Anti-Infective Drugs Advisory Committee
Center for Drug Evaluation and Research, Food and Drug Administration
April 24, 2001
Issue: Clinical Development of Products for Drooling in Neurologically Impaired Children
QuQuestions/Discussion Points for the Advisory SubCcommittee:
Because these products will likely reduce salivation at some doses, the questions for the subcommittee are directed to safety, dose titration, and ethical issues as follows:
Patients with neurologic impairment, cognitive impairment, and/or inability to communicate are at a distinct disadvantage with respect regards to the measurement of anticipated pharmacologically induced adverse events. The development of measures for pain and discomfort in individuals with disabilities has been limited, and there is very little information available in the literature.
Please include in your discussion measurement instruments/approaches and who should perform the assessments.
Currently, the majority of antimuscarinics are extemporaneously compounded into pediatric formulations using either the IV preparation or crushed tablets. The concentrations of the active ingredients as well as the excipients may vary.. This can affect stability and absorption. It also may increase the possibility of dosing errors. Also, there is variation in the way that individual patients respond to medications. There may be some patients who are unable to tolerate even the minimal effective dose because of undesirable side effects. The optimal dosing regimen will need to be individualized. It will require a balance between inhibition of saliva production and adverse events for any given patient.
FDA thinks an optimal dosing regimen should include a formulation which is not extemporaneously compounded and the formulation which can be titrated.
Patients with disabilities are a unique and vulnerable population. While they are frequently viewed to be similar to pre-communicative children, there are important differences. These patients will have neurologic deficits that affect motor function, but within this population, there are varying degrees of cognitive function and ability to communicate. Communication and sensory disorders may mask a normal intellect.
Please consider in your discussion: