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 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)

Plavix (May)

Lescol (June)

Lunesta (July)

Detrol (Sept.)

Diovan (Sept.)

Lidoderm (Nov.)

Atacand (Dec.)Lunesta (July)

Actos (Aug.)

Singulair (Aug.)

Atacand (Dec.)

Maxalt (Dec.)

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 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 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 mellitus2 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 Exenatide 2 mg weekly (n=129)

Exenatide twice 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 therapiesconsider 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 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 COPDtreatment 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 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 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 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 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 dailyenoxaparin 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 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 WarfarinRivaroxaban 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 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: 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 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 syndromessyndromes

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 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%*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 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%

Loading Dose: 180 mg

Maintenance Dose: 90 mg twice daily

REMS: Medication Guide

Life-threatening or fatal bleeding 5.8% 5.8%

Bradycardia 4% 4.4%

Syncope 0.8% 1.1%

Boceprevir capsule(Victrelis, Merck) Approved May 13, 2011

Chronic hepatitis C genotype 1 infection in adult patientsadult 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 patientsadult patients Treatment naïve or failed previous interferon-

based treatment, including prior null responders, partial responders, and relapsers

HCV NS3/4A protease inhibitor

Boceprevir-PEG-Ribavirin(SPRINT-2, RESPOND -2)

Telaprevir-PEG-Ribavirin

(ADVANCE, REALIZE)

PEG-Ribavirin

Treatment-naïve 63-66% 69-75% 38-44%

Treatment-experienced

Boceprevir- and Telaprevir-Based Regimens: Summary of SVR Rates

RelapserPartial responderNull responder

69-75%40-52%

N/A

83-88%54-59%29-33%

24-29%7-15%

5%

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.

Adherence is critical!

Boceprevir Telaprevir4-Wk Lead-In withPEG-IFN/RBV

Yes No

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

Dosing: Boceprevir vs Telaprevir

Total TreatmentDuration

28-48 weeks 24-48 weeks

Candidates for Response Guided Therapy (RGT)

NONCIRRHOTICS:Treatment-naïve: 28 wks

Prior relapser / partial responder: 36 weeks

NONCIRRHOTICS:Treatment-naïve: 24 wks Prior relapser: 24 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 24: HCV RNA detected

Wk 4 or 12: HCV RNA > 1,000IU/mL

Wk 24: HCV RNA detected

Important PK/PD Considerations

Boceprevir TelaprevirFood Effect Increases exposure 40-60%

•Take with foodSubstantially increases exposure•Take with snack/meal with 20 g fat

Metabolism 2 pathways: Aldoketoreductase (AKR) and CYP3A4/5

Hepatic via CYP3A4

Potential for CYP3A4: strong inhibitor CYP3A4: strong inhibitor and Potential for Drug Interactions

CYP3A4: strong inhibitor P-gp: substrate and moderate inhibitor

CYP3A4: strong inhibitor and substrateP-gp: substrate and local inhibitor

Hepatic Impairment

No dose adjustment required Should not be administered to patients with moderate to severe hepatic impairment

Renal Impairment

No dose adjustment required Exposure may be greater in renally impaired patients

32

Boceprevir & Telaprevir…Boceprevir Telaprevir

Contraindications*

CYP3A4/5 substrates X X

Potent CYP3A4/5 inducers X X

Warnings & Precautions*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 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

Telaprevir

Fidaxomicin tablet(Dificid, Optimer) Approved May 27, 2011

Treatment of Clostridium difficile-associated diarrhea in adultsdiarrhea 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%

Difference largely driven by difference in population notinfected with NAP1/BI/027 strains

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%

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%

Dose: 200 mg orally twice daily x 10 days

Abdominal pain 6% 4%

Gastrointestinal hemorrhage 4% 2%

Anemia 2% 2%

Neutropenia 2% 1%

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 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 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 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 Adjunctive treatment of partial-onset seizures in adults

Mechanism: opens KCNQ2/3 potassium channels in the brain

Ezogabine…Study 1 Study 2

Ezogabine 1,200

mg/day

Placebo Ezogabine900

mg/day

Placebo

Median baseline seizure frequency^

11-12 / month 9-10 / monthfrequency^

11-12 / month 9-10 / month

Median reduction from baseline

44%* 18% 40%* 16%

% with greater than 50% reduction from baseline

56%* 23% 47%* 19%

^ 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 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%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 syndromewith 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 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 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 adultsangioedema 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 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% 0Transaminase 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 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 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 melanomamelanoma 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 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 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, 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 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 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, periorbitaledema, 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 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 Neutropenia – monitor CBC

CYP3A4 inhibitors/inducers/substrates

Crizotinib…

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

Dose: 250 mg orally twice daily 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

chemotherapychemotherapy 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 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

Levient@wsu.edu

Pharmacy.druginfo@wsu.edu