Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Discovery and development of ACE inhibitors wikipedia , lookup
Discovery and development of direct Xa inhibitors wikipedia , lookup
Discovery and development of neuraminidase inhibitors wikipedia , lookup
Adherence (medicine) wikipedia , lookup
Pharmacogenomics wikipedia , lookup
Discovery and development of direct thrombin inhibitors wikipedia , lookup
Theralizumab wikipedia , lookup
4/21/2013 Terri L. Levien, Pharm.D. WSU Drug Information Center Objectives 1. 2. 3. 4. Describe indications, pharmacology, adverse effects, and dosing of new drugs and dosage forms recently or soon to be approved by the FDA. Discuss key counseling and monitoring issues for the new drugs g and the role these p products may y play in the participant’s practice. Compare the new drugs against existing agents. Identify products approved with REMS, and describe the role of the pharmacist in the strategy. Possible Generics in 2013 Zoledronic acid inj (Zometa) Duloxetine (Cymbalta) Vanganciclovir (Valcyte) Estradiol (Vivelle-DOT) Sodium phosphate (Visicol) Rabeprazole (Aciphex) Capecitabine (Xeloda) Brinzolamide (Azopt) T Temozolomide l id (Temodar) (T d ) Zolmitriptan (Zomig & Zomig ZMT) Niacin extended-release (Niaspan) Lovastatin/niacin (Advicor) 1 4/21/2013 Alogliptin tablets (Nesina, Takeda) Approved January 25, 2013 Improve glycemic control in type 2 diabetes Dipeptidyl peptidase-4 inhibitor Dose: 25 mg once daily without regard to meals Alogliptin… How does it differ from other DPP-4 inhibitors? Adjust dose in renal impairment ○ Like sitagliptin & saxagliptin Available in combination with pioglitazone ○ (Oseni, Takeda) tablets 12.5 or 25 mg + 15, 30, or 45 mg Cases of hepatic failure ○ Check liver function tests before therapy & if any symptoms indicative of liver toxicity Canagliflozin tablets (Invokana, Janssen) Approved March 29, 2013 Improve glycemic control in adults with type 2 diabetes Sodium-glucose co-transporter 2 (SGLT2) inhibitor Increased urinary glucose excretion Reduces plasma glucose Promotes weight loss 2 4/21/2013 Canagliflozin… Contraindications Hypersensitivity Severe renal impairment Cautions Hypotension H i – volume l status Hyperkalemia Hypoglycemia – with insulin or insulin secretagogues Genital mycotic infections Hypersensitivity reactions - urticaria Increased LDL-cholesterol Monitor renal function Avoid in severe hepatic dysfunction Canagliflozin… Common ADRs Genital mycotic infections, urinary tract infection, increased urination Initial dose: 100 mg g orally y once daily, y, before the first meal of the day Can increase to 300 mg once daily if eGFR > 60 mL/min/1.73 m2 Limit to 100 mg daily if eGFR 45 – 59 mL/min/1.73 m2 Do not use if eGFR < 45 mL/min/1.73 m2 Aclidinium bromide inhalation powder (Tudorza Pressair, Forest) Approved July 23, 2012 Long-term maintenance treatment of bronchospasm associated with COPD Long-acting anticholinergic bronchodilator Class cautions 3 4/21/2013 Aclidinium… Efficacy: Improved pulmonary function (FEV1) ○ Change in trough FEV1 from baseline relative to placebo: 128 mL with aclidinium and 161 mL with tiotropium ○ Change in trough FEV1 from baseline: 186 mL with aclidinium and 150 mL with tiotropium Delayed exacerbations ○ Compared to placebo ○ Delayed in one phase 3 study (HR 0.7, 95% CI 0.55 to 0.9), but not in the other (HR 1, 95% CI 0.72 to 1.33) Pulm Pharmacol Ther 2010;23(1):15-21, Chest 2012;141(3):745-752 Aclidinium… Dose: 1 inhalation by mouth twice daily 400 mcg per actuation Discard inhaler after 60 doses 45 days after opening pouch Dose indicator shows “0” Device locks out Investigational Agents - Pulmonary Fluticasone furoate/vilanterol trifenatate (Breo, GlaxoSmithKline) Once daily corticosteroid/LABA in COPD Advisory committee voted to recommend - April 2013 Olodaterol (Striverdi, Boehringer Ingelheim) Long-acting beta-agonist Once daily in COPD Advisory panel voted to recommend - January 2013 4 4/21/2013 Apixaban Tablets (Eliquis, Bristol Myers Squibb) Approved December 28, 2012 Reduce risk of stroke in nonvalvular atrial fibrillation Also Al under d evaluation l ti iin Prevention of DVT/PE in patients undergoing hip or knee replacement surgery Treatment and prevention of VTE Oral direct Factor Xa inhibitor Apixaban… ARISTOTLE trial – noninferiority vs warfarin 18,201 patients with afib & stroke risk factors Apixaban Warfarin Difference Stroke or systemic embolism 1.27%/yr 1.6%/yr HR 0.79 95% CI 0.66 to 0.95 P 0.001 P<0.001 All-cause mortality 3.52%/yr 3.94%/yr HR 0.89 95% CI 0.8 to 0.99 P=0.047 Major bleeding 2.13%/yr 3.09%/yr HR 0.69 95% CI 0.6 to 0.8 P<0.001 Net clinical outcome 6.13%/yr 7.2%/yr HR 0.85 95% CI 0.78 to 0.92 P<0.001 N Engl J Med 2011;365:981-992 Apixaban… AVERROES trial 5,599 patients with afib for whom warfarin was unsuitable Apixaban vs aspirin 81-324 mg daily Apixaban Aspirin Difference Stroke or systemic embolism 1.6%/yr 3.7%/yr HR 0.45 95% CI 0.32 to 0.62 P<0.001 All cause mortality 3.51%/yr 4.42%/yr HR 0.79 95% CI 0.62 to 1.02 P=0.068 Major bleeding 1.4%/yr 1.2%/yr HR 1.13 95% CI 0.74 to 1.75 P=0.068 N Engl J Med 2011;364:806-817 5 4/21/2013 Apixaban… Bleeding risk – ARISTOTLE study Apixaban Major bleeding Warfarin 2.13%/yr* 3.09%/yr Gastrointestinal bleeding 0.83%/yr 0.93%/yr Intracranial bleeding 0.33%/yr* 0.8%/yr Intraocular bleeding 0.21%/yr 0.14%/yr 0.06%/yr 0.24%/yr 2.08%/yr* 3%/yr Fatal bleeding Clinically relevant nonmajor bleeding *P<0.001 Apixaban… Cautions: Bleeding Discontinuation of therapy in Afib Prosthetic heart valves – not studied Renal impairment ○ Reduce dose if SCr >1.5 mg/mL AND age >80 yr and/or weight <60 kg Hepatic impairment ○ Caution in moderate; avoid in severe hepatic impairment Drug interactions ○ P-glycoprotein & CYP3A4 inhibitors/inducers ○ Drugs that affect hemostasis Apixaban… Dose: 5 mg orally twice daily Reduced dose: 2.5 mg twice daily ○ 2 of the following characteristics: Age > 80 yrs Body weight <60 kg SCr > 1.5 mg/mL ○ Concomitant strong CYP3A4 & P-glycoprotein inhibitors 6 4/21/2013 Question RJ is a 75 year old male with afib and a CHADS2 score of 2 for whom apixaban is being prescribed for stroke prevention. He weighs 165 pounds. His SCr is 1.7. What is the recommended apixaban dose? a. 2.5 mg once daily b. 2.5 mg twice daily c. 5 mg once daily d. 5 mg twice daily Rivaroxaban tablets (Xarelto, Janssen) New indication approved November 2, 2012 Treatment of DVT and/or PE, and reduction in the risk of recurrence of DVT and PE Other indications: DVT prophylaxis in patients undergoing knee or hip replacement surgery Reduce risk of stroke or systemic embolism in patients with nonvalvular atrial fibrillation Oral direct Factor Xa inhibitor Rivaroxaban… EINSTEIN-DVT & EINSTEIN-PE Trials Rivaroxaban vs enoxaparin 1 mg/kg twice daily x ~5 d, then warfarin Rivaroxaban Enoxaparin / Warfarin Hazard Ratio Symptomatic recurrent VTE – DVT study 2.1% 3% HR 0.68 95% CI 0.44 to 1.04 Symptomatic recurrent VTE – PE study 2.1% 1.8% HR 1.12 95% CI 0.75 to 1.68 Major bleeding Clinically relevant nonmajor bleeding 1% 1.7% 8.6% 8.7% N Engl J Med 2010;363:2499-2510; N Engl J Med 2012;366:1287-1297 7 4/21/2013 Rivaroxaban… Cautions: Bleeding Discontinuation of therapy in Afib Renal impairment ○ DVT/PE: Avoid if CrCl < 30 mL/min ○ Afib: Avoid if CrCl < 15 mL/min Hepatic impairment ○ Avoid in moderate or severe hepatic impairment Drug interactions ○ P-glycoprotein & CYP3A4 inhibitors/inducers Rivaroxaban… DVT/PE treatment dose: 15 mg twice daily x 21 days Then 20 mg once daily With food to improve bioavailability DVT surgical i l prophylaxis h l i d dose: 10 mg orally once daily With or without food Afib dose: CrCl > 50 mL/min: 20 mg once daily CrCl 15-50 mL/min: 15 mg once daily With the evening meal Icosapent ethyl capsules (Vascepa, Amarin) Approved July 26, 2012 Adjunct to diet to reduce triglyceride levels in adults with severe hypertriglyceridemia ((>500 500 mg/dL) Ethyl ester of eicosapentaenoic acid (EPA)/fish oil 4 g/day (2 capsules twice daily) reduced TG ~30% 8 4/21/2013 Lomitapide Capsules (Juxtapid, Aegerion) Approved December 21, 2012 Adjunct to low-fat diet and other lipid lowering therapies (including LDL apheresis) in patients with ith homozygous h ffamilial ili l h hypercholesterolemia h l t l i Microsomal triglyceride transfer protein inhibitor Inhibits synthesis of chylomicrons & VLDL Reduced LDL-C 40% Reduced TG 45% Mipomersen Injection (Kynamro, Genzyme) Approved January 29, 2013 Adjunct to low-fat diet and other lipid lowering therapies in patients with homozygous familial hypercholesterolemia Use as an adjunct to LDL apheresis is not recommended Oligonucleotide inhibitor of apolipoprotein B-100 messenger RNA synthesis Prevents formation of LDL and VLDL particles Reduced LDL-C 25-28% Reduced TG 21% Phentermine & Topiramate ER Capsules (Qsymia, Vivus) Approved July 17, 2012 Chronic weight management Adjunct to reduced-calorie diet and physical activity Adults with BMI > 30 kg/m2 or > 27 kg/m2 with at least 1 weight-related comorbid condition Phentermine - sympathomimetic amine Topiramate – mechanism? Appetite suppression & satiety enhancement 9 4/21/2013 Phentermine & Topiramate… Efficacy at 1 year in 2 large studies: Mean weight loss 8.6-10.9% of body weight (~10 kg) 5% or greater loss: 67-70% of patients 10% or greater loss: 48-54% 48 54% of patients At 2 years: Mean weight loss 10.5% of body weight (~11 kg) 5% or greater loss: 79% of patients (compared to 30% treated with placebo) 20% or greater loss: 15% (vs 2% with placebo) Obesity 2012;20(2):330-342, Lancet 2011;377(9774):1341-1352 Phentermine & Topiramate… Contraindications Pregnancy Glaucoma Hyperthyroidism MAOIs Hypersensitivity Phentermine & Topiramate… Warnings and Precautions Pregnancy Increased heart rate Mood disorders / suicidal thoughts Cognitive dysfunction Metabolic acidosis Increased serum creatinine Concurrent alcohol use Kidney stone formation Decreased sweating Hypokalemia Taper upon discontinuation Renal impairment – reduced maximum dose Hepatic impairment – adjust dose/avoid 10 4/21/2013 Phentermine & Topiramate… Adverse effects: paresthesia, dizziness, dysgeusia, insomnia, constipation, dry mouth Dose Phentermine 3.75 mg/topiramate 23 mg ER once daily x 14 days, then Phentermine 7.5 7 5 mg/topiramate 46 mg ER once daily If less than 3% weight loss at 12 weeks, titrate to max of phentermine 15 mg/topiramate 92 mg ER once daily Schedule IV REMS: teratogenic risk Only available by mail order through certified pharmacies Available at certified retail pharmacies by July Lorcaserin Tablets (Belviq, Arena) Approved June 27, 2012 Chronic weight management Adjunct to reduced-calorie diet and physical activity ti it Adults with BMI > 30 kg/m2 or > 27 kg/m2 with at least 1 weight-related comorbid condition 5-HT2C receptor agonist Mediator of satiety Reduced food intake Lorcaserin… Efficacy at 1 year in 2 large studies: Mean weight loss 5.8% of body weight (~5-6 kg) 5% or greater loss: 47% of patients 10% or greater loss: 22% of patients At 2 years: 5% or greater loss: 68% of patients J Clin Endocrinol Metab 2011;96:3067-3077, N Engl J Med 2010;363:245-256 11 4/21/2013 Lorcaserin… Contraindications Warnings & Precautions Pregnancy Serotonin syndrome Valvular heart disease Cognitive dysfunction E h i Euphoria Mood changes / suicidal thoughts Priapism Reduced heart rate Decreased WBC/RBC counts Elevated prolactin levels Renal impairment Hepatic impairment Lorcaserin… Adverse effects: headache, dizziness, fatigue, nausea, dry mouth, constipation, plus hypoglycemia in patients with diabetes Dose: 10 mg orally twice daily If 5% weight loss not achieved by week 12, discontinue therapy Schedule IV? – awaiting final DEA scheduling Question Paresthesias are a common side effect of which of the following medications? a Mipomersen a. b. Lomitapide c. Lorcaserin d. Phentermine/topiramate 12 4/21/2013 Linaclotide Capsules (Linzess, Forest) Approved August 30, 2012 Treatment of irritable bowel syndrome with constipation p Treatment of chronic idiopathic constipation in adults Peptide homologous to bacterial enterotoxin Guanylate cyclase agonist Chloride and fluid secretion Linaclotide… Contraindications Pediatric patients < 6 years of age GI obstruction Warnings & Precautions Severe diarrhea Adverse effects: diarrhea, abdominal pain, flatulence Linaclotide… Dose: IBS-C: 290 mcg orally once daily Constipation: 145 mcg orally once daily Empty stomach at least 30 minutes prior to first meal of the day Swallow capsules whole Store in original container with desiccant 13 4/21/2013 Sodium picosulfate, magnesium oxide, citric acid powder for reconstitution (Prepopik, Ferring) Approved July 16, 2012 Cleansing of the colon as a preparation for colonoscopy in adults Osmotic and stimulant laxative Picosulfate… Contraindications CrCl < 30 mL/min GI obstruction or ileus, bowel perforation, toxic colitis, gastric retention Hypersensitivity H iti it Warnings & Precautions Dehydration Electrolyte abnormalities / seizures Arrhythmias Concomitant GI stimulants Sodium picosulfate… Split dose: preferred First dose evening before colonoscopy Second dose morning prior to colonoscopy Day before: alternative method First Fi t d dose afternoon ft or early l evening i b before f colonoscopy Second dose 6 hour later during evening before colonoscopy Mix with 5 ounces cold water Drink five 8-ounce glasses of clear liquid after the first dose and three 8-ounce glasses after the second 14 4/21/2013 Teduglutide Injection (Gattex, NPS) Approved December 21, 2012 Adults with short bowel syndrome who are dependent on parenteral support Glucagon-like peptide (GLP)-2 receptor analog Increased absorption of GI fluids, energy, and electrolytes Increased villus height and crypt depth of mucosa Crofelemer Delayed-Release Tablets (Fulyzaq, Salix) Approved December 31, 2012 Symptomatic relief of non-infectious diarrhea in p patients with HIV/AIDS on antiretroviral therapy Chloride channel antagonist Normalized chloride secretion and water loss in the GI tract Dragon’s Blood http://www.altoona.psu.edu/academics/ww w/mns/plants/dragonblood.htm Crofelemer… Efficacy: reduced frequency & volume Warnings & Precautions Rule R le o outt infectio infectiouss etiologies Dose: 125 mg orally twice daily 15 4/21/2013 Doxylamine & pyridoxine delayed-release tablets (Diclegis, Duchesnay) Approved April 8, 2013 Formerly Bendectin (1956-1983) Treatment of nausea and vomiting of pregnancy in i women who h d do not respond d to conservative management Delayed release tablets containing: Doxylamine – antihistamine – 10 mg Pyridoxine – vitamin B6 – 10 mg Doxylamine & Pyridoxine… Dose: 2 tablets at bedtime Can increase to max dose of 4 tablets/day 1 in the morning, 1 mid-afternoon, 2 at bedtime Contraindications: Hypersensitivity MAOIs Cautions: Mental alertness Anticholinergic effects Adverse effects: somnolence Pregnancy Category A Question Which of the following must be stored in the original container with the enclosed desiccant? a. Icosapent b. Linaclotide c. Lomitapide d. Lorcaserin 16 4/21/2013 Ospemifene Tablets (Osphena, Shionogi) Approved February 26, 2013 Treatment of moderate to severe dyspareunia due to menopause p Painful intercourse due to vulvar and vaginal atrophy Selective estrogen receptor modulator (SERM) Estrogen agonist/antagonist Reduced vaginal dryness and pain scores Ospemifene… Contraindications: Undiagnosed abnormal genital bleeding Estrogen-dependent neoplasia Active or history of DVT/PE Active or history of stroke or MI Boxed warnings: Endometrial cancer – use with progestin? Cardiovascular disorders – stroke Ospemifene… Cautions Surgery – discontinue 4-6 weeks before Breast cancer risk unknown Severe hepatic impairment – avoid use Common side effects: hot flush, vaginal discharge, muscle spasms, hyperhidrosis Dose: 60 mg (1 tablet) once daily with food Consider concomitant progestin 17 4/21/2013 Avanafil Tablets (Stendra, Vivus) Approved April 27, 2012 Treatment of erectile dysfunction Phosphodiesterase type 5 inhibitor Cautions similar to tadalafil Avanafil… Dose 100 mg orally 30 minutes prior to sexual activity Maximum dose 200 mg Maximum dose 100 mg in elderly, mild to moderate hepatic or renal impairment Maximum dose 50 mg if on moderate CYP3A4 inhibitor Avoid if severe hepatic or renal impairment, dialysis, or concomitant strong CYP3A4 inhibitor Mirabegron Extended-Release Tablets (Myrbetriq, Astellas) Approved June 28, 2012 Treatment of overactive bladder Beta-3 adrenergic agonist Increased bladder filling & storage 18 4/21/2013 Mirabegron… Adverse effects: headache, hypertension, nasopharyngitis, UTI Dose: 25 mg g once daily y Swallow tablets whole May increase to 50 mg once daily after 8 weeks Max dose 25 mg in severe renal impairment or moderate hepatic impairment Avoid in end-stage renal disease or severe hepatic impairment Oxybutynin transdermal (Oxytrol for Women, MSD Consumer) OTC approved January 25, 2013 Treatment of overactive bladder in women Transdermal system, 3.9 mg/day Apply every 4 days Limit to 2 weeks if no response Tofacitinib Tablets (Xeljanz, Pfizer) Approved November 6, 2012 Treatment of adult patients with moderate to severe rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate Monotherapy Combination with methotrexate or other nonbiologic DMARDs Janus-associated kinase (JAK) inhibitor Mediator of inflammatory immune responses 19 4/21/2013 Tofacitinib… Efficacy More effective than placebo Comparable to adalimumab ACR20 responses: 40-70% 40 70% ACR50 responses: 26-42% ACR70 responses: 11-22% N Engl J Med 2012;367:508-19 Tofacitinib… Warnings & Precautions Infections Malignancy & lymphoproliferative disorders Gastrointestinal perforation Lymphocytosis L h t i Neutropenia Hemoglobin levels Liver enzyme elevations Increased lipid parameters Severe hepatic impairment Immunizations Tofacitinib… Drug interactions CYP3A4 inducers/inhibitors Adverse effects: Ad ff t infections, i f ti diarrhea, di h dyspepsia, nausea 20 4/21/2013 Tofacitinib… Monitoring: Infection Tuberculosis Lymphocyte counts Neutrophil counts Hemoglobin Liver function tests Lipid panel Tofacitinib… Dose: 5 mg orally twice daily Reduced dose of 5 mg once daily Moderate and severe renal impairment Moderate hepatic impairment Potent CYP3A4 inhibitors Moderate CYP3A4 + potent CYP2C19 inhibition Dispensed with Medication Guide Teriflunomide Tablets (Aubagio, Sanofi Aventis) Approved September 12, 2012 Treatment of patients with relapsing forms of multiple p sclerosis Immunomodulatory & anti-inflammatory Leflunomide (Arava) metabolite Mitochondrial dihydroorotate dehydrogenase inhibitor 21 4/21/2013 Teriflunomide… Efficacy TOWER study – monotherapy ○ 36% reduction in annualized relapse rate vs placebo TENERE trial – monotherapy ○ Annualized relapse rates: 0.26 with teriflunomide 14 mg 0.41 with teriflunomide 7 mg 0.22 with interferon beta Ongoing studies in conjunction with interferon beta and glatiramer acetate Teriflunomide… Contraindications Severe hepatic impairment Pregnant women or women of childbearing potential Warnings & Precautions Severe liver S li iinjury j Accelerated elimination procedure Infection risk Malignancy and lymphoproliferative disorders Vaccinations Peripheral neuropathy Transient acute renal failure Hyperkalemia Teriflunomide… Adverse effects: elevated ALT, alopecia, diarrhea, influenza, nausea, paresthesia Drug interactions Warfarin Oral contraceptives CYP2C8 substrates CYP1A2 substrates 22 4/21/2013 Teriflunomide… Monitoring: Serum transaminases and bilirubin Complete blood cell count Tuberculin skin test Potassium levels Renal function Blood pressure Dose: 7 or 14 mg orally once daily Dimethyl fumarate delayed-release capsules (Tecfidera, Biogen Idec) Approved March 27, 2013 Treatment of patients with relapsing forms of multiple p sclerosis Reduces neuroinflammation and oxidative stress Reduced relapse rate and progression of disability Dimethyl fumarate… CONFIRM Study – 2 years Dimethyl fumarate, glatiramer, or placebo Relative reduction relapse rate: 44% % with BG-12 G ((P<0.001) 0 00 ) 29% with glatiramer (P=0.01) Relative reduction in disability progression: 21% with BG-12 7% with glatiramer Improved MRI outcomes N Engl J Med 2012:367:1087-1097 23 4/21/2013 Dimethyl fumarate… Cautions Lymphopenia Flushing Monitoring CBC Common ADRs Flushing, abdominal pain, diarrhea and nausea Dimethyl fumarate… Initial dose: 120 mg (1 capsule) twice daily for 7 days Maintenance dose: 240 mg (1 capsule) twice daily Swallow capsules whole Do not open, crush or chew Take with or without food Taking with food reduces flushing and GI side effects Question Monitoring of liver function tests is NOT required with which of the following agents? a. Linaclotide b. Lomitapide c. Teriflunomide d. Tofacitinib 24 4/21/2013 Sumatriptan iontophoretic transdermal (Zecuity, NuPathe) Approved January 17, 2013 Acute treatment of migraine with or without aura Iontophoretic transdermal system Delivers 6.5 mg over 4 hours Must be applied and activated within 15 minutes of assembly Loxapine inhalation powder (Adasuve, Alexza) Approved December 21, 2012 Acute treatment of agitation associated with p or bipolar p I disorder in adults schizophrenia Typical antipsychotic in a single use inhaler Bronchospasm risk Limited to use in an enrolled healthcare facility Aripiprazole Extended-Release Injection (Abilify Maintena, Otsuka) Approved February 2013 Treatment of schizophrenia Extended-release suspension IM injection every 4 weeks Time to peak 5-7 days Steady state – after 4 doses Half-life 30-45 days 25 4/21/2013 Aripiprazole… Establish tolerability with oral aripiprazole 400 mg IM every 4 weeks Continue oral for first 14 days Gluteal muscle – deep IM injection Inject immediately after reconstitution Reduced dose: Tolerability CYP2D6 poor metabolizers CYP2D6 & CYP3A4 drug interactions Question Which of the following unique dosage forms does not contain a battery? a Aclidinium inhalation (Tudorza Pressair) a. b. Fentanyl iontophoretic (Ionsys) c. Loxapine inhalation (Adasuve) d. Sumatriptin iontophoretic (Zecuity) Perampanel tablets (Fycompa, Eisai) Approved October 22, 2012 Not yet available Awaiting DEA scheduling Adjunctive treatment of partial-onset seizures with or without secondary generalized seizures in patients 12 years and older with epilepsy AMPA-type glutamate receptor antagonist 26 4/21/2013 Perampanel… Efficacy in patients with therapy-resistant, partial-onset seizures on 1-3 antiepileptic drugs Seizure frequency q y reduced 31% % with 8 mg g dose vs 11% with placebo 50% reduction in seizure frequency in 35% with 8 mg dose vs 18% with placebo (NNT 6) Seizure-free control: 4.8% with 8 mg dose vs 1.2% with placebo (NNT 28) Neurology 2012;78(18):1408-1415 Perampanel… Warnings Class warning – suicidal behavior Hostility and aggression Dizziness and gait disturbance Somnolence and fatigue Falls Gradual withdrawal Perampanel… Drug interactions: CYP3A4 inducers/inhibitors Alcohol Levonorgestrel Adverse effects: dizziness, somnolence, fatigue, irritability, falls, nausea, weight gain, vertigo, ataxia, gait disturbances, and balance disorder 27 4/21/2013 Perampanel… Initial dose: 2 mg once daily at bedtime if not on enzyme-inducing AED and 4 mg once daily if on enzyme-inducing AED Increase by y 2 mg g every y 1-2 weeks Maximum 12 mg if normal hepatic and renal function Maximum 6 mg in mild hepatic impairment Maximum 4 mg in moderate hepatic impairment Bedaquiline Tablets (Sirturo, Janssen) Approved December 28, 2012 As part of a combination regimen in adults with p pulmonary y multi-drug g resistant tuberculosis Should be administered using a directly observed program Diarylquinoline anti-mycobacterial Elvitegravir / Cobicistat / Emtricitabine / Tenofovir disoproxil fumarate tablets (Stribild, Gilead) Approved August 27, 2012 Complete regimen for treatment of HIV HIV-1 1 infection in adults who are antiretroviral treatment naïve One tablet once daily with food Elvitegravir – integrase inhibitor Cobicistat – pharmacokinetic booster 28 4/21/2013 Peginesatide Injection (Omontys, Affymax/Takeda) Approved March 27, 2012 Treatment of anemia due to chronic kidney disease in adult patients on dialysis Erythropoiesis stimulating agent Initial dose: 0.04 mg/kg IV or SC once monthly Cabozantinib Capsules (Cometriq, Exelixis) Approved November 29, 2012 Treatment of patients with progressive, metastatic medullary thyroid cancer Tyrosine kinase inhibitor Pertuzumab Injection (Perjeta, Genentech) Approved June 8, 2012 For use in combination with trastuzumab and docetaxel for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease Monoclonal antibody that binds to HER2 29 4/21/2013 Enzalutamide Capsules (Xtandi, Medivation) Approved August 31, 2012 Treatment of patients with metastatic castration resistant prostate cancer who castration-resistant have previously received docetaxel Androgen receptor inhibitor Ziv-Aflibercept Injection (Zaltrap, Sanofi Aventis) Approved August 3, 2012 Metastatic colorectal cancer that is resistant to or has p progressed g following g an oxaliplatinp containing regimen Use in conjunction with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) Vascular endothelial growth factor inhibitor Regorafenib Tablets (Stivarga, Bayer/Onyx) Approved September 27, 2012 Metastatic colorectal cancer in patients who have been previously treated with fluoropyrimidine-, fl i idi oxaliplatin-, li l ti and d irinotecan-based chemotherapies, an antiVEGF therapy, and if KRAS wild type, an anti-EGFR therapy Oral multikinase inhibitor 30 4/21/2013 Carfilzomib Injection (Kyprolis, Onyx) Approved July 20, 2012 Treatment of patients with multiple myeloma who have received at least two prior therapies including bortezomib and an immunomodulatory agent and have demonstrated disease progression on or within 60 days of completion of last therapy Proteasome inhibitor Omacetaxine Mepesuccinate Injection (Synribo, Teva) Approved October 26, 2012 Treatment of adults with chronic or accelerated phase chronic myelocytic l k i (CML) with leukemia ith resistance i t or intolerance to two or more tyrosine kinase inhibitors (eg, imatinib, dasatinib, nilotinib) Cephalotaxine ester Protein synthesis inhibitor Bosutinib Tablets (Bosulif, Pfizer) Approved September 4, 2012 Treatment of adult patients with chronic, accelerated,, or blast phase p Philadelphia p chromosome positive (Ph+) chronic myelocytic leukemia with resistance or intolerance to prior therapy Tyrosine kinase inhibitor 31 4/21/2013 Ponatinib Tablets (Iclusig, Ariad) Approved December 14, 2012 Chronic phase, accelerated phase, or blast phase chronic myeloid leukemia or Philadelphia chromosome positive acute lymphoblastic leukemia resistant or intolerant to tyrosine kinase inhibitor therapy Multi-kinase inhibitor Vincristine sulfate LIPOSOME Injection (Marqibo, Talon) Approved August 9, 2012 Treatment of adult patients with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) in second or greater relapse or whose disease has progressed following two or more anti-leukemia therapies Sphingomyelin/cholesterol liposomeencapsulated formulation of vincristine sulfate WSU Drug Information Center (509) 358-7662 [email protected] [email protected] 32