Clarithromycin vs. Azithromycin: Which Antibiotic Works Better for Your Infection?

When your doctor prescribes an antibiotic for a stubborn infection, you might not think twice about the name-until you start comparing clarithromycin and azithromycin. Both are macrolide antibiotics, both are used for respiratory and skin infections, and both come in pill form. But they’re not the same. One might clear your sinus infection faster. The other might cause less stomach upset. Choosing between them isn’t about which is "better" overall-it’s about which fits your body, your infection, and your lifestyle.

How Clarithromycin and Azithromycin Work

Both clarithromycin and azithromycin belong to the macrolide class of antibiotics. They stop bacteria from making proteins they need to survive and multiply. Think of it like cutting off the factory lines that produce weapons for an invading army. Without those proteins, the bacteria can’t spread, and your immune system can clean up the rest.

Clarithromycin, sold under brand names like Biaxin, was approved in the U.S. in 1991. It’s a slightly modified version of erythromycin, designed to be more stable in the stomach and more effective against certain bacteria. Azithromycin, sold as Zithromax or Z-Pak, came out in 1992 and was engineered to last longer in the body. That’s why you often take azithromycin for just five days-or even just one big dose-while clarithromycin usually requires twice-daily pills for 7 to 14 days.

What Each Antibiotic Treats

There’s overlap in what they treat, but the differences matter.

• Clarithromycin is often used for sinus infections, bronchitis, pneumonia, and skin infections. It’s also a key part of the triple therapy used to kill H. pylori, the bacteria that cause stomach ulcers. In fact, the CDC recommends clarithromycin as a first-line option for this specific use.
• Azithromycin is the go-to for chlamydia, gonorrhea (when combined with ceftriaxone), and some ear infections in kids. It’s also preferred for walking pneumonia caused by Mycoplasma pneumoniae. Because of its long half-life, it’s often used in single-dose regimens for sexually transmitted infections, making it easier for patients to complete treatment.

For strep throat, both work-but azithromycin is sometimes chosen for people who can’t take penicillin and need a shorter course. For chronic bronchitis flare-ups, clarithromycin has shown better results in some studies because it stays active in lung tissue longer.

Dosing: Convenience vs. Consistency

One of the biggest practical differences is how you take them.

Azithromycin’s magic trick is its long half-life-68 hours. That means after you take a dose, it keeps working in your body for days. A typical Z-Pak is: one 500 mg pill on day one, then 250 mg daily for four more days. Some doctors even prescribe a single 1-gram dose for chlamydia.

Clarithromycin? You take 250 to 500 mg twice a day, every 12 hours, for 7 to 14 days. Missing a dose can drop your blood levels too low, letting bacteria bounce back. If you’re the type who forgets to take pills, azithromycin’s simpler schedule might be the better fit.

But here’s the catch: azithromycin’s long stay in your system means it can interact with more drugs over a longer window. Clarithromycin, while requiring more pills, clears out faster and has fewer lingering interactions.

Side Effects: Stomach Trouble and More

Both can cause nausea, diarrhea, and stomach cramps. But studies show azithromycin causes less gastrointestinal upset overall. One 2020 meta-analysis in the Journal of Antimicrobial Chemotherapy found that 18% of people on clarithromycin reported moderate to severe stomach issues, compared to 11% on azithromycin.

Clarithromycin has a higher risk of interacting with other medications. It blocks an enzyme in your liver called CYP3A4, which breaks down many common drugs. That means if you’re on statins like simvastatin, blood thinners like warfarin, or certain heart rhythm meds, clarithromycin can cause dangerous buildup. Azithromycin doesn’t do this as strongly-making it safer for people on multiple prescriptions.

Both can rarely cause heart rhythm problems, especially in older adults or those with existing heart conditions. The FDA issued a warning in 2013 about azithromycin and QT prolongation, but the actual risk is low for healthy people. Clarithromycin carries a similar warning, but it’s more likely to cause liver enzyme spikes.

Cost and Accessibility

Generic versions of both are widely available and cheap. In the U.S., a 5-day course of azithromycin can cost as little as $10 at Walmart or CVS with a GoodRx coupon. Clarithromycin isn’t much more-usually $15 to $25 for a 10-day course.

Insurance plans often favor azithromycin because of its shorter course and lower risk of drug interactions. Some formularies list it as preferred for community-acquired pneumonia. Clarithromycin might require prior authorization if you’re on other meds.

When One Wins Over the Other

There’s no universal winner. It depends on your situation.

Choose azithromycin if:

• You have chlamydia or gonorrhea
• You need a simple, short course (like a Z-Pak for bronchitis)
• You’re on other medications that interact with clarithromycin
• You have trouble remembering to take pills twice a day

Choose clarithromycin if:

• You have a stomach ulcer caused by H. pylori
• You have a stubborn sinus infection that didn’t respond to other antibiotics
• Your doctor suspects a more resistant strain of bacteria
• You’re not taking other drugs that could interact dangerously

For pneumonia, some guidelines now prefer azithromycin because it covers atypical bacteria like Mycoplasma and Chlamydophila. But for severe pneumonia in older adults, clarithromycin might be preferred because it penetrates lung tissue more deeply.

What Patients Say

Real-world feedback backs up the data. On patient review sites, azithromycin gets higher ratings for ease of use. One 62-year-old woman wrote: "I took Z-Pak for my cough. One pill a day for five days. I didn’t miss a single one. Clarithromycin? I’d forget the afternoon dose every time. And my stomach hated it."

But another patient with a recurring sinus infection said: "I took azithromycin twice. It didn’t touch my infection. My doctor switched me to clarithromycin-and within three days, I could breathe again. It worked where the other didn’t."

That’s the point: bacteria adapt. Your body reacts differently. What worked for your neighbor might not work for you.

Resistance and Long-Term Use

Overuse of any antibiotic leads to resistance. Macrolides aren’t immune. In fact, resistance to azithromycin is rising faster in some regions, especially for strep throat and gonorrhea. The CDC reports that over 20% of gonorrhea strains in the U.S. are now resistant to azithromycin, which is why it’s now always given with another antibiotic.

Clarithromycin resistance is also growing, especially in H. pylori. That’s why triple therapy now often includes a proton pump inhibitor and another antibiotic like metronidazole. If clarithromycin fails, your doctor won’t try it again.

The bottom line: neither drug is a magic bullet. They’re tools. And like any tool, their effectiveness depends on how-and when-you use them.

What to Ask Your Doctor

Before you take either, ask:

• What infection am I treating, and which bacteria is most likely causing it?
• Do I have any other health conditions or medications that could interact with this drug?
• Is there a reason you’re choosing this one over the other?
• What should I do if I don’t feel better in 3 to 4 days?

Don’t assume one is "stronger" or "better." The best antibiotic is the one that matches your infection, your body, and your life.

Next Steps

If your doctor prescribes clarithromycin or azithromycin, take it exactly as directed. Keep a list of all your other medications and supplements to avoid dangerous interactions. If you’ve had side effects from antibiotics before, tell your doctor. They can choose one that’s less likely to cause problems.

Antibiotics aren’t interchangeable. They’re targeted weapons. The right one, at the right time, makes all the difference. Don’t guess. Ask questions. And trust your doctor’s choice-not the internet.