Hydrocortisone and Licorice: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Hydrocortisone
Licorice
No brand names on record
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Increased risk of corticosteroid adverse effects
Interaction Deep Dive
Licorice component glycyrrhizine increased the area-under-the-curve (AUC) of prednisolone and decreased clearance in healthy subjects321. The activity of topically administered hydrocortisone was potentiated by glycyrrhetinic acid in healthy subjects 4. The glycyrrhetinic acid component of licorice is metabolized to 3-monoglucuronyl-glycyrrhetinic acid (3MGA), which inhibits 11-beta-hydroxysteroid dehydrogenase and reduces cortisol breakdown, resulting in a hypermineralocorticoid effect 56.
Why it happens (mechanism)
Inhibition of corticosteroid metabolism by licorice
Literature reports
3 reports — tap to read
a) Glycyrrhizin (licorice) significantly increased the area-under-the curve of free and total prednisolone in 6 healthy men. Subjects received glycyrrhizin 200 milligrams (mg) and prednisolone hemisuccinate 0.096 milligrams/kilogram (mg/kg) intravenously. Area-under-the curve (AUC) of free prednisolone increased (p less than 0.05) and clearance decreased (p less than 0.05). Total and free prednisolone concentration was increased at 6 and 8 hours after the prednisolone hemisuccinate infusion (p less than 0.05). Proposed mechanisms for the alteration of prednisolone pharmacokinetics by glycyrrhizin or its metabolites were (1) inhibition of protein binding, (2) inhibition of hydrolysis of prednisolone hemisuccinate to prednisolone, and (3) inhibition or metabolism of free prednisolone 1.
b) Oral glycyrrhizin significantly increased the area-under-the-curve (AUC) of prednisolone in 6 healthy men. Subjects received oral glycyrrhizin 200 milligrams (mg) prior to intravenous administration of prednisolone hemisuccinate 0.096 milligrams/kilogram (mg/kg). AUC of both total and free prednisolone increased significantly (p less than 0.05). Clearance of both total and free prednisolone decreased significantly (p less than 0.05). Total and free prednisolone concentration was increased at 6 and 8 hours post-prednisolone infusion (p less than 0.05). Volume of distribution was not significantly altered, suggesting that oral glycyrrhizin increases prednisolone concentrations by inhibiting metabolism, not by affecting distribution 2.
c) A licorice-containing herbal combination (Saiboku-to) significantly increased the area-under-the-curve (AUC) of prednisolone in an open, cross-over study of 9 subjects. Subjects received a single oral dose of prednisolone 10 milligrams (mg) and Saiboku-To, a formula of ten herbs including Glycyrrhiza glabra (licorice), three times daily for 3 days. The area under the curve (AUC) of prednisolone increased while the clearance decreased (p less than 0.01). The Saiboku-To preparation provided glycyrrhizin 63.5 mg daily. The AUC ratio of prednisone to prednisolone decreased significantly (p less than 0.01), indicating inhibition of 11-beta-hydroxysteroid dehydrogenase 3.
Common questions
Can I take Hydrocortisone and Licorice together?
Increased risk of corticosteroid adverse effects Always confirm with your pharmacist or prescriber before making any change.
How serious is the Hydrocortisone and Licorice interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Hydrocortisone or Licorice need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there anything you'd monitor while I'm on both?
References (6)
- Chen MF, Shimada F, Kato H, et al: Effect of glycyrrhizin on the pharmacokinetics of prednisolone following low dosage of prednisolone hemisuccinate. Endocrinol Japon 1990; 37:331-341. PubMed
- Chen MF, Shimada F, Kato H, et al: Effect of oral administration of glycyrrhizin on the pharmacokinetics of prednisolone. Endocrinol Japon 1991; 38:167-174. DOI
- Homma M, Oka K, Niitsuma T, et al: A novel 11-beta-hydroxysteroid dehydrogenase inhibitor contained in Saiboku-To, a herbal remedy for steroid-dependent bronchial asthma. J Pharm Pharmacol 1994; 46(4):305-309.
- Teelucksingh S, Mackie AD, Burt D, et al: Potentiation of hydrocortisone activity in skin by glycyrrhetinic acid. Lancet 1990; 335(8697):1060-1063. PubMed
- Kato H, Kanaoka M, Yano S, et al: 3-Monoglucuronyl-glycyrrhetinic acid is a major metabolite that causes licorice-induced pseudoaldosteronism. J Clin Endocrinol Metab 1995; 80(6):1929-1933. DOI
- Walker BR & Edwards CRW: Licorice-induced hypertension and syndromes of apparent mineralocorticoid excess. Endocrinol Metab Clin North Am 1994; 23:359-377. DOI
Keep reading about Hydrocortisone
Keep reading about Licorice
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Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
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