Ondansetron risk med långtidsbehandling

Fråga: Finns risk med långtidsbehandling med odansetron 4-8 mg/dag? Utsättningsfenomen?

Svar:
Sammanfattning

Vi har inte hittat evidens om effekt eller säkerhet vid långtidsbehandling med ondansetron mot illamående och kräkningar.
En fallrapport om en patient med en arteriovenös missbildning i cerebellum, beskriver mild tremor och ökad flush i huvud- och halsregionen efter abrupt utsättande av ondansetron efter fyra dagars behandling mot extremt illamående och kräkningar.

Svar

The Canadian Agency for Drugs And Technologies in Health published in 2014 a review of the clinical effectiveness and safety of the long-term use (more than five days) of the serotonin receptor antagonists (5-HT3 RAs, including ondansetron, granisetron and dolasetron) for the prevention of nausea and vomiting (1). The key message from the review was that no evidence on the efficacy and safety of long-term use of 5-HT3 RAs for preventing nausea and vomiting was found.

The review article (1) also had a key message for the long-term use of 5-HT3 RAs for conditions other than nausea and vomiting. Effectiveness and safety of longer-term uses of ondansetron and granisetron have been investigated in randomized controlled trials (RCTs) enrolling patients with conditions such as alcohol dependence, stable schizophrenia, and tinnitus. Treatment durations ranged from 4 to 12 weeks. Treatment with these 5-HT3 RAs was not related with higher risk of adverse events, although patients were more likely to report constipation than placebo. No serious adverse events were reported in these RCTs.

We have not found any articles about the long-term safety of ondansetron published after this review from 2014 (2).

A Google search identifies two abstracts (3,4, attached). The first concludes that 17 patients with refractory nausea and vomiting appear to benefit from long term ondansetron therapy. The second abstract is based on a follow-up of the same patients seven years later, but only 8 of the 17 patients were available. Four of the 17 patients had DM and all four had died, and the authors speculate that the high death rate in the DM group may be related to the seriousness of their underlying conditions. Based on symptom scores from the 8 available patients, the authors conclude that long-term therapy with ondansetron is associated with continued improvements in symptoms of chronic nausea and vomiting in patients with moderate to severe GI motility disorders.

It is of course difficult to draw conclusions from these abstracts. They come from the same research group, involve the same (and very few) patients and were published as abstracts in 1995 and 2000, but have (strangely enough) never been published as full-length articles in peer-reviewed journals. They did not meet the inclusion criteria for the Canadian review described above.

Regarding withdrawal symptoms we have only found one case report, which states that it is the first clinical report demonstrating acute withdrawal from an antiemetic agent. It describes a 67-year-old male with an arteriovenous malformation located near the nausea and vomiting control center in brachium pontis in the cerebellum, who demonstrated acute withdrawal symptoms (mild tremor, increased head and neck flushing) after the abrupt discontinuation of ondansetron after 4 days of i.v. treatment (5, attached). Ondansetron was reinstated and 20 minutes later his tremors resolved with a reduction in his head and neck flushing to admission appearance.

1. https://www.cadth.ca/sites/default/files/pdf/htis/nov-2014/RC0530_5-HT3RA%20for%20nausea%20and%20vomiting_Final.pdf
2. http://www.ncbi.nlm.nih.gov/pubmed
3. Abell TL et al. Long-term therapy with ondansetron is effective in patients with refractory nausea and vomiting. Gastroenterology 1995;108: suppl 1 page A1.
4. El-Gammal A et al. Long term ondansetron therapy is beneficial in patients with chronic nausea and vomiting. Gastroenterology 2000;118: Abstract 5381.
5. Vadivelu S et al. Acute anti-emetic withdrawal associated with a hemorrhagic cerebellar arteriovenous malformation. J Clin Neuroscience 2010;17:1061-3.