Upload
others
View
6
Download
0
Embed Size (px)
Citation preview
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