FDA Announces the Federal Register Notice Requesting Comments on the Use of Codeine-Containing Analgesics in Children Under 12 Years of Age Subsequent to CYP2D6 Genetic Testing

FDA Announces the Publication of a Federal Register Notice Establishing a Public Docket Requesting Comments on the Use of Codeine-Containing Analgesics in Children Under 12 Years of Age Subsequent to CYP2D6 Genetic Testing

On June 29, 2020, the U.S. Food and Drug Administration (FDA) announced the publication of a Federal Register notice titled “Use of Codeine-Containing Analgesics in Children Under 12 Years of Age Subsequent to CYP2D6 Genetic Testing.” This notice establishes a public docket intended to solicit public comments on specific questions related to the use of codeine for analgesia in children under 12 years of age and the use of cytochrome P450 2D6 (CYP2D6) testing in children under 12 years of age prior to treatment with codeine-containing analgesics. Analgesic products with codeine as an active ingredient are opioids that are generally indicated for the relief of mild to moderate pain where the use of an opioid analgesic is appropriate and for which alternative treatments are inadequate. Codeine is partially metabolized to morphine, its most potent analgesic metabolite, through the CYP2D6 pathway. CYP2D6 is a polymorphic enzyme, leading to a high degree of variability for metabolism of codeine because of underlying genetic differences in CYP2D6 activity. Because of this variability, depending on CYP2D6 activity, patients may be at risk for therapeutic failure (‘‘poor metabolizers’’) or at risk for opioid-related toxicity (‘‘ultra-rapid metabolizers’’). Codeine-containing prescription analgesic products approved by the FDA are currently contraindicated in children under 12 years of age. The Agency is considering a request for regulatory action to amend this contraindication to provide for use in children under 12 years of age who are shown to be CYP2D6 normal metabolizers (also known as ‘‘extensive metabolizers’’) or CYP2D6 intermediate metabolizers based on pharmacogenetic testing that includes CYP2D6 copy number or gene duplication detection. To properly assess the appropriateness and potential impact of making this amendment to the contraindication, the Agency seeks input from the healthcare community and the public on the following issues: (1) Pain management in children under 12 years of age; (2) availability and clinical utility of CYP2D6 genotyping tests; and (3) e-prescribing availability as a potential mitigation approach for opioid analgesic access in urgent situations. The “Use of Codeine-Containing Analgesics in Children Under 12 Years of Age Subsequent to CYP2D6 Genetic Testing” public docket is available at https://go.usa.gov/xfvCs. Please refer to the public docket for more details. FDA established this public docket to collect public comments. FDA will consider all information and comments submitted. You may submit your comments to this public docket by August 28, 2020 to the Docket No. FDA–2020–N–1046 available at https://www.regulations.gov. Your comments do make a difference and can impact the outcomes of FDA regulatory policy. Share your knowledge and experience and make your voice count.