Tag Archives: nausea

FDA Approves New Drug for Nausea/Vomiting

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FDA Announcement -here’s excerpt:

The U.S. Food and Drug Administration approved Varubi (rolapitant) to prevent delayed phase chemotherapy-induced nausea and vomiting (emesis). Varubi is approved in adults in combination with other drugs (antiemetic agents) that prevent nausea and vomiting associated with initial and repeat courses of vomit-inducing (emetogenic and highly emetogenic) cancer chemotherapy….

“Chemotherapy-induced nausea and vomiting remains a major issue that can disrupt patients’ lives and sometimes their therapy,” said Amy Egan, M.D., M.P.H., deputy director of the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research. “Today’s approval provides cancer patients with another treatment option for the prevention of the delayed phase of nausea and vomiting caused by chemotherapy.”

Varubi is a substance P/neurokinin-1 (NK-1) receptor antagonist. Activation of NK-1 receptors plays a central role in nausea and vomiting induced by certain cancer chemotherapies, particularly in the delayed phase. Varubi is provided to patients in tablet form.

The safety and efficacy of Varubi were established in three randomized, double-blind, controlled clinical trials where Varubi in combination with granisetron and dexamethasone was compared with a control therapy (placebo, granisetron and dexamethasone) in 2,800 patients receiving a chemotherapy regimen that included highly emetogenic (such as cisplatin and the combination of anthracycline and cyclophosphamide) and moderately emetogenic chemotherapy drugs. Those patients treated with Varubi had a greater reduction in vomiting and use of rescue medication for nausea and vomiting during the delayed phase compared to those receiving the control therapy…

The most common side effects in patients treated with Varubi include a low white blood cell count (neutropenia), hiccups, decreased appetite and dizziness.

Varubi is marketed by Tesaro Inc., based in Waltham, Massachusetts.

Teaching an Old Drug New Tricks

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A couple recent articles focused on the new uses of methotrexate (MTX) and how to handle potential hepatotoxicity:

  1. J Pediatr 2014; 164: 231-36
  2. Inflamm Bowel Dis 2014; 20: 47-59

In the first medical review article, the authors note the efficacy of MTX for the following:

  • Juvenile idiopathic arthritis
  • Uveitis
  • Psoriasis
  • Crohn disease
  • Juvenile dermatomyositis
  • Localized scleroderma
  • Vasculitis

This review article discusses mechanism of action which is poorly understood along with pharmacogenomics and practical issues in usage.  The latter includes the need for supplemental folic acid.  Other points:

  • “The long-term safety of MTX is remarkable”
  • “The issue of nausea and vomiting…can be especially disturbing.”  They note that one study demonstrated that ondansetron 1 hour prior to MTX from the first injection prevented nausea, which was often difficult to treat once developed.
  • “Liver enzyme abnormalities occur frequently (up to 30% of patients) but are usually of minimal clinical significance.”  Best to draw blood tests 1-2 days before MTX dosing.
  • “In children, unlike adults, MTX-related pulmonary adverse events are very rare.”
  • “In recent years it was shown that live vaccine boosters are effective and safe during MTX use (caution may be needed if MTX is used with other immunosuppression medications)” Ref: JAMA 2013; 309: 2449–56.
  • “Use during pregnancy or within 3 months of planning pregnancy is contraindicated”

The second article was a systemic review which identified 12 high-quality studies which focused on MTX hepatotoxicity in children.  Key findings:

  • 57 of 457 developed some degree of abnormal liver biochemistries.
  • Due to hepatotoxicity, dose reductions were undertaken in 6.4% and 4.5% discontinued MTX.

The authors note that studies of MTX in adults with IBD have not demonstrated cumulative liver toxicity from MTX.  In addition, many of the patients with hepatotoxicity may have had  other reasons for abnormal liver biochemistries including other medications (eg. glucocorticoids).  “Confirmation of MTX hepatotoxicity with a liver biopsy is seldom performed in children;” as a consequence, the exact rate of MTX hepatotoxicity is unknown.

The authors propose that liver biochemistry monitoring occur at baseline, biweekly x 2, then every 2-3 months.  Also, the authors recommend:

  • If ALT < 2 times upper limit of normal (ULN), check liver biochemistries every 2 weeks
  • If persistent abnormalities, the authors recommend an ultrasound
  • If ALT ≥ 2 times ULN, repeat testing should be obtained and consider consultation with a hepatologist

Bottomline: Methotrexate is an important medication for Crohn disease –there are not very many available.  If there are persistent liver enzyme elevations, dose reduction of MTX (or cessation) may be necessary.  As a practical matter, it is advisable to obtain blood draws 1-2 days prior to MTX rather than afterwards. Nausea can be minimized with ondansetron and weekend dosing.

Related blog posts:

There must be a reason for intractable vomiting

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There are cases when patients are clearly ill and the potential explanations are quite unsatisfactory.  Most patients with intractable nausea and vomiting have a specific etiology for this.  A disorder, rarely seen by gastroenterologists, has been identified that provides a detailed reason for a few patients with an “idiopathic vomiting” diagnosis (Clin Gastroenterol Hepatol 2013; 11: 240-5).

The authors examined a database of patients who presented with vomiting for autoantibodies to aquaporin-4 (AQP4).

Background: These autoantibodies are sensitive and specific for neuromyelitis optica (NMO).  In fact, finding these autoantibodies in serum or spinal fluid allows distinction of NMO spectrum disorders (NMOSDs) from multiple sclerosis.

In patients with NMOSDs, there are typical brain MRI findings in AQP4-enriched areas, including the fourth ventricle floor which contains the chemosenisitve nausea and vomiting center (area postrema).  AQP4 is the principal water channel in the central nervous system.

Design: The authors reviewed their database of 70 NMOSD patients to determine how many presented with vomiting.  In addition, they tested serum samples from patients who presented with idiopathic nausea and vomiting for AQP4-IgG from the gastroparesis research registry.  This included 318 patients with gastroparesis and 117 patients without gastroparesis.

Results:  Ten patients (14% of NMOSD database) presented with intractable vomiting. The youngest patient in this group was 26 years old.  All of these patients had a noncyclic pattern of vomiting.  Four had associated hiccups.  No control patients from the gastroparesis database was identified as having AQP4-IgG.

Why this is important: Early diagnosis allows initiation of immunosuppressant therapy which may modify the disease course. AQP4-IgG positivity predicts a high likelihood of relapsing attacks of optic neuritis and transverse myelitis.