ld-Pugh scores above 9. Crestor is contraindicated in patients with active liver disease (see section 4.3).
Race
Increased systemic exposure has been seen in Asian subjects (see sections 4.3, 4.4 and 5.2). The recommended start dose is 5 mg for patients of Asian ancestry. The 40 mg dose is contraindicated in these patients.
Genetic polymorphisms
Specific types of genetic polymorphisms are known that can lead to increased rosuvastatin exposure (see section 5.2). For patients who are known to have such specific types of polymorphisms, a lower daily dose of Crestor is recommended.
Dosage in patients with pre-disposing factors to myopathy
The recommended start dose is 5 mg in patients with predisposing factors to myopathy (see section 4.4).
The 40 mg dose is contraindicated in some of these patients (see section 4.3).
Concomitant therapy
Rosuvastatin is a substrate of various transporter proteins (e.g. OATP1B1 and BCRP). The risk of myopathy (including rhabdomyolysis) is increased when Crestor is administered concomitantly with certain medicinal products that may increase the plasma concentration of rosuvastatin due to interactions with these transporter proteins (e.g. ciclosporin and certain protease inhibitors including combinations of ritonavir with atazanavir, lopinavir and/or tipranavir; see sections 4.4 and 4.5). Whenever possible, alternative medications should be considered, and, if necessary, consider temporarily discontinuing Crestor therapy. In situations where co-administration of these medicinal products with Crestor is unavoidable, the benefit and the risk of concurrent treatment and Crestor dosing adjustments should be carefully considered (see section 4.5).
4.3 Contraindications
Crestor is contraindicated:
- in patients with hypersensitivity to rosuvastatin or to any of the excipients.
- in patients with active liver disease including unexplained, persistent elevations of serum transaminases and any serum transaminase elevation exceeding 3 times the upper limit of normal (ULN).
- in patients with severe renal impairment (creatinine clearance <30 ml/min).
- in patients with myopathy.
- in patients receiving concomitant ciclosporin.
- during pregnancy and lactation and in women of childbearing potential not using appropriate contraceptive measures.
The 40 mg dose is contraindicated in patients with pre-disposing factors for myopathy/rhabdomyolysis. Such factors include:
- moderate renal impairment (creatinine clearance < 60 ml/min)
- hypothyroidism
- personal or family history of hereditary muscular disorders
- previous history of muscular toxicity with another HMG-CoA reductase inhibitor or fibrate
- alcohol abuse
- situations where an increase in plasma levels may occur
- Asian patients
- concomitant use of fibrates.
(See sections 4.4, 4.5 and 5.2)
4.4 Special warnings and precautions for use
Renal Effects
Proteinuria, detected by dipstick testing and mostly tubular in origin, has been observed in patients treated with higher doses of Crestor, in particular 40 mg, where it was transient or intermittent in most cases. Proteinuria has not been shown to be predictive of acute or progressive renal disease (see section 4.8). The reporting rate for serious renal events in post-marketing use is higher at the 40 mg dose. An assessment of renal function should be considered during routine follow-up of patients treated with a dose of 40 mg.
Skeletal Muscle Effects
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