MONDAY, June 17, 2013 ”” Older patients on lipid-lowering drugs known as statins shouldn’t take antibiotics clarithromycin or erythromycin because of an increased risk for drug toxicity, according to a large Canadian study published today in the clinical journal Annals of Internal Medicine.

If you are on a statin, avoiding these particular antibiotics may keep you safe from uncommon ”” but potentially life-threatening ”” drug-drug interactions. The antibiotics clarithromycin or erythromycin increase the levels of commonly used lipid-lowering drugs, because both drugs interact with the same liver enzyme.

When certain antibiotics slow down the liver enzyme (known as a cytochrome P450 isoenzyme 3A4) it can no longer process the statin that builds up in the blood and can become toxic. Symptoms of toxicity include muscle aches, kidney injury, and kidney failure or worse ”” it can even be fatal.

A Close Look at Statin-Antibiotic Adverse Events

“I see patients who come in with kidney toxicity and if there are harms, I wanted to bring attention to it,” said study author, Amit X. Garg, MD, PhD, a nephrologist at the London Kidney Clinical Research Unit of London Health Science Centre in Ontario, Canada.

Dr. Garg and colleagues combed through the medical and drug records of more than 144,000 Canadian patients aged 65 and up. They found that patients taking statins were twice as likely to be hospitalized with muscle breakdown (called rhabdomyolysis) in those co-prescribed the antibiotics clarithromycin or erythromycin. The relative risk of death at 30 days was one and a half times higher for patients on statins who took clarithromycin or erythromycin.

Patients taking statins and a different antibiotic, azithromycin ”” which works through another pathway ”” did not experience this increased toxicity.

“The interaction has been described in pharmacokinetic studies, but this is the first population-based study looking at large numbers of patients,” Garg said. “To prevent these from being prescribed together, we are making people aware of this issue.”

Garg cautioned that both prescriptions are frequently given to older patients. “Looking forward, statin prescriptions are very common,” he said. “Clarithromycin and erythromycin are common antibiotics used to treat pneumonia, upper respiratory and sinus infections.”

“If after having an infection, it is not improving after a few days of antibiotic, it can be because of reactions the patients are having, and they should get in touch with the prescribing physician,” Garg noted.

Cardiologist Christopher P. Cannon MD, FACC, cautioned, “This is observational, so not definitive.” Dr. Cannon is in the Cardiovascular Division, Brigham and Women’s Hospital and Professor at Harvard Medical School, Boston.

Recognizing a Harmful Drug-Drug Interaction

How can a patient recognize the warning signs and symptoms of an adverse event from statin and antibiotic interactions? Garg explained that it is difficult to pick up this kind of adverse event.

“They are nonspecific symptoms, like bad muscle aches with statin toxicity,” said Garg. “You often get these symptoms with a bad cold, and so it is hard to tell. If someone comes in with statin toxicity, they are quite ill. We look at the kidney function, they may need urgent dialysis.” Garg added that sometimes the patient knew what medications he took, and in other cases the physician called the pharmacy to find out what was prescribed.

Be on the lookout for unusual symptoms that can indicate an adverse event from medication. “Muscle pains are usually the warning sign of rhabdomyolysis [muscle breakdown] ”” calling your doctor if you have just started a new medicine and you have a side effect would be the way to go,” said Dr. Cannon.

How to Avoid Drug Interactions

Which antibiotic you use makes a difference, and both doctors noted that azithromycin may be a safer choice for patients on statin medications. Azithromycin (also known as Zithromax, Zmax, or Z-Pak) is effective against infections like pneumonia and is usually given for five days. “There are many antibiotics that can be used for the same kinds of infections,” said Garg.

An alternative is to suspend the statin medication only temporarily, for the duration of the antibiotic prescription. “Statins can be stopped for 5 or 10 days and then restarted when the antibiotic is stopped,” Garg said. But statins are central to the control of cholesterol. “Statins have tremendous advantages including survival advantage,” in the long term, Garg noted.

Computer order entry at the pharmacy is one of the advances that helps prevent drug-drug interactions for people with multiple conditions on polypharmacy.

Talk to your doctor to prevent harmful co-prescriptions. “If a new med or antibiotic is used, it is reasonable to ask if it will be OK with other medications,” Cannon said.