Does Nexplanon (etonogestrel implant) interfere with valproate, lamotrigine, or clobazam?

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Nexplanon's Interactions with Valproate, Lamotrigine, and Clobazam

Nexplanon (etonogestrel implant) does not interact with valproate or clobazam, but may have reduced effectiveness when used with lamotrigine. 1

Interactions with Each Medication

Valproate

  • No clinically significant drug interactions have been reported between progestin-only contraceptives (including implants) and valproate 1, 2
  • Population pharmacokinetic analysis showed that valproate did not affect the exposure of etonogestrel implants 1
  • Nexplanon can be safely used with valproate without dosage adjustments or concerns about reduced contraceptive efficacy

Lamotrigine

  • No drug interactions have been reported between lamotrigine and progestin-only contraceptives, including implants 1
  • This is in contrast to combined hormonal contraceptives, which can significantly decrease lamotrigine levels and potentially increase seizure activity 1
  • Nexplanon is classified as Category 1 (no restriction) for use with lamotrigine according to the U.S. Medical Eligibility Criteria for Contraceptive Use 1

Clobazam

  • No significant interactions between clobazam and progestin-only contraceptives have been documented 3, 4
  • Clobazam primarily undergoes metabolism through CYP3A4 and CYP2C19 pathways 3
  • Studies show clobazam did not affect the exposure of drugs metabolized by UGT enzymes (like lamotrigine), suggesting it would not affect etonogestrel metabolism 4

Clinical Implications

Contraceptive Efficacy

  • Nexplanon maintains its contraceptive efficacy when used with valproate, lamotrigine, or clobazam
  • This is important because unintended pregnancy in women with epilepsy carries significant risks related to:
    • Potential teratogenic effects of antiepileptic medications
    • Risks of seizures during pregnancy
    • Complications of medication management during pregnancy

Seizure Control

  • Unlike combined hormonal contraceptives, Nexplanon does not appear to affect seizure control in women taking these antiepileptic medications 1
  • This is particularly important for lamotrigine, where combined hormonal contraceptives can significantly reduce lamotrigine levels and potentially worsen seizure control

Practical Considerations

Monitoring Recommendations

  • No special monitoring of drug levels is required when using Nexplanon with these medications
  • Regular follow-up for seizure control is still recommended as part of standard epilepsy care

Potential Pitfalls to Avoid

  • Do not confuse the drug interaction profile of Nexplanon (progestin-only implant) with combined hormonal contraceptives, which have more significant interactions with antiepileptic drugs
  • Be aware that other enzyme-inducing antiepileptic drugs (carbamazepine, phenytoin, phenobarbital, topiramate) can reduce the effectiveness of Nexplanon and should be avoided or alternative contraception considered 1, 5

Alternative Options

  • If there are concerns about using Nexplanon with these medications, depot medroxyprogesterone acetate (DMPA) injections are another excellent option as they have no interactions with any of these antiepileptic drugs 1

In summary, Nexplanon is a safe and effective contraceptive option for women taking valproate, lamotrigine, or clobazam, without significant drug interactions that would compromise either contraceptive efficacy or seizure control.

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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