Tylenol with Codeine
From Pharmacopedia
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Opioid analgesic (codeine, weak), Non-opioid analgesic (acetaminophen), Schedule III controlled substance, Fixed-dose combination
Codeine / Acetaminophen
Tylenol with Codeine #3 (30 mg codeine), Tylenol #4 (60 mg codeine), Capital with Codeine, Phenaphen with Codeine
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Summary
Classes
Common uses
Mild to moderate acute pain0, Postoperative pain (mild)0
Pharmacy
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
US FDA Max
Acetaminophen 4 g/d absolute; codeine 240-360 mg/d typical practical limit
Pharmacology
Routes
Oral
Onset
30-60 minutes
Duration
4-6 hours
Half-life
Codeine 2.5-3.5 hours; acetaminophen 1-3 hours[2]
Bioavailability
Codeine ~60% (oral); acetaminophen 85-98%[2]
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 status
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)[2]
Purported mechanism
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.0 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[1].
References
- ↑ CPIC Guideline for CYP2D6, OPRM1, and COMT and Opioid Use, 2021. https://cpicpgx.org/guidelines/cpic-guideline-for-codeine-and-cyp2d6/
- ↑ 2.0 2.1 2.2 FDA Prescribing Information, Tylenol with Codeine (codeine phosphate / acetaminophen), Janssen, current revision. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/009898s071lbl.pdf