Crestor Alcohol Interaction Profile: What You Need to Know Before You Drink

What the Crestor label says about alcohol

The label's alcohol statement sits in the pharmacokinetics section: chronic alcohol liver disease modestly raises rosuvastatin exposure [1]. The same section gives the size of the effect in liver impairment generally. In Child-Pugh A, Cmax rose 60% and AUC 5%; in Child-Pugh B, Cmax rose 100% and AUC 21% [1].

The contraindication is narrower than 'any liver disease': acute liver failure or decompensated cirrhosis [1]. A review of lipid-lowering drug hepatotoxicity took a compatible position, concluding that patients with chronic liver disease and compensated cirrhosis should not be precluded from statins when treatment is indicated [3].

In pooled placebo-controlled trials, transaminases above 3 times the upper limit of normal occurred in 1.1% of people on Crestor and 0.5% on placebo [1]. The label asks for liver enzyme testing before starting and as clinically indicated, and notes rare fatal and non-fatal hepatic failure with statins [1]. In METEOR, ALT above 3 times the upper limit occurred in 2.2% on rosuvastatin 40 mg versus 0.7% on placebo over a mean 1.7 years [1].

Does heavy drinking change the liver picture?

Alcoholic liver disease runs from fatty liver through alcoholic hepatitis to cirrhosis, and prolonged abstinence is the most effective strategy for preventing progression [4].

A prospective study of 515 consecutive statin users aged 80 to 98 found aminotransferase elevation in 24 patients, 4.7% (95% CI 2.7 to 6.6) [2]. Multivariable analysis in that cohort identified chronic hepatitis B infection and alcohol consumption as independent factors [2]. None of the patients developed hepatic failure [2]. The cohort took several different statins, not rosuvastatin alone [2].

Muscle: two separate problems that can overlap

Rosuvastatin has no boxed warning, but the label lists myopathy and rhabdomyolysis as risks, with acute kidney injury from myoglobinuria and rare fatalities reported with statins [1]. Risk factors named in the label are age 65 or older, uncontrolled hypothyroidism, renal impairment, certain other drugs and higher dosage; Asian patients may be at higher risk, and myopathy risk is greater at 40 mg than at lower doses [1]. Rare immune-mediated necrotizing myopathy also occurs [1].

Muscle symptoms are common in the trials. JUPITER randomized 17,802 apparently healthy adults to rosuvastatin 20 mg daily or placebo and was stopped after a median of 1.9 years [6]. In the label's JUPITER adverse-reaction data (8,901 per arm), myalgia was reported by 7.6% on rosuvastatin and 6.6% on placebo, and arthralgia by 3.8% and 3.2% [1]. In METEOR, myalgia was 12.7% versus 12.1%, and raised CPK 2.6% versus 0.7% [1].

Alcohol causes its own muscle disease. A review of alcoholic myopathy describes selective atrophy of Type II fibres, muscle mass reduction of up to 30%, and direct inhibition of muscle protein synthesis by alcohol and acetaldehyde; the authors estimate the condition occurs in approximately 50% of alcohol misusers [7]. That work examined alcohol alone, not people taking statins [7].

What the label tells patients to report

The label instructs patients to promptly report unexplained muscle pain, tenderness or weakness, particularly with malaise or fever [1]. It directs temporary discontinuation during acute conditions that risk renal failure from rhabdomyolysis, such as sepsis, shock or major surgery [1]. Alcoholic hepatitis can present with rapid onset or worsening jaundice [4].

Is there an alcohol-based dose limit?

The Crestor label's dose-limit table is built around other drugs, not alcohol [1]. Dosing is once daily at any time of day, with or without food [1].

One secondary analysis of 147 HIV-infected adults in a 96-week rosuvastatin trial did track drinking: 45% of participants consumed alcohol, and alcohol use was associated with several markers of gut integrity and inflammation [8]. That analysis measured those markers, not rosuvastatin concentrations, so it does not show whether drinking shifts the drug's levels [8].

How much drinking counts as heavy

NIAAA defines a standard drink as 0.6 fl oz or 14 g of pure alcohol [9]. Heavy drinking is 5 or more drinks on any day or 15 or more per week for men and 4 or more on any day or 8 or more per week for women; binge drinking is 5 or more drinks for men or 4 or more for women in about two hours [9]. NIAAA also notes that harms may be associated with any amount of drinking, and that risk rises as consumption rises [9].