Doxazozin Sanofi (Tablets) Instructions for Use

Marketing Authorization Holder

Sanofi Russia JSC (Russia)

Manufactured By

Zentiva, k.s. (Czech Republic)

ATC Code

C02CA04 (Doxazosin)

Active Substance

Doxazosin (Rec.INN registered by WHO)

Dosage Forms

	Doxazosin Sanofi	Tablets 1 mg: 15 or 30 pcs.
		Tablets 2 mg: 10, 30, 60 or 90 pcs.
		Tablets 4 mg: 30, 60, 90 or 100 pcs.

Dosage Form, Packaging, and Composition

Tablets white or almost white, round, flat, with an engraving “ZX 1” on one side.

Excipients : lactose – 40 mg, granulated microcrystalline cellulose – 31.267 mg, microcrystalline cellulose – 45 mg, sodium carboxymethyl starch (type A) – 1.2 mg, anhydrous colloidal silicon dioxide – 0.12 mg, sodium lauryl sulfate – 0.12 mg, magnesium stearate – 1.08 mg.

15 pcs. – blisters (1) – cardboard packs.
15 pcs. – blisters (2) – cardboard packs.

Tablets white or almost white, oblong, biconvex, with an engraving “ZX 2” and a score line for division on one side.

Excipients : lactose – 40 mg, granulated microcrystalline cellulose – 45 mg, microcrystalline cellulose – 30.055 mg, sodium carboxymethyl starch (type A) – 1.2 mg, anhydrous colloidal silicon dioxide – 0.12 mg, sodium lauryl sulfate – 0.12 mg, magnesium stearate – 1.08 mg.

10 pcs. – blisters (1) – cardboard packs.
10 pcs. – blisters (3) – cardboard packs.
10 pcs. – blisters (6) – cardboard packs.
10 pcs. – blisters (9) – cardboard packs

Tablets white or almost white, oblong, biconvex, with an engraving “ZX 4” and a score line for division on one side.

Excipients : lactose – 80 mg, granulated microcrystalline cellulose – 90 mg, microcrystalline cellulose – 60.11 mg, sodium carboxymethyl starch (type A) – 2.4 mg, anhydrous colloidal silicon dioxide – 0.24 mg, sodium lauryl sulfate – 0.24 mg, magnesium stearate – 2.16 mg.

10 pcs. – blisters (3) – cardboard packs.
10 pcs. – blisters (6) – cardboard packs.
10 pcs. – blisters (9) – cardboard packs.
10 pcs. – blisters (10) – cardboard packs.

Clinical-Pharmacological Group

Alpha₁-adrenergic blocker. Antihypertensive agent. Agent used for urination disorders in benign prostatic hyperplasia

Pharmacotherapeutic Group

Alpha1-adrenergic blocker

Pharmacological Action

Selective competitive blocker of postsynaptic α₁-adrenergic receptors. Causes dilation of peripheral vessels, which leads to a decrease in total peripheral vascular resistance and a decrease in blood pressure. Promotes an increase in the HDL/total cholesterol ratio, a decrease in the total levels of triglycerides and cholesterol.

With long-term use, regression of left ventricular hypertrophy is observed, platelet aggregation is suppressed, and the content of plasminogen activator in tissues is increased. Blockade of α₁-adrenergic receptors located in the stroma and capsule of the prostate gland, in the bladder neck leads to a decrease in resistance and pressure in the urethra, and a decrease in resistance in its internal opening. Improves urodynamics and reduces the manifestations of benign prostatic hyperplasia (BPH).

Pharmacokinetics

After oral administration, it is well absorbed from the gastrointestinal tract. C_max in plasma is reached after 1.5-3.6 hours. Binding to plasma proteins is 98-99%. Intensively metabolized in the liver. T_1/2 is 19-22 hours. It is excreted mainly through the intestines in the form of metabolites, 5% – unchanged; 9% is excreted by the kidneys.

Indications

Benign prostatic hyperplasia (BPH); arterial hypertension (including symptomatic) as part of combination therapy.

ICD codes

Dosage Regimen

Orally. The dose and regimen are determined individually, depending on the indications and clinical situation.

For BPH, the recommended initial dose is 1 mg/day. Depending on the clinical situation, the dose may be increased to achieve the optimal therapeutic effect. The average daily dose is 2-4 mg. The maximum daily dose is 8 mg.

For arterial hypertension, the dose ranges from 1 to 16 mg/day. It is recommended to start treatment with a dose of 1 mg once a day. To achieve the desired reduction in blood pressure, if necessary, the daily dose should be increased gradually, maintaining equal intervals to 4 mg, 8 mg and up to the maximum – 16 mg, depending on the severity of the patient’s response to doxazosin. The average daily dose is 2-4 mg.

Adverse Reactions

From the hematopoietic system: rarely – leukopenia, thrombocytopenia.

From the immune system very rarely – anaphylactic reactions.

From the metabolism: infrequently – anorexia; rarely – gout, increased appetite.

From the psyche: often – agitation, anxiety, insomnia; infrequently – depression.

From the nervous system very often – dizziness, headache; often – paresthesia, postural dizziness (after taking the first dose, a pronounced decrease in blood pressure is possible, which can lead to orthostatic dizziness, in severe cases, especially with a rapid transition from a “lying” position to a “standing” or “sitting” position – to fainting), drowsiness; infrequently – hypesthesia, fainting, tremor.

Infectious and parasitic diseases: often – respiratory tract infections, urinary tract infections.

From the organ of vision: often – impaired color perception; infrequently – intraoperative floppy iris syndrome.

From the organ of hearing and labyrinthine disorders: often – vertigo; infrequently – tinnitus.

From the cardiovascular system: often – tachycardia; infrequently – flushing, pronounced decrease in blood pressure, postural hypotension; rarely – angina pectoris, myocardial infarction, cardiac arrhythmia; very rarely – bradycardia, arterial hypertension.

From the respiratory system: often – dyspnea, rhinitis; infrequently – cough, epistaxis; very rarely – exacerbation of existing bronchospasm.

From the digestive system: often – nausea, abdominal pain, diarrhea, dyspepsia, dry oral mucosa; infrequently – flatulence, constipation, gastroenteritis, vomiting; frequency unknown – taste disturbance.

From the liver and biliary tract very rarely – cholestasis, hepatitis, jaundice, increased activity of liver transaminases.

From the skin and subcutaneous tissues: infrequently – alopecia, skin itching, skin rash, purpura; very rarely – urticaria.

From the musculoskeletal system infrequently – arthralgia, back pain, muscle spasms, muscle weakness, myalgia.

From the urinary system: often – cystitis, urinary incontinence; infrequently – increased frequency of urination, polyuria; very rarely – dysuria, hematuria, nocturia.

From the reproductive system: infrequently – impotence; very rarely – gynecomastia, priapism, retrograde ejaculation.

Other: often – asthenia, lower limb edema, fatigue, weakness; infrequently – pain of various localization, weight gain.

Contraindications

Hypersensitivity to doxazosin and other quinazoline derivatives; severe hepatic insufficiency (in the absence of experience of use in this category of patients); urinary tract infections; anuria; progressive renal failure; arterial hypotension and tendency to orthostatic disorders (including in history); concomitant obstruction of the upper urinary tract; bladder stones; urinary incontinence due to bladder overflow (paradoxical ischuria); children and adolescents under 18 years of age.

With caution pulmonary edema caused by mitral valve stenosis 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; cerebrovascular accidents; age over 65 years due to the risk of developing orthostatic symptoms (fainting, dizziness); simultaneous use with phosphodiesterase type 5 inhibitors (PDE-5) (risk of symptomatic arterial hypotension); impaired liver function; pregnancy; during cataract surgery.

Use in Pregnancy and Lactation

Adequate and strictly controlled studies of the safety of doxazosin use during pregnancy and lactation (breastfeeding) have not been conducted. During pregnancy and breastfeeding, it should be used only after consultation with a doctor, in cases where the intended benefit to the mother outweighs the potential risk to the fetus or infant.

Use in Hepatic Impairment

Contraindicated in severe hepatic insufficiency.

Use in Renal Impairment

Contraindicated in progressive renal failure.

Pediatric Use

Contraindicated in children and adolescents under 18 years of age.

Geriatric Use

Should be used with caution in patients over 65 years of age due to the risk of developing orthostatic symptoms (fainting, dizziness).

Special Precautions

After taking the initial dose of doxazosin, orthostatic hypotension may develop (first-dose phenomenon), especially in a standing position. This condition is more often observed in patients with hypovolemia, sodium deficiency, and in the elderly. In this regard, it is recommended to take the initial dose at bedtime.

Doxazosin 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 about the increased risk of orthostatic hypotension when drinking alcohol, prolonged standing or exercising, as well as in hot weather.

In patients with BPH, Doxazosin can be prescribed both in the presence of arterial hypertension and with normal blood pressure. When used in patients with BPH with normal blood pressure, the change in the latter is insignificant. At the same time, in patients with a combination of arterial hypertension and BPH, monotherapy is possible.

Before starting therapy for BPH, its cancerous degeneration must be excluded. Doxazosin does not affect the concentration of prostate-specific antigen (PSA) in the blood plasma.

Caution should be exercised when prescribing doxazosin, as well as other drugs that are completely biotransformed in the liver, to patients with impaired liver function, avoiding the prescription of maximum doses.

Intraoperative floppy iris syndrome. Intraoperative floppy iris syndrome (a variant of the “small pupil” syndrome) was observed in some patients during cataract surgery who were receiving or had previously received treatment with α₁-adrenergic blockers. The surgeon must be warned that the patient is currently taking or has previously taken α₁-adrenergic blockers before surgery.

Priapism. Cases of prolonged erection and priapism have been reported during therapy with α₁-adrenergic receptor blockers, including doxazosin. If an erection persists for more than 4 hours, you should immediately seek medical help. If therapy for priapism is not carried out immediately, this can lead to damage to the penile tissue and irreversible loss of potency.

There is no clinical experience with the use of doxazosin in children.

Effect on the ability to drive vehicles and mechanisms

At the beginning of therapy or when increasing the dose of doxazosin, a sharp decrease in blood pressure is possible, as a result of which dizziness may develop. In this regard, it is necessary to exercise caution when driving vehicles and working with complex technical devices that require increased concentration and speed of psychomotor reactions.

Drug Interactions

With simultaneous use with antihypertensive drugs, mutual enhancement of effects is possible.

With simultaneous use with PDE5 inhibitors (sildenafil, tadalafil, vardenafil), some patients may develop symptomatic arterial hypotension.

It is not recommended to take Doxazosin simultaneously with other α₁-adrenergic receptor blockers.

With simultaneous use with calcium channel blockers, there is some risk of developing severe arterial hypotension.

With simultaneous use with nitrates, agents for general anesthesia, tricyclic antidepressants, ethanol, an increase in the hypotensive effect is possible.

With simultaneous use of agents that affect the rate of metabolism in the liver, a slowdown or acceleration of doxazosin metabolism is possible.

NSAIDs (especially indomethacin), estrogens and sympathomimetic agents may reduce the hypotensive effect of doxazosin. By eliminating the alpha-adrenostimulating effects of epinephrine (adrenaline), Doxazosin can lead to tachycardia and arterial hypotension.

With simultaneous use with sildenafil for the treatment of pulmonary hypertension, the risk of orthostatic hypotension increases.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.