allopurinol

[ALLO- + PURIN(E) + -OL².]

Key Terms: ACE inhibitors, Gout, Kidney stone, Tumor lysis syndrome.

Definition

This medication, also known as (Zyloprim), is used for the treatment and prevention of gout attacks and certain types of kidney stones. It is also used to treat elevated uric acid levels in the blood and urine, which can occur in patients receiving chemotherapy for the treatment of leukemia, lymphoma and other types of cancer. If left untreated, high uric acid levels in patients receiving cancer chemotherapy can cause kidney stones and kidney failure.

Description

Allopurinol decreases uric acid levels in the blood and urine by inhibiting a certain enzyme responsible for production of uric acid. It has been used for over three decades for prevention of gouty arthritis, kidney stones, and tumor lysis syndrome in cancer patients.

Recommended Dosage

Adults

Gout

200-300 mg per day for mild gout and 400-600 mg per day for severe gout. Patients greater than 65 years of age should be started at 100 mg per day. Their dose can be increased until desired uric acid levels in the blood are reached.

Children Over 10 Years of Age and Adults

Prevention of Uric Acid Kidney Stones in Cancer Patients

600-800 mg per day divided into several doses, usually starting 1-2 days before cancer chemotherapy and stopped two to three days after the chemotherapy is completed for that cycle.

Total daily dose greater than 300 mg should be given in divided doses.

Children Less Than 10 Years of Age

Prevention of Uric Acid Kidney Stones in Cancer Patients

10 mg per kg per day of allopurinol in two to three divided doses up to a maximum dose of 800 mg per day. Another alternative is to give 150 mg per day in three divided doses for children 6 years of age and 300 mg per day in two to three divided doses for children 6-10 years of age.

Administration

Allopurinol should be taken after meals to avoid stomach upset. Patients should drink plenty of fluids (at least eight glasses of water per day) while taking this medicine unless otherwise directed by a physician. Drinking a lot of water can prevent formation of kidney stones.

Precautions

The use of allopurinol in pregnant women should be avoided whenever possible because its effects on the human fetus are not known.

Allopurinol should be used with caution by the following populations:

• Patients who have had an allergic reaction to allopurinol in the past.
• Patients who are taking certain medicines for high blood pressure such as diuretics (water pills) or angiotensin converting enzyme (ACE) inhibitors (captopril, lisinopril, enalapril). These people may be at higher risk of hypersensitivity with allopurinol.
• Breast-feeding mothers.
• Children (except those who have high uric acid levels caused by cancer, chemotherapy, or genetic diseases).

Patients should call a doctor immediately if any of these symptoms develop:

• rash, itching, swelling of lips or mouth, trouble breathing (also known as hypersensitivity reaction)
• yellowing of the skin or eyes
• pain when urinating or blood in the urine
• unusual bleeding or bruising

Patients with kidney problems may need to use lower doses of allopurinol.

Patients taking allopurinol will need to see a physician before starting therapy and occasionally during therapy to do blood tests for monitoring of kidney and liver function and complete blood count.

Side Effects

Allopurinol is usually well tolerated by most patients. The most common side effect is skin rash, hives and itching. Loss of hair, fever, and feelings of discomfort or uneasiness can happen alone or in combination with a rash. The risk of rash is higher in people with kidney disease or people taking amoxicillin or ampicillin. The use of allopurinol should be discontinued at first sign of a rash. Other side effects include nausea, vomiting, decreased kidney function and drowsiness (especially during the first few days of therapy). Because allopurinol can cause drowsiness, caution should be taken when performing tasks requiring alertness, such as cooking or driving.

Interactions

Patients should consult their doctor before drinking alcoholic beverages; alcohol can decrease the effectiveness of allopurinol. People consuming large amounts of vitamin C can be at an increased risk for kidney stones.

Allopurinol can prolong the effects of blood thinners such as warfarin (Coumadin) and put patients at risk for bleeding. It can also increase chances of low blood sugar with chlorpropamide (Diabinese) and nerve toxicity with vidarabine. Allopurinol can decrease breakdown of azathioprine (Imuran), mercaptopurine (6-MP), cyclosporine (Neoral, Sandimmune) and theophylline (Theo-Dur, Theolair, Theo- 24) by the liver, increasing blood levels and side effects. Doses of azathioprine and mercaptopurine need to be reduced when they are used together with allopurinol. Mercaptopurine can be substituted for thioguanine (6-TG) to avoid this interaction altogether.

The use of amoxicillin and ampicillin should be avoided if possible in patients taking allopurinol because of increased risk of rash. Water pills such as hydrochlorthiazide (Diuril) can increase the risk of toxicity and allergic reaction when used with allopurinol.

—Olga Bessmertny, Pharm.D.

trade names: Lopurin, Zyloprim; drug class: antigout drug; action: inhibits the enzyme xanthine oxidase, reducing uric acid synthesis; uses: chronic gout, hyperuricemia associated with malignancies.

Brand names: Aloprim™Zyloprim®

Chemical formula:

Drug Forms:
• Allopurinol Oral tablet (below)
• Allopurinol tablets
• Allopurinol injection
• Allopurinol Sodium Solution for injection

Español:
• Alopurinol, Tableta oral
• Tabletas de alopurinol
• Inyección de alopurinol
• Alopurinol Sódico, Solución para inyección

Allopurinol Oral tablet

What is this medicine?

ALLOPURINOL (al oh PURE i nole) reduces the amount of uric acid the body makes. It is used to treat the symptoms of gout. It is also used to treat or prevent high uric acid levels that occur as a result of certain types of chemotherapy. This medicine may also help patients who frequently have kidney stones.
 
This medicine may be used for other purposes; ask your health care provider or pharmacist if you have questions.

What should I tell my health care provider before I take this medicine?

They need to know if you have any of these conditions:
•kidney or liver disease
•an unusual or allergic reaction to allopurinol, other medicines, foods, dyes, or preservatives
•pregnant or trying to get pregnant
•breast feeding

How should I use this medicine?

Take this medicine by mouth with a glass of water. Follow the directions on the prescription label. If this medicine upsets your stomach, take it with food or milk. Take your doses at regular intervals. Do not take your medicine more often than directed.

Talk to your pediatrician regarding the use of this medicine in children. Special care may be needed. While this drug may be prescribed for children as young as 6 years for selected conditions, precautions do apply.

Overdosage: If you think you have taken too much of this medicine contact a poison control center or emergency room at once.
NOTE: This medicine is only for you. Do not share this medicine with others.

What may interact with this medicine?

Do not take this medicine with the following medication:
•didanosine, ddI
 
This medicine may also interact with the following medications:
•amoxicillin or ampicillin
•azathioprine
•certain medicines used to treat gout
•certain types of diuretics
•chlorpropamide
•cyclosporine
•dicumarol
•mercaptopurine
•tolbutamide
•warfarin
 
This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.

What should I watch for while using this medicine?

Visit your doctor or health care professional for regular checks on your progress. If you are taking this medicine to treat gout, you may not have less frequent attacks at first. Keep taking your medicine regularly and the attacks should get better within 2 to 6 weeks. Drink plenty of water (10 to 12 full glasses a day) while you are taking this medicine. This will help to reduce stomach upset and reduce the risk of getting gout or kidney stones.
 
Call your doctor or health care professional at once if you get a skin rash together with chills, fever, sore throat, or nausea and vomiting, if you have blood in your urine, or difficulty passing urine.
 
Do not take vitamin C without asking your doctor or health care professional. Too much vitamin C can increase the chance of getting kidney stones.
 
You may get drowsy or dizzy. Do not drive, use machinery, or do anything that needs mental alertness until you know how this drug affects you. Do not stand or sit up quickly, especially if you are an older patient. This reduces the risk of dizzy or fainting spells. Alcohol can make you more drowsy and dizzy. Alcohol can also increase the chance of stomach problems and increase the amount of uric acid in your blood. Avoid alcoholic drinks.

What side effects may I notice from receiving this medicine?

Side effects that you should report to your doctor or health care professional as soon as possible:
•allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue
•breathing problems
•muscle aches or pains
•redness, blistering, peeling or loosening of the skin, including inside the mouth

Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):
•changes in taste
•diarrhea
•indigestion
•stomach pain or cramps

This list may not describe all possible side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Where should I keep my medicine?

Keep out of the reach of children.

Store at room temperature between 15 and 25 degrees C (59 and 77 degrees F). Protect from light and moisture. Throw away any unused medicine after the expiration date.

Last updated: 7/1/2002

Important Disclaimer: The drug information provided here is for educational purposes only. It is intended to supplement, not substitute for, the diagnosis, treatment and advice of a medical professional. This drug information does not cover all possible uses, precautions, side effects and interactions. It should not be construed to indicate that this or any drug is safe for you. Consult your medical professional for guidance before using any prescription or over the counter drugs.

A drug that inhibits uric acid production and reduces serum and urinary uric acid levels; used in the treatment of urate uroliths in dogs.

Not to be confused with Enalapril.

Allopurinol

Systematic (IUPAC) name
3,5,7,8-tetrazabicyclo[4.3.0] nona-3,5,9-trien-2-one
Identifiers
CAS number	315-30-0
ATC code	M04AA01
PubChem	2094
DrugBank	APRD00435
ChemSpider	2010
Chemical data
Formula	C5H4N4O
Mol. mass	136.112 g/mol
SMILES	eMolecules & PubChem
Pharmacokinetic data
Bioavailability	78±20%
Protein binding	Negligible
Metabolism	hepatic (80% oxypurinol, 10% allopurinol ribosides)
Half life	2 hours (oxypurinol 18-30 hours)
Excretion	?
Therapeutic considerations
Pregnancy cat.	C(USA)
Legal status	℞-only(US)
Routes	tablet (100, 300 mg)
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Allopurinol is a drug used primarily to treat hyperuricemia (excess uric acid in blood plasma) and its complications, including chronic gout.^[1]

Contents 1 Mechanism of action 2 Uses 3 Metabolism 4 Side effects 5 Brand names 6 References 7 Further reading

Mechanism of action

Allopurinol is a structural isomer of hypoxanthine (a naturally occurring purine in the body) and is an enzyme inhibitor, inhibiting xanthine oxidase.^[1] Xanthine oxidase is responsible for the successive oxidation of hypoxanthine and xanthine resulting in the production of uric acid, the product of human purine metabolism.^[1] In addition to blocking uric acid production, inhibition of xanthine oxidase causes an increase in hypoxanthine and xanthine, which are converted to closely related purine ribotides adenosine and guanosine monophosphates. Increased levels of these ribotides causes feedback inhibition of amidophosphoribosyl transferase, the first and rate-limiting enzyme of purine biosynthesis. Allopurinol therefore decreases both uric acid formation and purine synthesis.

Uses

The primary use of allopurinol is to treat hyperuricemia (excess uric acid in blood plasma) and its complications. Allopurinol does not alleviate acute attacks of gout, but is useful in chronic gout to prevent future attacks. Similarly, allopurinol commonly is used as prophylaxis with chemotherapeutic treatments, which can rapidly produce severe hyperuricemia. Other established indications for allopurinol therapy include ischaemic reperfusion injury, kidney stones with a uric acid component (uric acid nephrolithiasis) and protozoal infections (Leishmaniasis). Also used to prevent tumor lysis with certain types of cancer.

Because allopurinol is not a uricosuric, it can be used in patients who have poor kidney function. However, allopurinol has two important disadvantages: its dosing is complex,^[2] and some patients will be hypersensitive to it. Therefore, use of this drug requires careful monitoring.

Metabolism

Allopurinol is rapidly metabolized by its target, xanthine oxidase, to its active metabolite oxypurinol, which is also an inhibitor of xanthine oxidase. Allopurinol is almost completely metabolized to oxypurinol within two hours of oral administration, whereas oxypurinol is slowly excreted by the kidneys over 18-30 hours. For this reason, oxypurinol is believed to be responsible for the majority of allopurinol's effect.

Side effects

Side effects of allopurinol are rare, though significant when they occur. A small percentage of people develop a rash and must discontinue this drug. The most serious adverse effect is a hypersensitivity syndrome consisting of fever, skin rash, eosinophilia, hepatitis, worsened renal function and, in some cases, allopurinol hypersensitivity syndrome. Allopurinol is one of the drugs commonly known to cause Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TENS), two life-threatening dermatological conditions.

Allopurinol can cause severe pancytopenia if given with azathioprine or mercaptopurine, due to inhibition of xanthine oxidase which metabolizes these drugs. It can also cause breast enlargement in both males and females.

Brand names

Allopurinol has been marketed in the United States since 1964. Allopurinol is marketed by Prometheus in the United States as Zyloprim, while in other countries it continues to be marketed by GlaxoSmithKline. Other brand names are Allohexal, Allosig, Milurit, Progout, and Zyloric. In South Africa, Allopurinol is marketed under the brand name Puricos.

References

1. ^ ^{a b c} Pacher P, Nivorozhkin A, Szabó C (March 2006). "Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol". Pharmacol. Rev. 58 (1): 87–114. doi:10.1124/pr.58.1.6. PMID 16507884. 
2. ^ Dalbeth N, Stamp L (2007). "Allopurinol dosing in renal impairment: walking the tightrope between adequate urate lowering and adverse events". Semin Dial 20The primary use of allopurinol is to treat hyperuricemia (excess uric acid in blood plasma) and its complications. Allopurinol does not alleviate acute attacks of gout, but is useful in chronic gout to prevent future attacks. Similarly, allopurinol commonly is used as prophylaxis with chemotherapeutic treatments, which can rapidly produce severe hyperuricemia. Other established indications for allopurinol therapy include ischaemic reperfusion injury, kidney stones with a uric acid component (uric acid nephrolithiasis) and protozoal infections (Leishmaniasis). Also used to prevent tumor lysis with certain types of cancer. Because allopurinol is not a uricosuric, it can be used in patients who have poor kidney function. However, allopurinol has two important disadvantages: its dosing is complex,[2] and some patients will be hypersensitive to it. Therefore, use of this drug requires careful monitoring. (5): 391–5. doi:10.1111/j.1525-139X.2007.00270.x. PMID 17897242. 

it also known as zyrik 300 in India.

Further reading

• Zahran AM, Azab KS, Abbady MI (2006). "Modulatory role of allopurinol on xanthine oxidoreductase system and antioxidant status in irradiated rats". Egypt. J. Rad. Sci. Applic. 19 (2): 373-388. 

v • d • e Antigout preparations (M04) Uricosurics primary: Probenecid · Sulfinpyrazone · Benzbromarone · Isobromindione secondary: Amlodipine · Atorvastatin · Fenofibrate · Guaifenesin · Losartan Xanthine oxidase inhibitors purine analogues: Allopurinol# · Oxypurinol · Tisopurine other: Febuxostat · Inositols (Phytic acid, Myo-inositol) Mitotic inhibitors Colchicine Other Cinchophen · NSAIDs except aspirin · Sevelamer · Urate oxidase (Rasburicase, Pegloticase†) #WHO-EM. ‡Withdrawn from market. CLINICAL TRIALS: †Phase III. §Never to phase III

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