Flecainide - Uses, Dosage, Precautions, Side Effects, and Pharmacological Aspects

Overview:

Flecainide is a medication used to treat irregular heartbeats, specifically ventricular arrhythmias (abnormal heartbeats). It is among the members of the class of drugs referred to as antiarrhythmics, which control heart rhythm. Patients with atrial fibrillation (irregular heart rhythm), atrial flutter (heart beats quickly), or other diseases that result in irregular heartbeats. The United States Food and Drug Administration approved Flecainide for treating ventricular arrhythmias in 1985. The medication is typically taken orally, either in tablet or capsule form. Among the negative effects of Flecainide are nausea, headaches, dizziness, and changes in heart rate.

How Does Flecainide Work?

Flecainide slows or stabilizes irregular cardiac rhythms by obstructing the entry of sodium ions into heart cells. It specifically blocks sodium channels in the heart that are in charge of the quick influx of sodium ions into cardiac cells during the first phase of the action potential. This causes the cell membrane to depolarize and the heart muscle to contract. Flecainide can reduce the rate at which the heart beats and assist in reestablishing a normal rhythm by obstructing these pathways.

Available Doses and Dosage Forms:

Flecainide is available in tablet form in strengths of 50 milligrams (mg), 100 mg, and 150 mg. The tablets are usually taken two or three times per day, depending on the condition being treated and the individual patient's needs.

For Patients:

What Is Ventricular Arrhythmia?

Ventricular arrhythmia is a type of abnormal heart rhythm that originates in the lower chambers of the heart, known as the ventricles. Normally, the heart's electrical signals originate in the sinoatrial node (SA node), located in the right atrium, and then travel through the atria and into the ventricles. This coordinated flow of electricity causes the heart muscle to contract and pump blood throughout the body.

In ventricular arrhythmia, the electrical signals in the ventricles become disrupted, causing the heart to beat too fast, too slowly, or irregularly. Dizziness, chest pain, shortness of breath, fainting, or even loss of consciousness may result from this interfering with the heart's capacity to pump blood efficiently. Ventricular arrhythmias can be life-threatening in severe situations and may call for immediate medical attention.

Learn More About Flecainide:

Before Starting Flecainide:

When and Why to Take Flecainide?

Flecainide is typically prescribed to treat irregular heartbeats, specifically ventricular arrhythmias, including ventricular tachycardia and premature ventricular contractions. The medication is usually administered two to three times daily. Patients should take the drug only as instructed by their healthcare provider. When using Flecainide, patients should let their doctor know if they develop any new or unexpected symptoms because this can mean that the medicine needs to be changed or stopped altogether.

How Effective is Flecainide?

According to studies, Flecainide can help certain people have less frequent and severe ventricular arrhythmias. Studies show that individuals with a history of ventricular tachycardia (increased heart rate) respond well to Flecainide for lowering the disease frequency.

Things to Inform the Doctor Before Taking Flecainide:

The administration of Flecainide is not advised in the following conditions:

• Allergy: Avoid drug administration if the patient is allergic to Flecainide acetate or any of the drug's inactive components.

• Heart Failure and Rhythm Disorders: If the patient suffers from heart failure or certain heart rhythm disorders.

• History of Heart Attacks: If the patient has had a history of heart attacks, avoid using Flecainide.

• Heart Diseases: It is not advised for patients with a history of heart valve disease or a slow heartbeat.

• Cardiogenic Shock: Flecainide should not be taken if the patient has had a cardiogenic shock (a serious cardiac disorder that can cause symptoms like rapid breathing, weakness, looking pale, confusion, and even loss of consciousness).

• Brugada Syndrome: Avoid using Flecainide in Brugada syndrome, a heart ailment that can result in potentially fatal heart rhythm problems.

• Disopyramide: Flecainide should not be taken if the patient is already taking Disopyramide to control the heartbeat.

Additional warnings and precautions relating to drug use include the following:

• Electrolyte Imbalances: When using Flecainide, it is crucial to inform the physician whether the patient has electrolyte imbalances, like changes in blood potassium levels.

• Liver or Kidney Issues: Flecainide should be used cautiously if the patient has liver disease or renal issues. A dose adjustment may be required in such cases.

• Sick Sinus Syndrome: Flecainide should only be used under medical supervision if the patient suffers from the heart rhythm issue called "sick sinus syndrome," which impairs the heart's natural pacemaker.

• Pacemaker: Flecainide should be used cautiously if has a pacemaker. Pay attention to the directions provided by the physician for drug use carefully.

• Heart Enlargement: Flecainide should only be used under medical supervision in cases of an enlarged heart. Routine checking of cardiac function may be necessary in these cases.

What Are the Side Effects of Flecainide?

Common side effects include:

• Fast or irregular heartbeats.

• Feeling giddy, dizzy, or lightheaded.

• Blurred or double vision.

• Breathlessness, difficulty breathing.

• Weakness.

• Tiredness.

• Fever.

• Excessive fluid in the body (swelling).

Uncommon side effects include:

• Red blood cell count reduction may create a pale complexion, weakness, or shortness of breath.

• Reduction in white blood cell count, which makes you prone to infections.

• Reduction in platelet count can make you bleed or bruise more easily than normal.

• Feeling or being sick.

• Constipation.

• Stomach pain or discomfort.

• Reduced appetite.

• Diarrhea.

• Indigestion.

• Inflammation of the skin due to allergies, including rash.

• Hair loss.

Rare side effects include:

• Inflammation of the lungs can cause weakness, breathlessness, coughing, and raised temperature (pneumonitis).

• Changes in liver function with or without yellowing of the skin or whites of the eyes (jaundice), usually reversible after stopping treatment.

• Fits (convulsions).

• Depression.

• Confusion or anxiety.

• Loss of memory.

• Difficulty sleeping or sleepiness.

• Seeing, hearing, or feeling things that are not there (hallucinations).

• Nervousness.

• Tingling or a weakened feeling in the arms and legs.

• Tingling, pins, and needles.

• Sudden uncontrollable or abnormal body movements, shaking.

• Reduced sensation or sensitivity, particularly in the skin.

• Increased sweating.

• Fainting.

• Redness of the skin (flushing).

• Headache.

• Ringing in the ears.

• Nettle-like rash, hives.

Very rare side effects include:

• Worsening of eyesight.

• Dry mouth or taste changes.

• Sensitivity of the skin to light.

• Painful, swollen joints or muscle pain.

• Impotence.

• Raised levels of certain antibodies, which may cause inflammation.

Report to the doctor immediately if any of these side effects are experienced and seek immediate medical help if these adverse effects worsen or persist for longer.

How to Use Flecainide?

• Take the medication as instructed by the doctor.

• The medication may be taken by mouth with a glass of water.

• Food has no apparent effect on the absorption of the drug.

• In case of doubts or queries, contact the pharmacist.

Dietary Alterations:

Patients or caregivers are instructed to report any changes in dietary milk intake while on the drug therapy, as changes in the drug dose may be required.

What Should Be Done If a Dose Is Missed?

Missed doses must be taken immediately after the patient remembers it. However, if the next dose is near, it is advised to skip the previous dose and continue with the next dose.

What Should Be Done to Treat a Flecainide Overdose?

In case of an overdose, immediately contact the emergency department or the nearest poison control center.

How to Store Flecainide?

• Keep Flecainide out of the reach and sight of children.

• Do not use this medication after its expiration date, indicated on the packaging, such as the carton, bottle, or blister pack, after the abbreviation "exp."

• This medicine does not have any specific storage requirements.

• Do not dispose of any medications in wastewater or household waste to safeguard the environment. Instead, ask your pharmacist for guidance on how to dispose of unused medicines.

For Doctors:

Indication

FDA (the United States Food and Drug Administration)-labeled indications of Flecainide include

• Prophylaxis of paroxysmal atrial fibrillation.

• Prophylaxis of paroxysmal atrial flutter.

• Prophylaxis of paroxysmal supraventricular tachycardia.

• Prophylaxis of ventricular arrhythmia.

Dosing:

For Ventricular Arrhythmia: Start with 100 mg orally every 12 hours titration, increase by 50 mg orally twice daily at intervals of at least four days. Maximum dose 400 mg.

Dosing Considerations:

Dosage recommendations for Flecainide based on specific conditions:

Renal Impairment:

• In patients with creatinine clearance (CrCl) greater than 35 mL/min/1.73m(2): m(2), an initial dose of 100 mg orally every 12 hours.

• In patients with CrCl of 35 mL/min/1.73m(2) or less: an initial dose of 100 mg orally once daily or 50 mg every 12 hours.

• Consider monitoring Flecainide plasma levels during dosage adjustment.

• Increasing the dose should be carried out cautiously when plasma levels of the drug have plateaued (after more than four days).

Hepatic Impairment:

• Avoid use in patients with significant hepatic impairment unless the potential benefit is expected to exceed the risk.

• Monitor Flecainide levels to guide dosage.

• Only increase once the level has plateaued (for more than 4 days).

Hemodialysis: Dose reductions are necessary. The magnitude of clearance by dialysis is not known. Monitor drug levels in plasma.

Congestive Heart Failure: Initial dose, no more than 100 mg orally every 12 hours.

Pharmacology:

Mechanism of Action:

Flecainide blocks fast inward sodium channels, which gradually unbind during diastole and lengthen the heart's refractory period. The duration of action potentials that travel via the Purkinje fibers is also shortened due to this obstruction. Flecainide also delays the opening of delayed rectifier potassium channels, extending the ventricular and atrial muscle fiber action potential. Flecainide also prevents ryanodine receptors from opening, reducing the sarcoplasmic reticulum's release of calcium and, consequently, the depolarization of cells.

Pharmacodynamics:

Flecainide works by inhibiting the activity of the heart's sodium and potassium ion channels, which increases the threshold for depolarization and helps to correct arrhythmias. Due to its long duration of action, Flecainide can be taken once daily. However, it has a narrow therapeutic index, and patients with structural heart disease or left ventricular systolic dysfunction should not take this medication.

Pharmacokinetics:

Absorption:

Flecainide is well absorbed after oral administration, with a bioavailability of 90 percent. The maximum concentration in the blood (Tmax) is achieved within three to four hours. Taking Flecainide with food or aluminum hydroxide antacids does not significantly affect its absorption.

Distribution:

Flecainide is 40 percent bound to proteins in serum, mainly alpha-1-acid glycoprotein and, minorly, serum albumin.

Metabolism:

Flecainide is mainly metabolized to meta-O-dealkylated Flecainide or the meta-O-dealkylated lactam of Flecainide by the action of CYP2D6 and CYP1A2. Both metabolites are generally detected as glucuronide or sulfate conjugates.

Excretion:

Approximately 86 percent of a single oral dose is eliminated in the urine, with 42 percent as unchanged Flecainide and 14 percent as meta-O-dealkylated Flecainide, a similar amount of the meta-O-dealkylated lactam of Flecainide, approximately three percent as an unidentified acid metabolite, and less than one percent as two other unknown metabolites. Five percent of the drug is eliminated in the feces.

Clinical Toxicity:

Patients experiencing an overdose may present anomalies in the electrocardiogram (ECG), such as a prolonged PR interval, prolonged QRS duration, prolonged QT interval, increased T wave amplitude, decreased heart rate and contractility, hypotension, or even death.

Supportive and symptomatic therapy is used to treat overdoses, such as inotropic medication, assisted breathing, circulatory support, and acidity of the urine.

Warnings and Precautions:

Cardiovascular Events:

• New or worsening ventricular arrhythmia, sometimes fatal, may occur, particularly in patients with sustained ventricular tachycardia or serious underlying heart disease.

• New or worsening congestive heart failure has been reported, particularly in patients with a history of cardiomyopathy, NYHA (New York Heart Association) functional class III or IV heart failure, or low ejection fraction.

• Closely monitor patients with a history of congestive heart failure or myocardial dysfunction.

• Decreased ejection fraction in individuals with heart failure, class 1C antiarrhythmic drugs may increase mortality risk.

• Cardiac conduction changes have been reported.

• Decreased ejection fraction in individuals with heart failure, class 1C antiarrhythmic drugs may increase mortality risk.

• Cardiac conduction changes have been reported.

• Rare cases of Torsade de Pointes-type arrhythmia have been reported.

• Use extreme caution in patients with sick sinus syndrome (bradycardia-tachycardia syndrome).

• Use caution in patients with permanent pacemakers or temporary pacing electrodes, as Flecainide may affect pacemaker thresholds.

• Do not initiate pacing in patients with poor thresholds or non-programmable pacemakers unless appropriate pacing rescue is available.

Endocrine and Metabolic Effects

• Electrolyte abnormalities (hypokalemia or hyperkalemia) may alter the effects of Flecainide; correct before initiating the drug.

Hepatic Effects

• Use is not advised for those with major hepatic impairment; assess risk or benefit before administration, monitor plasma levels, and titrate dose cautiously.

Special Populations

• Cardiac arrest and death in pediatric patients with structural heart disease have been reported; initiation in hospital and monitoring is recommended.

Contraindications:

Flecainide is contraindicated in the following conditions:

• In those who have had a cardiogenic shock.

• Known history of hypersensitivity to Flecainide or its components.

• Right bundle block with left hemiblock and without a pacemaker.

• Second or third-degree atrioventricular block without a pacemaker.

Drug Interactions:

The drug interactions of Flecainide are as follows:

• Imipramine.

• Inotuzumab ozogamicin.

• Isoflurane.

• Isradipine.

• Ivabradine.

• Ivosidenib.

• Ketoconazole.

• Lacosamide.

• Lapatinib.

• Lefamulin.

• Lenvatinib.

• Leuprolide.

• Levofloxacin.

• Lidocaine.

• Lidoflazine.

• Lofexidine.

• Lorcainide.

• Lumefantrine.

• Macimorelin.

• Mefloquine.

• Methadone.

• Metolazone.

• Metronidazole.

• Mifepristone.

• Mirtazapine.

• Mobocertinib.

• Moxifloxacin.

• Nafarelin.

• Nilotinib.

• Norfloxacin.

• Nortriptyline.

• Octreotide.

• Ofloxacin.

• Ombitasvir.

• Ondansetron.

• Osilodrostat.

• Osimertinib.

• Oxaliplatin.

• Ozanimod.

• Pacritinib.

• Paliperidone.

• Panobinostat.

• Paritaprevir.

• Pasireotide.

• Pazopanib.

• Peginterferon Alfa-2b.

• Pentamidine.

• Pimavanserin.

• Pirmenol.

• Pitolisant.

• Polythiazide.

• Ponesimod.

• Posaconazole.

• Prajmaline.

• Prilocaine.

• Probucol.

• Procainamide.

• Prochlorperazine.

• Promethazine.

• Propafenone.

• Protriptyline.

• Quetiapine.

• Quinidine.

• Ranolazine.

• Ribociclib.

• Risperidone.

• Selpercatinib.

• Sematilide.

• Sertindole.

• Sertraline.

• Sevoflurane.

• Simeprevir.

• Siponimod.

• Sodium Phosphate.

• Sodium Phosphate, Dibasic.

• Sodium Phosphate, Monobasic.

• Solifenacin.

• Sorafenib.

• Sotalol.

• Spiramycin.

• Sulfamethoxazole.

• Sulpiride.

• Sultopride.

• Sunitinib.

• Tacrolimus.

• Tedisamil.

• Telaprevir.

• Telavancin.

• Telithromycin.

• Tetrabenazine.

• Toremifene.

• Trazodone.

• Trichlormethiazide.

• Triclabendazole.

• Trifluoperazine.

• Trimethoprim.

• Trimipramine.

• Triptorelin.

• Vandetanib.

• Vardenafil.

• Vemurafenib.

• Venlafaxine.

• Vilanterol.

• Vinflunine.

• Voclosporin.

• Voriconazole.

• Zolmitriptan.

• Zotepine.

• Zuclopenthixol.

Other Specifications:

Flecainide in Pregnant Women:

There is only limited data available on its safety and efficacy. High dosages of flecainide have been proven in animal studies to cause fetal harm, but the risk to humans is not yet fully understood. Therefore, Flecainide should only be used during pregnancy If the mother's potential advantages outweigh the danger to the baby or fetus.

Flecainide in Lactating Women:

There is limited information available on the safety of Flecainide use during lactation. However, it is known that Flecainide is excreted in human milk. Therefore, women taking Flecainide should talk to their healthcare provider before breastfeeding.

Flecainide in Geriatrics:

Flecainide is eliminated more slowly from the body in the elderly than younger patients. Therefore, elderly patients may be more susceptible to the adverse effects of Flecainide.