Siponimod is metabolized by the liver to inactive metabolites. The protein in the liver responsible for the majority of this metabolism is the cytochrome p450 enzyme CYP2C9 (pronounced "sip two see nine").  

Across populations, CYP2C9 protein alleles can have different genetic variants that impact their ability to metabolize siponimod and other medications. The different alleles can produce three different metabolism phenotypes: normal, intermediate, and poor metabolizers.  Per the FDA drug label, patients must be genotyped for CYP2C9 to determine their CYP2C9 metabolizer phenotype before initiating therapy with siponimod.

The FDA requires that patients be genotyped for CYP2C9 to determine their CYP2C9 metabolizer phenotype to guide initial siponimod dosing. The FDA provides recommendations based on CYP2C9 metabolizer phenotype, which can be found here: https://www.pharmgkb.org/labelAnnotation/PA166182738

At UCHealth the use of pharmacogenetics when prescribing siponimod will occur in patients who meet the following conditions:

At UCHealth the use of pharmacogenetics when prescribing codeine or tramadol will occur in patients who meet the following conditions:
1) Provided a blood or saliva sample to the CCPM biobank, consented for the return of their results, and this sample has undergone genotyping OR the patient is being seen in a clinic which is currently using pharmacogenetic testing as part of standard care (e.g., the UCHealth GI Oncology Clinic).  
2) Are prescribed siponimod.

This process takes a minimum of 4-6 weeks but may take several years. Therefore, results will not be available at initial presentation if a patient has not previously enrolled in the biobank.  

If you are a provider AND your patient has a CYP2C9 metabolizer phenotype available, an inline medication warning a best practice alert (BPA) will warn you if you attempt to prescribe or refill siponimod.  If the BPA alerts, clinical guidance and associated resources will be listed for your reference. There is patient education text available for UCHealth providers to use in discharge paperwork or the after visit summary (AVS).

Visit our Provider FAQs page here.  For immediate questions, secure chat Groups: Pharmacogenomics Service in UCHealth's EHR.