be observed in the absence of treatment with this drug: frequent - tachycardia, palpitations, chest pain; uncommon - angina pectoris, myocardial infarction and arrhythmias, very rare - bradycardia, cerebrovascular accidents.
Interactions of the drug Cardura
Most (98%) of the drug binds to blood plasma proteins. in vitro study indicate that the drug does not affect the binding of digoxin, warfarin, phenytoin or indomethacin to human plasma proteins. In clinical practice, there are no signs of interaction of Cardura with thiazide diuretics, furosemide, β-adrenergic receptor blockers, NSAIDs, antibiotics, oral hypoglycemic agents, uricosurics and anticoagulants.
