CPIC publishes guidelines for DPYD and fluoropyrimidines

The Clinical Pharmacogenetics Implementation Consortium (CPIC) has published guidelines for the use of genetic test results for DPYD in fluoropyrimidine dosing. The guideline in Clinical Pharmacology and Therapeutics recommends strategies for drug dosing or alternative drug choice in cancer patients who have known variants in the

dihydropyrimidine dehydrogenase (DPYD) gene to avoid serious toxicity.

DPYD is a VIP gene that encodes the enzyme for the rate limiting step in the metabolism of 5-fluorouracil (5-FU) and other fluoropyrimidines such as capecitabine (see the Fluoropyrimidine Pathway, Pharmacokinetics). DPD catalyses the conversion of 5-FU to dihydrofluorouracil (DHFU) leading to its inactivation, blockage of this route of the pathway leads to high levels of active drug metabolites and severe and sometimes fatal toxicity. Inactivating variants of DPYD such as DPYD*2A (rs3918290), DPYD*13 (rs55886062)(<!-- /* Font Definitions */ @font-face {font-family:Cambria; panose-1:2 4 5 3 5 4 6 3 2 4; mso-font-charset:0; mso-generic-font-family:auto; mso-font-pitch:variable; mso-font-signature:3 0 0 0 1 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-unhide:no; mso-style-qformat:yes; mso-style-parent:""; margin-top:0in; margin-right:0in; margin-bottom:10.0pt; margin-left:0in; mso-pagination:widow-orphan; font-size:12.0pt; font-family:Cambria; mso-fareast-font-family:Cambria; mso-bidi-font-family:"Times New Roman";} .MsoChpDefault {mso-style-type:export-only; mso-default-props:yes; font-size:10.0pt; mso-ansi-font-size:10.0pt; mso-bidi-font-size:10.0pt; font-family:Cambria; mso-ascii-font-family:Cambria; mso-fareast-font-family:Cambria; mso-hansi-font-family:Cambria;} @page WordSection1 {size:8.5in 11.0in; margin:1.0in 1.25in 1.0in 1.25in; mso-header-margin:.5in; mso-footer-margin:.5in; mso-paper-source:0;} div.WordSection1 {page:WordSection1;} -

, or rs67376798 result in non-functional protein. The guideline suggests dose reduction for individuals known to be heterozygous for these inactivating variants, and avoidance of fluoropyrimidines for homozygotes of these inactivating variants.

For details see the CPIC guideline and supplement for capecitabine, fluorouracil, tegafur and DPYD

Read the updated DPYD VIP Summary

For other CPIC guidelines see the list of CPIC publications and guidelines in progress

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