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Medication Side Effects

Zithromax (azithromycin):

FDA Statement on risk of cardiovascular death

Audience: Primary Care, Pharmacy

ISSUE: FDA notified healthcare professionals that it is aware of the study published in the New England Journal of Medicine  May 17, 2012disclaimer icon reporting a small increase in cardiovascular deaths, and in the risk of death from any cause, in persons treated with a 5-day course of azithromycin (Zithromax) compared to persons treated with amoxicillin, ciprofloxacin, or no drug. FDA is reviewing the results from this study and will communicate any new information on azithromycin and this study or the potential risk of QT interval prolongation after the agency has completed its review.

BACKGROUND: Azithromycin belongs to a class of antibacterial drugs called macrolides, which have been associated with cardiovascular effects; specifically, prolongation of the QT interval. In 2011, FDA reviewed macrolide drug labeling information related to QT interval prolongation and TdP. The WARNINGS AND PRECAUTIONS section of the Zmax drug label (azithromycin extended release for oral suspension) was revised in March 2012 to include new information regarding risk for QT interval prolongation, which appears to be low. The drug labels for clarithromycin and erythromycin also contain information about QT interval prolongation in the WARNINGS section. FDA is in the process of updating risk information in the drug labels for additional macrolide antibacterial drugs.

RECOMMENDATION: Patients taking azithromycin should not stop taking their medicine without talking to their healthcare professional. Healthcare professionals should be aware of the potential for QT interval prolongation and heart arrhythmias when prescribing or administering macrolides.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

 

  • Complete and submit the report Online: www.fda.gov/MedWatch/report.htm

[05/17/2012 - Statement - CDER]

[03/15/2012 - Azithromycin Prescribing Information - Pfizer]

[03/15/2012 - target=""> MedWatch Safety Labeling - FDA]

[05/03/2012 - Clarithromycin Prescribing Information - Abbott]

 

Zithromax Cardiovascular Side effects

http://www.nejm.org/doi/full/10.1056/NEJMoa1003833

Azithromycin and the Risk of Cardiovascular Death

Wayne A. Ray, Ph.D., Katherine T. Murray, M.D., Kathi Hall, B.S., Patrick G. Arbogast, Ph.D., and C. Michael Stein, M.B., Ch.B.

N Engl J Med 2012; 366:1881-1890

May 17, 2012

Although several macrolide antibiotics are proarrhythmic and associated with an increased risk of sudden cardiac death, azithromycin is thought to have minimal cardiotoxicity. However, published reports of arrhythmias suggest that azithromycin may increase the risk of cardiovascular death.

We studied a Tennessee Medicaid cohort designed to detect an increased risk of death related to short-term cardiac effects of medication, excluding patients with serious noncardiovascular illness and person-time during and shortly after hospitalization. The cohort included patients who took azithromycin (347,795 prescriptions), propensity-score–matched persons who took no antibiotics (1,391,180 control periods), and patients who took amoxicillin (1,348,672 prescriptions), ciprofloxacin (264,626 prescriptions), or levofloxacin (193,906 prescriptions).

During 5 days of therapy, patients taking azithromycin, as compared with those who took no antibiotics, had an increased risk of cardiovascular death (hazard ratio, 2.88; 95% confidence interval [CI], 1.79 to 4.63; P<0.001) and death from any cause (hazard ratio, 1.85; 95% CI, 1.25 to 2.75; P=0.002). Patients who took amoxicillin had no increase in the risk of death during this period. Relative to amoxicillin, azithromycin was associated with an increased risk of cardiovascular death (hazard ratio, 2.49; 95% CI, 1.38 to 4.50; P=0.002) and death from any cause (hazard ratio, 2.02; 95% CI, 1.24 to 3.30; P=0.005), with an estimated 47 additional cardiovascular deaths per 1 million courses; patients in the highest decile of risk for cardiovascular disease had an estimated 245 additional cardiovascular deaths per 1 million courses. The risk of cardiovascular death was significantly greater with azithromycin than with ciprofloxacin but did not differ significantly from that with levofloxacin.

Adverse effects of Zithromax reported to FDA

Potential Signals of Serious Risks/New Safety Information
Identified by the Adverse Event Reporting System (AERS) between
January – March 2010


The table below lists the names of products and potential signals of serious risks/new safety information that were identified for these products during the period January - March 2010 in the AERS database. The appearance of a drug on this list does not mean that FDA has concluded that the drug has the listed risk.


It means that FDA has identified a potential safety issue, but does not mean that FDA has identified a causal relationship between the drug and the listed risk. If after further evaluation the FDA determines that the drug is associated with the risk, it may take a variety of actions including requiring changes to the labeling of the drug, requiring development of a Risk Evaluation and Mitigation Strategy (REMS), or gathering additional data to better characterize the risk.


FDA wants to emphasize that the listing of a drug and a potential safety issue on this Web site does not mean that FDA is suggesting prescribers should not prescribe the drug or that patients taking the drug should stop taking the medication. Patients who have questions about their use of the identified drug should contact their health care provider. FDA will complete its evaluation of each potential signal/new safety information and issue additional public communications as appropriate.

FDA Safety Labeling Changes FDA Safety Changes: Zithromax,

Frova, Lexiscan News

Author: Yael Waknine CME Author: Yael Waknine Authors and Disclosures CME/CE Released: 05/13/2009;

May 13, 2009 — The US Food and Drug Administration (FDA) has approved safety labeling revisions to advise that concomitant use of azithromycin may potentiate the effects of oral anticoagulants, frovatriptan succinate is linked to a risk for serotonin syndrome that is increased by coadministration of antidepressants, and regadenoson injection may cause heart block and hypotension in some patients.

The Warnings and Precautions, Contraindications, and Adverse Reactions sections of the labeling for Zithromax were updated January 2011, to include liver failure. Azithromycin (Zithromax) Labeling approved January 28, 2011 (PDF - 459KB)

Zithromax Side Effects Report #5564775-0

Zithromax side effect was reported by a Consumer or non-health professional from UNITED STATES on Dec 13, 2007.

Male patient, child 12 years of age, weighting 115.0 lb, was diagnosed with bronchitis What is bronchitis and was treated with Zithromax. After drug was administered, patient experienced the following side effects: asthenia, eye disorder, liver disorder, photophobia, renal disorder, stevens-johnson syndrome. Zithromax dosage: unknown. Patient was hospitalized. Patient recovered.

Zithromax Side Effects Report #5025874-5

Zithromax side effect was reported by a Consumer or non-health professional from UNITED STATES on Apr 22, 2005.

Male patient, child 12 years of age, was diagnosed with bronchitis What is bronchitis, pyrexia and was treated with Zithromax. After drug was administered, patient experienced the following side effects: stevens-johnson syndrome. Zithromax dosage: unknown. During the same period patient was treated with MOTRIN. Patient recovered.

Zithromax Side Effects Report #5024731-8 Zithromax side effect was reported by a Physician from UNITED STATES on Feb 23, 2006.

Female patient, 38 years of age, was diagnosed with ill-defined disorder and was treated with Zithromax. After drug was administered, patient experienced the following side effects: stevens-johnson syndrome. Zithromax dosage: unknown. Patient recovered.

Zithromax Side Effects Report #5025737-5

Zithromax side effect was reported by a Consumer or non-health professional from UNITED STATES on Dec 02, 2005. Female patient, 16 years of age, was diagnosed with upper respiratory tract infection and was treated with Zithromax.

After drug was administered, patient experienced the following side effects: stevens-johnson syndrome, toxic epidermal necrolysis. Zithromax dosage: unknown. During the same period patient was treated with ACETAMINOPHEN, IBUPROFEN, ROBITUSSIN, CEFTRIAXONE, LIDOCAINE, DOPAMINE. Patient was hospitalized. Patient recovered.

Serious allergic reactions, including angioedema, anaphylaxis, and dermatologic reactions including Stevens Johnson Syndrome and toxic epidermal necrolysis  have been reported as a Zithromax Side Effect.