What You Need to Know About Depo-Medrol Drug Interactions

Depo-Medrol (Methylprednisolone Acetate) is an injectable corticosteroid used to treat inflammation from arthritis, allergies, skin conditions, and more. While it's generally safe when administered by a healthcare provider, it can interact with other medications, supplements, and even certain foods. These interactions can make Depo-Medrol less effective or increase the risk of side effects.

This guide covers the most important drug interactions to know about before your next Depo-Medrol injection.

How Drug Interactions Work With Depo-Medrol

Drug interactions happen in two main ways with corticosteroids like Depo-Medrol:

1. Other drugs change how Depo-Medrol is processed — Some medications speed up or slow down the enzymes in your liver that break down Methylprednisolone. This can make the steroid either less effective or more potent than intended.
2. Depo-Medrol changes how other drugs work — Corticosteroids can alter the effectiveness or side effect profile of medications you're already taking. For example, they raise blood sugar, which can interfere with diabetes medications.

Methylprednisolone is primarily metabolized by the liver enzyme CYP3A4. Drugs that inhibit or induce this enzyme can have significant effects on Methylprednisolone levels in your body.

Major Drug Interactions

These interactions are considered serious and may require dose adjustments, close monitoring, or avoidance:

CYP3A4 Inhibitors (Increase Depo-Medrol Levels)

These medications slow down the breakdown of Methylprednisolone, causing it to build up in your body and potentially increasing side effects:

• Ketoconazole (Nizoral) — An antifungal medication that strongly inhibits CYP3A4. Using it with Depo-Medrol can significantly increase steroid levels.
• Itraconazole (Sporanox) — Another antifungal with strong CYP3A4 inhibition.
• Ritonavir (Norvir) — An HIV protease inhibitor that powerfully inhibits CYP3A4. Even a single Depo-Medrol injection can lead to prolonged steroid effects when combined with Ritonavir.
• Cyclosporine (Sandimmune, Neoral) — Mutual inhibition of metabolism occurs, meaning both Cyclosporine and Methylprednisolone levels can increase, raising the risk of toxicity from both drugs.

CYP3A4 Inducers (Decrease Depo-Medrol Levels)

These medications speed up the breakdown of Methylprednisolone, making it less effective:

• Rifampin (Rifadin) — A tuberculosis medication that strongly induces CYP3A4. It can reduce the effectiveness of Depo-Medrol significantly.
• Phenytoin (Dilantin) — An anti-seizure medication that can lower Methylprednisolone levels.
• Phenobarbital — A barbiturate that induces liver enzymes and reduces corticosteroid effectiveness.
• Carbamazepine (Tegretol) — Another anti-seizure medication with CYP3A4 induction effects.

Other Major Interactions

• Live vaccines — Depo-Medrol suppresses the immune system. Receiving live or live-attenuated vaccines (such as MMR, varicella, or intranasal flu vaccine) while on immunosuppressive doses of corticosteroids can increase your risk of infection from the vaccine itself. Inactivated vaccines are generally safe but may be less effective.
• Aldesleukin (IL-2) (Proleukin) — Corticosteroids may reduce the effectiveness of this cancer immunotherapy drug.
• Mifepristone (Mifeprex, Korlym) — May reduce the effect of corticosteroids by blocking glucocorticoid receptors.
• Warfarin (Coumadin) and other anticoagulants — Corticosteroids can alter the anticoagulant effect, either increasing or decreasing it. If you take Warfarin, your doctor may need to check your INR more frequently after a Depo-Medrol injection.
• NSAIDs — Including Ibuprofen (Advil, Motrin), Naproxen (Aleve), Diclofenac (Voltaren), and Aspirin. Combining corticosteroids with NSAIDs significantly increases the risk of gastrointestinal bleeding and peptic ulcers.

Moderate Drug Interactions

These interactions may not be dangerous on their own but still warrant attention:

• Diabetes medications — Including Insulin, Metformin, Glipizide (Glucotrol), and Sitagliptin (Januvia). Corticosteroids raise blood sugar, which can make your diabetes medications less effective. Monitor blood sugar closely for 3-5 days after the injection.
• Diuretics — Including Furosemide (Lasix) and Hydrochlorothiazide (HCTZ). Both corticosteroids and diuretics can cause potassium loss, increasing the risk of hypokalemia (low potassium).
• Aspirin — Corticosteroids increase the clearance of Aspirin from the body, potentially reducing its effectiveness. If you take Aspirin for heart protection, discuss this with your doctor.
• Fluoroquinolone antibiotics — Including Ciprofloxacin (Cipro) and Levofloxacin (Levaquin). Both fluoroquinolones and corticosteroids increase the risk of tendon rupture, especially in patients over 60.
• Estrogens and oral contraceptives — May increase corticosteroid effects by slowing their metabolism.

Supplements and Over-the-Counter Medications to Watch

Don't forget about supplements and OTC products. These can interact with Depo-Medrol too:

• St. John's Wort — A popular herbal supplement for mood support. It induces CYP3A4 and can reduce the effectiveness of Methylprednisolone.
• Licorice root — Can enhance the effects of corticosteroids and worsen potassium loss.
• Over-the-counter NSAIDs — Ibuprofen (Advil, Motrin), Naproxen (Aleve), and Aspirin increase the risk of GI bleeding when combined with corticosteroids.
• Antacids — High doses of aluminum- or magnesium-based antacids may reduce absorption of oral corticosteroids (less relevant for injections but worth noting if you also take oral Prednisone or Medrol).

Food and Drink Interactions

Because Depo-Medrol is given by injection rather than taken by mouth, food interactions are minimal. However:

• Alcohol — May increase the risk of gastrointestinal irritation, especially if you also take NSAIDs. It's best to limit alcohol for 24-48 hours after an injection.
• Grapefruit juice — While grapefruit is a known CYP3A4 inhibitor for oral medications, its effect on injected Methylprednisolone is minimal. Still, if you consume large amounts of grapefruit regularly, mention it to your doctor.

What to Tell Your Doctor Before Your Injection

Before receiving a Depo-Medrol injection, make sure your doctor knows about:

• All prescription medications you're taking — especially blood thinners, seizure medications, antifungals, HIV medications, Cyclosporine, and diabetes medications.
• All over-the-counter medications — especially NSAIDs like Ibuprofen and Naproxen.
• All supplements and herbal products — especially St. John's Wort and licorice root.
• Any recent or planned vaccinations — especially live vaccines.
• Your alcohol consumption — especially if it's more than occasional.
• Any history of stomach ulcers or GI bleeding — corticosteroids plus NSAIDs significantly increase this risk.

Keeping an up-to-date medication list (including supplements) and bringing it to every appointment is one of the simplest and most effective ways to prevent drug interactions.

Final Thoughts

Depo-Medrol is a safe and effective medication for most people, but like any drug, it can interact with other things you take. The most important interactions involve liver enzyme inhibitors and inducers, blood thinners, NSAIDs, diabetes medications, and live vaccines. Being upfront with your doctor about everything you take — prescription, OTC, and supplements — is the best way to stay safe.

For more information about Depo-Medrol, including side effects, how it works, and how to find it in stock, explore our other guides. And if you're struggling to locate Depo-Medrol during the shortage, Medfinder can help.