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Wednesday, 23 November 2011

MHRA - Yellow Cards which made a difference—high-dose rosuvastatin and rhabdomyolysis - FIDDAMAN blog

Yellow Cards: helping safeguard public health


The Yellow Card Scheme principally acts as an early-warning system for identifying previously unrecognised adverse drug reactions (ADRs). It also provides valuable information on recognised ADRs, allowing us to identify and refine the understanding of risk factors that may affect the clinical management of patients.

http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON134928

The value of the Scheme has been demonstrated many times and it has helped to identify numerous important safety issues, many of which were not recognised as being related to a particular medicine until we received information on Yellow Cards.



Making a difference: Yellow Cards reporting rhabdomyolysis with rosuvastatin

In March 2003, rosuvastatin (Crestor) was launched in the UK. Consistent with other statins, muscle toxicity was recognised as a dose-related adverse reaction to rosuvastatin, leading in rare cases to rhabdomyolysis. The Summary of Product Characteristics for Crestor contained the warning:



…As with other HMG-CoA reductase inhibitors, effects on skeletal muscle e.g. uncomplicated myalgia and myopathy, have been reported in Crestor-treated patients. Rare cases of rhabdomyolysis have been reported in subjects receiving rosuvastatin 80 mg in investigational clinical trials which were occasionally associated with impairment of renal function. All cases improved on cessation of therapy.



In September 2003, we received the first reports of suspected rhabdomyolysis with rosuvastatin treatment. By February 2004, the rosuvastatin dose was reported to be at 40 mg or higher in four of the five reports received, and the reporting rate (taking prescribing data into account) was higher than expected relative to historical data with other statins.



This finding led to a thorough review of all available data sources, and to the following update to prescribing advice in June 2004:



The highest licensed dose (40 mg) was contraindicated in patients with predisposing risk factors for muscle toxicity

Specialist supervision was recommended when the 40 mg dose is initiated

Patients who were already taking 40 mg treatment were recommended to have a review of their treatment.

See also information in Current Problems in Pharmacovigilance, October 2004



In this example, a small number of Yellow Card reports of rhabdomyolysis with high-dose rosuvastatin, combined with data on the drug’s usage levels, provided enough evidence for us to trigger a full review that led to action to protect public health.



Reporting of ADRs is vital to enable us to identify potential drug-safety issues. Please report, even if you are unsure whether a reaction is linked to a medicine. Show your support for the Yellow Card Scheme by reporting adverse reactions and you can help make medicines safer.



Report online at www.mhra.gov.uk/yellowcard







Article citation: Drug Safety Update Nov 2011, vol 5 issue 4: Y1

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