Crestor (Rosuvastatin) After Bariatric Surgery: Clinical Guide

Does bariatric surgery change rosuvastatin absorption?

A systematic review of 26 studies on drug absorption after bariatric surgery found the effect is drug-specific, with the most consistent evidence of reduced absorption for cyclosporine, thyroxine, phenytoin and rifampin [2]. That review did not report rosuvastatin data, and the Crestor label gives no bariatric-specific dosing [1][2]. Label background: absolute bioavailability is about 20%, peak plasma levels come 3 to 5 hours after a dose, food does not change AUC, and about 90% of a dose is excreted in feces [1].

What the label supports

Adults take 5 to 40 mg once daily, any time of day, with or without food, swallowed whole; AUC is the same with morning and evening dosing, and LDL-C is assessed as early as 4 weeks after starting [1].

Dose limits in the label with other drugs and conditions [1][3]:

• Cyclosporine, belumosudil, darolutamide or vadadustat: no more than 5 mg daily.
• Gemfibrozil: avoid; if unavoidable, start at 5 mg and stay at or under 10 mg daily.
• Simeprevir, atazanavir/ritonavir, lopinavir/ritonavir and several hepatitis C regimens: start at 5 mg, no more than 10 mg daily. Sofosbuvir/velpatasvir/voxilaprevir and ledipasvir/sofosbuvir: avoid.
• Ticagrelor, febuxostat or fostamatinib: no more than 20 mg daily.
• Severe renal impairment (creatinine clearance under 30 mL/min/1.73 m2, not on dialysis): start at 5 mg, no more than 10 mg daily.
• Asian patients: start at 5 mg, because median exposure is about 2-fold higher than in White controls; if LDL-C is not controlled at doses up to 20 mg daily, the label says to consider the risks and benefits of treatment.

Crestor tablets come in 5, 10, 20 and 40 mg strengths, and the maximum labeled adult dose is 40 mg once daily [1].

Which interactions matter most

An aluminum/magnesium hydroxide antacid taken at the same time cut rosuvastatin AUC by about 50% (ratio 0.5); taken 2 hours apart the ratio was 0.8, and the label says to take Crestor at least 2 hours before the antacid [1]. In a 10-patient heart transplant study, cyclosporine raised steady-state rosuvastatin AUC 7.1-fold and Cmax 10.6-fold versus historical healthy controls, and rosuvastatin did not change cyclosporine levels [1][4]. Rosuvastatin significantly increased INR in patients on warfarin, and the label calls for INR checks before starting and often enough after starting, titration or stopping [1]. Clearance does not depend on CYP3A4 to a clinically significant extent; itraconazole 200 mg daily raised AUC only about 1.4-fold [1].

What to monitor

LDL-C as early as 4 weeks after starting. Liver enzymes are considered before starting and as clinically indicated; transaminases above 3 times the upper limit of normal occurred in 1.1% on Crestor versus 0.5% on placebo in pooled trials [1]. Myopathy risk is greater at 40 mg than at lower doses, with added risk at age 65 or older, uncontrolled hypothyroidism, renal impairment and certain other drugs. The label says patients should promptly report unexplained muscle pain, tenderness or weakness, particularly with malaise or fever, and that Crestor is temporarily stopped in acute conditions that risk renal failure from rhabdomyolysis [1]. HbA1c and fasting glucose can rise [1].