What are the potential interactions between medroxyprogesterone and carbamazepine (Tegretol)?

Medroxyprogesterone and Carbamazepine Interaction

Carbamazepine significantly reduces the effectiveness of medroxyprogesterone contraception through enzyme induction, and alternative contraceptive methods should be strongly considered for women requiring carbamazepine therapy.

Mechanism of Interaction

Carbamazepine is a potent inducer of cytochrome P450 3A4 enzymes, which accelerates the metabolism of hormonal contraceptives including medroxyprogesterone 1. This enzyme induction increases the clearance of contraceptive steroids, leading to subtherapeutic hormone levels and potential contraceptive failure 2, 3.

Clinical Impact on Different Medroxyprogesterone Formulations

Depot Medroxyprogesterone Acetate (DMPA)

• DMPA injections maintain effectiveness despite carbamazepine coadministration 4
• The interaction is classified as Category 1 (no restriction) because DMPA's effectiveness is not decreased by enzyme-inducing anticonvulsants 4
• Dosing adjustment recommended: Administer DMPA every 10 weeks instead of the standard 12-week interval to maintain adequate contraceptive coverage 2

Oral Medroxyprogesterone (Progestin-Only Pills)

• Carbamazepine substantially reduces contraceptive efficacy of progestin-only pills 4
• This combination is classified as Category 3 (use not recommended; risks usually outweigh benefits) 4
• The interaction is harmful not because of safety concerns, but because it likely reduces contraceptive effectiveness 4
• Alternative contraceptive methods should be strongly encouraged for women on long-term carbamazepine therapy 4

Contraceptive Implants (Etonogestrel)

• Carbamazepine reduces etonogestrel concentrations by approximately 68% (median reduction from 158.1 to 50.9 pg/mL) 5
• Eight of 10 women fell below the ovulatory suppression threshold (<90 pg/mL) after carbamazepine coadministration 5
• Implants containing progestins are classified as Category 2 (generally can be used, but careful follow-up required) with carbamazepine 4

Comparison with Combined Hormonal Contraceptives

Carbamazepine reduces both ethinylestradiol and levonorgestrel exposure by approximately 40-50% 3. The area under the curve for ethinylestradiol decreased from 1163 to 672 pg·mL⁻¹·h, and levonorgestrel decreased from 22.9 to 13.8 ng·mL⁻¹·h 3. Combined oral contraceptives are classified as Category 3 with carbamazepine 4.

Recommended Management Algorithm

For women already on carbamazepine who need contraception:

1. First choice: DMPA injections every 10 weeks (not 12 weeks) 4, 2
2. Second choice: Copper or levonorgestrel intrauterine devices (Category 1 - no interaction) 4
3. Avoid: Progestin-only pills, combined oral contraceptives, and contraceptive patches/rings 4
4. Use with caution: Contraceptive implants, with awareness of reduced efficacy 4, 5

For women on hormonal contraception who require carbamazepine:

• Switch to DMPA with shortened dosing interval or an IUD before initiating carbamazepine 4, 2
• If continuing progestin-only methods, counsel extensively about increased pregnancy risk and recommend backup barrier methods 4

Critical Pitfalls to Avoid

• Delayed onset: Enzyme induction develops gradually over several weeks, so contraceptive failure may not be immediate 6
• Withdrawal effects: If carbamazepine is discontinued after dose adjustments were made to compensate for the interaction, hormone levels may rise and cause adverse effects 6
• Incomplete medication history: Patients may not volunteer information about contraceptive use or anticonvulsant therapy; always perform thorough medication reconciliation 6
• Levonorgestrel implants are contraindicated with carbamazepine due to documented contraceptive failures 2

Non-Interacting Alternatives

If seizure control permits, consider switching to anticonvulsants without enzyme-inducing properties: valproic acid, lamotrigine (Category 1 with all hormonal contraceptives), gabapentin, levetiracetam, or topiramate at doses <200 mg/day 4, 2.