ABSTRACT
After generic phenytoin (PHT) was marketed, the authors identified eight adult patients (ages 34 to 49) whose seizures increased enough to require intervention after switching to generic PHT. The mean total PHT concentration on brand (before generic) was 17.7 +/- 5.3 mg/L, decreased to 12.5 +/- 2.7 mg/L with generic, and increased to 17.8 +/- 3.9 mg/L after brand was re-introduced. Brand and generic PHT do not yield equivalent concentrations in some patients and substitution should not be permitted without physician notification.
Subject(s)
Drugs, Generic/metabolism , Drugs, Generic/pharmacokinetics , Epilepsy/drug therapy , Phenytoin/blood , Phenytoin/pharmacokinetics , Adult , Anticonvulsants/administration & dosage , Anticonvulsants/blood , Anticonvulsants/chemical synthesis , Anticonvulsants/pharmacokinetics , Cost-Benefit Analysis , Dose-Response Relationship, Drug , Drugs, Generic/administration & dosage , Epilepsy/physiopathology , Female , Humans , Male , Middle Aged , Phenytoin/administration & dosage , Phenytoin/chemical synthesis , Retrospective Studies , Risk Assessment , Secondary Prevention , Therapeutic Equivalency , Treatment FailureABSTRACT
OBJECTIVE: To evaluate changes in lamotrigine (LTG) clearance before, during, and after pregnancy. METHODS: Twelve pregnancies that had complete steady-state data before, during, and after pregnancy were evaluated. Data included weight, LTG dose, and LTG blood levels at preconception, during pregnancy, and postpartum, and concomitant use of other antiepileptic drugs and their dosages. Apparent clearance (L/[kg.day]) of LTG was calculated by dose/level/weight for time points at preconception; during the first trimester, second trimester, and third trimester; and postpartum. Apparent clearance was compared between preconception and each of the three trimesters. Statistical analysis was performed using one-way analysis of variance, the Student-Newman-Keuls test, and the paired Student's t-test. RESULTS: An increase in apparent clearance (>65%) was observed between preconception and the second and third trimesters (p < 0.05). Eleven pregnancies required higher doses of LTG to maintain therapeutic levels during pregnancy. There was no significant change in apparent clearance between each trimester. A decrease in apparent clearance was observed between the last two trimesters and postpartum (p < 0.05). In the postpartum period, apparent clearances returned to the preconception baseline, and LTG doses needed to be reduced. CONCLUSION: Pregnancy increases LTG clearance by >50%. This effect occurs early in pregnancy and reverts quickly after delivery. LTG levels should be monitored before, during, and after pregnancy.
