Azithromycin

Is azithromycin safe?

Yes, for most people with a bacterial infection it is. Azithromycin, sold as Zithromax and handed out as the five-day Z-Pak, is a macrolide antibiotic that most people take for three to five days with nothing worse than an upset stomach. In Pfizer's trials only about 0.7% of patients stopped it because of side effects.

The concern is the heart. Azithromycin can slow the heart's electrical recovery between beats (QT prolongationQT prolongationA delay in the heart's electrical recovery between beats, seen on an ECG. Some medicines cause it, and in rare cases it leads to a serious heart rhythm problem.More in the glossary), and in March 2013 the FDA warned that this can, rarely, cause a fatal rhythm. The absolute risk is small and highest in people who already have heart disease, although the label says it does not appear to be limited to them. We score it 82, below amoxicillin (91) and doxycycline (86) and well above ciprofloxacin (64).

Does azithromycin cause heart problems?

The concern started with a study of Tennessee Medicaid patients published in the New England Journal of Medicine in May 2012. It compared 347,795 azithromycin prescriptions with amoxicillin, other antibiotics and no antibiotic:

The FDA then reviewed the study and Pfizer's own heart rhythm study and issued its safety communication on 12 March 2013. The label now says observational studies found about twice the short-term risk of cardiovascular death against other antibiotics, with 20 to 400 deaths per million courses in the first five days, and that the data can neither prove nor exclude cause.

A Danish study of more than a million courses in younger and middle-aged adults, published in 2013, found no extra risk against penicillin V. Read together, the studies point the same way: for a healthy 30-year-old the risk is close to nil, while an older person with heart failure or a slow pulse, or someone taking another QT-prolongingQT prolongationA delay in the heart's electrical recovery between beats, seen on an ECG. Some medicines cause it, and in rare cases it leads to a serious heart rhythm problem.More in the glossary drug, has a real reason for the prescriber to choose something else.

Stomach upset, liver and C. diff

The common side effects are digestive. Across the label's trials, diarrhoea affected 5 to 14% of patients, nausea 3 to 18%, abdominal pain 3 to 7% and vomiting 2 to 7%, with higher figures for the single large doses. These usually pass.

The rare serious ones are worth knowing by their signs:

• Severe allergic and skin reactions, including anaphylaxis, Stevens-Johnson syndrome and DRESS. Because azithromycin stays in the body for days (a half-life of about 68 hours), the label notes that allergic symptoms can return after treatment seems to have worked.
• Liver injuryDrug-induced liver injuryLiver damage caused by a medicine, herbal product or supplement. It is usually rare and unpredictable, but it can be serious.More in the glossary: hepatitis and, rarely, fatal liver failure. Yellow skin, dark urine or pain under the right ribs need prompt attention.
• C. difficile diarrhoea, which can start up to two months after the course ends.
• Pyloric stenosis in newborns given azithromycin in the first six weeks of life, and worse weakness in myasthenia gravis.

Hearing loss and ringing in the ears have also been reported after approval.

Interactions to tell your pharmacist about

The label's interaction list is short next to many antibiotics. The ones that matter:

• Other QT-prolongingQT prolongationA delay in the heart's electrical recovery between beats, seen on an ECG. Some medicines cause it, and in rare cases it leads to a serious heart rhythm problem.More in the glossary drugs: antiarrhythmics such as amiodarone, sotalol, dofetilide and quinidine, and also drugs like citalopram, some antipsychotics and methadone.
• Warfarin: reports of stronger anticoagulant effect, so the label advises checking clotting times.
• Digoxin, colchicine and phenytoin: other macrolides raise their levels, so the label advises careful monitoring.
• Antacids with aluminium or magnesium: do not take them at the same time. The NHS advises taking azithromycin at least an hour before or two hours after the antacid.

Resistance: why it is prescribed less than it used to be

Azithromycin's convenience made it heavily used, and bacteria have adapted. In US surveillance, gonorrhoea samples with reduced sensitivity rose more than sevenfold, from 0.6% in 2013 to 4.6% in 2018. In December 2020 the CDC dropped azithromycin from first-line gonorrhoea treatment and now recommends a single ceftriaxone injection alone. The label itself says that prescribing it without a proven or strongly suspected bacterial infection brings no benefit and breeds resistance, and that it should not be relied on to treat syphilis.

For most coughs, colds and sore throats, which are viral, the safest antibiotic is none. If you are offered azithromycin "just in case", ask whether you need it.

Who should be careful

Talk to your doctor or pharmacist before taking azithromycin if you:

• have a long QT intervalQT prolongationA delay in the heart's electrical recovery between beats, seen on an ECG. Some medicines cause it, and in rare cases it leads to a serious heart rhythm problem.More in the glossary, a slow or irregular heartbeat, or heart failure
• have low potassium or magnesium, or take diuretics that lower them
• take an antiarrhythmic, warfarin, digoxin, colchicine or any medicine that affects heart rhythm
• have liver or kidney disease or myasthenia gravis
• are giving it to a baby under six weeks old
• had jaundice or liver problems with azithromycin before

Get urgent help for fainting, a racing or pounding heartbeat, a blistering rash, swelling of the face or throat, or yellowing skin. Finish the course unless your prescriber tells you to stop.

How we scored it

Dependence (98), track record (95) and overdose marginOverdose marginHow far a normal dose is from a harmful one. A wide margin means an accidental extra dose is unlikely to cause serious harm.More in the glossary (88) are strong. Serious side effects (76) is lower than for amoxicillin because of the small but real cardiac death signal and rare liver and skin reactions. Interactions (68) and regulatory warnings (70) reflect the QT drug combinations and the 2013 FDA safety communication, though there is no boxed warningBoxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary.