Febuxostat

(feb- UX - o h- s t a t )
CLASSIFICATION(S): Antigout drug (xanthine oxidase inhibitor) PREGNANCY CATEGORY: C Rx: Uloric.
USES Chronic management of hyperuricemia in gout. ACTION/KINETICS Action As a xanthine oxidase inhibitor, it decreases serum uric acid. Pharmacokinetics Absorption is at least 49% after PO use. Cmax: 11.5 hr. Extensively metabolized by CYP1A2, 2C8, and 2C9 as well as UGT1A1, 1A3, 1A9, and 2B7. Excreted through both the urine (49%) and the feces (45%) as both unchanged drug 1 and metabolites. t /2, terminal elimination: 58 hr. Cmax and AUC are higher in women than in men. Plasma protein binding: 99.2% (mainly to albumin). CONTRAINDICATIONS Clients being treated with azathioprine, mercaptopurine, or theophylline. Use in clients in whom the rate of urate formation is greatly increased (e.g., malignant disease and its treatment, Lesch-Nyhan syndrome). SPECIAL CONCERNS Use with caution in severe renal impairment (CCR <30 mL/min), severe hepatic impairment (ChildPugh class C), and during lactation. Safety and efficacy not determined in children younger than 18 years of age. SIDE EFFECTS Most Common Abnormal liver function, arthralgia, nausea, rash. CNS: Agitation, altered taste, anxiety, balance disorder, depression, fatigue, gait disturbance, Guillain-Barre syndrome, headache, hemiparesis, hypoesthesia, hyposmia, insomnia, irritability, lacunar infarction, lethargy, decreased libido, mental impairment, migraine, nervousness, panic attack,

paresthesia, personality change, somnolence, tremor, vertigo. GI: Abdominal distention/pain, constipation, dry mouth, dyspepsia, flatulence, frequent stools, gastritis, GERD, GI discomfort, gingival pain, hematemesis, hematochezia, hyperchlorhydria, mouth ulceration, N&V, pancreatitis, peptic ulcer. Hepatic: Abnormal liver function, cholelithiasis/cholecystitis, hepatic steatosis, hepatitis, hepatomegaly. CV: Angina pectoris, atrial fibrillation/flutter, cardiac murmur, CVA, MI, abnormal ECG, hyper/hypotension, palpitations, sinus bradycardia, tachycardia, TIAs. Dermatologic: Rash, alopecia, angioedema, dermatitis, dermographism, ecchymosis, eczema, hair color changes, abnormal hair growth, hyperhidrosis, peeling skin, petechiae, photosensitivity, pruritus, purpura, skin discoloration/altered pigmentation, skin lesion, abnormal skin odor, urticaria. Musculoskeletal: Arthralgia, arthritis, joint stiffness/swelling, muscle spasms/ twitching/tightness/weakness, musculoskeletal pain/stiffness, myalgia. Respiratory: Bronchitis, cough, dyspnea, epistaxis, nasal dryness, paranasal sinus hypersecretion, pharyngeal edema, respiratory tract congestion, sneezing, throat irritation, URTI. GU: Breast pain, erectile dysfunction, gynecomastia, hematuria, incontinence, nephrolithiasis, pollakiuria, renal failure/insufficiency, urgency. Hematologic: Anemia, idiopathic thrombocytopenic purpura, leukocytosis/leukopenia, neutropenia, pancytopenia, splenomegaly, thrombocytopenia. Metabolic/Nutritional: Anorexia, decreased/increased appetite, dehydration, diabetes mellitus, hypercholesterolemia, hyperglycemia, hyperlipidemia, hypertriglyceridemia, hypokalemia, weight decreased/increased. Ophthalmic: Blurred vision. Otic: Deafness, tinnitus. Body as a whole: Asthenia, edema, abnormal feeling, flushing, hot flush, hypersensitivity, flulike symptoms, pain, thirst. Miscellaneous: Chest pain/discomfort, contusion, herpes zoster, mass. LABORATORY TEST CONSIDERATIONS ALT, AST, APTT, alkaline phosphatase, amylase, blood urea, cholesterol, creatine, CPK, creatinine, glucose, LDH,
IV = Intravenous

C = see color insert

H = Herbal

E = sound alike drug

LDL, mean corpuscular volume, potassium, PSA, PT, BUN/creatinine ratio, sodium, TSH, triglycerides. Bicarbonate, hematocrit, hemogblobin, lymphocyte count, neutrophil count, platelet count, RBC count. or Urine output, WBC count. Abnormal coagulation test, EEG. Presence of urinary casts, WBCs and protein in urine. DRUG INTERACTIONS Azathioprine / Plasma levels of azathioprine R/T inhibition of xanthine oxidase toxicity; do not use together Mercaptopurine / Plasma levels of mercaptopurine R/T inhibition of xanthine oxidase toxicity; do not use together Theophylline / Plasma levels of theophylline R/T inhibition of xanthine oxidase toxicity; do not use together HOW SUPPLIED Tablets: 40 mg, 80 mg. DOSAGE TABLETS Chronic management of hyperuricemia in gout. Adults, initial: 40 mg once a day; usual: 4080 mg once a day. For those who do not achieve a serum uric acid level of <6 mg/dL after 2 weeks with 40 mg, a dose of 80 mg is recommended.

NURSING CONSIDERATIONS
ADMINISTRATION/STORAGE 1. Gout flares may occur after beginning febuxostat therapy. Is due to changing serum uric acid levels resulting in mobilization of urate from tissue deposits. Undertake flare prophylaxis with a nonsteroidal antiinflammatory drug or colchicine. Prophylaxis may be beneficial for up to 6 months. 2. May be taken without regard to food or antacid use.

3. Store from 1530C (5986F); protect from light. ASSESSMENT 1. Note reasons for therapy, frequency of attacks, location, presentation, other agents trialed and outcome. Not for use with malignancy (increased urate formation). 2. Assess for any CAD and monitor for S&S of MI and/or stroke. 3. Check for the target serum uric acid level of <6 mg/dL; may check as early as 2 weeks after starting febuxostat therapy. If not attained may need to increase dose to 80 mg. 4. Assess renal function and obtain LFTs at 2 and 4 months following the start of therapy and periodically thereafter. 5. May start therapy with NSAID or colchicine to diminish gout flare R/T mobilization of urate from tissue deposits. CLIENT/FAMILY TEACHING 1. Take once a day without regard to food or antacid use. 2. May take with NSAID or colchicine to prevent gout flares upon starting therapy and with mobilization of urate from the tissues deposits. 3. Review risks related to gout flares, elevated liver enzymes and cardiovascular events with this therapy. 4. Report any chest pain, shortness of breath, rash, or symptoms suggestive of a stroke. 5. Avoid pregnancy unless benefits outweigh risks. 6. Keep all F/U to assess response, labs, and adverse SE. OUTCOMES/EVALUATE Symptomatic relief of gout pain Uric acid level of <6 mg/dL

Bold Italic = life threatening side effect

= black box warning

W = Available in Canada