febuxostat


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febuxostat

Uloric

Pharmacologic class: Xanthine oxidase inhibitor

Therapeutic class: Antigout agent

Pregnancy risk category C

Action

Decreases serum uric acid level

Availability

Tablets: 40 mg, 80 mg

Indications and dosages

Long-term management of hyperuricemia in patients with gout

Adults: Initially, 40 mg P.O. daily; for patients who don't achieve serum uric acid level of less than 6 mg/dl after 2 weeks with 40 mg, give 80 mg P.O. daily

Contraindications

• Concomitant use of azathioprine, mercaptopurine

Precautions

Use cautiously in:
• severe hepatic or renal impairment
• patients with greatly increased rate of urate formation, such as in malignant disease and its treatment and Lesch-Nyhan syndrome (use not recommended)
• concurrent use of theophylline
• pregnant or breastfeeding patients
• children younger than age 18 (safety and efficacy not established).

Administration

• Administer with or without food.

Adverse reactions

CNS: dizziness, nonfatal cerebrovascular accident (CVA)

CV: cardiovascular thromboembolic events (nonfatal myocardial infarction [MI], deaths)

GI: nausea

Hepatic: liver function abnormalities

Musculoskeletal: arthralgia

Skin: rash

Interactions

Drug-drug.Drugs metabolized by xanthine oxidase (such as azathioprine, mercaptopurine): may increase plasma concentrations of these drugs, leading to severe toxicity

Theophylline: altered theophylline metabolism

Drug-diagnostic tests.Alanine aminotransferase, aspartate aminotransferase: increased levels

Patient monitoring

Monitor patient for signs and symptoms of MI or CVA.
• Be aware that gout flares (caused by reduction in serum uric acid levels resulting in mobilization of urate from tissue deposits) may occur. To prevent such flares, provide concurrent prophylactic treatment with a non-steroidal anti-inflammatory drug or colchicine, as prescribed.
• Monitor liver function tests 2 months and 4 months after starting therapy and periodically thereafter.

Patient teaching

• Instruct patient to take drug with or without food.

Instruct patient to immediately report cardiovascular symptoms (such as shortness of breath or chest pain) or strokelike symptoms (such as headache or dizziness) to prescriber.
• Tell patient to inform prescriber of increased gout symptoms or rash.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

febuxostat

(fe-bux-o-stat) ,

Uloric

(trade name)

Classification

Therapeutic: antigout agents
Pharmacologic: xanthine oxidase inhibitors
Pregnancy Category: C

Indications

Chronic management of hyperuricemia in patients with a history of gout.

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: Well absorbed (49%) following oral administration.
Distribution: Unknown.
Protein Binding: 99.2%.
Metabolism and 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 (blood levels)

ROUTEONSETPEAKDURATION
POrapid1–1.5 hr*24 hr
*Maximum lowering of uric acid may take 2 wk

Contraindications/Precautions

Contraindicated in: Concurrent azathioprine or mercaptopurine.
Use Cautiously in: Severe renal impairment (CCr <30 mL/min);Severe hepatic impairment; Obstetric: Use only when potential maternal benefit outweighs potential fetal risk; Lactation: Unknown if excreted into breast milk; use caution when breast feeding; Pediatric: Safety in children <18 yr not established.

Adverse Reactions/Side Effects

Gastrointestinal

  • ↑ liver function tests
  • nausea

Dermatologic

  • rash

Musculoskeletal

  • gout flare
  • arthralgia

Interactions

Drug-Drug interaction

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

Route/Dosage

Oral (Adults) 40 mg once daily initially; if serum uric acid does not ↓ to <6 mg/dL, dose should be ↑ to 80 mg once daily.

Availability

Tablets: 40 mg, 80 mg

Nursing implications

Nursing assessment

  • 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.
  • Lab Test Considerations: Monitor serum uric acid levels prior to, 2 wk after intitiating, and periodically thereafter. If serum uric acid levels are ≥6 mg/dL after 2 wk of daily 40 mg therapy, increase dose to 80 mg daily.
    • Monitor liver function at 2 and 4 mo of therapy and periodically thereafter. May cause ↑ AST, ALT, CPK, LDH, alkaline phosphatase, and creatine.
    • May cause prolonged aPTT and PT, and ↓ hematocrit, hemoglobin, RBC, platelet count, and lymphocyte, neutrohpil counts. May cause ↑ or ↓ WBC.
    • May cause ↓ serum bicarbonate and ↑ serum sodium, glucose, potassium, and TSH levels.
    • May cause ↑ serum cholesterol, triglycerides, amylase, and LDL levels.
    • May cause ↑ BUN and serum creatinine and proteinuria.

Potential Nursing Diagnoses

Chronic pain (Indications)

Implementation

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

Patient/Family Teaching

  • 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, or stroke symptoms (weakness, 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 female patient to notify health care professional if pregnancy is planned or suspected or if breast feeding.
  • Emphasize the importance of follow-up lab tests to monitor therapy.

Evaluation/Desired Outcomes

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

febuxostat

A non-purine selective inhibitor of xanthine oxidase that has been tested as an alternative to allopurinol in patients with GOUT and HYPERURICAEMIA.
References in periodicals archive ?
Febuxostat is another xanthine oxidase inhibitor that is used to lower uric acid.
Members of the Food and Drug Administration's Arthritis Advisory Committee have voted in favor of recommending approval of the investigational uricosuric drug lesinurad at 200 mg daily for the proposed indication of treatment of hyperuricemia associated with gout in combination with a xanthine oxidase inhibitor, such as allopurinol or febuxostat.
Drugs profiles discussed in this report includes arhalofenate, febuxostat, febuxostat XR, JPH-367, KGO-2142, KGO-2173, KUX-1151, LC-350189, NC-2500, pegadricase, RDEA-3170, Small Molecule to Inhibit Xanthine Oxidase for Gout and Hyperuricemia, Small Molecule to Inhibit Xanthine Oxidase for Hyperuricemia, XEN-102.
Febuxostat is an alternative, and a newer drug, lesinurad, is still awaiting NICE approval.
Long-term inhibition of xanthine oxidase by febuxostat does not decrease blood pressure in deoxycorticosterone acetate (DOCA)-salt hypertensive rats.
One of these very potent new compounds is febuxostat [13], a non-purine inhibitor of XO that has a favorable toxicology profile, high bioavailability, more potent and longer-lasting hyperuricemia action than allopurinol [14].
The TFP recommended that initial therapy to lower serum urate should consist of a xanthine oxidase inhibitor, either allopurinol or febuxostat, with no preference asserted.
Allopurinol and febuxostat, urate lowering drugs, bring hyperuricemia under control by decreasing urate production, which allows for the recycling of urate deposits.
This edition has 200 new monographs, new and updated interactions advice, and the addition of drugs like febuxostat, ivabradine, lacosamide, pitavastatin, retigabine (ezogabine), rufinamide, and ulipristal.
There are currently five drugs that can be used to treat gout: allopurinol (Zyloprim), colchicine (Colcrys), febuxostat (Uloric), pegloticase (Krys-texxa), and probenecid.
Besides the newly developed and licensed synthetic XO-inhibitor febuxostat (Baker and Schumacher 2010), only a few ethnopharmacological approaches have been described (Cos et al.
Therapeutic use: Febuxostat (16, 17) is a xanthine oxidase inhibitor indicated for the chronic management of hyperuricemia in patients with gout.