View source for Tylenol with Codeine

{{MedTemplate
| generic           = Codeine / Acetaminophen
| brand             = Tylenol with Codeine #3 (30 mg codeine), Tylenol #4 (60 mg codeine), Capital with Codeine, Phenaphen with Codeine
| structure         =
| classes           = [[:Category:Opioid_analgesics|Opioid analgesic (codeine, weak)]], [[:Category:Non-opioid_analgesics|Non-opioid analgesic (acetaminophen)]], [[:Category:Schedule_III_controlled_substances|Schedule III controlled substance]], [[:Category:Fixed-dose_combinations|Fixed-dose combination]]
| uses              = <vote slug="moderate-acute-pain-use">Mild to moderate acute pain</vote>, <vote slug="post-surgical-mild-pain-use">Postoperative pain (mild)</vote>
| starting_dose     = 1-2 tablets (15-60 mg codeine, 300-600 mg acetaminophen) PO every 4-6 hours as needed
| preparations      = Codeine/acetaminophen 15/300 (#2 historical), 30/300 (#3), 60/300 (#4) mg tablets; 12/120 mg/5 mL elixir
| fda_max           = Acetaminophen 4 g/d absolute; codeine 240-360 mg/d typical practical limit
| pill_id           =
| routes            = Oral
| onset             = 30-60 minutes
| duration          = 4-6 hours
| halflife          = Codeine 2.5-3.5 hours; acetaminophen 1-3 hours<ref name="tylenol-codeine-label">FDA Prescribing Information, Tylenol with Codeine (codeine phosphate / acetaminophen), Janssen, current revision. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/009898s071lbl.pdf</ref>
| bioavailability   = Codeine ~60% (oral); acetaminophen 85-98%<ref name="tylenol-codeine-label" />
| 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" />
| mechanism         = <vote slug="codeine-acetaminophen-mech-claim">Codeine is a prodrug; 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>.
}}

== References ==
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