When a pharmaceutical company changes an SPC or PIL, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.
Section 4.2 and 4.4 - Addition of reference ‘(see Section 4.3)' Section 4.8 - Add Tendon disorder Section 10 Date of revision changed to 20th December 2011
Includes paediatric information.
Additional text:
Prevention of Cardiovascular Events
Prevention of major cardiovascular events in patients who are estimated to have a high risk for a first cardiovascular event (see Section 5.1), as an adjunct to correction of other risk factors.
Section 4.2
Crestor may be given at any time of day, with or without food.
In the cardiovascular events risk reduction study, the dose used was 20 mg daily (see Section 5.1).
Section 4.2 includes Paediatric information
Section 4.4 New indication for use in adult patients. Additional text Interstitial lung disease Exceptional cases of interstitial lung disease have been reported with some statins, especially with long term therapy (see Section 4.8). Presenting features can include dyspnoea, non-productive cough and deterioration in general health (fatigue, weight loss and fever). If it is suspected a patient has developed interstitial lung disease, statin therapy should be discontinued. Diabetes Mellitus In patients with fasting glucose 5.6 to 6.9 mmol/L, treatment with rosuvastatin has been associated with an increased risk of diabetes mellitus (see Section 4.8). Section 4.4 includes Paediatric information Section 4.8 New indication for use in adult patients. Additional side effect: Endocrine disorders Common: diabetes mellitus1 Additional adverse events under heading ‘Post marketing Experience Section 4.8 includes Paediatric information Section 5.1 Deletion of text: Rosuvastatin has not been proven to prevent the associated complications of lipid abnormalities, such as coronary heart disease as mortality and morbidity studies with Crestor have not yet been completed. Additional text – JUPITER study Section 5.1 includes Paediatric information Section 5.2 Additional text Special populations: Age and sex: There was no clinically relevant effect of age or sex on the pharmacokinetics of rosuvastatin in adults. The pharmacokinetics of rosuvastatin in children and adolescents with heterozygous familial hypercholesterolaemia was similar to that of adult volunteers (see “Paediatric population” below). Paediatric population: The pharmacokinetic parameters in paediatric patients with heterozygous familial hypercholesterolaemia aged 10 to 17 years have not been fully characterised. A small pharmacokinetic study with rosuvastatin (given as tablets) in 18 paediatric patients demonstrated that exposure in paediatric patients appears comparable to exposure in adult patients. In addition, the results indicate that a large deviation from dose proportionality is not expected. Section 10 Revision date of text: 14 May 2010
Section 4.4
New indication for use in adult patients.
Additional text
Interstitial lung disease
Exceptional cases of interstitial lung disease have been reported with some statins, especially with long term therapy (see Section 4.8). Presenting features can include dyspnoea, non-productive cough and deterioration in general health (fatigue, weight loss and fever). If it is suspected a patient has developed interstitial lung disease, statin therapy should be discontinued.
Diabetes Mellitus In patients with fasting glucose 5.6 to 6.9 mmol/L, treatment with rosuvastatin has been associated with an increased risk of diabetes mellitus (see Section 4.8).
Section 4.4 includes Paediatric information
Section 4.8
Additional side effect:
Endocrine disorders Common: diabetes mellitus1
Additional adverse events under heading ‘Post marketing Experience
Section 4.8 includes Paediatric information
Section 5.1
Deletion of text:
Rosuvastatin has not been proven to prevent the associated complications of lipid abnormalities, such as coronary heart disease as mortality and morbidity studies with Crestor have not yet been completed.
Additional text – JUPITER study
Section 5.1 includes Paediatric information
Section 5.2 Additional text Special populations: Age and sex: There was no clinically relevant effect of age or sex on the pharmacokinetics of rosuvastatin in adults. The pharmacokinetics of rosuvastatin in children and adolescents with heterozygous familial hypercholesterolaemia was similar to that of adult volunteers (see “Paediatric population” below). Paediatric population: The pharmacokinetic parameters in paediatric patients with heterozygous familial hypercholesterolaemia aged 10 to 17 years have not been fully characterised. A small pharmacokinetic study with rosuvastatin (given as tablets) in 18 paediatric patients demonstrated that exposure in paediatric patients appears comparable to exposure in adult patients. In addition, the results indicate that a large deviation from dose proportionality is not expected. Section 10 Revision date of text: 14 May 2010
Section 5.2
Special populations:
Age and sex: There was no clinically relevant effect of age or sex on the pharmacokinetics of rosuvastatin in adults. The pharmacokinetics of rosuvastatin in children and adolescents with heterozygous familial hypercholesterolaemia was similar to that of adult volunteers (see “Paediatric population” below).
Paediatric population: The pharmacokinetic parameters in paediatric patients with heterozygous familial hypercholesterolaemia aged 10 to 17 years have not been fully characterised. A small pharmacokinetic study with rosuvastatin (given as tablets) in 18 paediatric patients demonstrated that exposure in paediatric patients appears comparable to exposure in adult patients. In addition, the results indicate that a large deviation from dose proportionality is not expected.
Section 10 Revision date of text: 14 May 2010
Section 10
Revision date of text: 14 May 2010
Addition of paragraph on Lactose Intolerance:
Lactose intolerance
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Section 5.3
Replacement of paragraph:
Preclinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, genotoxicity and carcinogenicity potential. Specific tests for effects on hERG have not been evaluated. Adverse reactions not observed in clinical studies, but seen in animals at exposure levels similar to clinical exposure levels were as follows: In repeated-dose toxicity studies histopathologic liver changes likely due to the pharmacologic action of rosuvastatin were observed in mouse, rat, and to a lesser extent with effects in the gall bladder in dogs, but not in monkeys. In addition, testicular toxicity was observed in monkeys and dogs at higher dosages. Reproductive toxicity was evident in rats, with reduced litter sizes, litter weight and pup survival observed at maternally toxic doses, where systemic exposures were several times above the therapeutic exposure level.
Change of date:
4.4 Special warnings and special precautions for use
Protease inhibitors
The concomitant use with protease inhibitors is not recommended (see Section 4.5).
4.5 Interaction with other medicinal products and other forms of interaction
Protease inhibitors: Although the exact mechanism of interaction is unknown, concomitant protease inhibitor use may strongly increase rosuvastatin exposure. In a pharmacokinetic study, co-administration of 20 mg rosuvastatin and a combination product of two protease inhibitors (400 mg lopinavir / 100 mg ritonavir) in healthy volunteers was associated with an approximately two-fold and five-fold increase in rosuvastatin steady-state AUC(0-24) and Cmax respectively. Therefore, concomitant use of rosuvastatin in HIV patients receiving protease inhibitors is not recommended (see also Section 4.4).
5.1 Pharmacodynamic properties
In a multi-centre, double-blind, placebo-controlled clinical study (METEOR), 984 patients between 45 and 70 years of age and at low risk for coronary heart disease (defined as Framingham risk <10% over 10 years), with a mean LDL-C of 4.0 mmol/l (154.5 mg/dL), but with subclinical atherosclerosis (detected by Carotid Intima Media Thickness) were randomised to 40 mg rosuvastatin once daily or placebo for 2 years. Rosuvastatin significantly slowed the rate of progression of the maximum CIMT for the 12 carotid artery sites compared to placebo by -0.0145 mm/year [95% confidence interval -0.0196, -0.0093; p<0.0001]. The change from baseline was -0.0014 mm/year (-0.12%/year (non-significant)) for rosuvastatin compared to a progression of +0.0131 mm/year (1.12%/year (p<0.0001)) for placebo. No direct correlation between CIMT decrease and reduction of the risk of cardiovascular events has yet been demonstrated. The population studied in METEOR is low risk for coronary heart disease and does not represent the target population of Crestor 40mg. The 40mg dose should only be prescribed in patients with severe hypercholesterolaemia at high cardiovascular risk (see Section 4.2).
16th August 2007