Allopurinol side effects and how to avoid them

Common allopurinol side effects | Serious side effects |  Rash | Diarrhea | Gout flare-up | Drowsiness | Liver problems | Kidney problems | Bone marrow suppression | Side effects timeline | Contraindications | Warnings | Interactions | How to avoid side effects | How to treat side effects

Allopurinol is a generic prescription drug that is classified as a xanthine oxidase inhibitor. It works by reducing the body’s production of uric acid, a normal body waste product. Reducing uric acid helps people with gout, a type of arthritis caused by a buildup of uric acid. Left untreated, uric acid crystals can form in the joints, causing pain and inflammation. 

In addition to treating gout, allopurinol is FDA-approved to treat high uric acid levels caused by the treatment of certain blood cancers, such as leukemia. Allopurinol can also treat recurring kidney stones in people with high levels of uric acid in their urine. Allopurinol can be prescribed as an oral tablet under different brand names, including Zyloprim and Lopurin. It can also be administered as an injection, which may be prescribed under the brand name Aloprim. 

Allopurinol is considered an effective, long-term treatment for managing gout. Although it’s generally a safe drug, allopurinol may cause some side effects. Side effects are usually mild when the drug is taken as prescribed. Continue reading to learn more about the side effects of allopurinol. 

Common side effects of allopurinol

Most people who take allopurinol as prescribed don’t experience side effects. However, allopurinol can cause side effects that range in severity from mild to serious. You should seek medical attention if side effects persist or worsen. The most common side effects of allopurinol include:

• Skin rash
• Diarrhea
• Gout flare-ups
• Drowsiness
• Nausea
• Vomiting

Serious side effects of allopurinol

In rare cases, allopurinol may cause serious side effects. You should consult a healthcare provider if you experience any of the following serious side effects of allopurinol:

• Severe skin rash
• Allergic reaction with signs or symptoms such as rash, trouble breathing, and swelling of the face or throat
• Kidney problems, such as kidney failure, damage, or impairment
• Liver problems, such as liver failure, damage, or impairment
• Low white blood cell counts (leukopenia)
• Bone marrow suppression
• Gastrointestinal problems, such as gastrointestinal bleeding, inflammation of the pancreas (pancreatitis), and swelling of the tongue or salivary glands
• Respiratory problems, including asthma and bronchospasm
• Seizures
• Inflammation of the nerves in the arms, feet, hands, and eyes

Rash

Skin rash is one of the most common side effects of allopurinol reported. However, it develops in less than 1% of people taking allopurinol and is more likely to occur in people with decreased kidney function or who are also taking certain drugs, such as ampicillin or amoxicillin. Skin rash can indicate a potentially serious or even life-threatening problem. For this reason, always contact a healthcare professional and stop taking allopurinol even if you experience a mild skin rash. Other serious side effects, such as fever, chills, and joint pain, can accompany a skin rash and indicate a serious problem. 

Diarrhea

Diarrhea is an uncommon side effect of allopurinol, experienced by 1% or less of patients taking the drug. It is not typically life-threatening unless it persists or is watery or bloody. In severe cases, contact a healthcare professional for medical advice.

Gout flare-up

Allopurinol may cause acute gout attacks when the drug is first started due to the rapid lowering of uric acid levels. To avoid gout flare-ups, healthcare professionals usually recommend starting allopurinol at low doses. A healthcare provider may also prescribe colchicine or a nonsteroidal anti-inflammatory drug (NSAID) at the start of therapy to prevent gout attacks. Flare-ups are temporary and not life-threatening. You should continue taking allopurinol if you experience a gout attack at the start of treatment. 

Drowsiness

Drowsiness is not commonly experienced by people taking allopurinol. However, driving or operating machinery should be avoided while taking allopurinol until you’re aware of how allopurinol affects you. Talk to a healthcare provider if you experience drowsiness that interferes with your daily activities.

Liver problems

In rare cases, severe liver problems, such as liver toxicity, have been reported in people taking allopurinol. Liver toxicity, or hepatotoxicity, is usually reversible. Liver enzyme levels may need to be monitored, especially in people with liver disease, as allopurinol may cause elevations in liver enzyme levels.

Kidney problems

Kidney failure, although rare, has been reported in people taking allopurinol, especially those with pre-existing kidney problems. People with kidney problems may need to be started on lower doses than normal and monitored throughout treatment with allopurinol. Elevated blood urea nitrogen (BUN) levels have been reported in people with kidney disease who take allopurinol. 

Bone marrow suppression

People taking other drugs along with allopurinol have experienced bone marrow suppression as early as 6 weeks to as long as 6 years after starting allopurinol. Bone marrow suppression is a decrease in the production of blood cells in the bone marrow. 

How soon do allopurinol side effects start?

The side effects of allopurinol can develop early during treatment. For example, gout flare-ups typically occur at the start of treatment as uric acid levels rapidly drop. Allergic reactions, such as rash, itching, and trouble breathing, can develop right after the first dose. However, other serious side effects, such as liver problems, could take weeks to months to appear with symptoms. 

How long do allopurinol side effects last?

Most side effects of allopurinol, such as nausea and drowsiness, are mild and go away after treatment is discontinued. Severe side effects, such as severe allergic reactions, liver or kidney problems, and blood cell problems, may take weeks, months, or sometimes years to recover from. If mild side effects don’t resolve within one to two weeks, consult a healthcare provider for medical advice. 

What are the long-term side effects of allopurinol?

Allopurinol is considered a safe, long-term treatment for gout. Studies evaluating the long-term use of allopurinol have found that the risk of toxicity with allopurinol is low. The drug also remains effective for long-term use, with studies showing that long-term allopurinol treatment reliably helps reduce gout flare-ups. 

Allopurinol contraindications

Allopurinol is contraindicated in people who have had a hypersensitivity reaction to the drug.

Pregnancy

Allopurinol is prescribed cautiously and only as needed to pregnant women. There are no adequate studies that conclude whether allopurinol is safe in pregnant women. However, animal studies and limited human studies indicate that allopurinol may cause harmful effects in an unborn baby. Consult a healthcare provider before taking allopurinol while pregnant.

Breastfeeding

Allopurinol has been shown to pass through breast milk in mothers taking allopurinol. However, the exact effects of allopurinol in nursing infants is not known. Although allopurinol does not necessarily have to be discontinued while breastfeeding, healthcare providers may suggest monitoring the nursing infant for potential problems, particularly allergic reactions such as skin rash. 

Children

Allopurinol is rarely used in children. However, it may be used to treat high uric acid levels in children with certain cancers who are receiving chemotherapy or children with purine metabolism problems. Allopurinol IV injections have been studied in children and found to be safe and effective.

Allopurinol warnings

Even though allopurinol side effects are uncommon, allopurinol may cause problems in people with pre-existing medical conditions or who are taking certain types of drugs.

Cautions

Allopurinol can build up in the body in people with liver disease or kidney disease, so dose adjustments or extra monitoring may be required. 

In rare cases, some people may experience a potentially fatal adverse effect of allopurinol called allopurinol hypersensitivity syndrome, or AHS. Some people carry a gene variant called HLA-B*5801 that puts them at an increased risk for AHS. People who are positive for the HLA-B*5801 gene may be recommended to avoid the use of allopurinol. Some groups of people are more likely to carry this gene than others, including:

• Africans and African-Americans
• Asians (Han Chinese, Korean, Thai, etc.)
• Native Hawaiians and Pacific Islanders

Extra monitoring may be recommended for people who are at an increased risk of allergic reactions to allopurinol.

Abuse and dependence

Allopurinol does not carry a risk for abuse, physical dependence, or withdrawal. 

Overdose

Contact a poison control center or get emergency medical care if an overdose of allopurinol is suspected. An overdose of allopurinol can be fatal and require immediate medical attention. The maximum dosage of allopurinol is 800 mg per day. 

Allopurinol interactions

Like many other prescription drugs, allopurinol can interact with certain medications and substances. In some cases, drug interactions can decrease the effectiveness of allopurinol. In other cases, drug interactions can increase the risk of adverse effects. 

Problems can occur when allopurinol is combined with:

• Anticoagulants: Allopurinol may increase levels of anticoagulants, such as warfarin, which can increase the risk of bleeding problems.
• Certain antibiotics: There is an increased risk of skin rash when allopurinol is combined with drugs like ampicillin or amoxicillin.
• Certain immunosuppressants: Some immune suppressants, particularly azathioprine, mercaptopurine, and cyclosporine, may require a lower dose to prevent toxicity and serious side effects when combined with allopurinol.
• Thiazide diuretics: Thiazide diuretics, such as hydrochlorothiazide, may increase the risk of severe hypersensitivity reactions with allopurinol.
• Antacids: Aluminum hydroxide, found in antacid products like Maalox, may decrease the body’s absorption of an oral dose of allopurinol. Allopurinol should be taken at least three hours before or after taking an antacid. 

How to avoid allopurinol side effects

Fortunately, serious side effects of allopurinol are rare and often reversible. Some of the side effects, however, can be worrisome for some people. Taking allopurinol as prescribed and following a few good medication practices may help lower the risk of serious side effects. 

1. Discuss your medical history with your prescriber

For a drug like allopurinol, one of the surest ways to avoid side effects is to discuss your complete medical history with the prescribing healthcare provider. Some medical conditions, such as liver or kidney disease, may increase the risk of side effects with allopurinol. Make sure the prescriber knows about any of the following problems you may have:

• Allergic reactions to allopurinol
• Kidney disease
• Liver disease
• Heart failure
• An active gout attack

2. Tell the prescriber about any medications you take

Another way to avoid problems with allopurinol is to give the prescriber a complete list of prescription drugs, over-the-counter drugs, and dietary supplements you take. 

To prevent certain side effects, your healthcare provider may recommend adjusting doses, avoiding certain medications, or adjusting the timing of your medications. Tell your doctor if you take any of the following medications:

• Chemotherapy drugs
• Immunosuppressants
• Blood thinners
• Antibiotics
• Antacids
• Thiazide diuretics

3. Take allopurinol as instructed

Follow the instructions given by your prescriber or printed on the prescription label. If you miss a dose, take the dose as soon as you remember. If it’s almost time for the next dose, skip the missed dose and take the next dose as scheduled. Never take two doses to make up for a missed dose. 

4. Avoid driving or other risky activities

Although uncommon, allopurinol may cause drowsiness. When first taking this medicine, ease off on driving, operating machinery, or engaging in potentially hazardous activities that require alertness and focus.

5. Take allopurinol with a meal

Allopurinol may be better tolerated when taken with a meal. Taking allopurinol with food may help prevent certain gastrointestinal side effects, such as nausea.

6. Drink plenty of fluids

It’s important to drink plenty of fluids with allopurinol to prevent potential kidney problems and ensure the drug remains effective. It is recommended to drink at least 2 liters (68 ounces) of fluids each day while taking allopurinol.

7. Avoid heavy alcohol consumption

Alcohol is known to cause increased uric acid levels that may lead to a gout flare-up. The risk of a gout attack can increase with higher consumption of alcohol. Try to limit your alcohol intake while taking allopurinol, especially if you’re just starting treatment. 

8. Avoid certain antacids

Check the active ingredients of over-the-counter antacids. Any antacids that contain aluminum hydroxide may decrease your body’s ability to absorb allopurinol. If you need to take an antacid, don’t take a dose of allopurinol three hours before or three hours after taking the antacid.

How to treat side effects of allopurinol

Fortunately, most people don’t experience side effects when using allopurinol. In general, the side effects of allopurinol are mild. However, you should contact a healthcare provider or seek immediate medical attention if you experience side effects that are serious or particularly unusual.

Gout flare-up

Contact your healthcare provider for guidance if you experience a gout flare-up while taking allopurinol. Your healthcare provider will typically recommend continuing treatment with allopurinol. They may also recommend an NSAID or colchicine to prevent a gout flare-up when first starting treatment with allopurinol. 

Skin rash

Stop taking allopurinol and contact your healthcare provider. A skin rash may be an early sign of a severe hypersensitivity reaction. If you experience fever, chills, joint pain, trouble breathing, or swelling of the face or throat, seek medical attention immediately. 

Liver problems

Stop taking allopurinol and contact a healthcare professional if you experience signs of a serious decline in liver function including:

• Yellowing of the skin or eyes
• Smelly or dark urine
• Pale or clay-colored stools
• Weight loss
• Loss of appetite
• Pain in the upper right area of the stomach region
• Nausea
• Severe tiredness

Kidney problems

Stop taking allopurinol and contact a healthcare professional if you experience signs of a serious kidney problem including:

• Decreased urination
• Painful urination
• Blood in the urine

Allergic reactions

The most serious side effects of allopurinol include allergic reactions. Stop taking allopurinol and contact your healthcare provider if you experience signs or symptoms of an allergic reaction including:

• Skin rash (even a mild skin rash)
• Fever
• Swelling of the face
• Enlarged lymph nodes
• Blisters
• Trouble breathing

Sources

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• Allopurinol drug summary, Prescriber’s Digital Reference
• Allopurinol tablet prescribing information, U.S. National Library of Medicine
• Allopurinol sodium injection prescribing information, U.S. National Library of Medicine
•  Effect of allopurinol on mortality and hospitalisations in chronic heart failure: a retrospective cohort study, Heart
• Gout, StatPearls
• Long-term use of allopurinol in the treatment of gout, Annals of Rheumatic Diseases
• The allopurinol hypersensitivity syndrome, Journal of the American Academy of Dermatology