flecainide (Tambocor)

Introduction

Tradename: Tambocor.

Indications

• supraventricular arrhythmias
  • atrial fibrillation
  • atrial flutter
  • paroxysmal supraventricular tachycardia (PSVT)
• chemical cardioversion of atrial fibrillation
• prevention & suppression of documented life-threatening ventricular arrhythmias

Contraindications

• pre-existing 2nd or 3rd degree AV block
• right bundle branch block associated with left hemiblock
• cardiogenic shock
• myocardial depression (impaired ventricular function in the setting of coronary artery disease)
• ischemic heart disease

Caution:

• pre-existing sinus node dysfunction
• sick sinus syndrome
• history of congestive heart failure
• new bundle-branch block
• patients with pacemakers
• renal or hepatic impairment

pregnancy category = c

safety in lactation = -

Dosage

• start 50-100 mg PO BID
  • PRN dosing for paraxysmal atrial fibrillation
• max 400 mg/day

Tabs: 50, 100, 150 mg.

Dosage adjustment in renal failure

• for creatinine clearance < 20 mL/min, decrease dose by 25-50%

Pharmacokinetics

• metabolized in the liver by cyt P450 2D6

elimination via liver 65 %

elimination via kidney 35 %

1/2life = 7-23 hours

protein binding = 32-58 %

elimination by hemodialysis = -

Monitor

• baseline serum K+;
  • correct hypokalemia or hyperkalemia prior to administration
• plasma flecainide
  • hepatic insufficiency
  • heart failure (goal is trough < 0.7 ug/mL)
  • creatinine clearance < 35 mL/min/1.75 m2
  • concurrent administration of amiodarone (recommended)
  • elderly (daily during dose adjustment)

Adverse effects

• common (> 10%)
  • dizziness, visual disturbances (blurred vision), dyspnea
• less common (1-10%)
  • headache, nausea, fatigue, palpitations, chest pain, asthenia, tremor, constipation, edema, fever, abdominal pain, tachycardia, rash, exacerbation of ventricular arrhythmia (5%)
• uncommon (< 1%)
  • bradycardia, heart block, increased PR interval, increased QRS duration, congestive heart failure, nervousness, hypoesthesia, paresthesia, alopecia, blood dyscrasia, hepatic dysfunction
• other
  • negative inotropic effect
  • confusion
  • irritability

• drug adverse effects of antiarrhythmic agent, Group IC

Drug interactions

• flecainide increases serum levels of digoxin
• flecainide & propranolol increase each other's serum levels
• amiodarone, cimetidine, smoking, antacids, carbonic anhydrase inhibitors & verapamil increase flecainide levels
• flecainide potentiates AV block of beta blockers & Ca+2 channel blockers
• any pharmaceutical agent that inhibits cyt P450 2D6 may increased levels of flecainide

• drug interaction(s) of antiarrhythmic agents in combination with diuretics
• drug interaction(s) of beta-adrenergic receptor antagonists with flecainide

Laboratory

• specimen:
  • serum, plasma (heparin, EDTA)
  • collect at trough concentration
• methods: GLC, HPLC, FPIA, fluorometry
• interferences:
  • propranol & quinidine interfere with fluorometry
• flecainide in serum/plasma
  • therapeutic range: 0.2-1.0 ug/mL (trough)
• other labs with Loincs
  • flecainide in gastric fluid
  • flecainide in urine

Mechanism of action

• suppresses ventricular ectopy & non sustained ventricular tachycardia (variably effective & not routinely indicated because of proarrhythmic effects)
• does not favorably affect survival or sudden death
• increases PR interval > 300 ms
• increases QRS duration > 180 ms
• QTc increases

More general terms

• antiarrhythmic agent, Group IC

Additional terms

• cytochrome P450 2D6 (cytochrome P450 2D, cytochrome P450 DB1, debrisoquine-4-hydroxylase, CYP2D6)

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3356
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=41022
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3355