Allaforte^® (Tablets) Instructions for Use

Marketing Authorization Holder

Pharmtsentr Vilar JSC (Russia)

ATC Code

C01BC (Class Ic antiarrhythmic agents)

Active Substance

Lappaconitine hydrobromide (Grouping name)

Dosage Forms

	Allaforte®	Extended-release tablets 25 mg: 10, 15, 20, 30 or 45 pcs.
		Extended-release tablets 50 mg: 10, 15, 20, 30 or 45 pcs.

Dosage Form, Packaging, and Composition

Extended-release tablets white or white with a grayish or yellowish tint, round, biconvex in shape.

* (allapinin^®) (calculated as 100% substance).

Excipients: pregelatinized starch, lactose monohydrate, hypromellose, calcium stearate, colloidal silicon dioxide (aerosil A-380).

10 pcs. – contour cell packaging (1) – cardboard packs.
10 pcs. – contour cell packaging (2) – cardboard packs.
10 pcs. – contour cell packaging (3) – cardboard packs.
15 pcs. – contour cell packaging (1) – cardboard packs.
15 pcs. – contour cell packaging (2) – cardboard packs.
15 pcs. – contour cell packaging (3) – cardboard packs.

Extended-release tablets white or white with a grayish or yellowish tint, round, biconvex in shape.

* (allapinin^®) (calculated as 100% substance).

Excipients: pregelatinized starch, lactose monohydrate, hypromellose, calcium stearate, colloidal silicon dioxide (aerosil A-380).

10 pcs. – contour cell packaging (1) – cardboard packs.
10 pcs. – contour cell packaging (2) – cardboard packs.
10 pcs. – contour cell packaging (3) – cardboard packs.
15 pcs. – contour cell packaging (1) – cardboard packs.
15 pcs. – contour cell packaging (2) – cardboard packs.
15 pcs. – contour cell packaging (3) – cardboard packs.

Clinical-Pharmacological Group

Antiarrhythmic drug. Class I C

Pharmacotherapeutic Group

Means for the treatment of heart diseases; antiarrhythmic agents, classes I and III; antiarrhythmic agents, class IC

Pharmacological Action

Antiarrhythmic agent of class I C. It blocks the fast sodium channels of cardiomyocyte membranes. It causes slowing of AV and intraventricular conduction, shortens the effective and functional refractory periods of the atria, AV node, bundle of His and Purkinje fibers, does not affect the duration of the QT interval, conduction through the AV node in the anterograde direction, heart rate, blood pressure, myocardial contractility (in the initial absence of heart failure).

It does not depress the automaticity of the sinus node. It does not cause a negative inotropic and hypotensive effect, does not have an m-cholinolytic action.

It has a moderate antispasmodic, coronary vasodilating, cholinoblocking, local anesthetic and sedative effect. When taken orally, the effect develops after 40-60 minutes, reaches a maximum after 80 minutes and lasts for 8 hours or more.

Pharmacokinetics

When taken orally, lappaconitine hydrobromide is rapidly absorbed from the gastrointestinal tract; C_max in blood plasma is reached on average after 80 minutes, after which it rapidly decreases. It penetrates the blood-brain barrier. T_1/2 is 1.17-2.4 hours. Only about 10% of lappaconitine hydrobromide is excreted by the kidneys per day. The bioavailability of lappaconitine hydrobromide is 40-56%, which is associated with the “first-pass” effect through the liver. V_d is 690 L. Among the formed metabolites, the main pharmacologically active metabolite is deacetyllappaconitine.

In chronic heart failure of functional class II-III according to the NYHA classification, the absorption of lappaconitine hydrobromide is slowed (C_max in blood plasma is reached after 2 hours), and the role of renal excretion increases (up to 28% of lappaconitine hydrobromide is excreted by the kidneys per day).

Indications

Supraventricular and ventricular extrasystole, paroxysmal form of atrial fibrillation and flutter, paroxysmal supraventricular tachycardia, including in WPW syndrome, paroxysmal ventricular tachycardia (in the absence of organic changes in the myocardium).

ICD codes

Dosage Regimen

Initiate therapy at 25 mg three times daily, maintaining an 8-hour interval between doses.

If the therapeutic effect is inadequate, increase the dosing frequency to every 6 hours while maintaining the 25 mg single dose.

For patients requiring further dose escalation, increase the single dose to 50 mg.

Administer the 50 mg dose at intervals of every 6 to 8 hours based on individual patient response and tolerability.

Swallow the extended-release tablet whole; do not crush, chew, or split the tablet.

Take the drug with a sufficient amount of water, independent of meals.

Perform ECG monitoring before initiating treatment and regularly during therapy to assess efficacy and detect conduction abnormalities.

Monitor for adverse reactions such as dizziness, diplopia, or headache; reduce the dose if these occur.

Adjust the dosage regimen carefully in patients with mild to moderate hepatic or renal impairment; the drug is contraindicated in severe impairment.

This regimen is intended for long-term prophylactic antiarrhythmic therapy and not for the acute termination of arrhythmic paroxysms.

Adverse Reactions

From the nervous system very often – dizziness, headache, feeling of heaviness in the head, ataxia.

From the skin and subcutaneous tissues often – allergic reactions (skin hyperemia, skin itching).

From the organ of vision very often – diplopia.

From the cardiovascular system very often – disorders of intraventricular and AV conduction, changes on the ECG (prolongation of the PQ interval, widening of the QRS complex); often – sinus tachycardia (with prolonged use), increased blood pressure; infrequently – arrhythmogenic action.

Contraindications

Sinoatrial block, AV block of II and III degree (without an artificial pacemaker), cardiogenic shock, right bundle branch block combined with block of one of the branches of the left bundle branch, severe arterial hypotension (systolic blood pressure less than 90 mm Hg), moderate and severe chronic heart failure of functional class III-IV according to the NYHA classification, pronounced hypertrophy of the left ventricular myocardium (>1.4 cm), post-infarction cardiosclerosis, Brugada syndrome, acute myocardial infarction, severe impairment of liver and/or kidney function, age under 18 years, hypersensitivity to lappaconitine hydrobromide.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Use in Hepatic Impairment

Contraindication: severe liver dysfunction.

Use in Renal Impairment

Contraindication: severe kidney dysfunction.

Pediatric Use

The drug is contraindicated for use in children and adolescents under 18 years of age.

Special Precautions

Use with caution in patients with an artificial cardiac pacemaker, with first-degree AV block, chronic heart failure of functional class I-II according to the NYHA classification, impaired intraventricular conduction, sick sinus syndrome, bradycardia, severe peripheral circulation disorders, closed-angle glaucoma, benign prostatic hyperplasia, impaired conduction through the Purkinje fibers, block of one of the bundle branches, disorders of water-electrolyte metabolism (hypokalemia, hyperkalemia, hypomagnesemia).

Lappaconitine hydrobromide should be used with particular caution in patients with coronary artery disease and stable exertional angina, since one of the predisposing factors for the proarrhythmic action of class 1C antiarrhythmic drugs is transient myocardial ischemia and high heart rate. Use with caution in combination with other antiarrhythmic drugs due to the increased risk of proarrhythmic action.

Lappaconitine hydrobromide is intended for long-term prophylactic antiarrhythmic therapy. The available limited clinical experience does not allow recommending the use of lappaconitine hydrobromide orally for the relief of paroxysms of supraventricular and ventricular tachycardia.

Before starting use, it is necessary to eliminate disorders of water-electrolyte metabolism; during treatment, control of water-electrolyte balance in the blood is required.

Before starting use and during treatment, ECG and clinical examination should be performed for early detection of side effects, assessment of the drug’s effectiveness and determination of the need to continue therapy.

In patients with an established artificial cardiac pacemaker, its stimulation threshold may increase. Pacemakers should be checked and reprogrammed if necessary.

If headache, dizziness, diplopia develop, the dose should be reduced.

If sinus tachycardia appears during long-term use of the drug, the use of beta-blockers (in individually selected doses) is indicated.

When using class 1C antiarrhythmic agents in patients with severe organic changes in the myocardium, serious adverse reactions may occur. The use of lappaconitine hydrobromide in such patients is possible only after a thorough assessment of the expected benefit and possible risk for the patients, and should be carried out under the supervision of a cardiologist with experience in treating the corresponding cardiac arrhythmias.

Effect on the ability to drive vehicles and mechanisms

During treatment, caution should be exercised when engaging in potentially hazardous activities that require increased attention and rapid reactions (driving vehicles and working with moving mechanisms).

Drug Interactions

With simultaneous use of lappaconitine hydrobromide with other antiarrhythmic agents, the risk of developing arrhythmogenic action increases.

Lappaconitine hydrobromide enhances the effect of non-depolarizing muscle relaxants.

With simultaneous use of lappaconitine hydrobromide with other antiarrhythmic agents, the risk of developing side effects associated with the effect on the function of the sinus node and AV conduction increases. Individual dose selection of each of these drugs is required.

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.