fe-BUX-o-stat

Therapeutic Classification: antigout agents

Pharmacologic Classification: xanthine oxidase inhibitors

• 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.

• Decreases production of uric acid by inhibiting xanthine oxidase.

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

Absorption: Well absorbed (49%) 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.

(plasma concentrations)

*Maximum lowering of uric acid may take 2 wk.

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)
• Severe renal impairment (CCr <30 mL/min)
• Severe hepatic impairment
• Previous skin reaction with allopurinol
• 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.

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

GI: ↑liver enzymes, nausea.

MS: arthralgia, gout flare.

Drug-Drug:

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

• PO (Adults): 40 mg once daily initially; if serum uric acid does not ↓ to <6 mg/dL, ↑ to 80 mg once daily.

(Generic available)

• Tablets: 40 mg; 80 mg;

• Assess for joint pain and swelling, especially during early therapy. Changing serum uric acid levels from mobilization of urate from tissue deposits may cause gout flares. 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. Discontinue therapy if severe reactions or moderate rashes with systemic symptoms occur.

• Monitor serum uric acid levels prior to, 2 wk after initiating, and periodically thereafter. If serum uric acid levels are 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, and lymphocyte, neutrophil counts. May cause ↑ or ↓ WBC.
  • May cause ↓ serum bicarbonate and ↑ serum sodium, glucose, potassium, and TSH levels.
  • May cause ↑ serum cholesterol, triglycerides, amylase, and low-density lipoprotein cholesterol levels.
  • May cause ↑ BUN and serum creatinine and proteinuria.

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

• Instruct patient to take febuxostat as directed. If a gout flare occurs, continue febuxostat and consult health care professional; medications to manage gout flare may be added.
• Advise patient to notify health care professional 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 professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking any other Rx, OTC, or herbal products.
• Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
• Emphasize the importance of follow-up lab tests to monitor therapy.

• Reduction in serum uric acid levels and resultant gout attacks.

Uloric