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 this transporter can lead to increased plasma concentrations of statins and potentially an increased risk of statin related muscle toxicity (SRM) including myopathy and rhabdomyolysis.

Many variants have been found in the SLCO1B1 gene. The variant c.521T>C is a loss-of-function variant, which has been found to be associated with an increased risk of SRM. The c.521T>C variant is contained within SLCO1B1*5 and *15 allele haplotypes.

Pravastatin plasma levels are affected by SLCO1B1 polymorphism, but these effects are unlikely to be clinically significant enough at UK licensed doses to require therapy modification if no other risk factors for SRM are present. The main benefit of pharmacogenomic testing for pravastatin is to identify patients who have a higher potential to experience SRM and to aid drug choice and dose modification.

Testing recommendations

At the time of publication there are no UK recommendations for SLCO1B1 testing to guide the use of pravastatin.

Therapeutic recommendations

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  

• Increased plasma levels compared to individuals with SLCO1B1 normal function.
• Initiate and titrate according to disease-specific guidelines.
• Be aware of a possible increased risk of SRM, especially at doses >40mg (off-label dose in UK).
• 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  

• Increased plasma levels compared to normal or decreased function.
• Initiate and titrate according to disease-specific guidelines.
• Be aware of a possible increased risk of SRM.
• 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.

Further information

Drug interactions

The effects of drug-drug interactions with pravastatin may be more pronounced in people with reduced SLCO1B1 function and are likely to be additive to the impact of genetic variation. Multiple mechanisms may contribute to potential interactions with statins. Consult the SmPC for further information on drug interactions.

Other factors influencing risk of SRM 

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 SRM 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 SLCO1B1 function  

Pravastatin and fluvastatin are influenced to a lesser extent by SLCO1B1 variation than other statins and have low to moderate cholesterol lowering intensity. Pravastatin and fluvastatin may be suitable alternative statins in patients at higher risk of SRM or drug interactions, 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.

Aurobindo Pharma (2024) Pravastatin sodium 40mg Tablets SmPC. Available at: https://www.medicines.org.uk/emc/product/5322/smpc (Accessed online: 2/3/2026). 

Wolthuis D.F.G.J., Nijenhuis M., Soree B., de Boer-Veger N.J., Buunk A-M. 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.