Erythromycin Side Effects

The most common side effects of erythromycin are gastrointestinal: nausea, stomach cramps, vomiting, diarrhea and loss of appetite. They are usually mild and short-lived, but serious reactions — QT prolongation and heart rhythm problems, cholestatic hepatitis, C. difficile diarrhea and severe allergic reactions — are possible, so it helps to know which symptoms you can manage at home and which need prompt medical attention.

This page goes deeper on side effects than our safety overview. Drug combinations are covered on the interactions page, and cardiac risk in detail on erythromycin and QT prolongation.

Common Side Effects: Why Erythromycin Upsets the Stomach

Gastrointestinal symptoms are the side effect people most associate with erythromycin, and the main reason patients stop it early. They include:

• Nausea and vomiting
• Abdominal pain or cramping
• Diarrhea (usually loose, non-bloody stools)
• Loss of appetite and a feeling of fullness

Unlike most antibiotics, erythromycin causes these symptoms mainly through a direct drug effect rather than by disturbing gut bacteria. The erythromycin molecule mimics motilin, a hormone that triggers strong waves of contraction in the stomach and small intestine. Activating motilin receptors speeds gastric emptying and produces cramping — the same property that is put to deliberate use at low doses to treat gastroparesis. Because the effect is dose-related, symptoms tend to be worse with larger single doses and with intravenous administration. See how erythromycin works for the pharmacology.

How to Reduce GI Upset

• Check whether your product can be taken with food. Erythromycin ethylsuccinate (E.E.S., EryPed) and delayed-release base tablets such as Ery-Tab can generally be taken without regard to meals, and taking them with food often eases nausea. Erythromycin stearate and some base preparations are labeled to be taken on an empty stomach or just before meals for best absorption — follow the leaflet for your specific product.
• Ask about the formulation. Enteric-coated or film-coated tablets are often better tolerated than uncoated preparations. For children, a different suspension may be easier to take.
• Ask about the dosing schedule. Smaller, more frequent doses (for example 250 mg every 6 hours rather than 500 mg every 12 hours) give lower peak levels; your prescriber can decide if this suits your infection.
• Eat small, bland meals and keep up fluids, especially if you have diarrhea.
• Consider an alternative. If you cannot keep doses down, contact your prescriber. Azithromycin and clarithromycin act on motilin receptors far less and are usually better tolerated (see erythromycin vs azithromycin).

If you vomit soon after a dose, ask your pharmacist whether to repeat it rather than doubling the next one.

Less Common Side Effects

• Skin rash and itching. Mild itchy or blotchy rashes and hives can occur. Most are not dangerous, but any new rash should be reported (see rash while taking erythromycin below).
• Vaginal thrush and oral thrush. Like other antibiotics, erythromycin can allow Candida to overgrow, causing vaginal itching and discharge or white patches in the mouth. These are treatable, often with over-the-counter antifungals; ask a pharmacist.
• Mild, reversible changes in liver tests without symptoms are occasionally found on blood tests.

Serious Side Effects

QT Prolongation and Arrhythmia

Erythromycin blocks cardiac potassium (hERG) channels, which can prolong the QT interval and, rarely, cause torsades de pointes, a ventricular arrhythmia that can lead to fainting or sudden death. A large US cohort study found an increased rate of sudden cardiac death with oral erythromycin, concentrated in people also taking strong CYP3A4 inhibitors that raise erythromycin levels. Risk is greatest with IV administration, high doses, older age, female sex, low potassium or magnesium, slow heart rate, existing QT prolongation or heart disease, and other QT-prolonging drugs. Fainting, palpitations or a racing, irregular heartbeat need urgent assessment. Full details: QT prolongation.

Cholestatic Hepatitis

Erythromycin can cause liver injury with a cholestatic pattern (impaired bile flow). It typically appears after one or more weeks of treatment and presents with nausea, upper-right abdominal pain, itching, dark urine, pale stools and yellowing of the skin or eyes, sometimes with fever. It has been reported with all salts but is most strongly linked to the estolate ester, which is why estolate is contraindicated in pregnancy and avoided in liver disease. The injury is usually reversible after stopping the drug.

Clostridioides difficile Diarrhea

All antibiotics can disrupt the colonic flora and allow C. difficile to cause colitis. It can start during treatment or up to two months afterward. Frequent watery diarrhea (three or more episodes a day), blood or mucus in the stool, abdominal pain and fever are warning signs — tell a clinician promptly and avoid anti-diarrheal medicines unless advised.

Allergic Reactions, SJS and TEN

Anaphylaxis is rare. Signs include facial or throat swelling, wheezing, difficulty breathing, widespread hives and collapse — call emergency services. Severe cutaneous reactions, including Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and acute generalized exanthematous pustulosis, have been reported rarely. Early signs may be flu-like symptoms followed by a painful red or purple rash that blisters or peels, with sores in the mouth, eyes or genitals.

Reversible Hearing Loss

Hearing loss, tinnitus and occasionally vertigo have been reported, mostly with high doses (4 g/day or more), IV administration and in people with kidney or liver impairment or older age. Hearing usually recovers after stopping, though rare cases of persistent loss are described. Report any change in hearing or new ringing in the ears.

Worsening of Myasthenia Gravis

The FDA label warns that erythromycin can aggravate muscle weakness in people with myasthenia gravis and may unmask the condition. New difficulty swallowing, drooping eyelids, double vision or breathing weakness need urgent care.

Pyloric Stenosis in Infants

Oral erythromycin given to infants in the first weeks of life is associated with infantile hypertrophic pyloric stenosis (IHPS), a narrowing of the stomach outlet. The association is strongest in the first two weeks, and the risk applies to infants under about six weeks. Signs are forceful (projectile) vomiting after feeds, hunger after vomiting and poor weight gain. This is why azithromycin is preferred for pertussis in infants younger than one month. The eye ointment used at birth is not linked to IHPS. See pediatric dosing.

Side Effects by Formulation

When to Stop and Seek Care

How Long Do Side Effects Last?

GI symptoms usually begin within hours of a dose and ease within a day or two after the final dose; many people find they lessen after the first few days of treatment. Blurred vision from the eye ointment lasts minutes. Skin irritation from topical products often improves as the skin adapts over the first weeks. Cholestatic hepatitis typically resolves over several weeks after stopping, and drug-related hearing loss usually recovers within days to weeks. C. difficile diarrhea can begin weeks after the course ends, so mention recent antibiotic use to any clinician you see.

Rash While Taking Erythromycin: Should You Continue?

A common question is whether a rash will worsen if you keep taking erythromycin. The honest answer is that it might, and there is no reliable way to tell at home. Many antibiotic rashes are mild and fade, and some are caused by the infection itself rather than the drug. But a drug reaction generally continues or progresses while you keep taking the drug, and a mild early rash can be the first sign of a serious reaction such as SJS.

• Contact your prescriber before the next dose for any new rash. They may switch you to an antibiotic from a different class.
• Stop and seek emergency care if the rash blisters, peels, is painful, involves the lips, mouth, eyes or genitals, or comes with fever, facial swelling or breathing difficulty.
• Take a photo of the rash to show the clinician, and record the reaction so it appears in your allergy history.

Contraindications and Who Should Be Cautious

Under US labeling, erythromycin is contraindicated in people with known hypersensitivity to erythromycin or other macrolides, and with terfenadine, astemizole, cisapride, pimozide, ergotamine, dihydroergotamine, lovastatin or simvastatin. UK product information also advises against use in people with known QT prolongation, a history of ventricular arrhythmia, or uncorrected electrolyte disturbances. The estolate salt is contraindicated in pregnancy and in pre-existing liver disease. Use with caution in liver impairment, myasthenia gravis, older adults, and anyone taking drugs metabolized by CYP3A4. See drug interactions and erythromycin in pregnancy.

Limitations and Challenges of Erythromycin

Erythromycin's main practical limitations are its high rate of GI intolerance, frequent dosing (two to four times daily), a large number of CYP3A4 drug interactions, QT risk, and widespread bacterial resistance, particularly among Streptococcus pneumoniae and group A streptococci in many regions. These factors explain why azithromycin and clarithromycin have replaced it for many indications (see macrolide comparison), although erythromycin remains valuable for neonatal eye prophylaxis, acne, gastroparesis and selected infections.

Frequently Asked Questions

References

1. Ery-Tab (erythromycin delayed-release tablets) prescribing information. DailyMed, U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/
2. Erythrocin Lactobionate-IV (erythromycin lactobionate for injection) prescribing information. DailyMed, U.S. National Library of Medicine.
3. Erythromycin. British National Formulary (BNF). National Institute for Health and Care Excellence. https://bnf.nice.org.uk/
4. Erythromycin: side effects. NHS medicines information. https://www.nhs.uk/medicines/erythromycin/
5. Ray WA, Murray KT, Meredith S, Narasimhulu SS, Hall K, Stein CM. Oral erythromycin and the risk of sudden death from cardiac causes. N Engl J Med. 2004;351(11):1089–1096.
6. Honein MA, Paulozzi LJ, Himelright IM, et al. Infantile hypertrophic pyloric stenosis after pertussis prophylaxis with erythromycin: a case review and cohort study. Lancet. 1999;354(9196):2101–2105.
7. Centers for Disease Control and Prevention. Pertussis: treatment and postexposure prophylaxis guidance. https://www.cdc.gov/pertussis/

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