Safety and tolerability of nabiximols oromucosal spray: a review of more than 15 years" accumulated evidence from clinical trials

Abstract

Introduction: Nabiximols, a cannabinoid-based oromucosal spray, is indicated as add-on therapy for symptomatic relief of spasticity in persons with multiple sclerosis (MS). This review compiles tolerability and safety data from clinical trials that investigated nabiximols for spasticity and/or chronic pain.Areas covered: Systematic searches identified 38 placebo-controlled randomized controlled trials (RCTs) or post-RCT open-label studies reporting safety data: 15 in spasticity; 16 in neuropathic pain; six in chronic cancer pain; and one in rheumatoid arthritis pain. In RCTs, discontinuation rates due to adverse events (AEs) for nabiximols and placebo were lower in spasticity studies (5.4% and 2.8%) than in neuropathic pain (12.9% and 5.3%) or cancer pain (19.5% and 16.6%) studies. The most consistently identified AEs were dizziness, nausea and fatigue in spasticity or neuropathic pain studies; and dizziness, nausea, vomiting and somnolence in cancer pain studies. Serious AE (SAE) rates for nabiximols and placebo were higher in cancer pain (21.8% and 16.9%) than in MS spasticity (4.7% vs. 0.8%) and neuropathic pain (4.1% vs. 3.1%) studies despite similar dose ranges. Treatment-related SAEs showed no particular pattern.Expert opinion: More than 15 years of investigation of nabiximols oromucosal spray in spasticity and chronic pain conditions indicates an acceptable overall safety profile.

Keywords: Nabiximols; Sativex; chronic cancer pain; multiple sclerosis; neuropathic pain; safety; spasticity; tolerability.