Examples of some drug interactions with systemic glucocorticoids*^[1-3]

Interacting drug classes	Examples	Effect	Comment
Co-administration of drugs that are inducers of CYP 3A and/or P-gp may DECREASE glucocorticoid exposure and efficacy^¶
Antiseizure	Carbamazepine, fosphenytoin, phenobarbital, phenytoin, primidone	Reduced glucocorticoid effects due to increased clearance. Maximal effect occurs approximately 2 weeks after initiating a CYP inducer and can persist for 2 or more weeks following discontinuation of a CYP inducer.	Dose alteration of methylprednisolone may be needed. Prednisone and prednisolone are affected considerably less by this interaction.
Antimicrobials and antivirals (HIV)	Efavirenz, etravirine, nafcillin, rifampin, rifabutin, rifapentine		Rifampin can decrease methylprednisolone, prednisone, and prednisolone exposure. Efavirenz, etravirine, nafcillin, rifabutin, and rifapentine can decrease methylprednisolone exposure but are not likely to interact with prednisone or prednisolone.
Co-administration of drugs that are inhibitors of CYP 3A and/or P-gp may INCREASE glucocorticoid exposure and toxicity^¶
Antimicrobials	Clarithromycin, telithromycin	Increased glucocorticoid effects due to decreased clearance.	Methylprednisolone and dexamethasone clearance may be reduced by approximately 30 to 50%. Monitor biomarkers for exaggerated glucocorticoid effects.^Δ Dose alteration of methylprednisolone and dexamethasone may be needed. Interaction with prednisone or prednisolone appears less likely. However, in some pharmacokinetic studies, increased glucocorticoid exposure was observed. Monitoring for increased glucocorticoid effects is suggested.^Δ
Antifungal	Itraconazole, ketoconazole, posaconazole, voriconazole
Antivirals (HIV and HCV)	Atazanavir, darunavir, ritonavir, others
Estrogens	Estrogen-containing oral contraceptives, conjugated estrogens, esterified estrogens, others	Estrogens can significantly increase glucocorticoid exposure and effects. This may be due to alteration of steroid metabolism and protein binding.	Monitor biomarkers for exaggerated glucocorticoid effects.^Δ Dose alteration of glucocorticoid may be needed.
Multiple effects or additive toxicities
Anticoagulant, oral	Warfarin	Glucocorticoids may increase anticoagulant effect of warfarin.	Most patients stabilized on warfarin will require a significant alteration in warfarin dose within 3 to 7 days after initiating glucocorticoid. Monitor INR closely to determine need for dose adjustment.
Antidiabetics	Dulaglutide, glipizide, insulins, liraglutide, metformin, pioglitazone, semaglutide, sitagliptin, others	Glucose dysregulation.	Closely monitor blood glucose in patients at risk for glycemic dysregulation. Adjust therapy as needed.
Diuretics	Furosemide, hydrochlorothiazide, others	Glucocorticoids may potentiate potassium wasting effect.	Evaluate serum potassium levels to determine whether alteration of diuretic therapy and/or potassium supplementation is needed.
Fluoroquinolone	Ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin, others	Increased risk of tendinopathy.	Monitor for new-onset tendon and/or joint pain. Use combination cautiously in older adults and children.
NSAIDs	Ibuprofen, indomethacin, ketorolac, ketoprofen, naproxen, others	Increased risk of peptic ulcer disease.	Refer to UpToDate topic on major side effects of systemic glucocorticoids.

This table does not show all possible interactions. For additional interactions refer to appropriate UpToDate clinical topics and Lexicomp drug interactions program included with UpToDate.

CYP 3A: cytochrome P450 3A; P-gp: P-glycoprotein efflux membrane transporters; HIV: human immunodeficiency virus; HCV: hepatitis C virus; INR: international normalized ratio; NSAIDs: nonsteroidal antiinflammatory drugs.

* The classification of effects on drug metabolism are based upon US Food and Drug Administration (FDA) guidance.^[4,5] Other sources may use a different classification system resulting in some agents being classified differently. Weak inhibitor effects are not listed. Clinically significant interactions can occasionally occur due to weak inhibitors, particularly if the target drug has a narrow therapeutic margin. Refer to the Lexicomp drug interactions program for a full review of potential interactions.

¶ For a list of CYP 3A inducers/inhibitors (which include CYP 3A4 metabolism effects), refer to UpToDate content including a separate table that lists cytochrome P450 3A inhibitors and inducers.

Δ Biomarkers of glucocorticoid toxicity may include neuropsychiatric reactions, fluid and electrolyte disturbances, hypertension, and/or hyperglycemia.

References:

Czock D, Keller F, Rasche FM, Haussler U. Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids. Clin Pharmacokinet 2005; 44:61.
Clinical Manual of Drug Interaction Principles for Medical Practice, Wynn GH, Oesterhelf JR, Cozza KL, Armstrong SC (Eds), APA Publishing, Washington DC 2019.
US Food and Drug Administration. Clinical drug interaction studies — Cytochrome P450 enzyme- and transporter-mediated drug interactions guidance for industry, January 2020. Available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/clinical-drug-interaction-studies-cytochrome-p450-enzyme-and-transporter-mediated-drug-interactions (Accessed on June 5, 2020).
US Food & Drug Administration. Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers. Available at: https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers (Accessed on February 11, 2020).

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Examples of some drug interactions with systemic glucocorticoids*[1-3]

Examples of some drug interactions with systemic glucocorticoids*^[1-3]