Instructions Doxazosin tablets 4 mg blister No. 20
Composition
active ingredient: doxazosin;
1 tablet contains doxazosin mesylate equivalent to doxazosin 4 mg;
Excipients: microcrystalline cellulose; lactose monohydrate; corn starch; calcium stearate.
Dosage form
Pills.
Main physicochemical properties: white tablets with a biconvex surface.
Pharmacotherapeutic group
Antihypertensives. Antiadrenergic agents with a peripheral mechanism of action. α-adrenergic receptor blockers. ATC code C02C A04.
Pharmacological properties
Pharmacodynamics
Mechanism of action
Doxazosin is a potent and selective antagonist of postsynaptic α1-adrenoceptors. Blockade of these receptors leads to a decrease in systemic blood pressure. Doxazosin is intended for oral administration once daily to patients with essential hypertension.
Pharmacodynamic effects
It has been demonstrated that doxazosin does not cause adverse metabolic effects and can be used in patients with diabetes mellitus, gout, or insulin resistance.
Doxazosin can also be prescribed to patients with bronchial asthma, left ventricular hypertrophy and elderly patients. The use of the drug helps to reduce left ventricular hypertrophy, inhibits platelet aggregation and enhances the activity of tissue plasminogen activator. In addition, the use of doxazosin increases insulin sensitivity in those patients in whom such sensitivity is impaired.
It has also been reported that, in addition to its antihypertensive effect, doxazosin causes a modest decrease in plasma total cholesterol, low-density lipoproteins, and triglycerides, and therefore this drug may be particularly beneficial for patients with hypertension and hyperlipidemia.
The use of doxazosin in patients with symptomatic BPH leads to significant improvement in urodynamics and symptom relief. The effect of the drug in BPH is believed to be achieved through selective blockade of α1-adrenoceptors located in the muscular stroma and capsule of the prostate gland, as well as in the bladder neck.
Pharmacokinetics
Absorption: When administered orally to humans (young men or elderly people of either sex), doxazosin is rapidly absorbed with a bioavailability of approximately ⅔ of the dose.
Biotransformation/Elimination: Approximately 98% of doxazosin is bound to plasma proteins. Doxazosin has been shown to be extensively metabolized in humans and experimental animals and is excreted primarily in the feces.
The average half-life (T½) of the drug from blood plasma is 22 hours, which makes it possible to take the drug once a day.
When doxazosin is administered orally, the plasma concentrations of its metabolites are low. The plasma concentration of the most active metabolite, 6'-hydroxydoxazosin, in humans is 40 times lower than the plasma concentration of the parent compound, indicating that the antihypertensive effect of the drug is mainly due to doxazosin.
There are currently only limited data on the use of the drug in patients with impaired liver function and on the effects of drugs that can alter hepatic metabolism (e.g. cimetidine). As with other drugs that are completely metabolized by the liver, doxazosin should be used with caution in patients with signs of impaired liver function.
Indication
Arterial hypertension. The drug is indicated for the treatment of arterial hypertension and for most patients it can be used to control blood pressure as monotherapy. In case of ineffectiveness of monotherapy for the treatment of arterial hypertension, the drug can be used in combination with thiazide diuretics, β-adrenoceptor blockers, calcium channel blockers and angiotensin-converting enzyme inhibitors.
Benign prostatic hyperplasia. The drug is indicated for the treatment of urinary tract obstruction, as well as symptoms associated with benign prostatic hyperplasia (BPH). The drug can be prescribed to patients with BPH both in the presence of arterial hypertension and with normal blood pressure levels.
Contraindication
Hypersensitivity to the active substance or to quinazoline derivatives (e.g. prazosin, terazosin, doxazosin) or to any of the excipients listed in the "Composition" section; history of orthostatic hypotension; BPH and associated upper urinary tract obstruction, chronic urinary tract infections and bladder stones; during breastfeeding (only when used for the treatment of arterial hypertension (see section "Use during pregnancy or breastfeeding"); arterial hypotension (applies only to patients with BPH). Doxazosin as monotherapy is contraindicated in patients with bladder overfilling or anuria with or without progressive renal failure.
Interaction with other medicinal products and other types of interactions
Phosphodiesterase-5 inhibitors (e.g. sildenafil, tadalafil, vardenafil). Concomitant use of doxazosin with PDE-5 inhibitors may cause symptomatic hypotension in some patients. Doxazosin prolonged-release formulations have not been studied.
Doxazosin is highly bound to plasma proteins (98%). In vitro studies using human plasma indicate that the drug does not affect the protein binding of the test drugs (digoxin, phenytoin, warfarin or indomethacin).
No adverse interactions have been observed with concomitant use of doxazosin and thiazide diuretics, furosemide, β-blockers, nonsteroidal anti-inflammatory drugs, antibiotics, oral hypoglycemic agents, uricosuric agents, and anticoagulants. However, there are no formal drug interaction studies available.
Doxazosin potentiates the hypotensive effect of other α-blockers, as well as other antihypertensive agents.
There is evidence that a single dose of 1 mg doxazosin on the first day of a four-day course of oral cimetidine (400 mg twice daily) resulted in a 10% increase in mean doxazosin AUC and no statistically significant changes in mean Cmax or mean T½ of doxazosin. This 10% increase in mean doxazosin AUC with cimetidine is within the range of interindividual variability (27%) in mean doxazosin AUC compared to placebo.
Application features
Orthostatic hypotension/syncope. Initiation of therapy. As with other α-adrenergic blockers, orthostatic hypotension occurs in a very small percentage of patients with doxazosin, presenting as dizziness and weakness or, more rarely, loss of consciousness (syncope), especially at the beginning of therapy. Therefore, blood pressure should be monitored at the beginning of therapy to minimize possible postural effects.
When prescribing therapy with any effective α-adrenergic blocker, the patient should be informed about how to avoid symptoms of orthostatic hypotension and how to deal with them if they occur. The patient should also be warned about the need to avoid situations in which there is a risk of injury, taking into account the possibility of dizziness or weakness at the beginning of therapy with doxazosin.
Use in acute cardiac conditions. As with other vasodilating antihypertensive agents, doxazosin should be used with caution in patients with the following acute cardiac conditions:
Pulmonary edema caused by aortic or mitral stenosis; hypersystolic heart failure; right ventricular heart failure caused by pulmonary embolism or pericardial effusion; left ventricular heart failure with low filling pressure.
Use in hepatic impairment. As with other drugs that are completely metabolized by the liver, doxazosin should be administered with extreme caution to patients with signs of hepatic impairment. Due to the lack of clinical experience with the drug in patients with severe hepatic impairment, the drug is not recommended for this category of patients.
Use with PDE5 inhibitors. Doxazosin should be used with caution in combination with phosphodiesterase-5 inhibitors (e.g. sildenafil, tadalafil and vardenafil) as these medicinal products cause vasodilation and may therefore cause symptomatic hypotension in some patients. To reduce the risk of orthostatic hypotension, it is recommended that phosphodiesterase-5 inhibitor therapy be initiated only if the patient is haemodynamically stable on α-blockers. It is also recommended that phosphodiesterase-5 inhibitor therapy be initiated at the lowest possible dose and that a 6-hour interval be maintained between the administration of doxazosin and phosphodiesterase-5 inhibitors.
Use in patients undergoing cataract surgery. Some patients who received tamsulosin during or before cataract surgery developed intraoperative atonic iris syndrome (IAIS – a variant of the narrow pupil syndrome) during the procedure. Isolated cases of this side effect have been reported with other α1-blockers, so the possibility of this effect with other drugs of this class cannot be excluded. Since IAS may increase the incidence of procedural complications during surgery, ophthalmic surgeons should be informed in preparation for surgery whether the patient is using or has used α1-adrenergic blockers.
Screening for prostate cancer. Prostate cancer causes many of the symptoms associated with BPH, and the two conditions may coexist. Therefore, prostate cancer should be ruled out before initiating doxazosin therapy for BPH symptoms.
This medicine contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
Ability to influence reaction speed when driving vehicles or other mechanisms
The ability to drive and use machines may be impaired, especially at the beginning of treatment.
Use during pregnancy or breastfeeding
Patients with arterial hypertension
Pregnancy
Due to the lack of adequate and well-controlled studies in pregnant women, the safety of doxazosin during pregnancy remains unknown. Therefore, the drug should be used only if the potential benefit justifies the potential risk, in the opinion of the physician. Although there is evidence that the drug was not teratogenic in animal studies, its use at very high doses, approximately 300 times the maximum recommended human dose, resulted in reduced fetal survival.
Breast-feeding
Doxazosin is contraindicated during breastfeeding, as animal studies have shown that doxazosin accumulates in the milk of lactating rats and as there are no data on the excretion of doxazosin in human milk during breastfeeding. If doxazosin is necessary, breastfeeding should be discontinued.
Patients with BPH
The information in this section does not apply to patients with BPH.
Method of administration and doses
Doxazosin can be taken both in the morning and in the evening.
The drug is administered orally.
Arterial hypertension. The drug should be used once a day. The initial dose is 1 mg to minimize the risk of orthostatic hypotension and/or syncope. After 1-2 weeks of initial therapy, the dose can be increased to 2 mg, and then, if necessary, to 4 mg. In most patients, the response to therapy is observed when using the drug at a dose of 4 mg or lower. If necessary, the dose of the drug can be increased to 8 mg or to the maximum recommended dose of 16 mg.
Benign prostatic hyperplasia. The recommended starting dose of doxazosin is 1 mg once daily to minimize the risk of orthostatic hypotension and/or syncope. Depending on the individual patient's urodynamics and symptoms of BPH, the dose may be increased to 2 mg, then to 4 mg and up to the maximum recommended dose of 8 mg. The recommended dose adjustment interval is 1-2 weeks. The usual recommended dose is 2-4 mg per day.
Elderly patients should use the usual adult doses.
Patients with renal impairment should use the usual adult doses, as the pharmacokinetic parameters of the drug do not change in renal impairment.
Doxazosin is not removed from the body by hemodialysis.
Patients with impaired liver function. Currently, information on the use of the drug in patients with impaired liver function and on the effects of drugs that can alter hepatic metabolism (e.g. cimetidine) is limited. As with other drugs that are completely metabolized by the liver, the drug should be prescribed with caution to patients with signs of impaired liver function.
Children
The safety and efficacy of the drug in children have not been studied.
Overdose
If an overdose of the drug has led to arterial hypotension, the patient should be urgently placed on his back with his head down. In some cases, other symptomatic measures may be taken.
If symptomatic measures are not sufficient, shock should be treated primarily with plasma substitutes. This should be followed by vasoconstrictors if necessary. Renal function should be monitored and supportive measures should be applied if necessary.
Hemodialysis is not indicated because doxazosin is extensively bound to plasma proteins.
Adverse reactions
Infections and infestations: respiratory tract infections, urinary tract infections.
From the blood and lymphatic system: leukopenia, thrombocytopenia.
On the part of the immune system: allergic reactions.
Metabolic and nutritional disorders: gout, increased appetite, lack of appetite.
Mental disorders: agitation, depression, anxiety, insomnia, nervousness.
Nervous system: drowsiness, dizziness, headache, stroke, hypoesthesia, syncope, tremor, orthostatic dizziness, paresthesia.
From the organs of vision: blurred vision, intraoperative atonic iris syndrome.
From the organs of hearing and balance: vertigo, tinnitus.
Vascular disorders: hypotension, orthostatic hypotension, hot flashes.
From the respiratory system, chest and mediastinum: bronchitis, cough, shortness of breath, rhinitis, nosebleeds, exacerbation of existing bronchospasm.
Gastrointestinal: abdominal pain, dyspepsia, dry mouth, nausea, constipation, flatulence, vomiting, gastroenteritis, diarrhea.
From the hepatobiliary system: abnormal liver function tests, cholestasis, hepatitis, jaundice.
Skin and subcutaneous tissue disorders: itching, skin rash, urticaria, alopecia, purpura.
Musculoskeletal and connective tissue disorders: back pain, myalgia, arthralgia, muscle spasms, muscle weakness.
Renal and urinary disorders: cystitis, urinary incontinence, dysuria, frequent urination, hematuria, polyuria, increased diuresis, urination disorders, nocturia.
From the reproductive system and mammary glands: impotence, gynecomastia, priapism, retrograde ejaculation.
General disorders and administration site conditions: asthenia, chest pain, influenza-like symptoms, peripheral edema, body pain, facial edema, fatigue, malaise.
Research results: weight gain.
Expiration date
5 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
10 tablets in a blister; 2 blisters in a box.
Vacation category
According to the recipe.
Producer
Limited Liability Company "Research Plant "GNTSLS".
Location of the manufacturer and its business address
Ukraine, 61057, Kharkiv region, Kharkiv city, Vorobyovy street, building 8.
