Based on reports from post-marketing experience, Spravato’s warnings and precautions section now includes the risk of respiratory depression.
Johnson & Johnson has updated the safety labeling of the antidepressant Spravato (esketamine) to include a risk of respiratory depression and respiratory arrest. These adverse events were seen with postmarketing experience.
From March 2019 to February 2023, there were 40 cases of respiratory depression and two cases of respiratory arrest out of 868,000 treatment sessions, Reina Benabou, M.D., Ph.D., vice president, medical affairs, U.S. Neuroscience at J&J., said in an interview. Since its approval, Spravato has been used by 47,000 patients.
The FDA approved Spravato in March 2019 to treat adults with treatment-resistant depression, and the following year to treat adults with major depressive disorder with suicidal thoughts. In the United States, about 21 million adults have had at least one major depressive episode, with an estimated one-third — or 2.8 million — of those living with major depressive disorder who are treatment resistant.
Delivered as a nasal spray, Spravato is a chemical variant of ketamine and acts on the glutamate receptor (NMDA receptor). Taken with an antidepressant, it provides faster response than antidepressants alone.
As part of its Risk Evaluation and Mitigation Strategies (REMS), Spravato is only administered in certified centers where trained healthcare professionals are required to monitor patients for at least two hours after administration to ensure the response is well tolerated. The label update adds monitoring with pulse oximetry, which measures the oxygen in a person’s blood.
Benabous said specific details about pulse oximetry monitoring are pending with the FDA and will be included in Spravato’s REMS when that is finalized.
“The safety of our patients is our top priority,” Benabou said. “We’re working very closely with the FDA to be transparent with the data that we have. The label has been updated effective immediately and we want to raise awareness about these issues.”
Regulators did not recommend any constraints for use, but Benabou suggested that providers with patients with COPD, cardiac failure, or who are taking concomitant CNS-acting drugs will have to use discretion when prescribing Spravato.
The newly added subsection under warnings and precautions reads:
“In post marketing experience, respiratory depression was observed with the use of SPRAVATO. In addition, there were rare reports of respiratory arrest
Because of the risks of respiratory depression, patients must be monitored for changes in respiratory status by a healthcare provider for at least 2 hours (including pulse oximetry) at each treatment session, followed by an assessment to determine when the patient is considered clinically stable and ready to leave the healthcare setting.
Spravato is available only through a restricted program under a REMS.”
The REMS program was added to Spravato’s use when it was approved because of the risk of serious adverse outcomes resulting from sedation and dissociation associated with it, and the potential for abuse and misuse of the drug.
Research on Spravato continues. Earlier this month, J&J released data from a head-to-head phase 3 study of Spravato and quetiapine extended release (Seroquel XR) in patients with treatment-resistant depression. Patients treated with Spravato were 1.54 times as likely to reach remission after eight weeks than those treated with quetiapine and were also 1.55 times as likely to stay relapse-free up to 32 weeks. The results of this study were published in The New England Journal Medicine.