11 Prednisone Interactions and How to Manage Them

Prednisone (Rayos) is a prescription medication that comes as an oral tablet and liquid. It’s a common corticosteroid that works by calming down the immune system to lower inflammation. This can be especially helpful for managing allergic reactions and health conditions such as rheumatoid arthritis, multiple sclerosis, and more.

While prednisone is effective for these conditions, it can interact with certain medications and vaccines. These interactions may worsen certain side effects or compromise the effectiveness of your treatment. Below, we’ll discuss 11 common prednisone interactions and how to manage them.

1. Other immunosuppressants

In addition to corticosteroids like prednisone, several other immunosuppressants are available for use. Cyclosporine (Sandimmune) is one example. It helps prevent your body from rejecting a new organ after transplant surgery. But taking cyclosporine and prednisone together can raise the risk of side effects from both medications.

Other immunosuppressant interactions can weaken your immune system too much. Taking prednisone alongside immunosuppressants, such as chemotherapy, certain biologics, or biosimilars, can make it harder to fight off infections. Your healthcare professional (HCP) will likely monitor you frequently if you’re taking prednisone along with medications such as these. Keep an eye out for any symptoms of an infection, such as fever or cough, and report them to your HCP.

Good to know: Even though combining immunosuppressants may increase the risk of side effects, this type of combination treatment is common practice for certain health conditions. 

2. Diabetes medications

Diabetes medications manage blood glucose (sugar) levels. Metformin, semaglutide (Ozempic, Rybelsus), and sitagliptin (Januvia) are a few of the many options. But prednisone can actually raise your blood glucose — making diabetes medications less effective.

Prednisone contributes to insulin resistance. Insulin is a hormone made by the pancreas that keeps your blood glucose in check. If your blood glucose is too high, the pancreas releases insulin to lower it. But if you have insulin resistance, your body has trouble responding to insulin. This can cause hyperglycemia (high blood glucose). Frequent urination, feeling thirsty, and dry mouth are hallmark symptoms of hyperglycemia to watch for.

If you take or inject diabetes medications, your HCP may recommend checking your blood glucose at home more often while you’re taking prednisone. The dose(s) of your diabetes medication may also need to be increased.

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3. Warfarin

Warfarin (Coumadin, Jantoven) is a blood thinner that treats and prevents blood clots. It’s also known for having many drug interactions.

The potential interaction between prednisone and warfarin is unpredictable. In some cases, it can enhance warfarin’s effects and raise the risk of bleeding. Prednisone can also make warfarin less effective — raising the risk of blood clots.

We can’t predict how your body will respond to a potential interaction with warfarin. That’s why your HCP may perform blood tests to monitor warfarin more frequently while you’re taking prednisone.

Even without blood tests, you may be able to tell if a negative interaction is occurring between prednisone and warfarin. Any unusual bleeding, such as black or red stools or bloody vomit, should be reported immediately to your HCP. And if you experience any bleeding that doesn’t stop, you should seek emergency care by calling 911 or going to the nearest ER. Leg pain, sudden swelling, and shortness of breath are also important to watch for as these may indicate you have a blood clot. These symptoms also warrant emergency care.

4. NSAIDs

Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective medications for managing pain, inflammation, and fever. Aspirin, ibuprofen (Advil, Motrin), and naproxen (Aleve, Naprosyn) are a few examples. But these medications are well-known culprits for causing stomach upset. This can be an even bigger problem when they’re taken with prednisone.

Taking prednisone and an NSAID at the same time raises the risk of stomach-related side effects, including bleeding and ulcers. It’s best to avoid taking NSAIDs and prednisone together for this reason. Talk to your HCP about taking acetaminophen (Tylenol) for pain instead of an NSAID. Acetaminophen is easier on the stomach.

Good to know: There are some situations where you may need to take an NSAID and prednisone together. It’s ideal to take each medication with food to prevent stomach irritation, but this recommendation is even more important if you take them together. Your HCP may also recommend a medication such as omeprazole (Prilosec) for added stomach protection.

5. Loop diuretics like furosemide

Loop diuretics (“water pills”) remove extra fluid from the body, making them good treatment options for people with heart failure or high blood pressure. Furosemide (Lasix), bumetanide (Bumex), and torsemide are common loop diuretics.

However, loop diuretics can cause hypokalemia (low potassium). Prednisone can also cause hypokalemia. Taking prednisone and loop diuretics at the same time can raise your risk of experiencing this side effect. Symptoms such as muscle cramps, constipation, and abnormal heartbeats can range from mild to severe.

Low potassium levels aren’t always noticeable though. Your HCP may want to routinely monitor your potassium levels if you take both medications. If your reading becomes low, they may recommend a potassium supplement. Foods high in potassium, such as bananas, can also help raise your potassium levels.

6. Alcohol

Try your best to avoid combining alcohol and prednisone. Even though there isn’t a direct interaction, they can both suppress the immune system. This can make it easier to get an infection. It can also make it harder to fully recover if you’re currently sick.

This combination can also be a double whammy when it comes to side effects. Alcohol and prednisone share similar side effects, including headache, stomach irritation, and mood changes. Both alcohol and prednisone can also weaken your bones with prolonged use, potentially causing osteoporosis.

7. Medications that impact prednisone’s effectiveness, like phenytoin

Certain medications can speed up prednisone’s breakdown (metabolism) in your body. These interactions can make prednisone less effective. Anti-seizure medications, such as phenytoin (Dilantin, Phenytek), carbamazepine (Tegretol), and phenobarbital, are all common offenders.

If you’re taking one or more of these medications, your HCP may raise your prednisone dose. This will help you experience the full benefits of your prescription.

8. Medications that worsen the risk for prednisone side effects, like ketoconazole

Medications such as ketoconazole can make prednisone last longer in your body. They do this by slowing down its metabolism. This raises the risk of prednisone side effects, such as insomnia, mood changes, and elevated blood pressure.

Other medications that cause this interaction include:

• Itraconazole

• Fluconazole (Diflucan)

• Verapamil

• Medications containing ritonavir, such as Paxlovid and certain HIV medications

If you’re taking any of these medications, your HCP may lower your prednisone dose in an attempt to prevent side effects.

9. Certain vaccines

Vaccines protect you from many diseases. But prednisone may interfere with some of them — especially if you’re taking a high dose.

Live vaccines, such as MMR (measles, mumps, and rubella), are the main suspects to watch for. If you’re taking at least 20 mg of prednisone per day for 14 days or more, it’s a good idea to temporarily avoid live vaccines. This helps prevent infection since live vaccines contain a weakened form of a virus. Your HCP will likely recommend waiting at least 1 month after stopping prednisone to get a live vaccine.

Good to know: These vaccination restrictions don't typically apply to short courses and/or doses of prednisone below 20 mg.

10. Certain antibiotics

It’s common to leave a medical office with a prescription in hand for both prednisone and an antibiotic. But in limited cases, prednisone may interact with your antibiotic. For instance, rifampin (Rifadin) can make prednisone less effective. Your HCP may raise your prednisone dose if you’re taking these medications together.

Other antibiotics, such as clarithromycin and erythromycin, may cause prednisone levels to build up in your body. Your HCP may lower your prednisone dose if you’re taking it with one of these antibiotics to prevent added side effects.

What’s more, taking prednisone with fluoroquinolone antibiotics, such as levofloxacin and ciprofloxacin (Cipro), can raise the risk of tendon problems. This includes tendon tears, which can be painful. That’s why fluoroquinolones are typically reserved for when other antibiotics don't work. Fluoroquinolones even carry a boxed warning — the FDA’s most serious medication warning — about the risk of tendon problems.

If you need to take prednisone and a fluoroquinolone together, keep an eye out for any pain or swelling. Your HCP will likely recommend stopping the fluoroquinolone and switching to a different antibiotic if you experience any tendon problems.

11. ​​Bupropion

Bupropion (Wellbutrin XL, Wellbutrin SR) treats depression and helps people quit smoking. But it can also raise your risk of experiencing a seizure.

Corticosteroids can also raise your seizure risk. This interaction with bupropion can make it more likely for you to experience a seizure. Let your HCP know if you have a history of seizures before starting bupropion or prednisone.

Can you take Benadryl with prednisone?

Yes, it’s OK to take Benadryl (diphenhydramine) with prednisone. There isn’t an interaction. Benadryl is an antihistamine that treats allergies and cold symptoms. It can even work as a team with prednisone to manage allergies and infusion reactions.

When should I contact my healthcare professional about a prednisone interaction?

Try to be proactive. Keep an updated medication list handy so your HCP can check for prednisone interactions in advance. It’s ideal if they do this before you start taking prednisone.

Yet, interactions aren’t always preventable. Reach out to your HCP if you’re experiencing any new or worsening side effects after starting prednisone. In some cases, they could be related to a drug interaction. If your symptoms feel severe, it’s better to go to the nearest ER as soon as you can.

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Written by:

Jennifer Gershman, PharmD, CPh, PACS

Jennifer Gershman, PharmD, is a licensed pharmacist in Florida. She has worked in the pharmacy industry for more than 15 years and is currently a medical writer.

Edited by:

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.

Reviewed by:

Amy B. Gragnolati, PharmD, BCPS

Amy Gragnolati, PharmD, BCPS, is a pharmacy editor for GoodRx. Amy currently holds her pharmacist license in Georgia and California.

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