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. |
CYP 3A: cytochrome P450 3A; HCV: hepatitis C virus; HIV: human immunodeficiency virus; INR: international normalized ratio; NSAIDs: nonsteroidal antiinflammatory drugs; P-gp: P-glycoprotein efflux membrane transporters.
* 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 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.Do you want to add Medilib to your home screen?