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Olanzapine: An Effective Agent for Preventing Nausea

January 24, 2017
Treatment of symptoms associated with chemotherapy is a crucial aim for practitioners; olanzapine, an atypical antipsychotic medication, could be a valuable supplement to the usual therapeutic options for preventing nausea.

When faced with complaints of nausea and vomiting, common symptoms reported by patients with advanced malignancy, clinicians have had few appealing options given the usual treatments come with untenable, adverse side effects.

Much like severe pain symptoms, chemotherapy-induced nausea and vomiting may seriously compromise a patient's quality of life, and oftentimes, is perceived by patients as an unnecessarily and avoidable aspect of their cancer treatment.1

Preventing nausea and vomiting typically requires a combination of agents, such as 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists2 and neurokinin-1 (NK1) receptor antagonists.3-9 Despite these recommended and usual treatments,10-12 nausea still remains a frequent source of distress for most patients.1,2

Olanzaine, may prove an effective agent for preventing nausea.

However, new findings suggest that olanzapine, an atypical antipsychotic that works by blocking multiple receptors in the body, may offer an effective treatment option to significantly inhibiting nausea and vomiting symptoms in patients receiving highly emetogenic chemotherapy treatments.13

“As a pharmacist, we often must look beyond the package insert and consider unique pharmacologic mechanisms when standard therapy is not successful; it is something I spend hours teaching to student pharmacists and residents. When you think about it, olanzapine offers several pharmacological mechanisms that mimic what we offer these patients anyway,” Dr. Fudin told Practical Pain Management.

Counteracting the Effects of Nausea and Vomiting

The study, published in the The New England Journal of Medicine, was a double-blind, phase III trial to incorporate olanzapine into a treatment regimen for patients receiving highly emetogenic chemotherapy treatments. All 308 patients (olanzapine group n=192; placebo group n=188) received some form of 5-HT3–receptor antagonist [palonosetron (i.v. 0.25 mg); granisetron (i.v. 1 mg or oral 2 mg); ondansetron (i.v. or oral 8 mg)] as well as dosages of dexamethasone and an NK1-receptor antagonist.

Of the 192 patients also taking olanzapine, a higher proportion reported not having any have any nausea as compared to patients on the standard treatment regimen, 74% versus 45% (P = 0.002), respectively, during the early period of the study; 42% versus 25% (P = 0.002) during the later period, and 37% vs. 22% (P = 0.002) overall.

Blocking dopamine receptors is the typical method by which clinicians have provided treatment to counteract the emetogenic effects of chemotherapy. Until now, clinicians have relied on other antipsychotics, like prochlorperazine (Compazine) or haloperidol (Haldol), to do this, Dr. Fudin noted.  

However, olanzapine’s pharmacokinetic activity introduces a bevy of other influences on the body, blocking a number of serotonin receptors, catecholamines at alpha1-adrenergic receptors, acetylcholine at muscarinic receptors, and histamine at H1 receptors found in the central nervous system.8,9,14

According to researchers, olanzapine’s eclectic antagonistic effects on the body may make it a desirable agent for use in combination with an NK1-receptor antagonist, a 5-HT3–receptor antagonist, and dexamethasone for patients who have not received chemotherapy in the past but are currently undergoing highly emetogenic chemotherapy treatments.

Clinical Benefits of Olanzapine

Olanzapine frequently has been a useful agent in this context, according to Dr. Fudin. Operating as an effective anticholinergic, olanzapine affects the vagus nerve, thereby reducing gastric secretions, Dr. Fudin noted.

“The anticholinergic activity also prevents tardive dyskinesia and various side effects seen with metoclopramide (Reglan), which has lost favor for chemotherapy-induced emesis, but is sometimes employed,” Dr. Fudin said. Olanzapine also works by blocking serotonin type 3, “which is the very mechanism by which ondansetron and other newer antiemetics work.”

“Sometimes we use proton pump inhibitors to lessen the extended burden of stomach upset, but these can cause constipation, which is enhanced by opioids and anticholinergic drugs,” and patients usually find the extended bouts of nausea more troubling than intermittent vomiting, Dr. Fudin pointed out. Because of this, enhancing pharmaceutical regimens to counteract nausea and vomiting should be a significant goal of palliative treatments during chemotherapy.

In his own practice, Dr. Fudin has used olanzapine, particularly for chemotherapy patients taking some of the newer oral drugs for neoplastic disease. Given olanzapine’s mechanisms of action, the study’s evidence on the drug’s efficacy as an antiemetic were not surprising, said Dr. Fudin, who regards the drug as a no-brainer in terms of its utility to clinicians.

Indeed, the study results also indicate that 87% of patients receiving olanzapine during the early period of the study reported no clinically significant nausea at all, compared to 70% of patients on the standard therapy regimen (P =0.001), a trend that continued throughout the course of the study. Complete response to treatment also was significantly higher in the olanzapine group compared to the placebo group.

“One of the major adverse effects associated with olanzapine was sedation, usually around day 2 and then resolving afterward," said Dr. Fudin. Although the study authors mentioned the possibility of smaller dosages of the drug (5mg) having less of this side effect, this study limitation will be remedied in the future, Dr. Fudin said.

“No doubt lower doses of olanzapine and other atypical antipsychotics have less sedating activity.  In fact, it is often better to use smaller doses of several antiemetics that have pharmacologically variable mechanisms of action as this helps to reduce side effects, and may be additive or synergistic in allaying nausea and/or vomiting with a better side effect profile," said Dr. Fudin.

Using this method of “rational polypharmacy,” doctors may be better informed to treat nausea and vomiting that often burdens patients, while also managing curative treatments and pain management therapies. However, sedation may not necessarily be an unwanted side effect for some patients.

“We must also keep in mind that sedation is some cases may be desirable for a good night sleep, but reducing the dose to 2.5 or 5mg in combination with other antiemetics could be beneficial…controlled studies with various combinations would be helpful,” Dr. Fudin noted.

Long-term use of olanzapine is another issue doctors should consider, given the risk of olanzapine raising blood glucose levels. “This this could be more pronounced in patients that are receiving pulsed glucocorticoids as part of their chemotherapeutic regimen or even IV push once prior to chemotherapy,” Dr. Fudin noted.

“Overall, it’s a pharmacologically complex issue, but olanzapine does offer an exciting option as part of the armamentarium against antineoplastic-induced emesis,” said Dr. Fudin.

Dr. Fudin serves as a member of the speakers bureau for opioid-induced constipation for AstraZeneca, manufacturer of quetiapine (Seroquel). Dr. Fudin has no other potential conflicts of interest to report.

Last updated on: January 26, 2017
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