The Experts below are selected from a list of 6096 Experts worldwide ranked by ideXlab platform
Bruce Carleton - One of the best experts on this subject based on the ideXlab platform.
-
The pharmacogenetics of codeine Pain relief in the Postpartum period
The Pharmacogenomics Journal, 2015Co-Authors: Marta Baber, Bruce Carleton, S Chaudhry, C Ross, Howard Berger, L Kelly, G KorenAbstract:The objective of this study was to examine interindividual variability in codeine requirements and Pain management by examining select genetic polymorphisms in the codeine pharmacological pathway. The study included a nested cohort of 98 women who were prescribed codeine following cesarean section. Participants were genotyped for select polymorphisms of the COMT , ABCB1 , CYP2D6 , UGT2B7 and OPRM1 genes and instructed to describe their level of Pain using the visual analog scale (mm) 1 h following each dose of codeine. Analysis revealed that reported Pain increases with maternal age ( P =0.041). Asians required more codeine than Caucasians ( P =0.048). Significant differences in mean dose consumption were seen among the genotypic groups of the OPRM1 A118G ( P =0.001) and UGT2B7 C802T ( P =0.015) variants. These variants were found to predict codeine consumption in the cohort overall ( P =0.000) and among Caucasians ( P =0.001). These findings will assist in customizing therapy to effectively manage Postpartum Pain.
-
cyp2d6 polymorphisms and codeine analgesia in Postpartum Pain management a pilot study
Therapeutic Drug Monitoring, 2011Co-Authors: Sondra Vandervaart, Johanna Sistonen, Parvaz Madadi, Violette M G J Gijsen, Saskia N De Wildt, Colin J D Ross, Ilan Matok, Howard Berger, Anna Taddio, Bruce CarletonAbstract:BACKGROUND: Codeine, a common opiate prescribed for Pain postcesarean section (c-section), is biotransformed by the highly polymorphic Cytochrome P450 enzyme 2D6 (CYP2D6). Ultrarapid metabolizers (UMs), individuals with multiple active copies of CYP2D6, can biotranform up to 50% more codeine into morphine than normal individuals can. In contrast, poor metabolizers (PMs), individuals who have no active CYP2D6 genes, convert almost no codeine into morphine and as a result may take multiple doses of codeine without attaining analgesia. OBJECTIVE: The aim was to study the relationship between CYP2D6 genotype and codeine analgesia among women recovering from c-section. METHODS: Forty-five mothers prescribed codeine provided a blood sample for CYP2D6 genotyping and recorded their Pain level 4 times a day for 3 days immediately after a c-section. Codeine was used on an as-needed basis; doses and times were recorded. The relationship between CYP2D6 genotype, Pain scores, need for codeine, and adverse events was studied. Theoretical morphine dose, based on CYP2D6 genotype, was estimated. RESULTS: Women at the genotypic extremes reported codeine effects consistent with their genotype: the 2 PMs of codeine reported no analgesia as a result of taking codeine, whereas 2 of the 3 UMs reported immediate Pain relief from codeine but stopped taking it due to dizziness and constipation. Much larger numbers are needed to study similar correlations among extensive and intermediate metabolizers. CONCLUSIONS: In this pilot study, the extreme CYP2D6 genotypes (PMs and UMs) seemed to predict Pain response and adverse events. Larger sample sizes are needed to correlate the range of genotypes with Pain response.
-
cyp2d6 polymorphisms and codeine analgesia in Postpartum Pain management a pilot study
Therapeutic Drug Monitoring, 2011Co-Authors: Sondra Vandervaart, Johanna Sistonen, Parvaz Madadi, Violette M G J Gijsen, Saskia N De Wildt, Colin J D Ross, Ilan Matok, Howard Berger, Anna Taddio, Bruce CarletonAbstract:Background:Codeine, a common opiate prescribed for Pain postcesarean section (c-section), is biotransformed by the highly polymorphic Cytochrome P450 enzyme 2D6 (CYP2D6). Ultrarapid metabolizers (UMs), individuals with multiple active copies of CYP2D6, can biotranform up to 50% more codeine into mor
Howard Berger - One of the best experts on this subject based on the ideXlab platform.
-
a cost effectiveness analysis of maternal cyp2d6 genetic testing to guide treatment for Postpartum Pain and avert infant adverse events
Pharmacogenomics Journal, 2018Co-Authors: Myla E Moretti, Howard Berger, Gideon Koren, D F Lato, S Ito, Wendy J UngarAbstract:Mothers with a CYP2D6 ultrarapid metabolizer phenotype may expose their infants to risk of adverse events when taking codeine while breastfeeding, by producing more of the active metabolite, morphine. Pharmacogenetic testing may be a valuable tool to identify such mothers, but testing can be costly. The objective of the study was to determine the incremental costs of genotyping to avert neonatal adverse events during maternal pharmacotherapy. A cost-effectiveness analysis, using a decision model, was performed with a hypothetical cohort of prenatal subjects. Parameter estimates, costs and ranges for sensitivity analyses were ascertained from the literature and expert opinion. Sensitivity analyses were conducted to assess the robustness of the results. Probabilistic sensitivity analysis revealed an incremental cost-effectiveness (ICER) of $10 433 (Canadian dollars) for genotyping compared to no genotyping per adverse event averted. Results were sensitive to hospital admission costs. The ICER was lower when evaluating only subjects having caesarean deliveries or those from ethnic populations known to have a high prevalence of ultra-rapid metabolizers. Although genotyping to guide pharmacotherapy was not cost saving, the cost to avert an infant adverse event may represent good value for money in specific populations. With a growing demand for personalized medicine, these findings are relevant for decision makers, clinicians and patients.
-
The pharmacogenetics of codeine Pain relief in the Postpartum period
The Pharmacogenomics Journal, 2015Co-Authors: Marta Baber, Bruce Carleton, S Chaudhry, C Ross, Howard Berger, L Kelly, G KorenAbstract:The objective of this study was to examine interindividual variability in codeine requirements and Pain management by examining select genetic polymorphisms in the codeine pharmacological pathway. The study included a nested cohort of 98 women who were prescribed codeine following cesarean section. Participants were genotyped for select polymorphisms of the COMT , ABCB1 , CYP2D6 , UGT2B7 and OPRM1 genes and instructed to describe their level of Pain using the visual analog scale (mm) 1 h following each dose of codeine. Analysis revealed that reported Pain increases with maternal age ( P =0.041). Asians required more codeine than Caucasians ( P =0.048). Significant differences in mean dose consumption were seen among the genotypic groups of the OPRM1 A118G ( P =0.001) and UGT2B7 C802T ( P =0.015) variants. These variants were found to predict codeine consumption in the cohort overall ( P =0.000) and among Caucasians ( P =0.001). These findings will assist in customizing therapy to effectively manage Postpartum Pain.
-
cyp2d6 polymorphisms and codeine analgesia in Postpartum Pain management a pilot study
Therapeutic Drug Monitoring, 2011Co-Authors: Sondra Vandervaart, Johanna Sistonen, Parvaz Madadi, Violette M G J Gijsen, Saskia N De Wildt, Colin J D Ross, Ilan Matok, Howard Berger, Anna Taddio, Bruce CarletonAbstract:BACKGROUND: Codeine, a common opiate prescribed for Pain postcesarean section (c-section), is biotransformed by the highly polymorphic Cytochrome P450 enzyme 2D6 (CYP2D6). Ultrarapid metabolizers (UMs), individuals with multiple active copies of CYP2D6, can biotranform up to 50% more codeine into morphine than normal individuals can. In contrast, poor metabolizers (PMs), individuals who have no active CYP2D6 genes, convert almost no codeine into morphine and as a result may take multiple doses of codeine without attaining analgesia. OBJECTIVE: The aim was to study the relationship between CYP2D6 genotype and codeine analgesia among women recovering from c-section. METHODS: Forty-five mothers prescribed codeine provided a blood sample for CYP2D6 genotyping and recorded their Pain level 4 times a day for 3 days immediately after a c-section. Codeine was used on an as-needed basis; doses and times were recorded. The relationship between CYP2D6 genotype, Pain scores, need for codeine, and adverse events was studied. Theoretical morphine dose, based on CYP2D6 genotype, was estimated. RESULTS: Women at the genotypic extremes reported codeine effects consistent with their genotype: the 2 PMs of codeine reported no analgesia as a result of taking codeine, whereas 2 of the 3 UMs reported immediate Pain relief from codeine but stopped taking it due to dizziness and constipation. Much larger numbers are needed to study similar correlations among extensive and intermediate metabolizers. CONCLUSIONS: In this pilot study, the extreme CYP2D6 genotypes (PMs and UMs) seemed to predict Pain response and adverse events. Larger sample sizes are needed to correlate the range of genotypes with Pain response.
-
cyp2d6 polymorphisms and codeine analgesia in Postpartum Pain management a pilot study
Therapeutic Drug Monitoring, 2011Co-Authors: Sondra Vandervaart, Johanna Sistonen, Parvaz Madadi, Violette M G J Gijsen, Saskia N De Wildt, Colin J D Ross, Ilan Matok, Howard Berger, Anna Taddio, Bruce CarletonAbstract:Background:Codeine, a common opiate prescribed for Pain postcesarean section (c-section), is biotransformed by the highly polymorphic Cytochrome P450 enzyme 2D6 (CYP2D6). Ultrarapid metabolizers (UMs), individuals with multiple active copies of CYP2D6, can biotranform up to 50% more codeine into mor
Gideon Koren - One of the best experts on this subject based on the ideXlab platform.
-
a cost effectiveness analysis of maternal cyp2d6 genetic testing to guide treatment for Postpartum Pain and avert infant adverse events
Pharmacogenomics Journal, 2018Co-Authors: Myla E Moretti, Howard Berger, Gideon Koren, D F Lato, S Ito, Wendy J UngarAbstract:Mothers with a CYP2D6 ultrarapid metabolizer phenotype may expose their infants to risk of adverse events when taking codeine while breastfeeding, by producing more of the active metabolite, morphine. Pharmacogenetic testing may be a valuable tool to identify such mothers, but testing can be costly. The objective of the study was to determine the incremental costs of genotyping to avert neonatal adverse events during maternal pharmacotherapy. A cost-effectiveness analysis, using a decision model, was performed with a hypothetical cohort of prenatal subjects. Parameter estimates, costs and ranges for sensitivity analyses were ascertained from the literature and expert opinion. Sensitivity analyses were conducted to assess the robustness of the results. Probabilistic sensitivity analysis revealed an incremental cost-effectiveness (ICER) of $10 433 (Canadian dollars) for genotyping compared to no genotyping per adverse event averted. Results were sensitive to hospital admission costs. The ICER was lower when evaluating only subjects having caesarean deliveries or those from ethnic populations known to have a high prevalence of ultra-rapid metabolizers. Although genotyping to guide pharmacotherapy was not cost saving, the cost to avert an infant adverse event may represent good value for money in specific populations. With a growing demand for personalized medicine, these findings are relevant for decision makers, clinicians and patients.
-
the pharmacogenetics of opioid therapy in the management of Postpartum Pain a systematic review
Pharmacogenomics, 2016Co-Authors: Marta Baber, Priya Bapat, Gail Nichol, Gideon KorenAbstract:Aims: Opioids are commonly prescribed for Postpartum Pain. Yet, providing adequate Pain relief, while ensuring that the mother and her breastfeeding infant are protected from adverse events can be challenging. The objective of this systematic review was to identify the role of opioid pharmacogenetics in analgesia and adverse events among patients being treated for Postpartum Pain, along with their breastfeeding infants. Methods: A comprehensive search of the literature was conducted in seven databases on June 3–4, 2015. Two reviewers independently screened studies for eligibility, extracted data and evaluated study quality using the Newcastle–Ottawa Scale. Results: Among the 2082 papers retrieved from the search, 17 were included in the review. These 17 papers consisted of various study designs, opioids, polymorphisms and patient outcomes. This systematic review reveals that CYP2D6, OPRM1 A118G, UGT2B7 C802T and ABCB1 G2677AT may contribute to Postpartum analgesia or adverse events. Conclusion: These find...
-
genetic transmission of cytochrome p450 2d6 cyp2d6 ultrarapid metabolism implications for breastfeeding women taking codeine
Current Drug Safety, 2011Co-Authors: Parvaz Madadi, Andrea Gaedigk, Steven J Leeder, Ronni Teitelbaum, David Chitayat, Catherine Ciszkowski, Gideon KorenAbstract:The pro-drug codeine is commonly prescribed for Postpartum Pain relief in North America. The safety of codeine during breastfeeding is related in part to the extent of the active morphine metabolite catalyzed from codeine via the cytochrome P450 2D6 (CYP2D6) enzyme. In mothers who have greater than two functional copies of the CYP2D6 gene (CYP2D6 ultrarapid metabolism phenotype; UM) a substantially higher proportion of morphine is produced. Label changes on codeine-containing medications will highlight the risks associated with this genotype for breastfeeding mothers, but are not supported by translation strategies on how to incorporate this pharmacogenetic knowledge into clinical practice. To address the immediate issue of CYP2D6 UM inheritance in family members of a breastfed infant who succumbed to fatal opioid intoxication and whose codeine-prescribed mother was a CYP2D6 UM, we constructed a pedigree. While the pedigree approach is helpful to aid diagnosis, identify other at risk family members, and simplify pharmacogenetic analysis, its clinical usefulness is dependant on an institutional framework which is not available in most centers at this time.
-
codeine acetaminophen versus nonsteroidal anti inflammatory drugs in the treatment of post abdominal surgery Pain a systematic review of randomized trials
American Journal of Surgery, 2009Co-Authors: Marieke Nauta, Marieke L A Landsmeer, Gideon KorenAbstract:BACKGROUND: Cesarean section, episiotomy, and third and perineal tears are associated with significant tissue damage, causing Pain in the immediate Postpartum period. The current standard in North America is to prescribe oral acetaminophen/codeine (A + C) for Postpartum Pain. Codeine has opioid-related adverse effects and may not be safe during breastfeeding in the Postpartum period for all neonates. Nonsteroidal anti-inflammatory drugs (NSAIDs) are devoid of opioid-related adverse effects and could be a possible alternative for analgesia in Postpartum Pain. The objective of this systematic review was to compare the analgesic effect and safety profile of acetaminophen/codeine (A + C) with NSAIDs in the management of Pain after laparotomy. METHODS: A systematic search was performed by using MEDLINE, EMBASE, CINAHL, and Cochrane Library databases to identify randomized controlled trials comparing A + C to NSAIDs for postlaparotomy Pain. Selected articles were critically appraised by using the CONSORT method and Jadad score. RESULTS: Nine relevant articles were identified. All 9 studies used a visual analog scale for Pain intensity and reported the incidence of adverse effects as an outcome. None of the studies showed lower Pain intensity scores after treatment with A + C compared with different NSAIDs. In 3 studies, the number of patients with adverse effects was significantly lower in the NSAID group compared with the A + C-group. In 1 other study, the rate of constipation was significantly lower in the NSAID group when compared with the A + C-group. The other 5 studies did not report any significant differences in the rates of adverse effects between the 2 groups. CONCLUSIONS: None of the studies found A + C to be superior to NSAIDs in controlling postlaparotomy Pain. NSAIDs appear to be an equipotent alternative in the treatment of postlaparotomy Pain. Four of the 9 studies reported less adverse effects in the NSAID group. There appears to be an overall better risk/benefit ratio for the use of NSAIDs for Postpartum Pain.
Brian Cleary - One of the best experts on this subject based on the ideXlab platform.
-
oral non steroidal anti inflammatory drugs single dose for perineal Pain in the early Postpartum period
Cochrane Database of Systematic Reviews, 2016Co-Authors: Francesca Wuytack, Valerie Smith, Brian ClearyAbstract:Background Many women experience perineal Pain after childbirth, especially after having sustained perineal trauma. Perineal Pain-management strategies are thus an important part of postnatal care. Non-steroidal anti-inflammatory drugs (NSAIDs) are a commonly used type of medication in the management of Postpartum Pain and their effectiveness and safety should be assessed. Objectives To determine the effectiveness of a single dose of an oral NSAID for relief of acute perineal Pain in the early Postpartum period. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2016), OpenSIGLE, ProQuest Dissertations and Theses, the ISRCTN Registry and ClinicalTrials.gov (31 March 2016). We also reviewed reference lists of retrieved papers and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) assessing a single dose of a NSAID versus a single dose of placebo, paracetamol or another NSAID for women with perineal Pain in the early Postpartum period. Quasi-RCTs and cross-over trials were excluded. Data collection and analysis Two review authors (FW and VS) independently assessed all identified papers for inclusion and risk of bias. Any discrepancies were resolved through discussion and consensus. Data extraction, including calculations of Pain relief scores, was also conducted independently by two review authors and checked for accuracy. Main results We included 28 studies that examined 13 different NSAIDs and involved 4181 women (none of whom were breastfeeding). Studies were published between 1967 and 2013, with the majority published in the 1980s. Of the 4181 women involved in the studies, 2642 received a NSAID and 1539 received placebo or paracetamol. Risk of bias was generally unclear due to poor reporting, but in most studies the participants and personnel were blinded, outcome data were complete and the outcomes that were specified in the methods section were reported. None of the included studies reported on any of this review's secondary outcomes: prolonged hospitalisation or re-hospitalisation due to perineal Pain; breastfeeding (fully or mixed) at discharge; breastfeeding (fully or mixed) at six weeks; perineal Pain at six weeks; maternal views; Postpartum depression; instrumental measures of disability due to perineal Pain. NSAID versus placebo Compared to women who received a placebo, more women who received a single dose NSAID achieved adequate Pain relief at four hours (risk ratio (RR) 1.91, 95% confidence interval (CI) 1.64 to 2.23, 10 studies, 1573 participants (low-quality evidence)) and adequate Pain relief at six hours (RR 1.92, 95% CI 1.69 to 2.17, 17 studies, 2079 participants (very low-quality evidence)). Women who received a NSAID were also less likely to need additional analgesia compared to women who received placebo at four hours (RR 0.39, 95% CI 0.26 to 0.58, four studies, 486 participants (low-quality evidence)) and at six hours after initial administration (RR 0.32, 95% CI 0.26 to 0.40, 10 studies, 1012 participants (low-quality evidence)). Fourteen maternal adverse effects were reported in the NSAID group (drowsiness (5), abdominal discomfort (2), weakness (1), dizziness (2), headache (2), moderate epigastralgia (1), not specified (1)) and eight in the placebo group (drowsiness (2), light headed (1), nausea (1), backache (1), dizziness (1), epigastric Pain (1), not specified (1)), although not all studies assessed adverse effects. There was no difference in overall maternal adverse effects between NSAIDs and placebo at six hours post-administration (RR 1.38, 95% CI 0.71 to 2.70, 13 studies, 1388 participants (very low-quality evidence)). One small study (with two treatment arms) assessed maternal adverse effects at four hours post-administration, but there were no maternal adverse effects observed (one study, 90 participants (low-quality evidence)). Neonatal adverse effects were not assessed in any of the included studies. NSAID versus paracetamol NSAIDs versus paracetamol were also more effective for adequate Pain relief at four hours (RR 1.54, 95% CI 1.07 to 2.22, three studies, 342 participants) but not at six hours post-administration. There was no difference in the need for additional analgesia between the two groups at four hours (RR 0.55, 95% CI 0.27 to 1.13, one study, 73 participants), but women in the NSAID group were less likely to need any additional analgesia at six hours (RR 0.28, 95% CI 0.12 to 0.67, one study, 59 participants). No maternal adverse effects were reported four hours after drug administration (one study). Six hours post-administration, there was no difference between the groups in the number of maternal adverse effects (RR 0.74, 95% CI 0.27 to 2.08, three studies, 300 participants), with one case of pruritis in the NSAID group and one case of sleepiness in the paracetamol group. Neonatal adverse effects were not assessed in any of the included studies. Comparisons of different NSAIDs and different doses of the same NSAID did not demonstrate any differences in their effectiveness on any of the primary outcome measures; however, few data were available on some NSAIDs. Authors' conclusions In women who are not breastfeeding and who sustained perineal trauma, NSAIDs (compared to placebo) provide greater Pain relief for acute Postpartum perineal Pain and fewer women need additional analgesia when treated with a NSAID. However, the risk of bias was unclear for many of the included studies, adverse effects were often not assessed and breastfeeding women were not included in the studies. The overall quality of the evidence (GRADE) was low with the evidence for all outcomes rated as low or very low. The main reasons for downgrading were inclusion of studies with high risk of bias and inconsistency of findings of individual studies. NSAIDs also appear to be more effective in providing relief for perineal Pain than paracetamol, but few studies were included in this analysis. Future studies should examine NSAIDs' adverse effects profile including neonatal adverse effects and the compatibility of NSAIDs with breastfeeding, and assess other important secondary outcomes of this review. Moreover, studies mostly included women who had episiotomies. Future research should consider women with and without perineal trauma, including perineal tears. High-quality studies should be conducted to further assess the efficacy of NSAIDs versus paracetamol and the efficacy of multimodal treatments.
Parvaz Madadi - One of the best experts on this subject based on the ideXlab platform.
-
cyp2d6 polymorphisms and codeine analgesia in Postpartum Pain management a pilot study
Therapeutic Drug Monitoring, 2011Co-Authors: Sondra Vandervaart, Johanna Sistonen, Parvaz Madadi, Violette M G J Gijsen, Saskia N De Wildt, Colin J D Ross, Ilan Matok, Howard Berger, Anna Taddio, Bruce CarletonAbstract:BACKGROUND: Codeine, a common opiate prescribed for Pain postcesarean section (c-section), is biotransformed by the highly polymorphic Cytochrome P450 enzyme 2D6 (CYP2D6). Ultrarapid metabolizers (UMs), individuals with multiple active copies of CYP2D6, can biotranform up to 50% more codeine into morphine than normal individuals can. In contrast, poor metabolizers (PMs), individuals who have no active CYP2D6 genes, convert almost no codeine into morphine and as a result may take multiple doses of codeine without attaining analgesia. OBJECTIVE: The aim was to study the relationship between CYP2D6 genotype and codeine analgesia among women recovering from c-section. METHODS: Forty-five mothers prescribed codeine provided a blood sample for CYP2D6 genotyping and recorded their Pain level 4 times a day for 3 days immediately after a c-section. Codeine was used on an as-needed basis; doses and times were recorded. The relationship between CYP2D6 genotype, Pain scores, need for codeine, and adverse events was studied. Theoretical morphine dose, based on CYP2D6 genotype, was estimated. RESULTS: Women at the genotypic extremes reported codeine effects consistent with their genotype: the 2 PMs of codeine reported no analgesia as a result of taking codeine, whereas 2 of the 3 UMs reported immediate Pain relief from codeine but stopped taking it due to dizziness and constipation. Much larger numbers are needed to study similar correlations among extensive and intermediate metabolizers. CONCLUSIONS: In this pilot study, the extreme CYP2D6 genotypes (PMs and UMs) seemed to predict Pain response and adverse events. Larger sample sizes are needed to correlate the range of genotypes with Pain response.
-
cyp2d6 polymorphisms and codeine analgesia in Postpartum Pain management a pilot study
Therapeutic Drug Monitoring, 2011Co-Authors: Sondra Vandervaart, Johanna Sistonen, Parvaz Madadi, Violette M G J Gijsen, Saskia N De Wildt, Colin J D Ross, Ilan Matok, Howard Berger, Anna Taddio, Bruce CarletonAbstract:Background:Codeine, a common opiate prescribed for Pain postcesarean section (c-section), is biotransformed by the highly polymorphic Cytochrome P450 enzyme 2D6 (CYP2D6). Ultrarapid metabolizers (UMs), individuals with multiple active copies of CYP2D6, can biotranform up to 50% more codeine into mor
-
genetic transmission of cytochrome p450 2d6 cyp2d6 ultrarapid metabolism implications for breastfeeding women taking codeine
Current Drug Safety, 2011Co-Authors: Parvaz Madadi, Andrea Gaedigk, Steven J Leeder, Ronni Teitelbaum, David Chitayat, Catherine Ciszkowski, Gideon KorenAbstract:The pro-drug codeine is commonly prescribed for Postpartum Pain relief in North America. The safety of codeine during breastfeeding is related in part to the extent of the active morphine metabolite catalyzed from codeine via the cytochrome P450 2D6 (CYP2D6) enzyme. In mothers who have greater than two functional copies of the CYP2D6 gene (CYP2D6 ultrarapid metabolism phenotype; UM) a substantially higher proportion of morphine is produced. Label changes on codeine-containing medications will highlight the risks associated with this genotype for breastfeeding mothers, but are not supported by translation strategies on how to incorporate this pharmacogenetic knowledge into clinical practice. To address the immediate issue of CYP2D6 UM inheritance in family members of a breastfed infant who succumbed to fatal opioid intoxication and whose codeine-prescribed mother was a CYP2D6 UM, we constructed a pedigree. While the pedigree approach is helpful to aid diagnosis, identify other at risk family members, and simplify pharmacogenetic analysis, its clinical usefulness is dependant on an institutional framework which is not available in most centers at this time.