Allopurinol

Name: Allopurinol

Allopurinol Brand Names

Allopurinol may be found in some form under the following brand names:

  • Aloprim

  • Lopurin

  • Zyloprim

Stability

Storage

Oral

Tablets

15–25°C in dry place; protect from light.156

Parenteral

Powder for Injection

25°C (may be exposed to 15–30°C).152

Store diluted allopurinol sodium solutions containing ≤6 mg/mL of allopurinol at 20–25°C; use within 10 hours of reconstitution.152 Do not refrigerate reconstituted and/or diluted solutions.152

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility152

Compatible

Dextrose 5% in water

Sodium chloride 0.9%

Drug Compatibility Y-Site Compatibilityb

Compatible

Acyclovir sodium

Aminophylline

Aztreonam

Bleomycin sulfate

Bumetanide

Buprenorphine HCl

Butorphanol tartrate

Calcium gluconate

Carboplatin

Cefazolin sodium

Cefotetan disodium

Ceftazidime

Ceftizoxime sodium

Ceftriaxone sodium

Cefuroxime sodium

Cisplatin

Co-trimoxazole

Cyclophosphamide

Dactinomycin

Dexamethasone sodium phosphate

Doxorubicin HCl liposome injection

Enalaprilat

Etoposide

Famotidine

Fluconazole

Fludarabine phosphate

Fluorouracil

Furosemide

Ganciclovir sodium

Granisetron HCl

Heparin sodium

Hydrocortisone sodium phosphate

Hydrocortisone sodium succinate

Hydromorphone HCl

Ifosfamide

Lorazepam

Mannitol

Mesna

Methotrexate sodium

Metronidazole

Mitoxantrone HCl

Morphine sulfate

Plicamycin

Potassium chloride

Ranitidine HCl

Teniposide

Thiotepa

Ticarcillin disodium

Ticarcillin disodium–clavulanate potassium

Vancomycin HCl

Vinblastine sulfate

Vincristine sulfate

Zidovudine

Incompatible

Amikacin sulfate

Amphotericin B

Carmustine

Cefotaxime sodium

Chlorpromazine HCl

Cimetidine HCl

Clindamycin phosphate

Cytarabine

Dacarbazine

Daunorubicin HCl

Diphenhydramine HCl

Doxorubicin HCl

Doxycycline hyclate

Droperidol

Floxuridine

Gentamicin sulfate

Haloperidol lactate

Hydroxyzine HCl

Idarubicin HCl

Imipenem–cilastatin sodium

Mechlorethamine HCl

Meperidine HCl

Methylprednisolone sodium succinate

Metoclopramide HCl

Minocycline HCl

Nalbuphine HCl

Ondansetron HCl

Prochlorperazine edisylate

Promethazine HCl

Sodium bicarbonate

Streptozocin

Tobramycin sulfate

Vinorelbine tartrate

Actions

  • Allopurinol and its active metabolite, oxypurinol, inhibit xanthine oxidase.152 156 Inhibition of xanthine oxidase blocks conversion of oxypurines (hypoxanthine, xanthine) to uric acid, resulting in decreases in serum and urine uric acid concentrations and increases in serum and urine concentrations of hypoxanthine and xanthine.152 156

  • Decreases de novo purine biosynthesis by indirectly increasing oxypurine and allopurinol ribonucleotide concentrations and decreasing phosphoribosylpyrophosphate concentrations.a Also decreases serum uric acid concentrations by increasing incorporation of hypoxanthine and xanthine into DNA and RNA.152 a

  • Has no analgesic, anti-inflammatory, or uricosuric activity.153

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Allopurinol

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

100 mg*

Zyloprim (with povidone; scored)

Prometheus

300 mg*

Zyloprim (with povidone; scored)

Prometheus

Allopurinol Sodium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV infustion only

500 mg (of allopurinol)

Aloprim

Nabi

Proper Use of allopurinol

Take allopurinol exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. To do so may increase the chance of side effects.

Take allopurinol after meals to avoid stomach upset.

Take allopurinol with plenty of liquids to help prevent kidney stones. Check with your doctor about the amount of liquid you or your child should drink each day.

Dosing

The dose of allopurinol will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of allopurinol. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

  • For oral dosage form (tablets):
    • For treatment of gout:
      • Adults—At first, 100 to 300 milligrams (mg) per day, taken once a day or in divided doses. Your doctor may adjust your dose as needed. However, the dose is usually not more than 800 mg per day.
      • Children—Use and dose must be determined by your doctor.
    • For treatment of high uric acid levels caused by cancer medicines:
      • Adults, teenagers, and children 11 years of age and older—600 to 800 milligrams (mg) per day, taken in divided doses for 2 to 3 days.
      • Children 6 to 10 years of age—300 mg per day, taken once a day for 2 to 3 days.
      • Children younger than 6 years of age—150 mg per day, taken once a day for 2 to 3 days.
    • For treatment of kidney stones:
      • Adults—200 to 300 milligrams (mg) per day, taken once a day or in divided doses. Your doctor may adjust your dose as needed. However, the dose is usually not more than 800 mg per day.
      • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of allopurinol, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

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.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Pharmacologic Category

  • Antigout Agent
  • Xanthine Oxidase Inhibitor

Administration

Administer fluids sufficient to yield daily urinary output of at least 2 L and to maintain neutral or, preferably, slightly alkaline urine.

Oral: Administer after meals.

IV: The rate of infusion depends on the volume of the infusion; infuse maximum single daily doses (600 mg/day) over ≥30 minutes. Whenever possible, therapy should be initiated at 24 to 48 hours before the start of chemotherapy known to cause tumor lysis (including adrenocorticosteroids). IV daily dose can be administered as a single infusion or in equally divided doses at 6-, 8-, or 12-hour interval.

Adverse Reactions

Most commonly reported:

Dermatologic: Skin rash

Endocrine & metabolic: Gout (acute)

Gastrointestinal: Diarrhea, nausea

Hepatic: Increased liver enzymes, increased serum alkaline phosphatase

<1% (Limited to important or life-threatening): Ageusia, agranulocytosis, alopecia, angioedema, aplastic anemia, cataract, cholestatic jaundice, ecchymoses, eczematoid dermatitis, eosinophilia, exfoliative dermatitis, hepatic necrosis, hepatitis, hepatomegaly, hepatotoxicity (idiosyncratic) (Chalasani, 2014), hyperbilirubinemia, hypersensitivity reaction, leukocytosis, leukopenia, lichen planus, macular retinitis, myopathy, necrotizing angiitis, nephritis, neuritis, neuropathy, onycholysis, pancreatitis, purpura, renal failure, skin granuloma (annulare), Stevens-Johnson syndrome, thrombocytopenia, toxic epidermal necrolysis, toxic pustuloderma, uremia, vasculitis, vesicobullous dermatitis

Pharmacology

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%)

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Usual Adult Dose for Hyperuricemia Secondary to Chemotherapy

Parenteral:
200 to 400 mg/m2/day IV as a single infusion or in equally divided infusions at 6, 8, or 12 hour intervals
Maximum dose: 600 mg/day

Oral:
Initial dose: 600 to 800 mg/day in divided doses
Maintenance: Adjust dose as needed using serum uric acid levels
Maximum dose: 800 mg per day

Comments:
-When possible, therapy should be initiated 24 to 48 hours before the start of chemotherapy; treatment should be discontinued when the potential for overproduction of uric acid is no longer present.
-Oral doses in excess of 300 mg/day should be given in divided doses, preferably after meals to minimize gastric irritation.
-Fluid intake should be sufficient to maintain a daily urinary output of at least 2 L; neutral or preferably slightly alkaline urine is desirable.

Use: For the management of patients with leukemia, lymphoma, and malignancies who are receiving cancer therapy which causes elevations of serum and urinary uric acid levels; IV therapy is available for patients who cannot tolerate oral therapy.

Liver Dose Adjustments

Use with caution.

If anorexia, weight loss, or pruritus develops, an evaluation of liver function tests should be part of diagnostic workup.

Allopurinol Breastfeeding Warnings

Caution is recommended Excreted into human milk: Yes Comments: The effects in the nursing infant are unknown.

Allopurinol and its active metabolite oxypurinol are excreted into human breast milk. Based on a case study in a 5-week old breastfed infant, the calculated daily dose of allopurinol and oxypurinol received by an exclusively breastfed infant would be between 0.14 and 0.2 mg/kg and 7.2 to 8 mg/kg, respectively. Limited data have found no observable side effects in breastfed infants. If this drug is needed, monitor breastfed infants closely for allergic reactions (e.g. rash), and perform periodic blood counts (including a differential).

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

(web3)