Aprepitant for CVS

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Last year at NASPGHAN meeting (NASPGHAN Highlights and Tweets), there was data presented on aprepitant for cyclic vomiting syndrome (CVS).  This came up at a recent hospital PNT meeting as well.

  • Aprepitant (Emend) is an anti-emetic that works by blocking the NK1 receptor.
  • It has FDA approval for prevention of nausea and vomiting in moderate and highly emetogenic chemotherapy (adults and pediatrics) and prevention of post-operative nausea and vomiting (adult only).

Supporting Data for use of Aprepitant

An abstract published in 2006 reported on the use of aprepitant in 11 children (3-16 years)2.   Patients were refractory to/had poor response to pizotifen (not available in US – serotonin and histamine antagonist), propranol, and ondansetron.  Aprepitant was dosed at 80 mg/m2 up to twice weekly in combination with ondansetron.  Nine out of 11 patients had reduction in cycle frequency, duration of vomiting episodes and intensity of vomiting.  Three patients achieved complete cycle abolishment.

Cristoferi et al retrospectively reviewed 41 patients (age range 4-16.5 years, median 8 years) treated acutely or prophylactically with aprepitant.3  The primary outcome was decrease in frequency and intensity of CVS episodes.  The follow up period was 18-60 months.  The majority of patients failed cyproheptadine/pizotiphen, ondansetron, and amitriptyline as prophylactic medications.

Dosing regimens utilized in Cristoferi paper:

Prophylactic regimen (oral):

  • < 40 kg, 40 mg twice/week = $220/week (average wholesale price)
  • >40 kg to < 60 kg, 80 mg twice/week = $408/week
  • > 60 kg, 125 mg twice/week = $612/week

Acute regimen (oral):

  • >20 kg, 125 mg x 1 followed by 80 mg on day 2 and day 3 = $714
  • 15-<20 kg, 80 mg x 3 days = $612
  • < 15 kg, 80 mg x 1 followed by 40 mg on day 2 and day 3 = $424

Response rates:

  • With the prophylactic regimen, the authors reported a complete response in 3/16 (19%) and a partial response 10/16 (62%) [partial response was considered if there was ≥50% decrease in CVS episode frequency and intensity].
  • With the acute regimen, the authors reported 19/25 (76%) with a complete response and 3/25 (12%) with a partial response.

My take: Aprepitant appears promising as an agent for children who fail first-line therapies like periactin, tricyclic antidepressants, and ondansetron.

References

  1. Bhandari S and Venkatesan T.  Novel treatments for cyclic vomiting syndrome:  beyond ondansetron and amitriptyline.  Curr Treat Options Gastro 2016;14:495-506.
  2. Russell RK, et al. NK1 receptor antagonism ameliorates nausea and emesis in typical and atypical variants of treatment refractory cyclical vomiting syndrome.  J Pediatr Gastroenterol Nutr 2006;42:E13.
  3. Cristoferi F, et al. Efficacy of the neurokin-1 receptor antagonist aprepitant in children with cyclical vomiting syndrome.  Aliment Pharmacol Ther 2014;40:309-17.

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Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.