What is the risk of elevated liver enzymes and hepatitis as a side effect of flecainide therapy?/nT

Fråga: What is the risk of elevated liver enzymes and hepatitis as a side effect of flecainide therapy?<br><br>The question concerns an otherwise healthy 58-years-old man with paroxysmal atrial fibrillation. The patient is treated with warfarin anticoagulation. Two to three weeks before the patient presented with elevated liver enzymes, flecainide 100 mgx2 was initiated. There were no other concomitant medications. After initiating flecainide therapy the patient travelled to Spain. Upon returning he consulted his doctor due to poor control of his cardiac arythmia. The laboratory workup revealed elevated liver enzymes, with ASAT 6.20 (reference value <0.8 ukat/L) ALAT 14.4 (reference value <0.8 ukat/L). ALP was not elevated. There was no jaundice or nausea. Albumin was slightly lowered, and PK-INR was elevated beyond the therapeutic interval. There were no serological evidence of acute viral hepatitis. An ultrasonography of the liver was normal. No history of heavy drinking or use of recreational drugs or herbal remedies was elicited. At the time of admission flecainide was discontinued. The laboratory profile has since improved considerably. The total liver workup is not completed, but there is a strong suspicion of a causal relationship between the flecainide medication and the liver reaction.

Sammanfattning: Elevated transaminases and hepatitis have been described as rare side effects of flecainide therapy. If no other cause of the clinical findings is found, flecainide must be considered a possible causative agent in the aforementioned case.

Svar: Flecainide is a class 1C antiarrythmic agent. It is mainly excreted renally, but a small part is metabolised, mainly by CYP2D6 (1). In some trials ASAT/ALAT elevations have been noted in up to 45% of the patients (2). However, in clinical practise this seems rather more rare. The SWEDIS adverse drug reaction register cites only one case of elevated transaminases and no other hepatic side effects among a total of 41 reports. The FASS cites elevated transaminases as very rare (1). There exists only a handful of reports of frank hepatitis due to flecainide therapy. These have been both of the cholestatic and hepatocellular kind, and have been reversible upon discontinuation of the drug (2).<br><br>Flecainide-associated liver injury is probably an idiosyncratic (type B) side effect, calling for the discontinuation of the drug. If the findings are interpreted as an adverse effect of flecainide therapy, it could, however, be interesting to evaluate whether the patient is a poor metaboliser at CYP2D6. Testing for creatinine clearance could also be worthwhile, even in the presence of normal serum creatinine levels, in order to fully evaluate the metabolic and excretory pathways of flecainide. If no other cause of the patient´s condition is found, we recommend that the case be reported to the regional centre of SADRAC (The Swedish Adverse Drug Reaction Advisory Committee).<div id="referenser" style="display:none;">1 FASS 2003 (The Swedish catalogue of approved medical products)<br>2 Stricker BHCh. Drug-induced hepatic injury. 2nd ed. Elsevier: Amsterdam; 1992. p. 313-4.</div>