DRUG PROFILE
2. Brand(s):
| Brand name | Manufacturer | Dosage Form | Pack Size | MRP |
| Zyloric | GlaxoSmithKline | Film Coated Tablet | 100mg 5*10s 300mg 3*10s | Rs 120.98 |
| Zynol | Pharmedic | Film Coated Tablet | 300mg 100 Tabs in blisters | Rs 77.00 |
| URIK | Raazee Therapeutics | Film Coated Tablet | 300mg 30,s | Rs 98.70 |
3. Pharmacological Group:
Xanthine-Oxidase Inhibitor
4. Formulations:
Film Coated Tablet Containing 300mg of Allopurinol
5. General Information:
Allopurinol is a drug used primarily to treat conditions arising from excess uric acid, most notably chronic gout. Allopurinol does not alleviate acute attacks of gout, but is useful in preventing recurrence.
6. Dosage Form:
Solids
| Tablets ◙ |
| Capsules | ||
| Hard Capsules | Soft Capsules | Modified Released Capsules |
| Uncoated Tablets | Coated Tablets ◙ | Modified Released Tablets | Sublingual Tablets |
| Powders | |
| Powders for suspension | Powders for Inhalers |
| Others |
| Liquids | Syrup | Oral drops | Nasal Drops | Topical Solutions | Eye Preparations | Ear Preparations | Others |
| Parenterals Preparations ◙ | Injections | Infusions | Powders for injection ◙ | Others |
| Topical Solids | Ointment | Creams | lotions | Gels | Pastes | Others |
6. Therapeutic Uses:
It is used to treat gout, high levels of uric acid in the body caused by certain cancer medications, and kidney stones .In addition Allopurinol is also commonly used as prophylaxis with chemotherapeutic treatments, which can rapidly result in very high uric acid concentrations due to widespread cell death (tumour lysis syndrome). Other established indications for Allopurinol therapy include ischaemic reperfusion injury, kidney stones (urolithiasis) and protozoal infections (Leishmaniasis).
7. Information for the user:
i. How to take:
Preferably after a meal. Drink at least eight glasses of water or other fluids each day while taking Allopurinol unless directed to do otherwise by your doctor.
ii. Frequency & Time of Dosing:
It is usually taken once or twice a day. Take it around the same time every day.
iii. Recommended Dosage Range:
| Neonates/ Children | Adult | Geriatric | Dose according to clinical condition |
| a) Children up to 6 years of age: 50 mg b) Children 6 to 10 years of age: One 100-mg tablet three times a day or one 300-mg tablet a day. c) Children under 15years: 10 to 20 mg/kg of body weight or up to 400mg daily For the parenteral dosage form (injection): At first, 200 mg per square meter of body surface area (mg/m2) per day, injected into a vein. | Should be introduced with low doses of 100mg/day Or 100 to 200 mg in mild conditions 300 to 600 mg in moderately severe conditions 700 to 900 mg in severe conditions Or 2 to 10 mg/kg of body weight/day 200 to 400 mg per square meter of body surface area (mg/m2) a day, injected into a vein. | Dose should be reduced due to less functionality of Liver and kidney. | In the patients of Renal Impairment Less then100mg per day or single doses of 100 mg at longer intervals. Try to keep the plasma level below 100 µmol/liter(15.2mg/liter) In the patient of hepatic impairment Dose should be reduced with regular LFTs |
iv. Onset of effect:
Studies have shown the presence of drug in the blood after the 30-60 minutes of administration.
v. Duration of Action:
Effective inhibition of Xanthine-Oxidase is maintained for 24 hours with single daily dose.
vi. Diet Advice:
Drinking too much alcohol may increase the amount of uric acid in the blood and lessen the effects of Allopurinol. Therefore, people with gout and other people with too much uric acid in the body should be careful to limit the amount of alcohol they drink.
Taking too much vitamin C may make the urine more acidic and increase the possibility of kidney stones forming while you are taking Allopurinol. Therefore, check with your doctor before you take vitamin C while taking this medicine.
vii. Storage:
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.
viii: Missed Dose:
Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.
ix. Stopping the drug:
Stopping the Drug at once after the completion of therapy may not produce any harmful symptoms but a low dose regime is required to avoid relpse.
x. Exceeding the dose (overdose):
Ingestion of up to 22.5 g Allopurinol without effect has been reported. Symptoms and signs including nausea, vomiting and dizziness have been reported in a patient who ingested 20g Allopurinol.
8. Possible Adverse 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, worsening 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 Syndrome (TENS) which is an adverse drug reaction.
9. Contraindications:
There appear to be no specific contraindication to the use of Allopurinol, other then known intolerance so it must not be used in those who are very sensitive to Allopurinol. However a reduction in dose should be considered in Renal and Hepatic patients.
10. Interactions:
| Drug-Drug Interactions | Drug-Food Interactions |
| Patients under treatment of hypertension (ACE inhibitors and Diuretics) may have some concomitant impairment of renal function. Under mentioned should be used with precautions. § Alacepril § Captopril § Mercaptopurine § Cyclophosphamide | Using alcohol or tobacco with Allopurinol may cause interactions to occur. Vit C rich food can leads to Kidney stones. |
11. Prolonged Use:
Prolonged use may increase the concentration of Allopurinol in the body because it inhibits its own metabolism and decreases the clearance. So prolonged use needs the frequent dose adjustments.
12. Special Precautions:
i. Be sure to tell your doctor if:
- You are allergic to allopurinol or any other medications.
- Prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking. Be sure to mention any of the following: amoxicillin (Amoxil, Trimox); ampicillin (Polycillin, Principen); anticoagulants ('blood thinners') such as warfarin (Coumadin); cancer chemotherapy drugs such as cyclophosphamide (Cytoxan) and mercaptopurine (Purinethol); chlorpropamide (Diabinese); diuretics ('water pills'); medications that suppress the immune system such as azathioprine (Imuran) and cyclosporine (Neoral, Sandimmune); other medications for gout such as probenecid (Benemid) and sulfinpyrazone (Anturane); and tolbutamide (Orinase).
- You have or have ever had kidney or liver disease or heart failure.
- You are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking allopurinol, call your doctor.
ii. Pregnancy:
It is approved as Class C (no animal studies have been conducted and there are no adequate studies in pregnant women.) drug in pregnancy.
iii. Breast Feeding/Lactation:
Allopurinol and Oxypurinol are excreted in human breast milk. Concentrations are 1.4mg/liter Allopurinol and 53.7mg/liter Oxipurinol after taking 300mg/day. No data is there showing effect of Allopurinol and Oxypurinol in infants.
iv. Infants & Children:
In Children it is mainly indicated in malignant conditions, especially leukemia. Can be given safely in children and infants
v. Over 60:
In the absence of specific data, the lowest dosage which produces satisfactory urate reduction data should be used.
vi. Driving & Hazardous work:
Allopurinol may cause some people to become drowsy or less alert than they are normally. So do not drive, use machines, or do anything else that could be dangerous if you are not alert.
vii. Alcohol:
Alcohol may decrease the effectiveness of Allopurinol.
13. Pharmacological Properties:
13.(i). Pharmacodynamic Properties:
Allopurinol is a structural isomer of hypoxanthine (a naturally occurring purine in the body) and acts to inhibit xanthine oxidase. This enzyme is responsible for the successive oxidation of hypoxanthine and xanthine resulting in the production of uric acid, the product of human purine metabolism. 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
13.(ii). Pharmacokinetic Properties:
i. Absorption:
Allopurinol is active when given orally and is rapidly absorbed (90%) from the upper GIT.
ii. Distribution:
| Bioavailability | %Protein binding | Half Life | Volume of distribution | Blood Brain Barrier | Placental Barrier |
| 78±20% or 67% to 90% | Negligible | 2 hours for Allopurinol and (oxypurinol 18-30 hours) | 1.6 liter/kg | Croses the BBB | Crosses and have teratogenic activity in test Animals |
iii. Metabolism
| Site of Metabolism | Active Metabolites |
| oxypurinol, Allopurinol-riboside, Oxypurinol-7-riboside |
iv. Elimination:
| Elimination Half Life | Route of Elimination |
| 13.6 to 29 Hours | Urine (10% unchanged) and Faeces (20%) |
15. Preclinical Safety Data:
Cytogenesis studies show that Allopurinol does not induce chromosome aberrations in human blood cells in vitro at concentration up to 100µg/ml and In vivo at doses up to 60 mg/day for a mean period of 40 month.
No evidence of carcinogenicity has been found in mice and rats treated with Allopurinol for up to two years.
One study in mice receiving intraperitonial doses of 50 or 100 mg/kg on days 10 or 13 of gestation resulted in foetal abnormalities. However in rats at higher doses no evidence found.
16. Instructions for Handling:
Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.
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