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5 Azithromycin Interactions You Should Know About

Daisy Chau, PharmDAlyssa Billingsley, PharmD
Updated on June 13, 2023

Key takeaways:

  • Azithromycin (Zithromax) is an antibiotic used to treat bacterial infections. It’s often referred to as a “Z-Pak.” 

  • Azithromycin doesn’t have as many interactions as some other antibiotics. But it still can interact with medications like amiodarone (Pacerone) and atorvastatin (Lipitor). This can cause dangerous heart and muscle problems, respectively.

  • Before starting azithromycin, make sure your healthcare provider and pharmacist have an updated list of medications you’re taking. This will help them screen for interactions up front.

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Azithromycin (Zithromax) is a common antibiotic used to treat bacterial infections. It’s a widely available resource for conditions like pneumonia, chlamydia, and strep throat. It’s typically taken short-term, and it can be used by both kids and adults. Many people know it informally as a “Z-Pak,” which is one of the available formulations of azithromycin.

As a macrolide antibiotic, azithromycin is in the same family as medications like clarithromycin and erythromycin. Yet, azithromycin is one of the more prescribed antibiotics in the U.S. since it’s considered a safer option than some of its relatives.

Azithromycin also has fewer drug interactions than other macrolide antibiotics. But it still has some important ones to be aware of. In fact, some interactions can even lead to dangerous heart and muscle problems. So before you head to the pharmacy to fill your new prescription, it’s a good idea to keep certain azithromycin interactions in mind.

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1. Antiarrhythmics

Antiarrhythmics are medications that treat abnormal heart rhythms. Common examples are amiodarone (Pacerone), quinidine, and sotalol (Betapace). They work by slowing down electrical activity in your heart to stabilize its rhythm.

While they’re beneficial medications for many people, many antiarrhythmics may cause a serious side effect called QT prolongation. It’s a type of disruption in your heart’s electrical activity that can increase the risk of developing a dangerous irregular heartbeat

Azithromycin also carries a risk of QT prolongation. In fact, in 2013, the FDA released a safety warning about how taking azithromycin may lead to life-threatening heart rhythm problems. This risk is higher in older adults and people with a history of heart rhythm problems.

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Combining medications that affect your heart rhythm also worsens this risk. Taking antiarrhythmics and azithromycin together is no exception. Depending on your risk factors for these heart-related issues, your healthcare provider will help you weigh the pros and cons of combining these medications. If you do take them together, be on the lookout for symptoms like lightheadedness, heart palpitations, and blurred vision. Make sure to report these symptoms to your healthcare provider.

2. Most antacids

Antacids are medications that treat heartburn. Not all antacids need to be avoided with azithromycin, but many can interact with it. This is partly due to antacids binding to azithromycin when they’re in your gut at the same time. This can affect how much of your azithromycin dose is absorbed, which can make it less effective.

You should watch out for antacids that contain salts of aluminum, magnesium, and/or calcium. Common examples include Rolaids (calcium carbonate/magnesium hydroxide) and Milk of Magnesia (magnesium hydroxide).

As a precaution, avoid taking these antacids and azithromycin at the same time. If you still need to take one of these antacids, ask your pharmacist how to separate the two medications. This helps make sure azithromycin continues to fight your infection.

3. Statins

Statins are common medications used to treat high cholesterol and high triglycerides (a type of fat in your blood). They also help reduce the risk of heart attacks and strokes for certain people. Top examples are atorvastatin (Lipitor) and simvastatin (Zocor). 

Although rare, statins may cause a serious side effect called rhabdomyolysis. This is a dangerous condition that causes intense muscle damage. It can also lead to more serious problems in other parts of the body, like the kidneys and heart. Symptoms include muscle pain, dark colored urine, and muscle weakness.

Azithromycin is generally regarded as a safe macrolide antibiotic to take with a statin, but the combination may still worsen the risk of rhabdomyolysis. Ask your healthcare provider how to best manage this interaction. Depending on your risk factors, they may tell you to temporarily lower or stop your statin dose. They may also recommend taking a different antibiotic.

4. Warfarin

Warfarin (Coumadin, Jantoven) is a blood thinner used to treat and prevent blood clots. There’s a delicate balance between having too much and too little warfarin in your body. Too much warfarin can increase your risk of easy bleeding or bruising. What’s more, certain medications and foods can affect this balance.

Studies have shown mixed results on whether or not there’s an interaction between azithromycin and warfarin. There have been case reports suggesting that taking azithromycin may lead to a potential increased risk of bleeding in people taking warfarin. But a different study found that there was no interaction between the two medications. 

Even though the data is conflicting, know that azithromycin could enhance warfarin’s effects. This could raise the risk of potentially dangerous bleeding or bruising. To be safe, your healthcare provider may want to monitor your blood work more closely while you’re taking azithromycin.

5. Nelfinavir

Nelfinavir (Viracept) is an antiviral medication that’s used to treat HIV. It’s less commonly prescribed than other HIV medications, but it’s still available for use.

There’s not much data, but nelfinavir may increase the amount of azithromycin that your body absorbs into its bloodstream. This can raise the risk of possible azithromycin side effects, like liver and hearing problems.

If you’re taking nelfinavir, your healthcare provider will likely check your blood work for any changes while you’re taking azithromycin.

Can you take azithromycin and prednisone together?

Yes, it’s safe to take azithromycin and prednisone together. Prednisone is a common corticosteroid medication that’s available with a prescription from your healthcare provider. 

In fact, many situations call for both an antibiotic and a corticosteroid. This is especially true for respiratory and sinus infections. The antibiotic fights bacteria causing an infection, and the steroid helps keep inflammation (swelling) at bay.

Can you take ibuprofen or Tylenol with azithromycin?

Yes, it’s safe to take azithromycin with ibuprofen (Advil, Motrin) or acetaminophen (Tylenol). While these over-the-counter (OTC) pain relievers won’t treat your infection, they can help temporarily relieve pain and fever you may be experiencing. You can take one or the other or alternate between them while you’re taking azithromycin.

However, before you purchase a bottle of ibuprofen or acetaminophen, make sure to check in with your healthcare provider or pharmacist. Interactions aside, both medications can be no-go’s for people with certain medical conditions.

When should you contact my healthcare provider about an azithromycin interaction?

Azithromycin has fewer drug interactions than other macrolide antibiotics. But these interactions can still cause serious side effects, like heart rhythm problems or muscle damage. In rare cases, these can be life-threatening. If you start experiencing heart palpitations, intense muscle pain, or dark-colored urine, seek medical help right away. 

Also, the list above doesn’t include all possible interactions. Make sure your healthcare provider and pharmacist have an updated list of all medications you take. This list should include any prescription or OTC medications, supplements, and vitamins you’re taking. This will help prevent any unwanted interactions from happening in the first place.

The bottom line

Azithromycin has fewer interactions than other macrolide antibiotics, but some are still possible. It can interact with medications like antiarrhythmics, many antacids, and statins. Before starting azithromycin, talk to your healthcare provider and pharmacist about all medications and supplements you’re taking. This will help them prevent interactions before they happen.

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Why trust our experts?

Daisy Chau, PharmD
Daisy Chau, PharmD, is the drug information pharmacist manager at GoodRx. She is licensed in California and has more than 6 years of experience working as a pharmacist in drug information.
Joshua Murdock, PharmD, BCBBS
Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.
Alyssa Billingsley, PharmD
Alyssa Billingsley, PharmD, is the director of pharmacy content for GoodRx. She has over a decade of experience as a pharmacist and has worked in clinical, academic, and administrative roles.

References

Amsden, G. W., et al. (2000). A study of the pharmacokinetics of azithromycin and nelfinavir when coadministered in healthy volunteers. Journal of Clinical Pharmacology. 

A-S Medication Solutions. (2023). AZITHROMYCIN- azithromycin tablet, film coated [package insert]

View All References (11)

Beckey, N. P., et al. (2000). Retrospective evaluation of a potential interaction between azithromycine and warfarin in patients stabilized on warfarin. Pharmacotherapy. 

Farzam, K., et al. (2023). QT prolonging drugs. StatPearls. 

Food and Drug Administration. (2018). FDA Drug Safety Communication: Azithromycin (Zithromax or Zmax) and the risk of potentially fatal heart rhythms

MedlinePlus. (2022). Azithromycin

Mellal, A. A., et al. (2019). The clinical significance of statins-macrolides interaction: comprehensive review of in vivo studies, case reports, and population studies. Therapeutics and Clinical Risk Management. 

Salisbury, B. H., et al. (2022). Antacids. StatPearls. 

Samarendra, P., et al. (2001). QT prolongation associated with azithromycin/amiodarone combination. Pacing and Clinical Electrophysiology.  

Sandman, Z., et al. (2023). Azithromycin. StatPearls. 

Shrader, S. P., et al. (2004). Azithromycin and warfarin interaction. Pharmacotherapy. 

Strandell, J., et al. (2009). Rhabdomyolysis a result of azithromycin and statins: An unrecognized interaction. British Journal of Clinical Pharmacology.  

Westphal, J. F. (2000). Macrolide – induced clinically relevant drug interactions with cytochrome P-450A (CYP) 3A4: An update focused on clarithromycin, azithromycin and dirithromycin. British Journal of Clinical Pharmacology. 

GoodRx Health has strict sourcing policies and relies on primary sources such as medical organizations, governmental agencies, academic institutions, and peer-reviewed scientific journals. Learn more about how we ensure our content is accurate, thorough, and unbiased by reading our editorial guidelines.

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