CYP2D6 Screening for Adverse Drug Reactions to Codeine in Breast Milk
Information source: Lawson Health Research Institute
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Cytochrome P450 2D6 Ultra-rapid Metabolism
Intervention: Cytochrome P450 2D6 (CYP2D6) genetic screening. (Genetic)
Phase: N/A
Status: Recruiting
Sponsored by: Lawson Health Research Institute Official(s) and/or principal investigator(s): Gideon Koren, MD, Principal Investigator, Affiliation: University of Western Ontario, Canada
Overall contact: Catherine Ciszkowski, BMSc, Phone: 519-661-2111, Ext: 83221, Email: dnastudy@uwo.ca
Summary
The purpose of this study is to determine if non-invasive salivary genetic screening of
breastfeeding mothers taking codeine will allow for the successful identification of
mother-infant pairs susceptible to adverse events and to prevent these adverse events by
personalizing their medication to their genetics.
Clinical Details
Official title: CYP2D6 Screening for Adverse Drug Reactions to Codeine in Breast Milk
Study design: Time Perspective: Prospective
Primary outcome: Incidence of maternal and neonatal CNS depression in the prospective pharmacogenetic screening group to that of a retrospectively screened population
Secondary outcome: Incidence of the phase II uridine diphosphate glucuronyltransferase 2B7 (UGT2B7)*2/*2 variant which has been associated with higher morphine 6-glucuronide to morphine ratios.Incidence of the C3435T polymorphism in the multi-drug resistance gene (MDR1) which has been associated with significantly greater pain relief from morphine treatment. Incidence of the A118G polymorphism in the opioid receptor 1 (OPRM1) which has been associated with reduced response to morphine treatment.
Detailed description:
Currently, the opioid analgesic codeine is commonly administered to breastfeeding mothers
after Caesarean section for pain relief. Codeine was originally considered safe to use while
breastfeeding however, increased risk of adverse drug reactions has been demonstrated in
mothers taking codeine, as well as their breastfed infants, when the mother possesses a
genetic variation resulting in cytochrome P450 2D6 (CYP2D6) ultra-rapid metabolizer (UM)
phenotype. On average, most people convert about 10-15% of their codeine dose to morphine
resulting in pain relief however, UM individuals can convert up to 50% of their codeine
doses into active morphine. As many as 4% of North Americans may be UMs and these mothers
and their breastfed infants are at high risk of serious adverse events despite "safe"
codeine dosing due to morphine overproduction and accumulation in the mother and her breast
milk. Observed side effects include severe sedation, decreased rate and depth of breathing
and even infant death. In response to this problem, our hospital-based clinical trial
strives to identify at-risk UM mother-infant pairs by performing a genetic test on
non-invasive, voluntary saliva samples from mothers giving birth by Caesarean section and
who will need codeine for pain relief while breastfeeding. We believe that this test will
allow us to reliably identify at-risk UM mother-infant pairs and prevent adverse drug
reactions in both by tailoring analgesic therapy to their genetic results: mothers
identified as being UMs will be given other suitable analgesics, such as ibuprofen, in place
of codeine-containing preparations. We propose that this prospective study will generate
high-level data supporting the cost-effective genetic screening of mothers who will be
taking codeine while breastfeeding before they begin taking their medications. Such testing
is currently possible on a nation-wide scale through collaboration with the Canadian
Pharmacogenomics Network for Drug Safety (CPNDS).
Eligibility
Minimum age: N/A.
Maximum age: N/A.
Gender(s): Female.
Criteria:
Inclusion Criteria:
Women who:
- Have a pre-scheduled Caesarean section
- Provide DNA for CYP2D6 genetic analysis
- Breastfeed their infants
- Take codeine-containing medication during breastfeeding (retrospective screening
group and non-CYP2D6 ultrarapid metabolizers in prospective screening group)
Exclusion Criteria:
- Mothers who do not provide consent prior to Caesarian section surgery
- Mothers who take other sedative medications besides codeine during breastfeeding
(these include benzodiazepines, skeletal muscle relaxants, psychotropic agents).
Locations and Contacts
Catherine Ciszkowski, BMSc, Phone: 519-661-2111, Ext: 83221, Email: dnastudy@uwo.ca
St. Joseph's Hospital, London, Ontario N6A 4V2, Canada; Recruiting Gideon Koren, MD, Principal Investigator
Additional Information
Starting date: October 2009
Last updated: January 13, 2010
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