Zithromax and Stevens Johnson Syndrome latest articles suggest a potentially troubling trend with regard to disseminating information to the public.

On the official Pfizer website, physician information for Zithromax articulates the potential for rare but serious adverse reactions that can start with a Zithromax rash and possible fatality.

While reviewing Zithromax information for patients and consumers from the same page, the result is a short pdf document that appears to be directed to parents of children prescribed cherry-flavored suspension.

Allergic reactions to ZITHROMAX are rare, but these can be very serious if not treated right away by a doctor. If you think your child might be having an reaction to ZITHROMAX, stop the medicine and call the doctor right away. If you cannot reach the doctor, go to the nearest hospital emergency room. Symptoms of a severe allergic reaction may include severe skin rash or blisters.

 

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, 2012 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:

 

[05/17/2012 - Statement - CDER]

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

[03/15/2012 - 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; 366:1881-1890May 17, 2012

Background

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.

Methods

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).

Results

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.

NEJM: Common antibiotic linked to a few CV deaths, prompting FDA review

There was a small absolute increase in cardiovascular deaths, which was most pronounced among patients with a high baseline risk of cardiovascular disease during the five-day administration of the antibiotic azithromycin (Zithromax, Pfizer) therapy. This study, which evaluated nearly 350,000 prescriptions of azithromycin and was published May 17 in the New England Journal of Medicine, has prompted an FDA review of its results.
 
Although several macrolide antibiotics are proarrhythmic and associated with an increased risk of sudden cardiac death, azithromycin is thought to have minimal cardiotoxicity, according to the study authors. However, they added published reports of arrhythmias suggest that azithromycin may increase the risk of cardiovascular death.

Specifically, azithromycin, a broad-spectrum macrolide antibiotic that is used to treat infections caused by bacteria, has been reported to be relatively free of cardiotoxic effects. However, there are at least seven published reports of patients with normal baseline QT intervals in whom azithromycin had arrhythmia-related adverse cardiac effects, including pronounced QT-interval prolongation, Torsades de pointes and polymorphic ventricular tachycardia in the absence of QT-interval prolongation. The FDA's Adverse Event Reporting System includes at least 20 reports of Torsades de pointes associated with azithromycin.

In the study, Wayne A. Ray, PhD, a professor of preventive medicine at Vanderbilt University Medical Center in Nashville, Tenn., and colleagues studied a Tennessee Medicaid cohort designed to detect an increased risk of death related to short-term cardiac effects of medications, and excluded patients with serious non-cardiovascular illness and person-time during and shortly after hospitalization.

“An important concern in this observational study was confounding by factors associated with both azithromycin use and an increased risk of cardiovascular death,” wrote the study authors. “These factors include cardiovascular disease and other coexisting conditions, behavioral risk factors associated with cardiovascular disease (e.g., smoking, high body mass index, poor diet and low physical activity) and indication for antibiotic therapy.....”

http://www.cardiovascularbusiness.com/http://www.stevens-johnsonsyndrome.org/index.php?option=com_articles&view=article&id=34047:nejm-common-antibiotic-linked-to-a-few-cv-deaths-prompting-fda-review Stevens Johnson Syndrome ICD-9 Code Description

ICD-9

 695.10   ERYTHEMA MULTIFORME, UNSPECIFIED
695.11   ERYTHEMA MULTIFORME MINOR
695.12   ERYTHEMA MULTIFORME MAJOR
695.13   STEVENS-JOHNSON SYNDROME
695.14   STEVENS-JOHNSON SYNDROME-TOXIC EPIDERMAL NECROLYSIS OVERLAP SYNDROME 695.15   TOXIC EPIDERMAL NECROLYSIS 695.19   OTHER ERYTHEMA MULTIFORME