Aprepitant Interferes with Oral Hormonal Contraception
Aprepitant is the antiemetic that reduces the effectiveness of oral hormonal contraceptives. Ondansetron and metoclopramide do not have this interaction.
Mechanism and Clinical Significance
Aprepitant is a substrate, moderate inhibitor, and moderate inducer of cytochrome P450 enzyme 3A4 (CYP3A4), and also induces CYP2C9 1. Through these mechanisms, aprepitant decreases the area under the curve (AUC) of oral contraceptives, reducing their efficacy 1.
FDA-Mandated Warnings
The FDA drug label explicitly states: "Advise patients that administration of aprepitant may reduce the efficacy of hormonal contraceptives. Instruct patients to use effective alternative or back-up methods of contraception (such as condoms and spermicides) during treatment with aprepitant and for 1 month following the last dose of aprepitant" 2.
This warning applies to:
- All formulations of aprepitant (oral capsules and intravenous fosaprepitant)
- All hormonal contraceptive methods containing hormones (pills, patches, implants, and certain IUDs)
Clinical Recommendations
Patients taking aprepitant must use backup contraception:
- Begin alternative/backup methods (condoms, spermicides) before starting aprepitant
- Continue backup contraception during the entire treatment course
- Maintain backup contraception for 1 full month after the last dose of aprepitant 2
The guidelines consistently emphasize this drug interaction across multiple NCCN antiemesis guidelines 1, reflecting its clinical importance.
Why Not the Other Options
Ondansetron (a 5-HT₃ receptor antagonist) does not interact with hormonal contraceptives. It has a different mechanism of action and does not significantly affect CYP450 enzymes in a way that would reduce contraceptive efficacy 3, 4.
Metoclopramide (a dopamine antagonist) similarly does not have documented interactions with hormonal contraceptives 5, 6.
Common Pitfall
The interaction is dose-independent and occurs with all aprepitant regimens, including:
- The standard 3-day chemotherapy regimen (125 mg day 1, then 80 mg days 2-3)
- Single-dose postoperative regimens (40 mg)
- Intravenous fosaprepitant formulations
Healthcare providers must counsel all reproductive-age women receiving aprepitant about this interaction, regardless of the indication or duration of therapy 2.
Answer: a) Aprepitant