allopurinol (Rx)

1-10%

Rash (1.5%)

Nausea (1.3%)

Renal failure (1.2%)

Vomiting (1.2%)

Frequency Not Defined

Amblyopia

Arthralgias

Blood dyscrasias

Bronchospasm

Cardiovascular abnormalities

Cataracts

Confusion

Decrease in libido

Dizziness

Ecchymosis

Electrolyte abnormalities

Epistaxis

Foot drop

Hematuria

Hepatotoxicity

Hypotonia

Iritis

Kidney function abnormality

Macular retinitis

Malaise

Neuritis

Pharyngitis

Pruritus

Skin edema

Stevens-Johnson syndrome

Sweating

Tinnitus

Contraindications

Hypersensitivity to allopurinol

Cautions

Discontinue at first sign of allergic reactions (first sign of rash, vasculitis, or Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms (DRESS) and/or generalized vasculitis, irreversible hepatotoxicity)

The HLA-B*58:01 allele is a genetic marker for severe skin reactions indicative of hypersensitivity to allopurinol; patients who carry the HLA-B*58:01 allele are at a higher risk of allopurinol hypersensitivity syndrome (AHS); however, hypersensitivity reactions reported in patients who do not carry this allele; frequency of this allele is higher in individuals of African, Asian (e.g., Han Chinese, Korean, Thai), and Native Hawaiian/Pacific Islander ancestry; prior to starting therapy, consider testing for the HLA-B*58:01 allele in genetically at-risk populations; therapy not recommended in HLA-B*58:01 positive patients unless benefits clearly outweigh risks

Myelosuppression reported; use caution when administering other drugs known to cause myelosuppression

Hepatotoxicity (reversible) reported

Not for treatment of asymptomatic hyperuricemia

Use with caution in renal impairment

Risk of hypersensitivity increased in patients treated with angiotensin-converting emzyme (ACE) inhibitors

When taken with amoxicillin or ampicillin, may increase risk of skin rash

During concomitant treatment, reduce dosages of azathioprine and mercaptopurine to 25-33% of usual

Occurrence of hypersensitivity reactions may be increased in patients with renal impairment, especially in patients who are receiving thiazide diuretics; reduce dose in patients with impaired renal function

Risk of hypersensitivity may increase with concomitant administration of thiazides

Maintain fluid intake necessary to yield urine output of at least 2 L/day in adults

Pregnancy

Experience with human pregnancy limited partly because women of reproductive age rarely require treatment with drug; in 2011, a literature publication case report describes outcome of a full term pregnancy in a 35 year-old woman who had recurrent kidney stones since age 18 who took allopurinol throughout pregnancy; the child had multiple complex birth defects and died at 8 days of life; a second report on 31 prospectively ascertained pregnancies involving mothers exposed to allopurinol for varying durations during first trimester; the overall rate of major fetal malformations and spontaneous abortions was reported to be within normal expected range; however, one child had severe malformations similar to those described in earlier case report

Animal data

• Reproductive studies performed in rats and rabbits at doses up to twenty times usual human dose (5 mg/kg per day) concluded that there was no impaired fertility or harm to fetus due to allopurinol; there is a published report of a study in pregnant mice given 50 or 100 mg/kg allopurinol intraperitoneally on gestation days 10 or 13; there were increased numbers of dead fetuses in dams given 100 mg/kg allopurinol but not in those given 50 mg/kg; there were increased numbers of external malformations in fetuses at both doses of allopurinol on gestation day 10 and increased numbers of skeletal malformations in fetuses at both doses on gestation day 13; it cannot be determined whether this represented a fetal effect or an effect secondary to maternal toxicity; there are, however, no adequate or well controlled studies in pregnant women; because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed

Lactation

Allopurinol and oxipurinol have been found in milk of mother who was receiving drug; since effect of allopurinol on nursing infant is unknown, exercise caution when therapy is administered to nursing woman

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Xanthine oxidase inhibitor; inhibits conversion of hypoxanthine to xanthine to uric acid; decreases production of uric acid without disrupting synthesis of vital purines

Pharmacokinetics

Bioavailability: 49-53%

Onset: 2-3 days

Peak plasma time: 0.5-2 hr

Time to peak effect: 7-14 days

Distribution

Protein bound: <1%

Vd: 1.6-2.4 L/kg

Metabolism

Metabolized in liver

Metabolites: Oxypurinol (active), allopurinol riboside (activity unknown)

Elimination

Half-life: Parent drug, 1-3 hr; active metabolite, 15-20 hr

Dialyzable: Yes (both hemodialysis and peritoneal dialysis)

Renal clearance: 30 mL/min

Total body clearance: 16 mL/min/kg

Excretion: Urine (80%), feces (10-20%)

IV Compatibilities

Y-site (partial list): Acyclovir, calcium gluconate, cefazolin, ceftriaxone, carboplatin, cisplatin, cyclophosphamide, dactinomycin, doxorubicin liposomal, fluorouracil, ifosfamide, mesna, metronidazole, mitoxantrone, morphine sulfate, potassium chloride, thiotepa, vancomycin

IV Incompatibities

Y-site: Amikacin, amphotericin B, carmustine, cefotaxime, chlorpromazine, cimetidine, clindamycin, cytarabine, dacarbazine, daunorubicin, diphenhydramine, doxorubicin, doxycycline, droperidol, floxuridine, gentamicin, haloperidol, hydroxyzine, idarubicin, imipenem-cilastatin, mechlorethamine, meperidine, methylprednisolone sodium succinate, metoclopramide, minocycline, nalbuphine, netilmicin, ondansetron, prochlorperazine, promethazine, sodium bicarbonate, streptozocin, tobramycin, vinorelbine

IV Preparation

Reconstitute with 25 mL SWI

Dilute to desired concentration with NS or D5W; do not use sodium bicarbonate-containing solutions; final concentration of ≤6 mg/mL is recommended

Store solution at 20-25°C (do not refrigerate), and use within 10 hours after reconstitution

IV Administration

In both adults and children, daily dose can be given as single infusion or in equally divided infusions q6hr, q8hr, or q12hr

Whenever possible, administration should be initiated 1-2 days before start of chemotherapy known to cause tumor cell lysis (including adrenocorticosteroids)