Side Effects of Rosuvastatin
Rosuvastatin is generally safe and well-tolerated, with muscle-related symptoms being the most frequent side effect (5-20% in real-world practice), though serious complications like rhabdomyolysis remain exceedingly rare. 1
Muscle-Related Side Effects (Most Common)
Myalgia (muscle pain/aches) is the most frequent presentation, typically bilateral, involving proximal muscles, with normal creatine kinase (CK) levels. 1 Symptoms usually begin within weeks to months after starting therapy and resolve after discontinuation. 1
- Myositis/myopathy (elevated CK with concerning symptoms or objective weakness) is rare 1
- Rhabdomyolysis (CK >10 times upper limit of normal with renal injury) is exceedingly rare and typically occurs only with multiple predisposing factors 1, 2
- Very few patients (0.2-0.4%) experienced CPK elevations over 10-fold the upper limit of normal, and treatment-related myopathy occurred in ≤0.1% at dosages of 5-40 mg/day 3
Risk Factors for Muscle Symptoms
Your patient is at higher risk if they have: 1
- Advanced age (especially >80 years), with women at higher risk than men
- Small body frame, frailty, and low body mass index
- Asian ancestry (requires dose reduction)
- Multisystem disease, particularly chronic renal insufficiency from diabetes
- Drug interactions: CYP3A4 inhibitors, OATP1B1 inhibitors, cyclosporine, gemfibrozil, macrolide antibiotics, antifungal agents
Hepatic Side Effects
Transaminase elevation (>3 times upper limit of normal) is infrequent (0.5-2.0% of patients), and progression to liver failure is exceedingly rare. 1 Asymptomatic liver enzyme elevations often resolve with dose reduction or rechallenge with alternative statins. 1 Statins can be safely used in patients with chronic, stable liver disease (including non-alcoholic fatty liver disease) after obtaining baseline measurements and establishing monitoring schedules. 1, 4
New-Onset Diabetes Mellitus
Rosuvastatin modestly increases the risk of developing type 2 diabetes in susceptible individuals, but this should NOT be cause for discontinuation as cardiovascular benefits far outweigh this risk. 1, 4 The absolute risk increase is small (1.2% placebo vs 1.5% rosuvastatin over 5 years), and cardiovascular event rate reduction outweighs diabetes risk. 1 For every 255 patients treated with rosuvastatin for 4 years, one additional case of diabetes occurs while simultaneously preventing 5.4 vascular events. 1
Risk factors include: 1
- BMI ≥30
- Fasting glucose ≥100 mg/dL
- Metabolic syndrome
- HbA1c ≥6%
High-intensity rosuvastatin (20 mg) was associated with a 36% increased risk of new-onset diabetes compared to placebo (rate ratio 1.36,95% CI 1.25-1.48). 4 In the JUPITER trial, women taking rosuvastatin had a small but significant increase in HbA1c compared with placebo (5.9 vs 5.8, P = 0.001). 4
Renal Effects
Proteinuria and microscopic hematuria can occur, particularly at higher doses (≥40 mg/day), with incidence <1% at 10-20 mg/day versus <1.5% at 40 mg/day. 3 These events are mostly transient and not associated with acute or progressive deterioration in renal function at recommended dosages. 3 The proteinuria is likely a mild form of "tubular" proteinuria associated with statin-provoked inhibition of low-molecular-weight protein reabsorption by the renal tubules. 5, 2
Common Gastrointestinal and Other Side Effects
The most commonly reported treatment-related adverse events were: 3, 6
These were mostly transient and mild. 3
Monitoring Recommendations
Routine monitoring of CK and liver enzymes in asymptomatic patients is NOT recommended as it leads to unnecessary discontinuation without improving clinical outcomes. 1
- Obtain baseline liver function tests before starting therapy 1, 6
- Measure CK levels ONLY in patients with severe muscle symptoms or objective muscle weakness—NOT routinely 1
- If protein or blood develops in urine, your healthcare provider may decrease the dose 6
Management of Side Effects
Use a "reassess, rediscuss, and rechallenge" approach—the majority of patients can successfully tolerate at least one statin with this strategy. 1
- Temporarily discontinue rosuvastatin until symptoms resolve 1
- Rechallenge with a reduced dose, alternative statin, or alternative dosing regimen (including alternate-day dosing) 1
- For constipation: increase fluid intake and physical activity; consider stimulating laxatives or polyethylene glycol, lactulose, or magnesium citrate 7
Critical Drug Interactions to Avoid
Gemfibrozil should be avoided with rosuvastatin due to significantly increased risk of rhabdomyolysis (15 times higher than fenofibrate). 1 Use fenofibrate if fibrate therapy is needed. 1
Other important interactions: 1, 5
- Colchicine should be used with caution as it may produce synergistic muscle-related toxicity
- Vitamin K antagonists require caution
- Cyclosporine increases rosuvastatin blood levels and toxicity risk
- Antiretroviral agents may interact
Safe combinations include: fenofibrate, ezetimibe, omega-3-fatty acids, antifungal azoles, rifampin, and clopidogrel. 5
Key Clinical Pitfalls to Avoid
- DO NOT routinely measure CK or liver enzymes in asymptomatic patients—this leads to unnecessary discontinuation 1
- DO NOT discontinue rosuvastatin if diabetes develops—continue with lifestyle modifications 1
- DO NOT attribute all muscle symptoms to rosuvastatin without evaluating other causes (hypothyroidism, vitamin D deficiency, other medications) 1
- DO NOT use coenzyme Q10 for routine prevention or treatment of muscle symptoms—it is not recommended 1
- DO NOT avoid rosuvastatin in patients with stable liver disease—it can be used safely with appropriate monitoring 1
- DO NOT combine rosuvastatin with gemfibrozil—use fenofibrate if fibrate therapy is needed 1
Special Considerations
Rosuvastatin is pregnancy category X and should not be used in women of childbearing potential unless using effective contraception and not nursing. 4 If taking antacids containing aluminum and magnesium hydroxide, take rosuvastatin at least 2 hours before the antacid. 6