Zyloprim (Allopurinol)

(British Approved Name, US Adopted Name, rINN)

Why This Medication is Used

Cancer chemotherapy drugs or radiation therapy are given to kill cancer cells in the body. One of the waste products of the dead cancer cells is uric acid. If uric acid builds up in the body, it can cause kidney damage or joint pain (called gout). Allopurinol helps to prevent the build-up of uric acid.

Allopurinol belongs to a group of medicines called enzyme inhibitors, which is used for the long-term prevention of gout, the prevention of kidney stones, and the treatment of high levels of uric acid associated with tumors and their treatment, specific enzyme disorder, in particular Lesch Nyhan syndrome.

The tablets are only given to children with cancer, especially leukemia (cancer of the blood) and certain enzyme disorders (e.g., Lesch Nyhan).

Ingredients

The active ingredient is allopurinol.

The other substances are Lactose monohydrate, Maize Starch, Povidone K30, Sodium Starch Glycollate, and Magnesium Stearate.

What Allopurinol 100mg Tablets Look Like and Contents of the Pack

Allopurinol 100mg tablets are white, round, biconvex tablets embossed with MAL100 on one side and plain on the reverse.

The product is available in containers of 1000, 500, 250, 100, 84, 70, 56, 42, 28, 21,15 and 14 tablets. They are also available in blister packs of 84, 70, 56, 42, 28, 21, 15, and 14 tablets (not all pack sizes may be marketed).

Pharmacokinetics

Up to 90% of an oral allopurinol dose is rapidly absorbed from the gastrointestinal tract; its plasma half-life is about 1 to 2 hours. Allopurinol’s major metabolite is oxypurinol (alloxanthine), an inhibitor of xanthine oxidase with a plasma half-life of about 15 or more hours in patients with normal renal function. However, this is considerably prolonged by renal impairment. Both allopurinol and oxipurinol are conjugated to form their respective ribonucleosides.

Allopurinol and oxypurinol are not bound to plasma proteins. Excretion is mainly through the kidney but is slow since oxypurinol undergoes tubular reabsorption. About 70% of a daily dose may be excreted in the urine as oxypurinol and up to 10% as allopurinol; prolonged use may alter these proportions, as allopurinol inhibits its metabolism. The remainder of the dose is excreted in the feces. Allopurinol and oxypurinol have also been detected in breast milk.

How to Take Allopurinol 100 mg Tablets

Always take Allopurinol 100mg tablets exactly as your doctor has told you. You should check with your doctor or pharmacist if you need more information.

For oral use only. Allopurinol 100mg tablets should be swallowed without chewing, with half a glassful of water during or after meals.

Adults (Over 18 years)

The usual dose ranges from 100 to 900 mg each day. Initially, 100 to 300 mg daily is taken as a single dose.

Children (under 15 years)

The recommended dose is 10 to 20 mg/kg body weight/day up to 400mg daily.

Use in the Seniors (over 65 years)

The lowest dosage possible will be given as recommended by your doctor.

Use in Patients with Kidney Damage

Your doctor should recommend the level and frequency of dosage. Due to kidney damage, the dose may need to be decreased depending on blood uric acid levels, which means it takes longer to excrete allopurinol.

Use in Patients on Kidney Dialysis

Allopurinol and its by-products are removed by dialysis. If dialysis is done frequently, 300 to 400mg of allopurinol may be given after each dialysis, with none in the interim.

The dose should be adjusted by checking blood uric acid and/or urinary uric acid levels at appropriate intervals, which your doctor will do. It might take one to three weeks for blood and/or urinary uric acid to return to the desired levels.

Overdose

If you or someone else swallow several of these tablets together, contact your doctor or nearest hospital emergency department immediately. Always take the box, this leaflet, and any tablets that are left over with you, if you can.

If You Forget to Take Allopurinol 100mg Tablets

If you miss a dose, take it as soon as you remember and carry on as before. If it is almost time for your next dose, skip the forgotten dose and continue as usual. Do not take a double dose to make up for a forgotten dose.

If You Stop Taking Allopurinol 100mg Tablets

Please do not stop taking Allopurinol 100 mg tablets without discussing it with your doctor. Ask your doctor or pharmacist for further questions about using this product.

Adverse Effects

The most common adverse effect of allopurinol is skin rash. Rashes are generally maculopapular or pruritic, sometimes purpuric, but more severe hypersensitivity reactions may occur, including exfoliative rashes, the Stevens-Johnson syndrome, and toxic epidermal necrolysis. Therefore, allopurinol should be withdrawn immediately if a rash occurs. Further symptoms of hypersensitivity include fever and chills, lymphadenopathy, leucopenia or leucocytosis, eosinophilia, arthralgia, and vasculitis, leading to renal and hepatic damage and, very rarely, seizures. These hypersensitivity reactions may be severe or fatal, and patients with hepatic or renal impairment are at risk.

Hepatotoxicity and signs of altered liver function may also be found in patients who are not hypersensitive. Hematological effects include thrombocytopenia, aplastic anemia, agranulocytosis, and hemolytic anemia.

Many other adverse effects have been noted rarely, including paraesthesia, peripheral neuropathy, alopecia, gynecomastia, hypertension, taste disturbances, nausea, vomiting, abdominal pain, diarrhea, headache, malaise, drowsiness, vertigo, and visual disturbances.

Patients with gout may have increased acute attacks on beginning treatment with allopurinol, although attacks usually subside after several months.

Incidence of Adverse Effects

A Boston Collaborative Drug Surveillance Program involving 29 524 hospitalized patients found that, except for skin reactions, 33 of 1835 patients treated with allopurinol (1.8%) had adverse effects. These effects were dose-related, and the most frequent were hematological (11 patients, 0.6%), diarrhea (5 patients, 0.3%), and drug fever (5 patients, 0.3%). Hepatotoxicity was reported in 3 patients (0.2%). Two patients developed possible hypersensitivity reactions to allopurinol.

A further analysis involving 1748 outpatients indicated no acute blood disorders, skin diseases, or hypersensitivity warranted hospital treatment. Liver disease, although found, was not considered to be associated with allopurinol.

There were only two patients in whom allopurinol could have caused renal disease.

Effects on the Blood

In addition to the hematological abnormalities of leucopenia, thrombocytopenia, hemolytic anemia, and clotting abnormalities noted in the Boston Collaborative Drug Surveillance Program, aplastic anemia has also been reported, sometimes in patients with renal impairment. Pure red cell aplasia has also been reported.

Effects on the Eyes

Some case reports have suggested an association between allopurinol use and the development of cataracts, but a detailed ophthalmological survey involving 51 patients who had taken allopurinol failed to confirm this. However, a large retrospective case-control study in elderly patients concluded that long-term, or high-dose, allopurinol therapy did increase the risk of cataract extraction.

Effects on the Skin

Skin reactions are the most common adverse effects of allopurinol.

One report calculated that of 215 adverse effects noted over 16 years, 188 (87.4%) were related to the skin or mucous membranes. Data analysis by the Boston Collaborative Drug Surveillance Program on 15 438 patients hospitalized between 1975 and 1982 detected six allergic skin reactions attributed to allopurinol among 784 drug recipients. Desensitization protocols and alternative drugs have been used after cutaneous reactions to allopurinol.

Severe skin reactions to allopurinol may occur as part of a generalized hypersensitivity reaction. A literature review between 1970 and the end of 1990 revealed 101 cases of allopurinol hypersensitivity syndrome, 94 of which involved the skin. Skin reactions included erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, or diffuse maculopapular or exfoliative dermatitis; 27 of the 101 patients died. The relative risk of toxic epidermal necrolysis or Stevens-Johnson syndrome occurring with allopurinol was high (calculated to be 5.5) in a case-control study including 13 patients with these cutaneous reactions who had received allopurinol.

This risk was not constant over time, higher during the first two months of treatment. During these two months, the estimated excess risk was 1.5 cases per million weekly users. Another case-control study involving 379 patients with Stevens-Johnson syndrome or toxic epidermal necrolysis found that allopurinol was most frequently associated with these reactions. The risk appeared to be restricted to short-term use (less than eight weeks) and was greater in patients taking 200 mg or more daily.

Precautions

Allopurinol should not be used to treat an acute gout attack; additionally, allopurinol therapy should not be begun for any purpose during an acute attack. However, allopurinol is continued when acute attacks occur in patients already receiving the drug, and the acute attack is treated separately. Treatment should be stopped immediately if skin reactions or other signs of hypersensitivity develop. A cautious reintroduction at a low dose may be attempted when mild skin reactions have cleared; allopurinol should not be reintroduced in those patients who have experienced other forms of hypersensitivity reaction.

Dosage should be reduced in renal or hepatic impairment. Care is advised in patients treated for hypertension or cardiac insufficiency who may also have renal impairment. An adequate fluid intake (2 to 3 liters daily) is required to reduce the risk of renal xanthine deposition. In addition, a neutral or slightly alkaline urine may be desirable.

Pregnancy and Breastfeeding

If you are planning to become pregnant or are pregnant, do not take Allopurinol 100 mg tablets and contact your doctor for further advice. Ask your doctor or pharmacist for advice if you plan to breastfeed your baby.

Allopurinol and its metabolite, oxypurinol, are distributed into breast milk, and licensed product information recommends that allopurinol should be used cautiously in breastfeeding women. Although oxipurinol was detected in the plasma of a breastfed infant, no adverse effects were noted in the infant during six weeks of maternal treatment with allopurinol. The American Academy of Pediatrics noted that there had been no documented problems with allopurinol and considered its use to be usually compatible with breastfeeding.

Before you take Allopurinol 100mg Tablets

Do not take Allopurinol 100mg tablets if you are sensitive or allergic to allopurinol or any of the ingredients in the tablets.

Do not take Allopurinol tablets if the above applies to you. If you are not sure, talk to your doctor or pharmacist before taking Allopurinol tablets.

Take Special Care With Allopurinol 100 mg Tablets

Check with your doctor before taking Allopurinol 100mg tablets:

• If you have problems with your liver or kidneys. Your doctor may give you a lower dose or ask you to take it less often than each day. They will also monitor you more closely.
• If you have heart problems or high blood pressure.
• If you are currently having an attack of gout.
• If you are not sure if any of the above applies to you, talk to your doctor or pharmacist before taking Allopurinol tablets.

Taking Other Medicines

Please inform your doctor if you are taking or have recently taken any other medicines, including those obtained without a prescription.

Before taking Allopurinol 100mg tablets, tell your doctor if you are already taking any of the following:

• 6-mercaptopurine to treat cancer of the blood cells;
• anticoagulants (drugs to prevent blood clotting, such as Warfarin).

Other products used to treat high uric acid levels, e.g., probenecid:

• some drugs used to reduce excess water in the body (thiazide diuretics), ampicillin (antibiotic);
• aspirin;
• theophylline used for breathing problems;
• medicines used for fits (epilepsy);
• didanosine used to treat HIV infection;
• medicines used to treat diabetes;
• medicines used to reduce your immune response (immunosuppressant);
• medicines for heart problems or high blood pressure, such as ACE inhibitors or water tablets (diuretics).

Driving and Using Machines

Allopurinol 100 mg tablets may cause drowsiness or affect your vision. If you experience these symptoms, you should avoid driving or operating machinery.

Important information about some of the ingredients

These tablets contain lactose. If your doctor has told you that you are intolerant to some sugars, do not take these tablets until you have consulted with your doctor.

Interactions

Drugs that can increase uric acid concentrations may decrease the efficacy of allopurinol. Aspirin and salicylates possess this activity and should generally be avoided in hyperuricemia and gout. An increase in hypersensitivity reactions, and possibly also other adverse effects, have been reported in patients taking allopurinol with ACE inhibitors or thiazide diuretics, particularly in patients with renal impairment.

The metabolism of azathioprine and mercaptopurine is inhibited by allopurinol, and their doses should be markedly reduced when either of them is given with allopurinol to avoid potentially life-threatening toxicity. There have also been reports of allopurinol enhancing the activity of, and possibly increasing the toxicity of, some other drugs, including some antibacterial, some anticoagulants, some other antineoplastics, ciclosporin, some sulfonylurea antidiabetics, theophylline, and vidarabine.

ACE inhibitors

An apparent interaction between allopurinol and captopril has been reported in patients with chronic renal failure. In one patient, it was suggested that the development of fatal Stevens-Johnson syndrome after the introduction of allopurinol was due to potentiation by captopril. In the second patient, hypersensitivity, characterized by fever, arthralgia, and myalgia, occurred and was believed to be due to captopril, or one of its metabolites, potentiated by adding allopurinol. Care is advised if allopurinol is used with captopril, especially in patients with chronic renal failure.

Antacids

Allopurinol failed to reduce blood uric acid concentrations when given at the same time as aluminum hydroxide in 3 patients on chronic hemodialysis. However, if allopurinol was given 3 hours before aluminum hydroxide, the expected decrease in uric acid concentration did occur.

Antibacte Rials

Although an increased incidence of skin rashes has been noted when allopurinol has been used with ampicillin or amoxicillin, data currently available are insufficient to confirm whether this is due to allopurinol or not. For further details, see ampicillin.

Anticoagulants

For the effect of allopurinol on dicoumarol, phenprocoumon, or warfarin, see Warfarin.

Antiepileptics

For a report of allopurinol possibly inhibiting the metabolism of phenytoin, see Antigout Drugs.

Antigout Drugs

Uricosuric drugs are likely to increase the renal elimination of oxypurinol (the major active metabolite of allopurinol). For example, benzbromarone lowered plasma concentrations of oxypurinol by about 40% when used with allopurinol, although plasma concentrations of allopurinol were unaffected. The interaction was not of concern since the combination was more effective than allopurinol alone in lowering serum concentrations of uric acid.

Licensed product information recommends reassessing allopurinol dosage individually when adding a uricosuric drug. Probenecid has been reported to decrease the clearance of oral allopurinol riboside. In a pharmacokinetic study in healthy subjects, giving allopurinol and probenecid significantly reduced oxypurinol concentrations; however, this combination had a more significant hypouricaemic effect than either drug given alone.

Antineoplastics

Allopurinol inhibits the metabolism of mercaptopurine, and a marked dosage reduction of this drug to one-quarter to one-third of the usual dose is required if it is used with allopurinol. There are also reports of interactions between allopurinol and other antineoplastics. Mild chronic allopurinol-induced hepatotoxicity has been reported in a male patient to have been exacerbated by tamoxifen. Hypersensitivity vasculitis resulting in the death of a patient receiving allopurinol and pentostatin has been described. Although it could not be ascertained whether this effect was due to one of the drugs alone or to an interaction, it was believed that this combination should not be used.

Immunosuppressants

Allopurinol inhibits the metabolism of mercaptopurine, the metabolite of azathioprine, and a marked dosage reduction of azathioprine to one-quarter to one-third of the usual dose is required if it is used with allopurinol. Similar caution is also required with mercaptopurine. The effects of allopurinol on ciclosporin concentrations (a marked increase) are reported.

Uses and Administration

Allopurinol treats hyperuricemia associated with chronic gout, acute uric acid nephropathy, recurrent uric acid stone formation, certain enzyme disorders, or cancer and its treatment. It is not used for asymptomatic hyperuricemia. Allopurinol is also used to manage renal calculi caused by the deposition of calcium oxalate (in the presence of hyperuricosuria) and 2,8-dihydroxyadenine. It may reduce oxidative stress by blocking the production of free radicals and is an ingredient of kidney preservation solutions. In addition, allopurinol has antiprotozoal activity and has been used in leishmaniasis and American trypanosomiasis.

Allopurinol is used in gout and hyperuricemia to inhibit the enzyme xanthine oxidase, thus preventing the oxidation of hypoxanthine to xanthine and xanthine to uric acid. The urinary purine load, typically almost entirely uric acid, is divided between hypoxanthine, xanthine, and uric acid, each with its independent solubility. This reduces urate and uric acid concentrations in plasma and urine, ideally to such an extent that deposits of monosodium urate monohydrate or uric acid are dissolved or prevented from forming. At low concentrations, allopurinol acts as a competitive inhibitor of xanthine oxidase and at higher concentrations as a non-competitive inhibitor. However, most of its activity is due to metabolite oxypurinol, a non-competitive xanthine oxidase inhibitor.

Allopurinol is used in chronic gout to correct hyperuricemia, reduce the likelihood of acute attacks, and prevent the sequelae of chronic gout. Initially, it may increase plasma concentrations of urate and uric acid by dissolving deposits. This can trigger or exacerbate acute attacks; hence, allopurinol should not be started until an acute attack has completely subsided, and treatment should be started with a low dose increased gradually; an NSAID (but not aspirin or salicylates) or colchicine should also be given for at least one month after hyperuricemia is corrected, usually three months. It may take several months to deplete the uric acid level to control acute attacks sufficiently.

A suggested oral starting dose of allopurinol is 100 mg daily, gradually increased by 100 mg, for example, at weekly intervals until the urate concentration in plasma is reduced to 0.36 mmol/liter (6 mg per 100 mL) or less. A daily dose range of 100 to 300 mg may be adequate for those with mild gout and up to 600 mg for moderately severe tophaceous gout. The maximum recommended daily dose is 800 mg in the USA and 900 mg in the UK. Up to 300 mg may be taken as a single daily dose; larger amounts should be taken in divided doses to reduce the risk of gastric irritation. Taking allopurinol after food will also minimize gastric irritation. Patients should maintain an adequate fluid intake to prevent renal xanthine deposition.

Doses of allopurinol should be reduced in patients with renal impairment.

When used to prevent uric acid nephropathy associated with cancer therapy, 600 to 800 mg may be given daily for 2 or 3 days before starting the cancer treatment. A high fluid intake is essential. In hyperuricemia, secondary to cancer or cancer chemotherapy, maintenance doses of allopurinol are similar to those used in gout and are given according to the response.

Allopurinol is primarily used in children for hyperuricemia associated with cancer or, cancer chemotherapy or enzyme disorders. The dosage used may vary: in the UK, a dose of 10 to 20 mg/kg daily up to a maximum of 400 mg daily is recommended for children under 15 years of age, while in the USA, the dose is 150 mg daily for children under six years of age and 300 mg daily for those aged 6 to 10 years, adjusted if necessary after 48 hours.

Allopurinol sodium has been given by intravenous infusion in sodium chloride 0.9% or glucose 5% to patients (usually cancer patients) unable to take allopurinol orally. The recommended dose in adults is the equivalent of allopurinol 200 to 400 mg/m daily up to a maximum of 600 mg daily. Allopurinol sodium 116.2 mg is equivalent to 100 mg of allopurinol.

Administration in Renal Impairment

Excretion of allopurinol and its active metabolite oxypurinol is primarily via the kidneys, and therefore, the dosage should be reduced in renal impairment according to creatinine clearance (CC).

In the USA, the following doses are suggested for oral and intravenous use:

• CC 10 to 20 mL/minute: 200 mg daily;
• CC less than 10 mL/minute: no more than 100 mg daily;
• CC less than 3 mL/minute: consider also a longer dosage interval.

In the UK, a maximum initial oral daily dosage of 100 mg is recommended for those with renal impairment, increased only if the response is inadequate. Doses less than 100 mg daily or 100 mg at intervals longer than one day are recommended for those with severe renal insufficiency. Because of the imprecision of low creatinine clearance values, it is suggested that, if facilities are available for monitoring, the allopurinol dose should be adjusted to maintain plasma-oxypurinol concentrations below 100 micromoles/liter (15.2 micrograms/ml). A suggested alternative dose for patients requiring dialysis two or three times weekly is 300 to 400 mg of allopurinol immediately after dialysis only.

The difficulties of maintaining an appropriate dose in such patients were illustrated by a study in New Zealand involving 227 allopurinol-treated patients. The guidelines used suggested maintenance doses based on CC as follows:

• less than 10 mL/minute: 100 mg every three days;
• 10 mL/minute: 100 mg every two days;
• 20 mL/minute: 100 mg daily;
• 40 mL/minute: 150 mg daily;
• 60 mL/minute: 200 mg daily.

The recommended dose or less was used in most cases (183 of 227). However, of 214 patients for whom serum-uric acid concentrations were available, only 48 achieved values of 0.36 mmol/liter or less. The proportion of patients achieving acceptable serum-uric acid concentrations was higher (38%) in patients given higher than recommended doses than in those on doses recommended by the guidelines (19%). Although guidelines might be helpful for initial dosing, longer-term use could lead to inadequate control of hyperuricemia.

Diagnosis and Testing

Deficiency of the enzyme ornithine carbamoyltransferase can result in severe CNS dysfunction or even death. The identification of women at risk of being carriers of this genetic enzyme deficiency has been described. The enzyme deficiency causes carbamoyl phosphate to accumulate, which stimulates the synthesis of orotidine. The test relies on giving a single dose of allopurinol, which will, in carriers, greatly increase the urinary excretion of orotidine. However, mutation analysis is now more usually used to establish the diagnosis.

Duchenne Muscular Dystrophy

Controlled studies of the use of allopurinol in an attempt to increase muscle ATP in Duchenne muscular dystrophy failed to show any benefit from treatment.

Epilepsy

Reduction in the frequency of seizures has been described in some patients with severe or intractable epilepsy when allopurinol was added to their existing antiepileptic therapy. Although the mode of action was unknown, it was noted that the patients were not hyperuricaemic and that allopurinol did not affect plasma concentrations of existing antiepileptics. However, others have seen no benefit.

Organ and Tissue Transplantation

Allopurinol 25 mg on alternate days has been added to the immunosuppressive treatment for renal transplantation and is reported to reduce the frequency of acute rejection. One possible explanation for this effect is the allopurinor’s ability to suppress the production of free radicals. Organ and tissue transplantation and the usual drugs used in immunosuppressive regimens are discussed. It should be noted that allopurinol interacts with azathioprine and ciclosporin.

Oxidative Stress

Allopurinol, by inhibiting xanthine oxidase, can block the development of superoxide free radicals during reperfusion after an ischaemic episode. Consequently, the ability of allopurinol to reduce oxidative stress has been investigated in some clinical situations. In a small study of patients with idiopathic dilated cardiomyopathy, short-term intracoronary allopurinol improved myocardial efficiency by decreasing the oxygen demand of left ventricular contraction.

In patients undergoing coronary artery bypass graft surgery, perioperative allopurinol reduced hospital mortality, arrhythmias, the number of ischaemic events, and the need for inotropic support. However, the findings were not consistent in all studies.

Improved endothelial dysfunction has been found in patients with chronic heart failure given allopurinol. A large study in neonates undergoing cardiac surgery found that allopurinol caused a reduction in seizures and cardiac events in those with hypoplastic left heart syndrome. No benefit was found in neonates with less severe forms of congenital heart disease, considered at lower risk of adverse surgical outcome or reperfusion injury.

Allopurinol also failed to reduce the incidence of periventricular leucomalacia (thought to represent ischaemic infarction of the developing brain) in preterm infants compared with placebo in a large study. Similarly, allopurinol did not reduce the incidence of infarct extension in patients with acute myocardial infarction.

The possibility that allopurinol limits the production of free radicals has also led to allopurinol sodium being included as an ingredient of the University of Wisconsin solution [UW Solution; Belzer UW Solution (commercially available as Viaspan)], which is used for the preservation of organs for transplantation. A pilot study using allopurinol showed a beneficial effect on free radical formation, cerebral blood volume, and electrical brain activity in severely asphyxiated newborns. However, a systematic review of this and two other studies in such infants could not determine whether allopurinol produced clinically important benefits.

Prostatitis

Although allopurinol has been reported to be beneficial in a small study in patients with chronic prostatitis, a systematic review found no other satisfactory evidence of benefit and considered that the clinical relevance of the original study results was unclear.

Protozoal Infections

Allopurinol has been widely used as an adjunct to pentavalent antimonials in treating Old World visceral leishmaniasis, mainly where resistance to antimony is likely. However, the degree of benefit has been questioned. It has also been used with other drugs, such as pentamidine or azole antifungals, including in transplant patients or those with AIDS or in whom antimonials were otherwise poorly tolerated. Allopurinol has also been tried alone or with other drugs in both Old World and New World cutaneous or mucocutaneous leishmaniasis; results have been variable, particularly in the latter.

Some beneficial results have been noted in indeterminate and chronic Chagas’ disease (American trypanosomiasis), although it may be less effective than itraconazole. The selective antiparasitic action of allopurinol is believed to be due to its incorporation into the protozoal, but not the mammalian, purine salvage pathway. This leads to the formation of 4-aminopyrazolopyrimidine ribonucleotide triphosphate, a highly toxic analog of adenosine triphosphate, that is incorporated into ribonucleic acid. This action of allopurinol is shared by allopurinol riboside, one of the minor metabolites in man, but not by oxypurinol, the major human metabolite. Thus, some studies have been conducted with allopurinol riboside rather than allopurinol to enhance activity by avoiding host-mediated inactivation.

Renal Calculi

In conjunction with a reduced dietary purine intake, high fluid intake, and potassium citrate, allopurinol may be used to prevent the recurrence of calcium oxalate renal calculi in patients with hyperuricosuria. The recommended oral dose of allopurinol is 200 to 300 mg daily, adjusted based on subsequent 24-hour urinary urate excretion. Allopurinol is also advocated for managing 2,8-dihydroxyadenine (2,8-DHA) renal stones associated with deficient activity of the enzyme adenine phosphoribosyltransferase.

Sarcoidosis

Although corticosteroids remain the mainstay of drug therapy for sarcoidosis, and other drugs are very much second line, there are reports of benefit in cutaneous disease from allopurinol.

Schizophrenia

Involvement of purinergic neurotransmission has been hypothesized to play some role in schizophrenia, and allopurinol has been investigated as a possible adjunctive treatment, with some evidence of benefit, especially in patients with refractory positive symptoms.

Skin Disorders

Reactive perforating collagenosis (RPC) is a condition in which altered collagen is eliminated through the epidermis; it may be inherited or acquired. In 3 of 4 patients with RPC refractory to antibacterials and oral and topical corticosteroids, significant improvement was seen with allopurinol in terms of reduction of new lesions, improvement of existing lesions, and reduction of pruritus. The fourth patient died from unrelated causes before review.

How to Store Allopurinol 100mg Tablets

Keep out of the reach and sight of children.

Do not store above 25°C. Store in the original package and keep containers tightly closed. Do not use the tablets after the expiry date is stated on the label.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines that are no longer required. These measures will help to protect the environment.

Drug Nomenclature

International Nonproprietary Names (INNs) in main languages (French, Latin, Russian, and Spanish):

Synonyms: Allopurinol; Allopurinoli; Allopurinolum; Alopurinol; Alopurinolis; BW-56-158; HPP; NSC-1390

BAN: Allopurinol

USAN: Allopurinol

INN: Allopurinol [rINN (en)]

INN: Alopurinol [rINN (es)]

INN: Allopurinol [rINN (fr)]

INN: Allopurinolum [rINN (la)]

INN: Аллопуринол [rINN (ru)]

Molecular formula: C5H4N4O =136.1

CAS: 315-30-0 (allopurinol); 17795-21-0 (allopurinol sodium)

ATC code: M04AA01

Read code: y0318

Description. Allopurinol is a tautomeric mixture of 1H-pyrazolo[3,4-d]pyrimidm-4-ol and l,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one.

Pharmacopoeias. In China, Europe, International, Japan, and the US

European Pharmacopoeia, 6th ed., 2008 and Supplements 6.1 and 6.2 (Allopurinol). A white or almost white powder. Very slightly soluble in water and alcohol; dissolves in dilute solutions of alkali hydroxides.

The United States Pharmacopeia 31, 2008, and Supplements 1 and 2 (Allopurinol). A fluffy white to an off-white powder having only a slight odor. Very slightly soluble in water and alcohol; practically insoluble in chloroform and ether; soluble in solutions of potassium and sodium hydroxides.

Preparations

British Pharmacopoeia 2008; Allopurinol Tablets;
The United States Pharmacopeia 31, 2008, and Supplements 1 and 2: Allopurinol Oral Suspension; Allopurinol Tablets.

Single-ingredient Preparations

The symbol ¤ denotes a preparation which is discontinued or no longer actively marketed.

Argentina: Alfadiman; Alloboxal¤; Gotir¤; Puritenk;
Australia: Allohexal; Alloremed¤; Allorin¤; Allosig; Capurate; Progout; Zygout¤; Zyloprim;
Austria: Allostad; Allotyrol; Apurin; Gewapurol; Gichtex; Purinol; Urosin; Zyloric; Belgium: Zyloric;
Brazil: Labopurinol; Lopurax; Uricemil; Zyloric;
Canada: Alloprin¤; Novo-Purol¤; Purinol¤; Zyloprim; Chile: Talol; Urogotan A; Zyloric;
Czech Republic: Apurol; Milurit; Purinol; Denmark: Abopur; Apurin; Hexanurat;
Finland: Allonol; Apurin; Arturic; Zyloric; France: Xanturic¤; Zyloric;
Germany: Allo-300-Tablinen¤; Allo-Efeka; Allo-Puren; Allo; Allobeta; Allohexal¤; Allop-Gry¤; Allpargin¤; Apulonga¤; Bleminol; Cellidrin; Dabroson¤; dura AL; Embarin¤; Epidropal; Foligan; Jenapurinol; Milurit; Pureduct¤; Remid; Sigapurol¤; Suspendol¤; Uribenz; Uripurinol¤; Urobenyl¤; Urosin¤; Urtias¤; Zyloric;
Greece: Soluric; Zylapour; Zyloric; Hong Kong: Allnol¤; Allorin¤; Caplenal¤; Mephanol¤; Milurit; Progout; Zyloric;
Hungary: Harpagin; Milurit; India: Ciploric; Zyloric; Ireland: Caplenal¤; Purinol; Tipuric; Zyloric;
Israel: Alloril; Zylol; Zyloric;
Italy: Allurit; Uricemil¤; Zyloric;
Malaysia: Harpagin¤; Uritab¤; Zyloric;
Mexico: Acyprin; Apo-Tinole; Atisuril; Aurigen¤; Darzune; Etindrax; Labypurol¤; Oloprim¤; Unizuric; Zyloprim;
Netherlands: Apurin; Zyloric;
Norway: Allopur; Arturic; Zyloric;
New Zealand: Allohexal; Allorin; Progout; Z 300¤; Zyloprim¤;
Portugal: Alosfar; Uriprim; Zurim; Zyloric; Russia: Purinol (Пуринол);
South Africa: Abburic¤; Be-Uric¤; Ethipurinol¤; Lo-Uric¤; Lonol; Puricos; Pyrazol¤; Ranpuric¤; Redurate; Urinol; Urozyl-SR¤; Zyloprim; Singapore: Allorin¤; Erloric¤; Progout; Valeric¤; Zyloric;
Spain: Allopurin¤; Allural¤; Zyloric;
Sweden: Zyloric; Switzerland: Allo-300-Tablinen¤; allo-basan; Allopur; Cellidrine; Foligan¤; Lysuron¤; Mephanol; Sigapurol N; Uredimin¤; Uriconorme; Zyloric;
Thailand: Alinol; Allopin; Allorin¤; Apnol; Apurol; Loporic¤; Medoric; Mephanol¤; Puricin; Puride; Sigapurol¤; Uricad; Valeric; Xanol; Zyloric;
United Kingdom: Aloral¤; Aluline¤; Caplenal; Cosuric; Hamarin¤; Progout¤; Rimapurinol; Xanthomax¤; Zyloric; United States: Aloprim; Lopurin¤; Zyloprim; Venezuela: Aluprol; Aluron; Zyloric

Multi-ingredient Preparations

Argentina: Artrex; Colpuril;
Austria: Allobenz; Duovitan¤; Gichtex plus; Uroplus¤;
Belgium: Comburic; France: Anurate¤; Desatura¤;
Germany: Acifugan¤; Allo.comp.; Allomaron¤; Harpagin; Uricovac comp¤;
Italy: Uricodue; Urifugan¤; Portugal: Acifugan¤;
South Africa: Allomaron;
Spain: Acifugan¤; Biuricowas¤; Facilit¤; Uricina¤;
Switzerland: Acifugan¤;
Thailand: Allomaron