Fatal Drug Interactions With Simvastatin (ZOCOR)

A report published in May 2010 describes an 80-year-old man taking simvastatin (ZOCOR) and danazol (DANOCRINE). The man’s muscles became so weak that he fell and injured his head. He also developed pain and cramping in his leg muscles.

He was treated in the emergency department of a hospital and released. Two days later, he was readmitted to the hospital with nausea, dark urine and low urine output.

By that time, his muscles were so weak he could not stand up or lift his arms. He had developed severe muscle damage, and, despite intensive treatment, he went into acute kidney failure and died six days later.

A similar interaction in a 68-year-old man taking simvastatin and danazol had been reported in 2003. The man also could not stand up or lift his arms, and he required hemodialysis for acute kidney failure. However, he survived.

What causes this reaction?

Simvastatin (and the other statins for high cholesterol) can occasionally cause muscle damage (myopathy), which in severe cases can progress to a life-threatening disorder called rhabdomyolysis. Although statin-induced rhabdomyolysis is somewhat rare, the risk is increased when excessive doses of statins are used or when a patient takes other drugs that increase statin blood levels.

In the case of the death of the 80-year-old man, the concurrent danazol therapy increased the simvastatin blood levels, resulting in the fatal muscle damage. Danazol — a drug used for various disorders such as endometriosis, fibrocystic breast disease, a severe allergic reaction called hereditary angioedema and a blood platelet disorder called idiopathic thrombocytopenic purpura — most likely increases the simvastatin blood levels by inhibiting the enzyme that metabolizes simvastatin and helps the body get rid of the drug: CYP3A4.

Do other statins interact with danazol?

Cases of rhabdomyolysis also have been reported when danazol was combined with lovastatin (MEVACOR), a statin that also is metabolized by CYP3A4. Atorvastatin (LIPITOR) is another statin metabolized by CYP3A4 and would also be expected to interact with danazol.

Some other statins, however, are not metabolized by CYP3A4 and theoretically would be less likely to interact with danazol. They include fluvastatin (LESCOL), pravastatin (PRAVACHOL) and rosuvastatin (CRESTOR).

Why should you be cautious about this interaction?

The two main reasons to be cautious about this interaction are 1) its adverse outcomes can be life-threatenin and 2) statins are widely used drugs.

Unfortunately, the diseases for which danazol is prescribed are often treated by doctors other than the doctor prescribing the simvastatin, lovastatin or atorvastatin. Because one prescriber may not be aware of the drugs ordered by another prescriber and/or the patient may get his or her drugs at different pharmacies, the risk of a drug interaction occurring with these drugs is significant.

What You Can Do

If you are taking a statin — regardless of whether or not you are taking any potentially interacting drugs — you should be alert for evidence of statin-induced muscle damage. A large proportion of these cases occur in people who are not taking drugs that interact with the statins. The symptoms are mainly muscle pain and muscle weakness, but a darkening of the urine often occurs as well. Some people who experience rhabdomyolysis describe their urine as “tea-colored,” but in severe cases it may be even darker.

You should be especially alert for these symptoms if new drugs are started with your statin therapy or if your statin dose has recently been increased. Catching these symptoms early can be lifesaving. Stopping the statin before a reaction gets too severe may increase your chances of recovering.

Merck & Co., the manufacturer of simvastatin, recommends that your dose of the drug not exceed 10 mg per day if danazol is used concurrently. Not all prescribers are aware of this, so it is important for you to be aware of these precautions when taking these drugs.

Danazol is normally used chronically, so making sure your simvastatin dose is not too high is a reasonable way to reduce the risk of an interaction. But some other drugs that interact with simvastatin are used only for a week or two. In those cases, most experts recommend stopping the simvastatin treatment while on the interacting drug.

Consumers may report serious adverse events with drugs to the FDA’s MedWatch Adverse Event Reporting program either online or by regular mail, fax or phone.

Online: www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm
Regular Mail: use postage-paid FDA form 3500 and mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787
Fax: (800) FDA-0178
Phone: (800) FDA-1088