What are the recommendations for using birth control with Lamictal (lamotrigine)?

Lamotrigine and Birth Control: Critical Bidirectional Interaction

Women taking lamotrigine (Lamictal) should avoid combined hormonal contraceptives (pills, patches, rings containing estrogen) because this combination creates a dangerous bidirectional drug interaction: estrogen-containing contraceptives reduce lamotrigine levels by more than 50% (increasing seizure risk), while lamotrigine is classified as Category 3 for combined hormonal contraceptive use (meaning the risks usually outweigh benefits). 1

The Bidirectional Problem

Estrogen Reduces Lamotrigine Levels (Primary Safety Concern)

• Combined oral contraceptives (COCs) containing ethinyl estradiol reduce lamotrigine plasma concentrations by 50-60%, significantly increasing the risk of breakthrough seizures 2, 3
• This occurs because estrogen induces glucuronidation enzymes that metabolize lamotrigine more rapidly 4, 2
• Women on lamotrigine who start COCs require approximately 2.5 times higher lamotrigine doses to maintain therapeutic levels (dose/weight/concentration ratio increases from 0.8 to 2.1 L/kg/day) 2
• This interaction applies to all estrogen-containing hormonal contraceptives, including patches and vaginal rings, not just pills 1

Lamotrigine Reduces Contraceptive Effectiveness

• The U.S. Medical Eligibility Criteria classifies lamotrigine as Category 3 for combined hormonal contraceptive use, meaning risks usually outweigh benefits 1
• Pharmacokinetic studies demonstrate that COCs significantly decrease lamotrigine serum levels, and some women experienced increased seizure activity when using both medications together 1
• This classification specifically applies to lamotrigine monotherapy; the interaction may differ when lamotrigine is combined with non-enzyme-inducing antiepileptic drugs like valproate 1

Recommended Contraceptive Options for Women on Lamotrigine

Safe First-Line Options (No Interaction)

Progestin-only methods and non-hormonal methods do not interact with lamotrigine and should be prioritized: 1, 3, 5

• Copper IUD (Cu-IUD): Category 1 - no restrictions, highly effective, no drug interaction 1
• Levonorgestrel IUD (LNG-IUD): Category 1 - no restrictions, no drug interaction 1
• Progestin-only pills (norethindrone or norgestrel): Category 1 - no interaction with lamotrigine 1, 3, 5
• Drospirenone progestin-only pill: Category 1 - no interaction 1
• DMPA injection (Depo-Provera): Category 1 - no interaction, though standard 12-week dosing interval is appropriate (unlike with enzyme-inducing anticonvulsants) 1, 3
• Etonogestrel implant: Category 1 - no interaction with lamotrigine 1, 3

Important Caveat About Progestin-Only Methods

• Progestin-only contraceptives do NOT reduce lamotrigine levels and are safe from a seizure control perspective 3, 5
• No significant drug interactions have been documented between lamotrigine and progestin-only methods 3, 5

If Combined Hormonal Contraceptives Must Be Used

This approach requires close monitoring and is not ideal: 1, 2

• Use a preparation containing at least 30 μg ethinyl estradiol (though this does not eliminate the interaction) 1
• Monitor lamotrigine plasma levels closely when initiating or discontinuing hormonal contraceptives 2
• Expect to need substantial lamotrigine dose increases (potentially 2-3 times the baseline dose) when starting COCs 2
• Conversely, expect lamotrigine toxicity risk if COCs are discontinued without dose reduction 2
• Check lamotrigine levels 2-4 weeks after any contraceptive change 2

Clinical Management Algorithm

1. First choice: Recommend copper IUD or levonorgestrel IUD for highly effective, long-acting contraception without drug interactions 1

2. Second choice: Offer progestin-only pills, DMPA injection, or etonogestrel implant if IUDs are declined 1, 3

3. Avoid: Combined hormonal contraceptives (pills, patches, rings) due to bidirectional interaction 1

4. If patient insists on combined hormonal contraceptives:

   • Counsel extensively about seizure risk and contraceptive failure risk 1
   • Obtain baseline lamotrigine level 2
   • Plan for lamotrigine dose adjustment 2
   • Arrange close follow-up with neurology 1

Common Pitfalls to Avoid

• Do not assume progestin-only methods are problematic - they are safe with lamotrigine, unlike with enzyme-inducing anticonvulsants 3, 5
• Do not confuse lamotrigine with enzyme-inducing anticonvulsants (phenytoin, carbamazepine, phenobarbital) - lamotrigine does NOT induce enzymes but is affected BY estrogen 1, 3
• Do not forget the reverse interaction - even if contraceptive efficacy were maintained, the reduction in lamotrigine levels poses serious seizure risk 2
• Remember that hormone replacement therapy (HRT) with estrogens may also reduce lamotrigine levels, similar to contraceptive estrogens 4