Therapeutic Safety Monitoring: What to Look for and When to Look for It

Abstract

Summary: This review focuses on the safety problems associated with antiepileptic drugs (AEDs) as rcvealed by laboratory testing and clinical examination. There are two classes of side effccts: (a) common and mild and (b) rare and severe. Allergic reactions to AEDs are common and usually mild. However, on rare occasions, they can progress to more severe cutaneous disorders, including Stevens-Johnson syndrome and toxic epidermal necrolysis. Severe allergic reactions to AEDs range from immune responses with fever to multiorgan dysfunction. Allergic rashes may be genetically or immunologically determined. Laboratory abnormalities produced by AEDs are common and mild, and include hepatic enzyme elevation associated with phenytoin and mild elevation in ammonia associated with valproate. Serious, although rarc, idiosyncratic side effects, such as aplastic anemia, hepatotoxicity, and thrombocytopenia, have also occurred with AEDs. These reactions are largely confined to the "classic" AEDs. With the exception of felbamate, AEDs approved in the past decade have not been plagued by severe idiosyncratic reactions. Subtle endocrine abnormalities, including variations in thyroid function tests and bone metabolism, and the often subclinical effects on peripheral nerve conduction produced by phenytoin and carbamazepine, are also examined. Key Words: Adverse effect-Allergic reaction-StevensJohnson syndrome-Endocrine abnormalities.The vast majority of prescribed medications produce mild and non-life-threatening adverse effects. Although life-threatening events do occur, they not only are rare but also are idiosyncratic, preventing sufficient anticipation. Allergic rash is a fairly common adverse effect of some classes of medication. On rare occasions, the rash can cross categories from the common and mild to the serious and life-threatening.This review of antiepileptic drugs (AEDs) examines the frequency, course, and management of common and nonserious adverse effects, the risk and timing of rare but serious adverse effects, the subtle effects of AEDs on endocrine dysfunction, including thyroid, reproductive, and bone metabolism systems, and the common but mild effect of some AEDs on nerve conduction.

Antiepileptic drugs and suicidality

“…Therefore, the ethics of disclosure and consent can be argued to suggest an obligation for the clinician to share these data when counseling patients regarding AED treatment 68. As an analogy, there is little controversy regarding the advisability of counseling for other rare yet potentially serious AED complications such as Stevens–Johnson syndrome and lamotrigine,69 hepatotoxicity and valproate,70 and aplastic anemia, hepatoxicity, and felbamate 71. Thus, we advocate a balanced discussion with patients regarding the FDA report recommendations, as well as the benefits of seizure control and improved quality of life that AEDs can bring.…”

Can We Prevent Fatal Liver Failure under Valproate?

“…Thus, we would like to encourage the discussion of modifying the recommendations concerning monitoring at the beginning of a VPA therapy, since it might be an option to detect hepatotoxicity at an early, subclinical stage. Therefore, we suggest considering a short interval of, e. g., one week, during at least the fi rst 3 months of therapy and an intensive clinical vigilance, since the rare occurrence of hepatotoxicity is usually manifest within the fi rst 90 days of treatment [6] . Moreover, the combined use of VPA and duloxetine should be observed with care.…”

Pathological Case of the Month: Sudden Death in a Child as a Result of Pancreatitis During Valproic Acid Therapy

“…In summary, it is crucial not to misinterpret and = or disregard gastrointestinal symptoms with or without lethargy in patients taking valproic acid, because these could represent the ¢rst clinical signs of pancreatitis and = or hepatic failure, which may become irreversible [19,28,29]. For forensic pathologists valproic acid-induced pancreatitis can be a challenging diagnosis which must not be mistaken for abdominal trauma.…”