Corticosteroids/Selected CYP3A4 Inducers Interactions

This information is generalized and not intended as specific medical advice. Consult your healthcare professional before taking or discontinuing any drug or commencing any course of treatment.

Medical warning:

Moderate. These medicines may cause some risk when taken together. Contact your healthcare professional (e.g. doctor or pharmacist) for more information.

How the interaction occurs:

When these two medicines are taken together, your body may not process your corticosteroid properly. The corticosteroid may also change the amount of the hydantoin (e.g. phenytoin) in your body.

What might happen:

The beneficial effects of your corticosteroid may decrease.In some patients, the amount of phenytoin in the blood may increase. This may result in more side effects than normal. In other patients, the amount of phenytoin in the blood may decrease and it may not work as well.

What you should do about this interaction:

If you notice a change in your condition, contact your healthcare professionals (e.g. doctor or pharmacist). It may be necessary to adjust the dose of your medicine.It may be necessary to monitor your hydantoin blood levels more frequently.Your healthcare professionals may already be aware of this interaction and may be monitoring you for it. Do not start, stop, or change the dosage of either medicine before checking with them first.

  • 1.Werk EE Jr, Choi Y, Sholiton L, Olinger C, Haque N. Interference in the effect of dexamethasone by diphenylhydantoin. N Engl J Med 1969 Jul 3; 281(1):32-4.
  • 2.Jubiz W, Meikle AW, Levinson RA, Mizutani S, West CD, Tyler FH. Effect of diphenylhydantoin on the metabolism of dexamethasone. N Engl J Med 1970 Jul 2;283(1):11-4.
  • 3.Haque N, Thrasher K, Werk EE Jr, Knowles HC Jr, Sholiton LJ. Studies on dexamethasone metabolism in man: effect of diphenylhydantoin. J Clin Endocrinol Metab 1972 Jan;34(1):44-50.
  • 4.Stjernholm MR, Katz FH. Effects of diphenylhydantoin, phenobarbital, and diazepam on the metabolism of methylprednisolone and its sodium succinate. J Clin Endocrinol Metab 1975 Nov;41(5):887-93.
  • 5.Boylan JJ, Owen DS, Chin JB. Letter: Phenytoin interference with dexamethasone. JAMA 1976 Feb 23;235(8):803-4.
  • 6.Wassner SJ, Malekzadeh MH, Pennisi AJ, Ettenger RB, Uittenbogaart CH, Fine RN. Allograft survival in patients receiving anticonvulsant medications. Clin Nephrol 1977 Jul;8(1):293-7.
  • 7.McLelland J, Jack W. Phenytoin/dexamethasone interaction: A clinical problem. Lancet 1978 May 20;1(8073):1096-7.
  • 8.Lawson LA, Blouin RA, Smith RB, Rapp RP, Young AB. Phenytoin-dexamethasone interaction: a previously unreported observation. Surg Neurol 1981 Jul; 16(1):23-4.
  • 9.Frey FJ, Frey BM. Urinary 6 beta-hydroxyprednisolone excretion indicates enhanced prednisolone catabolism. J Lab Clin Med 1983 Apr;101(4):593-604.
  • 10.Frey BM, Frey FJ. Phenytoin modulates the pharmacokinetics of prednisolone and the pharmacodynamics of prednisolone as assessed by the inhibition of the mixed lymphocyte reaction in humans. Eur J Clin Invest 1984 Feb;14(1):1-6.
  • 11.Wong DD, Longenecker RG, Liepman M, Baker S, LaVergne M. Phenytoin-dexamethasone: a possible drug-drug interaction. JAMA 1985 Oct 18;254(15):2062-3.
  • 12.Keilholz U, Guthrie GP Jr. Adverse effect of phenytoin on mineralocorticoid replacement with fludrocortisone in adrenal insufficiency. Am J Med Sci 1986 Apr;291(4):280-3.
  • 13.Lackner TE. Interaction of dexamethasone with phenytoin. Pharmacotherapy 1991;11(4):344-7.
  • 14.Sato A, Katada S, Sato M, Kobayashi H. A case of polymyalgia rheumatica with improved steroid-responsibility after discontinuing carbamazepine. No To Shinkei 2004 Jan;56(1):61-3.
  • 15.Bartoszek M, Brenner AM, Szefler SJ. Prednisolone and methylprednisolone kinetics in children receiving anticonvulsant therapy. Clin Pharmacol Ther 1987 Oct;42(4):424-32.
  • 16.Olivesi A. Modified elimination of prednisolone in epileptic patients on carbamazepine monotherapy, and in women using low-dose oral contraceptives. Biomed Pharmacother 1986;40(8):301-8.
  • 17.Buffington GA, Dominguez JH, Piering WF, Hebert LA, Kauffman HM Jr, Lemann J Jr. Interaction of rifampin and glucocorticoids. Adverse effect on renal allograft function. JAMA 1976 Oct 25;236(17):1958-60.
  • 18.Hendrickse W, McKiernan J, Pickup M, Lowe J. Rifampicin-induced non-responsiveness to corticosteroid treatment in nephrotic syndrome. Br Med J 1979 Feb 3;1(6159):306.
  • 19.Kawai S. A comparative study of the accelerated metabolism of cortisol, prednisolone and dexamethasone in patients under rifampicin therapy. Nippon Naibunpi Gakkai Zasshi 1985 Mar 20;61(3):145-61.
  • 20.Edwards OM, Courtenay-Evans RJ, Galley JM, Hunter J, Tait AD. Changes in cortisol metabolism following rifampicin therapy. Lancet 1974 Sep 7; 2(7880):548-51.
  • 21.Gabrielsen J, Bendtsen A, Eriksen H, Andersen S. Methylprednisolone half-life during simultaneous barbiturate treatment and mechanical hyperventilation of neurosurgical patients. J Neurosurg 1985 Feb; 62(2):182-5.
  • 22.Kuntzman R, Jacobson M, Levin W, Conney AH. Stimulatory effect of N-phenylbarbital (phetharbital) on cortisol hydroxylation in man. Biochem Pharmacol 1968 Apr;17(4):565-71.
  • 23.Brooks SM, Werk EE, Ackerman SJ, Sullivan I, Thrasher K. Adverse effects of phenobarbital on corticosteroid metabolism in patients with bronchial asthma. N Engl J Med 1972 May 25;286(21):1125-8.
  • 24.Brooks PM, Buchanan WW, Grove M, Downie WW. Effects of enzyme induction on metabolism of prednisolone. Clinical and laboratory study. Ann Rheum Dis 1976 AUG;35(4):339-43.
  • 25.Gambertoglio J, Kapusnik J, Holford J, Nishikawa R, Hau T, Birnbaum J, Amend W Jr. Enhancement of prednisolone elimination by anticonvulsants in renal transplant recipients. Clin Pharmacol Ther 1982 Feb;31(2):228.
  • 26.Gambertoglio JG, Holford NH, Kapusnik JE, Nishikawa R, Saltiel M, Stanik-Lizak P, Birnbaum JL, Hau T, Amend WJ Jr. Disposition of total and unbound prednisolone in renal transplant patients receiving anticonvulsants. Kidney Int 1984 Jan;25(1):119-23.
  • 27.Hancock KW, Levell MJ. Primidone/dexamethasone interaction. Lancet 1978 Jul 8;2(8080):97-8.
  • 28.Young MC, Hughes IA. Loss of therapeutic control in congenital adrenal hyperplasia due to interaction between dexamethasone and primidone. Acta Paediatr Scand 1991 Jan;80(1):120-4.
  • 29.This information is based on an extract from the Certara Drug Interaction Database (DIDB) Platform, Copyright Certara 1999-2023..

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CONDITIONS OF USE: The information in this database is intended to supplement, not substitute for, the expertise and judgment of healthcare professionals. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for you or anyone else. A healthcare professional should be consulted before taking any drug, changing any diet or commencing or discontinuing any course of treatment.