Zithromax (azithromycin), also known as Z-Pak, is an antibiotic used to treat bacterial infections such as bronchitis, pneumonia, and infections of the ears, lungs and other organs. First approved by the FDA in 1992 to treat certain respiratory and skin infections, its use has since expanded to include a wide variety of bacterial infections. These include sexually transmitted diseases, bacterial inflammations and middle-ear infections in children.
Zithromax has been highly profitable for its manufacturer, Pfizer. At the height of sales in 2002, it brought in over $1 billion for Pfizer. Although the wide availability of generics reduced the company’s revenue, U.S. sales still totaled $435 million in 2012.
This antibiotic is popular because it treats infections in adults and children. But, the drug is not without side effects — including fatal heart-related risks.
Zithromax also led to some legal trouble for Pfizer, including paying millions to several states to settle allegations that it used misleading tactics to market the drug to children.
How Zithromax Works
Zithromax belongs to a class of antibiotics called macrolides, which are bacteriostatic — meaning they treat infections by preventing bacteria from multiplying and producing the proteins that are essential for their growth. Eventually, the remaining bacteria die or are killed by the immune system, not by the drug itself. This is in contrast to bactericidal antibiotics, which kill bacteria. Bactericidal drugs include fluoroquinolones and penicillin.
Zithromax does not break down in the body as quickly as other antibiotics. Instead of floating freely in the blood, white blood cells that fight bacteria pick up the drug molecules. The white blood cells take the medicine to the front lines of their struggle with germs, where it becomes concentrated in the tissues surrounding the infection. That concentration helps it remain in the body longer, which means patients need fewer doses to beat their infections.
Zithromax and Z-Pak Dosage
Zithromax is most familiar to the public as the “Z-Pak,” a convenient five-day pill regimen with a dose of 500 mg the first day and 250 mg for the remaining four days. But, Zithromax comes in several dosages and forms, including oral tablets and liquids for oral use, injections and intravenous drips.
Dosage Forms and Strengths:
- Tablets: 250 mg, 500 mg, 600 mg
- Oral suspension (liquid): 100 mg/5 mL, 200 mg/5 mL, 1000 mg/5 mL
- Injection and IV: 10 mL vial of 500 mg
A doctor determines the dose depending on the infection being treated. For example, for pneumonia, pharyngitis or skin infections the recommended dose is the standard 500 mg for the first day and 250 mg for the remaining 4 days.
For more complicated disease such as acute sinusitis, doctors prescribe 500 mg a day for three days. In the case of sexually transmitted diseases, the dose is 1 gram, or 1000 mg, in one single dose.
Should I Take Zithromax?
According to the medication insert, certain people should not take Zithromax. Patients with allergies to azithromycin, erythromycin, or any macrolide or ketolide should not take Zithromax. People with liver problems or who had jaundice with prior use of Zithromax should not take it again.
In animal studies on mice and rats, researcher did not find evidence of birth defects at 3.2 times the human daily dose of 600 mg. But, because there are no actual studies on pregnant humans, pregnant mothers should only use Zithromax while pregnant if necessary. Breast feeding mothers also passed in breast milk. Health care providers should use caution in administering Zithromax to breast feeding mothers, according to the medication label.
In clinical trials, 9 percent of patients were at least 65 years of age, and 3 percent were at least 75 years of age. Researchers did not find any differences in effectiveness or safety between young patients and seniors.
Side Effects of Zithromax
In most cases, patients tolerate Z-Paks well. In clinical trials, side effects occurred in approximately 12 percent of patients, and less than 10 percent of those side effects were severe. The most common side effects were gastrointestinal and include diarrhea, stomach pain and nausea. Generally, side effects were more severe with a higher dose.
Less serious side effects include:
- Abdominal pain
- Diarrhea or loose stools
- Hearing problems
- Decreased sense of taste or smell
- Ringing in the ears
- Skin rash or itching
- Sleep problems (insomnia)
- Stomach upset
- Vaginal itching or discharge
Rare, serious side effects include:
- Allergic reactions
- Difficulty breathing
- Stevens-Johnson syndrome (a rare, serious disorder of skin and mucous membranes)
- Skin rash
- Liver problems, some resulting in death
- QT prolongation, irregular heart rhythm
- Clostridium difficile-Associated Diarrhea (CDAD)
- Myathenia gravis (muscle weakness)
Zithromax and Heart Problem Studies
In May 2012, a study in the New England Journal of Medicine reported an increase in cardiovascular death in patients treated with azithromycin compared with patients treated with amoxicillin, ciprofloxacin or no drug.
The study was prompted by evidence found in FDA adverse events databases that azithromycin promotes irregular heartbeats. This evidence led study authors to hypothesize that incidences of cardiovascular death may increase for patients on the drug.
Researchers concluded that certain patients were more likely to die while taking azithromycin than patients on other antibiotics or none at all.
Patients 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
- Taking drugs to treat arrhythmias
The risk of death while on azithromycin increased proportionally with the patients’ Cardiovascular Risk Score. The study found 245 deaths in patients with the highest risk scores, compared with just 9 deaths in patients with the lowest risk scores.
Since this increased death rate did not continue once patients finished their 5-day courses of azithromycin, researchers concluded the increased risk must stem from the drug and only lasts as long as the drug remains in the body. Following this study, the FDA issued a public statement detailing the study and warning that the Z-Pak may have previously unknown side effects relating to risk of cardiovascular death.
In March 2013, the FDA issued a stronger public warning based on new studies funded by Pfizer in response to the research in the New England Journal of Medicine (NEJM). The agency warned that azithromycin, including brand names Zithromax, Zmax, Azithrocin and Azin, “can cause abnormal changes in the electrical activity of the heart that may lead to a potentially fatal irregular heart rhythm.”
People with diabetes, a high risk of heart failure or a previous heart attack are at the most risk of abnormal heart rhythms while taking Zithromax.
“People with diabetes, heart failure or a previous heart attack are at the most risk while taking Zithromax”
The authors of the New England Journal study say doctors should consider prescribing a different drug, such as amoxicillin, for such high-risk patients. For the vast majority of patients who have no heart problems, there is no increased risk. The original NEJM study found only 47 additional deaths per 1 million courses of treatment, most of which occurred in patients with serious preexisting heart conditions.
A recent 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.
Zithromax Drug Interactions
In clinical trials, Zithromax had the potential to interact with three different types of drugs. Taking Zithromax with alcohol could also intensify side effects.
Drugs that react to Zithromax include:
- Nelfinavir is a drug doctors prescribe to treat HIV infections. This drug can increase the amount of Zithromax in body. The medication insert does not recommend the use of these two drugs together. Health care providers should check for liver abnormalities and hearing impairment.
- Warfarin is a blood thinner. Taking Warfarin with Zithromax increased the blood thinning effect. Doctors should monitor patients taking both drugs.
- Macrolides are a class of antibiotic, and Zithromax belongs to this class. Researchers observed interactions between Zithromax and other macrolides. Patients who use Zithromax with another macrolides should be carefully monitored for drug interactions.
Zithromax Effectiveness in Clinical Trials
In clinical trials, Zithromax was effective at fighting bacterial infection, including some antibiotic-resistant strains.
Studies conducted before approval of the drug measured its minimum inhibitory concentration (MIC) in relation to a host of bacteria. MIC is the lowest concentration of an antibiotic that will inhibit the growth of bacteria and thereby kill them. A lower MIC means a more effective antibiotic.
In a 1991 study in the European Journal of Clinical Microbiology and Infectious Diseases, researchers found Zithromax had a markedly low MIC compared with three other types of antibiotics, meaning it was highly effective — for example, resolving 92 percent of gonorrhea infections treated.
In 2003, Pfizer agreed to pay $6 million to settle deceptive Zithromax marketing allegations from 19 states. Oregon’s attorney general, Hardy Myers, led the investigation. According to court documents, Pfizer misrepresented the effectiveness of Zithromax in its ads and failed to disclose the risks of antibiotic overuse.
Pfizer admitted no wrongdoing and said the FDA approved its advertising and promotional materials. It claimed it was settling to avoid unnecessary costs.
The drugmaker created a mascot for Zithromax, a zebra named Max, to use in its marketing. Pfizer sent plastic zebras that hang on stethoscopes and medical journals wrapped in zebra stripes to pediatricians. It also donated a zebra named Max to the San Francisco Zoo and invited children to a naming celebration.
The 2013 FDA heart rhythm warning prompted some lawyers to investigate and file Zithromax lawsuits. According to plaintiffs, Zithromax caused abnormal heart rhythms. But there have been no settlements or trial dates set.