Allopurinol – Uses

What is allopurinol?

Patients with large tumor masses, leukemia, or gout sometimes receive allopurinol (also called Zyloprimâ) which is a medicine used to decrease the level of uric acid in the blood.

Allopurinol is a xanthine oxidase enzyme inhibitor that is considered to be one of the most effective drugs used to decrease urate levels and is frequently used in the treatment of chronic gout. It was initially approved by the FDA in 1966 12 and is now formulated by several manufacturers.

Brand names

Lopurin®, Zyloprim®, Uricto

Storage of Allopurinol

• Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.
• Keep out of the reach of children.
• Do not keep outdated medicine or medicine no longer needed.

Identity of Allopurinol

Type of medicine	Antigout agents, Antihyperuricemic agents
Synonyms	4-HPP, Allopurinol, Allopurinolum, Alopurinol
Molecular Formula	C5H4N4O
Molecular Weight	136.1115 g/mol
IUPAC Names	1H-pyrazolo[3,4-d]pyrimidin-4-ol
Structural formula of main components
Pure active ingredient	Allopurinol sodium
Appearance	White crystals or powder
Melting point	>350°C
Available as	Tablet, Injection, powder, lyophilized, for solution
Prescription	Prescription is required

Why is this medication prescribed?

Allopurinol is used to treat gout (a type of arthritis in which uric acid, a naturally occurring substance in the body, builds up in the joints and causes sudden attacks of redness, swelling, pain, and heat in one or more joints). Allopurinol is also used to treat high levels of uric acid that builds up in the blood as tumors break down in people with certain types of cancer who are being treated with chemotherapy medications. It is also used to treat kidney stones that have come back in people who have high levels of uric acid in their urine. Allopurinol is in a class of medications called xanthine oxidase inhibitors. It works by reducing the production of uric acid in the body. High levels of uric acid may cause gout attacks or kidney stones. Allopurinol is used to prevent gout attacks, not to treat them once they occur.

What side effects can this medication cause?

Allopurinol may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• Nausea
• Diarrhea
• Drowsiness

Some side effects can be serious. The following symptoms are uncommon, but if you experience any of them, stop taking allopurinol and call your doctor immediately or get emergency treatment:

• Rash, itching, or hives
• Peeling, blistering, or shedding skin
• Red or purple spots on skin
• Painful urination
• Blood in the urine
• Irritation of the eyes
• Swelling of the lips or mouth
• Fever or flu-like symptoms
• Swollen glands
• Yellowing of the skin or eyes, pain in the upper right part of the stomach, nausea, vomiting, itching, or extreme tiredness

Allopurinol may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

Mechanism of action

Allopurinol is a structural analog of the natural purine base, hypoxanthine. After ingestion, allopurinol is metabolized to its active metabolite, oxypurinol (alloxanthine) in the liver, which acts as an inhibitor of xanthine oxidase enzyme Label.

Allopurinol and its active metabolite inhibit xanthine oxidase, the enzyme that converts hypoxanthine to xanthine and xanthine to uric acid. Inhibition of this enzyme is responsible for the effects of allopurinol. This drug increases the reutilization of hypoxanthine and xanthine for nucleotide and nucleic acid synthesis by a process that involves the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRTase). This process results in an increased nucleotide concentration, which causes feedback inhibition of de novo purine synthesis. The end result is decreased urine and serum uric acid concentrations, which decreases the incidence of gout symptoms.

Accompanying the reduction of serum uric acid by allopurinol is an increase in the serum and urine concentrations of hypoxanthine and xanthine (due to inhibition of xanthine oxidase). In the absence of allopurinol, regular urinary excretion of oxypurines almost entirely occurs in the form of uric acid. After the ingestion of allopurinol, the contents of excreted urine are hypoxanthine, xanthine, and uric acid. Because each substance has its own individual solubility, the concentration of uric acid in plasma is decreased without exposing the renal tissues to a high load of uric acid, thereby decreasing the risk of crystalluria. By lowering the uric acid concentration in the plasma below its limits of solubility, allopurinol encourages the dissolution of gout tophi. Although the levels of hypoxanthine and xanthine are found to be increased after allopurinol ingestion, the risk of deposition in renal tissues is less than that of uric acid, as they become more soluble and are rapidly excreted by the kidney.

Effects on other treatments

Some drugs interact with allopurinol, so you should discuss any new medication with your doctor before starting it. You should also tell anyone else treating you that you’re taking allopurinol.

Do not use complementary treatments, such as herbal remedies, without discussing this first with your doctor or pharmacist. Some of them could react with allopurinol.

You should avoid taking aspirin while you’re being treated for gout. If you’re in pain, you can take paracetamol and NSAIDs. But remember you should only take one NSAID at a time – so do not take another if you have already been prescribed one to reduce the effects of gout attacks.

Allopurinol can also react with drugs that are often prescribed for high blood pressure, such as bendroflumethiazide, indapamide, lisinopril, ramipril.

Allopurinol reduces the breakdown of azathioprine, which is used to treat conditions such as rheumatoid arthritis and lupus. Your doctor may change your dose of azathioprine to account for this.

It can also reduce the breakdown of the leukaemia drug mercaptopurine, so the dose of mercaptopurine will need to be reduced if you take this drug.

Allopurinol may also increase the risk of developing a rash if you take them with the antibiotics ampicillin or amoxicillin.

Allopurinol may also increase the effect of warfarin and other drugs that thin the blood. These are known as anticoagulants. If you’re taking blood thinners, you may need your clotting time tested more frequently to check you’re still on the right dose.

Dosage and Forms of Allopurinol

Allopurinol is available in the following forms:

• A white 100-mg tablet taken by mouth
• An orange 300-mg tablet taken by mouth
• A white 20 mg/mL liquid taken by mouth
• A clear liquid given by vein (IV)

Dosing

The dose of this medicine will be different for different patients. Follow your doctor’s orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For oral dosage form (tablets)

For gout:

• Adults—At first, 100 to 300 milligrams (mg) per day, taken once a day or in divided doses. Your doctor may adjust your dose as needed. However, the dose is usually not more than 800 mg per day.
• Children—Use and dose must be determined by your doctor.

For high uric acid levels caused by cancer medicines:

• Adults and children 11 years of age and older—600 to 800 milligrams (mg) per day, taken in divided doses for 2 to 3 days.
• Children 6 to 10 years of age—300 mg per day, taken once a day for 2 to 3 days.
• Children younger than 6 years of age—150 mg per day, taken once a day for 2 to 3 days.

For kidney stones:

• Adults—200 to 300 milligrams (mg) per day, taken once a day or in divided doses. Your doctor may adjust your dose as needed. However, the dose is usually not more than 800 mg per day.
• Children—Use and dose must be determined by your doctor.

Precautions

Before taking allopurinol, tell your doctor or pharmacist if you are allergic to it; or if you have had a severe reaction to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver disease, kidney disease, diabetes, high blood pressure (hypertension), unusual diets (such as fasting).

This drug may make you drowsy. Alcohol or marijuana (cannabis) can make you more drowsy. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Alcohol may also decrease the effectiveness of this drug. Limit alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

Allopurinol passes into breast milk. Consult your doctor before breast-feeding.

Pregnancy, breastfeeding and fertility while taking allopurinol

Allopurinol and pregnancy

Allopurinol is not usually recommended during pregnancy. There is not enough evidence to say that it’s safe.

Talk to a doctor if you’re thinking about trying for a baby. There may be other medicines that are more suitable for you to take during pregnancy.

Allopurinol and breastfeeding

If your doctor or health visitor says your baby is healthy, you can take allopurinol while you’re breastfeeding.

There is not much information about using allopurinol while breastfeeding, but it is likely that allopurinol passes into breast milk in small amounts

If you notice that your baby is not feeding as well as usual, is being sick (vomiting), has diarrhoea or a rash, or if you have any other concerns about your baby, then talk to your doctor, pharmacist, midwife or health visitor.

Allopurinol and fertility

There is no evidence to suggest that taking allopurinol reduces fertility in either men or women. However, talk to a doctor if you want to try for a baby while taking allopurinol.