Drug Interactions between conjugated estrogens / medroxyprogesterone and Dexacort Phosphate in Respihaler

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations and pharmacologic effects of medroxyprogesterone, which is primarily metabolized by the isoenzyme. Aminoglutethimide, a CYP450 3A4 inducer, has been shown to significantly decrease the serum levels of medroxyprogesterone by 50% or more when administered at 250 mg two to four times daily to women with breast cancer receiving high-dose medroxyprogesterone orally. The decrease was accompanied by an increase in serum cortisol level, which suggests diminished adrenal suppressive effect of medroxyprogesterone. The interaction has not been studied with depot formulations of medroxyprogesterone. Because the clearance of medroxyprogesterone is approximately equal to the rate of hepatic blood flow, drugs that induce CYP450 3A4 are not expected to significantly affect the pharmacokinetics of medroxyprogesterone administered parenterally. In one study, no interaction was reported when medroxyprogesterone was administered intravenously with aminoglutethimide.

MANAGEMENT: Pharmacologic response to medroxyprogesterone should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy, and the dosage adjusted as necessary. When administered as the depot formulation for contraception, no dosage adjustment for medroxyprogesterone is currently recommended during coadministration with CYP450 3A4 inducers. However, consideration may be given to decreasing the dosing interval (e.g., from one injection every 12 weeks to every 10 weeks) if an interaction is suspected.

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MONITOR: Estrogens may enhance the systemic effects of both endogenous and exogenous corticosteroids. The proposed mechanism is an increase in serum cortisol-binding globulin (transcortin) induced by estrogens, resulting in a decreased rate of corticosteroid metabolic clearance. The interaction has been reported with estrogens or estrogen-containing oral contraceptives (OCs) and hydrocortisone, prednisone, and prednisolone. In one pharmacokinetic study, the mean plasma clearance of total prednisolone (40 mg IV) in eight female OC users was less than half that of five healthy female non-OC users and eight healthy males, and the prednisolone half-life and mean residence time were longer. There was also a 2-fold increase in the area under the plasma concentration-time curve for unbound prednisolone compared to controls.

MANAGEMENT: Patients treated concomitantly with an estrogen-containing drug may require lower dosages of corticosteroids or adrenocorticotropic agents. Pharmacologic response to these agents should be monitored more closely whenever an estrogen is added to or withdrawn from therapy in patients stabilized on their existing corticosteroid or adrenocorticotropic regimen, and the dosage(s) adjusted as necessary.

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