February 8, 2023

This is a summary of the CPIC guideline for statins and variation in the genes SLCO1B1, ABCG2 and CYP2C9.

And variation in the genes slco1b1, abcg2 and cyp2c9. this video will specifically discuss the recommendations for slco1b1, abcg2 and rosuvastatin. videos covering the recommendations for atorvastatin, lovastatin, pitavastatin, pravastatin, simvastatin and fluvastatin can be found on the pharmgkb website this guideline was published in february 2022 and

Replaces the previous cpic guideline on simvastatin and slco1b1. patients with reduced slco1b1 function may be at an increased risk of experiencing statin-induced myopathy when treated with rosuvastatin while patients with reduced abcg2 function may have increased exposure to rosuvastatin. the guideline therefore recommends a reduction in

The starting dose for patients with poor slco1b1 function or poor abcg2 function. this is the pharmgkb rosuvastatin pharmacokinetics pathway. a link to the original pathway is provided in the description below this video. like other statins, rosuvastatin used to lower cholesterol production in the body by inhibiting the enzyme hmg-coa

Reductase.   it is transported into liver cells by transporter proteins encoded by the gene slco1b1 and transported out of liver cells by transporter proteins encoded by abcg2. patients with decreased slco1b1 function have increased exposure to rosuvastatin, which can increase the risk of statin-induced myopathy.   patients

With decreased abcg2 function have increased exposure to rosuvastatin in the liver. this can increase the cholesterol-lowering effects of rosuvastatin but the impact on myopathy risk is unknown. patients can be assigned a slco1b1 phenotype based on the functional status of their slco1b1 alleles. this table shows the different phenotypes that can

Be assigned, along with example diplotypes. this information can also be found in table 1 of the guideline. gene information tables for slco1b1 are available on the pharmgkb website. a link to these tables is given in the description below this video. as part of producing this guideline, slco1b1 allele nomenclature was curated and centralized

Into pharmvar. this has resulted in significant changes, including the merging or reassignment of alleles. the slco1b1 page on pharmvar contains a change log with further details. this guideline also assigns abcg2 phenotypes to patients, based on their genotype at rs2231142, also known as the 421 c>a snp. this information is also shown in table 1

Of the guideline. gene information tables for abcg2 are also available on the pharmgkb website. a link to these tables is given in the description below this video. the cpic recommendations for slco1b1 decreased function, possible decreased function and however, the recommendations for increased function and normal function patients are the same for all

Statins. patients with increased or normal function may have typical statin exposure and a typical risk of myopathy when treated with statins. these patients can be prescribed the desired starting dose of statin. the potential for drug-drug interactions and the effects of renal function,   hepatic function and ancestry should also be

Considered when prescribing statins. these are the cpic recommendations for rosuvastatin in patients with decreased or poor slco1b1 function. patients with decreased or possible decreased function may have increased exposure to rosuvastatin but have a typical risk of myopathy with doses under 20mg. these patients can be prescribed the

Desired starting dose. patients with poor function may have increased exposure to rosuvastatin but have a typical risk of myopathy with doses under 20mg. as with all statins, the potential for drug-drug interactions and the effects of renal function,   hepatic function and ancestry should also be considered. the effects of drug-drug  

Interactions may be more pronounced in patients with decreased or poor slco1b1 function. these are the cpic recommendations for rosuvastatin by abcg2 phenotype. patients with normal abcg2 function have normal exposure to rosuvastatin. these patients can be given the desired starting dose. patients with decreased abcg2 function may have increased exposure

To rosuvastatin. patients with poor abcg2 function may have increased exposure to rosuvastatin. these patients should be prescribed a starting dose of no more than 20mg. hepatic function and ancestry should also be considered. the effects of drug-drug interactions   may be more pronounced in patients who have decreased or poor abcg2 function.

Table 5 in the guideline publication gives recommendations for rosuvastatin figure 1 in the guideline publication gives an overview of the recommendations with statin intensity and dose stratified by slco1b1 phenotype. it can be used to guide the selection of alternative statins. this guideline has been annotated on the pharmgkb website.  this

Includes a drop-down menu where an activity summary can be given for specific combinations of slco1b1 and abcg2 alleles. the activity summary includes implications for the patient’s response to rosuvastatin, the appropriate dosing recommendation for the specific genotypes and the strength of that recommendation. remember that variation in other genes

In addition to demographic and clinical factors, including concomitant medications, can affect treatment. it remains the responsibility of the clinician to determine the best course of treatment for a patient. cpic and pharmgkb assume no responsibility for any injury to persons or damage to persons or property   arising out of or related

To any use of cpic’s guideline, or for any errors or omissions. the guideline itself and supplementary information are freely available at the pharmgkb and cpic websites. you can access relevant pages using the links in the description below this video.

Transcribed from video
CPIC guideline for rosuvastatin and SLCO1B1, ABCG2 By PharmGKB