Unintentional 4-Aminopyridine Overdose in a Multiple Sclerosis Patient

Abstract

Objective:To discuss the clinical presentation and treatment of a 4-aminopyridine overdose resulting from a pharmacy prescription compounding error. Case Summary: A 55-year-old female with a 12-year history of multiple sclerosis is reintroduced to immediate-release 4-aminopydrine for symptom management. Four hours after the second dose, she is admitted to the emergency room with altered mental status, pulmonary edema, and seizures progressing to status epilepticus. She is intubated and managed with benzodiazepines followed by a propofol infusion. After 5 days she is discharged to home. Laboratory analysis of the capsules detected 127 mg of 4-aminopyridine, yet the prescription label indicated the contents as 12.5 mg capsules, to be taken twice a day. Discussion: There are 14 cases of previously published 4-aminopyridine toxicity in the literature. Four of those cases are due to pharmacy compounding errors. This case presents with typical and anticipated symptomatology such as acute delirium, cognitive changes, speech changes, elevated blood pressure, tachycardia, seizures, and status epilepticus. However, this case is unique in that the patient also presented with pulmonary edema, a finding not mentioned in the previous 14 cases. These adverse drug events are due to the neurotransmitter release induced through potassium channel blockade afforded by 4-aminopyridine when ingested in excessive amounts. In the context of adverse drug events, the 4-aminopyridine overdose as the causal link for the clinical findings in this case as determined by the Naranjo probability scale is ranked as definite. Conclusion: 4-Aminopyridine is a potent potassium (Kv) channel blocker and is accepted as a therapeutic agent for multiple sclerosis patients. In excess, 4-aminopyridine can produce significant adverse neurological effects most notable being status epilepticus. To date, no 4-aminopyridine overdose case reported has ended in death. Caution is advised to those pharmacists who provide compounding services.