PsychotropicsFocus on www.uspharmacist.com HEALTH SYSTEMS EDITION N U.S. Pharmacist OV 09 EMBER 20 THE JOURNAL FOR PHARMACISTS’ EDUCATION Health Systems Edition Treating Alcoholism for Optimal Results Vol. 34, No. 11 November 2009 Vol. Opioid Dependence & Withdrawal Controlling Schizophrenia Symptoms Prophylactic Medications in Traumatic Brain Injury 2 CE Credits Emergency Contraception: Clinical and Regulatory Update New Products in This Issue: Afinitor / Novartis Pharmaceuticals Corporation • Authorized Generics / Greenstone LLC • Distinctive Labeling / Baxter Healthcare • Embeda / King Pharmaceuticals • Injectables / Pfizer Injectables • Kapidex / Takeda Pharmaceuticals • Onglyza / AstraZeneca • Product Labeling / Teva Pharmaceuticals • Uloric / Takeda Pharmaceuticals • Welchol / Daiichi-Sankyo FOR FREE CE, GO TO: www.uspharmacist.com A JOBSON PUBLICATION Indication Prophylactic therapy (i.e. - NSAIDs or colchicine) upon initiation of treatment may be benefi cial for ULORIC is a xanthine oxidase (XO) inhibitor indicated for up to six months. the chronic management of hyperuricemia in patients with gout. ULORIC is not recommended for the treatment • Cardiovascular Events: In randomized controlled studies, of asymptomatic hyperuricemia. there was a higher rate of cardiovascular thromboembolic events (cardiovascular deaths, non-fatal myocardial Important Safety Information infarctions, and non-fatal strokes) in patients treated with ULORIC [0.74 per 100 P-Y (95% CI 0.36-1.37)] than • ULORIC is contraindicated in patients being treated allopurinol [0.60 per 100 P-Y (95% CI 0.16-1.53)]. A causal with azathioprine, mercaptopurine, or theophylline. relationship with ULORIC has not been established. • An increase in gout fl ares is frequently observed Monitor for signs and symptoms of MI and stroke. during initiation of anti-hyperuricemic agents, • Liver Enzyme Elevations: In randomized controlled studies, including ULORIC. If a gout fl are occurs during transaminase elevations greater than 3 times the upper treatment, ULORIC need not be discontinued. limit of normal (ULN) were observed (AST: 2%, 2%, and ULORIC® is a registered trademark of Teijin Pharma Limited and used under license by Takeda Pharmaceuticals America, Inc. ©2009 Takeda Pharmaceuticals North America, Inc. TXF-00319 08/09 ULORIC powerfully lowers serum uric acid levels for long-term control of gout. Powerfully lowers serum uric acid1 • In the largest phase 3 study (6 months): - 45% of patients who received ULORIC 40 mg achieved serum uric acid levels of <6 mg/dL (N=757) compared to 42% of patients who received allopurinol 300 mg (N=755; p=0.233) - 67% of patients who received ULORIC 80 mg achieved serum uric acid levels of <6 mg/dL (N=756) compared to 42% of patients who received allopurinol 300 mg (N=755; p<0.001) Extensively studied safety profi le1 • The safety profi le of ULORIC has been evaluated2 - In more than 4000 patients - In some for more than 5 years Simple, once-daily dosing1 • Available in 40- and 80-mg tablets for once-daily dosing with a starting dose of 40 mg • No dose adjustments required in patients with mild to moderate renal or hepatic impairment* * There are insuffi cient data in patients with severe renal dysfunction, and no studies have been conducted in patients with severe hepatic impairment. Caution should be exercised in these patients. ALT: 3%, 2% in ULORIC and allopurinol-treated patients, For more information, respectively). No dose-effect relationship for these transaminase elevations was noted. Laboratory please visit www.ULORIC.com. assessment of liver function is recommended at, for example, 2 and 4 months following initiation of ULORIC and periodically thereafter. • Adverse reactions occurring in at least 1% of ULORIC-treated patients, and, at least 0.5% greater than placebo, are liver function abnormalities, nausea, arthralgia, and rash. Individual results may vary based on factors such as baseline serum uric acid levels. Please see brief summary of complete Prescribing Information on adjacent pages. References: 1. ULORIC® (febuxostat) full prescribing information, February 2009. 2. Data on fi le, Takeda Pharmaceuticals North America, Inc. BRIEF SUMMARY OF FULL PRESCRIBING INFORMATION for Blood and Lymphatic System Disorders: anemia, idiopathic thrombocytopenic ULORIC® (febuxostat) tablets purpura, leukocytosis/leukopenia, neutropenia, pancytopenia, splenomegaly, INDICATIONS AND USAGE throm bo cytopenia; Cardiac Disorders: angina pectoris, atrial fibrillation/flutter, ULORIC® is a xanthine oxidase (XO) inhibitor indicated for the chronic management cardiac murmur, ECG abnormal, palpitations, sinus bradycardia, tachycardia; of hyperuricemia in patients with gout. Ear and Labyrinth Disorders: deafness, tinnitus, vertigo; Eye Disorders: vision blurred; Gastrointestinal Disorders: abdominal distention, abdominal pain, ULORIC is not recommended for the treatment of asymptomatic hyperuricemia. constipation, dry mouth, dyspepsia, flatulence, frequent stools, gastritis, CONTRAINDICATIONS gastro esophageal reflux disease, gastrointestinal discomfort, gingival pain, ULORIC is contraindicated in patients being treated with azathioprine, mercapto- haematemesis, hyperchlorhydria, hematochezia, mouth ulceration, pancreatitis, purine, or theophylline [see Drug Interactions]. peptic ulcer, vomiting; General Disorders and Administration Site Conditions: asthenia, chest pain/discomfort, edema, fatigue, feeling abnormal, gait WARNINGS AND PRECAUTIONS disturbance, influenza-like symptoms, mass, pain, thirst; Hepatobiliary Gout Flare Disorders: cholelithiasis/cholecystitis, hepatic steatosis, hepatitis, hepatomegaly; After initiation of ULORIC, an increase in gout flares is frequently observed. This Immune System Disorder: hypersensitivity; Infections and Infestations: herpes increase is due to reduction in serum uric acid levels resulting in mobilization of zoster; Procedural Complications: contusion; Metabolism and Nutrition Disorders: urate from tissue deposits. anorexia, appetite decreased/increased, dehydration, diabetes mellitus, hyper- In order to prevent gout flares when ULORIC is initiated, concurrent prophylactic cholesterolemia, hyperglycemia, hyperlipidemia, hypertriglyceridemia, hypokalemia, treatment with an NSAID or colchicine is recommended. weight decreased/increased; Musculoskeletal and Connective Tissue Disorders: arthritis, joint stiffness, joint swelling, muscle spasms/twitching/tightness/weakness, Cardiovascular Events musculoskeletal pain/stiffness, myalgia; Nervous System Disorders: altered In the randomized controlled studies, there was a higher rate of cardiovascular taste, balance disorder, cerebrovascular accident, Guillain-Barré syndrome, headache, thrombo embolic events (cardiovascular deaths, non-fatal myocardial infarctions, hemiparesis, hypoesthesia, hyposmia, lacunar infarction, lethargy, mental and non-fatal strokes) in patients treated with ULORIC [0.74 per 100 P-Y impairment, migraine, paresthesia, somnolence, transient ischemic attack, (95% CI 0.36-1.37)] than allopurinol [0.60 per 100 P-Y (95% CI 0.16-1.53)] [see tremor; Psychiatric Disorders: agitation, anxiety, depression, insomnia, irritability, Adverse Reactions]. A causal relationship with ULORIC has not been established. libido decreased, nervousness, panic attack, personality change; Renal and Monitor for signs and symptoms of myocardial infarction (MI) and stroke. Urinary Disorders: hematuria, nephrolithiasis, pollakiuria, proteinuria, renal Liver Enzyme Elevations failure, renal insufficiency, urgency, incontinence; Reproductive System and During randomized controlled studies, transaminase elevations greater than 3 times Breast Changes: breast pain, erectile dysfunction, gynecomastia; Respiratory, the upper limit of normal (ULN) were observed (AST: 2%, 2%, and ALT: 3%, 2% Thoracic and Mediastinal Disorders: bronchitis, cough, dyspnea, epistaxis, in ULORIC and allopurinol-treated patients, respectively). No dose-effect nasal dryness, paranasal sinus hypersecretion, pharyngeal edema, respiratory relationship for these transaminase elevations was noted. Laboratory tract congestion, sneezing, throat irritation, upper respiratory tract infection; assessment of liver function is recommended at, for example, 2 and 4 months Skin and Subcutaneous Tissue Disorders: alopecia, angio edema, dermatitis, following initiation of ULORIC and periodically thereafter. dermographism, ecchymosis, eczema, hair color changes, hair growth abnormal, hyperhidrosis, peeling skin, petechiae, photosensitivity, pruritus, purpura, skin ADVERSE REACTIONS discoloration/altered pigmentation, skin lesion, skin odor abnormal, urticaria; Clinical Trials Experience Vascular Disorders: flushing, hot flush, hypertension, hypotension; Laboratory Because clinical trials are conducted under widely varying conditions, adverse Parameters: activated partial thromboplastin time prolonged, creatine increased, reaction rates observed in the clinical trials of a drug cannot be directly compared bicarbonate decreased, sodium increased, EEG abnormal, glucose increased, to rates in the clinical trials of another drug and may not reflect the rates observed cholesterol increased, triglycerides increased, amylase increased, potassium in practice. increased, TSH increased, platelet count decreased, hematocrit decreased, hemoglobin A total of 2757 subjects with hyperuricemia and gout were treated with ULORIC decreased, MCV increased, RBC decreased, creatinine increased, blood urea 40 mg or 80 mg daily in clinical studies.