Characterization of lamotrigine dosing scenarios when co-prescribed with combined oral contraceptives
Abstract number :
997
Submission category :
7. Antiepileptic Drugs / 7E. Other
Year :
2020
Submission ID :
2423330
Source :
www.aesnet.org
Presentation date :
12/7/2020 1:26:24 PM
Published date :
Nov 21, 2020, 02:24 AM
Authors :
Charul Avachat, University of Minnesota; Ashwin Karanam - University of Minnesota; Page Pennell - Brigham and Women's Hospital, Harvard Medical School; Alison Pack - Columbia University; Anne Davis - Columbia University; Angela Birnbaum - University of Mi
Rationale:
Lamotrigine (LTG) is one of the most commonly prescribed antiseizure medications in women with epilepsy (WWE) during childbearing years. Due to probable upregulation of glucuronidation involved in LTG metabolism by estradiol, addition of combined oral contraceptives (COCs; progestin and ethinyl estradiol) to LTG therapy can decrease LTG concentrations. Little data exist describing the extent of enzyme induction or changes in LTG concentrations making it difficult for clinicians to estimate the LTG dose changes needed when COCs are added. Our objective was to characterize the changes in LTG concentrations from different dosing scenarios using data from a cohort of women of childbearing age who were treated with co-administered COCs.
Method:
LTG apparent clearance (LTG CL) was determined from an observational study of WWE who were receiving LTG with or without COCs from a tertiary epilepsy clinic (Emory University, Atlanta, GA). Inclusion criteria were women 18-45 years prescribed COCs and LTG, stable LTG dose for > 4 weeks, for > 3 days, and no interacting co-medications. Additional pharmacokinetic parameters were identified from the literature.1 The pre-COC LTG baseline was designated the target concentration, and the ratio to target concentration (RTC) of < 0.65 was calculated as the threshold at which the risk of seizure worsening increases. LTG concentrations of > 15 ug/mL and > 2.0 RTC were used as thresholds at which LTG side effects were more likely.
We simulated LTG concentrations when COCs are co-administered with LTG using a commonly prescribed 24 days of active pill and 4 days of placebo pill COC formulation. Five LTG dose change scenarios were simulated for 200 individuals each : 1) no change in dose, 2) 25% increase in LTG dose when COC is added, 3) 50% increase in LTG dose, 4) 100 mg flat increase in LTG dose and, 5) a 100 mg increase if pre-COC total daily dose is < 400 mg/day, or otherwise a 200 mg increase in LTG dose. For every simulation, we calculated the following comparison metrics between scenarios: percentage of the population with at least one incidence of 0.65 RTC; at least one incidence of >
Antiepileptic Drugs