Aprepitant is a selective, high-affinity antagonist of human substance P/neurokinin 1 (NK1) receptors. This specific combination of a 125mg capsule on Day 1 followed by an 80mg capsule on Days 2 and 3 is a standard regimen for the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) associated with highly emetogenic chemotherapy (HEC). It is used in combination with a corticosteroid and a 5-HT3 antagonist. It works centrally in the brainstem vomiting center and peripherally in the gastrointestinal tract.
Adult: For prevention of CINV with HEC: Day 1: 125 mg orally 1 hour prior to chemotherapy. Days 2 and 3: 80 mg orally each morning. Must be given with a 5-HT3 antagonist (e.g., ondansetron) on Day 1 and a corticosteroid (e.g., dexamethasone) on Days 1-4 (dexamethasone dose must be reduced by approximately 50% when co-administered with aprepitant).
Note: Administer orally with or without food. Swallow the capsule whole with a glass of water. For patients unable to swallow capsules, the contents can be mixed in a small amount of soft food (e.g., applesauce) and consumed immediately without chewing. The Day 1 dose must be given 1 hour before chemotherapy. The Days 2 and 3 doses are given in the morning.
Aprepitant is a selective, high-affinity antagonist of the human substance P/neurokinin 1 (NK1) receptor. Substance P is involved in the final common pathway of emesis. By blocking NK1 receptors in the brainstem's vomiting center (area postrema and nucleus tractus solitarius) and in the gastrointestinal tract, aprepitant inhibits emesis signals triggered by chemotherapy.
Pregnancy: Category B: Animal studies have shown no risk, but no adequate and well-controlled studies in pregnant women. Use only if clearly needed and potential benefit justifies potential risk to the fetus.
Driving: May cause fatigue, dizziness, and somnolence. Patients should be cautioned about operating machinery or driving until they know how the medication affects them.
| Warfarin | Aprepitant induces CYP2C9, decreasing warfarin levels. INR can decrease by ~14% over 2 weeks. Requires close INR monitoring for 2 weeks after aprepitant regimen. | Major |
| Dexamethasone, Methylprednisolone | Aprepitant is a moderate CYP3A4 inhibitor, increasing corticosteroid AUC by ~2-3 fold. Dexamethasone dose must be reduced by approximately 50%. | Major |
| Midazolam, Triazolam | Increased plasma concentrations and sedation due to CYP3A4 inhibition. | Major |
| Pimozide | Increased pimozide levels, risk of QT prolongation and serious arrhythmias. Contraindicated. | Contraindicated |
| Oral Contraceptives (Ethinyl Estradiol, Norethindrone) | Decreased contraceptive efficacy during and for 28 days after aprepitant regimen due to CYP3A4 induction. Alternative non-hormonal contraception must be used. | Major |
| Chemotherapy agents metabolized by CYP3A4 (e.g., Docetaxel, Paclitaxel, Etoposide, Irinotecan, Vinblastine, Vincristine) | Potential increase in chemotherapeutic agent exposure and toxicity. Monitor for adverse effects. | Moderate |
| Rifampicin, Carbamazepine, Phenytoin | Strong CYP3A4 inducers decrease aprepitant plasma levels, reducing efficacy. Concomitant use not recommended. | Major |
| Ketoconazole, Itraconazole, Clarithromycin | Strong CYP3A4 inhibitors increase aprepitant plasma levels. Use with caution. | Moderate |
Same composition (Aprepitant (125mg) + Aprepitant (80mg)), different brands: