Stephanie Fox-Rawlings, PhD, National Center for Health Research, September 27, 2019
Thank you for the opportunity to speak today on behalf of the National Center for Health Research. I am Dr. Stephanie Fox-Rawlings. I am a neuroscientist trained at Case Western and Children’s National Medical Center. NCHR analyzes scientific and medical data to provide objective health information to patients, health professionals, and policy makers. We do not accept funding from drug and medical device companies, so I have no conflicts of interest.
The reports on neuropsychiatric adverse events during or after the use of montelukast (Singulair) deserve our thorough attention. We need better data to identify how likely patients are to experience these side effects. The studies conducted by FDA and sponsors tried to address these concerns but there are major limitations with the sources of the data used in the studies that makes the results inconclusive.
- FAERs reports are voluntary and lack a lot of basic information about the patient and the adverse event. Moreover, many clinicians don’t report side effects that are already listed on the label. We know that these reports are only available for a fraction of the actual occurrences, but we don’t know what percentage of events they represent nor are they necessarily characteristic of all events.
- The Sentinel database provides information based on claims data. So, patients’ adverse events are only identified if they were treated in a medical facility with properly coded claims data . Someone who, for example, became aggressive or suicidal but did not seek medical treatment would not be identified in the Sentinel database as having an adverse event.
- The Sponsor’s clinical trial data includes a large number of patients in randomized, double blind, controlled clinical trials, which seems like a good source for comparative data. However, many of the trials were short-term and not designed to capture information on these types of adverse events. Thus, it is likely that many patients who experienced these symptoms did not have them reported or recorded in these studies.
It may be difficult to determine the subset of patients who have an increased risk for harm, but it is important to do so. Studies have identified some genes that affect the efficacy of montelukast. It is likely that genetics or other inherent characteristics also affect its safety. In addition, we know that it can affect the brain. We encourage the FDA to require more definitive research on this topic as soon as possible.
In the meantime, patients, parents, and clinicians need to be aware of the risk for neuropsychiatric events so that they can weigh the benefits and risks for each patient – especially if the drug is prescribed for mild symptoms. Many patients and parents are not sufficiently informed about these risks so they can’t make an informed choice.
What can FDA do to help patients, parents, and prescribers make an informed decision on whether to use this drug? Require that a brief, easy-to-understand medication guide and checklist are provided by the prescriber prior to writing the prescription. FDA has required checklists on other medical products, which patients or parents must sign to show they understand the risks. The purpose is to improve informed consent and help patients recognize and appropriately respond to neuropsychiatric side effects.
In summary, we need much better data to determine the likely benefit and risk of harm for patients. FDA has an important role to play in encouraging this research. In the meantime, patients, parents, and clinicians must know about the risks so that they can make an informed decision about whether to use montelukast.
According to the Singulair label neuropsychiatric symptoms include, but are not limited to, agitation, aggressive behavior or hostility, anxiousness, depression, disorientation, disturbance in attention, dream abnormalities, dysphemia (stuttering), hallucinations, insomnia, irritability, memory impairment, obsessive compulsive symptoms, restlessness, somnambulism, suicidal thinking and behavior (including suicide), tic, and tremor.