Prescription Drug Guide

Rosuvastatin Calcium

SIDE EFFECTS

Rosuvastatin is generally well tolerated. Adverse reactions have usually been mild and transient. In clinical studies of 10,275 patients, 3.7% were discontinued due to adverse experiences attributable to rosuvastatin. The most frequent adverse events thought to be related to rosuvastatin were myalgia, constipation, asthenia, abdominal pain, and nausea.

Clinical Adverse Experiences

Adverse experiences, regardless of causality assessment, reported in >2% of patients in placebo-controlled clinical studies of rosuvastatin are shown in Table 6; discontinuations due to adverse events in these studies of up to 12 weeks duration occurred in 3% of patients on rosuvastatin and 5% on placebo.

Table 6. Adverse Events in Placebo-Controlled Studies

In addition, the following adverse events were reported, regardless of causality assessment, in ≥1% of 10,275 patients treated with rosuvastatin in clinical studies. The events in italics occurred in ≥2% of these patients.

Body as a Whole: Abdominal pain, accidental injury, chest pain, infection, pain, pelvic pain, and neck pain.

Cardiovascular System: Hypertension, angina pectoris, vasodilatation, and palpitation.

Digestive System: Constipation, gastroenteritis, vomiting, flatulence, periodontal abscess, and gastritis.

Endocrine: Diabetes mellitus.

Hemic and Lymphatic System: Anemia and ecchymosis.

Metabolic and Nutritional Disorders: Peripheral edema.

Musculoskeletal System: Arthritis, arthralgia, and pathological fracture.

Nervous System: Dizziness, insomnia, hypertonia, paresthesia, depression, anxiety, vertigo and neuralgia.

Respiratory System: Bronchitis, cough increased, dyspnea, pneumonia, and asthma.

Skin and Appendages: Rash and pruritus.

Laboratory Abnormalities: In the rosuvastatin clinical trial program, dipstick-positive proteinuria and microscopic hematuria were observed among rosuvastatin-treated patients, predominantly in patients dosed above the recommended dose range (i.e., 80 mg). However, this finding was more frequent in patients taking rosuvastatin 40 mg, when compared to lower doses of rosuvastatin or comparator statins, though it was generally transient and was not associated with worsening renal function. (See PRECAUTIONS, Laboratory Tests.)

Other abnormal laboratory values reported were elevated creatine phosphokinase, transaminases, hyperglycemia, glutamyl transpeptidase, alkaline phosphatase, bilirubin, and thyroid function abnormalities.

Other adverse events reported less frequently than 1% in the rosuvastatin clinical study program, regardless of causality assessment, included arrhythmia, hepatitis, hypersensitivity reactions (i.e., face edema, thrombocytopenia, leukopenia, vesiculobullous rash, urticaria, and angioedema), kidney failure, syncope, myasthenia, myositis, pancreatitis, photosensitivity reaction, myopathy, and rhabdomyolysis.

Postmarketing Experience

In addition to the events reported above, as with other drugs in this class, the following event has been reported during postmarketing experience with CRESTOR, regardless of causality assessment: very rare cases of jaundice.

DRUG INTERACTIONS

Cyclosporine: When rosuvastatin 10 mg was co-administered with cyclosporine in cardiac transplant patients, rosuvastatin mean c_max and mean AUC were increased 11-fold and 7-fold, respectively, compared with healthy volunteers. These increases are considered to be clinically significant and require special consideration in the dosing of rosuvastatin to patients taking concomitant cyclosporine (see WARNINGS, Myopathy/Rhabdomyolysis, and DOSAGE AND ADMINISTRATION).

Warfarin: Coadministration of rosuvastatin to patients on stable warfarin therapy resulted in clinically significant rises in INR (>4, baseline 2-3). In patients taking coumarin anticoagulants and rosuvastatin concomitantly, INR should be determined before starting rosuvastatin and frequently enough during early therapy to ensure that no significant alteration of INR occurs. Once a stable INR time has been documented, INR can be monitored at the intervals usually recommended for patients on coumarin anticoagulants. If the dose of rosuvastatin is changed, the same procedure should be repeated. Rosuvastatin therapy has not been associated with bleeding or with changes in INR in patients not taking anticoagulants.

Gemfibrozil: Coadministration of a single rosuvastatin dose to healthy volunteers on gemfibrozil (600 mg twice daily) resulted in 2.2- and 1.9-fold, respectively, increase in mean c_max and mean AUC of rosuvastatin (see DOSAGE AND ADMINISTRATION).

Endocrine Function

Although clinical studies have shown that rosuvastatin alone does not reduce basal plasma cortisol concentration or impair adrenal reserve, caution should be exercised if any HMG-CoA reductase inhibitor or other agent used to lower cholesterol levels is administered concomitantly with drugs that may decrease the levels or activity of endogenous steroid hormones such as ketoconazole, spironolactone, and cimetidine.

CNS Toxicity

CNS vascular lesions, characterized by perivascular hemorrhages, edema, and mononuclear cell infiltration of perivascular spaces, have been observed in dogs treated with several other members of this drug class. A chemically similar drug in this class produced dose-dependent optic nerve degeneration (Wallerian degeneration of retinogeniculate fibers) in dogs, at a dose that produced plasma drug levels about 30 times higher than the mean drug level in humans taking the highest recommended dose. Edema, hemorrhage, and partial necrosis in the interstitium of the choroid plexus was observed in a female dog sacrificed moribund at day 24 at 90 mg/kg/day by oral gavage (systemic exposures 100 times the human exposure at 40 mg/day based on AUC comparisons). Corneal opacity was seen in dogs treated for 52 weeks at 6 mg/kg/day by oral gavage (systemic exposures 20 times the human exposure at 40 mg/day based on AUC comparisons). Cataracts were seen in dogs treated for 12 weeks by oral gavage at 30 mg/kg/day (systemic exposures 60 times the human exposure at 40 mg/day based on AUC comparisons). Retinal dysplasia and retinal loss were seen in dogs treated for 4 weeks by oral gavage at 90 mg/kg/day (systemic exposures 100 times the human exposure at 40 mg/day based on AUC). Doses ≤30 mg/kg/day (systemic exposures ≤60 times the human exposure at 40 mg/day based on AUC comparisons) following treatment up to one year, did not reveal retinal findings.