Dexamethasone is in several references listed as a weak or as a strong inducer of CYP 3A4. It is also listed as an inducer of multiple other CYP enzymes. Although drug-drug interaction databases warn against the concomitant use of dexamethasone with substrates of CYP 3A4 due to possible induction of their metabolism by dexamethasone, clinical evidence of such interaction is sparse. The CYP 3A4 induction potential of dexamethasone is suggested to be dose-dependent, and the effect also seems to vary greatly between different individuals. In spite of being listed as a safe drug in acute porphyria, a possible porphyrinogenic potential of dexamethasone under some circumstances cannot be ruled out. Rise in endogenous glucose production by dexamethasone might theoretically be an anti-porphyrinogenic effect.

Dexamethasone is a potent anti-inflammatory 9-fluoro-glucocorticoid

Dexamethasone is used in the treatment of endocrine disorders, rheumatic disorders, collagen diseases, dermatologic diseases, allergic states, ophthalmic diseases, gastrointestinal diseases, respiratory diseases, hematologic disorders, neoplastic diseases, edematous states and cerebral edema. Route of administration depends on indication, may be taken orally or as injection. The glucocorticoid potency of dexamethasone is approximately equal to betamethasone. Dexamethasone has an elimination half-life of 3 to 5 hours. Dexamethasone binds to the glucocorticoid receptor and gives rise to endogenous glucose production. This may theoretically counteract possible porphyrinogenic pharmacokinetic effects, but the clinical outcome of this effect needs to be further evaluated.

Dexamethasone is by several references and in drug-drug interaction databases listed as a substrate and an inducer of CYP 1A1, 1A2, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 3A4, 3A5, (Pascussi 2000a, 2000b, Drugbank 2014, RXlist). In vitro studies with human hepatocytes have found dexamethasone to be a potent inducer of CYP3A4 (Pichard 1992). In a small clinical study where dexamethasone was administered together with the CYP 3A4 substrate triazolam, dexamethasone only had a small and not statistically significant effect on the pharmacokinetics of triazolam. It was mentioned by the authors that since glucocorticoids (including dexamethasone) themselves are metabolized by CYP 3A4, administration with another CYP 3A4 substrate might lead to a competitive inhibition of the metabolizing enzyme and thus complicating the measured degree of induction (Villika 1998). In a clinical study performed by Teo et al 2012, dexamethasone gave an increased occurrence of hepatotoxicity when taken concurrently with lapatinib. The suggested mechanism for this effect was induction of CYP 3A4 by dexamethasone leading to an increase in the formation of reactive metabolites from lapatinib. Another small clinical study showed that the degree of CYP 3A4 induction was subject for great intersubjective variability (McCune 2000). It is suggested that dexamethasone induces CYP3A4 in human hepatocytes both via direct activation of the Pregnane X receptor (PXR) at high concentrations (above 10 μM) and via activation of the glucocorticoid receptor which in turn induces transcription of PXR leading to increased expression of CYP3A4 at low concentrations. The induction of CYP3A4 by dexamethasone at low concentrations is considered modest whereas the induction response by dexamethasone at higher concentrations (bolus or stress conditions) results in much greater mRNA expression (Pascussi 2000). Different mechanisms for regulation of CYP enzymes by glucocorticoids are discussed (El-Sankary 2002, Pascussi 2002, 2003).

Uneventfully used by one patient with VP (scarlett 1995).

Uneventful use reported in 3 patients with acute porphyria.