Can you take allopurinol and Tylenol (acetaminophen) together?

Allopurinol and Acetaminophen (Tylenol) Compatibility

Yes, allopurinol and acetaminophen (Tylenol) can be safely taken together as there are no significant drug interactions between these medications.

Medication Overview

Allopurinol

• Mechanism: Xanthine oxidase inhibitor that reduces uric acid production
• Primary uses: Treatment of gout, tumor lysis syndrome, and certain types of kidney stones
• Metabolism: Converted to active metabolite oxypurinol with elimination half-life of 23.3 ± 6.0 hours 1

Acetaminophen (Tylenol)

• Mechanism: Analgesic and antipyretic that inhibits prostaglandin synthesis
• Primary uses: Pain relief and fever reduction
• Metabolism: Primarily hepatic through glucuronidation and sulfation

Evidence for Safety of Combination

The available clinical guidelines do not list acetaminophen as having significant interactions with allopurinol. The British Association of Dermatologists' guidelines for allopurinol prescribing specifically mention several drug interactions but do not include acetaminophen 2. Similarly, the EULAR guidelines for gout management do not list acetaminophen as having interactions with allopurinol 2.

Known Drug Interactions with Allopurinol

Allopurinol does have important interactions with other medications that should be monitored:

1. Azathioprine and 6-mercaptopurine: Require 65-75% dose reduction when used with allopurinol 2
2. Thiazide diuretics: May increase risk of hypersensitivity reactions 2, 3
3. Warfarin (dicumarol): May require dose adjustment 2, 3
4. Cyclosporine: May require dose adjustment 2
5. Chlorpropamide: May require dose adjustment 2

Research on Allopurinol and Acetaminophen

Interestingly, some research suggests that allopurinol may actually have protective effects against acetaminophen-induced hepatotoxicity:

• A 2014 study found that pretreatment with allopurinol (18 hours prior) reduced liver injury by 88% in mice given acetaminophen overdose 4
• A 2016 study demonstrated that allopurinol protected against acetaminophen-induced hepatotoxicity in rats 5
• Earlier research (1990) showed allopurinol had protective effects against oxidative stress during acetaminophen-induced hepatotoxicity 6

Clinical Considerations

While these medications can be taken together, there are important clinical considerations:

1. Renal function: Allopurinol dosage should be reduced in patients with renal impairment 1
2. Hypersensitivity risk: Monitor for allopurinol hypersensitivity syndrome, which can be severe and potentially fatal 7
3. Appropriate prescribing: Ensure allopurinol is prescribed for appropriate indications (gout, tumor lysis syndrome) 3

Practical Recommendations

• No dose adjustments are needed when taking allopurinol and acetaminophen together
• Maintain regular monitoring of renal and hepatic function when on long-term allopurinol therapy
• Be vigilant for signs of hypersensitivity reactions (rash, fever, eosinophilia, hepatic or renal dysfunction)
• Consider HLA-B*5801 testing in high-risk populations before initiating allopurinol 3

In conclusion, acetaminophen and allopurinol do not have clinically significant interactions and can be safely taken together, with appropriate monitoring for the known side effects of each medication individually.