Flecainide is an oral class 1c antiarrhythmic drug used to treat atrial fibrillation or supraventricular tachycardia, particularly when conventional treatment agents fail. Because it is available commercially only as 50 mg, 100 mg, and 150 mg tablets, it must be compounded into a suspension when needed for infants and children. Unfortunately, errors during preparation and dosing of the suspension have led to serious overdoses that resulted in cardiac emergencies. Overdoses can lead to seizures and cardiotoxicity, including ventricular tachycardia and fibrillation due to sodium channel blockade (Wang et al., 2012). Treatment includes sodium bicarbonate boluses or sodium chloride boluses and extracorporeal circulatory support.
We first learned of a flecainide suspension-related error from a report submitted to Institute for Safe Medication Practices (ISMP) in 2007. A 4-month-old infant had been receiving 8 mg twice daily as an 8 mg/mL suspension (1 mL per dose). When the dose was later increased to 10 mg, a suspension purported to be 10 mg/mL was compounded. However, the baby's mother complained that the suspension was too thick to withdraw from the bottle. The pharmacist asked the mother to return the suspension and elected to compound a 7 mg/mL suspension, instructing the parent to give 1.4 mL per dose. Due to a math error, this replacement suspension was actually compounded with 6 g (6,000 mg) of flecainide instead of 600 mg. Therefore, each dose represented 100 mg, not 10 mg. It is unclear whether the previous 10 mg/mL suspension may also have been prepared incorrectly.
Additional errors with compounded flecainide suspension have appeared in the literature. A 2-year-old child received a fivefold overdose when unlabeled oral syringes of nadolol (CORGARD) and flecainide were used. Instead of withdrawing 5 mL of nadolol suspension (concentration not specified) and 1 mL of flecainide suspension (20 mg/mL), the nurse administered the opposite and the child received 5 mL of flecainide (100 mg) (D'Alessandro et al., 2009). In a second case, an 18-day-old infant received four doses of flecainide 8 mg (0.8 mL of a 10 mg/mL suspension) instead of 4 mg (0.8 mL of a 5 mg/mL), also resulting in wide complex tachycardia and cardiac arrest from which the child recovered (Jang et al., 2013). A third case involved a 9-month-old infant whose parents were told to increase the dose of flecainide to 4 mL, assuming the concentration was 5 mg/mL as in the original prescription (Wang et al., 2012). But the parents refilled the prescription at another pharmacy, receiving the drug in a 20 mg/mL concentration. The patient received 80 mg/4 mL, a fourfold overdose, resulting in wide complex tachycardia and QRS prolongation. Finally, an event published in December 2014 described an error in which the aunt of a 7-month-old child unknowingly gave her nephew a fivefold overdose of flecainide (Kwan et al., 2014). She pulled the suspension into an oral syringe that had both a teaspoon and mL scale and measured 5 mL (one teaspoon) instead of 1 mL. The child was hospitalized and suffered a cardiac arrest but was successfully resuscitated. Fortunately, all of the children recovered without neurologic sequelae following life-threatening flecainide overdoses.
Unrecognized changes in drug concentration, math errors, labeling errors, and inaccurate dosing instructions led to the confusion in these cases. In one case, the authors indicated that all of their local pharmacies had agreed to compound flecainide in one standard concentration of 20 mg/mL (Wang et al., 2012). A Michigan state-wide initiative agreed to standardize the flecainide concentration and other compounded liquid medication concentrations for pediatric patients. The initiative, which received a 2014 ISMP Cheers Award, provides the preparation directions, final concentration, stability data, storage information, and information for prescribers and families about the standards (Michigan Pediatric Safety Collaboration, 2014). Such efforts to standardize concentrations in both inpatient and outpatient pharmacies can help eliminate these medication errors. The American Society of Health-System Pharmacists, in cooperation with ISMP, the US Food and Drug Administration, and other stakeholders, is trying to broaden this initiative nationwide.
To reduce the risk of errors, prescribers should order flecainide in terms of the mg dose. This allows pharmacists to address the suspension concentration (mg/mL) and volume per dose, which should be expressed in mL (metric). For neonates and infants, a lower concentration may be required. If the drug is prescribed by volume (mL), the concentration MUST be specified, or the prescriber must be contacted for clarification.
In ambulatory care, when dispensing the medication, the pharmacy should provide liquid suspensions with a flow restrictor embedded in the neck of the bottle (Figure 1) along with an oral syringe to measure and administer doses. Be sure to remind the patient or parents to secure the child-resistant cap after each use. Label directions should include the dose in terms of mL, such as "Flecainide 0.25 mL by mouth every 8 hours." The community pharmacy label should also include the concentration next to the drug name. To be sure parents give a proper dose, use "teach-back" methods to demonstrate how to measure and administer proper amounts. This also gives pharmacists and parents an opportunity to catch an error.
Transdermal patches and heat sources. While hospitalized, a woman with multiple myeloma was placed on transdermal fentaNYL (DURAGESIC) 25 mcg per hour for back pain. Soon after returning home a family member noticed the patient seemed disoriented, was losing her balance, and had nausea and vomiting. A thorough investigation was conducted, and it was discovered that the fentaNYL patch was being applied to the patient's back. At the same time, the patient routinely sat in a recliner that vibrates and has a heating component that was activated. The heat from this chair over the area that the patch was applied likely led to the patient's symptoms of fentaNYL toxicity.
It's important to remind patients and caregivers to avoid exposing transdermal fentaNYL and other transdermal medication patches to heat from heating pads, electric blankets, heat or tanning lamps, sunbathing, hot baths, saunas, hot tubs, and heated water beds, as this could increase the rate of drug delivery from the patch into the body. Also, avoid tight coverings over the patch and strenuous exercise, which can heat the body. The person who reported this wanted us to remind others that heated loungers and vehicles with heated seats can affect absorption. Also, remind patients to apply patches to nonirritated and nonirradiated skin on the chest, back, flank, or upper arm, but to avoid applying the patch to body areas that might come in contact with heat sources. They should understand that the medication works systemically regardless of where the patch is placed on the body, so it does not need to be placed directly on or near the area that hurts.
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