Statin-associated muscle pain

What acts on it

1. Concomitant use of gemfibrozil with statins, and particularly with cerivastatin, increases the risk of rhabdomyolysis, and this study was undertaken because the mechanism of that potentially fatal interaction was unclear.

   Plasma cerivastatin exposure → Statin-associated muscle pain source_derived_draftungraded
   Experimental context and source evidence

   duration

   Not applicable

   evidence_access

   Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

   experimental_model

   Stated as the background to a 10-volunteer pharmacokinetic study

   exposure

   Gemfibrozil with cerivastatin

   limitations

   This is the study's framing of an established clinical association rather than a measurement made in it; no muscle outcome was recorded in the ten volunteers.

   organism

   Stated as the background to a 10-volunteer pharmacokinetic study

   plain_language

   Concomitant use of gemfibrozil with statins, and particularly with cerivastatin, increases the risk of rhabdomyolysis, and this study was undertaken because the mechanism of that potentially fatal interaction was unclear.

   primary_references

   Gemfibrozil greatly increases plasma concentrations of cerivastatin. (2002). https://pubmed.ncbi.nlm.nih.gov/12496749/ DOI: 10.1067/mcp.2002.128469

   route

   Oral

   tissue

   Skeletal muscle injury risk during combined treatment

   Statin plasma exposure and muscle injury: dose randomisation and a drug interaction (2026-09-22) · lines 57–66

   Original AI-assisted curation of three primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Two share a research group with the OATP1B1 collection and are recorded as one line of evidence with it. Study-specific doses, effect sizes and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

   ## cerivastatin-exposure-and-rhabdomyolysis-risk Concomitant use of gemfibrozil with statins, and particularly with cerivastatin, increases the risk of rhabdomyolysis, and this study was undertaken because the mechanism of that potentially fatal interaction was unclear. Model/species: Stated as the background to a 10-volunteer pharmacokinetic study Tissue/system: Skeletal muscle injury risk during combined treatment Exposure: Gemfibrozil with cerivastatin Route: Oral Duration: Not applicable Limits: This is the study's framing of an established clinical association rather than a measurement made in it; no muscle outcome was recorded in the ten volunteers. Primary reference: Gemfibrozil greatly increases plasma concentrations of cerivastatin. (2002). https://pubmed.ncbi.nlm.nih.gov/12496749/ DOI: 10.1067/mcp.2002.128469 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

   Complete structured claim and evidence

2. Myopathy occurred in 2 of 6,033 participants taking 20 mg simvastatin daily and in 53 of 6,031 taking 80 mg daily.

   Simvastatin 80 mg daily → Statin-associated muscle pain source_derived_draftungraded
   Experimental context and source evidence

   duration

   Mean follow-up 6.7 years

   evidence_access

   Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

   experimental_model

   12,064 men and women aged 18-80 with a history of myocardial infarction

   exposure

   80 mg versus 20 mg simvastatin daily, randomised double-blind

   limitations

   Dose is the randomised variable, not measured plasma concentration; the trial's primary endpoint was major vascular events and myopathy was a safety outcome. The trial was funded by the drug's manufacturer.

   organism

   12,064 men and women aged 18-80 with a history of myocardial infarction

   plain_language

   Myopathy occurred in 2 of 6,033 participants taking 20 mg simvastatin daily and in 53 of 6,031 taking 80 mg daily.

   primary_references

   Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial. (2010). https://pubmed.ncbi.nlm.nih.gov/21067805/ DOI: 10.1016/S0140-6736(10)60310-8

   route

   Oral

   tissue

   Myopathy as an adverse outcome

   Statin plasma exposure and muscle injury: dose randomisation and a drug interaction (2026-09-22) · lines 13–22

   Original AI-assisted curation of three primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Two share a research group with the OATP1B1 collection and are recorded as one line of evidence with it. Study-specific doses, effect sizes and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

   ## simvastatin-dose-raises-myopathy Myopathy occurred in 2 of 6,033 participants taking 20 mg simvastatin daily and in 53 of 6,031 taking 80 mg daily. Model/species: 12,064 men and women aged 18-80 with a history of myocardial infarction Tissue/system: Myopathy as an adverse outcome Exposure: 80 mg versus 20 mg simvastatin daily, randomised double-blind Route: Oral Duration: Mean follow-up 6.7 years Limits: Dose is the randomised variable, not measured plasma concentration; the trial's primary endpoint was major vascular events and myopathy was a safety outcome. The trial was funded by the drug's manufacturer. Primary reference: Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial. (2010). https://pubmed.ncbi.nlm.nih.gov/21067805/ DOI: 10.1016/S0140-6736(10)60310-8 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

   Complete structured claim and evidence

3. The investigators concluded that the increased risk of myopathy during combined simvastatin and gemfibrozil treatment is at least partially of pharmacokinetic origin.

   Plasma simvastatin exposure → Statin-associated muscle pain source_derived_draftungraded
   Experimental context and source evidence

   duration

   3 days

   evidence_access

   Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

   experimental_model

   10 healthy volunteers, with the myopathy association drawn from prior case reports

   exposure

   Gemfibrozil co-treatment raising simvastatin acid exposure by 185 percent

   limitations

   This is the authors' mechanistic conclusion linking their measured exposure change to a myopathy risk reported elsewhere, not a measurement of muscle injury in these ten volunteers.

   organism

   10 healthy volunteers, with the myopathy association drawn from prior case reports

   plain_language

   The investigators concluded that the increased risk of myopathy during combined simvastatin and gemfibrozil treatment is at least partially of pharmacokinetic origin.

   primary_references

   Plasma concentrations of active simvastatin acid are increased by gemfibrozil. (2000). https://pubmed.ncbi.nlm.nih.gov/10976543/ DOI: 10.1067/mcp.2000.108507

   route

   Oral

   tissue

   Plasma simvastatin acid concentration and muscle injury risk

   Statin plasma exposure and muscle injury: dose randomisation and a drug interaction (2026-09-22) · lines 35–44

   Original AI-assisted curation of three primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Two share a research group with the OATP1B1 collection and are recorded as one line of evidence with it. Study-specific doses, effect sizes and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

   ## simvastatin-exposure-raises-myopathy The investigators concluded that the increased risk of myopathy during combined simvastatin and gemfibrozil treatment is at least partially of pharmacokinetic origin. Model/species: 10 healthy volunteers, with the myopathy association drawn from prior case reports Tissue/system: Plasma simvastatin acid concentration and muscle injury risk Exposure: Gemfibrozil co-treatment raising simvastatin acid exposure by 185 percent Route: Oral Duration: 3 days Limits: This is the authors' mechanistic conclusion linking their measured exposure change to a myopathy risk reported elsewhere, not a measurement of muscle injury in these ten volunteers. Primary reference: Plasma concentrations of active simvastatin acid are increased by gemfibrozil. (2000). https://pubmed.ncbi.nlm.nih.gov/10976543/ DOI: 10.1067/mcp.2000.108507 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

   Complete structured claim and evidence

4. A genome-wide association study found a single strong association of statin myopathy with the rs4363657 variant within SLCO1B1, which encodes the hepatic uptake transporter OATP1B1.

   SLCO1B1 rs4363657 variant → Statin-associated muscle pain source_derived_draftungraded
   Experimental context and source evidence

   duration

   Trial duration, not stated here

   evidence_access

   Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

   experimental_model

   85 subjects with definite or incipient myopathy and 90 controls, replicated in a separate trial

   exposure

   Simvastatin 80 mg daily, replication at simvastatin 40 mg daily

   limitations

   The statin was simvastatin, not atorvastatin, and the association is with a noncoding variant rather than a demonstrated change in transporter function in these subjects.

   organism

   85 subjects with definite or incipient myopathy and 90 controls, replicated in a separate trial

   plain_language

   A genome-wide association study found a single strong association of statin myopathy with the rs4363657 variant within SLCO1B1, which encodes the hepatic uptake transporter OATP1B1.

   primary_references

   SLCO1B1 variants and statin-induced myopathy--a genomewide study. (2008). https://pubmed.ncbi.nlm.nih.gov/18650507/ DOI: 10.1056/NEJMoa0801936

   route

   Oral

   tissue

   Hepatic statin uptake and skeletal muscle injury

   Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22) · lines 133–142

   Original AI-assisted curation of twelve primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Findings obtained with mevastatin, simvastatin or the statin class are recorded against those subjects. Study-specific citations, doses, negative findings and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

   ## slco1b1-variant-and-statin-myopathy A genome-wide association study found a single strong association of statin myopathy with the rs4363657 variant within SLCO1B1, which encodes the hepatic uptake transporter OATP1B1. Model/species: 85 subjects with definite or incipient myopathy and 90 controls, replicated in a separate trial Tissue/system: Hepatic statin uptake and skeletal muscle injury Exposure: Simvastatin 80 mg daily, replication at simvastatin 40 mg daily Route: Oral Duration: Trial duration, not stated here Limits: The statin was simvastatin, not atorvastatin, and the association is with a noncoding variant rather than a demonstrated change in transporter function in these subjects. Primary reference: SLCO1B1 variants and statin-induced myopathy--a genomewide study. (2008). https://pubmed.ncbi.nlm.nih.gov/18650507/ DOI: 10.1056/NEJMoa0801936 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

   Complete structured claim and evidence

5. The 2022 trial found no effect on myalgia; individual changes in muscle CoQ did not correlate with changes in symptom intensity.

   Coenzyme Q10 / CoQ10 redox system → Statin-associated muscle pain source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/coq10-research/36139772.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "07baaf957ba2b166fce6e23f157e7d2123c92bea20032628c332c0a40639b992", "start_char": 0, "end_char": 1370, "text_sha256": "07baaf957ba2b166fce6e23f157e7d2123c92bea20032628c332c0a40639b992"}

   experimental_model

   Randomized placebo-controlled muscle-biopsy supplementation trial

   exposure

   CoQ10 400 mg/day for eight weeks

   limitations

   One formulation/regimen and a small sample; a failed tissue or clinical response cannot establish universal nonresponse.

   nutrient_topic

   Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system

   organism

   37 simvastatin-treated adults with or without myalgia

   plain_language

   A measured muscle pool and the pain outcome must be assessed separately.

   primary_references

   [coq10-p36139772] Coenzyme Q10 Supplementation in Statin Treated Patients: A Double-Blinded Randomized Placebo-Controlled Trial. (2022). https://pubmed.ncbi.nlm.nih.gov/36139772/ DOI: 10.3390/antiox11091698

   tissue_or_cell_type

   Muscle CoQ, mitochondrial function and symptoms

   Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 996–1007

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized placebo-controlled muscle-biopsy supplementation trial · source_derived_draft · unverified_draft

   ### coq10-statin-2022-pain-null The 2022 trial found no effect on myalgia; individual changes in muscle CoQ did not correlate with changes in symptom intensity. Condition category: normal nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A measured muscle pool and the pain outcome must be assessed separately. organism: 37 simvastatin-treated adults with or without myalgia tissue_or_cell_type: Muscle CoQ, mitochondrial function and symptoms experimental_model: Randomized placebo-controlled muscle-biopsy supplementation trial limitations: One formulation/regimen and a small sample; a failed tissue or clinical response cannot establish universal nonresponse. exposure: CoQ10 400 mg/day for eight weeks evidence_span: {"source_cache": "artifacts/coq10-research/36139772.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "07baaf957ba2b166fce6e23f157e7d2123c92bea20032628c332c0a40639b992", "start_char": 0, "end_char": 1370, "text_sha256": "07baaf957ba2b166fce6e23f157e7d2123c92bea20032628c332c0a40639b992"} [coq10-p36139772] Coenzyme Q10 Supplementation in Statin Treated Patients: A Double-Blinded Randomized Placebo-Controlled Trial. (2022). https://pubmed.ncbi.nlm.nih.gov/36139772/ DOI: 10.3390/antiox11091698

   Complete structured claim and evidence

6. Ubiquinol did not reduce pain severity or interference versus placebo in confirmed simvastatin myalgia.

   Reduced CoQ10 → Statin-associated muscle pain source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/coq10-research/25545331.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2aad217d0053cae8ea41f5be8ee7e0be0fa83f83d779f34e30fabe2a0b29c837", "start_char": 0, "end_char": 1976, "text_sha256": "2aad217d0053cae8ea41f5be8ee7e0be0fa83f83d779f34e30fabe2a0b29c837"}

   experimental_model

   Randomized double-blind trial after blinded symptom confirmation

   exposure

   600 mg/day ubiquinol with simvastatin 20 mg/day for eight weeks

   limitations

   Small confirmed-myalgia sample; null outcome is not proof that every other regimen is ineffective.

   nutrient_topic

   Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system

   organism

   41 subjects with confirmed simvastatin myalgia

   plain_language

   A more strictly selected trial did not reproduce the pain benefit.

   primary_references

   [coq10-p25545331] A randomized trial of coenzyme Q10 in patients with confirmed statin myopathy. (2015). https://pubmed.ncbi.nlm.nih.gov/25545331/ DOI: 10.1016/j.atherosclerosis.2014.12.016

   tissue_or_cell_type

   Pain, muscle performance and serum CoQ

   Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 1165–1176

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind trial after blinded symptom confirmation · source_derived_draft · unverified_draft

   ### coq10-statin-pain-null Ubiquinol did not reduce pain severity or interference versus placebo in confirmed simvastatin myalgia. Condition category: normal nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A more strictly selected trial did not reproduce the pain benefit. organism: 41 subjects with confirmed simvastatin myalgia tissue_or_cell_type: Pain, muscle performance and serum CoQ experimental_model: Randomized double-blind trial after blinded symptom confirmation limitations: Small confirmed-myalgia sample; null outcome is not proof that every other regimen is ineffective. exposure: 600 mg/day ubiquinol with simvastatin 20 mg/day for eight weeks evidence_span: {"source_cache": "artifacts/coq10-research/25545331.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2aad217d0053cae8ea41f5be8ee7e0be0fa83f83d779f34e30fabe2a0b29c837", "start_char": 0, "end_char": 1976, "text_sha256": "2aad217d0053cae8ea41f5be8ee7e0be0fa83f83d779f34e30fabe2a0b29c837"} [coq10-p25545331] A randomized trial of coenzyme Q10 in patients with confirmed statin myopathy. (2015). https://pubmed.ncbi.nlm.nih.gov/25545331/ DOI: 10.1016/j.atherosclerosis.2014.12.016

   Complete structured claim and evidence

7. Pain severity and interference improved relative to placebo after 30 days of CoQ in the 50-patient study.

   Coenzyme Q10 / CoQ10 redox system → Statin-associated muscle pain source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/coq10-research/25375075.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c1b3bae22ef80093dd226d2bebbc1791ac08e3952c694f801a72f308fd7258e4", "start_char": 0, "end_char": 1622, "text_sha256": "c1b3bae22ef80093dd226d2bebbc1791ac08e3952c694f801a72f308fd7258e4"}

   experimental_model

   Randomized placebo-controlled study

   exposure

   CoQ10 50 mg twice daily for 30 days

   limitations

   Small short study; symptoms were not confirmed by a blinded statin-placebo lead-in as in the later trial.

   nutrient_topic

   Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system

   organism

   50 statin-treated patients reporting mild-to-moderate muscle symptoms

   plain_language

   One trial found less muscle pain with added CoQ.

   primary_references

   [coq10-p25375075] Coenzyme Q10 supplementation decreases statin-related mild-to-moderate muscle symptoms: a randomized clinical study. (2014). https://pubmed.ncbi.nlm.nih.gov/25375075/ DOI: 10.12659/msm.890777

   tissue_or_cell_type

   Brief Pain Inventory scores

   Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 1152–1163

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized placebo-controlled study · source_derived_draft · unverified_draft

   ### coq10-statin-pain-positive Pain severity and interference improved relative to placebo after 30 days of CoQ in the 50-patient study. Condition category: normal nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: One trial found less muscle pain with added CoQ. organism: 50 statin-treated patients reporting mild-to-moderate muscle symptoms tissue_or_cell_type: Brief Pain Inventory scores experimental_model: Randomized placebo-controlled study limitations: Small short study; symptoms were not confirmed by a blinded statin-placebo lead-in as in the later trial. exposure: CoQ10 50 mg twice daily for 30 days evidence_span: {"source_cache": "artifacts/coq10-research/25375075.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c1b3bae22ef80093dd226d2bebbc1791ac08e3952c694f801a72f308fd7258e4", "start_char": 0, "end_char": 1622, "text_sha256": "c1b3bae22ef80093dd226d2bebbc1791ac08e3952c694f801a72f308fd7258e4"} [coq10-p25375075] Coenzyme Q10 supplementation decreases statin-related mild-to-moderate muscle symptoms: a randomized clinical study. (2014). https://pubmed.ncbi.nlm.nih.gov/25375075/ DOI: 10.12659/msm.890777

   Complete structured claim and evidence

8. The SLCO1B1 c.521T>C variant decreases OATP1B1 transporting activity, markedly increasing plasma statin concentrations, and thereby enhances the risk of statin-induced myopathy and decreases the therapeutic index of statins.

   Human OATP1B1 / SLCO1B1 → Statin-associated muscle pain source_derived_draftungraded
   Experimental context and source evidence

   duration

   Not applicable

   evidence_access

   Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

   experimental_model

   Review of human pharmacogenetic and pharmacokinetic studies

   exposure

   SLCO1B1 c.521T>C, protein p.V174A, rs4149056

   limitations

   This is a review statement summarising several studies rather than a single measurement, the effect differs between statins, and it describes the variant's effect on activity rather than a directly measured activity-to-myopathy relationship.

   organism

   Review of human pharmacogenetic and pharmacokinetic studies

   plain_language

   The SLCO1B1 c.521T>C variant decreases OATP1B1 transporting activity, markedly increasing plasma statin concentrations, and thereby enhances the risk of statin-induced myopathy and decreases the therapeutic index of statins.

   primary_references

   Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. (2011). https://pubmed.ncbi.nlm.nih.gov/21245207/ DOI: 10.1124/pr.110.002857

   route

   Oral statins

   tissue

   Hepatic uptake, plasma statin concentration and skeletal muscle injury

   OATP1B1 activity and statin exposure: the step between transporter inhibition and drug concentration (2026-09-22) · lines 68–77

   Original AI-assisted curation of four primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Three of the four share one research group and are recorded as one line of evidence. Study-specific citations, doses and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

   ## oatp1b1-activity-lowers-statin-myopathy-risk The SLCO1B1 c.521T>C variant decreases OATP1B1 transporting activity, markedly increasing plasma statin concentrations, and thereby enhances the risk of statin-induced myopathy and decreases the therapeutic index of statins. Model/species: Review of human pharmacogenetic and pharmacokinetic studies Tissue/system: Hepatic uptake, plasma statin concentration and skeletal muscle injury Exposure: SLCO1B1 c.521T>C, protein p.V174A, rs4149056 Route: Oral statins Duration: Not applicable Limits: This is a review statement summarising several studies rather than a single measurement, the effect differs between statins, and it describes the variant's effect on activity rather than a directly measured activity-to-myopathy relationship. Primary reference: Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. (2011). https://pubmed.ncbi.nlm.nih.gov/21245207/ DOI: 10.1124/pr.110.002857 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

   Complete structured claim and evidence