Safety and tolerability of nabiximols oromucosal spray: a review of real-world experience in observational studies, registries, and case reports

ABSTRACT

Introduction

: Nabiximols oromucosal spray,a cannabis-based medicine containing a balanced ratio of Δ-9-tetrahydrocannabinol and cannabidiol, is approved widely as an add-on therapy for symptomatic relief of spasticity in people with multiple sclerosis (MS). Most safety data for nabiximols derive from use in MS spasticity, with some data available from the analgesia area.

Areas covered

: This review compiles safety and tolerability data from all published observational studies, registry analyses, and case reports identified in systematic searches in which nabiximols oromucosal spray was investigated for spasticity (n = 20) and/or chronic non-cancer pain (n = 4). Aligning with the known safety profile of nabiximols as demonstrated in randomized controlled trials, common adverse events reported consistently across studies conducted under clinical practice conditions were dizziness, fatigue and somnolence. The serious adverse event (SAE) rate with nabiximols in MS spasticityobservational studies was 3.1% (137/4351). A total of 39 treatment-related SAEs were reported in 32 patients with spasticity, all of which (where specified) were resolved. No treatment-related SAEs were recorded in nabiximols pain studies.

Expert opinion

: Real-world experience with nabiximols oromucosal spray in treating spasticity and chronic pain indicates that, overall, it is well tolerated and has a good safety profile.

KEYWORDS:

• Nabiximols
• sativex
• safety
• tolerability
• multiple sclerosis spasticity
• neurological pain
• observational studies

Article highlights

• This review compiles safety and tolerability data from all published observational studies, registry analyses, and case reports which investigated nabiximols oromucosal spray for treatment of spasticity and/or chronic pain.

• Systematic searches identified 20 studies or case reports of spasticity (19 in MS spasticity) and four studies or case reports of non-cancer pain.

• Observation periods in studies of nabiximols in MS spasticity ranged from 1 month to nearly 12 years’ exposure. The mean treatment discontinuation rate due to adverse events (AEs) was 16.8%. The most consistently reported AEs were dizziness, somnolence, and fatigue. The serious AE (SAE) rate was 3.1% (137/4351).

• Observational studies of nabiximols in chronic pain ranged from 4 to 12 weeks’ duration; one e-registry study accounted for 800 of the 830 total patients. The treatment end rate due to AEs was 4.6% (38/830). The most common treatment-emergent AE in the e-registry study was increased appetite (6.3%).

• A total of 39 treatment-related SAEs were recorded in 32 (2.5%) of 1265 patients treated with nabiximols for spasticity. No treatment-related SAEs were recorded in patients treated with nabiximols for pain.

• Real-world experience of nabiximols in patients with spasticity or chronic pain confirms that the medicine is generally well tolerated and has a good safety profile.

Acknowledgments

Writing assistance for this article was provided by Rob Furlong and Kerry Dechant on behalf of Content Ed Net (Madrid, Spain) with funding from Almirall S.A. (Barcelona, Spain).

Reviewer disclosures

The reviewer of this manuscript has disclosed that he or she has been a co-author on some publications on the effects of nabiximol on MS spasticity and the first author of a consensus paper on the treatment of MS spasticity. Peer reviewers of this manuscript have no other relevant financial relationships or otherwise to disclose.

Declaration of interest

JM Prieto González has received honoraria as a consultant for advisory boards, and as chairman or lecturer in meetings, and has participated in clinical trials and other research projects promoted by Actelion, Almirall, Bayer-Schering, Biogen-Idec, Merck-Serono, Novartis, Roche, Sanofi-Genzyme, and Teva. C Vila is a full-time employee of Almirall S.A. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

Writing assistance for this article was funded by Almirall S.A. (Barcelona, Spain).