Uloric vs Allopurinol

Top 3 Differences Between Uloric & Allopurinol Gout Drugs:

  • Uloric patients had a 34% higher risk of cardiovascular death and 22% higher risk of death from any cause versus those taking allopurinol.
  • Uloric is only recommended for patients who cannot take allopurinol for any reason.
  • Uloric may be more effective at decreasing uric acid levels than allopurinol.

Allopurinol was FDA approved for the treatment of hyperuricemia (uric acid buildup) in 1966, but only three other drugs have received approval for the same indication since then. Uloric (febuxostat) was the most recent addition to this class of gout prescription, but it quickly generated controversy. According to several Uloric lawsuits and manufacturer Takeda's own clinical trial data, patients who use Uloric may have a substantially higher risk of serious cardiovascular events and even death.

Millions of Americans take Uloric or allopurinol on a daily basis. These patients may be confused about the safety and efficacy of their gout treatments. In an effort to dispel some of that confusion, we've put together this quick comparison to highlight the differences and similarities between Uloric and allopurinol.

Important: This comparison is not medical advice. You should speak with your doctor or pharmacist about how these gout drugs may or may not fit into your healthcare regimen.

Understanding Gout

What is gout?
A form of inflammatory arthritisWhat are the symptoms of gout?
Redness, pain and swelling of the joints, often starting with the big toeWhat causes gout?
Uric acid accumulation (often referred to as high serum urate levels) and crystallizationHow is gout treated?

  1. Anti-inflammatory drugs like colchicine (colcrys), corticosteroids, and non-steroidal anti-inflammatories (NSAIDs)
  2. Urate-lowering therapies (aka xanthine oxidase inhibitors) like allopurinol (Zyloprim), febuxostat (Uloric), pegloticase (Krystexxa), and probenecid

Uloric and Allopurinol Similarities

Uloric and allopurinol both reduce gout flares by decreasing the amount of uric acid in your blood. They do this by blocking the function of xanthine oxidase, an enzyme that makes uric acid.

Aside from their general purpose, Uloric and allopurinol also share the following qualities:

  • Available in two dosages
  • Taken daily in tablet form
  • Associated with a long list of side effects ranging from minor to life-threatening
  • Not recommended for patients who do not show symptoms of gout
  • Require a lower dose for patients with kidney failure
  • Often cause increased gout flares immediately after starting the drug
  • Associated with severe skin rashes
  • Interact or cannot be used with azathioprine, an anti-rejection drug, and mercaptopurine, a cancer drug
  • Unknown effects on infants

Uloric Has More Side Effects Than Allopurinol

Allopurinol has been used for over 50 years, and its side effects and efficacy are very well established. Uloric is much newer, having received FDA approval only ten years ago. Even so, the types and number of side effects known for Uloric significantly outnumber those of allopurinol. You can explore those differences in the table below.

Please note: the table below is not a comprehensive listing of Uloric and allopurinol side effects.

Uloric vs Allopurinol Side Effects

Allopurinol Uloric
  • Necrotizing angitis (severe blood vessel inflammation that decreases or prevents blood flow to tissue, causing the affected tissue to die)
  • Diarrhea
  • Peripheral neuropathy
  • Bone marrow lesion
  • Cardiovascular death
  • Blurred vision
  • Hearing loss
  • Ringing in the ears
  • Vertigo
  • Acid reflux
  • Constipation
  • Ulcers
  • Tremor
  • Temporary loss of blood flow to certain brain structures
  • Guillain-Barré syndrome (nerve damage caused by your own immune system)
  • Breast pain
  • Abnormal breast tissue growth in males
  • Erectile dysfunction
Source: Uloric Drug Label (Takeda Pharmaceuticals) and Zyloprim Drug Label (Casper Pharma)

Uloric vs Allopurinol Indications and Efficacy

Allopurinol Indications: for the treatment of gout, management of elevated uric acid levels caused by cancer therapy, and management of elevated uric acid levels in patients with recurrent kidney stones

Uloric Indications: for the chronic management of elevated uric acid levels (gout) in adults who cannot use allopurinol

Uloric May Be More Effective Than Allopurinol

Though both drugs decrease uric acid levels, one study indicates that Uloric may be more effective in that endeavor. According to researchers, 56.9% of Uloric users achieved satisfactory depression of uric acid levels versus only 44.8% of allopurinol users.

Uloric Is Deadlier Than Allopurinol

A 2018 study with an average of 2.6 years follow-up investigated the safety of febuxostat (Uloric) and allopurinol in gout patients with existing cardiovascular disease. Researchers found that Uloric was "non-inferior to allopurinol" when examining the time to first occurrence of a major adverse cardiovascular event (MACE). They included:

  • cardiovascular death
  • nonfatal myocardial infarction (heart attack)
  • nonfatal stroke
  • unstable angina (decreased blood flow to the heart) with urgent coronary revascularization

Despite this seeming similarity, the two drugs differed sharply in terms of how many patients died during the study. Patients in the febuxostat group were more likely to suffer either cardiovascular death (1.34x) or all-cause death (1.22x) than those in the allopurinol group. In total, 243 out of 3098 febuxostat patients and 199 out of 3092 allopurinol patients died during the course of the study. As a result, Uloric is only recommended for patients for whom allopurinol is ineffective.

Uloric is More Expensive Than Allopurinol

As of July 2019, a 30 tablet prescription for the lowest dose of Uloric costs around $350 without health insurance. In comparison, allopurinol is incredibly affordable at an average price of $33 for 30 tablets of the lowest available dose, also without health insurance.

Uloric Shortcomings and Legal Troubles

Uloric was initially celebrated as an advancement in gout treatment, but that sentiment shifted when the drug gained a black box warning in early 2018. Uloric has since been relegated to second-line treatment status, only prescribed to patients for whom allopurinol has failed. This forces such patients to choose between living with the higher risks of Uloric or the debilitating symptoms of unmanaged gout.

In addition to depriving gout patients of a much-needed treatment option, Uloric's lack of cardiovascular safety has given its manufacturer a plethora of legal troubles. Law firms nationwide have filed lawsuits against Takeda Pharmaceuticals claiming they failed to warn patients of Uloric's increased risk of death.

Authored by Katy Moncivais, Ph.D.Medical Editor
Photo of Katy Moncivais, Ph.D.
Katy Moncivais holds a Ph.D. in Biomedical Engineering from The University of Texas at Austin. She’s an experienced Regenerative Medicine Consultant with a demonstrated history of working in the hospital & healthcare industry. Skilled in adult stem cells, medical devices, biomechanics, bacterial and mammalian cell culture, and regenerative medicine, she provides guidance on an array of topics affecting consumers. In her role at ConsumerSafety.org, Dr. Moncivais works alongside the writing and research staff to help deliver fact-based news stories to consumers. Her unique professional history alongside her rigorous educational background allows her to contribute to a variety of consumer-focused topics with a fresh perspective. In addition, Dr. Moncivais reviews portions of medically driven content to ensure scientific accuracy.
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