AJN, American Journal of Nursing:
Aschenbrenner, Diane S. MS, RN
Diane S. Aschenbrenner is the course coordinator for undergraduate pharmacology at Johns Hopkins University School of Nursing in Baltimore, MD. She also coordinates Drug Watch: email@example.com.
* The Food and Drug Administration has strengthened its warnings related to the risk of seizures from the multiple sclerosis drug dalfampridine (Ampyra). The drug's label now warns that even mild renal impairment can allow serum levels of the drug to increase enough to induce seizures. To minimize the risk of seizures the patient's creatinine clearance should be determined prior to the start of dalfampridine therapy and at least yearly while she or he is receiving the drug.
Dalfampridine (Ampyra) is a potassium channel blocker used in the treatment of multiple sclerosis (MS) to improve walking speed. It has long been known that dalfampridine can produce seizures and that the risk of seizure increases with higher blood levels of the drug. Dalfampridine is eliminated through the kidneys, and patients with impaired kidney function will have greater circulating levels of the drug, increasing their risk of seizures. Dalfampridine has always been contraindicated in patients with a history of seizures or moderate-to-severe renal impairment (a creatinine clearance of 50 mL per minute or lower).
The Food and Drug Administration (FDA) recently evaluated the risk of seizures in MS patients after receiving several postmarketing reports of seizures that occurred even though the recommended dose of the drug was used. The majority of seizures occurred within days or weeks after the start of dalfampridine therapy in patients who had no history of seizures. Based on its analysis, the FDA updated the label, stating that mild renal impairment (a creatinine clearance of 51 to 80 mL per minute, even if the creatinine level is normal) also increases the risk of seizures in patients with MS. In normal aging, mild renal impairment is common after age 50. The FDA now recommends that creatinine clearance be assessed before beginning dalfampridine therapy and then reassessed at least yearly while the patient is taking the drug. Patients with a creatinine clearance of 51 to 80 mL per minute should be considered at greater risk for a drug-induced seizure, even if their serum creatinine level is normal. Use of dalfampridine in these patients requires a clinical decision that the benefit to a particular individual would exceed the risk of seizures.
Nurses working with MS patients who receive dalfampridine should provide patient education on the risk of seizures. They should also instruct patients not to divide, crush, chew, or dissolve the dalfampridine tablet because such actions will increase the rate of drug absorption and lead to higher-than-normal circulating levels. For similar reasons, patients should be instructed to take the tablet twice a day, 12 hours apart, and never to take more than two per day or more than one at a time. If a dose is missed, it should be omitted. The patient's creatinine clearance should be measured to assess for renal impairment. If creatinine clearance isn't known, it can be estimated using the Cockcroft-Gault equation.
If patients experience seizures while taking dalfampridine, the drug should be permanently discontinued. Adverse events from dalfampridine can be reported to the FDA MedWatch system online, at www.fda.gov/medwatch. To read the FDA Drug Safety Communication regarding dalfampridine, go to http://1.usa.gov/LJhEmA.
© 2012 Lippincott Williams & Wilkins, Inc.