Dexamethasone Aminoglutethimide

Such a medical adrenalectomy is an efficacious treatment for metastatic breast and prostate cancer, since it diminishes the levels of circulating sex hormones. Glucocorticoids are administered concomitantly to suppress enhanced corticotrophin release. Cortisol is preferable to dexamethasone in this situation because aminoglutethimide markedly enhances the hepatic microsomal metabolism of dexamethasone. Hepatic enzyme induction may be responsible for the development of tolerance to the side effects of aminoglutethimide, such as ataxia, lethargy, dizziness, and rashes. 

Aminoglutethimide also apparently increases the clearance of some steroids. It has been shown to enhance the metabolism of dexamethasone, reducing its half-life from 4-5 hours to 2 hours. 

Aminoglutethimide [ah me no glue TETH i mide] is useful in second line therapy for the treatment of metastatic breast cancer. It inhibits the adrenal synthesis of pregnenolone from cholesterol, and the extra-adrenal aromatase reaction responsible for the synthesis of estrogen from androstenedione. Aminoglutethimide is administered orally, and is metabolized by the hepatic cytochrome P-450 system to inactive products. Because of its ability to induce this system, its own metabolism is accelerated, and interactions that increase the metabolism of dexamethasone (see p. 275), theophylline (see p. 220) and digoxin (see p. 158) can occur. Aminoglutethimide causes transient CNS depression and a maculopapular rash. 

Androgens Fluoxymesterone Testosterone Androgen antagonists Bicalutamide Flutamide Ketoconazole Nilutamide Aromatase inhibitors Aminoglutethimide Anastrazole Exemestane Letrozole Corticosteroids Dexamethasone Prednisone Estrogens Diethylstilbesterol Estradiol... 

The effects of dexamethasone, but not hydrocortisone, can be reduced or abolished by aminoglutethimide. 

Aminoglutethimide 500 to 750 mg daily reduced the half-life of dexamethasone 1 mg from 264 to 120 minutes in 6 patients. In another 22 patients it was found that larger doses of dexamethasone (1.5 to 3 mg daily) compensated for the increased dexamethasone metabolism caused by aminoglutethimide and complete adrenal suppression was achieved over a prolonged period. Another study found a fourfold increase in dexamethasone clearance in 10 patients taking aminoglutethimide 1 g daily. ... 

A patient, dependent on dexamethasone due to brain oedema caused by a tumour, deteriorated rapidly, with headache and lethargy, when aminoglutethimide was also given. The problem was solved by withdrawing the aminoglutethimide and temporarily increasing the dexamethasone dosage from 6 to 16 mg daily. ... 

Aminoglutethimide is an enzyme inducer and it seems likely that it interacts by increasing the metabolism and clearance of dexamethasone by the liver, thereby reducing its effects. ... 

Information is limited but the interaction between dexamethasone and aminoglutethimide is established. The reduction in the serum corticosteroid levels can be enough to reduce or even abolish the effects of corticosteroid replacement therapy or to cause loss of control of a disease condition. This has been successfully accommodated by increasing the dosage of the dexamethasone. Hydrocortisone is routinely used with aminoglutethimide as replacement therapy, and would seem to be a suitable alternative to dexamethasone, where clinically appropriate. Other synthetic corticosteroids are predicted to interact in the same way as dexamethasone, but this needs confirmation. 

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