What is the equivalent dose of Tramadol to Tylenol (Acetaminophen) with Codeine?

Tramadol to Tylenol with Codeine Equivalence

Tramadol 100 mg is approximately equivalent to Tylenol (acetaminophen) 300 mg with codeine 30 mg (Tylenol #3). 1

Potency Comparison

Tramadol and codeine are both considered weak opioids with similar analgesic properties, though they work through different mechanisms:

• Tramadol has a dual mechanism of action:

  • Weak mu-opioid receptor agonist
  • Inhibition of norepinephrine and serotonin reuptake 2

• Codeine is a prodrug that requires CYP2D6 metabolism to morphine for analgesic effect 3

Clinical Evidence Supporting Equivalence

The FDA label for tramadol indicates that in clinical trials:

• Average daily doses of approximately 250 mg of tramadol in divided doses were generally comparable to five doses of acetaminophen 300 mg with codeine phosphate 30 mg daily 1
• This translates to tramadol 50 mg being roughly equivalent to one Tylenol #3 tablet

Additional evidence shows:

• In comparative trials, tramadol 37.5 mg/acetaminophen 325 mg combination tablets provided similar pain relief to codeine 30 mg/acetaminophen 300 mg capsules for chronic pain 4
• Tramadol 100 mg tended to provide analgesia superior to codeine 60 mg alone, but was not as effective as aspirin 650 mg with codeine 60 mg 1

Important Clinical Considerations

Genetic Variability

• Codeine efficacy varies significantly based on CYP2D6 metabolism:
  • Patients with genetic polymorphism of CYP2D6 (more common among Asians) may have less response to codeine 3
  • Drugs that inhibit CYP2D6 might reduce codeine's analgesic effects 3

Side Effect Profile

• Tramadol has:

  • Higher risk of serotonin syndrome
  • Lower risk of constipation compared to codeine 4
  • Potential for seizures in susceptible individuals 2

• Codeine has:

  • Higher rates of constipation (21% vs 11% with tramadol) 4
  • Higher rates of somnolence (24% vs 17% with tramadol) 4

Dosing Limitations

• Tramadol:

  • Maximum daily dose: 400 mg for adults, 300 mg for patients >75 years 2
  • Has limitations in dose titration related to neurotoxicity 3

• Codeine:

  • Limited by acetaminophen content in combination products
  • Typically dosed as 30-60 mg every 4-6 hours

Clinical Application

When converting between these medications:

1. Tramadol 50 mg ≈ Tylenol with codeine #3 (acetaminophen 300 mg/codeine 30 mg)
2. For daily dosing: Tramadol 250 mg daily ≈ 5 tablets of Tylenol with codeine #3 daily 1

Pitfalls to Avoid

• Do not exceed maximum acetaminophen dose (4000 mg/day) when using combination products
• Be cautious with tramadol in patients taking serotonergic medications due to risk of serotonin syndrome 2
• Consider reduced dosing in elderly patients, and those with hepatic or renal impairment 2
• Be aware that both medications may have different efficacy in patients with genetic variations in CYP2D6 metabolism 3

For optimal pain management, consider that both tramadol and codeine have limitations that may make them less desirable than other opioids, particularly in cancer pain settings 3.