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| Clinical data | |
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| Pronunciation | /flɛˈkeɪnaɪd/fleh-KAY-nyde |
| Trade names | Tambocor, others |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a608040 |
| Drug class | Ic antiarrhythmic[1] |
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| Pharmacokinetic data | |
| Bioavailability | 95% |
| Protein binding | 40% |
| Metabolism | CYP2D6 (limited) |
| Eliminationhalf-life | 20 hours (range 12–27 hours) |
| Excretion | Kidney |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.211.334 |
| Chemical and physical data | |
| Formula | C17H20F6N2O3 |
| Molar mass | 414.348 g·mol−1 |
| 3D model (JSmol) | |
| Chirality | Racemic mixture |
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Flecainide is a medication used to prevent and treatabnormally fast heart rates.[1] This includesventricular andsupraventricular tachycardias.[1] Its use is only recommended in those with dangerous arrhythmias or when significant symptoms cannot be managed with other treatments.[1] Its use does not decrease a person's risk of death.[1] It is takenby mouth orinjection into a vein.[1][3]
Common side effects include dizziness, problems seeing, shortness of breath, chest pain, and tiredness.[1] Serious side effects may includecardiac arrest,arrhythmias, andheart failure.[1] It may be used inpregnancy, but has not been well studied in this population.[3][4] Use is not recommended in those withstructural heart disease orischemic heart disease.[1] Flecainide is a class Icantiarrhythmic agent.[1] It works by decreasing the entry ofsodium in heart cells, causing prolongation of thecardiac action potential.[1]
Flecainide was approved for medical use in the United States in 1985.[1] It is available as ageneric medication.[3] In 2021, it was the 205th most commonly prescribed medication in the United States, with more than 2 million prescriptions.[5][6]
Flecainide is used in the treatment of many types ofsupraventricular tachycardias, includingAV nodal re-entrant tachycardia (AVNRT) andWolff-Parkinson-White syndrome (WPW).
It also has limited use in the treatment of certain forms ofventricular tachycardia (VT). In particular, flecainide has been useful in the treatment of ventricular tachycardias that are not in the setting of an acute ischemic event. It has use in the treatment of right ventricular outflow tract (RVOT) tachycardia[7] and in the suppression of arrhythmias inarrhythmogenic right ventricular dysplasia (ARVD).[8] Studies (notably theCardiac Arrhythmia Suppression Trial) have shown an increased mortality when flecainide is used to suppress ventricularextrasystoles in the setting of acute myocardial infarction.[9][10]
In individuals suspected of having theBrugada syndrome, the administration of flecainide may help reveal theECG findings that are characteristic of the disease process. This may help make the diagnosis of the disease in equivocal cases.[11]
Flecainide has been introduced into the treatment of arrhythmias in children.
In the long-term, flecainide seems to be safe in people with a healthy heart with no signs ofleft ventricular hypertrophy,ischemic heart disease, orheart failure.[12]
Results of a medical study known as theCardiac Arrhythmia Suppression Trial (CAST) demonstrated that patients with structural heart disease (such as a history of MI (heart attack), or left ventricular dysfunction) and also patients with ventricular arrhythmias, should not take this drug. The results were so significant that the trial was stopped early and preliminary results were published.[13]
The dose may need to be adjusted in certain clinical scenarios. As with all otherantiarrhythmic agents, there is a risk ofproarrhythmia associated with the use of flecainide. This risk is probably increased when flecainide is co-administered with other class Ic antiarrhythmics, such asencainide. The risk of proarrhythmia may also be increased byhypokalemia.[14] The risk of proarrhythmia is not necessarily associated with the length of time an individual is taking flecainide, and cases of late proarrhythmia have been reported.[15] Because of the role of both the liver and the kidneys in the elimination of flecainide, the dosing of flecainide may need to be adjusted in individuals who develop either liver failure orkidney failure.
Because of the negative inotropic effects of flecainide, it should be used with caution in individuals with depressedejection fraction, and may worsencongestive heart failure in these individuals. It should be avoided in people with ischaemic heart disease and the elderly.[16]
As with all class Iantiarrhythmic agents, flecainide increases the capture thresholds ofpacemakers.[17][18]
Due to the narrow therapeutic index of flecainide, physicians should be alert for signs of toxicity before life-threatening arrhythmias occur liketorsades de pointes. While the toxic effects of flecainide are closely related to the plasma levels of the drug,[19] it is unfeasible to check the plasma concentration in an individual on a regular basis.
Signs of flecainide toxicity include marked prolongation of the PR interval and widening of the QRS duration on the surface ECG. There may be signs and symptoms attributable to overtheart failure secondary to sudden decreasedmyocardial contractility.
Treatment of flecainide cardiac toxicity involves increasing the excretion of flecainide, blocking its effects in the heart, and (rarely) institution of cardiovascular support to avoid impending lethal arrhythmias. Modalities that have had success include administration of a beta-sympathomimetic agent,[19] and administration of a sodium load[19](often in the form ofhypertonicsodium bicarbonate). Placing the individual oncardiopulmonary bypass support may be necessary in order to temporarily remove the need for a beating heart and to increase blood flow to the liver.[20][21]
Flecainide has a very high affinity for lung tissue[22] and is associated with drug-inducedinterstitial lung disease.[23][24][25][26][27]
Flecainide has highbioavailability after an oral dose,[28] meaning that most of the drug that is ingested will enter the systemic blood stream. Peak serum concentrations can be seen 1 to 6 hours after ingestion of an oral dose. While the plasmahalf-life is about 20 hours, it is quite variable, and can range from 12 to 27 hours.[29] During oral loading with flecainide, a steady state equilibrium is typically achieved in 3 to 5 days.
The majority of flecainide is eliminated by thekidneys, with the remainder metabolized by thecytochrome P450 2D6 isoenzyme in the liver.[30] Therefore, alterations in renal function or urine pH will greatly affect the elimination of flecainide, as more is eliminated by the kidney than by the hepatic route.
Because of the dual elimination routes of flecainide and its tendency to decreasemyocardial contractility,[16] flecainide interacts with numerous pharmaceuticals and can potentiate the effects of other myocardial depressants and AV node blocking agents. In addition, flecainide can decrease the metabolism or elimination of many (but not all) agents that use thecytochrome P450 enzyme system.
A full list of drug interactions with flecainide can be obtained from the manufacturer. Some important drug interactions with flecainide include:[citation needed]
Flecainide intoxication is rare but serious due to the cardiogenic shock that it provokes. Its diagnosis can be difficult in the lack of contributing anamnestic elements. Clinical and paraclinical signs are not specific. Treatment is primarily symptomatic, which gives good results thanks to the hypertonic solution of sodium salts. Organ donation is possible in the case of braindead patients who had a flecainide intoxication.[31]
Flecainide works by blocking theNav1.5sodium channel in the heart, slowing the upstroke of thecardiac action potential.[32] This thereby slows conduction of the electrical impulse within the heart, i.e. it "reduces excitability". The greatest effect is on theHis-Purkinje system and ventricularmyocardium. The effect of flecainide on the ventricular myocardium causes decreased contractility of the muscle, which leads to a decrease in the ejection fraction.
The effect of flecainide on thesodium channels of the heart increases as the heart rate increases; This is known as use-dependence and is why that flecainide is useful to break atachyarrhythmia.[33]
Flecainide also inhibitsryanodine receptor 2 (RyR2),[34] a major regulator ofsarcoplasmic release of stored calcium ions. It can reducecalcium sparks and thus arrhythmogenic calcium waves in the heart.[35] While Flecainide therapy has been shown to suppress ventricular arrhythmias in patients withcatecholaminergic polymorphic ventricular tachycardia (CPVT) and mouse models of this disease, the relative contribution from the inhibition of sodium channels and of RyR2 in this effect on CPVT is unclear.[36]
Flecainide is sold under the trade name Tambocor (manufactured by3M pharmaceuticals). Flecainide went off-patent in February 2004. In addition to being marketed as Tambocor, it is available in generic version and under the brand names Almarytm, Apocard, Ecrinal, and Flécaine.
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