— Is labeling enough for users to take the drug correctly and self-deselect?
Rachael Robertson, Enterprise & Investigative Writer, MedPage Today
May 5, 2023
FDA staff raised concerns over the prospect of a contraceptive pill for over the counter (OTC) use, and questioned whether sufficient evidence exists that consumers would take the pill appropriately, according to briefing documents released ahead of a 2-day advisory committee meeting.
At a joint meeting of the Nonprescription Drugs Advisory Committee and the Obstetrics, Reproductive, and Urologic Drugs Advisory Committee next Tuesday and Wednesday, the agency’s outside experts will consider the proposed first-in-class prescription-to-nonprescription switch of daily 0.075 mg norgestrel tablets (Opill) by drug manufacturer HRA Pharma.
Advisors will be tasked with weighing whether benefits, such as greater access, outweigh the various possible risks, including the potential for contraceptive failure due to adherence issues and use by women with contraindications. If ultimately approved by the FDA, Opill would be the first OTC birth control pill.
Its safety and efficacy “is contingent on whether a consumer can appropriately self-select and adhere closely to the directions for use, or correctly choose not to use the product (deselect),” FDA staff wrote in their briefing document.
For example, in women with breast cancer or a history of the malignancy, labeling comprehension studies performed by the applicant found that comprehension of this contraindication “did not approach the prespecified target threshold,” with some participants failing to correctly deselect.
“Norgestrel use in consumers with a history of breast cancer and other progestin-sensitive cancers may stimulate growth of progesterone-receptor positive tumor cells and can increase the risk of recurrence,” the FDA explained.
HRA Pharma submitted three consumer behavior studies, one of which was the ACCESS study, which had improbable dosing for a third of participants (meaning they reported taking more tablets than dispensed), a finding which may “call into question the reliability of all of the actual use data,” said FDA staff.
ACCESS investigators also reported that half of women with abnormal bleeding — where users would be told to consult with a doctor before use — had not discussed it with their healthcare provider yet identified themselves as eligible for the medicine anyhow. Comprehension for hormonal birth control was adequate overall, but 1% of participants still used other forms of hormonal birth control while on norgestrel.
Another of the FDA staff’s concerns was the potential for drug interactions.
“Using medications that interact with norgestrel can result in decreased efficacy of norgestrel or the other medication or both. The consequences of this can be severe, potentially resulting in unintended pregnancy or seizures in an individual with a seizure disorder,” the document stated. “Therefore, FDA emphasizes deselection as the critical endpoint in self-selection studies.”
FDA advisory committee members will be tasked with discussing whether consumers will correctly and consistently take the pill without guidance from a healthcare professional. In addition to assessing the general population, they will discuss this likelihood for adolescents, people with limited literacy, and people using concomitant products that could interact with or reduce the efficacy of norgestrel tablets.
Norgestrel tablets, originally called Ovrette, were first approved by the FDA as birth control 50 years ago. Ovrette was discontinued in 2005, but not for safety or efficacy issues. It was rebranded and renamed in 2017 as Opill in preparation for a nonprescription application. In 2019, the American College of Obstetricians and Gynecologists released a statement voicing general support for OTC contraceptives, including oral contraceptive pills.
While the FDA is not required to follow the recommendations of its advisory committees, it typically does.