Impact of genetic variation on response to therapy
The SLCO1B1 transporter (also known as OATP1B1 and OATP-C) plays an important role in the transfer of statins from the blood into the liver. Reduced function of the SLCO1B1 transporter can lead to increased plasma concentrations of statins and potentially an increased risk of statin related muscle toxicity (SRM) such as myopathy and rhabdomyolysis.
Fluvastatin plasma levels are affected by variants in the SLCO1B1 gene, but these effects are unlikely to be clinically significant enough to require therapy modification if no other risk factors are present. Fluvastatin is influenced to a lesser extent by SLCO1B1 in comparison to other statins. The SLCO1B1 variant c.521 T > C is a loss-of-function variant that is contained within SLCO1B1*5 and *15 allele haplotypes.
The metabolism of fluvastatin has also been reported to be influenced by genetic variations in the CYP2C9 gene. Carriers of the loss-of-function CYP2C9*2 or CYP2C9*3 alleles (CYP2C9 intermediate or poor metabolisers) may be at risk of increased fluvastatin plasma concentrations although the SmPC states that there are multiple alternative CYP pathways for fluvastatin metabolism and that fluvastatin is relatively insensitive to CYP450 enzyme inhibition.
The main benefit of pharmacogenomic testing for fluvastatin is to identify patients who have a higher potential to experience SRM and to aid drug choice.
Testing recommendations
At the time of publication there are no UK recommendations for SLCO1B1 or CYP2C9 testing to guide the use of fluvastatin.
Therapeutic recommendations
SLCO1B1
SLCO1B1 status unknown
- Initiate and titrate according to disease-specific guidelines.
SLCO1B1 increased function
Some examples of SLCO1B1 genotypes include (see note): *14/*14
- Initiate and titrate according to disease-specific guidelines.
SLCO1B1 normal function
Some examples of SLCO1B1 genotypes include (see note): *1/*1, *1/*14, c.521T/T
- Initiate and titrate according to disease-specific guidelines.
SLCO1B1 decreased function
Some examples of SLCO1B1 genotypes include (see note): *1/*5, *1/*15, c.521T/C
- Predictive of higher plasma levels compared to individuals with SLCO1B1 normal function.
- Initiate and titrate according to disease-specific guidelines but be aware of possible increased risk of SRM, especially with doses >40mg daily.
- Monitor for adverse effects and advise patient on action to take if they experience muscle toxicity symptoms.
SLCO1B1 poor function
Some examples of SLCO1B1 genotypes include (see note): *5/*5, *5/*15, *15/*15, c.521C/C
- Predictive of higher plasma levels compared to individuals with SLCO1B1 normal or decreased function.
- Initiate and titrate according to disease-specific guidelines but be aware of possible increased risk of SRM, especially with doses >40mg daily.
- Monitor for adverse effects and advise patient on action to take if they experience muscle toxicity symptoms.
Note: Both the star(*) allele and c.521T>C genotype are provided as examples. Reporting methodology may vary by laboratory.
CYP2C9
CYP2C9 unknown metaboliser status
- Initiate and titrate according to disease-specific guidelines.
CYP2C9 normal metaboliser status: Activity score 2.0
Some examples of CYP2C9 genotypes include: *1/*1
- Initiate and titrate according to disease-specific guidelines.
CYP2C9 intermediate metabolisers: Activity score 1.5 or 1.0
Some examples of CYP2C9 genotypes include: *1/*2, *1/*3, *2/*2
- Predictive of higher plasma levels compared to normal metabolisers.
- Initiate and titrate according to disease-specific guidelines but be aware of possible increased risk of SRM, especially with doses >40mg daily. If >40mg daily is required, consider an alternative statin if clinically appropriate (see Further information), or keep the dose as low as possible (e.g. by adding non-statin cholesterol lowering agent).
- Monitor for adverse effects and advise patient on action to take if they experience muscle toxicity symptoms.
CYP2C9 poor metabolisers: Activity score 0.5 or 0.0
Some examples of CYP2C9 genotypes include (see note): *2/*3, *3/*3
- Predictive of higher plasma levels compared to normal or intermediate metabolisers.
- Initiate and titrate according to disease-specific guidelines but be aware of possible increased risk of SRM, especially with doses >20mg daily. If >20mg daily is required, consider an alternative statin if clinically appropriate (see Further information), or keep the dose as low as possible (e.g. by adding non-statin cholesterol lowering agent).
- Monitor for adverse effects and advise patient on action to take if they experience muscle toxicity symptoms.
SLCO1B1 and CYP2C9 combined therapeutic recommendations
- Evidence for dose adjustments based on combined genotype or phenotype information is limited.
- Combinations of SLCO1B1 and CYP2C9 variants and phenotypes are likely to have additive effects on the pharmacokinetics of fluvastatin.
- Where the phenotype of one gene recommends a greater dose reduction than the other, follow the greater dose reduction of the two recommendations.
- For CYP2C9 poor metabolisers who also have SLCO1B1 decreased or poor function, consider an alternative statin.
Further information
Drug interactions
The effects of drug-drug interactions with fluvastatin may be more pronounced in people with reduced SLCO1B1 or CYP2C9 function and are likely to be additive to the impact of genetic variation. Multiple mechanisms may contribute to potential interactions with statins. Drugs or herbal products that inhibit certain enzymes (e.g. CYP2C9) and/or transporter pathways (e.g. SLCO1B1) may increase fluvastatin plasma concentrations and may lead to an increased risk of myopathy or rhabdomyolysis. Consult the SmPC of fluvastatin for further information about drug interactions.
Other factors influencing risk of SAMS
The risk of SRM is influenced by a variety of factors in addition to genotype. These include dose, age, gender, comorbidities and drug interactions. Additional risk factors for SAMS should be considered when prescribing statins.
Patients already on stable and effective statin therapy
The main benefit of pharmacogenomic testing for statins is to aid in medication selection by identifying patients who are more or less likely to experience adverse effects including SRM. For patients who have already been on a stable and effective statin dose for more than 1 year without concerns regarding adverse effects, it is likely to be safe to continue.
Choice of statins in individuals with reduced CYP2C9 and/or SLCO1B1 function
Fluvastatin and pravastatin are influenced to a lesser extent by SLCO1B1 variation than other statins and have low to moderate cholesterol lowering intensity. Pravastatin is not influenced by CYP2C9 genotype. Fluvastatin and pravastatin may be suitable alternative statins in patients at higher risk of SRM, or with intolerance to other statins. Choice of statin should consider lipid lowering intensity, and local and national statin prescribing guidelines. See individual drug monographs for further information.
References
Clinical Pharmacogenetics Implementation Consortium CPIC® (2022) Guideline for statins and SLCO1B1, ABCG2, and CYP2C9. Available at: https://www.clinpgx.org/guideline/PA166264281 Accessed online 12/2/2026.
Sandoz (2024) Fluvastatin 20mg Capsules SmPC. Available at: https://www.medicines.org.uk/emc/product/4465/smpc (Accessed online: 3/3/2026).
Aspire Pharma (2023) Fluvastatin 80mg prolonged release Tablets SmPC. Available at: https://www.medicines.org.uk/emc/product/10501/smpc (Accessed online: 3/3/2026).
Wolthuis et al. (2025). Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction between SLCO1B1 and statins and CYP2C9 and sulfonylureas. European Journal of Human Genetics, 33(4):413-420. https://doi.org/10.1038/s41431-024-01769-7 Accessed online 12/2/2026.
NHS England (2023) Statin intolerance pathway. Available at: https://www.england.nhs.uk/aac/publication/statin-intolerance-pathway/ Accessed online 27th May 2026.
