Zithromax Side Effects

Zithromax, commonly called Z-Pak, is a macrolide antibacterial drug that doctors prescribe to treat a variety of mild to moderate infections. The drug’s active ingredient, azithromycin, can cause rare but serious side effects such as severe or life-threatening allergic reactions, irregular heartbeats, Clostridium difficile-associated diarrhea and liver damage. More common side effects include nausea or vomiting, diarrhea and abdominal pain.

Zithromax (Z-pak) tablet
Z-Pak Side Effects
  1. Common Side Effects The most common side effects of Zithromax include diarrhea, nausea, abdominal pain and vomiting.
  2. Serious Side Effects Z-Pak can cause serious side effects, including severe allergic and skin reactions, liver damage, infantile hypertrophic pyloric stenosis, serious heart rhythm changes, worsening of myasthenia gravis and Clostridium difficile-associated diarrhea.

Most people tolerate Zithromax, or Z-Pak, well. The prescription antibiotic is a common substitute for patients with a penicillin allergy because its active ingredient, azithromycin, can fight a slightly wider spectrum of bacteria. However, as much as 18 percent of people who took the drug during clinical trials reported some minor side effects.

Nausea was the most common side effect reported during clinical trials. About 3 percent to 18 percent of patients reported the adverse reaction.

Meanwhile, 5 percent to 14 percent of patients reported diarrhea, and between 2 percent and 7 percent of patients reported abdominal pain or vomiting. All other common side effects identified during clinical trials were reported by less than 1 percent of patients.

Common Z-Pak side effects reported during clinical trials:
  • Nausea
  • Diarrhea
  • Abdominal Pain
  • Vomiting
  • Blood in feces
  • Dizziness
  • Fatigue
  • Flatulence
  • Headache
  • Heart palpitations or chest pain
  • Indigestion
  • Kidney inflammation
  • Lack of energy or motivation
  • Rash
  • Yeast infections
  • Severe itching of the skin
  • Skin sensitivity to bright light
  • Swelling in the lower layers of the skin
  • Vaginal inflammation
  • Vertigo
  • Reduction in bile flow (cholestatic jaundice)

Clinical studies and post-marketing reports have also suggested several rare but serious Zithromax side effects. These include severe and potentially life-threatening conditions such as allergic and skin reactions, liver damage, heart problems and Clostridium difficile-associated diarrhea.

The drug can also cause worsening or new onset of myasthenia gravis, a disease that causes muscle weakness. Infants who take the medication may develop an intestinal condition known as infantile hypertrophic pyloric stenosis, which happens when the opening between the stomach and small intestine thickens. And people who have beaten cancer of the blood or lymph nodes may experience a relapse if they use Z-Pak.

Allergic and Skin Reactions

People have suffered serious and sometimes deadly allergic reactions to azithromycin. Reported reactions include angioedema, which causes swelling under the skin, and anaphylaxis, which is a full-body reaction that can be fatal.

Since the U.S. Food and Drug Administration approved azithromycin in 1991, studies and adverse event reports have also associated the drug with several skin reactions including: Acute Generalized Exanthematous Pustulosis (AGEP), a sudden skin eruption that appears approximately five days after treatment starts; Stevens-Johnson syndrome, a serious disorder that causes blistering and peeling of skin and mucous membranes; and toxic epidermal necrolysis, a potentially deadly reaction that can lead to cell death in organs or blistering and skin peeling that can lead to sepsis.

“Allergic reactions can happen in people taking azithromycin the active ingredient in Zithromax, even after only 1 dose,” according to the Zithromax prescribing information.

“Allergic reactions can happen in people taking azithromycin the active ingredient in Zithromax, even after only 1 dose.”

Source: Zithromax Prescribing Information

Some people who used Z-Pak reported a condition called drug reaction with eosinophilia and systemic symptoms (DRESS). This is a rare but potentially fatal condition, and genetic factors play a significant role in who may develop it.

The condition causes an influx of infection-fighting white blood cells called eosinophils which cause severe inflammation. DRESS may start as a rash that can spread all over the body. It can cause injury to the liver, kidneys, lungs, heart or pancreas.

The drug’s label warns that some patients’ allergic symptoms initially went away with treatment but came back when treatment was stopped. This happened even without further exposure to azithromycin. The patients needed long-term observation and treatment.

Cancer Relapse

In 2018, the FDA warned long-term use of azithromycin can cause cancer relapse in patients who have had cancer of the blood or lymph nodes and have undergone a donor stem cell transplant. The agency based its warning on results from a clinical trial that found about one-third of these patients who had taken azithromycin experienced a relapse in their cancer.

Researchers stopped the trial after about a year because of an “unexpected increase in the rate of both relapses and death.” A total of 95 patients who had been treated with the antibiotic died. The two-year survival rate for azithromycin-treated patients was 56 percent compared to 70 percent in patients who took a placebo.

Cancer patients who undergo donor stem cell transplants are at risk for a serious lung condition called bronchiolitis obliterans syndrome. Doctors sometimes prescribe azithromycin to prevent the condition. But the FDA did not approve the drug for this use.

“Health care professionals should not prescribe long-term azithromycin for prophylaxis of bronchiolitis obliterans syndrome to patients who undergo donor stem cell transplants because of the increased potential for cancer relapse and death.”

Source: FDA Safety Announcement, Aug. 3, 2018

Pfizer Inc. sent out a warning letter to doctors telling them to stop the practice. The FDA warned patients who have had a stem cell transplant not to stop taking the drug without a doctor’s direct supervision.

“Health care professionals should not prescribe long-term azithromycin for prophylaxis of bronchiolitis obliterans syndrome to patients who undergo donor stem cell transplants because of the increased potential for cancer relapse and death,” the agency said.

Heart Problems

Zithromax has also been associated with heart problems, including prolonged QT interval, which throws off the electrical cycle of the heart. A prolonged QT interval can lead to dangerous irregular heart rhythms that can sometimes cause sudden cardiac death.

In May 2012, a study in The New England Journal of Medicine reported a small increase in cardiovascular death in patients treated with azithromycin compared with patients treated with amoxicillin, ciprofloxacin or no drug.

“As compared with amoxicillin, there were 47 additional cardiovascular deaths per 1 million courses of azithromycin therapy.”

Source: New England Journal of Medicine, May 17, 2012

Adverse event reports to the FDA associating azithromycin with irregular heartbeats prompted the study. Researchers concluded certain patients were more likely to die while taking azithromycin than while using other antibiotics or none at all.

“As compared with amoxicillin, there were 47 additional cardiovascular deaths per 1 million courses of azithromycin therapy,” the researchers wrote.

Z-Pak users at high risk for cardiovascular death include those:
  • With existing QT interval prolongation
  • With low blood levels of potassium or magnesium
  • With a slower than normal heart rate
  • Who take drugs to treat arrhythmias

The risk of death while on azithromycin increased proportionally with the patients’ cardiovascular risk score. The study found 245 deaths per million five-day courses in patients with the highest risk scores compared with just nine deaths in patients with the lowest risk scores.

The increased death rate did not continue once patients finished their five-day Z-Pak courses. The increased risk stemmed from the drug and lasted as long as the drug levels were high in the blood.

The FDA issued a public statement in March 2013 that detailed the study and warned the medication may have previously unknown side effects relating to risk of cardiovascular death. The agency said patients who are most at risk are those with known risk factors such as existing heart problems.

A study sponsored by the Danish Medical Research Council found no evidence of increased risk of death for young and middle-aged adults without heart problems who took Zithromax compared with those who took a different antibiotic such as penicillin. Researchers concluded that any increased risk of cardiovascular death associated with azithromycin is restricted to high-risk patients with a history of heart disease or problems.

The drug’s label also includes a warning about a potentially fatal condition called torsades de pointes (TdP). The condition involves rapid heartbeats that start in the ventricles.

Researchers reported cases of TdP during postmarketing surveillance of patients taking Zithromax. Once this serious heart condition develops, few patients will survive it without prompt treatment.

Clostridium difficile-Associated Diarrhea (CDAD)

Clostridium difficile-associated Diarrhea (CDAD) is a side effect reported with nearly all antibiotics, including Zithromax. It can range in severity from mild diarrhea to fatal inflammation of the colon called colitis. Reports say patients have experienced the side effect over two months after taking an antibiotic.

Antibiotics alter the normal gut flora, or the good and bad bacteria that live in the digestive tract and colon. This can kill off so-called “good bacteria” and lead to an overgrowth of Clostridium difficile, or C. difficile.

C. difficile is an antibiotic-resistant bacterium. Quick treatment is crucial to managing the infection.

Azithromycin and other macrolide antibiotics are considered to have a moderate risk of causing or contributing to C. difficile infections. Medical professionals have suggested substituting tetracyclines for macrolides when treating some conditions in older patients who are at greater risk of C. difficile infection.

Liver Damage

The National Institutes of Health says azithromycin’s popularity has made it “one of the more common causes of drug-induced liver injury.”

It has been linked in rare cases to hepatotoxicity, which refers to chemical- or medication-driven liver damage. Liver damage associated with the antibiotic has sometimes resulted in death.

Conditions of liver impairment and/or injury reported in patients include:
  • Abnormal liver function
  • Hepatitis
  • Cholestatic jaundice
  • Hepatic necrosis
  • Liver failure

A 2014 study in the journal Clinical Gastroenterology and Hepatology found azithromycin-induced liver injury can happen within one to three weeks after a person starts taking the drug. The researchers said the damage tended to happen at the cellular level.

“Although most patients recover fully, severe cutaneous (skin-related) reactions, chronic injury, and serious complications leading to death or liver transplantation can occur,” the authors wrote.

Other research suggests Z-Pak treatment may be riskier for people who have previously experienced a liver condition.

A study published in 2015 in the journal Gastroenterology looked at 899 patients with drug-induced liver injury. Ten percent of the patients had a pre-existing liver disease.

The researchers found azithromycin was associated with 6.7 percent of liver injuries among those with pre-existing liver conditions compared with 1.5 percent of cases among those who had no pre-existing condition.

Please seek the advice of a medical professional before making health care decisions.

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Terry Turner
Written By Terry Turner Writer

Terry Turner has been writing articles and producing news broadcasts for more than 25 years. He covers FDA policy, proton pump inhibitors, and medical devices such as hernia mesh, IVC filters, and hip and knee implants. An Emmy-winning journalist, he has reported on health and medical policy issues before Congress, the FDA and other federal agencies. Some of his qualifications include:

  • American Medical Writers Association (AMWA) and The Alliance of Professional Health Advocates member
  • Centers for Disease Control and Prevention Health Literacy certificates
  • Original works published or cited in Washington Examiner, MedPage Today and The New York Times
  • Appeared as an expert panelist on hernia mesh lawsuits on the BBC
Edited By

40 Cited Research Articles

  1. Centers for Disease Control and Prevention. (2015, February 24). Clostridium difficile Infection Information for Patients. Retrieved from  https://www.cdc.gov/hai/organisms/cdiff/cdiff-patient.html
  2. Chalasani, N. et al. (2015, March 6). Features and Outcomes of 899 Patients with Drug-Induced Liver Injury: The DILIN Prospective Study. Gastroenterology. Retrieved from https://www.sciencedirect.com/science/article/pii/S001650851500311X
  3. DailyMed. NIH. (2017, April 13). Label: Zithromax – azithromycin dihydrate tablet, film coated; Zithromax – azithromycin dihydrate powder, for suspension. Retrieved from  https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=B749DF83-49B0-433E-8A62-589A048DD716
  4. Dave, J. (2017, February 1). Torsade de Pointes. Retrieved from  https://emedicine.medscape.com/article/1950863-overview
  5. Deshpande, A. et al. (2014, June). Antibiotic-Associated Diarrhea and Clostridium Difficile. Retrieved from  http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/gastroenterology/antibiotic-associated-diarrhea/
  6. Di Bella, S., Taglietti, F. and Petrosillo, N. (2013, August). Are There Reasons to Prefer Tetracyclines to Macrolides in Older Patients with Community-Acquired Pneumonia? Antimicrobial Agents and Chemotherapy. Retrieved from https://aac.asm.org/content/57/8/4093
  7. Doheny, K. (2013, May 1). Antibiotic Azithromycin Won’t Harm Healthy Hearts: Study. Health Day. Retrieved from  http://health.usnews.com/health-news/news/articles/2013/05/01/antibiotic-azithromycin-wont-harm-healthy-hearts-study
  8. Martinez, M.A. et al. (2014, August 9). Clinical and Histological Features of Azithromycin-Induced Liver Injury. Clinical Gastroenterology and Hepatology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4321982/
  9. MedlinePlus. NIH. (2016, March 14). Allergic reactions. Retrieved from   https://medlineplus.gov/ency/article/000005.htm
  10. MedlinePlus. NIH. (2016, March 20). Anaphylaxis. Retrieved from  https://medlineplus.gov/ency/article/000844.htm
  11. National Heart, Lung, and Blood Institute. NIH. (2011, September 21). What Is Long QT Syndrome? Retrieved from  https://www.nhlbi.nih.gov/health/health-topics/topics/qt/
  12. National Institutes of Health. Drug Record; Azithromycin. LiverTox. Retrieved from https://livertox.nih.gov/Azithromycin.htm
  13. Ray, W.A. et al. (2012, May 17). Azithromycin and the Risk of Cardiovascular Death. New England Journal of Medicine. Retrieved from https://www.nejm.org/doi/full/10.1056/NEJMoa1003833
  14. Schroeder, S. (2005, March 1). Clostridium difficile-Associated Diarrhea. Retrieved from  http://www.aafp.org/afp/2005/0301/p921.html
  15. Tas, S. and Simonart, T. (2003). Management of Drug Rash with Eosinophilia and Systemic Symptoms (DRESS Syndrome): An Update. Retrieved from  http://www.ucdenver.edu/academics/colleges/medicalschool/departments/surgery/divisions/GITES/burn/Documents/Drug%20Rash%20with%20Eosinophilia%20and%20Systemic%20Symptoms.pdf
  16. U.S. Food and Drug Administration. (2016, May 10). FDA Drug Safety Communication: FDA warns about rare but serious skin reactions with mental health drug olanzapine (Zyprexa, Zyprexa Zydis, Zyprexa Relprevv, and Symbyax). Retrieved from  https://www.fda.gov/Drugs/DrugSafety/ucm499441.htm
  17. U.S. Food and Drug Administration. (2017, March). Zithromax 250 mg and 500 mg Tablets and Oral Suspension Label. Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/050670s032,050710s046,050711s043,050784s030lbl.pdf
  18. U.S. Food and Drug Administration. (2018, August 3). Zithromax, Zmax (azithromycin): FDA Warning - Increased Risk of Cancer Relapse With Long-Term Use After Donor Stem Cell Transplant. Retrieved from  https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm615738.htm?utm_campaign=FDA%20MedWatch%20-%20Zithromax%2C%20Zmax%20%28azithromycin%29%3A%20Warning&utm_medium=email&utm_source=Eloqua
  19. U.S. Food and Drug Administration. (2013, March 12). FDA Drug Safety Communication: Azithromycin (Zithromax or Zmax) and the risk of potentially fatal heart rhythms. Retrieved from https://www.fda.gov/Drugs/DrugSafety/ucm341822.htm
  20. Van Noord, C. et al. (2010, July). Drug- and non-drug-associated QT interval prolongation. Retrieved from  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2909803/
  21. Centers for Disease Control and Prevention. (2015, February 24). Clostridium difficile Infection Information for Patients. Retrieved from  https://www.cdc.gov/hai/organisms/cdiff/cdiff-patient.html
  22. Chalasani, N. et al. (2015, March 6). Features and Outcomes of 899 Patients with Drug-Induced Liver Injury: The DILIN Prospective Study. Gastroenterology. Retrieved from https://www.sciencedirect.com/science/article/pii/S001650851500311X
  23. DailyMed. NIH. (2017, April 13). Label: Zithromax – azithromycin dihydrate tablet, film coated; Zithromax – azithromycin dihydrate powder, for suspension. Retrieved from  https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=B749DF83-49B0-433E-8A62-589A048DD716
  24. Dave, J. (2017, February 1). Torsade de Pointes. Retrieved from  https://emedicine.medscape.com/article/1950863-overview
  25. Deshpande, A. et al. (2014, June). Antibiotic-Associated Diarrhea and Clostridium Difficile. Retrieved from  http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/gastroenterology/antibiotic-associated-diarrhea/
  26. Di Bella, S., Taglietti, F. and Petrosillo, N. (2013, August). Are There Reasons to Prefer Tetracyclines to Macrolides in Older Patients with Community-Acquired Pneumonia? Antimicrobial Agents and Chemotherapy. Retrieved from https://aac.asm.org/content/57/8/4093
  27. Doheny, K. (2013, May 1). Antibiotic Azithromycin Won’t Harm Healthy Hearts: Study. Health Day. Retrieved from  http://health.usnews.com/health-news/news/articles/2013/05/01/antibiotic-azithromycin-wont-harm-healthy-hearts-study
  28. Martinez, M.A. et al. (2014, August 9). Clinical and Histological Features of Azithromycin-Induced Liver Injury. Clinical Gastroenterology and Hepatology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4321982/
  29. MedlinePlus. NIH. (2016, March 14). Allergic reactions. Retrieved from   https://medlineplus.gov/ency/article/000005.htm
  30. MedlinePlus. NIH. (2016, March 20). Anaphylaxis. Retrieved from  https://medlineplus.gov/ency/article/000844.htm
  31. National Heart, Lung, and Blood Institute. NIH. (2011, September 21). What Is Long QT Syndrome? Retrieved from  https://www.nhlbi.nih.gov/health/health-topics/topics/qt/
  32. National Institutes of Health. Drug Record; Azithromycin. LiverTox. Retrieved from https://livertox.nih.gov/Azithromycin.htm
  33. Ray, W.A. et al. (2012, May 17). Azithromycin and the Risk of Cardiovascular Death. New England Journal of Medicine. Retrieved from https://www.nejm.org/doi/full/10.1056/NEJMoa1003833
  34. Schroeder, S. (2005, March 1). Clostridium difficile-Associated Diarrhea. Retrieved from  http://www.aafp.org/afp/2005/0301/p921.html
  35. Tas, S. and Simonart, T. (2003). Management of Drug Rash with Eosinophilia and Systemic Symptoms (DRESS Syndrome): An Update. Retrieved from  http://www.ucdenver.edu/academics/colleges/medicalschool/departments/surgery/divisions/GITES/burn/Documents/Drug%20Rash%20with%20Eosinophilia%20and%20Systemic%20Symptoms.pdf
  36. U.S. Food and Drug Administration. (2016, May 10). FDA Drug Safety Communication: FDA warns about rare but serious skin reactions with mental health drug olanzapine (Zyprexa, Zyprexa Zydis, Zyprexa Relprevv, and Symbyax). Retrieved from  https://www.fda.gov/Drugs/DrugSafety/ucm499441.htm
  37. U.S. Food and Drug Administration. (2017, March). Zithromax 250 mg and 500 mg Tablets and Oral Suspension Label. Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/050670s032,050710s046,050711s043,050784s030lbl.pdf
  38. U.S. Food and Drug Administration. (2018, August 3). Zithromax, Zmax (azithromycin): FDA Warning - Increased Risk of Cancer Relapse With Long-Term Use After Donor Stem Cell Transplant. Retrieved from  https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm615738.htm?utm_campaign=FDA%20MedWatch%20-%20Zithromax%2C%20Zmax%20%28azithromycin%29%3A%20Warning&utm_medium=email&utm_source=Eloqua
  39. U.S. Food and Drug Administration. (2013, March 12). FDA Drug Safety Communication: Azithromycin (Zithromax or Zmax) and the risk of potentially fatal heart rhythms. Retrieved from https://www.fda.gov/Drugs/DrugSafety/ucm341822.htm
  40. Van Noord, C. et al. (2010, July). Drug- and non-drug-associated QT interval prolongation. Retrieved from  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2909803/
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