Flecainide toxicity in a pediatric patient due to differences in pharmacy compounding

Abstract

Flecainide is a Vaughn–Williams class 1c antidysrhythmic. It is typically an oral medication administered for the treatment of atrial fibrillation or supraventricular tachycardia (SVT) [1,2]. It is sparingly used in the pediatric population, but can be used in the treatment of SVT [1,2]. We describe a 9 month old male who received an accidental overdose of his medication due to differences in pharmacy compounding. A 9 month old male with a history of Wolff–Parkinson White (WPW) and SVT was seen at a local children's hospital the day prior to admission due to breakthrough SVT. At that time, he was initially refractory to adenosine, and his SVT resolved with propranolol. His maintenance medication was flecainide 15 mg (3 ml) twice daily. He was discharged home on an increased dose of flecainide to 21 mg (4 ml) by mouth twice daily. Later that morning, patient received 4 ml of his home flecainide when his mother noted him to be pale and fussy. EMS was called and brought him to a local emergency department. En route, he was noted to be in ventricular tachycardia (VT). Upon arrival to the emergency department (ED), his vitals were 37 ° C, RR of 24, and a HR of 180. He was alert, crying and fighting IV attempts. He was noted to be tachycardic on cardiovascular exam withoutmurmurs, rubs or gallops, no hepatosplenomegaly, and normal perfusion. ECG revealed sinus tachycardia with a PR interval of 160 ms and QRS interval of 180 ms. The patient had intermittent episodes of VT in the ED with normal pulses and without change in his clinical status (Fig. 1). It was eventually noted that his original concentration was changed to 20 mg/1 ml rather than the originally prescribed 5 mg/1 ml. Toxicology and cardiology were consulted at that time. IV access was obtained after 1 h in the ED, at that time, no episodes of VT were noted, and the QRS interval was 160 ms. Electrolytes including sodium, potassium, bicarbonate, magnesium, phosphorus, and calcium were all within normal range. Patient was admitted and placed on telemetry upon in the intensive care unit (ICU). Approximately 8 h into his hospital stay, QRS interval widened from 140 ms to 160 ms, his clinical status remained stable. Per toxicology recommendations, 2 mEq/kg of NaHCO3 IV was given and QRS interval was reduced to 120 ms. He subsequently remained hemodynamically stable during his ICU stay without further episodes of ventricular tachycardia, and his QRS narrowed to his baseline. Flecainide overdose can lead to seizures and cardiotoxicity including PR and QRS widening, bradycardia, ventricular tachycardia, and ventricular fibrillation due to its mechanism of action, Na channel blockade. Treatment for flecainide toxicity includes NaHCO3 boluses, hypertonic saline boluses, and extracorporeal circulatory support. Our patient presented immediately after a 4 fold overdose in a wide complex tachycardia, consistent with flecainide toxicity. Previous ECGs showed normal QRS complexes and he had never presented with a wide complex tachycardia due to his WPW. There have been four prior reports of pediatric patients and the toxic effects of flecainide, including an accidental double dose leading to toxicity, and reversal of medication syringes [3–6]. After further investigation for our patient, with the help of access to 2 separate electronic medical records (EMR), a difference in pharmacy compounding was discovered. The child had a flecainide prescription originally written for 15 mg using a 5 mg/1 ml concentration. However, his initial prescription was filled at another pharmacy which compounded the formulation to 20 mg/1 ml and no communication to the original prescribing facilitywasmade.When he returned to the ED, his dose was increased to 21 mg, but hospital records showed he was still using a concentration of 5 mg/1 ml. He was instructed to finish his home medication at the new dose prior to filling the new prescription. Consequently the patient took the correct volume, however at a higher concentration, leading to a 4 fold overdose. Since this case, all the pharmacies in the local metro area have agreed to compound the medication in one standard concentration of 20 mg/1 ml. Other common cardiac medications that are available as multiple concentrations for oral suspensions include verapamil, atenolol, carvedilol, labetalol, propranolol, and tacrolimus. Unverified concentrations in many of these medications can lead to serious morbidity and mortality. Flecainide is a Vaughn–Williams class 1c antidysrhythmic rarely used in pediatrics, indications include SVT. Cardiotoxicity stems from Na channel blockade and includes PR and QRS widening, bradycardia, ventricular tachycardia, ventricular fibrillation. Treatment for toxicity includes NaHCO3 boluses, hypertonic saline boluses, and extracorporeal circulatory support [7,8]. Our case is a reminder when dosing of medications are changed, especially in liquid formulations and with cardiovascular medications, both dosing and concentrations of medications must be confirmed, as accidental overdose and potentially poor comes can result. Finally, access to EMRs remotely can help quickly discover and prevent medical errors.