The following serious adverse reactions are discussed in greater detail in other sections of the label:
- Rhabdomyolysis with myoglobinuria and acute renal failure and myopathy (including myositis) [see WARNINGS AND PRECAUTIONS]
- Liver enzyme abnormalities [see WARNINGS AND PRECAUTIONS]
In the CRESTOR controlled clinical trials database (placebo or active-controlled) of 5394 patients with a mean treatment duration of 15 weeks, 1.4% of patients discontinued due to adverse reactions. The most common adverse reactions that led to treatment discontinuation were:
- abdominal pain
The most commonly reported adverse reactions (incidence ≥ 2%) in the CRESTOR controlled clinical trial database of 5394 patients were:
- abdominal pain
Clinical Studies Experience
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice.
Adverse reactions reported in ≥ 2% of patients in placebocontrolled clinical studies and at a rate greater than placebo are shown in Table 1. These studies had a treatment duration of up to 12 weeks.
Table 1: Adverse Reactions* Reported in ≥ 2% of Patients Treated with CRESTOR and > Placebo in Placebo-Controlled Trials (% of Patients)
|Adverse Reactions||CRESTOR 5 mg
|CRESTOR 10 mg
|CRESTOR 20 mg
|CRESTOR 40 mg
|Total CRESTOR 5 mg - 40 mg
|* Adverse reactions by COSTART preferred term.|
Other adverse reactions reported in clinical studies were abdominal pain, dizziness, hypersensitivity (including rash, pruritus, urticaria, and angioedema) and pancreatitis. The following laboratory abnormalities have also been reported: dipstick-positive proteinuria and microscopic hematuria [see WARNINGS AND PRECAUTIONS]; elevated creatine phosphokinase, transaminases, glucose, glutamyl transpeptidase, alkaline phosphatase, and bilirubin; and thyroid function abnormalities.
In the METEOR study, involving 981 participants treated with rosuvastatin 40 mg (n=700) or placebo (n=281) with a mean treatment duration of 1.7 years, 5.6% of subjects treated with CRESTOR versus 2.8% of placebo—treated subjects discontinued due to adverse reactions. The most common adverse reactions that led to treatment discontinuation were: myalgia, hepatic enzyme increased, headache, and nausea [see Clinical Studies].
Adverse reactions reported in ≥ 2% of patients and at a rate greater than placebo are shown in Table 2.
Table 2: Adverse Reactions* Reported in ≥ 2% of Patients Treated with CRESTOR and > Placebo in the METEOR Trial (% of Patients)
|Adverse Reactions||CRESTOR 40 mg
|†ALT > 3x ULN||2.2||0.7|
|* Adverse reactions by MedDRA preferred term.
† Frequency recorded as abnormal laboratory value.
In the JUPITER study, 17,802 participants were treated with rosuvastatin 20 mg (n=8901) or placebo (n=8901) for a mean duration of 2 years. A higher percentage of rosuvastatin-treated patients versus placebo-treated patients, 6.6% and 6.2%, respectively, discontinued study medication due to an adverse event, irrespective of treatment causality. Myalgia was the most common adverse reaction that led to treatment discontinuation.
In JUPITER, there was a significantly higher frequency of diabetes mellitus reported in patients taking rosuvastatin (2.8%) versus patients taking placebo (2.3%). Mean HbA1c was significantly increased by 0.1% in rosuvastatin-treated patients compared to placebo-treated patients. The number of patients with a HbA1c > 6.5% at the end of the trial was significantly higher in rosuvastatin-treated versus placebo-treated patients [see WARNINGS AND PRECAUTIONS and Clinical Studies].
Adverse reactions reported in ≥ 2% of patients and at a rate greater than placebo are shown in Table 3.
Table 3: Adverse Reactions* Reported in ≥ 2% of Patients Treated with CRESTOR and > Placebo in the JUPITER Trial (% of Patients)
|Adverse Reactions||CRESTOR 20 mg
|* Treatment-emergent adverse reactions by MedDRA preferred term.|
Pediatric patients 10 to 17 years of age
In a 12-week controlled study in boys and postmenarchal girls, the safety and tolerability profile of CRESTOR 5 to 20 mg daily was generally similar to that of placebo [see Clinical Studies and Use in Specific Populations, Pediatric Use].
However, elevations in serum creatine phosphokinase (CK) > 10 x ULN were observed more frequently in rosuvastatin compared with placebo-treated children. Four of 130 (3%) children treated with rosuvastatin (2 treated with 10 mg and 2 treated with 20 mg) had increased CK > 10 x ULN, compared to 0 of 46 children on placebo.
The following adverse reactions have been identified during postapproval use of CRESTOR: arthralgia, fatal and non-fatal hepatic failure, hepatitis, jaundice, thrombocytopenia, depression, sleep disorders (including insomnia and nightmares) and gynecomastia. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
There have been rare reports of immune-mediated necrotizing myopathy associated with statin use [see WARNINGS AND PRECAUTIONS].
There have been rare postmarketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. These cognitive issues have been reported for all statins. The reports are generally nonserious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks).