Month: August 2017

Query 16-08: Ondansetron use in pregnancy and risk of fetal abnormality.

This research was funded by the Drug Safety and Effectiveness Network (DSEN) and conducted by the following investigators: Anick Berard, Odile Sheehy, Jessica Gorgui, Jin-Ping Zhao, Cristiano S Moura, Sasha Bernatsky.

Issue:

• Nausea and vomiting of pregnancy affect up to 80% of pregnancies and typically occurs during the first trimester, the most sensitive time for environmental exposures.
• Antiemetics such as metoclopramide and ondansetron may be prescribed for severe NVP. The number of ondansetron-exposed pregnancies markedly increased between 2006 and 2014.
• A recent multinational study showed that Canada had the highest prevalence (42%) of antiemetic use for the treatment of nausea and vomiting in pregnancy, yet evidence regarding the risk of fetal abnormalities related to ondansetron remains inconsistent and inconclusive.

Study aim:

• We aimed to quantify the risk of fetal abnormalities (overall and organ-specific) associated with ondansetron use during pregnancy.
• Given that organogenesis occurs in the first trimester, the first trimester will be the preferred exposure time-window (primary analysis) but the risk associated with second and third-trimester exposures will also be studied (secondary analysis). weaknesses using qualitative methods.

Study description:

• We used the Quebec Pregnancy Cohort, an ongoing population-based cohort with prospective data collection on all pregnancies that occurred between January 1998 and December 2015 in the province of Quebec, including the RAMQ medical service database, the Quebec Public Prescription Drug Insurance database, the MedEcho hospitalization database, and the Quebec Statistics database. Exposure to ondansetron was defined based on prescriptions filled, and major congenital malformations in the RAMQ and MedEcho databases were defined according to ICD-9 and ICD-10 diagnostic codes. Generalized estimating equations models were used, with pregnancy as a unit of analysis.

Study findings:

• Among the 31 pregnancies exposed to ondansetron, two resulted in a major congenital malformation(congenital hydronephrosis, an anomaly of the tongue).
• No statistically significant association was found between ondansetron exposure and the risk of overall major congenital malformations.
• Caution is warranted, given the relatively low number of exposed pregnancies.

Summary:

• Nausea and vomiting of pregnancy affect the vast majority of pregnancies and antiemetics such as metoclopramide and ondansetron may be prescribed for the management of these symptoms.
• A recent multinational study showed that Canada had the highest prevalence (42%) of antiemetic use during pregnancy, yet the potential for increased risk of fetal abnormalities remains unknown.
• The goal of the study is to quantify the risk of fetal abnormalities (overall and organ-specific) associated with ondansetron use during pregnancy.
• We found no statistically significant association between ondansetron exposure and risk of overall major congenital malformation, but caution is warranted due to small numbers of ondansetron exposure in the cohort.

The full results of this analysis were presented in a separate report in June 2017.

Berard A, Sheehy O, Gorgui J, Zhao J-P, Soares de Moura, Bernatsky S. New evidence for concern over the risk of birth defects from medications for nausea and vomiting for pregnancy. Journal of Clinical Epidemiology. December 2019; 116:39-48.

For more information, contact: Autumn Neville, Research Coordinator. [email protected]

Query 16-07: Options for appropriate prescribing.

This research was funded by the Drug Safety and Effectiveness Network (DSEN) and conducted by the following investigators: Yola Moride, Danae Lemieux-Uresandi, Genaro Castillon, Cristiano S Moura, Louise Pilote, Mareva Faure, Sasha Bernatsky.

Issue:

• Canada and the United States have the highest levels of prescription opioid consumption in the world. A variety of interventions have been implemented to curb the opioid epidemic. Thus far, evidence regarding their effectiveness has not been consolidated.

Study aim:

• To identify interventions that target opioid prescribing, assessing their effectiveness and evaluating their methodological aspects.

Study description:

• We searched bibliographic databases (MEDLINE, Embase, and LILACS) for studies published between January 1, 2005, and September 23, 2016 describing any intervention that targeted the prescription of opioids. We also examined websites of relevant organizations and scanned bibliographies of included articles and reviews for additional references. The target population was that of all health care providers (HCPs) or users of opioids with no restriction on indication. Endpoints were those related to process (implementation), outcomes effectiveness), or impact. Sources were screened independently by two reviewers using predefined eligibility criteria. The synthesis of findings was qualitative; no pooling of results was conducted.

Study findings:

• A total of 95 distinct interventions were identified; over half consisted of prescription monitoring programs (PMPs) and mainly targeted HCPs.
• Evaluation studies addressed mainly opioid prescription rates (30.6%) but fewer studies considered overdose death (9.7%) or abuse (9.7%).
• Although PMPs and policies are associated with a reduction in opioid prescriptions, their impact on appropriateness and restriction of access to patients in need is inconsistent.
• Continuing medical education (CME) and pain management programs effectively improved chronic pain management, but studies were conducted in specific settings. The impact of interventions on abuse and overdose-death is conflicting.

Summary:

• The authors conducted a systematic review of the literature to identify interventions that target opioid prescribing and assess their effectiveness. Our study suggests that existing interventions have not addressed all determinants of inappropriate opioid prescribing and usage.
• Data on the impact of interventions targeting the prescription of opioids is limited. Our review suggests that existing interventions have not addressed the essential determinants of inappropriate opioid prescribing and usage.

Phase 1 of this project, a systematic review, has been completed. Health Canada determined a separate query needed for Phase 2.

Moride et al. A systematic review of interventions and programs targeting appropriate prescribing of opioids. 2017 (ICPE abstract)

Moride Y, Lemieux-Uresandi D, Castillon G, Soares de Moura C, Pilote L, Faure M, Bernatsky S. A systematic review of interventions and programs targeting appropriate prescribing of opioids. Pain Physician. 2019 May;22(3):229-240.

For more information, contact: Autumn Neville, Research Coordinator. [email protected]

Pharmacovigilance entails monitoring drug safety in the real world. Millions of people share their experiences using medications on social media platforms. This is may be a valuable resource to detect emerging safety signals and contribute to improved ppharmacovigilance. The objective of this study was to assess the value and feasibility of social media pharmacovigilance and estimate the agreement of potential adverse events detected through social media posts, with adverse events available through an existing spontaneous reporting drug safety databases. Research findings, looking at 10 drug products, suggest pharmacosurveillance using social media to be feasible.   

For more information, contact: Autumn Neville, Research Coordinator. [email protected]

This research is funded by CIHR-DSEN 
Lead investigator: Dr. David Buckeridge
Query 16-01 raised by Health Canada, Health Products and Food Branch (HPFB) and Resource Management and Operations Directorate