December 8, 2022

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

This is a summary of the cpic dosing guideline for statins and variation in the genes this video will specifically discuss the recommendations for slco1b1, cyp2c9 and fluvastatin. atorvastatin, lovastatin, pitavastatin,   this guideline was published in february 2022   and replaces the previous cpic guideline on simvastatin and slco1b1. patients

With reduced slco1b1 function or reduced cyp2c9 function may be at an increased risk of experiencing statin-induced myopathy when treated with fluvastatin. the guideline therefore recommends either a reduction in the starting dose or selection of an alternative statin for these patients. this is the pharmgkb fluvastatin pharmacokinetics pathway.

A link to the original pathway is provided in the description below this video. like other statins, fluvastatin 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. once inside liver cells, it is metabolized by

Several enzymes, including cyp2c9. patients with decreased slco1b1 function or decreased cyp2c9 function have increased exposure to fluvastatin. this can increase the risk of statin-induced myopathy. 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. there are over 70 defined cyp2c9 alleles, known as star alleles. star alleles are assigned an activity value relative to the *1 allele,   which is designated as

A normal function allele.  the activity scores of a patient’s cyp2c9 star alleles can be combined together to make a total cyp2c9 activity score. this activity score is then used to assign a metabolizer phenotype to the patient, as shown in this table and in table 1 of the guideline. note that, as more evidence becomes available, new star alleles can

Be added and the functional definition of some star alleles may change. an important caveat for all genotyping tests is that any alleles which are not detected in the assay are designated as *1. this can include rare increased-function, reduced-function and non-functional alleles   which are not routinely screened for in some genotyping tests.

Further information about slco1b1 and cyp2c9 alleles can also be found at the pharmvar website at a link to pharmvar is also given in the description below this video. the cpic recommendations for slco1b1 decreased function, possible decreased function and poor   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, 

And ancestry should also be considered when prescribing statins. these are the cpic recommendations for fluvastatin in patients with decreased or poor slco1b1 function. patients with decreased or possible decreased function may have increased exposure to fluvastatin but have a typical risk of myopathy with doses under 40mg. these patients can

Be prescribed the desired starting dose. patients with poor function may have increased exposure to fluvastatin these patients should be prescribed a starting dose of no more than 40mg. as with all statins, the potential for drug-drug  interactions and the effects of renal function,   hepatic function and ancestry should all 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 fluvastatin by cyp2c9 phenotype. patients who are cyp2c9 normal metabolizers may have normal exposure to fluvastatin. these patients can be given the desired starting dose. patients who are

Cyp2c9 intermediate metabolizers may have an increased risk of myopathy when treated with fluvastatin. these patients should be prescribed a starting dose of no more than 40mg. patients who are cyp2c9 poor metabolizers may have an increased risk of myopathy when treated with fluvastatin. these patients should be prescribed a starting dose of

No more than 20mg. as with all statins, the potential for drug-drug interactions and the effects of renal function, hepatic function   the effects of drug-drug interactions may be more pronounced in patients who are cyp2c9 intermediate or poor metabolizers. table 6 in the guideline publication gives recommendations for fluvastatin and

Combined slco1b1 and cyp2c9 phenotypes. 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 cyp2c9 alleles. the activity summary includes implications for the patient’s response to fluvastatin, 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 fluvastatin and SLCO1B1, CYP2C9 By PharmGKB