Terri L. Levien, Pharm.D. WSU Drug Information Center Objectives

1. Describe indications, pharmacology, adverse effects, and dosing of new drugs and dosage forms recently or soon to be approved by the FDA. 2. Discuss key counseling and monitoring issues for the new drugs and the role these products may play in the participant’s practice. 3. Compare the new drugs against existing agents. 4. Identify products approved with REMS, and describe the role of the pharmacist in the strategy. Possible Generics in 2012

Provigil (April) Detrol (Sept.) Plavix (May) Diovan (Sept.) Lescol (June) Lidoderm (Nov.) Lunesta (July) Atacand (Dec.) Actos (Aug.) Maxalt (Dec.) Singulair (Aug.) Linagliptin tablets (Tradjenta, Boehringer Ingelheim)  Approved May 2, 2011

 Improve glycemic control in type 2 diabetes

 Dipeptidyl peptidase-4 inhibitor

 Dose: 5 mg once daily without regard to meals Linagliptin…

 How differ from other DPP-4 inhibitors?  Not FDA approved for use with insulin or thiazolidinediones  No dosage adjustment in renal impairment  Avoid use with strong P-glycoprotein or CYP3A4 inducers Investigational Agents: Diabetes

 Alogliptin (Takeda)  DPP-4 inhibitor  Awaiting FDA decision April 25, 2012

 Dapagliflozin (Bristol-Myers Squibb/AstraZeneca  Sodium glucose cotransporter-2 inhibitor  FDA needs more risk and benefit data

 Rapid-acting insulin (VIAject, Biodel)  Phase III studies

 Degludec insulin (NovoNordisk)  Ultra long-acting insulin  Submitted for FDA approval in October 2011 Exenatide extended-release injection (Bydureon, Amylin)  Approved January 27, 2012

 Improve glycemic control in adults with type 2 diabetes mellitus  Adjunct to diet and exercise  Not first-line

 Glucagon-like peptide-1 receptor agonist Exenatide extended-release…  DURATION-5 Study  Randomized, open-label, 24-week  Addition of exenatide weekly vs exenatide twice daily to oral therapy Exenatide 2 mg Exenatide twice weekly (n=129) daily (n=123) HbA1C baseline 8.5 8.4 mean change -1.6* -0.9 HbA1C < 7% 58%* 30% Fasting glucose baseline 173 mg/dL 168 mg/dL mean change -35 mg/dL* -12 mg/dL Change in body weight -2.3 kg -1.4 kg Nausea 14% 35% *P<0.05 J Clin Endocrinol Metab 2011;96(5):1301-10 Exenatide extended-release…

 Contraindications  Medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2  History of serious hypersensitivity  Not studied in patients with history of pancreatitis – consider other therapies

 Cautions (REMS Communication Plan)  Thyroid carcinoma  Pancreatitis  Hypoglycemia – with sulfonylurea  Renal impairment – avoid if severe  Severe gastrointestinal disease Exenatide extended-release…

 Adverse effects  Nausea, diarrhea, vomiting, constipation, injection site itching/nodule, dyspepsia

 Dose: 2 mg subcutaneously once every 7 days  Any time of day  With or without meals  Requires suspension  Supplied with vial, vial connector, diluent syringe, needles Indacaterol (Arcapta Neohaler, Novartis)  Approved July 1, 2011

 Long-term maintenance bronchodilator treatment in COPD

 Ultra long-acting beta2-adrenergic agonist Indacaterol…

 Studies with 75 mcg dose  Improved trough FEV1 and health status  Reduced albuterol use  No long term or exacerbation data at this dose

 Common Adverse Effects: cough, oropharyngeal pain, nasopharyngitis, headache, nausea Indacaterol…  Contraindications  Treatment of asthma without long-term asthma control medication  Not indicated in asthma  Black box warning – class  Asthma related death  Warnings – Class  Paradoxical bronchospasm  Cardiovascular effects  Hypokalemia  Hyperglycemia Indacaterol…

 One 75 mcg capsule inhaled once daily  75 mcg capsule used in Neohaler inhaler  Remove from blister immediately before use  DO NOT SWALLOW CAPSULES  New inhaler provided with each prescription Rivaroxaban tablets (Xarelto, Janssen/Bayer)  Approved July 1, 2011

 Prevention of DVT/PE in patients undergoing hip or knee replacement surgery  Reduce risk of stroke in nonvalvular atrial fibrillation  Under FDA review: reduce risk of thrombotic cardiovascular events in acute coronary syndrome

 Oral, once-daily direct Factor Xa inhibitor Rivaroxaban…  Meta-analysis: 8 randomized controlled trials (N=15,246) comparing rivaroxaban & enoxaparin for VTE prophylaxis after knee or hip replacement  VTE incidence lower with rivaroxaban than enoxaparin 40 mg once daily ○ (RR 0.38, 95% CI 0.25 to 0.59) ○ Noninferior to enoxaparin 30 mg twice daily  Major VTE incidence lower with rivaroxaban than enoxaparin 40 mg once daily ○ (RR 0.19, 95% CI 0.12 to 0.29) ○ Noninferior to enoxaparin 30 mg twice daily

Thrombosis Res 2011;127:525-34 Rivaroxaban…

 Meta-analysis…  Major bleeding: no difference vs either enoxaparin dose  Clinically relevant non-major bleeding more frequent with rivaroxaban than enoxaparin 40 mg once daily (RR 1.28, 95% CI 1.01 to 1.61) ○ No difference vs enoxaparin 30 mg twice daily

Thrombosis Res 2011;127:525-34 Rivaroxaban…  ROCKET AF Study  Randomized, double-dummy, noninferiority study  14,264 patients with nonvalvular Afib and history of stroke or 2 additional stroke risk factors

Rivaroxaban Warfarin Composite: stroke or systemic embolism 3.8% 4.3% Stroke 3.6% 4% Hemorrhagic stroke 0.5% 0.8% Ischemic stroke 2.9% 2.9% Non-CNS systemic embolism 0.3% 0.4% Major bleeding 5.6% 5.4%

N Engl J Med 2011;365(10):883-91 Rivaroxaban…

 ROCKET AF bleeding risk

Rivaroxaban Warfarin Major bleeding 5.6% 5.4% Gastrointestinal bleeding 3.1%* 2% Bleeding resulting in transfusion of 2+ units 2.6%* 2.1% Critical bleedinga 1.3%* 1.9% Intracranial hemorrhage 0.8%* 1.2% Fatal bleeding 0.4%* 0.8%

*P<0.05; ableeding defined as critical if it occurred in intracranial, intraspinal, intraocular, pericardial, intraarticular, intramuscular, or retroperitoneal sites N Engl J Med 2011;365:883-91 Rivaroxaban…

 Cautions:  Bleeding  Discontinuation of therapy in Afib  Renal impairment ○ DVT: 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 prophylaxis 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  Feeding tube – OK to crush, but must confirm gastric placement Investigational

 Apixaban (Eliquis, Bristol-Myers Squibb/Pfizer)  Oral factor Xa inhibitor  Stroke prevention in atrial fibrillation  Awaiting FDA decision June 28, 2012

 Edoxaban (Daiichi Sankyo)  Oral factor Xa inhibitor  Prevention of postoperative VTE  Phase 3 studies Ticagrelor tablets (Brilinta, AstraZeneca)  Approved July 20, 2011

 Reduce the rate of thrombotic cardiovascular events in patients with acute coronary syndromes

 Oral platelet aggregation inhibitor  Reversible P2Y12 ADP receptor antagonist  Not structurally related to clopidogrel or prasugrel  Does not require hepatic activation  Rapid onset and offset of activity Ticagrelor…

 PLATO trial  18,624 patients with ACS  Ticagrelor + aspirin vs clopidogrel + aspirin  Ticagrelor 180 mg loading dose, followed by 90 mg twice daily x 12 months  Clopidogrel 300 mg loading dose, followed by 75 mg once daily x 12 months

N Engl J Med 2009;361:1045-57 Ticagrelor… Clopidogrel Ticagrelor Efficacy Endpoints Death from vascular causes, MI, or stroke 11.7% 9.8%* MI 6.9% 5.8%* Death from vascular causes 5.1% 4%* Stent thrombosis 3.8% 2.9%* Safety Endpoints Major bleeding 11.2% 11.6% Bleeding requiring transfusion 8.9% 8.9% CABG-related bleeding 7.9% 7.4% Non-CABG-related bleeding 3.8% 4.5%* Intracranial bleeding 0.2% 0.3%

*P<0.05 N Engl J Med 2009;361:1045-57 Ticagrelor…

 Contraindications  Active bleeding  History of intracranial bleeding  Severe liver impairment  Black Box Warnings  Bleeding risk  Diminished effectiveness with aspirin dose > 100 mg  Cautions  CYP3A4 inhibitors or inducers  Hepatic impairment  Dyspnea Ticagrelor…  Common adverse events: Bleeding & dyspnea

Clopidogrel Ticagrelor Dyspnea 7.8% 13.8% Major bleeding 11.2% 11.6% Life-threatening or fatal bleeding 5.8% 5.8% Bradycardia 4% 4.4% Syncope 0.8% 1.1%

 Loading Dose: 180 mg  Maintenance Dose: 90 mg twice daily  REMS: Medication Guide Boceprevir capsule (Victrelis, Merck)  Approved May 13, 2011

 Chronic hepatitis C genotype 1 infection in adult patients  Treatment naïve or failed previous treatment with interferon and ribavirin

 HCV NS3/4A protease inhibitor Telaprevir tablet (Incivek, Vertex)  Approved May 23, 2011

 Chronic hepatitis C genotype 1 infection in adult patients  Treatment naïve or failed previous interferon- based treatment, including prior null responders, partial responders, and relapsers

 HCV NS3/4A protease inhibitor Boceprevir- and Telaprevir-Based Regimens: Summary of SVR Rates

Boceprevir- Telaprevir- PEG- PEG-Ribavirin PEG-Ribavirin Ribavirin (SPRINT-2, RESPOND -2) (ADVANCE, REALIZE) Treatment-naïve 63-66% 69-75% 38-44%

Treatment-experienced Relapser 69-75% 83-88% 24-29% Partial responder 40-52% 54-59% 7-15% Null responder N/A 29-33% 5%

Adherence is critical!

Poordad F et al. NEJM 2011;364:1195-206. Jacobson IM et al. NEJM 2011;364:2405-16. Bacon BR et al. NEJM 2011;364:1207-17. Zeuzem S et al. NEJM 2011; 364:364:2417-28. Dosing: Boceprevir vs Telaprevir Boceprevir Telaprevir 4-Wk Lead-In with Yes No PEG-IFN/RBV Dose 800 mg Q 8 hrs (12 caps/day) 750 mg Q 8 hrs (6 tabs/day) Food Effect Take with food Take with food (20 g fat) PI Duration 24-44 weeks 12 weeks Total Treatment 28-48 weeks 24-48 weeks Duration Candidates for NONCIRRHOTICS: NONCIRRHOTICS: Response Guided Treatment-naïve: 28 wks Treatment-naïve: 24 wks Therapy (RGT) Prior relapser / partial responder: Prior relapser: 24 weeks 36 weeks Criteria for RGT HCV RNA undetectable wks 8-24 HCV RNA undetectable wks 4 and 12 Futility Rules Wk 12: HCV RNA ≥ 100 IU/mL Wk 4 or 12: HCV RNA > 1,000 Wk 24: HCV RNA detected IU/mL Wk 24: HCV RNA detected Important PK/PD Considerations

Boceprevir Telaprevir Food Effect Increases exposure 40-60% Substantially increases exposure •Take with food •Take with snack/meal with 20 g fat Metabolism 2 pathways: Hepatic via CYP3A4 Aldoketoreductase (AKR) and CYP3A4/5 Potential for CYP3A4: strong inhibitor CYP3A4: strong inhibitor and Drug P-gp: substrate and moderate substrate Interactions inhibitor P-gp: substrate and local inhibitor

Hepatic No dose adjustment required Should not be administered to Impairment patients with moderate to severe hepatic impairment Renal No dose adjustment required Exposure may be greater in renally Impairment impaired patients

32 Boceprevir & Telaprevir… Boceprevir Telaprevir Contraindications* CYP3A4/5 substrates X X Potent CYP3A4/5 inducers X X Warnings & Precautions* Reduced hemoglobin X X Neutropenia X Serious skin reactions X

*plus contraindications, warnings & precautions to peginterferon and ribavirin Contraindicated Drugs

Potential for increased toxicity of concomitant medication Alpha-1 adrenergic antagonist Alfuzosin Ergot derivatives Dihydroergotamine, ergonovine, methylergonavine HMG CoA reductase inhibitors Atorvastatina, lovastatin, simvastatin Neuroleptic Pimozide PDE5 Inhibitors Sildenafil or tadalafil for PAH Sedative / hypnotics Midazolam (oral) , triazolam Potential for loss of antiviral activity Antimycobacterial Rifampin Anticonvulsantsb Carbamazepine, phenytoin, phenobarb. Herbal products St. Johns Wort

a not contraindicated with boceprevir, b not contraindicated with telaprevir Boceprevir  Refrigerate prior to dispensing  Room temperature for 3 months  Packaged in bottles containing one day supply

Telaprevir

 Room temperature storage  Packaged in blister packs containing one day supply & multiple dose bottle that must be tightly closed and used within 28 days Fidaxomicin tablet (Dificid, Optimer)  Approved May 27, 2011

 Treatment of Clostridium difficile-associated diarrhea in adults

 Narrow-spectrum macrocyclic antimicrobial  Gram-positive aerobes & anaerobes Fidaxomicin…  Two noninferiority studies vs vancomycin Fidaxomicin Vancomycin Study 1 (N=535) Clinical response 92% 91% Global cure rate 80% (P<0.001) 66% Recurrence rate 13% (P=0.001) 25% Study 2 (N=629) Clinical response 92% 90% Global cure rate 78% (P=0.006) 67% Recurrence rate 13% (P=0.004) 24%

 Difference largely driven by difference in population not infected with NAP1/BI/027 strains N Engl J Med 2011;364:422-31, Gastroenterology 2010;139:e17 Fidaxomicin…  Adverse events:

Fidaxomicin Vancomycin Nausea 11% 11% Vomiting 7% 6% Abdominal pain 6% 4% Gastrointestinal hemorrhage 4% 2% Anemia 2% 2% Neutropenia 2% 1%

 Dose: 200 mg orally twice daily x 10 days Ivermectin 0.5% lotion (Sklice, Sanofi-Pasteur)  Approved February 7, 2012

 Topical treatment of head lice in patients 6 months of age and older

 Pediculocide  Free of live lice 14 days after treatment:  71-76% vs 16-19% with vehicle control  No studies with active control Ivermectin lotion…

 Apply sufficient lotion (up to 1 tube) to dry hair to thoroughly coat hair and scalp  After 10 minutes, rinse off with water  Nit combing not required

 Adverse effects (<1%): conjunctivitis, ocular hyperemia, eye irritation, dandruff, dry skin, skin burning sensation Ivacaftor 150 mg tablets (Kalydeco, Vertex)  Approved January 31, 2012

 Treatment of cystic fibrosis  Patients 6 years and older  With a G551D mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene (4-5% of the CF population)

 CFTR potentiator  Improve chloride transport Ivacaftor…  Randomized, double-blind, placebo-controlled, 48-week study in 161 patients with CF and at least 1 G551D mutation of the CFTR gene

Ivacaftor Placebo FEV1 mean change 10.4%* -0.2% Pulmonary exacerbation 33%* 59% Respiratory symptom score +5.9* -2.7 Weight change +3.1 kg* +0.4 kg Sweat chloride concentration -48.7 mmol/L* -0.8 mmol/L

*P<0.05 vs placebo N Engl J Med 2011;365:1663-72 Ivacaftor

 Cautions  Elevated transaminases – monitor  Hepatic impairment – reduce dose  CYP3A4 inducers – avoid  CYP3A4 inhibitors – reduce dose

 Adverse Events: headache, upper respiratory tract infection, rash, dizziness

 Dosing: 150 mg orally every 12 hours  With fat-containing food (eggs, butter, peanut butter, cheese pizza) Tafluprost 0.0015% ophthalmic soln (Zioptan, Merck)  Approved February 10, 2012

 Reducing elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension

 Prostaglandin analog Tafluprost…

 Class cautions:  Pigmentation & eyelash changes  Conjunctive hyperemia

 Dose: 1 drop in affected eye(s) once daily in the evening  Packaged in preservative-free individual units  Discard after administration Ezogabine tablets (Potiga, GlaxoSmithKline)  Approved June 10, 2011  Not yet available

 Adjunctive treatment of partial-onset seizures in adults

 Mechanism: opens KCNQ2/3 potassium channels in the brain Ezogabine…

Study 1 Study 2 Ezogabine Placebo Ezogabine Placebo 1,200 900 mg/day mg/day Median baseline seizure 11-12 / month 9-10 / month frequency^ Median reduction from 44%* 18% 40%* 16% baseline % with greater than 50% 56%* 23% 47%* 19% reduction from baseline

^ patients receiving 2-3 antiepileptic drugs at baseline

* P<0.001 Neurology 2011;76:1555-63; Neurology 2010;75:1817-24 Ezogabine…

 Warnings  Urinary retention  Psychiatric symptoms – psychosis, hallucinations  Dizziness & somnolence  QT interval prolongation  Controlled substance? – DEA reviewing Ezogabine…

Adverse Events Ezogabine Placebo Dizziness 23% 9% Somnolence 22% 12% Fatigue 15% 6% Confusion 9% 3% Vertigo 8% 2% Tremor 8% 3% Incoordination 7% 3% Diplopia 7% 2% Disturbance in attention 6% <1% Memory impairment 6% 3% Ezogabine…

 Not metabolized by CYP-450 system  Avoid alcohol – increased ezogabine levels

 Initial dose: 100 mg 3 times daily x 1 week  Increase weekly to maximum dose of 600 to 1200 mg/day (200-400 mg 3 times daily)  Reduced initial and maintenance dose in patients > 65 years of age, CrCl < 50 mL/min, or hepatic impairment Clobazam tablets (Onfi, Lundbeck)  Approved October 21, 2011

 Adjunctive treatment of seizures associated with Lennox-Gaustaut syndrome  Patients 2 years and older

 Benzodiazepine  68-93% reduction in frequency of “drop” seizures Clobazam…

 Pharmacokinetics:  Metabolized via CYPs 3A4, 2C19, 2B6 ○ Active metabolite  T1/2: 36-42 hours ○ Active metabolite T1/2: 71-82 hours  Cautions  Somnolence & sedation  Schedule IV  Drug interactions Clobazam…

 Common adverse events  Somnolence, pyrexia, lethargy, drooling, aggression

 Dosing  < 30 kg: 5 mg/day, titrated to 20 mg/day  > 30 kg: 10 mg/day, titrated to 40 mg/day  Weekly dose increases  Given twice daily  Tablets can be crushed and mixed with applesauce Icatibant injection (Firazyr, Shire)  Approved August 25, 2011

 Treatment of acute attacks of hereditary angioedema in adults  Rapid response: time to 50% reduction in symptoms 2 hrs vs. 20 hrs

 Bradykinin B2 receptor antagonist Icatibant…

 Prefilled syringe – 30 mg in 3 mLs  Self-administered  30 mg subcutaneously in the abdominal area  Over at least 30 seconds  Can repeat at 6 hour intervals up to 3 doses in 24 hours  Seek immediate medical attention following self-treatment of a laryngeal attack Icatibant…

Adverse Events Icatibant Placebo Injection site reactions 97% 33% Pyrexia 4% 0 Transaminase increased 4% 0 Dizziness 3% 1% Glucarpidase injection (Voraxaze, BTG International)

 Approved January 17, 2012

 Treatment of toxic plasma methotrexate concentrations in patients with impaired renal function

 Recombinant bacterial enzyme that hydrolyzes methotrexate into inactive metabolites that are further metabolized by the liver Glucarpidase…

 Avoid use of methotrexate immunoassay within 48 hours of glucarpidase administration  Unreliable due to methotrexate metabolite  Avoid leucovorin within 2 hours before or after glucarpidase administration  Leucovorin is a glucarpidase substrate

 Dose: 50 unit/kg via IV injection over 5 minutes Vemurafenib tablets (Zelboraf, Genentech/Daiichi Sankyo)  Approved August 17, 2011

 Treatment of patients with BRAF V600E mutation-positive unresectable or metastatic melanoma  48% response rate vs 5% with dacarbazine  Median progression free survival 5.3 months vs. 1.6 months with dacarbazine

 Selective inhibitor of V600 mutation of BRAF protein Vemurafenib…

 Cautions  Cutaneous squamous cell carcinoma - monitor  Hypersensitivity reactions  Severe dermatologic reactions – SJS & TEN  QT prolongation - monitor  Liver enzyme abnormalities – monitor  Photosensitivity – avoid sun exposure  Ophthalmic toxicities – monitor  CYP drug interactions Vemurafenib…

 Common adverse events: arthralgia, rash, fatigue, alopecia, photosensitivity, nausea, pruritus

 Dosing: 960 mg orally twice daily  Dose reductions in case of toxicity

 Supplied as 240 mg tablets  Limited distribution system Vismodegib capsules (Erivedge, Genentech)  Approved January 30, 2012

 Treatment of adults with metastatic basal cell carcinoma or locally advanced basal cell carcinoma that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation  46-60% response rates – few complete responses  Survival advantage?

 Inhibits the hedgehog signaling pathway  Signal cell growth and differentiation Vismodegib…

 Pregnancy risk – teratogenic  Males & females  Avoid donating blood or blood products

 Adverse effects: muscle spasms, alopecia, dysgeusia, weight loss, fatigue, nausea, diarrhea

 Dose: 150 mg once daily with or without food  Swallow capsules whole  Despite 10-14 day half-life, must be dosed daily Ingenol mebutate gel (Picato, LEO Pharma)  Approved January 23, 2012

 Topical treatment of actinic keratosis

 Induces cell death: mechanism unknown

 Response rates  Complete clearance of lesions: 37-47% of patients vs. 2-5% with vehicle  Partial clearance (> 75%): 60-68% of patients vs 7-8% with vehicle Ingenol mebutate…

 Face and scalp: 0.015% gel  Apply to affected area once daily for 3 consecutive days

 Trunk and extremities: 0.05% gel  Apply to affected area once daily for 2 consecutive days

 Supplied in unit dose tubes  Store in refrigerator Ingenol mebutate…

 Avoid contact with periocular area  Avoid washing or touching treated area for 6 hours after application

 Common adverse effects: local skin reactions, application site pain/pruritus/irritation/infection, periorbital edema, nasopharyngitis, headache Crizotinib capsules (Xalkori, Pfizer)  Approved August 26, 2011

 Treatment of locally advanced or metastatic non-small cell lung cancer  Anaplastic lymphoma kinase (ALK)-positive  Response rates about 60%  Apparent survival advantage compared to historical controls

 Inhibitor of receptor tyrosine kinases, including ALK Crizotinib…

 Cautions  Hepatotoxicity – monitor LFTs  Pneumonitis – discontinue therapy  QT prolongation  Neutropenia – monitor CBC  CYP3A4 inhibitors/inducers/substrates Crizotinib…

 Adverse effects: vision disturbances, nausea, diarrhea, vomiting, constipation, edema, fatigue

 Dose: 250 mg orally twice daily  With or without food  Swallow capsules whole  Dose interruption or reduction based on tolerability Abiraterone acetate tablets (Zytiga, Centocor Ortho Biotech)  Approved April 28, 2011

 Treatment of castration-resistant prostate cancer  Patients who have received prior docetaxel chemotherapy  Administered with prednisone  Survival 14.8 months vs 10.9 months with placebo

 CYP17 inhibitor  Increases ACTH  Decreases aldosterone, cortisol, DHEA, androstenedione, testosterone, and estradiol Abiraterone…  Contraindication  Pregnancy ○ Women who are pregnant or may be pregnant should wear gloves when handling abiraterone tablets

 Cautions  Secondary mineralocorticoid excess ○ Hypertension, hypokalemia, edema - monitor ○ Caution in patients with cardiovascular disease  Adrenocortical insufficiency  Hepatotoxicity – monitor LFTs  CYP2D6 substrates  CYP3A4 inhibitors and inducers Abiraterone…

 Adverse effects: joint swelling, hypokalemia, edema, muscle discomfort, hot flushes, diarrhea

 Dose: 1,000 mg once daily  Must be administered on empty stomach  Swallow capsules whole  Take with prednisone 5 mg twice daily WSU Drug Information Center (509) 358-7662 [email protected] [email protected]