Tambocor

Anti-arrhythmics, Class I-C

Oral Administration

Food decreases the rate, but not the extent of absorption.
Information regarding monitoring of serum flecainide concentrations is provided in the dosage section.

Severe

AV block / Early / 0-40.0
visual impairment / Early / 15.9-15.9
arrhythmia exacerbation / Early / 1.0-13.0
heart failure / Delayed / 0.4-9.1
bradycardia / Rapid / 1.2-1.2
torsade de pointes / Rapid / 0-1.0
hepatic failure / Delayed / 0-1.0
bronchospasm / Rapid / 0-1.0
exfoliative dermatitis / Delayed / 0-1.0
ventricular fibrillation / Early / Incidence not known
ventricular tachycardia / Early / Incidence not known

Moderate

dyspnea / Early / 10.3-10.3
palpitations / Early / 6.1-6.1
chest pain (unspecified) / Early / 5.4-5.4
constipation / Delayed / 4.4-4.4
edema / Delayed / 3.5-3.5
sinus tachycardia / Rapid / 0-3.0
depression / Delayed / 0-3.0
ataxia / Delayed / 0-3.0
paresis / Delayed / 0-3.0
hypertension / Early / 0-1.0
angina / Early / 0-1.0
hypotension / Rapid / 0-1.0
cholestasis / Delayed / 0-1.0
jaundice / Delayed / 0-1.0
elevated hepatic enzymes / Delayed / 0-1.0
thrombocytopenia / Delayed / 0-1.0
nystagmus / Delayed / 0-1.0
amnesia / Delayed / 0-1.0
leukopenia / Delayed / 0-1.0
urinary retention / Early / 0-1.0
impotence (erectile dysfunction) / Delayed / 0-1.0
photophobia / Early / 0-1.0
euphoria / Early / 0-1.0
confusion / Early / 0-1.0
pneumonitis / Delayed / 0-1.0
QT prolongation / Rapid / Incidence not known

Mild

dizziness / Early / 18.9-18.9
headache / Early / 9.6-9.6
nausea / Early / 8.9-8.9
fatigue / Early / 7.7-7.7
asthenia / Delayed / 4.9-4.9
tremor / Early / 4.7-4.7
abdominal pain / Early / 3.3-3.3
vomiting / Early / 0-3.0
flushing / Rapid / 0-3.0
vertigo / Early / 0-3.0
hypoesthesia / Delayed / 0-3.0
drowsiness / Early / 0-3.0
insomnia / Early / 0-3.0
syncope / Early / 0-3.0
tinnitus / Delayed / 0-3.0
anxiety / Delayed / 0-3.0
rash / Early / 0-3.0
diaphoresis / Early / 0-3.0
paresthesias / Delayed / 0-3.0
diplopia / Early / 0-3.0
anorexia / Delayed / 0-3.0
diarrhea / Early / 0-3.0
fever / Early / 0-3.0
dyspepsia / Early / 0-3.0
malaise / Early / 0-3.0
urticaria / Rapid / 0-1.0
dysgeusia / Early / 0-1.0
weakness / Early / 0-1.0
flatulence / Early / 0-1.0
ocular pain / Early / 0-1.0
myalgia / Early / 0-1.0
pruritus / Rapid / 0-1.0
arthralgia / Delayed / 0-1.0
polyuria / Early / 0-1.0
ocular irritation / Rapid / 0-1.0
alopecia / Delayed / 0-1.0
xerostomia / Early / 0-1.0
libido decrease / Delayed / 0-1.0
nightmares / Early / 0-1.0

Atrial fibrillation, AV block, bundle-branch block, cardiac arrhythmias, cardiac disease, sick sinus syndrome, ventricular arrhythmias

In general, use flecainide cautiously in patients with certain types of cardiac disease. Flecainide has proarrhythmic properties and can induce or worsen cardiac arrhythmias. Reduce the dose or discontinue treatment in patients who exhibit a prolonged QRS (more than 180 milliseconds) or PR (more than 300 milliseconds) interval. Flecainide is contraindicated for use in patients who have preexisting second- or third-degree AV block, or bifascicular or trifascicular bundle-branch block, unless a pacemaker is in place that could sustain cardiac rhythm in the event of complete heart block. In general, AV block may increase the risk of prolonging the QT interval. Although its effects on normal sinus node function are negligible, flecainide should be used only with extreme caution in patients with preexisting sick sinus syndrome or significant conduction delay because it may cause profound clinically low heart rate, sinus pause, or sinus arrest. Flecainide can increase endocardial pacing thresholds, so it is not recommended for use in patients with nonprogrammable pacemakers unless pacing rescue is available. The effects on pacing threshold are reversible following cessation of therapy. Because flecainide has been shown to worsen ventricular tachycardia in some patients, it should be used cautiously, if at all, in patients with these cardiac arrhythmias. Use in chronic atrial fibrillation has not been adequately studied and is not recommended by the manufacturer due to the reported risk of ventricular arrhythmias (about 10%) in this population.

Apheresis, bradycardia, cardiogenic shock, cardiomyopathy, celiac disease, electrolyte imbalance, females, fever, heart failure, human immunodeficiency virus (HIV) infection, hyperparathyroidism, hypocalcemia, hypokalemia, hypomagnesemia, hypothermia, hypothyroidism, long QT syndrome, mortality, myocardial infarction, pheochromocytoma, QT prolongation, rheumatoid arthritis, sickle cell disease, sleep deprivation, stroke, systemic lupus erythematosus (SLE), ventricular dysfunction

Flecainide is contraindicated for use in patients with cardiogenic shock. Due to its potential negative inotropic effects and high risk of proarrhythmias, avoid use in patients with congestive heart failure (CHF), acute myocardial infarction, or a history of myocardial infarction with ventricular dysfunction (LVEF less than 30%). Serum drug concentration monitoring is suggested for patients with CHF. The CAST trial, a randomized double-blind study in patients with asymptomatic non-life-threatening ventricular arrhythmias, demonstrated an excessive rate of mortality or non-fatal cardiac arrest in patients treated with encainide or flecainide (7.7%) compared to placebo (3%). The enrolled patients had a history of myocardial infarction (more than 6 days but less than 2 years); the average duration of antiarrhythmic therapy was 10 months. The applicability of the CAST results to other populations (e.g., those without recent myocardial infarction) or other antiarrhythmics is uncertain. It is prudent to consider Class 1C antiarrhythmics, including flecainide, to have significant risks in patients with structural heart disease. QT prolongation and torsade de pointes have occurred during therapy and flecainide should be avoided, when possible, in patients with congenital long QT syndrome or acquired QT prolongation syndromes or in patients with a history of torsade de pointes. Use flecainide with caution in patients with conditions that may increase the risk of QT prolongation including bradycardia, AV block, stress-related cardiomyopathy, stroke, or in patients receiving medications known to prolong the QT interval. Females, people 65 years and older, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation. Use flecainide with caution in patients with conditions that may increase the risk of QT prolongation including hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to cause electrolyte imbalances; correct any electrolyte imbalance before initiating therapy with any antiarrhythmic agent.

Tambocor

Rx

Oral Class IC antiarrhythmic; used to treat documented life-threatening ventricular arrhythmias; should be avoided in LVD or asymptomatic post-MI patients; also approved for prevention of PSVT; not considered first-line agent for suppression of ventricular arrhythmias due to risk of proarrhythmias (CAST trial).

For the prevention of life-threatening ventricular arrhythmias, such as sustained ventricular tachycardia (i.e., ventricular tachycardia prophylaxis). Oral dosage Adults

100 mg PO every 12 hours, initially. May increase the dose by 50 mg/dose every 4 days until efficacy is achieved. Usual dose: 150 mg PO every 12 hours. Max: 400 mg/day.

Infants, Children, and Adolescents 7 months to 17 years

100 mg/m2/day PO divided in 2 to 3 doses, initially. May increase the dose every 4 days until efficacy is achieved. Max: 200 mg/m2/day. Alternatively, 1 to 6 mg/kg/day PO divided in 2 to 3 doses and Max: 8 mg/kg/day.

Infants 1 to 6 months

50 mg/m2/day PO divided in 2 to 3 doses, initially. May increase the dose every 4 days until efficacy is achieved. Max: 200 mg/m2/day. Alternatively, 1 to 6 mg/kg/day PO divided in 2 to 3 doses and Max: 8 mg/kg/day.

For the conversion to† and/or prevention of paroxysmal atrial fibrillation and/or atrial flutter and paroxysmal supraventricular tachycardia (PSVT) prophylaxis in patients with AV reentry tachycardia and other supraventricular arrhythmias associated with disabling symptoms and without structural heart disease. For the pharmacological conversion† of atrial fibrillation or atrial flutter. Oral dosage Adults

200 to 300 mg PO as a single dose. Guidelines recommend flecainide for pharmacological cardioversion of atrial fibrillation or atrial flutter, if no contraindications exist. Flecainide is also recommended in combination with a beta blocker or nondihydropyridine calcium channel blocker to terminate atrial fibrillation out of the hospital once observed to be safe in a monitored setting. Administer beta blocker or nondihydropyridine calcium channel blocker 30 minutes or more before flecainide.

For the transplacental treatment of fetal supraventricular tachyarrhythmias†. Oral dosage Pregnant Adults

200 to 450 mg/day PO divided in 3 doses.

Oral dosage Adults

50 mg PO every 12 hours, initially. May increase the dose by 50 mg/dose every 4 days until efficacy is achieved. Max: 300 mg/day. Guidelines recommend flecainide 50 to 200 mg PO every 12 hours to maintain sinus rhythm in persons with atrial fibrillation without structural heart disease.

Infants, Children, and Adolescents 7 months to 17 years

100 mg/m2/day PO divided in 2 to 3 doses, initially. May increase the dose every 4 days until efficacy is achieved. Max: 200 mg/m2/day. Alternatively, 1 to 6 mg/kg/day PO in 2 to 3 divided doses and Max: 8 mg/kg/day.

Infants 1 to 6 months

50 mg/m2/day PO divided in 2 to 3 doses, initially. May increase the dose every 4 days until efficacy is achieved. Max: 200 mg/m2/day. Alternatively, 1 to 6 mg/kg/day PO divided in 2 to 3 doses and Max: 8 mg/kg/day.

Neonates

50 mg/m2/day PO divided in 2 to 3, initially. May increase the dose every 4 days until efficacy is achieved. Max: 200 mg/m2/day. Alternatively, 2 mg/kg/day PO in 2 divided doses and adjusted upward based on clinical response and weight gain was used in 20 neonates (mean postnatal age: 11.5 +/- 11.1 days, mean gestational age: 36.8 +/- 3 weeks) with SVT. A mean dose of 3.35 +/- 1.35 mg/kg/day PO was successful in controlling arrhythmias in 17 (85%) of the neonates. A maximum dose of 8 mg/kg/day has been recommended.

For the treatment of premature ventricular contractions (PVCs)†. Oral dosage Adults

50 to 200 mg PO every 12 hours. Guidelines suggest flecainide in the treatment of PVCs in the absence of structural heart disease; treatment with class I sodium channel-blocking medications is associated with an increased risk of death in the post-myocardial infarction population.

†Indicates off-label use

Hepatic Impairment

Use in patients with hepatic impairment only if benefits clearly outweigh the risks due to slower flecainide elimination. Frequent and early plasma drug monitoring is required for patients with severe hepatic disease. Adjust dosage at intervals of more than 4 days, since steady-state conditions may take longer to achieve in these patients.

Renal Impairment

Adult patients:
CrCl > 35 mL/min: No dosage adjustment is required.
CrCl <= 35 mL/min: Initially, 100 mg PO once daily or 50 mg PO twice daily. Frequent plasma concentration monitoring is required. Adjust dosage at intervals of more than 4 days, since steady-state conditions may take longer to achieve in these patients.
 
Pediatric patients: Specific recommendations for dosage adjustment in pediatric patients with renal impairment are not available.
 
Intermittent hemodialysis
See dosage for patients with CrCl <= 35 mL/min. No dosage supplement is needed for hemodialysis. Hemodialysis removes about 1% of an oral dose of unchanged flecainide.

Abarelix: (Major) Since abarelix can cause QT prolongation, abarelix should be used cautiously, if at all, with other drugs that are associated with QT prolongation, such as flecainide.
Abiraterone: (Moderate) Monitor for an increase in flecainide-related adverse reactions, including QT prolongation, if coadministration with abiraterone is necessary. Flecainide is a CYP2D6 substrate and abiraterone is a moderate CYP2D6 inhibitor. Plasma concentrations of flecainide may increase, especially in extensive CYP2D6 metabolizers.
Acebutolol: (Moderate) Pharmacologically, beta-blockers, like acebutolol, cause AV nodal conduction depression and additive effects are possible when used in combination with flecainide. When used together, AV block can occur. During flecainide clinical trials, increased adverse events have not been reported in patients receiving combination therapy with beta-blockers and flecainide. However, patients should be monitored closely and the dose should be adjusted according to clinical response.
Adagrasib: (Major) Avoid concomitant use of adagrasib and flecainide due to the potential for increased flecainide exposure and additive risk for QT/QTc prolongation and torsade de pointes (TdP). If use is necessary, monitor for flecainide-related adverse effects and consider taking additional steps to minimize the risk for QT prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Flecainide is a CYP2D6 substrate, adagrasib is a moderate CYP2D6 inhibitor, and both medications have been associated with QT interval prolongation.
Alfuzosin: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering alfuzosin with flecainide. Based on electrophysiology studies performed by the manufacturer, alfuzosin has a slight QT prolonging effect. The QT prolongation appeared less with alfuzosin 10 mg than with 40 mg. Flecainide, a Class IC antiarrhythmic, is also associated with a possible risk for QT prolongation and/or TdP; although, the increase in QT interval is largely due to prolongation of the QRS interval. Causality for TdP has not been established for flecainide.
Alkalinizing Agents: (Moderate) Urinary alkalinization can decrease the renal clearance of flecainide, resulting in an increased elimination half-life and AUC for flecainide.
Amiodarone: (Major) Flecainide has been used in combination with amiodarone in specialized settings to treat refractory arrhythmias. Combination therapy with Class III and Class IC antiarrhythmics has been reported to increase the risk of proarrhythmias. Close monitoring of therapeutic response is warranted for patients receiving combination therapy, including serum drug concentration monitoring. Amiodarone inhibits the hepatic metabolism of flecainide via CYP2D6 inhibition. When amiodarone is added to flecainide therapy, plasma flecainide levels may increase two-fold or more in some patients, if flecainide dosage is not reduced. When flecainide is given in the presence of amiodarone, reduce the usual flecainide dose by 50% and monitor the patient closely for adverse effects. Serum drug concentration monitoring is strongly recommended to guide dosage with such combination therapy. Coadministration of amiodarone with drugs that prolong the QT interval should be done with a careful assessment of risks versus benefits. Although rare, cases of QT prolongation and torsade de pointes (TdP) have been reported during flecainide therapy; causality has not been established. Based on theoretical considerations, the manufacturer recommends allowing at least 2 to 4 plasma half-lives to elapse following flecainide discontinuation before switching to another antiarrhythmic drug.
Amisulpride: (Major) Monitor ECGs for QT prolongation when amisulpride is administered with flecainide. Amisulpride causes dose- and concentration- dependent QT prolongation. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs that have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Amlodipine; Celecoxib: (Moderate) Monitor for an increase in flecainide-related adverse reactions, including QT prolongation, if coadministration with celecoxib is necessary. Flecainide is a CYP2D6 substrate and celecoxib is a weak CYP2D6 inhibitor. Plasma concentrations of flecainide may increase, especially in extensive CYP2D6 metabolizers.
Amoxapine: (Moderate) CYP2D6 substrates including flecainide may compete with amoxapine for the same metabolic pathway.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering clarithromycin with flecainide. Administration of clarithromycin has resulted in prolongation of the QT interval and TdP. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Anagrelide: (Major) Torsades de pointes (TdP) and ventricular tachycardia have been reported during post-marketing use of anagrelide. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with anagrelide include flecainide.
Apomorphine: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering flecainide with apomorphine. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Aripiprazole: (Major) Concomitant use of aripiprazole and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Arsenic Trioxide: (Major) Concurrent use of flecainide and arsenic trioxide should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If possible, flecainide should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. TdP and complete atrioventricular block have been reported. Flecainide, a Class IC antiarrhythmic, is also associated with a possible risk for QT prolongation and/or TdP; although, the increase in QT interval is largely due to prolongation of the QRS interval. Causality for TdP has not been established for flecainide.
Artemether; Lumefantrine: (Major) Artemether; lumefantrine is an inhibitor and flecainide is a substrate of the CYP2D6 isoenzyme; therefore, coadministration may lead to increased flecainide concentrations. Furthermore, although there are no studies examining the effects of artemether; lumefantrine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. Concomitant use of artemether; lumefantrine with drugs that may prolong the QT interval, such as flecainide should be avoided. Consider ECG monitoring if flecainide must be used with or after artemether; lumefantrine treatment. (Major) Concurrent use of flecainide and artemether; lumefantrine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Consider ECG monitoring if flecainide must be used with or after artemether; lumefantrine treatment. Artemether; lumefantrine is associated with a possible risk for QT prolongation and TdP. Flecainide, a Class IC antiarrhythmic, is also associated with a possible risk for QT prolongation and/or TdP; although, the increase in QT interval is largely due to prolongation of the QRS interval. Causality for TdP has not been established for flecainide. Additionally, artemether; lumefantrine is an inhibitor and flecainide is a substrate of the CYP2D6 isoenzyme; therefore, coadministration may lead to increased flecainide concentrations.
Asenapine: (Major) Asenapine has been associated with QT prolongation. According to the manufacturer, asenapine should not be used with other agents also known to have this effect (e.g., flecainide). Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsades de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Atazanavir; Cobicistat: (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of flecainide with cobicistat. Flecainide is a substrate for CYP2D6; cobicistat is an inhibitor of this enzyme. Concurrent use may result in elevated flecainde plasma concentration.
Atenolol: (Moderate) Pharmacologically, beta-blockers, like atenolol, cause AV nodal conduction depression and additive effects are possible when used in combination with flecainide. When used together, AV block can occur. During flecainide clinical trials, increased adverse events have not been reported in patients receiving combination therapy with beta-blockers and flecainide. However, patients should be monitored closely and the dose should be adjusted according to clinical response.
Atenolol; Chlorthalidone: (Moderate) Pharmacologically, beta-blockers, like atenolol, cause AV nodal conduction depression and additive effects are possible when used in combination with flecainide. When used together, AV block can occur. During flecainide clinical trials, increased adverse events have not been reported in patients receiving combination therapy with beta-blockers and flecainide. However, patients should be monitored closely and the dose should be adjusted according to clinical response.
Atomoxetine: (Major) Concomitant use of atomoxetine and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Azithromycin: (Major) Concomitant use of azithromycin and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bedaquiline: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering bedaquiline with flecainide. Bedaquiline has been reported to prolong the QT interval. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy. Flecainide, a Class IC antiarrhythmic, is also associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Berotralstat: (Moderate) Monitor for an increase in flecainide-related adverse reactions, including QT prolongation, if coadministration with berotralstat is necessary. Flecainide is a CYP2D6 substrate and berotralstat is a moderate CYP2D6 inhibitor. Plasma concentrations of flecainide may increase, especially in extensive CYP2D6 metabolizers.
Betaxolol: (Moderate) Pharmacologically, beta-blockers, like betaxolol, cause AV nodal conduction depression and additive effects are possible when used in combination with flecainide. When used together, AV block can occur. During flecainide clinical trials, increased adverse events have not been reported in patients receiving combination therapy with beta-blockers and flecainide. However, patients should be monitored closely and the dose should be adjusted according to clinical response.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bisoprolol: (Moderate) Pharmacologically, beta-blockers, like bisoprolol, cause AV nodal conduction depression and additive effects are possible when used in combination with flecainide. When used together, AV block can occur. During flecainide clinical trials, increased adverse events have not been reported in patients receiving combination therapy with beta-blockers and flecainide. However, patients should be monitored closely and the dose should be adjusted according to clinical response.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Pharmacologically, beta-blockers, like bisoprolol, cause AV nodal conduction depression and additive effects are possible when used in combination with flecainide. When used together, AV block can occur. During flecainide clinical trials, increased adverse events have not been reported in patients receiving combination therapy with beta-blockers and flecainide. However, patients should be monitored closely and the dose should be adjusted according to clinical response.
Blinatumomab: (Moderate) No drug interaction studies have been performed with blinatumomab. The drug may cause a transient release of cytokines leading to an inhibition of CYP450 enzymes. The interaction risk with CYP450 substrates is likely the highest during the first 9 days of the first cycle and the first 2 days of the second cycle. Monitor patients receiving concurrent CYP450 substrates that have a narrow therapeutic index (NTI) such as flecainide. The dose of the concomitant drug may need to be adjusted.
Brimonidine; Timolol: (Moderate) Monitor heart rate during concomitant flecainide and timolol use due to risk for additive negative inotropic effects.
Bupivacaine; Lidocaine: (Major) Although causality for torsades de pointes has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation, such as local anesthetics, may have an increased risk of developing proarrhythmias. Use with caution.
Buprenorphine: (Major) Concomitant use of flecainide and buprenorphine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Buprenorphine; Naloxone: (Major) Concomitant use of flecainide and buprenorphine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bupropion: (Moderate) Monitor for an increase in flecainide-related adverse reactions, including QT prolongation, if coadministration with bupropion is necessary. Flecainide is a CYP2D6 substrate and bupropion is a strong CYP2D6 inhibitor. Plasma concentrations of flecainide may increase, especially in extensive CYP2D6 metabolizers.
Bupropion; Naltrexone: (Moderate) Monitor for an increase in flecainide-related adverse reactions, including QT prolongation, if coadministration with bupropion is necessary. Flecainide is a CYP2D6 substrate and bupropion is a strong CYP2D6 inhibitor. Plasma concentrations of flecainide may increase, especially in extensive CYP2D6 metabolizers.
Cabotegravir; Rilpivirine: (Major) Concomitant use of rilpivirine and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Carbonic anhydrase inhibitors: (Moderate) Carbonic anhydrase inhibitors can decrease the urinary excretion and enhance the clinical effects of flecainide. Carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized drug available for renal tubular reabsorption into the systemic circulation.
Cardiac glycosides: (Moderate) Monitor for signs and symptoms of digoxin toxicity during concomitant flecainide use. Small increases in plasma digoxin concentrations are seen during coadministration with flecainide; during administration of multiple oral doses of flecainide to healthy persons stabilized on a maintenance dose of digoxin, a 13% to 19% increase in plasma digoxin concentrations occurred at 6 hours postdose.
Carvedilol: (Moderate) Pharmacologically, beta-blockers, like carvedilol, cause AV nodal conduction depression and additive effects are possible when used in combination with flecainide. When used together, AV block can occur. During flecainide clinical trials, increased adverse events have not been reported in patients receiving combination therapy with beta-blockers and flecainide. However, patients should be monitored closely and the dose should be adjusted according to clinical response.
Celecoxib: (Moderate) Monitor for an increase in flecainide-related adverse reactions, including QT prolongation, if coadministration with celecoxib is necessary. Flecainide is a CYP2D6 substrate and celecoxib is a weak CYP2D6 inhibitor. Plasma concentrations of flecainide may increase, especially in extensive CYP2D6 metabolizers.
Celecoxib; Tramadol: (Moderate) Monitor for an increase in flecainide-related adverse reactions, including QT prolongation, if coadministration with celecoxib is necessary. Flecainide is a CYP2D6 substrate and celecoxib is a weak CYP2D6 inhibitor. Plasma concentrations of flecainide may increase, especially in extensive CYP2D6 metabolizers.
Ceritinib: (Major) Avoid coadministration of ceritinib with flecainide if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsade de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Chloroquine: (Major) Avoid coadministration of chloroquine with flecainide due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs that have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Chlorpromazine: (Major) Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsades de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. In addition, flecainide is significantly metabolized by CYP2D6 isoenzymes. The coadministration of flecainide with drugs that are CYP2D6 inhibitors may result in increased plasma concentrations of flecainide and an increased risk of QT prolongation. Chlorpromazine prolongs the QT interval and is also a CYP2D6 inhibitor and should be used cautiously with flecainide.
Cimetidine: (Moderate) Monitor for an increase in flecainide-related adverse reactions, including QT prolongation, if coadministration with cimetidine is necessary. Flecainide is a CYP2D6 substrate and cimetidine is a weak CYP2D6 inhibitor. Plasma concentrations of flecainide may increase, especially in extensive CYP2D6 metabolizers.
Cinacalcet: (Moderate) Monitor for an increase in flecainide-related adverse reactions, including QT prolongation, if coadministration with cinacalcet is necessary. Flecainide is a CYP2D6 substrate and cinacalcet is a moderate CYP2D6 inhibitor. Plasma concentrations of flecainide may increase, especially in extensive CYP2D6 metabolizers.
Ciprofloxacin: (Major) Concomitant use of ciprofloxacin and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Cisapride: (Contraindicated) Avoid concomitant use of flecainide and cisapride due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Citalopram: (Major) Concomitant use of flecainide and citalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Concomitant use may also increase the exposure of flecainide, further increasing the risk of adverse effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Flecainide is a CYP2D6 substrate and citalopram is a weak CYP2D6 inhibitor.
Citric Acid; Potassium Citrate; Sodium Citrate: (Moderate) Urinary alkalinization can decrease the renal clearance of flecainide, resulting in an increased elimination half-life and AUC for flecainide.
Clarithromycin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering clarithromycin with flecainide. Administration of clarithromycin has resulted in prolongation of the QT interval and TdP. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Clobazam: (Moderate) A dosage reduction of CYP2D6 substrates, such as flecainide, may be necessary during co-administration of clobazam. Limited in vivo data suggest that clobazam is an inhibitor of CYP2D6. If these agents are used in combination, it is advisable to monitor the patient for flecainide-related adverse reactions.
Clofazimine: (Major) Concomitant use of clofazimine and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Clozapine: (Major) Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. The manufacturer of clozapine recommends caution during concurrent use with medications known to cause QT prolongation. Flecainide should be used cautiously and with close monitoring with clozapine. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsades de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Cobicistat: (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of flecainide with cobicistat. Flecainide is a substrate for CYP2D6; cobicistat is an inhibitor of this enzyme. Concurrent use may result in elevated flecainde plasma concentration.
Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of promethazine and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Codeine; Promethazine: (Major) Concomitant use of promethazine and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Colesevelam: (Moderate) Colesevelam may decrease the bioavailability of flecainide if coadministered. To minimize potential for interactions, consider administering oral antiarrhythmics such as flecainide at least 1 hour before or at least 4 hours after colesevelam.
Crizotinib: (Major) Avoid coadministration of crizotinib with flecainide due to the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsade de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs that have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Dacomitinib: (Moderate) Monitor for increased toxicity of flecainide if coadministered with dacomitinib. Coadministration may increase serum concentrations of flecainide. Flecainide is a CYP2D6 substrate; dacomitinib is a strong CYP2D6 inhibitor.
Darifenacin: (Moderate) Caution should be exercised when darifenacin is used in combination with medications that are predominantly metabolized by CYP2D6 with narrow therapeutic windows, such as flecainide, as the serum concentrations of such drugs could be greatly increased in the presence of darifenacin.
Darunavir: (Major) Coadministration of darunavir with flecainide should be done with extreme caution. Therapeutic monitoring of antiarrhythmic concentrations is recommended. Darunavir is an inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme should be expected with concurrent use.
Darunavir; Cobicistat: (Major) Coadministration of darunavir with flecainide should be done with extreme caution. Therapeutic monitoring of antiarrhythmic concentrations is recommended. Darunavir is an inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme should be expected with concurrent use. (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of flecainide with cobicistat. Flecainide is a substrate for CYP2D6; cobicistat is an inhibitor of this enzyme. Concurrent use may result in elevated flecainde plasma concentration.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Coadministration of darunavir with flecainide should be done with extreme caution. Therapeutic monitoring of antiarrhythmic concentrations is recommended. Darunavir is an inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme should be expected with concurrent use. (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of flecainide with cobicistat. Flecainide is a substrate for CYP2D6; cobicistat is an inhibitor of this enzyme. Concurrent use may result in elevated flecainde plasma concentration.
Dasatinib: (Major) Dasatinib should be used cautiously and with close monitoring with flecainide. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsades de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias. In vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval). Cautious dasatinib administration is recommended to patients who have or may develop QT prolongation such as patients taking drugs that lead to QT prolongation.
Degarelix: (Major) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents like flecainide. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsade de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs that have the potential for QT prolongation may have an increased risk of developing proarrhythmias. Androgen deprivation therapy (i.e., degarelix) may also prolong the QT/QTc interval.
Delavirdine: (Contraindicated) Delavirdine inhibits CYP2D6 and may increase concentrations of other drugs metabolized by this enzyme, such as flecainide. Caution is recommended when administering these drugs together, as flecainide exhibits a narrow therapeutic range and large increases in serum concentrations may be associated with severe adverse reactions.
Deutetrabenazine: (Major) Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsade de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range.
Dexmedetomidine: (Major) Concomitant use of dexmedetomidine and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Dextromethorphan; Bupropion: (Moderate) Monitor for an increase in flecainide-related adverse reactions, including QT prolongation, if coadministration with bupropion is necessary. Flecainide is a CYP2D6 substrate and bupropion is a strong CYP2D6 inhibitor. Plasma concentrations of flecainide may increase, especially in extensive CYP2D6 metabolizers.
Dextromethorphan; Quinidine: (Contraindicated) Class IC antiarrhythmic agents, such as flecainide, have proarrhythmic properties, and may have additive electrophysiologic effects with other Class I agents such as quinidine. In addition, quinidine should be considered contraindicated with flecainide. Quinidine and flecainide are associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; therefore, the effects on the QT interval may be increased during concurrent use of quinidine with flecainide or propafenone.
Diltiazem: (Moderate) Limit use of flecainide and diltiazem when possible, and do not exceed maximum daily doses. Coadministration of flecainide with diltiazem increases the risk of bradycardia, AV block, and hypotension.
Disopyramide: (Major) The effects of concomitant administration of flecainide with other antiarrhythmics can be synergistic, additive, or antagonistic, and adverse cardiac effects can be additive. There has been little experience with the coadministration of flecainide with Class IA antiarrhythmics. Based on drug pharmacology, additive Class I electrophysiologic effects may be expected with potential for increased risk of proarrhythmias. Flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Rare cases of QT prolongation and torsades de pointes (TdP) have been reported during flecainide therapy. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias. Class IA antiarrhythmics are associated with a substantial risk for QT prolongation and torsades de pointes (TdP). In addition, flecainide should not be coadministered with disopyramide or quinidine (including dextromethorphan; quinidine) due to the potential for additive negative inotropic effects, unless the benefits of combined therapy outweigh the risks. Quinidine, a CYP2D6 inhibitor may increase the plasma concentrations of flecainide, especially in patients who are extensive metabolizers. Based on theoretical considerations, the manufacturer recommends allowing at least 2-4 plasma half-lives to elapse following flecainide discontinuation before switching to another antiarrhythmic drug. In patients for whom withdrawal of a prior antiarrhythmic drug is likely to produce life-threatening arrhythmias, the physician should consider hospitalizing the patient.
Dofetilide: (Major) Coadministration of dofetilide and flecainide is not recommended as concurrent use may increase the risk of QT prolongation. Class I antiarrhythmic agents, such as flecainide, should be withheld for at least 3 half-lives prior to initiating dofetilide therapy. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs that have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Dolasetron: (Major) Dolasetron should be used cautiously and with close monitoring with flecainide. Dolasetron has been associated with a dose-dependant prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Dolasetron injection is contraindicated for use for the prevention of chemotherapy-induced nausea and vomiting because the risk of QT prolongation is higher with the doses used for this indication; when the injection is used at lower doses (i.e., those approved for post-operative nausea and vomiting) or when the oral formulation is used, the risk of QT prolongation is lower and caution is advised. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsades de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Dolutegravir; Rilpivirine: (Major) Concomitant use of rilpivirine and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Donepezil: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with donepezil include flecainide.
Donepezil; Memantine: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with donepezil include flecainide.
Dorzolamide; Timolol: (Moderate) Monitor heart rate during concomitant flecainide and timolol use due to risk for additive negative inotropic effects.
Dronedarone: (Contraindicated) Avoid concomitant use of flecainide and dronedarone due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Droperidol: (Major) Droperidol should be used cautiously and with close monitoring with flecainide. Droperidol administration is associated with an established risk for QT prolongation and torsades de pointes (TdP). In December 2001, the FDA issued a black box warning regarding the use of droperidol and its association with QT prolongation and potential for cardiac arrhythmias based on post-marketing surveillance data. According to the revised 2001 labeling for droperidol, any drug known to have potential to prolong the QT interval should not be coadministered with droperidol. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsades de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Efavirenz: (Major) Coadministration of efavirenz and flecainide may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs that have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of efavirenz and flecainide may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs that have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of efavirenz and flecainide may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs that have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Eliglustat: (Major) Coadministration of flecainide and eliglustat may result in increased plasma concentrations of flecainide and an increased risk of QT prolongation. If concomitant use is necessary, monitor therapeutic flecainide concentrations as indicated; the dosage of flecainide may need to be reduced. Flecainide is a CYP2D6 substrate associated with a risk for QT prolongation and/or torsade de pointes (TdP). Eliglustat is a CYP2D6 inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Coadministration may result in additive effects on the QT interval, further increasing the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias).
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of flecainide with cobicistat. Flecainide is a substrate for CYP2D6; cobicistat is an inhibitor of this enzyme. Concurrent use may result in elevated flecainde plasma concentration.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of flecainide with cobicistat. Flecainide is a substrate for CYP2D6; cobicistat is an inhibitor of this enzyme. Concurrent use may result in elevated flecainde plasma concentration.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Concomitant use of rilpivirine and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Major) Concomitant use of rilpivirine and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Encorafenib: (Major) Avoid coadministration of encorafenib and flecainide due to QT prolongation. If concurrent use cannot be avoided, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib is associated with dose-dependent prolongation of the QT interval. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsade de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs that have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Entrectinib: (Major) Avoid coadministration of entrectinib with flecainide due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsade de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs that have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Eribulin: (Major) Flecainide should be used cautiously and with close monitoring with eribulin. Eribulin has been associated with QT prolongation. If eribulin and flecainide must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsades de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Erythromycin: (Major) Concurrent use of flecainide and erythromycin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias. Erythromycin administration is associated with QT prolongation and TdP. In addition, erythromycin may theoretically increase plasma concentrations of flecainide via inhibition of CYP3A4. Higher antiarrhythmic plasma concentrations increases the potential risk of QT prolongation, TdP or other proarrhythmias.
Escitalopram: (Major) Concomitant use of escitalopram and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Concomitant use may also increase the exposure of flecainide, further increasing the risk of adverse effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Flecainide is a CYP2D6 substrate and escitalopram is a moderate CYP2D6 inhibitor.
Esmolol: (Moderate) Pharmacologically, beta-blockers, like esmolol, cause AV nodal conduction depression and additive effects are possible when used in combination with flecainide. When used together, AV block can occur. During flecainide clinical trials, increased adverse events have not been reported in patients receiving combination therapy with beta-blockers and flecainide. However, patients should be monitored closely and the dose should be adjusted according to clinical response.
Etravirine: (Major) Flecainide concentrations may be decreased when coadministered with etravirine. Coadminister these drugs with caution and monitor flecainide concentrations when possible.
Everolimus: (Moderate) Monitor for an increase in flecainide-related adverse reactions, including QT prolongation, if coadministration with everolimus is necessary. Flecainide is a CYP2D6 substrate and everolimus is a CYP2D6 inhibitor; plasma concentrations of flecainide may increase, especially in extensive CYP2D6 metabolizers.
Fedratinib: (Moderate) Monitor for an increase in flecainide-related adverse reactions, including QT prolongation, if coadministration with fedratinib is necessary. Plasma concentrations of flecainide may increase, especially in extensive CYP2D6 metabolizers. Flecainide is a CYP2D6 substrate and fedratinib is a moderate CYP2D6 inhibitor.
Fingolimod: (Major) Flecainide should be used cautiously and with close monitoring with fingolimod. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsades de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. After the first fingolimod dose, overnight monitoring with continuous ECG in a medical facility is advised for patients taking QT prolonging drugs with a known risk of torsades de pointes (TdP). Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia.
Fluconazole: (Major) Concomitant use of flecainide and fluconazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fluoxetine: (Major) Concomitant use of flecainide and fluoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Concomitant use may also increase the exposure of flecainide, further increasing the risk of adverse effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Flecainide is a CYP2D6 substrate and fluoxetine is a strong CYP2D6 inhibitor.
Fluphenazine: (Minor) Flecainide should be used cautiously and with close monitoring with fluphenazine. Fluphenazine, a phenothiazine, is associated with a possible risk for QT prolongation. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsades de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Fluvoxamine: (Major) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of fluvoxamine and flecainide. Cases of QT prolongation and TdP have been reported during postmarketing use of fluvoxamine. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Fosamprenavir: (Major) Concurrent use of fosamprenavir boosted with ritonavir and flecainide is contraindicated. When administered with ritonavir, fosamprenavir is expected to increase plasma concentrations of flecainide, causing the potential for serious and/or life threatening adverse reactions, including cardiac arrhythmia.
Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as flecainide. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
Fostemsavir: (Major) Use flecanide and fostemsavir together with caution due to the increased risk of QT prolongation. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsade de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs that have the potential for QT prolongation may have an increased risk of developing proarrhythmias. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, 4 times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
Gemifloxacin: (Major) Flecainide should be used cautiously and with close monitoring with gemifloxacin. Gemifloxacin may prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5-10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher.
Gemtuzumab Ozogamicin: (Major) Use gemtuzumab ozogamicin and flecainide together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Gilteritinib: (Major) Use caution and monitor for evidence of QT prolongation if concurrent use of gilteritinib and flecainide is necessary. Gilteritinib has been associated with QT prolongation. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsade de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs that have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Ginger, Zingiber officinale: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of antiarrhythmics; however, no clinical data are available.
Glasdegib: (Major) Avoid coadministration of glasdegib with flecainide due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsade de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs that have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Goserelin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., goserelin) outweigh the potential risks of QT prolongation in patients receiving flecainide. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsade de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Androgen deprivation therapy may also prolong the QT/QTc interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs that have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Granisetron: (Major) Flecainide should be used cautiously and with close monitoring with granisetron. Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron in patients concurrently treated with drugs known to prolong the QT interval and/or are arrhythmogenic, may result in clinical consequences. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsades de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Halogenated Anesthetics: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with flecainide. Halogenated anesthetics can prolong the QT interval. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT

prolongation and/or torsades de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Haloperidol: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering haloperidol with flecainide. QT prolongation and TdP have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Flecainide, a Class IC antiarrhythmic, is also associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias. In addition, flecainide is significantly metabolized by CYP2D6, and haloperidol is a CYP2D6 inhibitor. Coadministration may result in elevated flecainide serum concentrations.
Histrelin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving flecainide. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsade de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Androgen deprivation therapy may also prolong the QT/QTc interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs that have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Hydroxychloroquine: (Major) Concomitant use of hydroxychloroquine and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Hydroxyzine: (Major) Concomitant use of hydroxyzine and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ibutilide: (Major) Combined use of antiarrhythmics can have additive, antagonistic, or synergistic electrophysiologic, pharmacodynamic, or toxic effects. In general, combination therapy with Class III and Class IC antiarrhythmics has been reported to increase the risk of proarrhythmias. However, combination antiarrhythmic therapy may be beneficial in some patients with refractory arrhythmias; close monitoring is prudent to reduce the risk of adverse effects. A recent study evaluated the use of ibutilide therapy in 71 patients receiving long-term treatment with Class IC agents (n=46 propafenone; n=25 flecainide) for atrial fibrillation or atrial flutter. The majority of patients had normal left ventricular systolic function (91.5%). Conversion of atrial fibrillation was achieved in 23 of 48 patients (47.9%) receiving ibutilide, while conversion of atrial flutter occurred in 17 of 23 patients (73.9%) studied. Ibutilide resulted in a small increase in the QTc interval (from 442 +/- 61 ms to 462 +/- 59 ms). Two patients developed proarrhythmias, non-sustained polymorphous ventricular tachycardia and sustained torsade de pointes (TdP), which were successfully treated. Administration of ibutilide to patients who have received flecainide should be done with cautious monitoring.
Iloperidone: (Major) Concurrent use of iloperidone and flecainide should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Iloperidone has been associated with QT prolongation; however, TdP has not been reported. Flecainide, a Class IC antiarrhythmic, is associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Imatinib: (Major) Flecainide is significantly metabolized by CYP2D6 isoenzymes. Caution is recommended when administering flecainide with CYP2D6 inhibitors including imatinib; flecainide exhibits a narrow therapeutic range and large increases in serum concentrations may be associated with severe adverse reactions.
Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with flecainide due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Itraconazole: (Major) Itraconazole has been associated with prolongation of the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with itraconazole include flecainide.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with flecainide due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsade de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs that have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and flecainide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Labetalol: (Moderate) Monitor heart rate during concomitant flecainide and labetalol use due to risk for additive negative inotropic effects.
Lacosamide: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as Class IC antiarrhythmics, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Lamotrigine: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as class IC antiarrhythmics. Concomitant use of class IC antiarrhythmics with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering clarithromycin with flecainide. Administration of clarithromycin has resulted in prolongation of the QT interval and TdP. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Lapatinib: (Major) Monitor ECGs for QT prolongation and monitor electrolytes if coadministration of lapatinib with flecainide is necessary; correct electrolyte abnormalities prior to treatment. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsade de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs that have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Lefamulin: (Major) Avoid coadministration of lefamulin with flecainide as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, monitor ECG during treatment. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsade de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs that have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Lenvatinib: (Major) Avoid coadministration of lenvatinib with flecainide due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsade de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs that have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Leuprolide: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving flecainide. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsade de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Androgen deprivation therapy may also prolong the QT/QTc interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs that have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Leuprolide; Norethindrone: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving flecainide. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsade de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Androgen deprivation therapy may also prolong the QT/QTc interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs that have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Levofloxacin: (Major) Concomitant use of levofloxacin and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and flecainide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Lidocaine: (Major) Although causality for torsades de pointes has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation, such as local anesthetics, may have an increased risk of developing proarrhythmias. Use with caution.
Lidocaine; Epinephrine: (Major) Although causality for torsades de pointes has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation, such as local anesthetics, may have an increased risk of developing proarrhythmias. Use with caution.
Lidocaine; Prilocaine: (Major) Although causality for torsades de pointes has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation, such as local anesthetics, may have an increased risk of developing proarrhythmias. Use with caution.
Lithium: (Major) Concomitant use of flecainide and lithium increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Lofexidine: (Major) Monitor ECG if lofexidine is coadministered with flecainide due to the potential for additive QT prolongation and torsade de pointes (TdP). Lofexidine prolongs the QT interval. In addition, there are postmarketing reports of TdP. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs that have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Loperamide: (Major) Concomitant use of flecainide and loperamide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Loperamide; Simethicone: (Major) Concomitant use of flecainide and loperamide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Lopinavir; Ritonavir: (Major) Concurrent use of HIV treatment doses of ritonavir with flecainide is contraindicated. Cautious consideration may be given to administering flecainide with boosting doses of ritonavir. The potential increase in plasma concentrations of flecainide could result in significant adverse effects. (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering lopinavir; ritonavir with flecainide. Lopinavir; ritonavir is associated with QT prolongation. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as flecainide. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsade de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs that have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Maprotiline: (Major) Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with maprotiline include flecainide, Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsades de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval.
Mavacamten: (Moderate) Expect additive negative inotropic effects during concomitant use of mavacamten and flecainide. If concomitant therapy with flecainide is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved.
Mefloquine: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering flecainide with mefloquine. There is evidence that the use of halofantrine after mefloquine causes significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation; however due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Causality for TdP has not been established for flecainide.
Methadone: (Major) Concomitant use of methadone and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Metoprolol: (Moderate) Monitor heart rate during concomitant flecainide and metoprolol use due to risk for additive negative inotropic effects.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor heart rate during concomitant flecainide and metoprolol use due to risk for additive negative inotropic effects.
Metronidazole: (Major) Concomitant use of metronidazole and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Midostaurin: (Major) Concomitant use of midostaurin and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mifepristone: (Major) Concomitant use of flecainide and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mirabegron: (Major) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as flecainide may be increased when administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Mirtazapine: (Major) Concomitant use of flecainide and mirtazapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mobocertinib: (Major) Concomitant use of mobocertinib and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Moxifloxacin: (Major) Concomitant use of flecainide and moxifloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Nadolol: (Moderate) Pharmacologically, beta-blockers, like nadolol, cause AV nodal conduction depression and additive effects are possible when used in combination with flecainide. When used together, AV block can occur. During flecainide clinical trials, increased adverse events have not been reported in patients receiving combination therapy with beta-blockers and flecainide. However, patients should be monitored closely and the dose should be adjusted according to clinical response.
Nebivolol: (Moderate) Monitor heart rate during concomitant flecainide and nebivolol use due to risk for additive negative inotropic effects.
Nebivolol; Valsartan: (Moderate) Monitor heart rate during concomitant flecainide and nebivolol use due to risk for additive negative inotropic effects.
Nifedipine: (Major) Because both flecainide and nifedipine have negative inotropic properties, additive effects are possible especially in patients with abnormal ventricular function. Per the manufacturer of flecainide, concomitant use with nifedipine is not recommended until more data is available.
Nilotinib: (Major) Concomitant use of flecainide and nilotinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Niraparib; Abiraterone: (Moderate) Monitor for an increase in flecainide-related adverse reactions, including QT prolongation, if coadministration with abiraterone is necessary. Flecainide is a CYP2D6 substrate and abiraterone is a moderate CYP2D6 inhibitor. Plasma concentrations of flecainide may increase, especially in extensive CYP2D6 metabolizers.
Nirmatrelvir; Ritonavir: (Contraindicated) Concomitant use of ritonavir-boosted nirmatrelvir and flecainide is contraindicated; consider an alternative COVID-19 therapy. Coadministration may increase flecainide exposure resulting in increased toxicity. Flecainide is a CYP3A substrate and nirmatrelvir is a CYP3A inhibitor. (Major) Concurrent use of HIV treatment doses of ritonavir with flecainide is contraindicated. Cautious consideration may be given to administering flecainide with boosting doses of ritonavir. The potential increase in plasma concentrations of flecainide could result in significant adverse effects.
Ofloxacin: (Major) Concomitant use of ofloxacin and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Olanzapine: (Moderate) Concomitant use of flecainide and olanzapine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Olanzapine; Fluoxetine: (Major) Concomitant use of flecainide and fluoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Concomitant use may also increase the exposure of flecainide, further increasing the risk of adverse effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Flecainide is a CYP2D6 substrate and fluoxetine is a strong CYP2D6 inhibitor. (Moderate) Concomitant use of flecainide and olanzapine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Olanzapine; Samidorphan: (Moderate) Concomitant use of flecainide and olanzapine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Ondansetron: (Major) Concomitant use of ondansetron and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Oritavancin: (Moderate) Flecainide is metabolized by CYP2D6; oritavancin is a weak CYP2D6 inducer. Plasma concentrations and efficacy of flecainide may be reduced if these drugs are administered concurrently.
Osilodrostat: (Major) Concomitant use of osilodrostat and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Osimertinib: (Major) Concomitant use of osimertinib and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Oxaliplatin: (Major) Concomitant use of oxaliplatin and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ozanimod: (Major) In general, do not initiate ozanimod in patients taking flecainide due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs that have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Pacritinib: (Major) Concomitant use of pacritinib and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Paliperidone: (Major) Concomitant use of paliperidone and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Panobinostat: (Major) The co-administration of panobinostat with flecainide is not recommended; QT prolongation has been reported with both of these agents. If concomitant use cannot be avoided, closely monitor patients for signs and symptoms of flecainide toxicity, including QT prolongation and cardiac arrhythmias. Panobinostat is a CYP2D6 inhibitor and flecainide is a CYP2D6 substrate. When a single-dose of a CYP2D6-sensitive substrate was administered after 3 doses of panobinostat (20 mg given on days 3, 5, and 8), the CYP2D6 substrate Cmax increased by 20% to 200% and the AUC value increased by 20% to 130% in 14 patients with advanced cancer; exposure was highly variable (coefficient of variance > 150%).
Paroxetine: (Moderate) Monitor for an increase in flecainide-related adverse reactions, including QT prolongation, if coadministration with paroxetine is necessary. Flecainide is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. Plasma concentrations of flecainide may increase, especially in extensive CYP2D6 metabolizers.
Pasireotide: (Major) Concomitant use of pasireotide and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Pazopanib: (Major) Concomitant use of pazopanib and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Peginterferon Alfa-2b: (Moderate) Monitor for adverse effects associated with increased exposure to flecainide if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while flecainide is a CYP2D6 substrate with a narrow therapeutic range.
Pentamidine: (Major) Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for torsade de pointes (TdP) has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias. Intravenous pentamidine has been associated with QT prolongation and may induce electrolyte abnormalities that may increase the risk of proarrhythmia. Monitoring of the ECG may be advisable with coadministration.
Perphenazine: (Minor) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering perphenazine with flecainide. Perphenazine, a phenothiazine, is associated with a possible risk for QT prolongation. Flecainide, a Class IC antiarrhythmic, is also associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval.
Perphenazine; Amitriptyline: (Minor) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering perphenazine with flecainide. Perphenazine, a phenothiazine, is associated with a possible risk for QT prolongation. Flecainide, a Class IC antiarrhythmic, is also associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval.
Pimavanserin: (Major) Concomitant use of pimavanserin and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Pimozide: (Contraindicated) Avoid concomitant use of pimozide and flecainide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Pindolol: (Moderate) Pharmacologically, beta-blockers, like pindolol, cause AV nodal conduction depression and additive effects are possible when used in combination with flecainide. When used together, AV block can occur. During flecainide clinical trials, increased adverse events have not been reported in patients receiving combination therapy with beta-blockers and flecainide. However, patients should be monitored closely and the dose should be adjusted according to clinical response.
Pitolisant: (Major) Concomitant use of pitolisant and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ponesimod: (Major) In general, do not initiate ponesimod in patients taking flecainide due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs that have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Posaconazole: (Major) Concomitant use of posaconazole and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Potassium Bicarbonate: (Moderate) Urinary alkalinization can decrease the renal clearance of flecainide, resulting in an increased elimination half-life and AUC for flecainide.
Potassium Chloride: (Moderate) Urinary alkalinization can decrease the renal clearance of flecainide, resulting in an increased elimination half-life and AUC for flecainide.
Potassium Citrate: (Moderate) Urinary alkalinization can decrease the renal clearance of flecainide, resulting in an increased elimination half-life and AUC for flecainide.
Potassium Citrate; Citric Acid: (Moderate) Urinary alkalinization can decrease the renal clearance of flecainide, resulting in an increased elimination half-life and AUC for flecainide.
Prilocaine: (Major) Although causality for torsades de pointes has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation, such as local anesthetics, may have an increased risk of developing proarrhythmias. Use with caution.
Prilocaine; Epinephrine: (Major) Although causality for torsades de pointes has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation, such as local anesthetics, may have an increased risk of developing proarrhythmias. Use with caution.
Primaquine: (Major) Concomitant use of primaquine and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Procainamide: (Major) Concomitant use of procainamide and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Prochlorperazine: (Minor) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering prochlorperazine with flecainide. If coadministration is considered necessary, and the patient has known risk factors for cardiac disease or arrhythmia, then close monitoring is essential. Phenothiazines, such as prochlorperazine, have been reported to prolong the QT interval. Flecainide, a Class IC antiarrhythmic, is also associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval.
Promethazine: (Major) Concomitant use of promethazine and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Promethazine; Dextromethorphan: (Major) Concomitant use of promethazine and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Promethazine; Phenylephrine: (Major) Concomitant use of promethazine and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Propafenone: (Major) Concomitant use of flecainide and propafenone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Concomitant use may also increase the exposure of flecainide, further increasing the risk of adverse effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Flecainide is a CYP2D6 substrate and propafenone is a moderate CYP2D6 inhibitor.
Propranolol: (Moderate) Monitor heart rate during concomitant flecainide and propranolol use due to risk for additive negative inotropic effects.
Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor heart rate during concomitant flecainide and propranolol use due to risk for additive negative inotropic effects.
Quetiapine: (Major) Concomitant use of flecainide and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quinidine: (Contraindicated) Class IC antiarrhythmic agents, such as flecainide, have proarrhythmic properties, and may have additive electrophysiologic effects with other Class I agents such as quinidine. In addition, quinidine should be considered contraindicated with flecainide. Quinidine and flecainide are associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; therefore, the effects on the QT interval may be increased during concurrent use of quinidine with flecainide or propafenone.
Quinine: (Major) Flecainide clearance can be modestly inhibited by quinine, increasing flecainide serum concentrations. Quinine is a CYP2D6 inhibitor, and flecainide is a CYP2D6 substrate. Additionally, both drugs are associated with prolongation of the QT internal. Until more data are available, concomitant use of these two drugs should be avoided whenever possible.
Quizartinib: (Major) Concomitant use of quizartinib and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ranolazine: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering ranolazine with flecainide. Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval. The mean increase in QTc is about 6 milliseconds, measured at the tmax of the maximum dosage (1000 mg PO twice daily). However, in 5% of the population studied, increases in the QTc of at least 15 milliseconds have been reported. Flecainide, a Class IC antiarrhythmic, is also associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias. In addition, ranolazine and/or metabolites are moderate inhibitors of CYP2D6, and flecainide is a CYP2D6 substrate. Coadministration may result in elevated flecainide serum concentrations. The manufacturer for ranolazine suggests that lower doses of CYP2D6 substrates may be required during concurrent treatment.
Relugolix: (Major) Concomitant use of relugolix and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Relugolix; Estradiol; Norethindrone acetate: (Major) Concomitant use of relugolix and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ribociclib: (Major) Concomitant use of ribociclib and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ribociclib; Letrozole: (Major) Concomitant use of ribociclib and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Rilpivirine: (Major) Concomitant use of rilpivirine and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Risperidone: (Major) Concomitant use of risperidone and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ritonavir: (Major) Concurrent use of HIV treatment doses of ritonavir with flecainide is contraindicated. Cautious consideration may be given to administering flecainide with boosting doses of ritonavir. The potential increase in plasma concentrations of flecainide could result in significant adverse effects.
Rolapitant: (Major) Avoid the concurrent use of flecainide and rolapitant if possible; if coadministration is necessary, monitor for flecainide-related adverse effects, including QT prolongation. Flecainide is a CYP2D6 substrate that is individually dose-titrated, and rolapitant is a moderate CYP2D6 inhibitor; the inhibitory effect of rolapitant is expected to persist beyond 28 days for an unknown duration. Exposure to another CYP2D6 substrate, following a single dose of rolapitant increased about 3-fold on Days 8 and Day 22. The inhibition of CYP2D6 persisted on Day 28 with a 2.3-fold increase in the CYP2D6 substrate concentrations, the last time point measured.
Romidepsin: (Major) Concomitant use of romidepsin and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Saquinavir: (Contraindicated) The concurrent use of flecainide and saquinavir boosted with ritonavir is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Saquinavir boosted with ritonavir causes dose-dependent QT and PR prolongation; avoid use with other drugs that may prolong the QT or PR interval, such as flecainide.
Selpercatinib: (Major) Concomitant use of selpercatinib and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sertraline: (Major) Use caution and monitor patients for QT prolongation when administering Class IC Antiarrhythmics with sertraline. Class IC antiarrhythmics increase the QT interval, but largely due to prolongation of the QRS interval. QTc prolongation and torsade de pointes (TdP) have been reported during postmarketing use of sertraline; most cases had confounding risk factors. The risk of sertraline-induced QT prolongation is generally considered to be low in clinical practice. Its effect on QTc interval is minimal (typically less than 5 msec), and the drug has been used safely in patients with cardiac disease (e.g., recent myocardial infarction, unstable angina, chronic heart failure). In addition, sertraline is a mild to moderate inhibitor of CYP2D6, and inhibition of CYP2D6 can result in increased concentrations of antiarrhythmic drugs metabolized via the same pathway, including flecainide and propafenone.
Siponimod: (Major) Concomitant use of siponimod and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sodium Stibogluconate: (Major) Concomitant use of sodium stibogluconate and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Solifenacin: (Moderate) Concomitant use of flecainide and solifenacin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Sorafenib: (Major) Concomitant use of sorafenib and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sotalol: (Major) Concomitant use of flecainide and sotalol increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sunitinib: (Major) Concomitant use of sunitinib and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Tacrolimus: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering tacrolimus with flecainide. Tacrolimus causes QT prolongation. Flecainide, a Class IC antiarrhythmic, is also associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Tamoxifen: (Major) Concomitant use of tamoxifen and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Teduglutide: (Moderate) Teduglutide may increase absorption of flecainide because of it's pharmacodynamic effect of improving intestinal absorption. Careful monitoring and possible dose adjustment of flecainide is recommended.
Telavancin: (Major) Concomitant use of telavancin and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Terbinafine: (Major) Class IC antiarrhythmics are metabolized by CYP2D6 isoenzymes. Caution is recommended when administering them with CYP2D6 inhibitors, such as terbinafine; Class IC antiarrhythmics exhibit a narrow therapeutic range and large increases in serum concentrations may be associated with severe adverse reactions.
Tetrabenazine: (Major) Concomitant use of tetrabenazine and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Thioridazine: (Contraindicated) Avoid concomitant use of thioridazine and flecainide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Timolol: (Moderate) Monitor heart rate during concomitant flecainide and timolol use due to risk for additive negative inotropic effects.
Tipranavir: (Contraindicated) When administered in the FDA approved dosage regimen, tipranavir is an inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as flecainide, should be expected with concurrent use. Coadministration of tipranavir and flecainide is contraindicated due to the potential for serious or life-threatening reactions, such as cardiac arrhythmias.
Tobacco: (Major) Advise patients to avoid smoking tobacco while taking flecainide. Smoking tobacco has been observed to decrease flecainide trough concentrations by 25% and may decrease efficacy.
Tolterodine: (Moderate) Tolterodine is associated with dose-dependent prolongation of the QT interval, especially in poor metabolizers of CYP2D6. Drugs that are also associated with QT prolongation and have antimuscarinic properties that should be used cautiously and with close monitoring with tolterodine include flecainide.
Toremifene: (Major) Concomitant use of toremifene and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Trandolapril; Verapamil: (Moderate) Limit use of flecainide and verapamil when possible, and do not exceed maximum daily doses. Coadministration of flecainide with verapamil increases the risk of bradycardia, AV block, and hypotension.
Trazodone: (Major) Concomitant use of flecainide and trazodone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Triclabendazole: (Major) Concomitant use of triclabendazole and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Trifluoperazine: (Minor) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering trifluoperazine with flecainide. Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation. Flecainide is a Class IC antiarrhythmic and is also associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval.
Triptorelin: (Major) Concomitant use of triptorelin and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Vandetanib: (Major) Concomitant use of vandetanib and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Vardenafil: (Major) Concomitant use of flecainide and vardenafil increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Vemurafenib: (Major) Vemurafenib has been associated with QT prolongation. If vemurafenib and another drug, such as flecainide, that is associated with a possible risk for QT prolongation and torsade de pointes (TdP) must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Also, flecainide is a CYP2D6 substrate, while vemurafenib is a weak CYP2D6 inhibitor; therefore concentrations of flecainide may be increased with concomitant use. Caution is warranted and patients should be monitored for increased side effects.
Venlafaxine: (Major) Concomitant use of flecainide and venlafaxine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Verapamil: (Moderate) Limit use of flecainide and verapamil when possible, and do not exceed maximum daily doses. Coadministration of flecainide with verapamil increases the risk of bradycardia, AV block, and hypotension.
Viloxazine: (Moderate) Monitor for an increase in flecainide-related adverse reactions, including QT prolongation, if coadministration with viloxazine is necessary. Flecainide is a CYP2D6 substrate and viloxazine is a weak CYP2D6 inhibitor. Plasma concentrations of flecainide may increase, especially in normal (extensive) CYP2D6 metabolizers.
Voclosporin: (Major) Concomitant use of voclosporin and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering clarithromycin with flecainide. Administration of clarithromycin has resulted in prolongation of the QT interval and TdP. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Voriconazole: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering voriconazole with flecainide. Voriconazole has been associated with prolongation of the QT interval and rare cases of arrhythmias, including TdP. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/orTdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval.
Vorinostat: (Moderate) Concomitant use of flecainide and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Ziprasidone: (Major) Concomitant use of ziprasidone and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.

Flecainide/Flecainide Acetate/Tambocor Oral Tab: 50mg, 100mg, 150mg

Adults

300 mg/day PO for paroxysmal supraventricular tachycardia (PSVT) prophylaxis, atrial fibrillation, or atrial flutter; 400 mg/day PO for ventricular tachycardia prophylaxis.

Geriatric

300 mg/day PO for paroxysmal supraventricular tachycardia (PSVT) prophylaxis, atrial fibrillation, or atrial flutter; 400 mg/day PO for ventricular tachycardia prophylaxis.

Adolescents

200 mg/m2/day PO or 8 mg/kg/day PO.

Children

200 mg/m2/day PO or 8 mg/kg/day PO.

Infants

200 mg/m2/day PO or 8 mg/kg/day PO.

Neonates

200 mg/m2/day PO or 8 mg/kg/day PO.

As a class, the IC agents have three primary electrophysiological effects. Potent inhibition of the fast sodium channels depresses the upstroke of the action potential, which is manifested as a decrease in the maximal rate of phase 0 depolarization. Secondly, the IC agents significantly slow His-Purkinje conduction and cause QRS widening. Finally, these agents shorten the action potential of Purkinje fibers without affecting the surrounding myocardial tissue.
Flecainide inhibits the fast sodium channels of the myocardial cell membrane, thereby increasing the recovery period after repolarization. The drug can inhibit extracellular calcium influx but only at high doses. Flecainide does not exhibit vagomimetic, vagolytic, or beta-adrenergic blocking properties. It slows intracardiac conduction and can slightly increase action potential duration in atrial and ventricular muscle. The PR, QRS, and QT intervals are usually prolonged.
 
Flecainide acts on the antegrade pathways of anomalous AV conduction, thereby terminating paroxysmal reentrant supraventricular tachycardias. In patients with Wolff-Parkinson-White syndrome, flecainide increases the refractoriness of the anterograde and/or retrograde pathways by decreasing conduction in these or accessory pathways. Although it may have mild to moderate negative intropic effects, flecainide generally has only minimal cardiovascular effects; blood pressure, heart rate, and left ventricular function are usually unchanged.

Flecainide is administered orally. It is 40% to 50% bound to plasma proteins, primarily alpha-1-acid glycoprotein (AGP). It appears to be well distributed, with a volume of distribution of approximately 7 L/kg. Although it is not known whether flecainide crosses the placenta, it does distribute into maternal breast milk. Recommended therapeutic serum concentrations are 0.2 to 1 mcg/mL. It is metabolized by dealkylation and conjugation to at least 5 metabolites that are excreted in the urine. Approximately 30% of the drug is excreted via renal pathways and 5% is excreted fecally. The terminal plasma half-life ranges from about 12 to 30 hours and the pharmacodynamic duration of activity is 1 to 2 days.
 
Affected cytochrome P450 isoenzymes: CYP2D6
Flecainide is primarily metabolized by CYP2D6. It has a narrow therapeutic range and caution is advised when administering with CYP2D6 inhibitors.

Oral Route

An oral dose of flecainide is almost completely absorbed, with a bioavailability approaching 95% and peak plasma concentrations occurring 2 to 3 hours after oral administration.

Pregnancy

Flecainide is classified in FDA pregnancy risk category C. Flecainide has been shown to have teratogenic and embryotoxic effects in certain breeds of laboratory animals. Because there are no well-controlled pregnancy studies in humans, flecainide should only be used in pregnant women if the potential benefits justify the possible risk to the fetus. It is not known if the use of flecainide during labor or delivery has immediate or delayed adverse effects on the mother or fetus, affects the duration of labor or delivery, or increases the possibility of forceps delivery or other obstetrical intervention.

According to the manufacturer, flecainide is excreted into breast milk in concentrations exceeding those in human plasma. Results from a multiple dose study conducted in mothers soon after delivery indicates that flecainide is excreted in human breast milk in concentrations as high as 4-fold (mean 2.5-fold) higher than maternal plasma levels. Assuming a maternal plasma level at the upper end of the therapeutic range (1 mcg/mL), the estimated daily dose ingested by a nursing infant (assuming 700 mL of breast milk intake per 24 hours) would be < 3 mg. The American Academy of Pediatrics considers flecainide to be usually compatible with breast-feeding. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.