| |
|
| ALLOPURINOL-HAKIM |
| :: Antihyperuricemic, Antigout, Antiurolithic :: |
|
 Tab. 100, 300 mg |
|
|
|
|
|
|
|
Pharmacologic category
Antihyperuricemic, Antigout agent, Antiurolithic
Mechanism of action
Allopurinol and its metabolite, oxipurinol (alloxanthine), decrease the production of uric acid by inhibiting the action of xanthine oxidase, the enzyme that converts hypoxanthine to xanthine and xanthine to uric acid. Also, allopurinol increases reutilization of hypoxanthine and xanthine for nucleotide and nucleic acid synthesis via an action involving the enzyme hypoxanthine – guanine phosphoribosyltransferase (HGPRTase). The resultant increase in nucleotide concentration leads to feedback inhibition of de novo purine synthesis. Allopurinol thereby decreases uric acid concentrations in both serum and urine.
Indications
Chronic gouty arthritis (treatment) – Allopurinol is indicated for the long – term management of hyperuricemia associated with primary or secondary gout to reduce the number of acute gout attacks and decrease the risk of uric acid calculi and urate nephropathy in patients with chronic gout.
Hyperuricemia (prophylaxis and treatment) – Allopurinol is indicated to control hyperuricemia secondary to blood dyscrasias (such as polycythemia vera or myeloid metaplasia ) , or their treatment . It is also indicated to prevent or treat hyperuricemia secondary to tumor lysis induced by cancer chemotherapy with cytotoxic antineoplastic agents or radiation therapy in patients with leukemias , lymphomas , or other neoplastic disease . Allupurinol is also used to control hyperuricemia in patients with Lesch – Nyhan syndrome .
Uric acid nephropathy (prophylaxis and treatment) , uric acid and calcium oxalate renal calculi (prophylaxis) are other indications.
Allopurinol is not recommended for treatment of asymptomatic hyperuricemia.
Side/Adverse effects
Allergic dermatitis (skin rash , hives , or itching) ; Agranulocytosis ; Vasculitis ; Aplastic anemia ; Exfoliative dermatitis ; Erythema multiforme ; Hepatotoxicity ; Loosening of fingernails; Toxic epidermal necrolysis ; Peripheral neuritis ; Xanthine renal calculus ; Acute renal failure; Stevens – Johnson syndrome; Thrombocytopenia ; Unexplained nosebleeds ; Diarrhea ; Drowsiness ; Headache ; Indigestion ; Nausea or vomiting ; Chills or fever ; Muscle aches ; Stomach pain ; Unusual hair loss.
Contraindications
Hypersensitivity to allopurinol or any component of the formulation.
Warnings / Precautions
Do not use to treat asymptomatic hyperuricemia . Discontinue at first signs of rash . Reduce dosage in renal insufficiency . Reinstate with caution in patients who have had a previous mild allergic reaction. Use with caution in children . Monitor liver function and CBC before initiating therapy and periodically during therapy.
Pregnancy
FDA pregnancy category C. Use only if potential benefit outweighs the potential risk to use.
Breast–Feeding
Allopurinol is distributed into breast milk . However , problems in humans have not been documented . Use with caution.
Drug Interactions
Urinary acidifiers such as ammonium chloride , ascorbic acid and potassium or sodium phosphate may increase the possibility of allopurinol – induced xanthine kidney stone formation . Concurrent use of amoxicillin and ampicillin with allopurinol may significantly increase the possibility of skin rash. Allopurinol may inhibit metabolism of the coumarin – or indandione – derivative anticoagulants, leading to potentiation of the anticoagulant effect. Concurrent use of allopurinol with cyclophosphamide , azathioprine and mercaptopurine may increase the potential for bone marrow depression. Allopurinol may inhibit renal tubular secretion of chlorpropamide ; patients receiving these medications concurrently should be monitored for possible increased hypoglycemic effect. Allopurinol decreases cyclosporine metabolism . Dacarbazine may cause additive hypouricemic effects when used concurrently with allopurinol . Thiazide diuretics increase toxicity and risk of hypersensitivity of allopurinol . Concurrent use of systemic vidarabine with allopurinol may increase the risk of neurotoxicity;caution is recommended.Concurrent use of large doses (600 mg per day) of allopurinol with aminophylline and theophylline may result in increased serum theophylline concentrations . Captopril may increase the risk of hypersensitivity.
Monitoring Parameters
CBC ; Serum uric acid levels , Hepatic and renal function , especially at start of therapy.
Dietary Considerations
Should administer allopurinol after meals with plenty of fluid.
Administration and dosage
- Usual adult and adolescent dose: Antigout agent – Initial – Oral , 100 mg once a day , to be increased by 100 mg per day at one – week intervals until the desired serum uric acid concentration is attained.
Maintenance – Oral , 100 to 200 mg two or three times a day ; or 300 mg as a single dose once a day . The usual maintenance dose is 200 to 300 mg per day in mild gout or 400 to 600 mg per day in moderately severe tophaceous gout .
Neoplastic disease therapy – Initial – Oral, 600 to 800 mg per day starting 12 hours to 3 days (preferably 2 to 3 days) prior to initiation of chemotherapy or radiation therapy .
Maintenance – Dosage should be based on serum uric acid determinations performed approximately 48 hours after initiation of allopurinol therapy and periodically thereafter.
Antiurolithic (uric acid calculi) – Oral , 100 to 200 mg one to four times a day ; or 300 mg as a single dose once a day .
Antiurolithic (calcium oxalate calculi) – Oral , 200 to 300 mg a day as a single dose or in divided doses.
- Usual adult prescribing limits: 300 mg per dose ; 800 mg per day.
- Usual pediatric dose: Antihyperuricemic , in neoplastic disease therapy – children up to 6 years of age : Oral , 50 mg 3 times a day.
- Children 6 to 10 years of age: Oral , 100 mg 3 times a day ; or 300 mg as a single dose once a day.
How Supplied
Tablet : 100 mg , 300 mg
Storage
Store below 30° C. Protect from moisture.
References
- USP DI, 2004
- Up To Date, Vol. 13.1 (2005)
- Martindale, The Complete Drug Reference, 33 rd edition 2002
|
