allopurinol

Absorption: Well absorbed (80%) following oral administration.

Distribution: Widely distributed in tissue and breast milk.

Protein Binding: <1%.

Metabolism/Excretion: Metabolized to oxypurinol, an active compound with a long half-life. 12% excreted unchanged, 76% excreted as oxypurinol.

Half-Life: 1–3 hr (oxypurinol 18–30 hr).

Time/Action Profile ⬆ ⬇

(hypouricemic effect)

ROUTE	ONSET	PEAK	DURATION
PO, IV	1–2 days	1–2 wk	1–3 wk‡

‡Duration after discontinuation of allopurinol.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Presence of HLA-B*58:01 allele (↑ risk of hypersensitivity reactions);
Lactation: Lactation.

Use Cautiously in:

Acute attacks of gout;
Renal impairment (dose ↓ required if CCr <20 mL/min);
Dehydration (adequate hydration necessary);
OB: Safety not established in pregnancy;
Geri: Begin at lower end of dosage range in older adults.

Adv. Reactions/Side Effects ⬆ ⬇

CV: bradycardia, flushing, heart failure (reported with IV administration), hypertension, hypotension

Derm: rash (discontinue drug at first sign of rash), DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, urticaria

GI: diarrhea, hepatitis, nausea, vomiting

GU: hematuria, renal failure

Hemat: bone marrow depression

Neuro: drowsiness

Misc: HYPERSENSITIVITY REACTIONS

Interactions ⬆ ⬇

Drug-drug:

Use with mercaptopurine and azathioprine↑ bone marrow depressant properties—doses of these drugs should be ↓.
Use with ampicillin or amoxicillin↑ risk of rash.
Use with oral hypoglycemic agents and warfarin↑ effects of these drugs.
Use with thiazide diuretics or ACE inhibitors↑ risk of hypersensitivity reactions.
Large doses of allopurinol may ↑ risk of theophylline toxicity.
May ↑ cyclosporine levels.

Route/Dosage ⬆ ⬇

Gout

PO (Adults and Children >10 yr): Initially: 100 mg/day; ↑ at weekly intervals based on serum uric acid (not to exceed 800 mg/day). Doses >300 mg/day should be given in divided doses; Maintenance dose: 100–200 mg 2–3 times daily. Doses of ≤300 mg may be given as a single daily dose.

Renal Impairment

(Adults and Children ): CCr 10–50 mL/min:↓ dose to 50% of recommended; CCr <10 mL/min:↓ dosage to 30% of recommended.

Secondary Hyperuricemia

PO (Adults and Children >10 yr): 600–800 mg/day in 2–3 divided doses starting 1–2 days before chemotherapy or radiation.
PO (Children 6–10 yr): 10 mg/kg/day in 2–3 divided doses (maximum 800 mg/day) or 300 mg daily in 2–3 divided doses.
PO (Children <6 yr): 10 mg/kg/day in 2–3 divided doses (maximum 800 mg/day) or 150 mg daily in 3 divided doses.
IV (Adults and Children >10 yr): 200–400 mg/m²/day (up to 600 mg/day) as a single daily dose or in divided doses every 8–24 hr.
IV (Children <10 yr): 200 mg/m²/day initially as a single daily dose or in divided doses every 8–24 hr (maximum dose 600 mg/day).

Renal Impairment

(Adults and Children ): CCr 10–50 mL/min:↓ dose to 50% of recommended; CCr <10 mL/min:↓ dosage to 30% of recommended.

Availability ⬆ ⬇

(Generic available)

Tablets: 100 mg; 200 mg; 300 mg
Powder for injection: 500 mg/vial

Assessment ⬆ ⬇

Monitor intake and output ratios. Decreased kidney function can cause drug accumulation and toxic effects. Ensure that patient maintains adequate fluid intake (minimum 2500–3000 mL/day) to minimize risk of kidney stone formation.
- Consider testing for the HLA-B*58:01 allele in patients of African, Asian, and Native Hawaiian/Pacific Islander ancestry prior to using allopurinol; use not recommended if allele present.
- Assess patient for rash or more severe hypersensitivity reactions. Discontinue allopurinol immediately if rash occurs. Therapy should be discontinued permanently if reaction is severe. Therapy may be reinstated after a mild reaction has subsided, at a lower dose (50 mg/day with very gradual titration). If skin rash recurs, discontinue permanently.
Monitor for signs and symptoms of DRESS (fever, rash, lymphadenopathy, and/or facial swelling, associated with involvement of other organ systems (hepatitis, nephritis, hematologic abnormalities, myocarditis, myositis) during therapy. May resemble an acute viral infection. Eosinophilia is often present. Discontinue therapy if signs occur.
Gout: Monitor for joint pain and swelling. Addition of colchicine or NSAIDs may be necessary for acute attacks. Prophylactic doses of colchicine or an NSAID should be administered concurrently during first 3–6 mo of therapy because of an increased frequency of acute attacks of gouty arthritis during early therapy.

Lab Test Considerations:

Serum and urine uric acid levels usually begin to ↓ 2–3 days after initiation of oral therapy.
- Monitor blood glucose in patients receiving oral hypoglycemic agents. May cause hypoglycemia.
- Monitor hematologic, renal, and liver function tests before and periodically during therapy, especially during the first few mo. May cause ↑ serum alkaline phosphatase, bilirubin, AST, and ALT levels. ↓ CBC and platelets may indicate bone marrow depression. ↑ BUN, serum creatinine may indicate nephrotoxicity. These are usually reversed with discontinuation of therapy.

Implementation ⬆ ⬇

Do not confuse Zyloprim with zolpidem.
PO: May be administered after milk or meals to minimize gastric irritation; give with plenty of fluid. May be crushed and given with fluid or mixed with food for patients who have difficulty swallowing.

IV Administration:

Intermittent Infusion: Reconstitution: Reconstitute each 500 mg vial with 25 mL of sterile water for injection. Solution is clear and almost colorless with only slight opalescence; do not administer solutions that are cloudy, discolored, or contain particulate matter. Diluent: Dilute to desired concentration with 0.9% NaCl or D5W. Administer within 10 hr of reconstitution; do not refrigerate. Do not administer solutions that are discolored or contain particulate matter.Concentration: Not >6 m g/mL.
Rate: Infusion should be initiated 24–48 hr before start of chemotherapy known to cause tumor cell lysis. Rate of infusion depends on volume of infusate (100–300 mg doses may be infused over 30 min). May be administered as a single infusion or equally divided infusions at 6-, 8-, or 12-hr intervals.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take allopurinol as directed. Take missed doses as soon as remembered. If dosing schedule is once daily, do not take if remembered the next day. If dosing schedule is more than once a day, take up to 300 mg for next dose.
Instruct patient to continue taking allopurinol along with an NSAID or colchicine during an acute attack of gout. Allopurinol helps prevent, but does not relieve, acute gout attacks.
Alkaline diet may be ordered. Urinary acidification with large doses of vitamin C or other acids may increase kidney stone formation (see Food Sources for Specific Nutrients). Advise patient of need for increased fluid intake.
May occasionally cause drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to drug is known.
Instruct patient to report skin rash, blood in urine, influenza symptoms (chills, fever, muscle aches and pains, nausea, or vomiting) or symptoms of DRESS to health care professional immediately; skin rash may indicate hypersensitivity.
Advise patient that large amounts of alcohol increase uric acid concentrations and may decrease the effectiveness of allopurinol.
Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding during therapy and for 1 wk after last dose.
Emphasize the importance of follow-up exams to monitor effectiveness and side effects.

section name header

Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇