Doxazosin

1 tablet contains:

active substance:

doxazosin mesylate 1.22 mg / 2.44 mg / 4.88 mg (calculated as doxazosin

1 mg / 2 mg / 4 mg);

Excipients:

lactose monohydrate 80.18 mg /

90.16 mg / 180.32 mg;

calcium phosphate 17.0 mg / 35.0 mg / 70.0 mg;

povidone K30 0.4 mg / 0.6 mg / 1.2 mg;

sodium lauryl sulfate 0.2 mg / 0.3 mg / 0.6 mg;

calcium stearate 0.5 mg / 1.0 mg / 2.0 mg;

talc

0.5 mg / 0.5 mg / 1.0 mg

Pharmaceutical group:

alpha1-blocker 
 

Pharmacodynamics: 

Doxazosin is a selective competitive blocker of postsynaptic alpha1-adrenergic receptors (affinity for alpha1-adrenergic receptors is 600 times higher than for alpha2-adrenergic receptors), reduces total peripheral vascular resistance (OPSR), prevents vasoconstriction caused by catecholamines, which ultimately leads to a decrease in arterial pressure (BP) without the development of reflex tachycardia.

Reduces pre- and afterload on the heart. After a single dose, the decrease in blood pressure develops gradually, the maximum decrease is observed after 2-6 hours and lasts for 24 hours.

After a single dose of the drug, the maximum hypotensive effect is observed in the period from 2 to 6 hours, and in general, the hypotensive effect lasts for 24 hours. During the treatment with doxazosin in patients with arterial hypertension (AH), there are no differences in blood pressure values ​​in the "standing" and "lying" positions.

Effective in hypertension, including those accompanied by metabolic disorders (obesity, decreased glucose tolerance).

Reduces the risk of developing coronary heart disease (CHD). Taking the drug in patients with normal blood pressure is not accompanied by a decrease in blood pressure. With prolonged use of doxazosin, patients develop tolerance.

During the period of treatment with doxazosin, a decrease in the concentration of triglycerides and total cholesterol in the blood plasma is observed. At the same time, there is a slight (by 4-13%) increase in the high density lipoprotein / total cholesterol ratio.

With long-term treatment with doxazosin, regression of left ventricular (LV) hypertrophy, suppression of platelet aggregation and an increase in the content of active plasminogen in tissues are observed.

Due to the fact that doxazosin blocks alpha1-adrenergic receptors located in the stroma and capsule of the prostate gland and in the bladder neck, there is a decrease in resistance and pressure in the urethra, a decrease in the resistance of the internal sphincter. Therefore, the appointment of doxazosin to patients with symptoms of benign prostatic hyperplasia (BPH) leads to a significant improvement in urodynamic parameters and a decrease in the manifestation of symptoms of the disease.

It has an effect in 66-71% of patients, the onset of action is after 1-2 weeks of treatment, maximum - after 14 weeks, the effect persists for a long time.

Pharmacokinetics: 

After oral administration in therapeutic doses, doxazosin is well absorbed, absorption is 80-90% (simultaneous food intake slows down absorption by 1 hour), the time to reach the maximum concentration in blood plasma (TCmax) is 3 hours, with evening TCmax it is extended to 5 hours.

Bioavailability is 60-70%. The connection with blood plasma proteins is about 98%. Excretion from blood plasma occurs in 2 phases, with a final half-life (T½) of 19-22 hours, which allows prescribing the drug once a day.

It is extensively metabolized in the liver by o-demethylation and hydroxylation. In patients with impaired liver function, as well as when taking drugs that can change the "hepatic" metabolism, the biotransformation of the drug may be disrupted. The main excretion is through the intestines (63-65% in the form of metabolites and about 5% in unchanged form).

About 10% is excreted by the kidneys. A study of the pharmacokinetics of doxazosin in elderly patients and patients with kidney disease did not reveal significant pharmacokinetic differences.

•  Benign prostatic hyperplasia: both in the presence of arterial hypertension and at normal blood pressure.
• Arterial hypertension (as part of combination therapy).

Hypersensitivity to doxazosin and other quinazoline derivatives (prazosin, terazosin) or to other components of the drug;

Tendency to orthostatic hypotension;

Hypertension (for patients with benign prostatic hyperplasia);

Patients with BPH and concomitant impairment of urine outflow from the upper urinary tract, chronic urinary tract infections, stones in the bladder;

Lactose intolerance, lactase deficiency or glucose-galactose malabsorption;

Lactation period;

Age up to 18 years (efficacy and safety have not been established);

As monotherapy in patients with either a congested bladder or anuria with or without progressive renal failure.

Precautions: Pulmonary edema due to aortic or mitral stenosis;

Right-sided heart failure due to pulmonary embolism or exudative pericarditispravostoronnyaya serdechnaya nedostatochnostʹ vsledstvie legochnoĭ embolii ili ekssudativnyĭ perikardit;

Left ventricular heart failure with low filling pressure;

Simultaneous use of phosphodiesterase-5 inhibitors (sildenafil, vardenafil, trandalafil);

Syndrome of intraoperative instability of the iris of the eye (narrow pupil syndrome);

Liver dysfunction.

The frequency of adverse reactions when using the drug Doxazosin is given below in accordance with the generally accepted classification:

very often (≥1 / 10); often (≥1 / 100, <1/10); infrequently (≥1 / 1000, <1/100); rarely (≥1 / 10000, <1/1000); very rare (<1/10000).

From the side of the cardiovascular system: often - hypertension (including orthostatic), palpitations, tachycardia; infrequently - angina pectoris, myocardial infarction; very rarely - bradycardia, rhythm disturbances, "hot flushes" of blood to the skin of the face, peripheral edema.

From the central and peripheral nervous system: often - drowsiness, dizziness, headache; infrequently - stroke, hypesthesia, fainting, tremor, agitation, depression, anxiety, insomnia, nervousness; very rarely - paresthesia, postural dizziness.

From the senses: often - vertigo; infrequently - ringing in the ears; very rarely - blurred vision, narrow pupil syndrome.

From the digestive system: often - abdominal pain, dyspepsia, dryness of the oral mucosa; infrequently - constipation, bloating, vomiting, diarrhea, increased activity of "liver" enzymes, loss of appetite, anorexia; very rarely - hepatitis, cholestasis, jaundice.

From the respiratory system: often - bronchitis, cough, shortness of breath, rhinitis, dryness of the nasal mucosa; infrequently - nosebleeds; very rarely bronchospasm.

From the side of hematopoiesis: leukopenia, thrombocytopenia.

From the musculoskeletal system: often - back pain, myalgia; not often - arthralgia; rarely - cramps, muscle weakness.

From the side of the skin: often - itching; infrequently - skin rash; very rarely urticaria, alopecia, purpura.

From the genitourinary system: often cystitis, urinary incontinence; not often - dysuria, increased frequency of urination, hematuria, impotence, gout; rarely, polyuria; very rarely - increased urine output, urinary disorder, nocturia, gynecomastia, priapism, retrograde ejaculation.

General reactions: often - asthenia, chest pain, malaise; infrequently - pain, facial swelling, weight loss; very rarely - allergic reactions, fatigue.

Doxazosin enhances the antihypertensive effect of antihypertensive drugs (when used in combination with them, dose adjustment is required).

No adverse interaction was noted with the simultaneous use of doxazosin and thiazide diuretics, furosemide, beta-blockers, blockers of "slow" calcium channels, angiotensin-converting enzyme inhibitors, antibacterial agents, hypoglycemic agents for oral administration, indirect anticoagulants and uricosuric agents.

The drug has no effect on the degree of binding to blood plasma proteins of digoxin, phenytoin.

With simultaneous use with inducers of enzymes of microsomal oxidation in the liver (ethanol, barbiturates, phenylbutazone, tricyclic antidepressants), an increase in the effectiveness of doxazosin is possible, with inhibitors (cimetidine) - a decrease.

Non-steroidal anti-inflammatory drugs (NSAIDs), especially indomethacin, estrogens (fluid retention) and sympathomimetic drugs can reduce the antihypertensive effect of doxazosin.

By eliminating the alpha-adrenostimulating effects of epinephrine, it can lead to tachycardia and arterial hypotension.

Concomitant use with selective phosphodiesterase-5 inhibitors (sildenafil, tadalafil, vardenafil) can lead to the development of arterial hypotension.

Inside, once a day (morning or evening), regardless of food intake, without chewing and drinking plenty of water.

Patients with hepatic impairment require lower doses due to the slower metabolism of the drug.

If the patient has forgotten to take the drug at the usual time, he should take the appropriate dose of the drug as soon as possible. If the time is right for the next dose, only that should be taken (not doubling the dose). It is important to take the drug regularly. If the patient has not taken the drug for several days, then a new therapeutic course should be started with the lowest dose.

BPH: The starting dose is 1 mg of doxazosin per day. The patient should take the first dose in the evening before bedtime. Depending on the urodynamic parameters and the presence of BPH symptoms, the dose can be gradually increased at intervals of 1-2 weeks up to 2 mg, 4 mg and 8 mg per day. The recommended maintenance dose is 2-4 mg per day. The maximum daily dose is 8 mg.

After achieving a stable therapeutic effect, the dose is usually reduced (the average therapeutic dose for maintenance therapy is usually 2-4 mg per day).

Hypertension: the initial dose of doxazosin is 1 mg per day at bedtime. After taking the first dose, the patient should be in bed for 6-8 hours. This is required due to the possibility of the development of the "first dose" phenomenon, especially pronounced against the background of previous diuretic administration. If the therapeutic effect of the drug is insufficient, the daily dose can be increased to 2 mg after 1-2 weeks.

Subsequently, every 1-2 weeks, the dose can be increased by 2 mg. In the vast majority of patients, the optimal therapeutic effect is achieved at a dose of 8 mg per day. The maximum daily dose is 16 mg.

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

Treatment: gastric lavage, intake of activated carbon.

The patient must be laid on his back and his legs raised. With a pronounced decrease in blood pressure, anti-shock measures are taken - the volume of circulating blood is replenished, and vasopressors are prescribed if necessary.

Hemodialysis is ineffective.

Particular care should be taken when using the drug Doxazosin in patients with impaired liver function, especially in cases where drugs that can alter the "hepatic" metabolism are used simultaneously (for example, ethanol, barbiturates, phenylbutazone, tricyclic antidepressants, cimetidine). In cases of deterioration of the indicators of the functional state of the liver, the drug is immediately canceled.

In order to prevent orthostatic reactions, patients should avoid sudden and abrupt changes in body position (transition from the "lying" position to the "standing" position).

Caution should be exercised when taking phosphodiesterase-5 inhibitors and doxazosin at the same time. development of arterial hypotension is possible. To reduce the risk of developing arterial hypotension (including orthostatic), it is necessary to start treatment with phosphodiesterase-5 inhibitors only if the patient has adapted to doxazosin therapy, in addition, a 6-hour time interval from doxazosin intake should be observed between taking drugs.

During surgical interventions for cataracts while taking the drug, it is possible to develop a syndrome of intraoperative instability of the iris of the eye (narrow pupil syndrome), which must be taken into account by the surgeon for the preoperative preparation of the patient and during the operation.

Alcohol intake can increase the adverse reactions of doxazosin.

The effect of the "first dose" of the drug is especially pronounced against the background of previous diuretic therapy and a sodium-restricted diet.

Before starting therapy, it is necessary to exclude cancerous degeneration of the prostate gland.

Influence on the ability to drive vehicles and other mechanisms

In the case of taking the drug Doxazosin, you should be careful when driving vehicles or when performing work that requires increased concentration of attention and speed of psychomotor reactions.

Tablets are white or white with a creamy shade, round, biconvex.