Ortho Tri-Cyclen first low-dose OC to be indicated for noncontraceptive use

Food and Drug Administration gives approval for treatment of acne

A 16-year-old sexually active female comes into your clinic for a pregnancy test. The test is negative, and you take this opportunity to talk to her about oral contraceptives. She seems uninterested until you point out the latest news: Ortho Tri-Cyclen has been approved by the Food and Drug Administration (FDA) to treat acne.

With clearance as the first hormonal treatment for moderate acne, Ortho Tri-Cyclen, manufactured by Ortho Pharmaceutical Corp. of Raritan, NJ, has crossed over the reproductive health line. Clinicians have long known of the oral contraceptive’s (OC’s) effects in lowering the level of serum testosterone, which contributes to acne-causing agents, but they now have clinical proof that has been accepted by the FDA, says Geoffrey P. Redmond, MD, a Cleveland endocrinologist who served as an investigator in the Ortho Tri-Cyclen trials.

"We now have unequivocal evidence that a particular OC is effective for acne, and the FDA has approved it for that indication," says Redmond, president of the Foundation of Developmental Endocrinology, a Cleveland independent research facility. "For women who want to be on the Pill and haven’t responded to topical [treatment], this gives physicians doing family planning a chance to treat many of the women they see with acne with a treatment method they are familiar with."

Ortho Tri-Cyclen relies on a graduated dose of the progestin norgestimate (180 mcg the first seven days, 215 mcg the next seven days, and 250 mcg the next seven days), with a constant dose of 35 mcg of ethinyl estradiol for its effectiveness.

Introduced in Europe in the late 1980s, the drug was made available in the United States in 1992, says Joel S. Lippman, MD, MPH, FACOG, Ortho’s executive director of clinical affairs.

Since its debut, the Pill has been accepted by clinicians for its good cycle control and tolerability by patients, he notes. (Contraceptive Technology Update readers named Ortho Tri-Cyclen as their second selection in the 1996 Pill Survey, elevating it from a fourth-place finish in the 1995 poll. For more information, see the October 1996 issue of CTU.)

Ortho looked at a number of formulations that would best be suited for acne treatment prior to seeking the FDA’s approval for the new indication, says Lippman.

"The regimen itself, the dose of estrogen, as well as the type and dose of progestin, led us to believe that Ortho Tri-Cyclen stood the best chance of being successfully [tested]," he concludes.

Two trials lead to new labeling

Two randomized, double-blind, placebo- controlled, six-month trials were conducted by Ortho in 19 clinical sites to test for the acne indication. Eighty percent of the 462 women participating in the studies demonstrated improvement, unpublished results show.

The design of the Ortho Tri-Cyclen trials differed from those normally performed for oral contraceptive use, notes Lippman.

"There are other studies on OCs and acne, but none of them are against placebo," he explains. "They’re all usually one drug vs. another, showing that they’re the same. That either means both work, or they both don’t work. Because they haven’t measured that placebo effect, they really don’t know. And frankly, the only regimen that has that measurement against placebo is Ortho Tri-Cyclen."

Both studies have been submitted for publication and will be presented at poster sessions this spring at meetings of the Schaumberg, IL-based American Academy of Dermatology and the Washington, DC-based American College of Obstetricians and Gynecologists. Expect more information to come from the Ortho Tri-Cyclen studies, says Lippman.

"In that it’s a novelty that it was double-blinded against placebo, we have some other data which hasn’t been analyzed yet, looking at tolerability [issues]," he states.

The new labeling will read that "Ortho Tri-Cyclen is indicated for the treatment of moderate acne vulgaris in females, Ž 15 years of age, who have no known contraindications to oral contraceptive therapy, desire contraception, have achieved menarche, and are unresponsive to topical anti-acne medications."

Noncontraceptive benefits aid acceptance

Getting clearance for a noncontraceptive use puts OCs in a different light, and may spark a broader knowledge base among the general public, says Kirtly Parker Jones, MD, associate professor of obstetrics and gynecology and chief of the division of reproductive endocrinology at the University of Utah in Salt Lake City. (See guest column on acne and other noncontraceptive uses of OCs, p. 27.)

"I think that it is a step in the right direction in recognizing the many noncontraceptive benefits of birth control pills," she offers. "Everything from the treatment of dysfunctional uterine bleeding to suppression of androgens in hirsutism, to the treatment of polycystic ovary disease — there are many things that we’ve been using pills for all along, and now we are actually beginning to make a step in recognizing these as primary steps that someone might take in treating diseases other than unwanted pregnancies."

The Washington, DC-based Association of Reproductive Health Professionals (ARHP), whose board of directors Jones chairs, has issued a letter to all OC manufacturers calling for them to seek updated labeling for birth control pills.

"This is an opportunity for visibility of the issue of contraceptive use [of birth control pills]," notes Dennis Barbour, JD, ARHP president. "It kind of begs the question for other oral contraceptive manufacturers to acquire labeling for other indications, as well. This is the beginning of a process which will end in all manufacturers submitting to [FDA] for other indications."

It is important that women understand the health benefits of oral contraceptives for their most effective use. In a 1996 national telephone survey of 280 women, ARHP found that 33% of women polled did not know of any benefits of the Pill beyond birth control.1

Indication benefits patient, clinician

The FDA approval comes as good news for family planning clinicians, many who see teen-agers and young women with concerns about acne.

"A lot of [patients] come in for that reason," says Gayle Whatley, CRNP, nurse practitioner supervisor with the Anniston, AL-based Family Health Service Program, Public Health Department Area Six. "A friend or somebody has told them that when they started taking pills, their complexion improved, so some of them come in for that specific reason."

With the FDA approval in hand, some of the stigma associated with taking birth control pills is now removed, says Jones.

"[This] gives credibility to those of us who have been treating patients, usually adolescents, with birth control pills," she observes. "Now we can talk to both the adolescents and the mothers who are very anxious about ‘birth control pills’ and say, ‘The FDA has actually approved this hormone formulation for the treatment of acne’."

If patients feel more comfortable using the Pill, then perhaps they will stay the course in their pill-taking regimen. That’s an important talking point for Sandra Curry, director of Grand Junction (CO) Women’s Clinic, an abortion-providing facility.

"We’ve had a goodly number of patients with acne problems, or self-perceived acne problems," she says. "If through use of an oral contraceptive, their skin problems could be improved, it would be an added incentive in taking the pills to prevent pregnancy."

Reference

1. Association of Reproductive Health Professionals. Women’s Attitudes and Perceptions about Health Benefits of Contraception. Washington; 1996.