Laporitmin, tablets 25 mg 30 pcs

Pharmacotherapeutic group: antiarrhythmic drug.

ATX code: C01BG

Pharmacological properties

Laporitmin® is bromine hydrogenate salt of lappaconitin alkaloid with the accompanying alkaloids, obtained from the grass of white bearded wormwood – Aconitum leucostomum Worosch. and rhizomes with roots of northern wolfberry (wolfsbane) – Aconitum septentrionale Koelle (A. Excelsum Reichenb.), family Ranunculaceae.

Pharmacodynamics

Antiarrhythmic drug of IC class. Blocks “fast” sodium channels of cardiomyocyte membranes. It causes delay in atrioventricular (AV) and intraventricular conduction, shortens effective and functional refractory periods of atria, AV node, Gis bundle and Nourkinje fibers and does not influence QT interval duration, conduction through AV node in anterograde direction, heart rate, myocardial contractility (in initial absence of cardiac insufficiency). It does not inhibit sinus node automatism, has no negative inotropic effect, has no antihypertensive and M-cholinolytic effects. It has moderate antispasmodic, coronary dilator, local anesthetic and sedative effect.

When taken orally, the effect develops in 40-60 minutes, reaches its maximum in 4-5 hours and lasts for 8 hours or more.

Pharmacokinetics

On oral administration, lappaconitine hydrobromide is rapidly absorbed in the gastrointestinal tract; maximum plasma concentration is reached in 80 minutes on average, after which it rapidly decreases. It penetrates the blood-brain barrier.

The elimination half-life (T1/2) is 1.17-2.4 hours. Only about 10% of lappaconitine hydrobromide is excreted by the kidneys during 24 hours. Bioavailability of lappaconitine hydrobromide is from 40 to 56%, which is associated with the effect of “primary passage” through the liver. The volume of distribution is 690 l. Among the metabolites formed the main pharmacologically active metabolite is deacetylappaconitine. In chronic heart failure IIb-III functional class according to NYHA classification absorption of lappaconitine hydrobromide is delayed (maximum concentration in blood plasma is reached after 2 hours), and the role of renal excretion is increased (kidneys excrete up to 28% of lappaconitine hydrobromide per day).

Indications

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

Pharmacological effect

Pharmacotherapeutic group: antiarrhythmic agent.

ATX code: C01BG

Pharmacological properties

Laporitmin® is a hydrobromic salt of the alkaloid lappaconitine with accompanying alkaloids, obtained from the grass of the white-mouthed fighter – Aconitum leucostomum Worosch. and rhizomes with roots of the northern fighter (high fighter) – Aconitum septentrionale Koelle (A. Excelsum Reichenb.), buttercup family – Ranunculaceae.

Pharmacodynamics

Class IC antiarrhythmic drug. Blocks “fast” sodium channels of cardiomyocyte membranes. Causes a slowdown in atrioventricular (AV) and intraventricular conduction, shortens the effective and functional refractory periods of the atria, AV node, His bundle and Nurkinje fibers, does not affect the duration of the QT interval, conduction through the AV node in the anterograde direction, heart rate (HR), myocardial contractility (in the initial absence of cardiac events insufficiency). It does not inhibit the automatism of the sinus node, does not have a negative inotropic effect, and does not have an antihypertensive or anticholinergic effect. It has a moderate antispasmodic, coronary dilation, local anesthetic and sedative effect.

When taken orally, the effect develops after 40-60 minutes, reaches a maximum after 4-5 hours and lasts 8 hours or more.

Pharmacokinetics

When taken orally, lappaconitine hydrobromide is rapidly absorbed from the gastrointestinal tract; the maximum concentration in blood plasma is reached on average after 80 minutes, after which it quickly decreases. Penetrates the blood-brain barrier.

The half-life (T1/2) is 1.17-2.4 hours. Only about 10% of lappaconitine hydrobromide is excreted by the kidneys per day. The bioavailability of lappaconitine hydrobromide ranges from 40 to 56%, which is associated with the “first pass” effect through the liver. Distribution volume 690 l. Among the metabolites formed, the main pharmacologically active metabolite is desacetyllappaconitine. In chronic heart failure of functional class IIb-III according to the NYHA classification, the absorption of lappaconitine hydrobromide is slowed down (the maximum concentration in the 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).

Special instructions

The drug is used as prescribed by a doctor.

Before starting to use the drug Laporitmin®, it is necessary to eliminate disturbances in water and electrolyte metabolism; during therapy, monitoring of the water and electrolyte balance of the blood is necessary.

Each patient who takes the drug Laporitmin® should undergo an electrocardiographic and clinical examination before starting therapy and during its implementation for early detection of side effects, assessing the effectiveness of the drug and the need to continue therapy.

In patients with a pacemaker installed, the pacemaker threshold may increase. Pacemakers must be checked and reprogrammed if necessary.

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

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

When using class IC antiarrhythmic drugs in patients with severe organic changes in the myocardium, serious adverse reactions may occur. The use of Laporitmin® in such patients is possible only after a careful assessment of the expected benefits and possible risks for patients, and should be carried out under the supervision of a cardiologist with experience in the treatment of relevant cardiac arrhythmias. The drug Laporitmin® should be used with extreme caution in patients with coronary heart disease and stable angina pectoris, since one of the predisposing factors for the proarrhythmogenic effect of class IC antiarrhythmic drugs is transient myocardial ischemia and high heart rate. The drug Laporitmin® should be used with caution in combination with other antiarrhythmic drugs due to the increased risk of proarrhythmic effects. The adverse effects of other IC class antiarrhythmic drugs on electrophysiological parameters and clinical manifestations in Brugada syndrome have been established. There is no experience with the use of lappaconitine hydrobromide in Brugada syndrome, and therefore the use of Laporitmin® in patients with Brugada syndrome is contraindicated.

The drug Laporitmin® is intended for long-term preventive antiarrhythmic therapy. The limited clinical experience available does not allow us to recommend the use of Laporitmin® orally to relieve paroxysms of supraventricular and ventricular tachycardia.

One tablet of the drug Laporitmin® contains about 0.007 XE (bread units).

Impact on the ability to drive vehicles and machinery

When using the drug, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions due to the risk of dizziness.

Active ingredient

Lappaconitine hydrobromide

Composition

Active ingredient:

Lappaconitine hydrobromide (calculated as 100% substance) – 25.0 mg

Excipients:

lactose monohydrate 63.5 mg,

potato starch 10.0 mg,

calcium stearate 1.0 mg,

colloidal silicon dioxide 0.5 mg.

Pregnancy

The use of the drug during pregnancy is not recommended due to the lack of controlled studies.

Animal studies have shown that lappaconitine hydrobromide in doses of 1-5 mg/kg does not have teratogenic or embryotoxic effects. The effect on fertility has not been studied.

It is possible to use the drug only for health reasons if the expected benefit to the mother outweighs the potential risk of side effects in the fetus/child.

There are no data on the excretion of lappaconitine hydrobromide into breast milk. The use of the drug is not recommended during breastfeeding.

If the use of Laporitmin® during lactation is necessary, breastfeeding should be discontinued.

Contraindications

Hypersensitivity to lappaconitine hydrobromide or to any other component of the drug, sinoatrial block, atrioventricular block II and III degrees (without pacemaker), cardiogenic shock, right bundle branch block combined with blockade of one of the branches of the left leg, 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, severe left ventricular myocardial hypertrophy (≥1.4 cm), post-infarction cardiosclerosis, severe liver and/or kidney dysfunction, age under 18 years (efficacy and safety have not been established), lactase deficiency, lactose intolerance, glucose-galactose malabsorption (the drug contains lactose), Brugada syndrome.

Use with caution in case of first degree atrioventricular block, intraventricular conduction disorder, sick sinus syndrome (SSNS), bradycardia, severe peripheral circulatory disorders, angle-closure glaucoma, benign prostatic hypertrophy, conduction disorder along Purkinje fibers, blockade of one of the bundle branches, impaired water-electrolyte metabolism (hypokalemia, hyperkalemia, hypomagnesemia), while taking other antiarrhythmic drugs.

Side Effects

According to the World Health Organization, adverse effects are classified according to their frequency as follows: very common (≥10% of prescriptions); often (≥1% and <10%); uncommon (≥0.1% and <1%); rare (≥0.01% and <0.1%); very rare (<0.01%); frequency unknown (insufficient data to estimate frequency of development).Nervous system disorders: Very common: dizziness, headache, feeling of heaviness in the head, ataxia.Disorders of the skin and subcutaneous tissues: Often: allergic reactions (hyperemia of the skin, itching).Visual disturbances: Very common: diplopia.Cardiac disorders:
Very common: intraventricular and AV conduction disorders.
Often: sinus tachycardia (with prolonged use), increased blood pressure (BP).
Uncommon: arrhythmogenic effect.
Laboratory and instrumental data: Very often: changes on the ECG: prolongation of the PQ interval, expansion of the QRS complex.

If you experience the side effects listed in the instructions or they get worse, or you notice any other side effects not listed in the instructions, tell your doctor.

Interaction

Inducers of microsomal liver enzymes do not affect the effectiveness of lappaconitine hydrobromide.

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

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

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

In a clinical study, when lappaconitine hydrobromide was used against the background of standard antihypertensive therapy with angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, blockers of “slow” calcium channels, dihydropyridine derivatives, and beta-blockers, no increase or decrease in the antihypertensive effect was observed.

There is no data on the adverse effects of lappaconitine hydrobromide on the effectiveness and safety of indirect anticoagulants.

Overdose

The drug has a small therapeutic breadth, so severe intoxication can easily occur (especially with simultaneous use of other antiarrhythmic drugs).

Symptoms: prolongation of PR and QT intervals, expansion of the QRS complex, increased amplitude of T waves, bradycardia, sinoatrial and AV blockade, asystole, paroxysms of polymorphic ventricular tachycardia, decreased myocardial contractility, marked decrease in blood pressure, dizziness, blurred vision, headache, gastrointestinal disorders.

Treatment: symptomatic; gastric lavage, defibrillation, administration of dobutamine, diazepam; if necessary, artificial ventilation and chest compressions; for the treatment of ventricular tachycardia, do not use class IA and IC antiarrhythmic drugs; sodium bicarbonate (intravenous drip) can eliminate the expansion of the QRS complex, bradycardia and arterial hypotension.

Storage conditions

In a dry place, protected from light, at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life

5 years.

Do not use after expiration date.

Manufacturer

PharmVilar NPO LLC, Russia