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.
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, 4 percent to 12 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.
- Abdominal pain
- Blood in feces
- Loss of sense of taste or smell
- Rash and itching
- Upset stomach
- Vaginal inflammation
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. Zithromax has also been linked to an increased risk of cancer relapse in people who have beaten cancer of the blood or lymph nodes when it is used as a long-term treatment.
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.”
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.
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 patients who had taken long-term azithromycin to prevent a lung condition called bronchiolitis obliterans syndrome 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.”
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.
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.”
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 or a history of QT interval prolongation
- With low blood levels of potassium or magnesium
- With a slower than normal heart rate
- Who take certain drugs to treat arrhythmias
The risk of death while on azithromycin increased proportionally with the patients’ cardiovascular risk score. The study found 245 additional deaths per million five-day courses in patients with the highest risk scores versus with just nine additional deaths in patients with the lowest risk scores as compared to amoxicillin.
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 developing abnormal heart rhythms that may be fatal. 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. CDAD typically develops within a few days after taking an antibiotic, however reports have shown that some 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.
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.
- Abnormal liver function
- 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.
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