How Rosuvastatin (Crestor) Affects ALT Levels

What the Crestor label reports about ALT

In the label's pooled placebo-controlled trials, transaminases above 3 times the upper limit of normal occurred in 1.1% of patients on Crestor and 0.5% on placebo [1].

The label's higher figure comes from METEOR, in which 984 adults were randomized to rosuvastatin 40 mg or placebo for 2 years. In the label's adverse-reaction table (700 on rosuvastatin, 281 on placebo, mean 1.7 years), ALT above 3 times the upper limit of normal occurred in 2.2% on rosuvastatin and 0.7% on placebo [1][2].

On monitoring, the label says to consider liver enzyme testing before starting Crestor and as clinically indicated during treatment [1]. It also states that rare fatal and non-fatal hepatic failure has been reported with statins, and it lists hepatitis and jaundice among postmarketing reports [1].

How often ALT rises above 3 times normal in other rosuvastatin studies

A prospective Taiwanese study followed 447 adults on rosuvastatin 10 mg daily for 12 weeks, including 375 who had taken no lipid-lowering drug before and 72 who switched from another one. ALT rose above 3 times the upper limit of normal in 0.6%, all of the abnormal laboratory values returned to the pretreatment level after the drug was stopped, and 2.7% discontinued because of adverse effects [3].

A UK observational study looked at 325 patients with documented adverse effects on other statins who were given rosuvastatin 5 mg, either daily or on fewer days per week. After a median follow-up of 14.9 months, ALT and creatine kinase were similar to baseline values [4]. That study had no placebo group, so it describes what happened in routine practice rather than a controlled comparison.

Does the 40 mg dose raise ALT more than lower doses?

The two label rates, 2.2% in METEOR at 40 mg and 1.1% across the 5 to 40 mg range in the pooled trials, come from separate programs of different lengths, so they are not a head-to-head dose comparison [1].

Who has higher rosuvastatin exposure

The label adjusts starting doses for some groups because of how much drug the body is exposed to.

• Liver impairment. In Child-Pugh A, peak concentration rose 60% and total exposure rose 5%; in Child-Pugh B, peak concentration rose 100% and total exposure rose 21%. Chronic alcohol-related liver disease modestly raises exposure [1].
• Severe kidney impairment. With a creatinine clearance under 30 mL/min/1.73 m2 and not on hemodialysis, exposure is about 3-fold higher, and the label starts at 5 mg and caps the dose at 10 mg daily [1].
• Asian ancestry. The label starts Asian patients at 5 mg daily because median exposure is roughly 2-fold higher [1]. In a single-dose study of 40 mg in 142 participants living in Singapore, exposure ratios compared with White participants were 2.31 in Chinese participants, 1.91 in Malay participants, and 1.63 in Asian-Indian participants; peak concentration ratios were 2.36, 2.00, and 1.68, respectively [5].
• SLCO1B1 genotype. In 32 healthy volunteers given 10 mg of rosuvastatin, the 4 people with two copies of the c.521C variant had 65% higher exposure and 79% higher peak concentration than the 16 with two copies of the reference variant [6]. The label describes very small groups with two reduced-function alleles and says the clinical impact of the genotype has not been established [1].

Liver disease and the contraindication

The label lists acute liver failure and decompensated cirrhosis as contraindications to rosuvastatin [1]. An isolated high ALT is not on that list.

After an ALT rise

The pooled trials and METEOR reported the percentage of patients whose transaminases or ALT rose above 3 times the upper limit of normal [1]. In the Taiwanese 10 mg cohort, all abnormal laboratory tests returned to pretreatment values after discontinuation [3].