Cyclizine pharmacovigilance in hospice/palliative care: net effects for nausea or vomiting.

OBJECTIVES: To describe the contemporary real-world use of cyclizine for nausea or vomiting, and the associated benefits and harms. METHODS: This was a prospective, consecutive case series of routine clinical use of cyclizine for nausea or vomiting in palliative care conducted across 19 sites in Australia, Aotearoa/New Zealand and the UK. Clinical outcomes were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events at baseline and 72 hours after initiation of cyclizine. Ad hoc safety reporting continued for 2 weeks. RESULTS: Data were collected from 101 patients between May 2018 and December 2020. Cyclizine was mostly used in combination with another antiemetic. Overall, 79 patients benefited and 32 experienced harm (56 had benefit without harm; 9 had harm without benefit). The most common harms were constipation (13%), somnolence (9%) and confusion (7%), adding to the already high rates of these symptoms at baseline. For the four patients with serious harms (grade ≥3), these were exacerbations of existing symptoms. Nine patients stopped cyclizine at 72 hours and a further 20 patients within 2 weeks. The most common reasons for stopping were lack of benefit and symptom resolution; none stopped because of harms. CONCLUSIONS: When used as described in a palliative care setting, cyclizine benefits about three-quarters of patients, with about one-third experiencing tolerable harms.

Treatment of nausea and vomiting in terminally ill cancer patients.

Nausea and vomiting is a common and distressing symptom complex in patients with far-advanced cancer, affecting up to 60% of individuals at some stage of their illness. The current approach to the palliative care of patients with nausea and vomiting is based on identifying the cause, understanding its pathophysiology and knowing the pharmacology of the drugs available for its amelioration. The following six main syndromes are identified: gastric stasis, biochemical, raised intracranial pressure, vestibular, mechanical bowel obstruction and ileus. A careful history, focused physical examination and appropriate investigations are needed to elucidate the syndrome and its cause, so that therapy is rational. Drugs are the mainstay of treatment in terminal cancer, and the main classes of antiemetic agents are prokinetics, dopamine antagonists, antihistamines, anticholinergics and serotonin antagonists. Dexamethasone and octreotide are also used, especially in bowel obstruction. Non-drug measures are important in relieving the associated distress. Patients should be able to die comfortably, without tubes. Despite decades of practice affirming this approach, the evidence base is weak and well designed studies are urgently needed.