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Drugs Aging. 2019 Apr;36(Suppl 1):129-143. doi: 10.1007/s40266-019-00666-9.

Safety of Opioids in Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis.

Author information

1
MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK.
2
Portsmouth Hospitals NHS Trust, Portsmouth, UK.
3
Department of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium.
4
WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and Aging, Liège, Belgium.
5
Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds and NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
6
Arthritis Research UK Primary Care Centre, Institute for Primary Care and Health Sciences, Keele University, Keele, UK.
7
Division of Musculoskeletal, Internal Medicine and Oncological Rehabilitation, Department of Orthopaedics and Traumatology, Hôpital du Valais (HVS), Centre Hospitalier du Valais Romand (CHVR), CVP, Crans-Montana, Switzerland.
8
Biochemistry Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia.
9
MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK. cc@mrc.soton.ac.uk.
10
WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and Aging, Liège, Belgium. cc@mrc.soton.ac.uk.
11
National Institute for Health Research (NIHR) Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK. cc@mrc.soton.ac.uk.

Abstract

OBJECTIVE:

We aimed to assess the safety of opioids in the management of osteoarthritis (OA) in a systematic review and meta-analysis of randomized, placebo-controlled trials.

METHODS:

A comprehensive literature search was undertaken in the MEDLINE, Cochrane Central Register of Controlled Trials (Ovid CENTRAL), and Scopus electronic databases. Randomized, double-blind, placebo-controlled, parallel-group trials that assessed adverse events (AEs) with opioids in patients with OA were eligible for inclusion. Two authors appraised titles, abstracts and full-text papers for suitability and then assessed the studies for random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data and selective outcomes reporting. The primary outcomes of interest were gastrointestinal (GI) disorders, cardiac disorders, vascular disorders, nervous system disorders, skin and subcutaneous tissue disorders, renal and urinary disorders, respiratory, thoracic and mediastinal disorders, as well as overall severe and serious AEs and drug-related AEs. Secondary outcomes were withdrawals due to AEs (i.e. the number of participants who stopped the treatment due to an AE) and total number of AEs (i.e. the number of patients who experienced any AE at least once).

RESULTS:

Database searches identified 2189 records, from which, after exclusions, 17 papers were included in the meta-analysis. More disorders of the lower GI tract (constipation, fecaloma) were reported with both immediate-release (IR) and extended-release (ER) formulations of opioids versus placebo: IR opioids (relative risk [RR] 5.20, 95% confidence interval [CI] 3.42-7.89); ER opioids (RR 4.22, 95% CI 3.44-5.17). The risk of upper GI AEs increased fourfold with ER opioids compared with placebo (RR 4.03, 95% CI 0.87-18.62), and the risk of nausea, vomiting or loss of appetite increased four- to fivefold with both formulations: IR opioids (RR 3.39, 95% CI 2.22-5.18); ER opioids (RR 4.03, 95% CI 3.37-4.83). An increased risk of dermatologic AEs (rash and pruritis; IR opioids: RR 3.60, 95% CI 1.74-7.43; ER opioids: RR 7.87, 95% CI 5.20-11.89) and central nervous system disorders (dizziness, headache, fatigue, somnolence, insomnia; IR opioids: RR 2.76, 95% CI 1.90-4.02; ER opioids: RR 2.76, 95% CI 2.19-3.47) was found with all opioid formulations versus placebo.

CONCLUSIONS:

Our results confirm that there are considerable safety and tolerability issues surrounding the use of opioids in OA, and support the recommendation of international and national guidelines to use opioids in OA after other analgesic options, and for short time periods.

PMID:
31073926
PMCID:
PMC6509215
DOI:
10.1007/s40266-019-00666-9
[Indexed for MEDLINE]
Free PMC Article

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