febuxostat

REMS

Chronic management of hyperuricemia in patients with gout who have an inadequate response to a maximally titrated dose of allopurinol, who are intolerant to allopurinol, or in whom allopurinol is not an appropriate treatment option.

Action ⬆ ⬇

Decreases production of uric acid by inhibiting xanthine oxidase.

Therapeutic effects:

Lowering of serum uric acid levels with resultant decrease in gouty attacks.

Pharmacokinetics ⬆ ⬇

Absorption: 49% absorbed following oral administration.

Distribution: Widely distributed to tissues.

Protein Binding: 99.2%.

Metabolism/Excretion: Extensively metabolized by the liver; minimal renal excretion of unchanged drug; 45% eliminated in feces as unchanged drug; remainder is eliminated in urine and feces as inactive metabolites.

Half-Life: 5–8 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	rapid	1–1.5 hr*	24 hr

*Maximum lowering of uric acid may take 2 wk.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Concurrent use of azathioprine or mercaptopurine.

Use Cautiously in:

Cardiovascular disease (↑ risk of cardiovascular death compared to allopurinol) (consider using low-dose aspirin when using febuxostat in these patients)
;
Previous skin reaction with allopurinol;
Severe renal impairment;
Severe hepatic impairment;
OB: Use during pregnancy only when potential maternal benefit justifies potential fetal risk;
Lactation: Safety not established in breastfeeding;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), rash, STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS

GI: ↑liver enzymes, nausea

MS: arthralgia, gout flare

Interactions ⬆ ⬇

Drug-drug:

Significantly ↑ levels of and risk of serious toxicity from azathioprine and mercaptopurine; concurrent use contraindicated.
May ↑ levels and risk of toxicity of theophylline; use cautiously together.

Route/Dosage ⬆ ⬇

Should only be used in patients who have an inadequate response to a maximally titrated dose of allopurinol, who are intolerant to allopurinol, or for whom treatment with allopurinol is not advisable.
PO (Adults ): 40 mg once daily initially; if serum uric acid does not ↓ to <6 mg/dL, ↑ to 80 mg once daily.

Renal Impairment

PO (Adults ): CCr <30 mL/min: Maximum dose = 40 mg/day.

Availability ⬆ ⬇

(Generic available)

Tablets: 40 mg; 80 mg

Assessment ⬆ ⬇

Assess for gout flares (joint pain, swelling), especially during early therapy. Use prophylactic NSAID or colchicine therapy for up to 6 mo. If a gout flare occurs, continue febuxostat therapy and treat flare concurrently.
Monitor for signs and symptoms of MI and stroke.
Assess patient for skin reactions throughout therapy. Reactions may be severe and life-threatening. If severe reaction suspected, discontinue febuxostat.

Lab Test Considerations:

Monitor serum uric acid levels prior to therapy, 2 wk after initiating, and periodically thereafter. If serum uric acid levels ≥6 mg/dL after 2 wk of daily 40 mg therapy,↑ dose to 80 mg daily.
- Monitor liver function at 2 and 4 mo of therapy and periodically thereafter. May cause ↑ AST, ALT, CK, LDH, and alkaline phosphatase.
- May cause prolonged aPTT and PT and ↓ hematocrit, hemoglobin, RBC, platelet count, lymphocyte count, and neutrophil counts. May cause ↑ or ↓ WBC.
- May ↓ serum bicarbonate and ↑ serum sodium, glucose, potassium, and TSH.
- May ↑ serum cholesterol, triglycerides, amylase, and low-density lipoprotein cholesterol.
- May cause ↑ BUN and serum creatinine and proteinuria.

Implementation ⬆ ⬇

PO: May be taken with or without food and with antacids.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy.
Advise patient if a gout flare occurs to continue febuxostat and notify a health care provider.
Advise patient to notify health care provider if rash, chest pain, shortness of breath, dizziness, rapid or irregular heartbeat, or stroke symptoms (weakness, blurred vision, headache, confusion, slurred speech) occur or if side effects are persistent or bothersome.
Instruct patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care provider before taking any other Rx, OTC, or herbal products.
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding.
Emphasize the importance of follow-up lab tests to monitor therapy.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇