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Patients taking the commonly prescribed antibiotic azithromycin (ZITHROMAX) should be aware that it has clinically important dangerous interactions with many other prescription medications.
Initially approved by the FDA in 1991, azithromycin is a macrolide antibiotic, a family of drugs that also includes clarithromycin (BIAXIN XL) and erythromycin (E.E.S., E.E.S. 400, ERY-TAB, ERYC, ERYPED). Azithromycin is approved for treating a variety of mild-to-moderate bacterial infections,...
Patients taking the commonly prescribed antibiotic azithromycin (ZITHROMAX) should be aware that it has clinically important dangerous interactions with many other prescription medications.
Initially approved by the FDA in 1991, azithromycin is a macrolide antibiotic, a family of drugs that also includes clarithromycin (BIAXIN XL) and erythromycin (E.E.S., E.E.S. 400, ERY-TAB, ERYC, ERYPED). Azithromycin is approved for treating a variety of mild-to-moderate bacterial infections, including acute (sudden-onset) bacterial flare-ups of chronic bronchitis in adults, community-acquired pneumonia, ear infections in children, acute sinusitis in adults, skin infections, tonsillitis and certain sexually transmitted diseases.[1]
Depending on the infection being treated, the drug typically is prescribed for adults at dosages ranging from 250 to 2,000 milligrams once daily for one to five days.
Increased risk of fatal heart rhythm abnormalities[2],[3]
Like other macrolide antibiotics, azithromycin has been linked to an increased risk of prolongation of the QT interval in the heart rhythm. QT prolongation is a change in the electrical activity of the heart that can lead to a potentially fatal heart rhythm disturbance called torsades de pointes, which can cause cardiac arrest and sudden death. Elderly patients are more susceptible to this adverse cardiac event.
Numerous oral drugs, when used concomitantly (at the same time) with azithromycin, further increase the risk of QT prolongation (see Table, below, for examples). The list of such drugs includes certain medications for treating abnormal heart rhythms, Alzheimer’s disease, bacterial infections, depression, fungal infections, HIV infection, opioid withdrawal and prostate enlargement, among others. In some cases, the other interacting drug itself also causes QT prolongation, beyond that caused by azithromycin.
For many of these interacting drugs — including pimozide (generic only), saquinavir (INVIRASE), thioridazine (generic only) and ziprasidone (GEODON) — the risk of QT prolongation and potentially fatal abnormal heart rhythms is so high that azithromycin should not be taken concomitantly with the interacting drugs.
Examples of Oral Drugs That Increase the Risk of Potentially Fatal Abnormal Heart Rhythms When Taken Concomitantly With Azithromycin
| Generic Name | Brand Name(s)† | Drug Class |
|---|---|---|
| alfuzosin* | UROXATRAL | Benign prostate enlargement drug |
| chloroquine | generic only | Drug for malaria |
| citalopram* | CELEXA | Antidepressant |
| disopyramide* | NORPACE | Abnormal heart rhythm drug |
| donepezil** | ARICEPT | Alzheimer’s disease drug |
| dronedarone** | MULTAQ | Abnormal heart rhythm drug |
| efavirenz | SUSTIVA | Antiviral drug for HIV infection |
| escitalopram* | LEXAPRO | Antidepressant |
| fluconazole* | DIFLUCAN | Antifungal drug |
| fluoxetine | PROZAC, SARAFEM, SELFEMRA | Antidepressant |
| gemifloxacin** | FACTIVE | Antibiotic |
| hydroxychloroquine | PLAQUENIL | Drug for malaria, rheumatoid arthritis and lupus erythematosus |
| ketoconazole** | generic only | Antifungal drug |
| lofexidine | LUCEMYRA | Opioid withdrawal syndrome drug |
| pimozide | generic only | Tourette’s syndrome drug |
| posaconazole | NOXAFIL | Antifungal drug |
| quetiapine* | SEROQUEL | Antipsychotic |
| saquinavir | INVIRASE | Antiviral drug for HIV infection |
| thioridazine** | generic only | Antipsychotic |
| ziprasidone** | GEODON | Antipsychotic |
†Brand-name combination products were excluded.
*Designated as Limited Use
**Designated as Do Not Use
Other important drug interactions[4]
Concomitant use of azithromycin and digoxin (LANOXIN) — which is used to treat heart failure and to control heart rate in patients with atrial fibrillation (a common abnormal heart rhythm characterized by an irregular and often rapid heartbeat) — can result in increased blood levels of digoxin, potentially leading to serious digoxin toxicity. Common symptoms of digoxin toxicity are loss of appetite, nausea, vomiting and fatigue. If concomitant use of azithromycin and digoxin is unavoidable, more frequent monitoring of blood digoxin levels should occur, especially during initiation and discontinuation of azithromycin.
Concomitant use of azithromycin and the anticoagulant (blood thinner) warfarin (COUMADIN, JANTOVEN) likewise can increase the anticoagulant effects of warfarin. This can increase the risk of bleeding complications. Ideally, concomitant use of these two drugs should be avoided. If such use is unavoidable, more frequent monitoring of warfarin levels should occur, especially during initiation and discontinuation of azithromycin.
Finally, concomitant use of azithromycin and the cholesterol-lowering statin drugs — such as atorvastatin (LIPITOR), lovastatin (ALTOPREV) and simvastatin (FLOLIPID, ZOCOR) — can increase the risk of statin-induced myopathy (muscle damage). In severe cases, this condition can progress to rhabdomyolysis, a life-threatening, muscle-destroying condition that can lead to sudden kidney failure and death.
What You Can Do
If you need treatment with azithromycin, review all your other medications with your doctor to assess for potentially significant drug interactions. If you are taking certain medications that interact with azithromycin, you may need to reduce the dosage of the interacting drug, or your doctor may advise you to stop the interacting drug. Be aware that many other drugs not listed in this article also may have dangerous interactions with azithromycin.
References
[1] Pfizer. Label: azithromycin (ZITHROMAX). April 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/050670s034lbl.pdf. Accessed April 27, 2020.
[2] Ibid.
[3] IBM Micromedex. Drug interactions. http://www.micromedexsolutions.com/home/dispatch. Search term: “azithromycin.” Accessed April 27, 2020.
[4] Ibid.
