.

Rule IDRule statusDrug substanceSexAge [2]Disease stateSourceGerm-line genetic marker (as appearing in source)Germ-line genetic marker (curated SNPs)Reference genome build variants refer toRecommendation (English)Simple SPARQL Rule (generated RDF) [3]Country, region or institution where applicableDescription of evidenceURL of evidenceLevel of evidenceClinical significanceClassification of recommendationDate of evidenceDate of additionDate of last update or validationAdded byCurator Notes

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http://safety-code.org/ont/cds.ttl#rule-1needs more work [1]WarfarinCoumadin Bristol Myers Squibb FDA drug labelCYP2C9*1/*1 VKORC1:rs9923231(G;G)not described in source5-7 mg warfarin per day should be considered as a starting dose range for a patient with this genotype according to the Warfarin drug label (Bristol-Myers Squibb).In Bearbeitung...USAFDA Drug label for Coumadin (warfarin sodium) tablet, Bristol-Myers Squibb Pharma Company
http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=d91934a0-902e-c26c-23ca-d5accc4151b6#section-5.325.12.201125.04.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-2needs more workWarfarinCoumadin Bristol Myers Squibb FDA drug labelCYP2C9*1/*1 rs9923231(A;G)not described in source5-7 mg warfarin per day should be considered as a starting dose range for a patient with this genotype according to the Warfarin drug label (Bristol-Myers Squibb).In Bearbeitung...USAFDA Drug label for Coumadin (warfarin sodium) tablet, Bristol-Myers Squibb Pharma Companyhttp://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=d91934a0-902e-c26c-23ca-d5accc4151b6#section-5.325.12.201125.04.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-3needs more workWarfarinCoumadin Bristol Myers Squibb FDA drug labelCYP2C9*1/*1 VKORC1:rs9923231(A;A)not described in source3-4 mg warfarin per day should be considered as a starting dose range for a patient with this genotype according to the Warfarin drug label (Bristol-Myers Squibb).In Bearbeitung...USAFDA Drug label for Coumadin (warfarin sodium) tablet, Bristol-Myers Squibb Pharma Companyhttp://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=d91934a0-902e-c26c-23ca-d5accc4151b6#section-5.325.12.201125.04.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-4needs more workWarfarinCoumadin Bristol Myers Squibb FDA drug labelCYP2C9*1/*2 VKORC1:rs9923231(G;G)not described in source5-7 mg warfarin per day should be considered as a starting dose range for a patient with this genotype according to the Warfarin drug label (Bristol-Myers Squibb).In Bearbeitung...USAFDA Drug label for Coumadin (warfarin sodium) tablet, Bristol-Myers Squibb Pharma Companyhttp://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=d91934a0-902e-c26c-23ca-d5accc4151b6#section-5.325.12.201125.04.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-5needs more workWarfarinCoumadin Bristol Myers Squibb FDA drug labelCYP2C9*1/*2 VKORC1:rs9923231(A;G)not described in source3-4 mg warfarin per day should be considered as a starting dose range for a patient with this genotype according to the Warfarin drug label (Bristol-Myers Squibb).In Bearbeitung...USAFDA Drug label for Coumadin (warfarin sodium) tablet, Bristol-Myers Squibb Pharma Companyhttp://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=d91934a0-902e-c26c-23ca-d5accc4151b6#section-5.325.12.201125.04.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-6needs more workWarfarinCoumadin Bristol Myers Squibb FDA drug labelCYP2C9*1/*2 VKORC1:rs9923231(A;A)not described in source3-4 mg warfarin per day should be considered as a starting dose range for a patient with this genotype according to the Warfarin drug label (Bristol-Myers Squibb).In Bearbeitung...USAFDA Drug label for Coumadin (warfarin sodium) tablet, Bristol-Myers Squibb Pharma Companyhttp://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=d91934a0-902e-c26c-23ca-d5accc4151b6#section-5.325.12.201125.04.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-7needs more workWarfarinCoumadin Bristol Myers Squibb FDA drug labelCYP2C9*1/*3 VKORC1:rs9923231(G;G)not described in source3-4 mg warfarin per day should be considered as a starting dose range for a patient with this genotype according to the Warfarin drug label (Bristol-Myers Squibb).In Bearbeitung...USAFDA Drug label for Coumadin (warfarin sodium) tablet, Bristol-Myers Squibb Pharma Companyhttp://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=d91934a0-902e-c26c-23ca-d5accc4151b6#section-5.325.12.201125.04.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-8needs more workWarfarinCoumadin Bristol Myers Squibb FDA drug labelCYP2C9*1/*3 VKORC1:rs9923231(A;G)not described in source3-4 mg warfarin per day should be considered as a starting dose range for a patient with this genotype according to the Warfarin drug label (Bristol-Myers Squibb).In Bearbeitung...USAFDA Drug label for Coumadin (warfarin sodium) tablet, Bristol-Myers Squibb Pharma Companyhttp://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=d91934a0-902e-c26c-23ca-d5accc4151b6#section-5.325.12.201125.04.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-9needs more workWarfarinCoumadin Bristol Myers Squibb FDA drug labelCYP2C9*1/*3 VKORC1:rs9923231(A;A)not described in source0.5-2 mg warfarin per day should be considered as a starting dose range for a patient with this genotype according to the Warfarin drug label (Bristol-Myers Squibb).In Bearbeitung...USAFDA Drug label for Coumadin (warfarin sodium) tablet, Bristol-Myers Squibb Pharma Companyhttp://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=d91934a0-902e-c26c-23ca-d5accc4151b6#section-5.325.12.201125.04.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-10needs more workWarfarinCoumadin Bristol Myers Squibb FDA drug labelCYP2C9*2/*2 VKORC1:rs9923231(G;G)rs1799853(T;T) rs9923231(C;C)not described in source3-4 mg warfarin per day should be considered as a starting dose range for a patient with this genotype according to the Warfarin drug label (Bristol-Myers Squibb).In Bearbeitung...USAFDA Drug label for Coumadin (warfarin sodium) tablet, Bristol-Myers Squibb Pharma Companyhttp://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=d91934a0-902e-c26c-23ca-d5accc4151b6#section-5.325.12.201109.05.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)CYP2C9 SNPs were added based on PharmGKB-derived allele table. rs9923231 SNP information is based on minus strand in source, so C/G and A/T were swapped to conform to the plus strand (as used in dbSNP)

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http://safety-code.org/ont/cds.ttl#rule-11needs more workWarfarinCoumadin Bristol Myers Squibb FDA drug labelCYP2C9*2/*2 VKORC1:rs9923231(A;G)rs1799853(T;T) rs9923231(C;T)not described in source3-4 mg warfarin per day should be considered as a starting dose range for a patient with this genotype according to the Warfarin drug label (Bristol-Myers Squibb).In Bearbeitung...USAFDA Drug label for Coumadin (warfarin sodium) tablet, Bristol-Myers Squibb Pharma Companyhttp://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=d91934a0-902e-c26c-23ca-d5accc4151b6#section-5.325.12.201109.05.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)CYP2C9 SNPs were added based on PharmGKB-derived allele table. rs9923231 SNP information is based on minus strand in source, so C/G and A/T were swapped to conform to the plus strand (as used in dbSNP)

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http://safety-code.org/ont/cds.ttl#rule-12needs more workWarfarinCoumadin Bristol Myers Squibb FDA drug labelCYP2C9*2/*2 VKORC1:rs9923231(A;A)rs1799853(T;T) rs9923231(T;T)not described in source0.5-2 mg warfarin per day should be considered as a starting dose range for a patient with this genotype according to the Warfarin drug label (Bristol-Myers Squibb).In Bearbeitung...USAFDA Drug label for Coumadin (warfarin sodium) tablet, Bristol-Myers Squibb Pharma Companyhttp://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=d91934a0-902e-c26c-23ca-d5accc4151b6#section-5.325.12.201109.05.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)CYP2C9 SNPs were added based on PharmGKB-derived allele table. rs9923231 SNP information is based on minus strand in source, so C/G and A/T were swapped to conform to the plus strand (as used in dbSNP)

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http://safety-code.org/ont/cds.ttl#rule-13needs more workWarfarinCoumadin Bristol Myers Squibb FDA drug labelCYP2C9*2/*3 VKORC1:rs9923231(G;G)rs1799853(C;T) rs1057910(A;C) rs1057911(A;A) rs9923231(C;C)not described in source3-4 mg warfarin per day should be considered as a starting dose range for a patient with this genotype according to the Warfarin drug label (Bristol-Myers Squibb).In Bearbeitung...USAFDA Drug label for Coumadin (warfarin sodium) tablet, Bristol-Myers Squibb Pharma Companyhttp://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=d91934a0-902e-c26c-23ca-d5accc4151b6#section-5.325.12.201109.05.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)CYP2C9 SNPs were added based on PharmGKB-derived allele table. rs9923231 SNP information is based on minus strand in source, so C/G and A/T were swapped to conform to the plus strand (as used in dbSNP)

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http://safety-code.org/ont/cds.ttl#rule-14needs more workWarfarinCoumadin Bristol Myers Squibb FDA drug labelCYP2C9*2/*3 VKORC1:rs9923231(A;G)rs1799853(C;T) rs1057910(A;C) rs1057911(A;A) rs9923231(C;T)not described in source0.5-2 mg warfarin per day should be considered as a starting dose range for a patient with this genotype according to the Warfarin drug label (Bristol-Myers Squibb).In Bearbeitung...USAFDA Drug label for Coumadin (warfarin sodium) tablet, Bristol-Myers Squibb Pharma Companyhttp://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=d91934a0-902e-c26c-23ca-d5accc4151b6#section-5.325.12.201109.05.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)CYP2C9 SNPs were added based on PharmGKB-derived allele table. rs9923231 SNP information is based on minus strand in source, so C/G and A/T were swapped to conform to the plus strand (as used in dbSNP)

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http://safety-code.org/ont/cds.ttl#rule-15needs more workWarfarinCoumadin Bristol Myers Squibb FDA drug labelCYP2C9*2/*3 VKORC1:rs9923231(A;A)rs1799853(C;T) rs1057910(A;C) rs1057911(A;A) rs9923231(T;T)not described in source0.5-2 mg warfarin per day should be considered as a starting dose range for a patient with this genotype according to the Warfarin drug label (Bristol-Myers Squibb).In Bearbeitung...USAFDA Drug label for Coumadin (warfarin sodium) tablet, Bristol-Myers Squibb Pharma Companyhttp://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=d91934a0-902e-c26c-23ca-d5accc4151b6#section-5.325.12.201109.05.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)CYP2C9 SNPs were added based on PharmGKB-derived allele table. rs9923231 SNP information is based on minus strand in source, so C/G and A/T were swapped to conform to the plus strand (as used in dbSNP)

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http://safety-code.org/ont/cds.ttl#rule-16needs more workWarfarinCoumadin Bristol Myers Squibb FDA drug labelCYP2C9*3/*3 VKORC1:rs9923231(G;G)rs1057910(C;C) rs1057911(A;A) rs9923231(C;C)not described in source0.5-2 mg warfarin per day should be considered as a starting dose range for a patient with this genotype according to the Warfarin drug label (Bristol-Myers Squibb).In Bearbeitung...USAFDA Drug label for Coumadin (warfarin sodium) tablet, Bristol-Myers Squibb Pharma Companyhttp://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=d91934a0-902e-c26c-23ca-d5accc4151b6#section-5.325.12.201109.05.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)CYP2C9 SNPs were added based on PharmGKB-derived allele table. rs9923231 SNP information is based on minus strand in source, so C/G and A/T were swapped to conform to the plus strand (as used in dbSNP)

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http://safety-code.org/ont/cds.ttl#rule-17needs more workWarfarinCoumadin Bristol Myers Squibb FDA drug labelCYP2C9*3/*3 VKORC1:rs9923231(A;G)rs1057910(C;C) rs1057911(A;A) rs9923231(C;T)not described in source0.5-2 mg warfarin per day should be considered as a starting dose range for a patient with this genotype according to the Warfarin drug label (Bristol-Myers Squibb).In Bearbeitung...USAFDA Drug label for Coumadin (warfarin sodium) tablet, Bristol-Myers Squibb Pharma Companyhttp://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=d91934a0-902e-c26c-23ca-d5accc4151b6#section-5.325.12.201109.05.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)CYP2C9 SNPs were added based on PharmGKB-derived allele table. rs9923231 SNP information is based on minus strand in source, so C/G and A/T were swapped to conform to the plus strand (as used in dbSNP)

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http://safety-code.org/ont/cds.ttl#rule-18needs more workWarfarinCoumadin Bristol Myers Squibb FDA drug labelCYP2C9*3/*3 VKORC1:rs9923231(A;A)rs1057910(C;C) rs1057911(A;A) rs9923231(T;T)not described in source0.5-2 mg warfarin per day should be considered as a starting dose range for a patient with this genotype according to the Warfarin drug label (Bristol-Myers Squibb).In Bearbeitung...USAFDA Drug label for Coumadin (warfarin sodium) tablet, Bristol-Myers Squibb Pharma Companyhttp://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=d91934a0-902e-c26c-23ca-d5accc4151b6#section-5.325.12.201109.05.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)CYP2C9 SNPs were added based on PharmGKB-derived allele table. rs9923231 SNP information is based on minus strand in source, so C/G and A/T were swapped to conform to the plus strand (as used in dbSNP)

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http://safety-code.org/ont/cds.ttl#rule-19needs more workClopidogrelClinical Pharmacogenetics Implementation Consortium (CPIC)CYP2C19 Ultrarapid metabolizer (UM) (*1/*17, *17/*17) and extensive metabolizer (EM) (*1/*1) Clopidogrel label-recommended dosage and administration http://pharmgkb.org/drug/PA449053#tabClinical
http://www.ncbi.nlm.nih.gov/pubmed/21716271
Strong14.06.201214.06.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-20needs more workClopidogrelClinical Pharmacogenetics Implementation Consortium (CPIC)CYP2C19 Intermediate metabolizer (IM) (*1/*2) Prasugrel or other alternative therapy (if no contraindication) http://pharmgkb.org/drug/PA449053#tabClinical
http://www.ncbi.nlm.nih.gov/pubmed/21716271
Moderate14.06.201214.06.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-21needs more workClopidogrelClinical Pharmacogenetics Implementation Consortium (CPIC)CYP2C19 Poor metabolizer (PM) (*2/*2) Prasugrel or other alternative therapy (if no contraindication) http://pharmgkb.org/drug/PA449053#tabClinical
http://www.ncbi.nlm.nih.gov/pubmed/21716271
Strong14.06.201214.06.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-22needs more workClopidogrelRoyal Dutch Pharmacists Association - Pharmacogenetics Working GroupCYP2C19 PM (*2/*2, *2/*3, *3/*3) Increased risk for reduced response to clopidogrel. Consider alternative drug. Prasugrel is not or to a much smaller extent metabolized by CYP2C19 but is associated with an increased bleeding risk compared to clopidogrel http://pharmgkb.org/drug/PA449053#tabClinicalPublished controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpointsClinical effect (statistically significant difference): death; arrhythmia; unanticipated myelosuppression 14.06.201214.06.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-23needs more workClopidogrelRoyal Dutch Pharmacists Association - Pharmacogenetics Working GroupCYP2C19 IM (*1/*2, *1/*3, *17/*2, *17/*3)Increased risk for reduced response to clopidogrel. Consider alternative drug. Prasugrel is not or to a much smaller extent metabolized by CYP2C19 but is associated with an increased bleeding risk compared to clopidogrel http://pharmgkb.org/drug/PA449053#tabClinicalPublished controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpointsClinical effect (statistically significant difference): death; arrhythmia; unanticipated myelosuppression 14.06.201214.06.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-24needs more workClopidogrelRoyal Dutch Pharmacists Association - Pharmacogenetics Working GroupCYP2C19 UM (*17/*17) None http://pharmgkb.org/drug/PA449053#tabClinicalPublished controlled studies of moderate quality# relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints Minor clinical effect (statistically significant difference): QTc prolongation (<450 ms female, <470 ms male); international normalized ratio increase < 4.5. Kinetic effect (statistically significant difference) 14.06.201214.06.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-25needs more workAzathioprineClinical Pharmacogenetics Implementation Consortium (CPIC)TPMT*1/*1Start with normal starting dose (e.g., 2-3 mg/kg/d) and adjust doses of azathioprine based on disease-specific guidelines. Allow 2 weeks to reach steady state after each dose adjustment.In Bearbeitung...Strong14.06.201214.06.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-26needs more workAzathioprineClinical Pharmacogenetics Implementation Consortium (CPIC)or(TPMT*1/*2,
TPMT*1/*3A,
TPMT*1/*3B,
TPMT*1/*3C,
TPMT*1/*4)
If disease treatment normally starts at the "full dose", consider starting at 30-70% of target dose (e.g., 1-1.5 mg/kg/d), and titrate based on tolerance. Allow 2-4 weeks to reach steady state after each dose adjustment. In Bearbeitung...Strong14.06.201214.06.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-27needs more workAzathioprineClinical Pharmacogenetics Implementation Consortium (CPIC)two nonfunctional alleles - *2, *3A, *3B, *3C, or *4Consider alternative agents. If using azathioprine start with drastically reduced doses (reduce daily dose by 10-fold and dose thrice weekly instead of daily) and adjust doses of azathioprine based on degree of myelosuppression and disease-specific guidelines. Allow 4-6 weeks to reach steady state after each dose adjustment. Azathioprine is the likely cause of myelosuppression. In Bearbeitung...Strong14.06.201214.06.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-28needs more workMercaptopurineClinical Pharmacogenetics Implementation Consortium (CPIC)TPMT*1/*1 Start with normal starting dose (e.g., 75 mg/m2/d or 1.5 mg/kg/d) and adjust doses of mercaptopurine (and of any other myelosuppressive therapy) without any special emphasis on mercaptopurine compared to other agents. Allow 2 weeks to reach steady state after each dose adjustment. In Bearbeitung...Strong14.06.201214.06.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-29needs more workMercaptopurineClinical Pharmacogenetics Implementation Consortium (CPIC)or(TPMT*1/*2,
TPMT*1/*3A,
TPMT*1/*3B,
TPMT*1/*3C,
TPMT*1/*4)
Start with reduced doses (start at 30-70% of full dose: e.g., at 50
mg/m2/d or 0.75 mg/kg/d) and adjust doses of MP based on degree of
myelosuppression and disease-specific guidelines. Allow 2-4 weeks to
reach steady state after each dose adjustment. In those who require a
dosage reduction based on myelosuppression, the median dose may be ~40%
lower (44 mg/m2) than that tolerated in wild-type patients (75 mg/m2).
In setting of myelosuppression, and depending on other therapy, emphasis
should be on reducing mercaptopurine over other agents.
In Bearbeitung...Strong14.06.201214.06.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-30needs more workMercaptopurineClinical Pharmacogenetics Implementation Consortium (CPIC)two nonfunctional alleles - *2, *3A, *3B, *3C, or *4For malignancy, start with drastically reduced doses (reduce daily dose
by 10-fold and reduce frequency to thrice weekly instead of daily, e.g.,
10 mg/m2/d given just 3 days/week) and adjust doses of MP based on
degree of myelosuppression and disease-specific guidelines. Allow 4-6
weeks to reach steady state after each dose adjustment. In setting of
myelosuppression, emphasis should be on reducing mercaptopurine over
other agents. For nonmalignant conditions, consider alternative
nonthiopurine immunosuppressant therapy.
Strong14.06.201214.06.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-31needs more workThioguanineClinical Pharmacogenetics Implementation Consortium (CPIC)TPMT*1/*1 Start with normal starting dose. Adjust doses of thioguanine and of other myelosuppressive therapy without any special emphasis on thioguanine . Allow 2 weeks to reach steady state after each dose adjustment. Strong14.06.201214.06.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-32needs more workThioguanineClinical Pharmacogenetics Implementation Consortium (CPIC)or(TPMT*1/*2,
TPMT*1/*3A,
TPMT*1/*3B,
TPMT*1/*3C,
TPMT*1/*4)
Start with reduced doses (reduce by 30-50%) and adjust doses of thioguanine based on degree of myelosuppression and disease-specific guidelines. Allow 2-4 weeks to reach steady state after each dose adjustment. In setting of myelosuppression, and depending on other therapy, emphasis should be on reducing thioguanine over other agents.Medium14.06.201214.06.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-33needs more workThioguanineClinical Pharmacogenetics Implementation Consortium (CPIC)TPMT: two nonfunctional alleles - *2, *3A, *3B, *3C, or *4Start with drastically reduced doses (reduce daily dose by 10-fold and dose thrice weekly instead of daily) and adjust doses of thioguanine based on degree of myelosuppression and disease-specific guidelines. Allow 4-6 weeks to reach steady state after each dose adjustment. In setting of myelosuppression, emphasis should be on reducing thioguanine over other agents. For nonmalignant conditions, consider alternative nonthiopurine immunosuppressant therapy. Strong14.06.201214.06.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-34needs more workAzathioprineRoyal Dutch Pharmacists Association - Pharmacogenetics Working GroupTPMT: one inactive allele: *2, *3, *4-*18Select alternative drug or reduce dose by 50%. Increase dose in response of hematologic monitoring and efficacy.http://www.ncbi.nlm.nih.gov/pubmed/21412232Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints. Clinical effect (statistically significant difference): Failure of lifesaving therapy e.g. anticipated myelosuppression; prevention of breast cancer relapse; arrhythmia; neutropenia < 0.5x109/l; leucopenia < 1.0x109/l; thrombocytopenia < 25x109/l; life-threatening complications from diarrhea. 14.06.201214.06.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-35needs more workAzathioprineRoyal Dutch Pharmacists Association - Pharmacogenetics Working GroupTPMT: two inactive alleles: *2, *3, *4-*18Select alternative drug or reduce dose by 90%. Increase dose in response of hematologic monitoring and efficacy.http://www.ncbi.nlm.nih.gov/pubmed/21412232Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints. Clinical effect (statistically significant difference): death; arrhythmia; unanticipated myelosuppression.14.06.201214.06.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-36needs more workMercaptopurineRoyal Dutch Pharmacists Association - Pharmacogenetics Working GroupTPMT: one inactive allele: *2, *3, *4-*18Select alternative drug or reduce dose by 50%. Increase dose in response of hematologic monitoring and efficacy.http://www.ncbi.nlm.nih.gov/pubmed/21412232Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints. Clinical effect (statistically significant difference): Failure of lifesaving therapy e.g. anticipated myelosuppression; prevention of breast cancer relapse; arrhythmia; neutropenia < 0.5x109/l; leucopenia < 1.0x109/l; thrombocytopenia < 25x109/l; life-threatening complications from diarrhea. 14.06.201214.06.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-37needs more workMercaptopurineRoyal Dutch Pharmacists Association - Pharmacogenetics Working GroupTPMT: two inactive alleles: *2, *3, *4-*18Select alternative drug or reduce dose by 90%. Increase dose in response of hematologic monitoring and efficacy.http://www.ncbi.nlm.nih.gov/pubmed/21412232Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints. Clinical effect (statistically significant difference): death; arrhythmia; unanticipated myelosuppression.14.06.201214.06.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-38needs more workThioguanineRoyal Dutch Pharmacists Association - Pharmacogenetics Working GroupTPMT: one inactive allele: *2, *3, *4-*18Select alternative drug. Insufficient data to allow calculation of dose adjustment. http://www.ncbi.nlm.nih.gov/pubmed/21412232Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.Clinical effect (S): long-standing discomfort (> 168 hr), permanent symptom or invalidating injury e.g. failure of prophylaxis of atrial fibrillation; venous thromboembolism; decreased effect of clopidogrel on inhibition of platelet aggregation; ADE resulting from increased bioavailability of phenytoin; INR > 6.0; neutropenia 0.5-1.0x109/l; leucopenia 1.0-2.0x109/l; thrombocytopenia 25-50x109/l; severe diarrhea14.06.201214.06.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-39needs more workThioguanineRoyal Dutch Pharmacists Association - Pharmacogenetics Working GroupTPMT: two inactive alleles: *2, *3, *4-*18Select alternative drug. Insufficient data to allow calculation of dose adjustment. http://www.ncbi.nlm.nih.gov/pubmed/21412232Published case reports, well documented, and having relevant pharmacokinetic or clinical endpoints. Well documented case series. Clinical effect (S): death; arrhythmia; unanticipated myelosuppression. 14.06.201214.06.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-40needs more workCodeineClinical Pharmacogenetics Implementation Consortium (CPIC)CYP2D6: two copies of functional alleles, e.g., *1/*1xN, *1/*2xN Ultrarapid metabolizer. Avoid codeine use due to potential for toxicity. Consider alternative analgesics such as morphine or a nonopiod. Consider avoiding tramadol. http://pharmgkb.org/download.action?filename=CPIC_2D6-Codeine.pdf http://pharmgkb.org/drug/PA449088#tabview=tab0&subtab=31Strong14.06.201214.06.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-41needs more workCodeineClinical Pharmacogenetics Implementation Consortium (CPIC)CYP2D6: two alleles encoding full or reduced function or one full function allele together with either one nonfunctional or one reduced-function allele, e.g., *1/*1, *1/*2, *2/*2, *1/*41, *1/*4, *2/*5, *10/*10 Extensive metabolizer. 15-50 mg every 4h as needed for pain (label recommendation) In Bearbeitung...http://pharmgkb.org/download.action?filename=CPIC_2D6-Codeine.pdf http://pharmgkb.org/drug/PA449088#tabview=tab0&subtab=31Strong14.06.201214.06.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-42needs more workCodeineClinical Pharmacogenetics Implementation Consortium (CPIC)CYP2D6: one reduced and one nonfunctional allele, e.g., *4/*10, *5/*41Intermediate metabolizer. Begin with 15-60 mg every 4h as needed for pain. If no response, consider alternative analgesics such as morphine or a nonopiod. Monitor tramadol use for response. In Bearbeitung...http://pharmgkb.org/download.action?filename=CPIC_2D6-Codeine.pdf http://pharmgkb.org/drug/PA449088#tabview=tab0&subtab=31Moderate14.06.201214.06.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-43needs more workCodeineClinical Pharmacogenetics Implementation Consortium (CPIC)CYP2D6: no functional alleles, e.g., *4/*4, *4/*5, *5/*5, *4/*6Poor metabolizer. Avoid codeine use due to lack of efficacy. Consider alternative analgesics such as morphine or a nonopiod. Consider avoiding tramadol. In Bearbeitung...http://pharmgkb.org/download.action?filename=CPIC_2D6-Codeine.pdf http://pharmgkb.org/drug/PA449088#tabview=tab0&subtab=31Strong 14.06.201214.06.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-44needs more workCodeineRoyal Dutch Pharmacists Association - Pharmacogenetics Working GroupCYP2D6: PM (two inactive (*3-*8, *11-*16, *19-*21, *38, *40, *42) alleles) Analgesia: select alternative drug (e.g., acetaminophen, NSAID, morphine-not tramadol or oxycodone) or be alert to symptoms of insufficient pain relief. Cough: no. In Bearbeitung...http://pharmgkb.org/download.action?filename=CPIC_2D6-Codeine.pdf http://pharmgkb.org/drug/PA449088#tabview=tab0&subtab=31Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints. Clinical effect (S): short-lived discomfort (< 48 hr) without permanent injury: e.g. reduced decrease in resting heart rate; reduction in exercise tachycardia; decreased pain relief from oxycodone; ADE resulting from increased bioavailability of atomoxetine (decreased appetite, insomnia, sleep disturbance etc); neutropenia > 1.5x109/l; leucopenia > 3.0x109/l; thrombocytopenia > 75x109/l; moderate diarrhea not affecting daily activities; reduced glucose increase following oral glucose tolerance test.14.06.201214.06.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-45needs more workCodeineRoyal Dutch Pharmacists Association - Pharmacogenetics Working GroupCYP2D6: IM (two decreased-activity (*9, *10, *17, *29, *36, *41) alleles or carrying one active (*1, *2, *33, *35) and one inactive (*3-*8, *11-*16, *19-*21, *38, *40, *42) allele, or carrying one decreased-activity (*9, *10, *17, *29, *36, *41) allele and one inactive (*3-*8, *11-*16, *19-*21, *38, *40, *42) allele) Analgesia: select alternative drug (e.g., acetaminophen, NSAID, morphine-not tramadol or oxycodone) or be alert to symptoms of insufficient pain relief. Cough: no In Bearbeitung...http://pharmgkb.org/drug/PA449088#tabview=tab0&subtab=31Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints. Minor clinical effect (S): QTc prolongation (<450 ms female, <470 ms male); INR increase < 4.5; Kinetic effect (S).14.06.201214.06.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-46needs more workCodeineRoyal Dutch Pharmacists Association - Pharmacogenetics Working GroupCYP2D6: UM (a gene duplication in absence of inactive (*3-*8, *11-*16, *19-*21, *38, *40, *42) or decreased-activity (*9, *10, *17, *29, *36, *41) alleles) Analgesia: select alternative drug (e.g., acetaminophen, NSAID, morphine-not tramadol or oxycodone) or be alert to ADE. Cough: be extra alert to ADEs due to increased morphine plasma concentration. In Bearbeitung...http://pharmgkb.org/drug/PA449088#tabview=tab0&subtab=31Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints. Clinical effect (S): death; arrhythmia; unanticipated myelosuppression. 14.06.201214.06.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-47needs more workSimvastatinClinical Pharmacogenetics Implementation Consortium (CPIC)rs4149056(T;T)rs4149056(T;T)Normal myopathy risk. FDA recommends against 80 mg (unless already tolerated 12 months). Prescribe desired starting dose and adjust doses of simvastatin based on disease-specific guidelines.In Bearbeitung...USAhttp://pharmgkb.org/drug/PA451363#tabview=tab0&subtab=31 http://pharmgkb.org/download.action?filename=cpic-slco1b1-simvastatin-article.pdfStrong26.06.201226.06.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-48needs more workSimvastatinClinical Pharmacogenetics Implementation Consortium (CPIC)rs4149056(C;T)rs4149056(C;T)Intermediate myopathy risk. FDA recommends against 80 mg. Consider a lower dose; if suboptimal efficacy, consider an alternative statin.In Bearbeitung...USAhttp://pharmgkb.org/drug/PA451363#tabview=tab0&subtab=31 http://pharmgkb.org/download.action?filename=cpic-slco1b1-simvastatin-article.pdfStrong26.06.201226.06.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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http://safety-code.org/ont/cds.ttl#rule-49needs more workSimvastatinClinical Pharmacogenetics Implementation Consortium (CPIC)rs4149056(C;C)rs4149056(C;C)High myopathy risk. FDA recommends against 80 mg. Prescribe a lower dose or consider an alternative statin; consider routine creatine kinase (CK) surveillance.In Bearbeitung...USAhttp://pharmgkb.org/drug/PA451363#tabview=tab0&subtab=31 http://pharmgkb.org/download.action?filename=cpic-slco1b1-simvastatin-article.pdfStrong26.06.201226.06.2012Matthias Samwald (matthias.samwald@meduniwien.ac.at)

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6IrinotecanUGT1A1*28/*28Dose >250mg/m^2: reduce initial dose by 30%. Increase dose in response to neutrophil count. Dose <=250mg/m^2: no dose adjustment. In Bearbeitung...http://pharmgkb.org/download.action?filename=cpic-tpmt-article.pdf
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[1] rules containing wild-type alleles are deprecated for now because of associated difficulty with calling wildtypes with certainty --matthiassamwald Montag, 16. April 2012 17:49:53
[2] Age range in years. Example: "18 to 100"
[3] values here are generated by a javascript function --matthiassamwald Mittwoch, 25. April 2012 11:58:40