5 Allopurinol Interactions You Should Know About
Key takeaways:
Allopurinol (Zyloprim) is a common medication used to treat gout. It can also treat kidney stones and high uric acid levels in people with cancer.
Allopurinol has several possible medication interactions. It can interact with some blood pressure medications, penicillin antibiotics, warfarin, and more.
Make sure your healthcare provider and pharmacist have an updated list of medications you take. They can check for interactions and talk to you about how to manage them.
Table of contents
If you have gout, you know how painful and disruptive a gout attack can be. A buildup of uric acid crystals in your joints can lead to sudden feelings of pain, swelling, and warmth in one or more joints. Preventing and treating these symptoms, understandably, is a priority.
Allopurinol (Zyloprim) is a popular medication for preventing and treating gout attacks. It works by blocking an enzyme (protein) in your body called xanthine oxidase. By blocking this enzyme, allopurinol lowers uric acid levels in your body to help control gout attacks. It can also help prevent certain types of kidney stones and treat tumor lysis syndrome (TLS). TLS is a condition that affects certain people with cancer.
Even though allopurinol has several benefits, it has several interactions to keep in mind. Some interactions are mild and manageable, while others are more serious. Below are five of the most important allopurinol interactions you should know.
1. Azathioprine and mercaptopurine
Azathioprine (Imuran) is a medication that treats rheumatoid arthritis (RA). It’s also prescribed to protect a new kidney after an organ transplant. Its sibling medication, mercaptopurine (Purinethol), aims to stop cancer growth in certain people living with blood cancer.
What’s more, azathioprine is a prodrug. A prodrug is a medication that changes into its active form once it enters your body. Like a caterpillar turning into a butterfly, enzymes in your body tell azathioprine to become mercaptopurine. This is the active form of azathioprine.
Allopurinol can get in the way of this conversion. It blocks xanthine oxidase, an enzyme that’s responsible for metabolizing azathioprine and mercaptopurine. This may cause higher levels of azathioprine or mercaptopurine in your body. And that could lead to a higher risk of side effects, such as low blood cell counts.
When possible, it’s best to avoid taking these medications with allopurinol. But if it’s necessary, your healthcare provider will likely lower your dose of azathioprine or mercaptopurine. They’ll also want to check in and ask about side effects.
2. ACE inhibitors
Angiotensin-converting enzyme (ACE) inhibitors are a group of medications used to treat high blood pressure. They’re also prescribed for conditions like diabetes and heart failure. Top examples are lisinopril (Zestril), captopril, and enalapril (Vasotec).
The specific reason isn’t clear, but ACE inhibitors like these may increase the risk of hypersensitivity reactions (allergic reactions) to allopurinol.
On its own, allopurinol has a risk for causing dangerous skin reactions. ACE inhibitors may also lead to a skin reaction called Stevens-Johnson syndrome (SJS). When they’re combined, it’s more likely to experience dangerous skin reactions. Rashes that aren’t caught early could become severe. Possible symptoms of SJS include fever, muscle aches, and severe skin blisters. This is a medical emergency.
As a precaution, you should stop taking allopurinol if you develop a rash of any severity. Contact your healthcare provider right away.
3. Thiazide diuretics
Thiazide diuretics are medications that treat high blood pressure and fluid buildup in your arms and legs (edema). A common example is hydrochlorothiazide (Microzide).
Like ACE inhibitors, thiazide diuretics increase the risk of hypersensitivity reactions to allopurinol. Combining them can lead to a rare but serious condition called drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome.
DRESS syndrome can occur anywhere from 2 to 8 weeks after starting a medication like allopurinol. Common signs of DRESS syndrome include an unexplained rash, fever, and swollen lymph nodes. Studies have found that older adults and people with kidney problems are at a higher risk for DRESS syndrome.
Like SJS, DRESS syndrome is a medical emergency. If you develop a rash while taking these medications, you should stop taking allopurinol and contact your healthcare provider right away. Rashes that aren’t caught early on could become serious.
4. Penicillin antibiotics
Penicillins antibiotics are widely available medications for bacterial infections. Examples include ampicillin, amoxicillin (Amoxil), and combination medications that contain them, like Augmentin (amoxicillin/clavulanate).
Again, rashes are a concern when combining allopurinol and penicillin antibiotics. Taking them together can increase the risk of skin rashes.
If you develop a rash while taking both medications, you should stop taking allopurinol. Contact your healthcare provider for next steps. But if you have a blistering rash, fever, or other severe symptoms, get medical help right away.
5. Warfarin
Warfarin (Coumadin, Jantoven) is a blood thinner used to prevent and treat blood clots. If you take warfarin, you’ll need regular blood tests (INR/PT test) to make sure your warfarin dose is safe over time. This is because many foods and medications can interact with warfarin.
Allopurinol is no exception. It can enhance warfarin’s effects. This can make your blood “too thin,” which worsens the risk of dangerous bleeding or bruising. Keep an eye out for symptoms like dark or bloody stools, bleeding from your gums, and unexplained bruising.
If you take warfarin, you may still be able to take these medications together. Your healthcare provider may want to lower your warfarin dose or check your blood work more often.
When should I contact my healthcare provider about an allopurinol interaction?
The list above isn’t a complete list of allopurinol interactions. To prevent other interactions, make sure your healthcare provider and pharmacist have an updated list of medications you take. This list should include all your prescriptions, over-the-counter medications, and supplements. This will help them prevent and manage interactions.
Otherwise, if you’re worried about an allopurinol interaction, contact your healthcare provider or pharmacist as soon as you can. This is especially true if you develop a skin rash. But if your symptoms feel severe, it's better to call 911 or go to the nearest emergency room.
The bottom line
Allopurinol prevents and treats gout attacks. But it can interact with certain blood pressure medications, penicillin antibiotics, warfarin, and more. Most interactions can be managed with extra monitoring. Certain interactions should be avoided altogether. Your healthcare provider and pharmacist can tell you more about what to expect.
Why trust our experts?
References
Casper Pharma LLC. (2022). Allopurinol [package insert].
Kinyó, A., et al. (2012). Allopurinol-induced hypersensitivity syndrome. Orvosi Hetilap.
National Cancer Institute. (n.d.). Tumor lysis syndrome.
Qurie, A., et al. (2022). Allopurinol. StatPearls.
Sevinc, C., et al. (2019). Approach to DRESS syndrome associated with allopurinol use in a geriatric patient. European Journal of Geriatrics and Gerontology.
Sica, D. (2007). Angiotensin-converting enzyme inhibitors' side effects—Physiologic and non-physiologic considerations. The Journal of Clinical Hypertension.
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