Domperidone has been used for years worldwide for its indicated use of nausea and vomiting. However, there have been recent safety concerns of its use in unapproved indications (e.g. lactation issues in breastfeeding) and increases in cardiac adverse events. In March 2013, the European Medicines Agency (EMA) Pharmacovigilance Risk Assessment Committee (PRAC), responsible for assessing and monitoring the safety of human medicines, initiated a review of domperidone-containing medicines. As a result, PRAC recommended that the product label be updated to strengthen the information regarding cardiac risks. PRAC also requested that domperidone's marketing authorisation holders (MAHs) perform a drug utilisation study to assess the effectiveness of these measures to reduce the occurrence or severity of these cardiac adverse events associated with domperidone use and to monitor the use of the drug for unapproved indications. The EMA suggested the use of a healthcare database as a data source to measure domperidone utilisation patterns pre- and post-implementation of these measures. This study is being conducted to assess if there are demonstrable differences in prescribing practices of domperidone before and after the implementation of these measures. This will then be used to inform the EMA as to the effectiveness of such measures.
This study will use primary care data from CPRD to describe the drug utilisation patterns of domperidone pre- and post-implementation of the risk minimisation measures in 2014. Data analysis will be descriptive and presented using appropriate descriptive statistics such as mean, median, standard deviation and range for continuous variables and percent and frequency tables for categorical variables. Endpoints such as daily dose, duration of use, and prescribing for off-label indications will be measured for both groups. Additionally, estimates of the overall proportion of domperidone prescriptions before and after the risk minimisation implementation will be used to generate a risk ratio with 95% confidence intervals for each of the components of the composite endpoints individually, the time trend of apparent indication, days supplied (<7 days vs. >7 days), and the age and sex of the people receiving prescriptions. To account for the uncertainty around unknown indication and duration of use the rates for the endpoints will be calculated four ways from optimistic scenario (unknown indication on label usage for <7 days) and pessimistic scenario (unknown indication assumed to be off-label usage for >7 days), plus other intermediate scenarios.
Demographics: Information on patients'age, sex, and geographic region will be extracted. Diagnoses will be extracted from a read codes or will be determined based on laboratory test results. Indication: Estimated from the diagnoses recorded in the time period preceding each domperidone prescription: The indication for the prescription will be defined as nausea/vomiting if the subject has a recorded diagnosis classified as nausea or as vomiting, on the day of the prescription or in the preceding 7 days. For those prescriptions whose indication is not defined as nausea/vomiting, the indication will be defined as off-label if the subject has, in the 2 months up to and including the date of domperidone prescription, a diagnosis classified as one of the following: - GERD; - Abdominal bloating, gastric dysmotility, delayed gastric emptying; - Irritable bowel syndrome (IBS); Suppressed lactation, failed lactation, lactation not established, decreased lactation, lactation problem; or - Orthostatic hypotension and a diagnosis of Parkinson's disease. For those prescriptions not classified as above, the indication will be classified as unknown.
Catrina Richards - Chief Investigator - IQVIA Ltd ( UK )
Sarah Jenner - Corresponding Applicant - IQVIA Ltd ( UK )
Carlo Appiani - Collaborator - Janssen France
Daniel Fife - Collaborator - Johnson & Johnson ( JnJ - USA )
Janette McQuillan - Collaborator - IQVIA ( IMS Health ) France
Louise Raiteri - Collaborator - IQVIA Ltd ( UK )
Peter Hu - Collaborator - Janssen France
Susan Oliveria - Collaborator - IQVIA
Syd Phillips - Collaborator - IQVIA
Ute Richarz - Collaborator - Janssen France