What is the timeframe for onset of liver dysfunction, kidney dysfunction, and rhabdomyolysis after a rosuvastatin (rosuvastatin) overdose?

Timeframe for Onset of Complications Following Rosuvastatin Overdose

Liver dysfunction, kidney dysfunction, and rhabdomyolysis typically develop within hours to days following a rosuvastatin overdose, with most cases showing laboratory abnormalities within 24-72 hours of ingestion.

Onset Timeline for Major Complications

Rhabdomyolysis

• Initial symptoms: Muscle pain, weakness, and dark urine typically appear within 24-48 hours after overdose 1
• Laboratory confirmation: Creatine kinase (CK) elevations become detectable within 12-24 hours and peak at 24-72 hours 2, 3
• Severe cases: Quadriparesis and significant muscle weakness may develop within 3-5 days of continued exposure 2

Kidney Dysfunction

• Early signs: Decreased urine output can occur within 24-48 hours following overdose 2
• Laboratory abnormalities: Elevated serum creatinine typically appears within 24-72 hours after the onset of rhabdomyolysis 3, 4
• Progression: Acute kidney injury may worsen over 3-5 days if the medication is not discontinued and appropriate treatment initiated 2

Liver Dysfunction

• Transaminase elevations: Typically begin within 24-72 hours after overdose 1
• Peak abnormalities: Liver enzyme elevations usually peak at 3-5 days post-ingestion 3, 5
• Resolution: With proper management, transaminase levels generally begin to normalize within 5-7 days after discontinuation of the medication 6

Risk Factors Affecting Onset Time

The timeline for symptom development can be accelerated by:

1. Pre-existing kidney disease: Patients with reduced renal function may develop complications more rapidly (within 12-24 hours) 3
2. Drug interactions: Concomitant use of medications that compete for CYP2C9 metabolism (like warfarin) can accelerate onset to within 24-48 hours 5
3. Dose-dependent effect: Higher doses lead to faster onset of symptoms, with doses >40mg daily showing complications within 24-48 hours 3
4. Age and comorbidities: Elderly patients and those with multiple comorbidities may develop symptoms more rapidly 2, 4

Clinical Monitoring Timeline

For suspected rosuvastatin overdose, monitoring should follow this timeline:

• 0-24 hours: Monitor for initial muscle pain, weakness, and dark urine; check CK, renal function, and liver enzymes
• 24-72 hours: Critical period for development of rhabdomyolysis and organ dysfunction; repeat laboratory tests every 12-24 hours
• 72-120 hours: Peak period for complications; continue monitoring until laboratory values begin to normalize
• 5-7 days: Most patients with appropriate management show improvement in laboratory values and symptoms

Management Considerations

Early recognition and prompt discontinuation of rosuvastatin are essential, as case reports demonstrate that patients who continued taking the medication despite early symptoms experienced more severe complications 2, 3. Aggressive intravenous fluid administration should be initiated immediately upon suspicion of rhabdomyolysis to prevent kidney injury 1.

In documented cases, patients who received prompt intervention typically showed normalization of laboratory values within 5-7 days of medication discontinuation 4, 5, while those with delayed recognition required more prolonged treatment, including hemodialysis 2.