3rd October 2004
But that is exactly the point. These drugs aren't tested in the populations and under the conditions that they will ultimately be prescribed for in real life. If the tests were conducted using these subjects they would never receive FDA approval. Pfizer is recommending that every diabetic should be taking Lipitor. If you look at table 1 diabetes is a risk factor for muscle disorders when taking Lipitor.
Australia has a very small population taking statins. You need to extrapolate the number of known adverse effects to the much larger statin using population in the U.S. You also need to keep in mind that many adverse effects are either never reported to doctors or doctors don't bother to report them to the FDA.
Table 1: Factors increasing the risk of muscle disorders with simvastatin and atorvastatin
Substances inhibiting metabolism by CYP3A4: cyclosporin, diltiazem, verapamil, macrolide antibiotics, azole antifungals, protease inhibitors, grapefruit juice
Medicine inhibiting metabolism by other means: gemfibrozil
Disease states: diabetes, hypothyroidism, renal and hepatic disease
Advanced age: ≥ 70 years
High statin dose: ≥ 40 mg/day
ADRAC has received 91 reports of rhabdomyolysis with simvastatin and 26 with atorvastatin, as well as many reports of myalgia, myopathy or creatine kinase (CK) increase. Table 2 (top section) shows the percentage of cases with identified risk factors, as defined in Table 1. For simvastatin the factors listed most commonly in reports describing rhabdomyolysis were age ≥ 70 years (40 reports) dose ≥ 40 mg (33), cyclosporin (19), gemfibrozil (21), diltiazem (20) and diabetes (15). Over half of the simvastatin cases with rhabdomyolysis had more than one identified risk factor. Individuals with several risk factors may be at risk of developing rhabdomyolysis, rather than a less serious muscle disorder.
A feature of the cases of rhabdomyolysis is that long term statin therapy was well tolerated until after a change in medication (e.g. increase in the dose of statin, or addition of clarithromycin or diltiazem).
Australia has a very small population taking statins. You need to extrapolate the number of known adverse effects to the much larger statin using population in the U.S. You also need to keep in mind that many adverse effects are either never reported to doctors or doctors don't bother to report them to the FDA.
Table 1: Factors increasing the risk of muscle disorders with simvastatin and atorvastatin
Substances inhibiting metabolism by CYP3A4: cyclosporin, diltiazem, verapamil, macrolide antibiotics, azole antifungals, protease inhibitors, grapefruit juice
Medicine inhibiting metabolism by other means: gemfibrozil
Disease states: diabetes, hypothyroidism, renal and hepatic disease
Advanced age: ≥ 70 years
High statin dose: ≥ 40 mg/day
ADRAC has received 91 reports of rhabdomyolysis with simvastatin and 26 with atorvastatin, as well as many reports of myalgia, myopathy or creatine kinase (CK) increase. Table 2 (top section) shows the percentage of cases with identified risk factors, as defined in Table 1. For simvastatin the factors listed most commonly in reports describing rhabdomyolysis were age ≥ 70 years (40 reports) dose ≥ 40 mg (33), cyclosporin (19), gemfibrozil (21), diltiazem (20) and diabetes (15). Over half of the simvastatin cases with rhabdomyolysis had more than one identified risk factor. Individuals with several risk factors may be at risk of developing rhabdomyolysis, rather than a less serious muscle disorder.
A feature of the cases of rhabdomyolysis is that long term statin therapy was well tolerated until after a change in medication (e.g. increase in the dose of statin, or addition of clarithromycin or diltiazem).