Risk of aplastic anemia in patients using antiepileptic drugs.
OBJECTIVE
To assess the association between exposure to antiepileptic drugs (AEDs) and the occurrence of aplastic anemia.


METHODS
A retrospective case-control study was conducted using data from the U.K. General Practitioners Research Database (GPRD). Cases were defined as patients diagnosed with aplastic anemia. For each case, up to three control patients were matched on age, sex, and medical practice. Cases and controls were compared with respect to AED use. The effects of duration of AED use were assessed. Characteristics of individual cases with AED use were reviewed.


RESULTS
The study population comprised 173 cases and 497 controls. AED use was more prevalent among cases (9.2%) than among controls (0.8%). After adjustment for confounders, the use of AEDs was significantly associated with aplastic anemia (adjusted odds ratio (OR), 9.5; 95% confidence interval (CI), 3.0-39.7). The most frequently used AEDs were carbamazepine (CBZ), valproic acid (VPA), and phenytoin. The 16 exposed cases were heterogeneous with respect to patient and exposure characteristics: the age of these patients varied from 1 to 92 years, and the duration of AED use varied from 17 days to 6.8 years.


CONCLUSIONS
This study indicates that use of AEDs, in particular CBZ and VPA, is associated with a ninefold increased risk of aplastic anemia. Physicians should be alert to the possibility of AED-associated aplastic anemia.
Handoko
Kim B
KB
Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, Utrecht, the Netherlands.
Souverein
Patrick C
PC
van Staa
Tjeerd P
TP
Meyboom
Ronald H B
RH
Leufkens
Hubert G M
HG
Egberts
Toine C G
TC
van den Bemt
Patricia M L A
PM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000741:Anemia, Aplastic / Q000139:chemically induced* / Q000453:epidemiology*; D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use*; D002220:Carbamazepine / Q000009:adverse effects / Q000627:therapeutic use; D016022:Case-Control Studies; D015897:Comorbidity; D015986:Confounding Factors, Epidemiologic; D004359:Drug Therapy, Combination; D004363:Drug Utilization; D005194:Family Practice / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010818:Practice Patterns, Physicians' / Q000706:statistics & numerical data; D015995:Prevalence; D012189:Retrospective Studies; D012307:Risk Factors; D014635:Valproic Acid / Q000009:adverse effects / Q000627:therapeutic use
D000927:Anticonvulsants; D002220:Carbamazepine; D014635:Valproic Acid