Each disposable intranasal delivery device contains 28 mg esketamine; it will come in prepackaged units of one, two, or three devices to deliver the prescribed doses of 28 mg, 56 mg, or 84 mg, respectively. The device does not require priming and, after use, contains only about 30 microliters of residual medication. Its interlocking design, with a glass vial inside the plastic outer assembly, would make it very difficult to pull apart, should anyone want to obtain the residue.

The proposed REMS – the key requirement for approval at this point – would include the following measures:

  • Prescriber training on the risks of esketamine and importance of monitoring patients after their dose is administered and the need to register patients
  • Administration of esketamine only in certain health care settings that ensure patient monitoring by a health care clinician for 2 hours after administration
  • Pharmacies, clinicians, or health care settings that dispense the drug are specially certified to ensure that esketamine is not dispensed directly to patients and that patients are monitored
  • Enrollment of patients who are treated with esketamine in a registry to better characterize the risks associated with esketamine administration and inform risk mitigation strategies

After administration, patients would be monitored for at least 2 hours for the common side effects, sedation and dissociation that typically clear within that time. Transient blood pressure fluctuations also can occur shortly after administration and would be monitored until stable. Patients should also be counseled not to drive the day of treatment, and to bring a companion along to drive them home.

Dr. Dunn, however, suggested that some facets of the proposed REMS might create unnecessary barriers for some patients and that stringent monitoring after every single dose – potentially for years – might not be necessary for everyone.

“The REM is certainly important to address the potential for diversion and misuse and adverse effects, but there needs to be a pathway to reduce monitoring requirements” on an individual basis. “If a patient is doing well for a year or so, in remission with no side effects, we should have a way to reduce the need for monitoring. If we make it too much of a burden to go in, get the medication, stay for a couple of hours for monitoring, it’s easy to skip a dose. And we know the number one predictor of relapse is medication nonadherence.”

The facility certification requirement also could curtail access to esketamine, said Steven B. Meisel, PharmD, of Minneapolis.

“How do we define a medically supervised center? Is it somewhere with a nurse onsite? A physician onsite? Does it have to have access to emergency services? This issue of access vs. control and safety is a very important one.”

He posed a clinical conundrum: A patient doing well on regular esketamine who wants to go on an extended trip. Under the proposed REMS, that patient would not be able to access his regular dose, which could only be handled, sorted, and administered by a certified health care clinician. “How are we going to deal with this? There will be great pressure to loosen this up in some manner. But if we allow a patient who’s been doing well on regular treatment with no relapse to have this at home, do we open the way for a teenager to take a bottle or two to a party? Those are real-world issues and must be considered when we establish a REM in a real world that demands access to needed therapy.”

Erring on the side of caution is the responsibility of policymakers, argued Kim Witczak, executive director of Woodymatters, a consumer-driven, nonprofit drug safety organization dedicated to FDA reform. Ms. Witczak was one of two dissenting voices on the vote.

“This has so much potential for so many people who just want a quick fix [for their mood disorders], and the marketing side will see this,” she predicted. “I would want to be very cautious. Once it gets out there into the real world, there will be a lot of people trying to get it. We don’t want to have ‘Esketamines “R” Us’ clinics popping up everywhere.”

The FDA usually follows its panels’ recommendations, which are not binding.

[Read the Original Post Here]