Ribociclib and Simvastatin: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 4, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Ribociclib
Simvastatin
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
These two medicines should not be taken together. Ribociclib (Kisqali) is a strong blocker of a liver enzyme called CYP3A4, which is the same enzyme your body uses to clear simvastatin (Zocor). When ribociclib blocks it, simvastatin builds up to much higher levels than intended.
That extra buildup raises the risk of serious muscle problems, including a dangerous condition called rhabdomyolysis, where muscle tissue breaks down. Warning signs include unexplained muscle pain, tenderness, weakness, or dark-colored urine. The good news is your care team can manage this by adjusting your cholesterol treatment while you are on ribociclib. Please talk with your doctor or pharmacist before changing anything.
Contraindicated combination. Ribociclib is a strong CYP3A4 inhibitor; simvastatin is a sensitive CYP3A4 substrate (active drug, not a prodrug). Inhibition reduces simvastatin metabolism, markedly increasing simvastatin AUC/Cmax and the risk of myopathy and rhabdomyolysis.
- Direction: increased simvastatin exposure/effect
- Onset: delayed; a case report described severe rhabdomyolysis after ~3 weeks of concomitant use
- Evidence: probable
- Management: avoid concomitant use. If a strong CYP3A4 inhibitor is unavoidable, suspend simvastatin during ribociclib therapy. If use is unavoidable, monitor creatine kinase and watch for muscle symptoms. Consider a statin less dependent on CYP3A4.
What happens
Increased simvastatin exposure and an increased the risk of myopathy and rhabdomyolysis
Interaction Deep Dive
Combining strong CYP3A4 inhibitors such as ribociclib with simvastatin (a CYP3A4 substrate) is contraindicated, because this combination can raise simvastatin exposure and heighten the risk of myopathy and rhabdomyolysis. When a CYP3A4 inhibitor must be used, simvastatin should be paused for the duration of strong CYP3A4 inhibitor therapy1. In one case report, a probable link was found between drug-induced severe rhabdomyolysis and 3 weeks of joint use of ribociclib and simvastatin. Their concurrent use should be avoided, and if it is required, creatine kinase should be monitored carefully2.
Why it happens (mechanism)
Inhibition CYP3A4-mediated simvastatin metabolism by ribociclib
How to manage this interaction
This pairing is contraindicated, so your care team will usually avoid using them together. Ribociclib is important cancer therapy, so the cholesterol medicine is typically the one that gets changed.
- Your team may suspend simvastatin during your ribociclib course, or switch you to a different cholesterol medicine that is handled differently by the body.
- If the two are ever used together, your team may monitor your creatine kinase (a muscle blood test) and watch for muscle symptoms.
- Keep taking both exactly as prescribed until you speak with your doctor, and report any muscle pain, weakness, tenderness, or dark urine right away.
Ask your pharmacist or prescriber to review your statin choice.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) A 68-year-old woman with HR-positive, HER2-negative left breast cancer and hypercholesterolemia that had been stable on simvastatin for years presented with generalized weakness and progressive paraplegia 3 weeks after starting ribociclib and letrozole. She reported a 4-day history of confusion and limb pain that made walking difficult. At presentation, notable laboratory findings included raised creatine kinase (CK; 5595 units/L), serum creatinine (Scr; 105 mcmol/L), and Grade 3 neutropenia with no signs of infection. Rhabdomyolysis was diagnosed; simvastatin and ribociclib were stopped and other causes were excluded, yet the patient's condition advanced to tetraplegia along with further increases in CK, Scr, and liver enzymes. Renal function improved with hydration, but CK kept rising on day 6 (37,000 units/L) accompanied by worsening hepatic impairment (AST, 1314 international units/L; ALT, 377 international units/L). Hydration was increased and IV niCARdipine was started for elevated blood pressure. After 1 week of intensive care, her condition began to improve and she regained the ability to walk. One month after hospital discharge, ribociclib was restarted at 200 mg/day for 1 week, 400 mg/day for week 2, and raised to 600 mg/day in week 3, followed by 600 mg daily for 3 weeks on/1 week off; this treatment was well tolerated. Simvastatin was not restarted. The Drug Interaction Probability Scale (DIPS) score for this case was 7, indicating a probable association of ribociclib-simvastatin induced rhabdomyolysis 2.
Common questions
Can I take Ribociclib and Simvastatin together?
Ribociclib strongly raises simvastatin levels and the risk of serious muscle breakdown, so this combination is contraindicated; your care team will typically pause or switch your statin while you are on ribociclib. Report any muscle pain, weakness, or dark urine promptly. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Ribociclib and Simvastatin interaction?
It is rated contraindicated. These should generally not be used together.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How is the Ribociclib and Simvastatin interaction managed?
This pairing is contraindicated, so your care team will usually avoid using them together. Ribociclib is important cancer therapy, so the cholesterol medicine is typically the one that gets changed. Your team may suspend simvastatin during your ribociclib course, or switch you to a different cholesterol medicine that is handled differently by the body. If the two are ever used together, your team… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Ribociclib or Simvastatin need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (2)
- Product Information: VYTORIN(R) oral tablets, ezetimibe simvastatin oral tablets. Organon LLC (per FDA), Jersey City, NJ, 2024. DailyMed
- Streicher C, Daulange A, Madranges N, et al: Severe rhabdomyolysis induced by possible drug-drug interaction between Ribociclib and Simvastatin. J Oncol Pharm Pract 2021; 27(3):722-726. PubMed
Keep reading about Ribociclib
Keep reading about Simvastatin
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