A randomized, controlled trial comparing acetaminophen plus ibuprofen versus acetaminophen plus codeine plus caffeine (Tylenol 3) after outpatient breast surgery

Ann Surg Oncol. 2012 Nov;19(12):3792-800. doi: 10.1245/s10434-012-2447-7. Epub 2012 Jun 20.


Background: The combination of acetaminophen, codeine, and caffeine (Tylenol 3, T3) is a standard postoperative analgesia after breast surgery despite the adverse effects and variable efficacy of narcotics. This study compared the efficacy of a nonnarcotic approach (acetaminophen and ibuprofen; AcIBU) to T3 after outpatient breast surgery.

Methods: This double-blind randomized equivalence trial involved patients undergoing outpatient breast surgery. Patients were randomized (stratified by procedure type) to receive AcIBU or T3 four times daily for 7 days, or until free of pain. Pain intensity, measured four times daily by the visual analog scale, was the primary outcome; secondary outcomes were pain relief with analgesic, days until freedom from pain, adverse effects, discontinuation of drug as a result of adverse effects, and patient satisfaction.

Results: There were 71 patients randomized to AcIBU and 70 patients to T3. Repeated measures analysis showed no significant difference in average pain intensity over 7 days (AcIBU 19.9 mm vs. T3 20.6 mm; P = 0.78). Similarly, there was no significant difference in pain relief with analgesic (P = 0.46). Although no difference in the incidence of adverse effects was observed (P = 0.94), discontinuation of the study drug as a result of adverse effects was more common with T3 (19 % vs. 6 %; P = 0.018). No significant differences were identified in days until freedom from pain or patient satisfaction; 92 % of AcIBU and 89 % of T3 patients were satisfied with their pain control (P = 0.55).

Conclusions: AcIBU is a safe, effective method of pain control after outpatient breast surgery. Compared to T3, it provides at least equivalent analgesia and has a more tolerable adverse effect profile.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen / administration & dosage*
  • Adult
  • Ambulatory Surgical Procedures / adverse effects
  • Analgesics, Non-Narcotic / administration & dosage
  • Breast Neoplasms / complications
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / surgery*
  • Caffeine / administration & dosage*
  • Central Nervous System Stimulants / administration & dosage
  • Codeine / administration & dosage*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Humans
  • Ibuprofen / administration & dosage*
  • Middle Aged
  • Narcotics / administration & dosage
  • Neoplasm Staging
  • Pain, Postoperative / drug therapy*
  • Pain, Postoperative / etiology
  • Postoperative Complications*
  • Prognosis
  • Prospective Studies
  • Tertiary Care Centers


  • Analgesics, Non-Narcotic
  • Central Nervous System Stimulants
  • Narcotics
  • Acetaminophen
  • Caffeine
  • Codeine
  • Ibuprofen