Fludrocortisone Acetate and Midodrine Hydrochloride

• Generic Name: fludrocortisone
• Dosage Forms: n.a.
• Other Brand Names: Florinef Acetate

Used for oral mineralocorticoid replacement therapy; use is contraindicated in all conditions except those that require a high degree of mineralocorticoid activity.

Partial replacement therapy, in combination with hydrocortisone or cortisone, for treatment of primary and secondary adrenocortical insufficiency in Addison’s disease after electrolyte balance has been restored.

Hydrocortisone or cortisone (in conjunction with liberal salt intake) usually is the corticosteroid of choice for replacement therapy; concomitant administration of fludrocortisone may be required in some patients.

Treatment of salt-losing congenital adrenogenital syndrome after electrolyte balance has been restored.

Has been used with some success to increase SBP and DBP in patients with severe, chronic postural hypotension (e.g., secondary to autonomic dysfunction, levodopa therapy) that does not respond adequately to nondrug therapy.

• Generic Name: midodrine
• Dosage Forms: n.a.
• Other Brand Names: Proamatine, Orvaten

Treatment of symptomatic orthostatic hypotension (designated an orphan drug by FDA for this use). Indication is based on effect on increases in 1-minute standing systolic BP, a surrogate marker; clinical benefits (principally improved ability to perform life activities) not established. Continue the drug only in patients who report substantial symptomatic improvement.

Use recommended only in patients whose lives are considerably impaired despite standard clinical care; use only after nondrug therapies (e.g., support hose, increased sodium intake, life-style modifications) and fluid expansion have failed. May be more effective than comparative drugs (e.g., ephedrine) in managing postural symptoms.

In August 2010, FDA proposed to withdraw approval of midodrine because required postapproval studies verifying the clinical benefit of the drug had not been done. FDA stated that neither the original manufacturer (Shire) nor any generic manufacturer had demonstrated clinical benefit (e.g., performance of life activities); data submitted had not verified expected clinical benefit. In September 2010, FDA clarified that its proposal was part of the regulatory process and that midodrine could remain on the market as that process moves forward. Subsequently, FDA and Shire reached an agreement that Shire would conduct 2 additional clinical studies to verify the clinical benefit of midodrine in patients with symptomatic orthostatic hypotension. In February 2012, FDA announced that the proposal to withdraw approval of midodrine will be deferred until these studies have been conducted; meanwhile, the drug remains approved and available on the US market. In September 2014, FDA extended the deadline to March 31, 2015 for final submission of study results and analyses for FDA review.