Aprepitant for CVS

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.

Most Popular Posts 2011-2018

Since this blog’s inception, there are now more than 2500 posts; these are the most popular (most views):

Most of these posts are referenced in more recent posts on the same or similar subjects.

Near Banff

 

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These five posts were the most popular (most views) in the past year:

This is a bike path from Canmore to Banff. I had a chance to ride an electric bike which was a lot of fun.

#NASPGHAN18 Highlights and Tweets (part 1)

I did not make it to this year’s meeting but did get a chance to catch up on a lot information via the PG 2018 Syllabus and based on information posted online.

Here are a couple of highlights for me:

Slides from postgraduate course on CVS from Dr. Katja Kovacic

The slide from Dr. Lightdale (pg 22 in Syllabus) below suggests it is OK for scope if platelets >20K and OK for biopsies if platelets >50K. It is worth noting that some adult data indicate that even lower biospy thresholds are reasonable for biopsies (Post: Lower Endoscopic Thresholds for Thrombocytopenia). As always, one needs to consider carefully the risks compared with the benefits.

From Postgraduate Course

 

 

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.

Costs/Yield of Diagnosing Cyclic Vomiting Syndrome

A recent retrospective study (CJ Lucia-Casadonte et al. JPGN 2018; 67: 13-17) examined the costs and yield of testing for Cyclic Vomiting Sydrome (CVS).

As a bonus –this is a study with CME available (& ABP MOC): NASPGHAN-JPGN CME The full text can be obtained at CME website.

This study looked at 503 charts from a single center using ICD-9 coding to identify patients. In this group, 165 (33%) had a diagnosis of CVS with 135 of this group (82%) meeting NASPGHAN diagnostic criteria with a mean age of 7.7 years.

Key findings:

  • 6 (4%) had a change in management based on CVS evaluation
  • The mean cost for screening was $6125.02 per patient
  • Atypical symptoms included bilious emesis in 9 (7%), abdominal pain in 67 (50%), attacks precipitated by fasting 1 (0.7%), and neurologic abnormalities in 3 (2%).
  • Brain MRI was performed in 68 patients and 10 were considered abnormal; though, only 1 (0.7%) had a change in management related to increased intracranial pressure (this patient had hx/o hydrocephalus). Other findings included Chiari I malformation, cerebral cyst, macrocephaly, and abnormal myelination pattern.
  • Other underlying diagnosis: UPJ obstruction (n=1), unspecified metabolic condition with carnitine deficiency (n=1), and eosinophilic esophagitis.
  • Given the costs involved, the authors reiterate NASPGHAN recommendations to avoid a ‘shotgun’ approach and note that it has previously been shown that “the most cost effective therapy in the management of CVS to be UGI with small bowel follow through (SBFT) with empiric treatment.”  Additional evaluation would be indicated for those with red flags and/or progressive or a changing pattern of vomiting episodes.
  • The authors indicate that endoscopy was the most costly evaluation tool at their institution ($11,500) and only used in 36 patients and was considered to have a low yield.

My take: This study underscores the low yield and expense involved in the evaluation of pediatric CVS; yet, it remains difficult to balance this with the concern of overlooking some anatomic and metabolic problems which can benefit from a timely diagnosis.

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Shem Creek, SC

Shem Creek, SC

Misdirection: False-postive Urine Cannaboid Screen due to Pantoprazole

First of all, this post is not a joke for April 1st. But if you have a good story to tell, please feel free to comment -I’ll share a story at the bottom of this post.

A case report (Felton D et al. Pediatrics 2015; 135: 2014-16) makes a few useful points regarding testing for cannaboids in a patient admitted for cyclic vomiting syndrome.

  1. Intravenous pantoprazole could lead to a false-positive urine cannaboid screen.
  2. Cannabis hyperemesis syndrome should be included in the differential diagnosis for cyclic vomiting. (see previous blog: Think Like a Doctor -Another Reason for Cyclic Vomiting …)
  3. Don’t order every test on the differential diagnosis (my point -not the authors).

With regard to the final point, this particular case report describes a highly-impaired 13 year old with previous diagnoses of intrauterine stroke, global developmental delays, and seizures; she was nonverbal and nonambulatory.  Therefore, despite a positive urine screen, it is not surprising that the confirmatory testing for cannabis via gas chromatography-mass spectrometry was negative.

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On a side note, several years ago we had a little fun in the spirit of April 1st.  One of our neighbors had been complaining for years that they had not received ‘yard of the month’ but had lived in the neighborhood for more than 16 years. So, one year when they were out of town, we managed to borrow the ‘yard of the month’ sign, placed it in their yard, and snapped a picture.  With the collusion of a different neighbor who sends out the monthly announcement, our neighbors were informed of the recognition of their yard. It was definitely a good laugh.  At the same time, I’m a little paranoid about potential payback.