What is the dose of aprepitant (neurokinin-1 receptor antagonist) for postoperative nausea and vomiting (PONV) management in adult and pediatric patients with varying levels of renal function?

Aprepitant Dosing for Postoperative Nausea and Vomiting (PONV)

For PONV prophylaxis in adults, administer a single oral dose of aprepitant 40 mg given 1-3 hours before induction of anesthesia, which provides superior vomiting prevention compared to ondansetron 4 mg IV for up to 48 hours postoperatively. 1, 2

Standard Dosing Regimen

• Oral aprepitant 40 mg as a single preoperative dose is the established regimen for PONV prevention, administered 1-3 hours before anesthesia induction 3, 1, 4
• Higher doses (80 mg or 125 mg) have been studied but offer no additional benefit over 40 mg for PONV, unlike the higher doses required for chemotherapy-induced nausea 1, 5, 2
• The 40 mg dose demonstrates efficacy for both early (0-24 hours) and delayed (24-48 hours) postoperative vomiting 1, 2

Combination Therapy Approach

• Aprepitant should be combined with dexamethasone 10 mg IV after anesthesia induction for enhanced efficacy in high-risk patients 3
• This combination (aprepitant 40 mg + dexamethasone 10 mg) reduced vomiting incidence to 16% at 48 hours compared to 38% with ondansetron + dexamethasone in craniotomy patients 3
• Aprepitant can be used as monotherapy or combined with other antiemetic classes, as multimodal prophylaxis is recommended for patients with ≥2 PONV risk factors 6

Efficacy Data

• Vomiting prevention rates with aprepitant 40 mg: 84% at 24 hours and 82% at 48 hours, compared to 71% and 66% with ondansetron 4 mg IV 1
• Meta-analysis data shows aprepitant reduces vomiting odds by approximately 50% (OR 0.48 on POD1, OR 0.54 on POD2) compared to conventional antiemetics 2
• Complete response rates (no vomiting, no rescue antiemetics) are significantly higher with aprepitant: 64% versus 55% with ondansetron at 24 hours 1

Clinical Context and Limitations

• While aprepitant effectively prevents vomiting, nausea control may be less robust, with some studies showing no significant difference in nausea incidence between aprepitant and ondansetron groups 3
• The evidence base shows unexplained heterogeneity (67-72%) across studies, which somewhat limits the strength of recommendations 2
• Aprepitant is not recommended as first-line for routine PONV prophylaxis in colorectal surgery, as it has not been shown superior to ondansetron in standard-risk patients 6

Special Populations and Considerations

• High-risk surgical patients (craniotomy, major abdominal surgery) benefit most from aprepitant-based regimens 3, 1
• Aprepitant is generally well-tolerated with minimal adverse effects at the 40 mg PONV dose 1, 4, 2
• No dose adjustment is specified for renal impairment in the available PONV literature, though this reflects limited data rather than established safety 3, 1

Drug Interactions

• Aprepitant is a CYP3A4 substrate, moderate inducer, and moderate inhibitor, which can affect metabolism of other perioperative medications 6, 7
• Contraindicated with pimozide, terfenadine, astemizole, or cisapride due to risk of serious cardiac reactions 6, 7
• When combined with dexamethasone, consider that aprepitant may increase dexamethasone exposure, though the 10 mg dexamethasone dose used in PONV studies accounts for this interaction 3

Practical Algorithm

For patients with 0-1 PONV risk factors: Use standard prophylaxis (5-HT3 antagonist ± dexamethasone); aprepitant not indicated 6

For patients with 2-3 PONV risk factors: Consider aprepitant 40 mg PO preoperatively + dexamethasone 10 mg IV as dual therapy 3, 1

For patients with ≥3 PONV risk factors or high-risk surgery: Use aprepitant 40 mg PO + dexamethasone 10 mg IV + 5-HT3 antagonist as triple therapy 6, 3