Amoxicillin/Clavulanate Drug Interactions: What You Need to Know

Amoxicillin/Clavulanate (brand name Augmentin) is a widely prescribed antibiotic used to treat bacterial infections like sinusitis, ear infections, and skin infections. While it's generally safe, it can interact with certain medications, supplements, and even foods — potentially making those drugs less effective or increasing the risk of side effects.

This guide covers the most important Amoxicillin/Clavulanate drug interactions so you know what to tell your doctor before starting treatment.

How Drug Interactions Work

A drug interaction happens when one substance changes the way another substance works in your body. With Amoxicillin/Clavulanate, interactions can happen in a few ways:

• Increased drug levels — another medication may slow down how quickly your body clears Amoxicillin, leading to higher-than-expected levels and greater risk of side effects
• Decreased effectiveness — Amoxicillin/Clavulanate may reduce the effectiveness of another medication, or vice versa
• Additive side effects — combining certain drugs can increase the risk of shared side effects like bleeding, liver damage, or GI problems

Not all interactions are dangerous, but your doctor needs to know about everything you're taking to prescribe safely.

Medications That Interact with Amoxicillin/Clavulanate

Major Interactions

These interactions carry significant risk and require careful monitoring or dose adjustments:

• Warfarin (Coumadin) — Amoxicillin/Clavulanate can increase the blood-thinning effects of Warfarin, raising your INR (a measure of blood clotting) and increasing bleeding risk. If you take Warfarin, your doctor may need to check your INR more frequently while you're on the antibiotic.
• Methotrexate (Trexall, Otrexup) — Amoxicillin can reduce the kidney's ability to clear Methotrexate from your body, leading to dangerously high Methotrexate levels. This can cause severe side effects including bone marrow suppression and liver toxicity. Close monitoring is essential.
• Mycophenolate (CellCept, Myfortic) — Amoxicillin/Clavulanate can reduce Mycophenolate blood levels, potentially making this immunosuppressant less effective. This is particularly concerning for organ transplant patients who depend on Mycophenolate to prevent rejection.

Moderate Interactions

• Probenecid (Benemid) — Probenecid slows kidney excretion of Amoxicillin, resulting in higher and longer-lasting Amoxicillin blood levels. While this is sometimes done intentionally, it increases the risk of side effects.
• Allopurinol (Zyloprim, Aloprim) — Taking Allopurinol with Amoxicillin-containing antibiotics increases the risk of developing a skin rash. This doesn't mean you can't take both, but you and your doctor should be aware of the risk.
• Oral contraceptives (birth control pills) — There is a historical concern that antibiotics like Amoxicillin may reduce the effectiveness of hormonal birth control. While current evidence suggests this risk is low, many providers still recommend using a backup method of contraception during antibiotic treatment and for 7 days after.

Supplements and Over-the-Counter Medications to Watch

Some supplements and OTC products can also interact with Amoxicillin/Clavulanate:

• Probiotics — While probiotics are often recommended alongside antibiotics to support gut health, take them at least 2 hours apart from your Amoxicillin/Clavulanate dose. Taking them at the same time reduces the effectiveness of both.
• Antacids — Antacids containing aluminum or magnesium may slightly reduce absorption of Amoxicillin. If you take antacids, space them at least 2 hours from your antibiotic dose.
• Blood thinners (aspirin, NSAIDs) — While not a direct drug interaction, combining Amoxicillin/Clavulanate with aspirin or NSAIDs like ibuprofen (Advil) or naproxen (Aleve) while also taking Warfarin can further increase bleeding risk.
• Iron supplements — Iron can reduce absorption of some antibiotics. While the effect on Amoxicillin is minimal, spacing doses by 2 hours is a safe practice.

Food and Drink Interactions

Amoxicillin/Clavulanate has few significant food interactions, which is one reason it's so widely prescribed. However, there are a couple of things to know:

• Take with food — Unlike some antibiotics that should be taken on an empty stomach, Amoxicillin/Clavulanate should be taken with a meal or snack. Food improves absorption and significantly reduces gastrointestinal side effects like nausea and diarrhea.
• Alcohol — There is no direct interaction between Amoxicillin/Clavulanate and alcohol. However, drinking while fighting an infection can impair your immune system, dehydrate you, and worsen side effects like nausea and diarrhea. It's best to limit or avoid alcohol while on antibiotics.
• Grapefruit — Unlike many medications, Amoxicillin/Clavulanate is not significantly affected by grapefruit juice.

What to Tell Your Doctor

Before starting Amoxicillin/Clavulanate, make sure your doctor and pharmacist know about:

1. All prescription medications you're currently taking — especially Warfarin, Methotrexate, Mycophenolate, Probenecid, and Allopurinol
2. Over-the-counter medications — including aspirin, ibuprofen, naproxen, and antacids
3. Vitamins and supplements — including iron, probiotics, and herbal products
4. Birth control method — so your provider can advise on backup contraception if needed
5. Drug allergies — especially to penicillin, cephalosporins, or any other antibiotics
6. Kidney or liver problems — as these affect how your body processes the medication
7. Pregnancy or breastfeeding status — Amoxicillin/Clavulanate is generally considered safe (Category B), but your doctor should know

If you're seeing a new doctor or using telehealth, bring a current medication list. Many pharmacies can print one for you.

Final Thoughts

Amoxicillin/Clavulanate has fewer drug interactions than many antibiotics, but the interactions it does have — particularly with Warfarin and Methotrexate — can be serious. The best way to stay safe is to give your doctor and pharmacist a complete picture of everything you take.

For more information about this medication, read our guides on what Amoxicillin/Clavulanate is and how to take it and side effects to watch for. If you need help finding this medication, Medfinder can help you locate it at a pharmacy near you.