How safe is acetaminophen use in patients treated with vitamin K antagonists? A systematic review and meta-analysis

source extracted confidence: high 2026-04-09
#acetaminophen #analgesics #blood-coagulation #humans #international-normalized-ratio

How safe is acetaminophen use in patients treated with vitamin K antagonists? A systematic review and meta-analysis

Caldeira et al., 2015 | Thromb Res | Meta Analysis

Citation

Caldeira Daniel, Costa João, ... Ferreira Joaquim J. How safe is acetaminophen use in patients treated with vitamin K antagonists? A systematic review and meta-analysis. Thromb Res. 2015-Jan;135(1):58-61. doi:10.1016/j.thromres.2014.10.011

Abstract

INTRODUCTION: Acetaminophen is a commonly prescribed and over-the-count used drug, and is considered to be the preferred treatment choice for anticoagulated patients requiring analgesic drug therapy. However, observational data have suggested that this drug combination may increase the International Normalized Ratio (INR) values and bleeding events in patients taking Vitamin K antagonists (VKAs). Still, the clinical impact of this putative effect remains unknown. Therefore, we performed a systematic review of randomized controlled trials (RCTs) to estimate the impact of concomitant use of acetaminophen and VKA in the INR measurements METHODS: Systematic review and meta-analysis of RCTs comparing acetaminophen versus placebo or no treatment, in VKA-treated patients and reporting INR estimates. Medline and Cochrane Library were searched up to April 2014. Primary outcome was the mean difference (MD) between the greatest INR elevations in each treatment arm. Random-effects meta-analysis was performed to derive pooled estimates and 95% Confidence Interval (CI). Heterogeneity was evaluated with I(2) test. RESULTS: Seven RCTs (n=225 patients) were included. Acetaminophen was associated with a mean 0.62 INR increase (95%CI: 0.46 to 0.78; I(2)=25%) compared to placebo in VKA-treated patients. Studies did not report any major bleeding event. Meta-regression showed a significant 0.17 mean increase of the INR per each daily gram of acetaminophen (95%CI: 0.004 to 0.33). CONCLUSION: Acetaminophen is associated with a statistically significant and possible clinically relevant increase in the INR, with a dose dependent relationship. Patients treated concomitantly with VKA and acetaminophen should be monitored more regularly for possible VKA dosage adjustment.

Key Findings

Seven RCTs (n=225 patients) were included. Acetaminophen was associated with a mean 0.62 INR increase (95%CI: 0.46 to 0.78; I(2)=25%) compared to placebo in VKA-treated patients. Studies did not report any major bleeding event. Meta-regression showed a significant 0.17 mean increase of the INR per each daily gram of acetaminophen (95%CI: 0.004 to 0.33).

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population See abstract
Sample Size 225
Age Range See abstract
Condition See abstract

MeSH Terms

  • Acetaminophen
  • Analgesics
  • Blood Coagulation
  • Humans
  • International Normalized Ratio
  • Observational Studies as Topic
  • Randomized Controlled Trials as Topic
  • Regression Analysis
  • Treatment Outcome
  • Vitamin K
  • Warfarin

Evidence Classification

  • Level: Meta Analysis
  • Publication Types: Journal Article, Meta-Analysis, Systematic Review
  • Vertical: vitamin-k

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09