Tonocardin^® (Tablets) Instructions for Use

Marketing Authorization Holder

Pliva Hrvatska, d.o.o. (Croatia)

ATC Code

C02CA04 (Doxazosin)

Active Substance

Doxazosin (Rec.INN registered by WHO)

Dosage Forms

	Tonocardin®	Tablets 2 mg: 20 pcs.
		Tablets 4 mg: 20 pcs.

Dosage Form, Packaging, and Composition

Tablets are white, round in shape with biconvex surfaces, with a score on one side and the embossed inscription “PLIVA” on the other.

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

10 pcs. – blisters (2) – cardboard packs.

Tablets are white, round in shape with biconvex surfaces, with a score on one side.

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

10 pcs. – blisters (2) – 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. The use of the drug leads to a decrease in total peripheral vascular resistance, which mainly determines its antihypertensive effect. After a single dose of the drug, the maximum decrease in blood pressure is observed between 2 hours and 6 hours; the antihypertensive effect persists for 24 hours. In patients with arterial hypertension during treatment with Tonocardin^®, blood pressure does not differ in the standing and lying positions.

The use of the drug leads to an increase in the HDL/total cholesterol ratio, and a decrease in the total levels of triglycerides and cholesterol. This favorable effect on lipid metabolism, as well as the antihypertensive effect of the drug, contribute to reducing the risk of developing coronary artery disease and stroke. During long-term treatment with Tonocardin^®, regression of left ventricular hypertrophy, suppression of platelet aggregation, and an increase in the tissue content of plasminogen activator are observed.

Prescribing Tonocardin^® to patients with benign prostatic hyperplasia leads to a significant improvement in urodynamic parameters and a reduction in the symptoms of this disease. The effect in patients with benign prostatic hyperplasia is associated with selective blockade of α₁-adrenergic receptors, which are localized in the muscular stroma and capsule of the prostate gland and in the bladder neck.

Pharmacokinetics

Absorption

After oral administration of a therapeutic dose of Tonocardin^®, the drug is well absorbed from the gastrointestinal tract. The time to reach C_max of the active substance in the blood serum is 2 hours. Bioavailability is approximately 65%.

Distribution

Plasma protein binding of doxazosin mesylate is about 98%.

Metabolism

Doxazosin mesylate is actively metabolized in the liver by O-demethylation and hydroxylation.

Excretion

The elimination of doxazosin mesylate from the blood plasma occurs in 2 phases. T_1/2 is 22 hours, which allows for once-daily administration of the drug. Doxazosin mesylate is excreted mainly through the intestines, predominantly as metabolites, and only 5% unchanged.

Pharmacokinetics in special clinical cases

Studies of the action of Tonocardin^® in elderly patients and patients with renal failure did not reveal significant pharmacological differences.

Indications

• Arterial hypertension (as monotherapy and as part of combined antihypertensive therapy);
• Benign prostatic hyperplasia (with worsening or obstruction of urine outflow) in patients with initially elevated and normal blood pressure.

ICD codes

Dosage Regimen

For arterial hypertension, the initial dose is 1 mg/day. The dose can be increased to achieve the desired antihypertensive effect from 1 mg to 2 mg/day only after 1-2 weeks of taking the drug at a dose of 1 mg/day. Subsequently, the dose is increased by 2 mg at intervals of 1-2 weeks until the desired antihypertensive effect is achieved. The maximum daily dose is 16 mg. On average, the effect is achieved when using the drug at a dose of 2-4 mg/day.

For benign prostatic hyperplasia, the initial dose of Tonocardin^® is 1 mg once/day. Depending on the urodynamic parameters and the severity of symptoms of benign prostatic hyperplasia, the daily dose can be increased to 2 mg, and then to 4 mg. The maximum daily dose is 8 mg. The recommended interval between dose increases is 1-2 weeks.

The drug is recommended to be taken once/day in the morning or evening.

Adverse Reactions

From the cardiovascular system, orthostatic hypotension, dizziness are possible; sometimes – fainting; rarely – tachycardia, edema.

From the central nervous system rarely – headache, weakness, asthenia; in some cases – blurred vision.

From the digestive system rarely – nausea; in isolated cases – impaired liver function parameters.

From the hematopoietic system in isolated cases – thrombocytopenia, leukopenia.

Other rarely – nasal congestion, rhinitis, skin rash, itching; in isolated cases – urinary incontinence, prolonged painful erection.

Side effects are usually moderate and tend to resolve on their own with continued treatment.

Contraindications

• Hypersensitivity to quinazolines.

Use in Pregnancy and Lactation

Due to the lack of adequate and strictly controlled studies on the safety of using Tonocardin^® during pregnancy and lactation (breastfeeding), the drug can be prescribed only if the potential benefit to the mother outweighs the possible risk to the fetus or child.

Use in Hepatic Impairment

When prescribing Tonocardin^® to patients with impaired liver function or when prescribing it in combination with drugs that adversely affect the liver, precautions must be taken.

Pediatric Use

There are no data on the safety and efficacy of the drug in children and adolescents under 18 years of age.

Special Precautions

When prescribing Tonocardin^® to patients with impaired liver function or when prescribing it in combination with drugs that adversely affect the liver, precautions must be taken.

The gradual decrease in blood pressure and orthostatic manifestations at the beginning of the drug’s action are similar to those when using other postsynaptic selective α₁-adrenergic receptor blockers.

Unlike non-selective alpha-blockers, long-term treatment with Tonocardin^® does not lead to tolerance, and tachycardia rarely occurs.

Use in pediatrics

There are no data on the safety and efficacy of the drug in children and adolescents under 18 years of age.

Effect on the ability to drive vehicles and operate machinery

At the beginning of the course of treatment, it is recommended to refrain from engaging in potentially hazardous activities, in particular, from driving vehicles and operating machinery.

Overdose

Symptoms pronounced decrease in blood pressure.

Treatment the patient should be immediately placed in a horizontal position with legs elevated. If necessary, the administration of vasopressor drugs is indicated. Hemodialysis is not effective.

Drug Interactions

No adverse interaction was noted with the simultaneous use of Tonocardin^® with thiazide diuretics, furosemide, beta-blockers, calcium channel blockers, ACE inhibitors, NSAIDs, antibiotics, oral hypoglycemic drugs, indirect anticoagulants, and uricosuric drugs.

Tonocardin^® does not affect the plasma protein binding of digoxin, phenytoin, warfarin, indomethacin.

Storage Conditions

The drug should be stored at room temperature (from 15°C (59°F) to 25°C (77°F)).

Shelf Life

The shelf life is 4 years.

Dispensing Status

The drug is dispensed by prescription.

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.