"The U.S. Food and Drug Administration today approved Kynamro (mipomersen sodium) injection as an addition to lipid-lowering medications and diet to treat patients with a rare type of high cholesterol called homozygous familial hypercholesterolemi"...
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 placebo-controlled 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 Reactions1 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
|1 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 Reactions1
Reported in ≥ 2% of Patients Treated with CRESTOR and > Placebo in the
METEOR Trial (% of Patients)
|Adverse Reactions||CRESTOR 40 mg
|ALT > 3x ULN2||2.2||0.7|
|1Adverse reactions by MedDRA preferred term.
2Frequency 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 Reactions1 Reported in
≥ 2% of Patients Treated with CRESTOR and > Placebo in the JUPITER
Trial (% of Patients)
|Adverse Reactions||CRESTOR 20 mg
|1 Treatment-emergent adverse reactions by MedDRA preferred term.|
Pediatric Patients 8 To 17 Years Of Age With Heterozygous Familial Hypercholesterolemia
In a 12-week controlled study in boys and postmenarcheal girls 10 to 17 years of age with heterozygous familial hypercholesterolemia, the safety and tolerability profile of CRESTOR 5 to 20 mg daily was generally similar to that of placebo [see Use in Specific Populations and Clinical Studies].
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.
In a separate two year open-label, uncontrolled, trial that included 175 children and adolescents 8 to 17 years of age with heterozygous familial hypercholesterolemia, patients were started on CRESTOR 5 mg and titrated to 10 mg or 20 mg according to age group and clinical response. The safety and tolerability profile was generally consistent with that reported for adult patients. Doses greater than CRESTOR 10 mg have not been studied in children less than 10 years of age, and doses greater than CRESTOR 20 mg have not been studied in children and adolescents 10 to 17 years of age [see Use in Specific Populationsand Clinical Studies].
The following adverse reactions have been identified during postapproval use of CRESTOR: arthralgia, fatal and nonfatal hepatic failure, hepatitis, jaundice, thrombocytopenia, depression, sleep disorders (including insomnia and nightmares), peripheral neuropathy 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).
Read the Crestor (rosuvastatin calcium) Side Effects Center for a complete guide to possible side effects
Cyclosporine increased rosuvastatin exposure (AUC) 7-fold. Therefore, in patients taking cyclosporine, the dose of CRESTOR should not exceed 5 mg once daily [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS, and CLINICAL PHARMACOLOGY].
Gemfibrozil significantly increased rosuvastatin exposure. Due to an observed increased risk of myopathy/rhabdomyolysis, combination therapy with CRESTOR and gemfibrozil should be avoided. If used together, the dose of CRESTOR should not exceed 10 mg once daily [see CLINICAL PHARMACOLOGY].
Coadministration of rosuvastatin with certain protease inhibitors has differing effects on rosuvastatin exposure. Simeprevir, which is a hepatitis C virus (HCV) protease inhibitor, or combinations of atazanavir/ritonavir or lopinavir/ritonavir, which are HIV-1 protease inhibitors, increase rosuvastatin exposure (AUC) up to threefold [see Table 4 – CLINICAL PHARMACOLOGY]. For these protease inhibitors, the dose of CRESTOR should not exceed 10 mg once daily. The combinations of fosamprenavir/ritonavir or tipranavir/ritonavir, which are HIV-1 protease inhibitors, produce little or no change in rosuvastatin exposure. Caution should be exercised when rosuvastatin is coadministered with protease inhibitors [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].
CRESTOR significantly increased INR in patients receiving coumarin anticoagulants. Therefore, caution should be exercised when coumarin anticoagulants are given in conjunction with CRESTOR. In patients taking coumarin anticoagulants and CRESTOR concomitantly, INR should be determined before starting CRESTOR and frequently enough during early therapy to ensure that no significant alteration of INR occurs [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].
The risk of skeletal muscle effects may be enhanced when CRESTOR is used in combination with lipid-modifying doses ( ≥ 1 g/day) of niacin; caution should be used when prescribing with CRESTOR [see WARNINGS AND PRECAUTIONS].
When CRESTOR was coadministered with fenofibrate, no clinically significant increase in the AUC of rosuvastatin or fenofibrate was observed. Because it is known that the risk of myopathy during treatment with HMG-CoA reductase inhibitors is increased with concomitant use of fenofibrates, caution should be used when prescribing fenofibrates with CRESTOR [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].
Cases of myopathy, including rhabdomyolysis, have been reported with HMG-CoA reductase inhibitors, including rosuvastatin, coadministered with colchicine, and caution should be exercised when prescribing CRESTOR with colchicine [see WARNINGS AND PRECAUTIONS].
Read the Crestor Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 1/5/2016
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