Pharmacology
Topical Corticosteroid Adrenal Suppression Risk Precludes Over-The-Counter Use
By FDA advisory committe
Mar 26, 2005, 09:37

Potentially fatal adverse events related to adrenal suppression of cortisol from �maximal use� of topical corticosteroids should preclude an Rx-to-OTC switch of those drugs, an FDA advisory committe said March 24.

�The reason we care� about hypothalamic, pituitary and adrenal axis suppression in unsupervised consumers is that the condition �could lead to sudden death,� committee consultant Constantine Stratakis (National Institutes of Health) said.

FDA's Nonprescription Drugs and Dermatologic & Ophthalmic Drugs Advisory Committee members voted 21-5 that any topical corticosteroid that causes HPA axis suppression �under maximal use conditions� is not an appropriate over-the-counter switch candidate.

Division of OTC Drug Products Director Charles Ganley defined maximal use as two weeks of topical corticosteroid therapy on over 30% of the body.

The HPA axis helps regulate stress response, Dermatologic & Dental Drug Products Division Lead Medical Officer Markham Luke explained.

HPA axis suppression �may lead to decreased ability of the adrenals to then respond and produce cortisol,� Luke said. �If there is a failure to mount such a response it can lead to hypertension and cardiovascular collapse.�

The committee was also concerned with the accepted method of testing for HPA axis suppression, the cosyntropin stimulation test.

The test �has a sensitivity of about 70% and specificity of about 95%-100%,� Stratakis observed.

The test �is only 70% sensitive so therefore we miss 30% of people,� committee member Mary Tinetti (Yale University) said.

Dermatologic committee member Elizabeth Whitmore (Wheaton, Ill.) noted she was not in favor of an OTC switch, but pointed out that �20% or 30% of our patients [who] are using the higher potency steroids are having this HPA suppression, which we are not doing anything about.�

�This is happening all the time, and there�s nothing that�s being done about it, so I don�t know that it makes any difference whether it�s over-the-counter or by prescription � still nothing is being done about it.�

Most committee members agreed that zero events out of a sample size of 1,000 would provide �confidence in ruling out HPA axis suppression at a desired upper limit.�

However, dermatologic committee chair Michael Bigby (Beth Israel Deaconess Medical Center) qualified his response: �I would say greater than 1,000, and then the other thing I would say is that we already have a signal in the lowest class of drugs that we can consider�so I don�t know why we�re giving a number.�

Dermatologic & Dental Drug Products Division Medical Officer Denise Cook presented HPA axis suppression results from pediatric trials in mid-potent topical corticosteroids that exhibited suppression signals in small patient populations.

In a 15-patient trial with Schering-Plough�s Dirposone (betamethasone diproprionate) lotion .05%, 73% of patients showed evidence of HPA axis suppression, Cook said. However, corticosteroid absorption may vary by drug vehicle used � cream, lotion or ointment.

All rights reserved by www.rxpgnews.com