Does Tylenol (Acetaminophen) Cause Constipation?
No, Tylenol (acetaminophen) does not cause constipation through the same mechanism as opioids, but there is epidemiological evidence suggesting a possible association that requires further investigation.
Key Evidence
The available evidence presents a nuanced picture regarding acetaminophen and constipation:
Epidemiological Association
A population-based study found that chronic constipation was significantly associated with acetaminophen use at ≥7 tablets per week [OR = 2.7 (1.1-6.6)], after adjusting for age, gender, and somatic symptom scores 1.
This same study also found associations with aspirin [OR = 1.7] and NSAIDs [OR = 1.8], suggesting the relationship may not be specific to acetaminophen alone 1.
Another study examining irritable bowel syndrome found associations between acetaminophen use and gastrointestinal symptoms, though this was confounded by other somatic pain complaints 2.
Clinical Trial Evidence
A large 12-month randomized controlled trial comparing acetaminophen 4g/day versus naproxen 750mg/day in 571 patients with osteoarthritis found that constipation was significantly MORE common with naproxen (9.9%) than with acetaminophen (3.1%, P<0.002) 3.
This trial demonstrated that acetaminophen was generally well tolerated with physician supervision for up to 12 months, with no hepatic or renal dysfunction observed 3.
Mechanism Considerations
Unlike opioids, which cause constipation through well-established μ-opioid receptor mechanisms in the gastrointestinal tract, acetaminophen has no known direct pharmacological mechanism that would cause constipation 4.
Opioid-induced constipation is a persistent and predictable adverse effect occurring in 41% of patients, requiring prophylactic bowel regimens 4.
Postoperative constipation is primarily attributed to opioid pain medications, anesthesia, and immobility—not to non-opioid analgesics like acetaminophen 4.
Clinical Interpretation
The epidemiological associations observed may reflect confounding factors rather than a direct causal relationship:
Patients taking frequent analgesics (≥7 tablets/week) likely have chronic pain conditions that independently affect bowel function 1.
The association was strongest in patients reporting multiple somatic symptoms, suggesting shared underlying factors 1, 2.
The controlled trial evidence showing lower constipation rates with acetaminophen compared to naproxen argues against a direct causative role 3.
Clinical Recommendations
Acetaminophen should NOT be avoided due to constipation concerns, as it does not share the well-established constipation risk of opioids 3.
When managing pain in patients prone to constipation, acetaminophen remains a safer choice than opioids, which require prophylactic laxative therapy 4.
If a patient on acetaminophen develops constipation, investigate other causes including: concurrent medications (especially opioids), reduced mobility, inadequate fluid intake, and underlying gastrointestinal conditions 4.
The multimodal analgesia approach combining acetaminophen with other non-opioid agents can reduce opioid requirements and thereby reduce constipation risk 4.
Important Caveats
The epidemiological studies showing associations had significant methodological limitations, including inability to establish causality and potential confounding by indication 1, 2.
Acetaminophen absorption occurs primarily in the small intestine via passive diffusion and is influenced by gastric emptying, but this does not translate to constipation as a common adverse effect 5.
While acetaminophen is generally safe, the primary concern remains hepatotoxicity with overdose, not gastrointestinal effects like constipation 5, 3.