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Allopurinol (Zyloprim)

Date Published: 05/30/2004
Date Reviewed/Revised: 02/17/2024

(For veterinary information only)

WARNING
The size of the tablet/medication is NOT an indication of a proper dose. Never administer any drug without your veterinarian's input. Serious side effects or death can occur if you use drugs on your pet without your veterinarian's advice. 

It is our policy not to give dosing information over the Internet.

Brand Name: Zyloprim

Available in 100 mg and 300 mg tablets  

Background

Allopurinol is used to reduce uric acid in the bloodstream. Uric acid is produced in the normal degradation of biochemicals called purines. We eat purines every day and normally convert them via a multi-step process to a substance called allantoin, which is water soluble and easily excreted in urine. In short, purines are converted to hypoxanthine, then to xanthine, then to uric acid, and finally to allantoin.

The final step of this conversion is worthy of the most attention. When something goes wrong when uric acid converts to allantoin, uric acid builds up. Uric acid, which is not as soluble in water as allantoin, begins to form crystals that can show up as kidney stones (especially in human patients), bladder stones (especially in Dalmatians and in dogs with liver shunts), joint deposits (birds or humans with gout), or as deposits in other unpleasant places.

In the past, treating uric acid crystals was the only use for allopurinol. There has been some recent work using allopurinol as an alternative treatment for an exotic infection called Leishmaniasis and in the treatment of American Trypanosomiasis as well. Allopurinol has an inactive metabolite called inosine that disrupts the RNA synthesis of the organisms involved in these two infections.

Whether the problem is the natural inability to produce allantoin (birds), the inability to get uric acid into liver cells for conversion to allantoin (Dalmatians and animals with liver shunts), or excessive purine intake (humans with gout), the goal in this situation is to reduce uric acid production. Allopurinol was developed for just this use but has not proven useful to prevent urate stones in dogs with liver shunts.

The enzyme that converts hypoxanthine to xanthine and onto uric acid is called xanthine oxidase. Allopurinol binds this enzyme so that uric acid is not produced. Instead, hypoxanthine and xanthine levels build up as they are not converted.

In the past, treatment of uric acid crystals was the only use for allopurinol. There has been some recent work using allopurinol as an alternative treatment for an exotic infection called Leishmaniasis and in the treatment of American Trypanosomiasis as well. Allopurinol has an inactive metabolite called inosine that disrupts the RNA synthesis of the organisms involved in these two infections.

How this Medication is Used

Leishmania organism
Image courtesy of CDC Public Health Image Library.

Mostly, in veterinary medicine, allopurinol is used in dogs, but it can also be used in birds where gout is a problem. In dogs, a therapeutic diet low in purines is generally prescribed. Recall purines are converted to hypoxanthine, then to xanthine, then to uric acid, and finally to allantoin. Allopurinol blocks the conversion to uric acid so that hypoxanthine and xanthine levels increase. If there is too much xanthine in the system, then xanthine stones will be created instead of uric acid stones, and the patient will be just as uncomfortable. The way to prevent this is by using a low-purine diet. If the diet is used, there will not be enough xanthine to make stones even when allopurinol is in use. No uric acid stones and no xanthine stones, either. If the diet is not controlled, allopurinol should not be used.

Allopurinol may also have some use in treating such infections as Leishmaniasis and Trypanosomiasis, as noted above.

  • Allopurinol works equally well whether given with food or not.
  • Allopurinol is typically given twice daily.
  • Allopurinol should be stored at room temperature and protected from light. Do not refrigerate.
  • If a dose is accidentally skipped, do not double up on the next dose. Give the dose when you remember and time the next dose accordingly

Side Effects

Side effects are not common with allopurinol, but the most common ones relate to upset stomach: diarrhea, cramping, and nausea. More severe side effects have been seen in humans: bone marrow suppression, hepatitis, and vasculitis have been reported. If the patient has kidney disease, it is best to decrease the dose of allopurinol. If the patient is not properly monitored with testing, xanthine may build up, and xanthine bladder stones may result (see below).

Interactions with Other Drugs

  • Allopurinol combined with ampicillin and amoxicillin has led to skin rashes in some humans. This has been seen in dogs as well. 

  • The use of diuretics (furosemide, thiazides, etc.) may increase uric acid levels and interfere with the function of allopurinol.  It is best not to use these medications when attempting to address uric acid stones.

  • Several chemotherapy agents interact with allopurinol. Cyclophosphamide use will have a greater tendency towards bone marrow suppression if it is used concurrently with allopurinol. This effect is magnified if cyclosporine (an immunomodulator) is added to the mix. Azathioprine is not removed from the body at a normal rate when it is used with allopurinol, thus increasing its potential for toxicity. 

  • In some human patients, the combination of allopurinol and trimethoprim sulfa has led to a drop in platelet count (possibly interfering with normal blood clotting mechanisms). 

  • Airway dilators such as theophylline are less effective when used with allopurinol.

Concerns and Cautions

The formation of xanthine bladder stones is probably the main concern when using allopurinol. This is most likely to happen if there is cheating on the therapeutic diet that accompanies allopurinol use.

  • Safe use of allopurinol in pregnancy has not been established.

  • Human patients with kidney failure have developed a life-threatening liver failure with fever, skin rashes, and worsening kidney failure. If allopurinol is to be used in a pet with poor liver or kidney function, the dose absolutely must be reduced, and close monitoring for any similar reaction is vital.

  • Allopurinol is not helpful in managing uric acid stones in patients with liver shunts.

See more information on uric acid bladder stones in dogs.

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