Hydrocortisone Injection and Saiboku-To: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Hydrocortisone Injection
Saiboku-To
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
Enhanced and prolonged effect of corticosteroids
Interaction Deep Dive
Saiboku-To components glycyrrhetinic acid and glycyrrhizin inhibit the metabolism of corticosteroids, delaying their excretion and prolonging their activity. In healthy subjects, area under the curve (AUC) of prednisolone was increased and clearance of prednisolone was decreased with concomitant use of Saiboku-To7 and licorice component glycyrrhizin 21. Patients taking Saiboku-To and corticosteroids concomitantly should be monitored closely for corticosteroid excess.
Why it happens (mechanism)
Inhibition of corticosteroid metabolism
Literature reports
6 reports — tap to read
a) In an open, cross-over study of 9 subjects receiving a single oral dose of 10 mg prednisolone, Saiboku-To given three times daily for 3 days increased the area under the curve (AUC) of prednisolone from 0.92 milligrams/hour/liter (mg/hour/L) to 1.06 mg/hour/L (p less than 0.01). Clearance of prednisolone was reduced by Saiboku-To from 10.9 +/- 0.9 L/hour to 9.6 +/- 1.1 L/hour (p less than 0.01). Subjects were nonsmokers, and were not taking any medication known to influence glucocorticoid hepatic metabolism or pharmacokinetics. The Saiboku-To preparation provided glycyrrhizin 63.5 mg daily. AUC ratio of prednisone to prednisolone decreased significantly (p less than 0.01), indicating inhibition of 11-beta-hydroxysteroid dehydrogenase 3.
b) Pharmacokinetics of prednisolone were significantly affected when glycyrrhizin 200 mg was administered intravenously (IV) with prednisolone hemisuccinate 0.096 milligrams/kilogram (mg/kg) IV in 6 healthy men. Total prednisolone concentration was increased at 6 and 8 hours and free prednisolone concentration was increased at 4, 6, and 8 hours after the prednisolone hemisuccinate infusion (p less than 0.05). Area under the curve (AUC) of free prednisolone increased from 126 +/- 10 micrograms/liter/hour (mcg/L/hour) to 199 +/- 24 mcg/L/hour (p less than 0.05). Clearance of free prednisolone decreased from 0.22 +/- 0.02 L/kg/hour to 0.38 +/- 0.05 L/kg/hour (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.
c) Oral glycyrrhizin significantly altered pharmacokinetics of prednisolone in 6 healthy men. Glycyrrhizin was administered as four 50 mg doses prior to intravenous administration of prednisolone hemisuccinate 0.096 mg/kg. Total prednisolone concentration was increased at 6 and 8 hours, and free prednisolone concentration was increased at 4, 6, and 8 hours post-prednisolone infusion (p less than 0.05). 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). Volume of distribution was not significantly altered, suggesting that oral glycyrrhizin increases prednisolone concentrations by inhibiting metabolism, not by affecting distribution 2.
d) In rats, glycyrrhizic acid and glycyrrhetinic acid inhibited 11 beta-dehydrogenase in a dose-dependent manner. Percent conversion of corticosterone to 11-dehydrocorticosterone was 51.7 +/- 1.5% in controls versus 43.2 +/- 2.3% (p less than 0.001) in rats receiving glycyrrhizic acid. While glycyrrhetinic acid inhibited the conversion in dose-dependent fashion, it required high concentrations to do so (0.0001 to 0.000001M) 4.
e) In male rats glycyrrhetinic acid 50 mg/100 grams body weight administered intramuscularly (IM) for 7 days, produced near complete inhibition of 5-beta reductase inhibition of cortisol (7.4 +/- 5.1%; p less than 0.001). Glycyrrhizin 50 mg/100 grams body weight was less effective, but still achieved statistical significance in 5-beta reductase inhibition of cortisol (75.0 +/- 4.4%; p less than 0.001) 5.
f) Glycyrrhizin has shown an enhancing effect on the immunosuppressive action of cortisone. In a study of immunized rats, glycyrrhizin administered as 15 mg/kg and 30 mg/kg suppressed the antibody titer to one-half and to one-fourth of the control, respectively. Glycyrrhizin had no effect on the antibody titer in adrenalectomized rats 6.
Common questions
Can I take Hydrocortisone Injection and Saiboku-To together?
Enhanced and prolonged effect of corticosteroids Always confirm with your pharmacist or prescriber before making any change.
How serious is the Hydrocortisone Injection and Saiboku-To 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.
Questions for your pharmacist
- Does my dose of Hydrocortisone Injection or Saiboku-To 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 (7)
- 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.
- Monder C, Stewart PM, & Lakshmi V: Licorice inhibits corticosteroid 11 beta-dehydrogenase of rat kidney and liver: in vivo and in vitro studies. Endocrinol 1989; 125:1046-1053.
- Tamura Y, Nishikawa T, Yamada K, et al: Effects of glycyrrhetinic acid and its derivatives of delta4-5-alpha- and 5-beta-reductase in rat liver. Arzneim Forsch/Drug Res 1979; 29:647-649.
- Kumagai A, Nanboshi M, Asanuma Y, et al: Effects of glycyrrhizin on thymolytic and immunosuppressive action of cortisone. Endocrinol Japon 1967; 14:39-42. PubMed
- Homma M, Oka K, Ikeshima K, et al: Different effects of traditional Chinese medicines containing similar herbal constituents on prednisolone pharmacokinetics. J Pharm Pharmacol 1994; 47(8):687-692. DOI
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