Febuxostat

Class and Category

Pharmacologic Class: Xanthine oxidase inhibitor

Therapeutic Class: Antigout

Indications and Dosages

To treat chronic hyperuricemia in patients with gout, 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

TABLETS

Adults

Initial: 40 mg once daily, increased after 2 wk to 80 mg once daily, if needed.

DOSAGE ADJUSTMENT For patients with severe renal impairment, the dosage is limited to 40 mg once daily.

Route	Onset	Peak	Duration
P.O.	2 - 3 Days	1–1.5 hr	Unknown

Mechanism of Action

Inhibits the action of xanthine oxidase, the key enzyme responsible for purine breakdown. Xanthine oxidase catalyzes the conversion of xanthine to uric acid, thereby increasing uric acid levels. High uric acid levels cause gout attacks. Inhibiting xanthine oxidase causes uric acid levels to drop, decreasing the risk of gout attack.

Contraindications

Concurrent use of azathioprine or mercaptopurine, hypersensitivity to febuxostat or its components.

Interactions

DRUGS

Azathioprine, Mercaptopurine, Theophylline: Possibly increased serum levels of these drugs, leading to toxicity

Adverse Reactions

1. CNS: Aggression, CVA, dizziness, hemiparesis, lacunar infarction, psychotic behavior, transient ischemic attack
2. CV: Angina, chest pain or discomfort, ECG abnormalities, MI
3. EENT: Blurred vision, deafness, epistaxis, nasal dryness, paranasal sinus hypersecretion, pharyngeal edema, sneezing, taste disturbance, throat irritation, tinnitus.
4. ENDO: Breast pain, gynecomastia, hot flashes, hypoglycemia
5. GI: Diarrhea, dyspepsia, elevated liver enzymes, GI discomfort, hepatic failure, hepatomegaly, jaundice, nausea, vomiting
6. GU: Decreased libido, erectile dysfunction, hematuria, nephrolithiasis, pollakiuria, proteinuria, renal failure or insufficiency, tubulointerstitial nephritis, urgency
7. HEME: Agranulocytosis, anemia, eosinophilia, idiopathic thrombocytopenic purpura, leukocytosis, leukopenia, neutropenia, pancytopenia, splenomegaly, thrombocytopenia
8. MS: Arthralgia, joint stiffness or swelling, rhabdomyolysis
9. RESP: Upper respiratory tract infection
10. SKIN: Dermatitis, eczema, erythema multiforme, flushing, hair color or growth changes, hyperhidrosis, peeling skin, petechiae, photosensitivity, pruritus, rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria
11. Other: Anaphylaxis, drug reaction with eosinophilia and systemic symptoms (DRESS), gout flares, hypersensitivity reactions

Childbearing Considerations

PREGNANCY

• It is not known if a drug causes fetal harm.
• Use with caution only if the benefit to the mother outweighs the potential risk to a fetus.

LACTATION

• It is not known if drug is present in breast milk.
• Patient should check with prescriber before breastfeeding.

Nursing Considerations

• Know that febuxostat therapy isn’t recommended for patients in whom the rate of urate formation is greatly increased, as in malignancy and its treatment or Lesch–Nyhan syndrome.
• Obtain a liver test panel, as ordered, prior to initiating febuxostat therapy and then periodically thereafter. Monitor the patient for signs and symptoms of liver dysfunction such as anorexia, dark urine, fatigue, jaundice, or right upper abdominal discomfort throughout therapy. If signs and symptoms occur or if abnormal liver tests occur, especially an elevated serum alanine aminotransferase level greater than 3 times the upper normal limit, notify the prescriber and expect the drug to be withheld until the underlying cause is determined. If no other cause can be found other than febuxostat therapy, expect the drug to be discontinued permanently.
• Monitor the patient’s serum uric acid level, as prescribed, to determine drug effectiveness. Expect it to take about 2 weeks for the uric acid level to be therapeutically altered. The dose may be increased from 40 to 80 mg daily if the target serum uric acid level fails to fall below 6 mg/dl.

• Monitor patient for gout flares, which may occur after therapy is started because of changing serum uric acid levels that result in mobilization of urate from tissue deposits. Expect the prescriber to order colchicine or an NSAID when febuxostat therapy starts. If the patient has a gout flare-up during treatment, notify the prescriber, and expect symptoms to be managed. Know that febuxostat therapy usually isn’t discontinued during this time.

WARNING: Monitor patients with established cardiovascular disease because the use of febuxostat increases the risk of death from cardiovascular conditions. Also monitor the patient for evidence of cardiovascular thrombosis, such as acute MI or stroke, because the drug may increase the patient’s risk of developing these disorders, which may result in death.

• Assess patient’s skin for abnormalities. At the first sign of a rash or other skin abnormality, notify the prescriber and expect the drug to be discontinued if serious skin reactions are suspected or occur, because febuxostat may cause severe skin reactions. Also, know that patients who have experienced hypersensitivity reactions to allopurinol may be at increased risk of developing serious skin reactions to febuxostat.

PATIENT TEACHING

• Inform patient that a gout attack may occur when febuxostat therapy starts and that colchicine or an NSAID may be prescribed, usually along with febuxostat, to treat it.
• Instruct patient to seek immediate emergency care for signs or symptoms of a heart attack or stroke.
• Tell patient that periodic blood tests will be needed to determine drug’s effectiveness and to detect adverse effects.
• Advise patient to notify prescriber at first sign of a rash or other skin abnormality.