Active substanceDoxazosinDoxazosin
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  • Dosage form: & nbspTabletki.
    Composition:

    1 tablet contains:

    Active substance: doxazosin mesylate 2.43 mg or 4.86 mg, calculated as doxazosin 2 and 4 mg, respectively.

    Excipients: sodium carboxymethyl starch, cellulose microcrystalline, lactose, magnesium stearate, sodium lauryl sulfate.

    Description:

    Tonocardine® 2 mg - Tablets are white, round in shape with biconvex surfaces, with a risk on one side and a squeezed PLIVA on the other side.

    Tonocardine® 4 mg - Tablets are white, round in shape with biconvex surfaces, with a risk on one side.

    Pharmacotherapeutic group:alpha1-blocker
    ATX: & nbsp

    C.02.C.A.04   Doxazosin

    Pharmacodynamics:

    Tonocardine® is a selective competitive blocker of postsynaptic alpha 1-adrenergic receptors. By reducing the tone of the muscles of blood vessels doxazosin reduces the overall peripheral vascular resistance, which leads to a decrease in blood pressure (BP).

    After a single dose of the drug, a maximum of hypotensive effect is observed in the period from 2 to 6 hours, in general the hypotensive effect persists for 24 hours. In patients with arterial hypertension, blood pressure during treatment with the drug was the same in the standing and lying position.

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

    Reduces the risk of coronary heart disease.

    Admission of the drug in "normotonics" is not accompanied by a decrease in blood pressure.

    With prolonged use of doxazosin, patients develop tolerance.

    During the treatment with doxazosin, a decrease in the plasma concentration of triglycerides, total cholesterol, is observed. At the same time, there is a certain increase (by 4-13%) of the HDL / total cholesterol ratio.

    With prolonged treatment with doxazosin, regression of left ventricular hypertrophy, suppression of platelet aggregation, and an increase in the content of plasminogen in the tissues are observed.

    Due to doxazosin blocks alpha1-adrenergic receptors located in the stroma and capsule of the prostate gland and in the neck of the bladder, the resistance and pressure in the urethra decrease, the resistance of the internal sphincter decreases. Therefore, the appointment of doxazosin to patients with symptoms of benign prostatic hyperplasia leads to a significant improvement in urodynamics and a decrease in symptoms of the disease.

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

    After oral administration at therapeutic doses doxazosin well absorbed, 80-90% absorption (simultaneous intake of food slows absorption by 1 hour). The maximum concentration in the blood plasma is created after 3 hours. At evening reception time of achievement of the maximum concentration is extended to 5 hours.

    Bioavailability - 60-70% (presystemic metabolism). The connection with blood proteins is about 98%.

    Excretion from the blood plasma occurs in two phases, with a finite half-life of 19-22 hours, which allows taking the drug once a day.

    Doxazosin 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 liver metabolism, the process of biotransformation of the drug may be disrupted.

    The main excretion through the intestine (65% in the form of metabolites and about 5% unchanged). The kidneys show 10%.

    Studies of the pharmacokinetics of doxazosin in elderly patients and in patients with kidney disease there were no significant pharmacokinetic differences.

    Indications:

    Benign prostatic hyperplasia: to treat the difficulty or delay of urinary outflow associated with benign prostatic hyperplasia (BPH). The drug can be used both in the presence of arterial hypertension, and with normal blood pressure.

    Arterial hypertension:

    Used in combination with other antihypertensive agents such as thiazide diuretics, beta-blockers, blockers "slow" calcium channels or angiotensin-converting enzyme (ACE).

    Contraindications:

    - Increased sensitivity to doxazosin, other quinazoline derivatives or to any of the auxiliary components of the drug;

    - age under 18 years (effectiveness and safety not established);

    - lactation period.

    Carefully:

    In patients with impaired liver function, aortic and mitral stenosis, orthostatic hypotension.

    Pregnancy and lactation:

    In connection with the lack of adequate and well-controlled studies in pregnant women, the safety of using Tonokardine® when pregnancy is not yet established.

    Tonocardine® should be used in these patient groups only if, in the opinion of the doctor, the potential benefit exceeds the possible risk to the fetus and / or the child.

    Dosing and Administration:

    Doxazosin should be taken 1 time per day (morning or evening), regardless of food intake, without chewing and drinking with sufficient water.

    Benign prostatic hyperplasia

    The initial dose of the drug is 1 mg per day to minimize the possibility of developing orthostatic hypotension / or fainting. If necessary, depending on the parameters of urodynamics and the presence of symptoms, BPH increase the dose (at intervals of 1-2 weeks) to 2-4 mg / day. The maximum permissible is a dose of 8 mg per day.

    The recommended maintenance dose is 2-4 mg / day.

    Arterial hypertension

    The initial dose of the drug is 1 mg per day before bedtime. After taking the first dose, the patient should be in bed for 6-8 hours. This is required in connection with the possibility of developing a "first-dose phenomenon", especially pronounced against the background of previous intake of diuretics.

    If the therapeutic effect is insufficient, the daily dose can be increased to 2 mg in 1-2 weeks. In the following, 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 of the drug 16 mg per day can not be exceeded. After achieving a stable therapeutic effect, the dose is usually reduced (the average therapeutic dose with maintenance therapy is usually 2-4 mg per day).

    The drug Tonokardine® take a long time. The duration of treatment is determined by the doctor.

    Side effects:

    Arterial hypertension

    In clinical studies, orthostatic hypotension was most often observed, especially in the beginning of treatment, which in rare cases can lead to fainting.

    General reactions: asthenia, fatigue, malaise:

    From the central nervous and peripheral system: headache, dizziness, drowsiness.

    Allergic reactions: skin rash, hives.

    From the digestive system: nausea.

    From the side of the cardiovascular system: peripheral edema, fainting.

    From the respiratory system: rhinitis.

    As well as the following adverse reactions in patients with arterial hypertension (cause-and-effect relationship not established): bradycardia, tachycardia, palpitations, chest pain, angina pectoris, myocardial infarction, cerebral circulation disorder, arrhythmias.

    Benign prostatic hyperplasia (BPH)

    Patients with BPH have the same side effects as patients with hypertension, as well as:

    General reactions: allergic reactions, skin rash, itching, urticaria, back pain, joint pain, muscle weakness, muscular spasms, sensation of heat ("hot flashes"), weight gain.

    From the central nervous and peripheral system: hypoesthesia, priapism, paresthesia, tremor, impotence, insomnia, increased excitability, anxiety, nervousness, depression, sleep disorders.

    From the side of the cardiovascular system: decreased blood pressure, orthostatic hypotension.

    From the respiratory system: bronchospasm, cough, shortness of breath, nosebleed.

    From the endocrine system: gynecomastia.

    From the digestive system: nausea, dry mouth, abdominal pain, constipation, diarrhea, dyspepsia, flatulence, loss of appetite, nausea, anorexia, cholestasis, jaundice, hepatitis, abnormal liver function tests.

    From the genitourinary system: dysuria, hematuria, urination disorder, nocturia, polyuria, incontinence

    From the hematopoiesis and hemostasis system: thrombocytopenia, thrombocytopenic purpura, and leukopenia.

    From the skin: alopecia, purpura.

    From the sense organs: blurred vision, tinnitus.

    Overdose:

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

    Treatment: The patient should immediately be placed in a horizontal position, raise his legs. Symptomatic therapy is performed. Hemodialysis is ineffective.

    Interaction:

    Doxazosin enhances the antihypertensive effect of antihypertensive agents.

    There was no adverse interaction with simultaneous use of doxazosin and thiazide diuretics, furosemide, beta-adrenoblockers, slow calcium channel blockers, ACE inhibitors, antibiotics, oral hypoglycemic agents, uricosuric agents and indirect anticoagulants.

    The drug does not affect the degree of binding to proteins of the blood plasma digoxin, phenytoin.

    With simultaneous application with induction of microsomal oxidation in the liver, it is possible to increase the efficiency of doxazosin, with inhibitors - decrease.

    Non-steroidal anti-inflammatory drugs (especially indomethacin), estrogens and sympathomimetic agents can reduce the hypotensive effect of doxazosin.

    Eliminating the alpha-adrenostimulating effects of epinephrine, doxazosin can lead to tachycardia and arterial hypotension.

    Cimetidine increases AUC doxazosin.

    Inhibitors of phosphodiesterase-5 may enhance the hypotensive effect of doxazosin (caution should be exercised).
    Special instructions:

    Doxazosin should be used with caution in patients with:

    - a violation of liver function, especially in cases of administration of drugs that can adversely affect liver function. In cases of impairment of the functional state of the liver, the drug is immediately withdrawn;

    - to prevent orthostatic reactions, patients should avoid sudden and abrupt changes in body position (transition from lying to standing position);

    - caution should be exercised when combined with phosphodiesterase inhibitors (agents for the treatment of erectile dysfunction), since in some patients this can lead to symptomatic hypotension.

    Taking alcohol can increase unwanted reactions.

    Effect on the ability to drive transp. cf. and fur:Due to doxazosin can cause orthostatic reactions at the beginning of treatment or during the period of increasing dosages, it is advisable to refrain from all potentially dangerous activities, in particular from the management of motor vehicles, other vehicles and mechanisms
    Form release / dosage:

    Tablets, 2 and 4 mg.

    Packaging:

    10 tablets per blister (PVC / PVDC and aluminum foil).

    2 blisters with instructions for use in a cardboard box.

    Storage conditions:

    Store at a temperature not exceeding 25 ° C.

    Keep out of the reach of children.

    Shelf life:

    4 years.

    Do not use after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:P N014913 / 01
    Date of registration:01.08.2008
    Expiration Date:Unlimited
    The owner of the registration certificate:Pliva of Hrvatska dooPliva of Hrvatska doo Croatia
    Manufacturer: & nbsp
    Representation: & nbspPliva of Hvartska dooPliva of Hvartska doo
    Information update date: & nbsp23.11.2016
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