Prasterone.

PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy, adverse effects and toxicities, drug interactions, dosage and administration, and safety issues related to the use of prasterone are discussed.

SUMMARY: Prasterone is a proprietary synthetic dehydroepiandrosterone product under investigation for use in women with systemic lupus erythematosus (SLE) who are taking glucocorticoids. Initial trials investigated prasterone as a treatment to improve disease activity and symptoms in women with mild to moderate SLE. The Food and Drug Administration (FDA) did not approve prasterone's labeling for these indications. Subsequent trials have focused on prasterone as a treatment to limit bone loss in women who have SLE. A study was conducted to assess bone mineral density in patients who had been taking glucocorticoids for six months or longer. The patients in the prasterone group showed an increase in bone mineral density, while the placebo group demonstrated a loss. The most common adverse effects of prasterone therapy were acne and hirsutism. Hematuria, hypertension, and serum creatinine concentration increases have also occurred. Interactions of prasterone potentially exist with 5-alpha reductase inhibitors and additive or antagonistic effects could possibly occur with androgens, estrogens, oral contraceptives, and progestins. In clinical trials, oral prasterone dosages of 100-200 mg/day were administered. These dosages have resulted in supraphysiological hormone levels.

CONCLUSION

FDA has granted orphan drug status for the prevention of loss of bone mineral density in SLE patients taking glucocorticoids. FDA is requesting additional Phase III trial data for the treatment of SLE and the prevention of loss of bone mineral density.