Allopurinol

Pronunciation: (AL-oh-PURE-ee-nahl)

Class: Agent for gout, Antimetabolite

Trade Names:

Aloprim

- Powder for injection, lyophilized 500 mg

Trade Names:

Zyloprim

- Tablets 100 mg

- Tablets 300 mg

Apo-Allopurinol (Canada)

Pharmacology

Inhibits xanthine oxidase, the enzyme responsible for conversion of hypoxanthine to xanthine and then to uric acid.

Pharmacokinetics

Absorption

About 90% absorbed from GI tract. T max is 1.5 h (allopurinol) and 4.5 h (oxipurinol). C max is 3 mcg/mL (allopurinol 300 mg) and 6.5 mcg/mL (oxipurinol).

Metabolism

Rapidly oxidized to oxipurinol.

Elimination

About 20% is excreted in the feces. Allopurinol is essentially cleared by glomerular filtration, whereas oxipurinol is reabsorbed in the kidney tubules. T 1/2 , plasma is about 1 to 2 h (allopurinol) and about 15 h (oxipurinol).

Onset

Uric acid decreases in about 2 to 3 days.

Peak

May require a week or more of treatment.

Duration

Xanthine oxidase inhibition is maintained over 24 h; however, uric acid levels may not return to pretreatment levels until 7 to 10 days following cessation of therapy.

Indications and Usage

Tablets

Treatment of primary or secondary gout, hyperuricemia resulting from chemotherapy for malignancies, recurrent calcium oxalate renal calculi.

Tablets and injections

Management of patients with leukemia, lymphoma, and solid tumor malignancies when concurrently receiving cancer therapy that causes elevations of serum and urinary uric acid levels. Use injection in patients who cannot tolerate oral therapy.

Unlabeled Uses

Prevention of fluorouracil-induced stomatitis and fluorouracil-induced granulocyte suppression.

Contraindications

Standard considerations.

Dosage and Administration

Control of Gout/Hyperuricemia

Adults

PO 100 to 800 mg/day. For amounts over 300 mg, give divided doses.

Secondary Hyperuricemia Associated with Malignancies

Children 6 to 10 yr of age

PO 300 mg/day.

Children under 6 yr of age

PO 150 mg/day.

Prevention of Uric Acid Nephropathy in Vigorous Chemotherapy of Neoplastic Disease

Adults

PO 600 to 800 mg/day for 2 to 3 days.

Reduction of Risk of Acute Gouty Attacks

Adults (initial dose)

PO 100 mg/day, increased by 100 mg at weekly intervals until adequate response is achieved or max recommended dose (800 mg/day) is reached.

Leukemia, Lymphoma, Solid Tumor Malignancies

Adults

IV 200 to 400 mg/m 2 /day (max 600 mg/day).

Children

IV Starting dose 200 mg/m 2 /day.

Storage/Stability

Reconstituted solution

Store reconstituted solution at 20° to 25°C; do not refrigerate or dilute product.

Tablets

Store tablets in tightly closed container in cool location.

Unreconstituted solution

Store unreconstituted powder at room temperature.


Drug Interactions




Amoxicillin increased risk of rash when allopurinol given with amoxicillin
Ampicillin increased risk of rash when allopurinol given with ampicillin
Azathioprine allopurinol enhances effects and increases toxicity of azathioprine (reduce dose of azathioprine to one quarter of usual dose)
Capecitabine avoidance of allopurinol advised by manufacturer of capecitabine Capecitabine is a prodrug of fluorouracil
Captopril increased risk of toxicity when allopurinol given with captopril especially in renal impairment
Ciclosporin allopurinol possibly increases plasma concentration of ciclosporin (risk of nephrotoxicity)
Coumarins allopurinol possibly enhances anticoagulant effect of coumarins Change in patient's clinical condition, particularly associated with liver disease, intercurrent illness, or drug administration, necessitates more frequent testing. Major changes in diet (especially involving salads and vegetables) and in alcohol consumption may also affect anticoagulant control
Didanosine allopurinol possibly increases plasma concentration of didanosine Antacids in tablet formulation may affect absorption of other drugs
Diuretics, Thiazide and related increased risk of hypersensitivity when allopurinol given with thiazides and related diuretics especially in renal impairment
Mercaptopurine allopurinol enhances effects and increases toxicity of mercaptopurine (reduce dose of mercaptopurine to one quarter of usual dose)
Theophylline allopurinol possibly increases plasma concentration of theophylline



Adverse Reactions

CNS

Drowsiness; generalized seizure (injectable); headache; neuritis; paresthesias; peripheral neuropathy.

Dermatologic

Allergic vasculitis; alopecia; ecchymosis; skin rash. Allergic reactions may be severe and sometimes fatal.

EENT

Epistaxis; myopathy; taste disturbance.

GI

Abdominal pain; diarrhea; dyspepsia; gastritis; granulomatous changes; nausea; vomiting.

Genitourinary

Renal failure; uremia.

Hematologic

Bone marrow depression; eosinophilia; leukocytosis; leukopenia; thrombocytopenia.

Hepatic

Cholestatic jaundice; elevated liver enzymes; hepatic necrosis; hepatitis; reversible hepatomegaly.

Other

Acute gouty attacks; arthralgia; fever; myopathy; necrotizing angiitis.

Precautions

Pregnancy

Category C .

Lactation

Excreted in breast milk.

Children

Allopurinol is rarely indicated for use in children, except for hyperuricemia resulting from malignancy or with certain rare inborn errors of purine metabolism.

Hypersensitivity

Discontinue drug at first appearance of skin rash or other signs of allergic reaction. Rash may be followed by more severe hypersensitivity reactions and, rarely, death.

Renal Function

Reduced dose is given in patients with this condition. Drug may exacerbate renal failure in certain patients.

Acute gouty attacks

May occur during initial stages of therapy.

Bone marrow depression

Reported in patients given allopurinol.

Patient Information

* Encourage patient to focus on weight loss or control.

* Tell patient to avoid purine-rich foods (eg, organ meats).

* Caution patient to avoid excessive intake of alcohol.

* Explain that gouty attacks may not end for 2 to 6 wk after beginning therapy.

* Instruct patient to stop taking medication and notify health care provider if rash or flu-like symptoms develop.

* Advise patient that drug may cause drowsiness, and to use caution while driving or performing other tasks requiring mental alertness.