Levomepromazine

Clinical question 2d:

What is the effect of levomepromazine in the treatment of nausea and/or vomiting in patients in the palliative phase of cancer, heart failure, COPD, MS, ALS or renal failure?

Recommendation

Treatment with levomepromazine orally (alternatively buccally or s.c.) is recommended for patients in the palliative phase with nausea and/or vomiting that responds insufficiently to other antiemetics.  

Introduction

Levomepromazine is a phenothiazine derivative with antidopaminergic, antiserotonergic, anticholinergic and antihistaminic action [Dietz 2013]. It may be administered orally, subcutaneously or intravenously. Sedation is the most important side effect.
It is not registered in the Netherlands for the treatment of nausea and vomiting.

In the following text, the role of levomepromazine in the prevention and treatment of nausea and vomiting as a result of chemotherapy will not be discussed.

Literature discussion

Two uncontrolled studies [Eisenchlas 2005; Kennet 2004] as well as two systematic reviews [Davis 2010; Dietz 2013] were found during the literature research.

Eisenchlas described a prospective open-label study in 70 patients with an advanced stage of cancer who suffered from severe nausea and/or vomiting (numeric rating scale (NRS) >7 on a scale of 0-10). All patients were treated previously with other antiemetics (especially metoclopramide, haloperidol and dexamethasone). The median dose of levomepromazine was 6.25 mg once daily (range 3-25) as subcutaneous bolus. After 48 hours, the NRS for nausea decreased by >6 points for 86% of patients; in 92% of patients who were vomiting, the vomiting disappeared completely. For all twelve patients who had a gastric tube due to the vomiting, the gastric tube could be removed. The median sedation score was 2; nine patients (13%) had a sedation score >3 [Eisenchlas 2005].

Kennet conducted a prospective open-label study in 65 patients (of which 53 were evaluable after 2 days and 34 after 5 days) with an advanced stage of cancer with a score for nausea or vomiting of >1 on a scale of 0-3. 57/65 patients were treated earlier with one or more antiemetics (mostly metoclopramide and cyclizine). Most patients received 12.5 mg orally once daily or 6.25 mg/24 hours as continuous subcutaneous infusion. After two and five days, 26% and 35% of patients had a complete remission (complete disappearance of nausea and/or vomiting), respectively, and 36% and 23% a partial remission (reduction of scores of nausea and/or vomiting)[Kennet 2004].

Both reviews concluded that, based on non-comparative prospective research, levomepromazine can be considered an effective antiemetic [Davis 2010; Dietz 2013].

There are indications that levomepromazine is an effective antiemetic for patients with an advanced stage of cancer, who have responded insufficiently to previous antiemetics. [Eisenchlas 2005; Kennet 2004]

Levomepromazine has not been studied in patients with diseases other than cancer. However, there is no reason to assume that it would be less effective in other diseases. For patients with therapy-resistant nausea and/or vomiting and a disease other than cancer, treatment with levomepromazine may therefore also be considered.
While a large proportion of patients in the research studies by Eisenchlas and Kennet were treated with subcutaneous levomepromazine, oral administration is preferable. It is recommended to administer the lowest possible effective dose, due to drowsiness as a possible side effect.

Levomepromazine is not reimbursed. However, given the low costs, this is not a reason not to prescribe the drug.