Muscle damage

Muscle Damage from Interactions Between Statins and
Other Commonly Prescribed Drugs
Worst Pills Best Pills Newsletter article July, 2009 Some of the widely used class of cholesterol-lowering drugs called statins may causerhabdomyolysis (severe, sometimes fatal, muscle damage) when taken with many othercommonly used drugs, such as clopidogrel (PLAVIX) and trimethoprim and sulfamethoxazole(BACTRIM).
What is rhabdomyolysis?
Rhabdomyolysis is the rapid breakdown of muscle tissue, resulting in the release of broken-down muscle tissue into the bloodstream. The broken-down tissue can cause kidney failure,requiring temporary or ongoing dialysis.
What are the symptoms of rhabdomyolysis?
Muscle pain and weakness are the most common signs of statin-induced muscle damage.
Sometimes these are signals of only mild to moderate muscle damage, but a person on a statinshould consult their prescriber if they have such symptoms.
In some people, a darkening of the urine from broken-down muscle tissue is the first sign ofmuscle damage, and people who develop this should immediately contact their prescriber.
All statin drugs can cause rhabdomyolysis, even when used alone. But the risk ofrhabdomyolysis varies depending on the statin. For instance, we list rosuvastatin (CRESTOR) asa Do Not Use drug due to its increased risk of rhabdomyolysis and kidney damage.
What drugs interact with statins?
For some statins, the risk of rhabdomyolysis is increased when combined with certain otherdrugs.
CYP3A4 inhibitors
Simvastatin (ZOCOR), lovastatin (MEVACOR) and atorvastatin (LIPITOR) are all metabolized bythe enzyme CYP3A4. Taking these statins with other drugs that inhibit CYP3A4, such astamoxifen (NOLVADEX) and verapamil (CALAN), can result in rhabdomyolysis because these tamoxifen (NOLVADEX) and verapamil (CALAN), can result in rhabdomyolysis because theselatter drugs can increase the blood levels of the three statins (See the list of CYP3A4 inhibitors,page 7).
A recent epidemiologic study looked at the risk of rhabdomyolysis in patients taking eithersimvastatin or pravastatin with and without drugs that inhibit CYP3A4. Rhabdomyolysis wasrare with both drugs, but in patients who took no drugs that inhibited CYP3A4, the risk ofrhabdomyolysis was higher in patients using simvastatin than in those using pravastatin.
People taking simvastatin with one or more CYP3A4 inhibitors experienced a six-fold increase inthe risk rhabdomyolysis, but the use of CYP3A4 inhibitors did not increase the risk ofrhabdomyolysis in people who used pravastatin. This is because pravastatin (PRAVACHOL) isnot metabolized by the enzyme CYP3A4 or other cytochrome P450 enzymes, so compared toother statins it appears to have the lowest risk of adverse drug interactions such asrhabdomyolysis.
CYP2C9 inhibitors
Fluvastatin (LESCOL) is metabolized by the enzyme CYP2C9, so, theoretically, drugs that inhibitthis enzyme,could increase the risk of muscle damage by increasing blood levels of fluvastatin(See the list of CYP2C9 inhibitors, page 7).
What You Can Do
You should only take a statin if diet and exercise have failed to bring your cholesterol to thedesired level. Some people can avoid the expense, bother and risk of statins through changesin lifestyle.
Do not use rosuvastatin (CRESTOR) because it has a greater risk of muscle damage and kidneyproblems than other statins.
If you must take a statin, consider using pravastatin (PRAVACHOL), now available in genericform, because it has the lowest risk of drug interactions among the statins. There is also someevidence to suggest that in addition to having less of a chance of interacting with other drugs,pravastatin has a lower overall risk of muscle damage than other statins.
If you are taking simvastatin (ZOCOR), lovastatin (MEVACOR) or atorvastatin (LIPITOR), andyou need to take a CYP3A4 inhibitor for a week or two, it may be prudent to stop the statinwhile you are taking the CYP3A4 inhibitor but first check with your prescriber about this. If theCYP3A4 inhibitor is to be given for a longer term, your prescriber may decide to lower the doseof your statin or give you pravastatin instead.
No matter what statin you are taking and regardless of any interacting drugs, you should notifyyour prescriber immediately if you develop muscle pain, weakness or a darkening of your urine.
Table. CYP3A4 and CYP2C9 inhibitors CYP3A4 Inhibitors
diltiazem (CARDIZEM, CARDIZEM CD, DILACOR XR,TIAZAC)** verapamil (CALAN, CALAN SR, COVERA-HS, ISOPTIN,ISOPTIN SR, VERELAN) CYP2C9 inhibitors trimethoprim and sulfamethoxazole(BACTRIM, COTRIM, SEPTRA) fluorouracil (5-FU, CARAC,EFUDEX,FLUOROPLEX) miconazole (MONISTAT 1, MONISTAT 3,MONISTAT 7, MONISTAT-DERM) * Do Not Use in Worst Pills, Best Pills** Limited Use in Worst Pills, Best Pills*** Last Choice Drug in Worst Pills, Best Pills Copyright 2000-2009 Public Citizen's Health Research Group. All rights reserved.


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