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Special Report: Concerns Grow as FDA Reviews Oral Contraceptives

Keeping patients informed of potential risks while placing current concerns in context is key.

By Paul Winnington, Editorial Director

With studies offering conflicting evidence about the influence of drosperinone-containing oral contraceptive pills (OCPs) on a woman's risk for venous thromboembolism (VTE), FDA will convene an advisory panel next month to review the safety of Yaz (Bayer) and similar formulations that have become popular for the treatment of acne. According to the agency, it is unable to draw a conclusion about the safety of the medications without input from members of the reproductive health and drug safety advisory committees.

Safety Review

At issue are studies published this year in British Medical Journal that suggest that OCPs containing the synthetic progestin may double or triple a woman's clotting risk. Other studies have failed to demonstrate any increased risk associated with the drugs. Unlike progestin, which can be associated with androgen-like activities (progestin-containing OCPs remain overall anti-androgenic), drosperinone has no androgenic activity and is in fact an analog of the widely used anti-acne agent spironolactone. As such, formulations containing drosperinone have been a particularly popular choice for women with acne who are also candidates for oral contraceptive therapy.

While some clinicians and many patients have expressed concern about FDA's decision to review the agents, dermatologist Julie Harper, MD says that the action itself need not cause anxiety about the future of the drugs. “This is the culture that we live in,” Dr. Harper says. “The FDA has to err on the side of being extraordinarily cautious.” The decision to review the safety of the drugs, “may be wise,” she says, though she adds that she hopes the agency interprets study findings accurately and wisely. If no significant risk is found, patients and prescribers can be reassured. “If there is anything found, I hope that they do put that identified risk in context,” she says.

Many popular media reports about the possible risk for VTE may be confusing for patients and some prescribers by stating that drosperinone-containing OCPs may triple a woman's risk for VTE. According to Dr. Harper, the overall incidence of VTE in any woman is a three per 10,000 women per year. With conventional OCPs, the incidence may be as high as six or seven per 10,000 women per year. If the studies on drosperinone are correct, the incidence of VTE associated with the agent is nine or 10 per 10,000 women per year. One of the challenges in determining the validity of studies is variability in study design, which makes it difficult to compare findings from one cohort to another.

Dr. Harper also reminds that there are known risk factors associated with an increased risk for VTE in women using OCPs. Increased BMI, recent surgery, or immobilization all increase a woman's risk for VTE.

Dermatologists responded favorably to drosperinone- containing OCPs when they came to market (Yaz is the only one of the next-generation OCPs with an acne indication), probably due to similarities between drosperinone and spironolactone, Dr. Harper suspects. Spironolactone has been used by dermatologists for many years, and many clinicians are familiar with its use in acne. However, it is associated with risks to a male fetus if a pregnant woman uses it, therefore most patients treated with spironolactone also receive a prescription for an OCP. Choosing a drosperinone-containing agent as the OCP can help to regulate the irregular menstrual periods that may be associated with spironolactone. Many women, however, can be treated with a drosperinone-containing OCP alone and won't need spironolactone.

In Context

The FDA's decision to analyze the drosperinone data should not in itself change prescribers' or patients' habits, Dr. Harper says. Patients already using a drosperinone-based OCP may be reassured that the risk for therapy-associated VTE is highest during the first six months of therapy. Patients should be informed at the time they received their prescription that OCPs are associated with a slightly increased risk of VTE. Therefore, those now concerned about the FDA action can be told that the concern is not entirely new; data are inconclusive, but there is some unconfirmed evidence that the risk may be slightly higher than thought. Finally, prescribers need not discontinue prescribing drosperinone-containing OCPs, however, they should be as vigilant as ever about screening patients for risk factors through an appropriate review of systems prior to writing the prescription and putting known risks in context.

Research Updates and News

No Degradation for Tretinoin

Data from an in vivo study presented at the annual meeting of the American Academy of Dermatology show that tretinoin in Atralin Gel 0.05% (Valeant) may not degrade on contact with benzoyl peroxide. Investigators mixed equal amounts of Atralin Gel and benzoyl peroxide gel in a sealed jar maintained at 32 degrees celcius and observed no significant loss of tretinoin over a seven-hour time period.

Positive Results for Rosacea Agent

CD07805/47, a proprietary topical gel under investigation for treating patients with moderate to severe facial erythema of rosacea, was safe and effective in a phase IIb trial, according to Galderma. In the trial CD07805/47 was shown to be rapidly effective at reducing facial redness. During the treatment and follow-up phases of the eight-week study, CD07805/47 was judged to be safe and well-tolerated. There was no evidence of tachyphylaxis or rebound in the study. Results will be submitted for publication where further data and analysis will be provided. Phase III studies are currently ongoing.

Briakinumab Outperforms Methotrexate: Study

Briakinumab was found to be more effective in treating plaque psoriasis than methotrexate in a new 52-week study (NEJM. 365:1586-1596). Researchers randomly assigned 317 patients with moderate-to-severe psoriasis to briakinumab, at a dose of 200mg at weeks zero and four and 100mg at week eight and every four weeks thereafter, or methotrexate, at a dose of 5 to 25mg weekly. The primary end points were the percentages of patients achieving PASI 75 at weeks 24 and 52 and PGA score of either zero or one. At week 24, a total of 81.8 percent of the patients in the briakinumab group versus 39.9 percent in the methotrexate group achieved PASI 75 and 80.5 percent versus 34.4 percent had PGA score succcess. The corresponding PASI 75 percentages at week 52 were 66.2 percent versus 23.9 percent, and 63 percent versus 20.2 percent with a score of 0 or 1 on the PGA. Serious adverse events occurred in 9.1 percent of the patients in the briakinumab group and in 6.1 percent in the methotrexate group.

Syneron Launches eTwo

Syneron Medical's new facial rejuvenation device eTwo combines Syneron's “Sublime” controlled heating and “Sublative” fractional skin treatment technologies, the company says. Sublime utilizes a safe and effective combination of infrared light and bipolar radio frequency energies to remodel the deep dermal layer of the skin by stimulating new collagen growth. The company's Sublative fractionated bipolar radio frequency technology offers high dermal impact with low epidermal disruption, they say.

Sublative places heat energy in the upper dermal layer, enabling significant enhancement in collagen and elastin.

Radiation Found Effective For SCCs

According to a new study, radiation therapy (RT) represents an important adjuvant treatment modality for high-risk squamous cell carcinomas (Dermatology, October 21). Investigators described two adolescent boys with XP and high-risk SCCs of the skin that were treated with standard RT regimens without acute or chronic complications. After follow-up periods of two and seven years, both patients had developed fewer skin cancers on the treated side of the face. In addition to these case studies, a review of reported cases revealed that XP patients generally have normal cellular and clinical responses to ionizing radiation, which reflects the specificity of their nucleotide excision repair defect for ultraviolet radiation- induced DNA damage.

Abbott Plans Spin-off of Branded Drugs Company

Abbott Laboratories says it plans to spin off a branded drug business from the medical products company. The new drug company, as yet unnamed, is estimated to have annual revenue of about $18 billion based on 2011 estimates, Abbott said. It will sell Humira, which treats psoriasis. Retaining the Abbott name, the medical products company, will continue to sell generics drugs, medical implants, diagnostic tests drugs and baby formula with annual revenue of about $22 billion.

Point-of-Care Syphilis Test Cleared in Europe

European regulators have conferred a CE mark on the DPP Syphilis Screen & Confirm Assay from Chembio Diagnostics, Inc. The point-of-care diagnostic test can confirm an active, previously untreated case of syphilis. The Company recently began clinical trials at the first of three sites in the US to support an application to the FDA for a 510(k) clearance. The company hopes to submit the application next year.

New Skin Health Book Available

A new book that provides tips on overall skin health is now available. Ava Shamban, MD shares her complete skin-healing program combining skin care, nutrition, and fitness. The book offers specific skin care regimens tailored to age, skin type, and internal condition, as well as tips for addressing issues related to acne, stress, pregnancy, menopause, chemotherapy, and more. The book is available in stores and online.

Restylane Indication Expanded

FDA recently approved the use of Restylane Injectable Gel (hyaluronic acid (HA), Medicis) for lip augmentation, specifically submucosal implantation for lip augmentation in patients over the age of 21. The approval was based on a pivotal study in which patients were randomized to receive either Restylane treatment once at the start of the study and then again after six months or to receive Restylane only after six months. Researchers found that Restylane was well tolerated and highly effective for lip augmentation for up to six months, meeting both primary and secondary endpoints. In addition, there were no serious adverse events.

According to cosmetic dermatologist Ava Shamban, MD, the approval is a welcome development that will assure patients of the safety of lip treatment, a popular request from cosmetic patients. “The lips are often the first place on the face that starts to show age,” Dr. Shamban observes. HA-based lip augmentation is particularly useful to treat asymmetry and/or traumatic injury defects, she says.

Key to success will be skillful placement of HA, Dr. Shamban asserts, noting that “features should be enhanced, not exaggerated.” Training for injectors will be available, or interested physicians can seek preceptorships, Dr. Shamban says.

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