Aprepitant
Regulatory sources consulted
Approved indications
- Prevention of chemotherapy-induced nausea and vomiting with other antiemetics, and prevention of postoperative nausea and vomiting in adults.
Contraindications
Absolute
- Hypersensitivity to aprepitant or its components and concomitant use with pimozide.
Clinical warnings
- Major warning · It is contraindicated with pimozide. It may reduce hormonal contraceptive effectiveness during treatment and for 28 days after the last dose. — FDA label
Drug interactions
- HighWarfarinB01AA03
Mechanism: CYP2C9 induction may decrease INR.
Recommendation: Monitor INR for 2 weeks after starting aprepitant, especially on days 7 to 10, according to the label.
FDA label
- HighDexamethasone or methylprednisolone
Mechanism: CYP3A4 inhibition increases exposure to these corticosteroids.
Recommendation: The antiemetic regimen should use the corticosteroid dose reductions specified in the label and determined by oncology.
FDA label
- HighCYP3A4 inhibitors, inducers, or substrates
Mechanism: Aprepitant is a CYP3A4 substrate, weak-to-moderate inhibitor, and inducer and may alter exposure in both directions.
Recommendation: Review all combinations with the prescribing or pharmacy team and follow label adjustments.
FDA label
- HighPimozide
Mechanism: CYP3A4 inhibition can increase pimozide exposure.
Recommendation: Do not use together.
FDA label
Recent literature (PubMed)
Cyclic vomiting syndrome (CVS) is a chronic disorder of gut-brain interaction characterized by recurrent disabling episodes of nausea, vomiting, and abdominal pain. CVS affects both children and adults with a prevalence of approximately 2% in the United States. CVS is more common in female individuals and affects all races. The pathophysiology of CVS is unknown and a combination of genetic, environmental, autonomic, and neurohormonal factors is believed to play a role. CVS is also closely associated with migraine headaches and likely have a shared pathophysiology. The diagnosis of CVS is based on the Rome criteria, and minimal recommended testing includes an upper endoscopy and imaging studies of the abdomen. CVS is frequently associated with anxiety, depression, and autonomic dysfunction. Patients with CVS commonly use cannabis therapeutically for symptom relief. By contrast, cannabinoid hyperemesis syndrome is believed to be a subset of CVS with chronic heavy cannabis use leading to hyperemesis. Due to the recalcitrant nature of the illness, patients often visit the emergency department and are hospitalized for acute CVS flares. Guidelines on the management of CVS recommend a biopsychosocial approach. Prophylactic therapy consists of tricyclic antidepressants (amitriptyline), antiepileptics (topiramate), and aprepitant in refractory patients. Abortive therapy consists of triptans, antiemetics (ondansetron), and sedation. Treatment of comorbid conditions is extremely important to improve overall patient outcomes. CVS has a significant negative impact on patients, families, and the healthcare system, and future research to understand its pathophysiology and develop targeted therapies is needed. No information is available on the use of aprepitant during breastfeeding. Because aprepitant is more than 95% bound to plasma proteins, the amount in milk is likely to be low. If the mother requires aprepitant, it is not a reason to discontinue breastfeeding. However, consid
Gastroparesis is a complex gastric motility disorder characterized by nausea, vomiting, and other symptoms associated with a delay in gastric emptying in the absence of mechanical obstruction. Variations in diagnostic testing and limited effective treatments make caring for this patient population challenging. The American Gastroenterological Association developed this guideline to provide recommendations for ensuring an accurate diagnosis and identifying evidence-based, effective treatments among the available pharmacologic and procedural interventions for patients with idiopathic gastroparesis or gastroparesis related to diabetes. The Grading of Recommendations Assessment, Development and Evaluation framework was used to assess evidence and develop this guideline. The Guideline Panel prioritized clinical questions and outcomes, conducted an evidence review, and used the Evidence to Decision Framework to develop recommendations. The Guideline Panel agreed on 12 recommendations. A conditional recommendation was issued against using 2-hour gastric emptying testing and in favor of 4-hour testing in patients with suspected gastroparesis. There are conditional recommendations for the use of metoclopramide and erythromycin in patients with gastroparesis. Conditional recommendations were issued against the use of domperidone, prucalopride, aprepitant, nortriptyline, buspirone, and cannabidiol as first-line therapies. In addition, conditional recommendations were issued against the routine initial use of gastric per-oral endoscopic pyloromyotomy or gastric electrical stimulation in patients with gastroparesis, reserving these treatments for select patients with symptoms refractory to medical therapies. No recommendation was given regarding the use of surgical pyloromyotomy and surgical pyloroplasty, which were identified as procedures with knowledge gaps in their use for treatment for gastroparesis. The diagnosis of gastroparesis requires the use of 4-hour gastric emptying
The prophylaxis and treatment of postoperative pain to enhance patient comfort has been a primary goal of anesthesiologists for the last decades; however, avoiding postoperative nausea and vomiting (PONV) is, from a patient's perspective, a highly relevant and equally important goal of anesthesia. Recent consensus-based guidelines suggest the assessment of risk factors including female gender, postoperative opioid administration, non-smoking status, a history of PONV or motion sickness, young patient age, longer duration of anesthesia, volatile anesthetics and the type of surgery and reducing the patient's baseline risk (e.g. through the use of regional anesthesia and administration of non-opioid analgesics as part of a multimodal approach). In general, a liberal PONV prophylaxis is encouraged for adult patients and children, which should also be administered when no risk assessment is made. The basis for every adult patient should be a standard prophylaxis with two antiemetics, such as dexamethasone in combination with a 5-HT3 receptor antagonist. In patients at high risk, this should be supplemented by a third and potentially a fourth antiemetic prophylaxis with a different mechanism of action. A recently published comprehensive Cochrane meta-analysis comparing available antiemetic prophylaxes reported the highest effectiveness to prevent PONV for the NK1 receptor antagonist aprepitant (relative risk, RR 0.26), followed by ramosetron (RR 0.44), granisetron (RR 0.45), dexamethasone (RR 0.51) and ondansetron (RR 0.55), thereby revising the dogma that every antiemetic is equally effective. Adverse events of antiemetics were generally rare and reported in less than half of the included studies, yielding a low quality of evidence for these end points. In general, combinations of different antiemetics were more effective than single prophylaxes. In children above 3 years of age, the same principles should be applied as in adults. For these patients, there is a high degr
Several forms of cannabinoids are currently being used to manage nausea and vomiting (N/V). Emerging cases of refractory N/V associated with chronic cannabis use among adults and older patients have been reported named cannabis hyperemesis syndrome (CHS). CHS is a condition that leads to repeated and severe N/V in long-term users of cannabinoids. The aim of this study was to outline current treatments for the management of CHS. A systematic review was conducted using PubMed, Ovid MEDLINE, Cochrane Central, EMBASE, and Google Scholar. Databases were used to search for articles on CHS published from January 2009 to June 2021, yielding 225 results of which 17 were deemed relevant and underwent review by 2 separate reviewers. The duration of cannabis administration ranged between 6 months to 11 years may precipitate symptoms of CHS. The Rome IV diagnostic criteria of CHS require cannabinoid use and persistence of N/V symptoms for at least the past 6 months. Cannabis cessation is noted to be the most successful management, but other treatments also demonstrated symptom relief; these include hot water hydrotherapy, topical capsaicin cream, haloperidol, droperidol, benzodiazepines, propranolol, and aprepitant administration. More research on CHS is needed to enhance knowledge translation, education, and create awareness in the medical community on the side effects of cannabinoids and to propose the best treatment options.