The metabolism of ethinyl estradiol and progestin are susceptible to CYP3A4 induction and increased glucuronidation. Serum concentrations may be reduced by ≥50% when used concomitantly with CYP enzyme–inducing medications, which could possibly result in subtherapeutic levels and unplanned pregnancy.3 CYP3A4 induction occurs for up to 4 weeks after discontinuation of an enzyme-inducing agent, pointing to the need for alternative or backup contraception during this time.3 Lamotrigine is not a CYP enzyme–inducing medication; it is unlikely to affect the efficacy of oral contraceptives in the same manner as other antiseizure medications. However, a study of lamotrigine and the combined hormonal contraceptive ethinyl estradiol and levonorgestrel demonstrated reduced exposure to levonorgestrel, resulting in breakthrough bleeding.5
In a study on the coadministration of lamotrigine and combined oral contraceptives, Sidhu et al4 observed a small mean reduction (20%) in progestin concentrations when lamotrigine was used at a dose of 300 mg/d. Although there is no research suggesting decreased effectiveness in preventing pregnancy when lamotrigine is used with combined oral contraceptives, progestin-only oral contraceptives, or progestin implants, additional or alternative contraceptive methods may be considered based on this pharmacokinetic data, particularly in patients who require lamotrigine doses ≥300 mg/d.5
CASE CONTINUED
Given when Ms. A started the oral contraceptive, the treatment team determines it is likely that an interaction with lamotrigine is causing her resurgence of depressive symptoms. Her care team decides to titrate the lamotrigine gradually to 300 mg/d, then 400 mg/d if needed, while carefully monitoring for signs of a serious rash. This dosage increase may help Ms. A achieve symptom remission. Monitoring plasma levels may be considered, although it is unknown what plasma level was effective for Ms. A before she started the oral contraceptive. Ms. A would need to be counseled regarding the effect of higher doses of lamotrigine on the effectiveness of the oral contraceptive.
Although it does not appear Ms. A is using the oral contraceptive specifically to prevent pregnancy, the team informs her about the possibility of unintended pregnancy with this medication combination. If Ms. A was also using the medication for this indication, alternative contraceptive options would include medroxyprogesterone acetate, levonorgestrel implants, or an intrauterine device (levonorgestrel or copper, though copper would not be effective for endometriosis symptom management). Ms. A should consult with her gynecologist regarding the most appropriate option for her endometriosis. If the decision is made to discontinue her oral contraceptive in the future, the lamotrigine dose should be decreased to her previously effective dose of 200 mg/d.
Related Resources
- Makino KK, Hatters Friedman S, Amin J. Emergency contraception for psychiatric patients. Current Psychiatry. 2022;21(11):34-39,44-45. doi:10.12788/cp.0300
- MGH Center for Women’s Mental Health. You asked: is there an interaction between lamotrigine and oral contraceptives? September 29, 2015. https://womensmentalhealth.org/posts/you-asked-is-there-an-interaction-between-lamotrigine-andoral-contraceptives/
Drug Brand Names
Bupropion extended-release • Wellbutrin XL
Carbamazepine • Equetro, Tegretol
Desogestrel • Cerazette
Divalproex sodium • Depakote
Ethinyl estradiol and etonogestrel • NuvaRing
Ethinyl estradiol and norelgestromin • Ortho Evra
Ethinyl estradiol and norgestimate • Ortho Tri-Cyclen, TriNessa, others
Etonogestrel • Implanon, Nexplanon
Gabapentin • Neurontin
Lamotrigine • Lamictal
Levonorgestrel emergency contraceptive pill • AfterPill, Plan B
Levonorgestrel intrauterine device • Mirena, Skyla
Medroxyprogesterone acetate • Depo-Provera
Oxcarbazepine • Trileptal
Topiramate • Topamax
Valproic acid • Depakene