Tylenol with Codeine: Difference between revisions
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| pregnancy = Limited use; codeine is excreted in breast milk and CYP2D6 ultra-rapid metabolizers can produce fatal neonatal opioid toxicity through breastfeeding (FDA 2017 contraindication in lactation).{{citation needed}} | | pregnancy = Limited use; codeine is excreted in breast milk and CYP2D6 ultra-rapid metabolizers can produce fatal neonatal opioid toxicity through breastfeeding (FDA 2017 contraindication in lactation).{{citation needed}} | ||
| legal = [[USLegal:Schedule III|Schedule III controlled substance]] in US. '''Contraindicated in children <12''' for any indication and in any age post-tonsillectomy/adenoidectomy (FDA 2017 black-box advisory)<ref name="tylenol-codeine-label" /> | | legal = [[USLegal:Schedule III|Schedule III controlled substance]] in US. '''Contraindicated in children <12''' for any indication and in any age post-tonsillectomy/adenoidectomy (FDA 2017 black-box advisory)<ref name="tylenol-codeine-label" /> | ||
| mechanism = <vote slug="codeine-acetaminophen-mech-claim">Codeine is | | mechanism = <vote slug="codeine-acetaminophen-mech-claim">Codeine is itself essentially inactive; its analgesic activity depends on CYP2D6-mediated O-demethylation to morphine (~10% conversion in normal metabolizers). CYP2D6 ultra-rapid metabolizers produce dangerously high morphine levels with risk of fatal respiratory depression, especially in children and infants exposed via breast milk; CYP2D6 poor metabolizers get little analgesic benefit.</vote> The combination with acetaminophen provides additive non-opioid analgesia and lowers required codeine dose. CYP2D6 PGx is one of the most clinically actionable in current pharmacology; CPIC supports genotype-guided opioid selection<ref name="cpic-opioid-cyp2d6">CPIC Guideline for CYP2D6, OPRM1, and COMT and Opioid Use, 2021. https://cpicpgx.org/guidelines/cpic-guideline-for-codeine-and-cyp2d6/</ref>. | ||
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== References == | == References == | ||
<references /> | <references /> | ||