THE PET PHARMACY By Wendy C. Brooks, DVM, DipABVP Educational Director, VeterinaryPartner.com

(for veterinary information only)

Brand Name: Zyloprim

Available in 100 mg and 300 mg tablets  

Background

Allopurinol is used to reduce uric acid in the blood stream. Uric acid is produced in the normal degradation of biochemicals called purines. We eat purines everyday and normally convert them in 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 with the conversion of uric acid 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 other unpleasant places.

Whether the problem is natural inability to produce allantoin (birds), 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.

The enzyme that converts hypoxanthine to xanthine and on to 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

Mostly, in veterinary medicine, allopurinol is used in dogs but it can also be used in birds when gout is a problem. In dogs, a therapeutic diet low in purines is generally prescribed. The low purine diet is crucial to avoid the formation of xanthine bladder stones. If the diet is not controlled, allopurinol should not be used.

Allopurinol may also have some use in the treatment of such infections as leishmaniasis and trypanosomiasis as noted above.

• Allopurinol works equally well whether given with food or not.

Side Effects

The most common side effects of allopurinol relate to upset stomach: diarrhea, cramping, nausea. In humans, bone marrow suppression, hepatitis, and vasculitis have been reported.

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. 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 in 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.
  

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

Date Published: 5/30/2004 5:30:00 PM
Date Reviewed/Revised: 12/12/2008