2008-2009 new drug approvals

2008-2009 New Drug 2008-2009 New Drug ApprovalsApprovals

Samuel Gurevitz PharmD, CGPSamuel Gurevitz PharmD, CGPAssistant ProfessorAssistant Professor

Physician Assistant ProgramPhysician Assistant ProgramButler UniversityButler University

College of Pharmacy and Health SciencesCollege of Pharmacy and Health Sciences

Financial DisclosureFinancial Disclosure

I have no actual or potential conflict I have no actual or potential conflict of interest in relation to this program.of interest in relation to this program.

Educational ObjectivesEducational Objectives

After participating in this activity, pharmacists After participating in this activity, pharmacists should be able to:should be able to: Discuss the clinical indications, the various Discuss the clinical indications, the various

mechanisms of action of the drugs approved in mechanisms of action of the drugs approved in 2008 and first quarter of 2009.2008 and first quarter of 2009.

Recognize the clinically relevant drug interactions Recognize the clinically relevant drug interactions and common adverse effects as well as monitoring and common adverse effects as well as monitoring parameters.parameters.

Recognize the contraindications and precautionsRecognize the contraindications and precautions Explain the dosing and recommended dosage Explain the dosing and recommended dosage

adjustmentsadjustments Compare to other members of the therapeutic Compare to other members of the therapeutic

classclass

FDA Ratings: NDA Chemical TypeFDA Ratings: NDA Chemical Type

1 = new molecular entity1 = new molecular entity 2 = new ester, new salt2 = new ester, new salt 3 = new dosage form3 = new dosage form 4 = new combination4 = new combination 5 = new formulation or new 5 = new formulation or new

manufacturemanufacture

FDA Ratings: Review ClassificationFDA Ratings: Review Classification

P = priority review*P = priority review* S = standard reviewS = standard review O = Orphan DesignationO = Orphan Designation

*significant improvement compared to *significant improvement compared to

marketed products, in the treatment, marketed products, in the treatment,

diagnosis, or prevention of disease)diagnosis, or prevention of disease)

Desvenlafaxine (PristiqDesvenlafaxine (Pristiq®)®)

FDA rating: 1 SFDA rating: 1 S MOA: selective serotonin and MOA: selective serotonin and

norepinephrine reuptake inhibitor norepinephrine reuptake inhibitor (SNRI)(SNRI)

Indication: major depressive disorderIndication: major depressive disorder Pharmacokinetics Pharmacokinetics

metabolized by conjugation, 3A4 minor metabolized by conjugation, 3A4 minor metabolic pathwaymetabolic pathway

45% excreted unchanged in urine45% excreted unchanged in urinePrestiq (package insert). Philadelphia, PA: Wyeth Pharmaceuticals Inc; February 2009


PrecautionsPrecautions Should not be used with a hypersensitivity Should not be used with a hypersensitivity

to desvenlafaxine (major metabolite) and to desvenlafaxine (major metabolite) and venlafaxinevenlafaxine

Concomitant use with monoamine oxidase Concomitant use with monoamine oxidase inhibitor (MAOI) is contraindicatedinhibitor (MAOI) is contraindicated

Should not be started within 14 days of Should not be started within 14 days of stopping a MOAIstopping a MOAI

MAOI should not be started within 7 days of MAOI should not be started within 7 days of stopping desvenlafaxinestopping desvenlafaxine

Prestiq (package insert). Philadelphia, PA: Wyeth Pharmaceuticals Inc; February 2009


PrecautionsPrecautions Increased risk of suicidal thinking and Increased risk of suicidal thinking and

behavior in children, adolescents, and behavior in children, adolescents, and young adultsyoung adults

May cause sustained elevated blood May cause sustained elevated blood pressurepressure

May cause elevated total cholesterol May cause elevated total cholesterol and triglyceride and triglyceride



PrecautionsPrecautions Mania or hypomaniaMania or hypomania SeizuresSeizures HyponatremiaHyponatremia Narrow angle glaucomaNarrow angle glaucoma



Drug interactionsDrug interactions Other serotonergic drugs: serotonin Other serotonergic drugs: serotonin

syndromesyndrome 3A4 potent inhibitors: may result in 3A4 potent inhibitors: may result in

higher concentrationshigher concentrations Adverse effectsAdverse effects

Nausea, constipation, dizzinessNausea, constipation, dizziness HyperhidrosisHyperhidrosis Anxiety, InsomniaAnxiety, Insomnia Decreased appetite Decreased appetite



DosageDosage 50 mg daily with or without food50 mg daily with or without food

Do not crushDo not crush No additional benefit with a higher doseNo additional benefit with a higher dose 50 mg daily in patients with CrCl 30-50 50 mg daily in patients with CrCl 30-50

ml/minml/min 50 mg every other day with CrCl < 30ml/min50 mg every other day with CrCl < 30ml/min Do not abruptly discontinueDo not abruptly discontinue

Available: 50 and 100 mg extended-Available: 50 and 100 mg extended-release tabletsrelease tablets


Milnacipran (SavellaMilnacipran (Savella®)®)

FDA rating: 1 SFDA rating: 1 S MOA: selectively inhibits reuptake of MOA: selectively inhibits reuptake of

serotonin and norepinephrineserotonin and norepinephrine Indication: fibromyalgiaIndication: fibromyalgia

Exact MOA for reducing pain in patients Exact MOA for reducing pain in patients with fibromyalgia is unknownwith fibromyalgia is unknown

PharmacokineticsPharmacokinetics Eliminated primarily by renal excretion Eliminated primarily by renal excretion

Savella (package insert). St. Louis, MO: Forest Pharmaceuticals Inc; January 2009


PrecautionPrecaution Increased risk of suicidal thinking and Increased risk of suicidal thinking and

behavior in children, adolescents, and behavior in children, adolescents, and young adultsyoung adults

Concomitant use with monoamine oxidase Concomitant use with monoamine oxidase inhibitor (MAOI) is contraindicatedinhibitor (MAOI) is contraindicated

Should not be started within 14 days of Should not be started within 14 days of stopping a MOAIstopping a MOAI

MAOI should not be started within 5 days of MAOI should not be started within 5 days of stopping milnacipranstopping milnacipran



PrecautionPrecaution Contraindicated in uncontrolled narrow Contraindicated in uncontrolled narrow

angle glaucomaangle glaucoma May cause elevated blood pressure and May cause elevated blood pressure and

heart rateheart rate May cause increases in LFTMay cause increases in LFT

Avoid in patients with substantial alcohol Avoid in patients with substantial alcohol use or evidence of chronic liver diseaseuse or evidence of chronic liver disease



PrecautionPrecaution Use cautiously in patients with history of Use cautiously in patients with history of

seizures seizures HyponatremiaHyponatremia Abnormal bleedingAbnormal bleeding



Adverse EffectsAdverse Effects NauseaNausea ConstipationConstipation Hot flushHot flush HyperhidrosisHyperhidrosis

Drug interactionsDrug interactions Other serotonergic drugs; serotonin Other serotonergic drugs; serotonin

syndromesyndrome Aspirin, NSAIDs and other drugs that Aspirin, NSAIDs and other drugs that

affect coagulation; increased bleedingaffect coagulation; increased bleedingSavella (package insert). St. Louis, MO: Forest Pharmaceuticals Inc; January 2009


Dosage: 50 mg tablet twice a day with Dosage: 50 mg tablet twice a day with or without food; maximum dose 200 or without food; maximum dose 200 mg/daymg/day Start with 12.5 mg daily (day 1), 12.5 mg Start with 12.5 mg daily (day 1), 12.5 mg

twice a day for days 2-3, 25 mg twice a twice a day for days 2-3, 25 mg twice a day for days 4-7, and 50 mg twice a day day for days 4-7, and 50 mg twice a day on day 8on day 8

CrCl 5 to 29 ml/min: maintenance dose CrCl 5 to 29 ml/min: maintenance dose reduced by 50% to 25 mg twice a day reduced by 50% to 25 mg twice a day

Discontinuation: gradual dose reductionDiscontinuation: gradual dose reductionSavella (package insert). St. Louis, MO: Forest Pharmaceuticals Inc; January 2009

Comparisons of SNRIsComparisons of SNRIs

DrugDrug FDA-Approved FDA-Approved IndicationsIndications

CYP 405 CYP 405 inhibitioninhibition

CommentsComments

DesvenlafaxinDesvenlafaxinee

(Prestiq)(Prestiq)

DepressionDepression

Not significantNot significantMonitor BPMonitor BP

Potent 3A4 inhibitors may Potent 3A4 inhibitors may result in higher desvenlafaxine result in higher desvenlafaxine concentrationconcentration

Active metabolite of Active metabolite of vanlafaxinevanlafaxine

VenlafaxineVenlafaxine Depression, GADDepression, GAD

SAD, Panic DisorderSAD, Panic Disorder2D6 (weak)2D6 (weak) Monitor BPMonitor BP

Reduce dose by 25% for CrCl < Reduce dose by 25% for CrCl < 70ml/min70ml/min

MilnacipranMilnacipran

(Savella)(Savella)FibromyalgiaFibromyalgia Not significantNot significant CrCl 5 to 29 ml/min: CrCl 5 to 29 ml/min:

maintenance dose reduced by maintenance dose reduced by 50% to 25 mg twice a day50% to 25 mg twice a day

DuloxetineDuloxetine

(Cymbalta)(Cymbalta)DepressionDepression

GAD, DPN, GAD, DPN, fibromyalgiafibromyalgia

2D6 2D6 (moderate)(moderate)

Monitor BPMonitor BP

Not recommended in CrCl < 30 Not recommended in CrCl < 30 ml/minml/min

GAD = general anxiety disorder, SAD = social anxiety disorder, DPH = diabetic peripheral neuropathy

Fesoteridone (ToviazFesoteridone (Toviaz®)®)

FDA rating: 1 SFDA rating: 1 S MOA: muscarinic receptor antagonistMOA: muscarinic receptor antagonist Indication: treatment of overactive bladder Indication: treatment of overactive bladder

with symptoms or urinary incontinence, with symptoms or urinary incontinence, urgency, and frequencyurgency, and frequency

PharmacokineticsPharmacokinetics Fesoterodine is a prodrug. It is broken down Fesoterodine is a prodrug. It is broken down

into its active metabolite, 5-hydroxymethyl into its active metabolite, 5-hydroxymethyl tolterodine, by plasma esterases tolterodine, by plasma esterases

5-hydroxy-methyl tolterodine metabolized by 5-hydroxy-methyl tolterodine metabolized by 2D6 and 3A4 to inactive metabolites2D6 and 3A4 to inactive metabolites

Toviaz (package insert). New York, NY: Pfizer Labs; November 2008


PrecautionsPrecautions Contraindicated in urinary retention, Contraindicated in urinary retention,

gastric retention, uncontrolled narrow gastric retention, uncontrolled narrow angle glaucomaangle glaucoma

Mild to moderate renal impairment, Mild to moderate renal impairment, urinary obstruction urinary obstruction

Myasthenia gravisMyasthenia gravis Extreme heat can induce hyperthermiaExtreme heat can induce hyperthermia



Drug interactionsDrug interactions 2D6 and 3A4 inhibitors may cause higher 2D6 and 3A4 inhibitors may cause higher

concentrationsconcentrations Do not exceed 4 mg with potent 3A4Do not exceed 4 mg with potent 3A4

Other anticholinergic/antimuscarinic drugsOther anticholinergic/antimuscarinic drugs Adverse effectsAdverse effects

Anticholinergic effectsAnticholinergic effects Increase in liver enzymesIncrease in liver enzymes QT prolongation, dose dependent increase QT prolongation, dose dependent increase

heart rateheart rate



DosageDosage Starting dose 4 mg daily; based on Starting dose 4 mg daily; based on

response and tolerability can be response and tolerability can be increased to 8 mg dailyincreased to 8 mg daily

Do not crush, chewed, or dividedDo not crush, chewed, or divided Should not receive more than 4 mg daily Should not receive more than 4 mg daily

with a CrCl < 30 ml/minwith a CrCl < 30 ml/min Available: 4 and 8 mg extended Available: 4 and 8 mg extended

tabletstabletsToviaz (package insert). New York, NY: Pfizer Labs; November 2008

Antimuscarinic Medications for Antimuscarinic Medications for Overactive BladderOveractive Bladder

DrugDrug Muscarinic Muscarinic

Receptor Receptor SpecifictySpecificty

Incidence of Incidence of Adverse EffectsAdverse Effects

CommentsComments

FesoterodineFesoterodine

(Toviaz)(Toviaz)M2 and M3 (?)M2 and M3 (?) Dry mouth 19%Dry mouth 19%

Constipation 4%Constipation 4%Do not exceed 4 mg with Do not exceed 4 mg with 3A4 inhibitors and CrCl < 3A4 inhibitors and CrCl < 30 ml/mim30 ml/mim

TolterodineTolterodine

(Detrol LA)(Detrol LA)M2 and M3M2 and M3 Dry mouth 23%Dry mouth 23%

Constipation 6%Constipation 6%Lower dose with 3A4 Lower dose with 3A4 inhibitors and CrCl < 30 inhibitors and CrCl < 30 ml/minml/min

Oxybutynin LAOxybutynin LA

(patch, gel)(patch, gel)Primarily M3Primarily M3 Dry mouth 61%Dry mouth 61%

Constipation 13%Constipation 13%Lower Adverse effects with Lower Adverse effects with patch and gelpatch and gel

DarifenacinDarifenacin

(Enablex)(Enablex)M3M3 Dry mouth 20%Dry mouth 20%

Constipation 15%Constipation 15%Do not exceed 7.5 mg with Do not exceed 7.5 mg with 3A4 inhibitors3A4 inhibitors

SolfenacinSolfenacin

(Vesicare)(Vesicare)Primarily M3Primarily M3 Dry mouth 10.9%Dry mouth 10.9%

Constipation 5.4% Constipation 5.4% Do not exceed 5 mg with Do not exceed 5 mg with 3A4 inhibitors and CrCl < 3A4 inhibitors and CrCl < 30 ml/mim30 ml/mim

TrospiumTrospium

(Sanctura or (Sanctura or Sacnctura XR)Sacnctura XR)

M2 and M3M2 and M3 Dry mouth 20%Dry mouth 20%

Constipation 10% Constipation 10% Do not exceed 20 mg if Do not exceed 20 mg if CrCl < 30 ml/minCrCl < 30 ml/min

Toviaz (package insert). New York, NY: Pfizer Labs; November 2008Pharmacist Letter/Prescriber’s Letter: January 2008 Volume 24 Number 24018

Silodosin (RapafloSilodosin (Rapaflo®®))

FDA rating: 1 SFDA rating: 1 S MOA: Alpha-1a antagonistMOA: Alpha-1a antagonist Indication: treatment of benign Indication: treatment of benign

prostate hyperplasiaprostate hyperplasia Pharmacokinetics:Pharmacokinetics:

Metabolized by 3A4Metabolized by 3A4 P-glycoprotein substrateP-glycoprotein substrate

Rapaflo (package insert). Corona, CA: Watson Labs; October 2008


Precaution: patients with orthostatic Precaution: patients with orthostatic hypotension and vertigohypotension and vertigo

Drug interactionsDrug interactions Drugs that inhibit CYP 3A4 and P-Drugs that inhibit CYP 3A4 and P-

glycoprotein: increase concentrationglycoprotein: increase concentration Concurrent antihypertensive therapy or Concurrent antihypertensive therapy or

phosphodiesterase-5 inhibitors: increase phosphodiesterase-5 inhibitors: increase risk of orthostatic hypertensionrisk of orthostatic hypertension



Adverse effects:Adverse effects: Dizziness, orthostatic hypotensionDizziness, orthostatic hypotension DiarrheaDiarrhea NasopharyngitisNasopharyngitis Nasal congestionNasal congestion

Dosage: 8 mg capsule daily with a mealDosage: 8 mg capsule daily with a meal CrCl 30 to 50 ml/min: 4 mg daily with a CrCl 30 to 50 ml/min: 4 mg daily with a

mealmeal CrCl < 30 ml/min: contraindicatedCrCl < 30 ml/min: contraindicated


Comparison of Alpha1-BlockersComparison of Alpha1-Blockers

AlfuzosinAlfuzosin DoxazosiDoxazosinn

SilodosinSilodosin TamsulosinTamsulosin TerazosinTerazosin

FDA-IndicationFDA-Indication BPHBPH BPHBPH

HTNHTNBPHBPH BPHBPH BPHBPH

HTNHTN

Requires Dose Requires Dose TitrationTitration

NoNo YesYes NoNo YesYes YesYes

Renal Renal PrecautionPrecaution

YesYes NoNo YesYes NoNo NoNo

Drug Drug InteractionsInteractions

3A4 3A4 inhibitorsinhibitors

PDE-5 PDE-5 inhibitorsinhibitors


3A4 inhibitors3A4 inhibitors

P-P-glycoprotein glycoprotein substratesubstrate




Affects QT Affects QT

IntervalIntervalYesYes NoNo NoNo NoNo NoNo

CommentsComments Selective Selective for alpha-1afor alpha-1a

NonselectiNonselectivealpha-1 vealpha-1

Selective for Selective for alpha-1aalpha-1a

Selective for Selective for alpha-1aalpha-1a

NonselectiNonselective for ve for alpha-1alpha-1Pharmacist Letter/Prescriber’s Letter: September 2003 Volume 19

Number 190909Rapaflo (package insert). Corona, CA: Watson Labs; October 2008

Lacosamide (VimpatLacosamide (Vimpat®)®)

FDA rating: 1 SFDA rating: 1 S MOAMOA

Selectively enhances slow inactivation Selectively enhances slow inactivation of voltage-gated channels and inhibits of voltage-gated channels and inhibits repetitive neuronal firingrepetitive neuronal firing

Binds to collapsing response mediator Binds to collapsing response mediator protein-2 (CRMP-2)protein-2 (CRMP-2)

Phosphoprotein expressed in nervous Phosphoprotein expressed in nervous system involved in neuronal differentiation system involved in neuronal differentiation and control of axonal outgrowthand control of axonal outgrowth

Vimpat (package insert). Smyrna, GA: UCB Inc; October 2008


Indication: adjunctive treatment of Indication: adjunctive treatment of partial-onset seizures in patients partial-onset seizures in patients >> 17 years17 years

PharmacokineticsPharmacokinetics IV and oral are bioequivalentIV and oral are bioequivalent

PrecautionsPrecautions Increased risk of suicidal thinking and Increased risk of suicidal thinking and

behaviorbehavior Should be tapered slowlyShould be tapered slowly



Drug interactionsDrug interactions No significant drug interactionsNo significant drug interactions Caution with drugs that prolong the QT Caution with drugs that prolong the QT

intervalinterval Adverse effectsAdverse effects

Dizziness, vertigo, ataxiaDizziness, vertigo, ataxia Blurred visionBlurred vision Elevated liver enzymes Elevated liver enzymes



DosageDosage Starting dose is 50 mg twice a day, may Starting dose is 50 mg twice a day, may

be increased weekly by 100 mg until be increased weekly by 100 mg until recommended dose of 200 to 400 recommended dose of 200 to 400 mg/daymg/day

Maximum dose of 300 mg/day Maximum dose of 300 mg/day recommended for severe renal impairment recommended for severe renal impairment or mild to moderate hepatic impairmentor mild to moderate hepatic impairment

Available: 50, 100, 150, and 200 mg Available: 50, 100, 150, and 200 mg tablets tablets


Methylnaltrexone (RelistorMethylnaltrexone (Relistor®)®)

FDA rating: 1 SFDA rating: 1 S MOA: peripheral selective mu-opioid MOA: peripheral selective mu-opioid

antagonistantagonist Does not cross the blood-brain barrierDoes not cross the blood-brain barrier Does not impact the opioid mediated Does not impact the opioid mediated

analgesic effectsanalgesic effects Indications: treatment of mediated Indications: treatment of mediated

opioid-induced constipation, when opioid-induced constipation, when response to laxatives has not been response to laxatives has not been sufficientsufficient

Relistor (package insert). Philadelphia, PA: Wyeth Pharmaceuticals Inc; April 2008Guay DRP. Consultant Pharmacist 2009;24:210-26


Precautions: suspected GI Precautions: suspected GI obstruction (do not use)obstruction (do not use)

Adverse effects:Adverse effects: Abdominal painAbdominal pain FlatulenceFlatulence NauseaNausea DizzinessDizziness DiarrheaDiarrhea



Dosage: Usual schedule is one dose Dosage: Usual schedule is one dose subcutaneous every other day as subcutaneous every other day as neededneeded Patients 38 to less than 62 kg: 8mgPatients 38 to less than 62 kg: 8mg Patients 62 to 114 kg: 12 mgPatients 62 to 114 kg: 12 mg Patients < 38 or > 114 kg: 0.15 mg/kgPatients < 38 or > 114 kg: 0.15 mg/kg Patients with CrCl < 30 ml/min dosage Patients with CrCl < 30 ml/min dosage

should be reduced by 50%should be reduced by 50% Use beyond 4 months has not been studiedUse beyond 4 months has not been studied

Available: 12mg/0.6ml single use vialAvailable: 12mg/0.6ml single use vial


Tetrabenazine (XenazineTetrabenazine (Xenazine®)®)

FDA rating: 1 P OFDA rating: 1 P O MOA: centrally acting depletor of MOA: centrally acting depletor of

monoamines (dopamine, serotonin, monoamines (dopamine, serotonin, norepinephrine, and histamine) from norepinephrine, and histamine) from nerve terminalsnerve terminals It inhibits vesicular monoamine It inhibits vesicular monoamine

transporter type 2, resulting in decreased transporter type 2, resulting in decreased uptake of monoamines in synaptic uptake of monoamines in synaptic vesicles and depletion of monoamine vesicles and depletion of monoamine storesstores

T.Yero, et al. P&T. 2008;33:690-94Xenazine (pakage insert). Deerfield, IL: Ovation Pharmaceuticals Inc.; September 2008


Indications: Treatment of chorea Indications: Treatment of chorea associated with Huntington’s diseaseassociated with Huntington’s disease

Pharmacokinetics:Pharmacokinetics: Metabolized by 2D6Metabolized by 2D6

PrecautionsPrecautions Contraindicated in patients treated Contraindicated in patients treated

inadequately for depressioninadequately for depression Should not be used in patients taking Should not be used in patients taking

monoamine oxidase inhibitors or monoamine oxidase inhibitors or reserpine reserpine

T.Yero, et al. P&T. 2008;33:690-94Xenazine (pakage insert). Deerfield, IL: Ovation Pharmaceuticals Inc.;

September 2008


PrecautionsPrecautions Contraindicated in patients treated Contraindicated in patients treated

inadequately for depressioninadequately for depression Should not be used in patients taking Should not be used in patients taking

monoamine oxidase inhibitors or reserpine monoamine oxidase inhibitors or reserpine Avoid in patients with long QT syndrome Avoid in patients with long QT syndrome

or other drugs that prolong QTc intervalor other drugs that prolong QTc interval Adverse Effects: depression, akathisia, Adverse Effects: depression, akathisia,

sedation, anxiety, insomniasedation, anxiety, insomnia

T.Yero, et al. P&T. 2008;33:690-94

Xenazine (pakage insert). Deerfield, IL: Ovation Pharmaceuticals Inc.; September 2008


Drug interactionsDrug interactions 2D6 inhibitors (Paroxetine and 2D6 inhibitors (Paroxetine and

fluoxetine)fluoxetine) Increase concentrations dose should be Increase concentrations dose should be

reduced by 50%reduced by 50% Drugs known to prolong QTc intervalDrugs known to prolong QTc interval

T.Yero, et al. P&T. 2008;33:690-94

Xenazine (pakage insert). Deerfield, IL: Ovation Pharmaceuticals Inc.; September 2008


Dosage: recommended maximum Dosage: recommended maximum dose is 25 mg tablet daily; doses dose is 25 mg tablet daily; doses above 100 mg not recommendedabove 100 mg not recommended Starting dose 12.5 mg daily, after one Starting dose 12.5 mg daily, after one

week 12.5 mg twice a day, titrate weekly week 12.5 mg twice a day, titrate weekly by 12.5 mg until desired effectby 12.5 mg until desired effect

If 37.5 to 50 mg/day is needed, it should If 37.5 to 50 mg/day is needed, it should be given in three divided dosesbe given in three divided doses

Patients requiring greater than 50 Patients requiring greater than 50 mg/day should undergo genotyping for mg/day should undergo genotyping for CYP2D6 CYP2D6

T.Yero, et al. P&T. 2008;33:690-94Xenazine (pakage insert). Deerfield, IL: Ovation Pharmaceuticals Inc.;

September 2008

Febuxostat (UloricFebuxostat (Uloric®)®)

FDA rating: 1 SFDA rating: 1 S MOA: inhibits xanthine oxidaseMOA: inhibits xanthine oxidase Indication: chronic management of Indication: chronic management of

hyperuricemia inpatients with gouthyperuricemia inpatients with gout Not recommended for asymptomatic Not recommended for asymptomatic

hyperuricemia hyperuricemia

Uloric (pakage insert). Deerfield, IL: Takeda Pharmaceuticals America Inc.; February 2009


PharmacokineticsPharmacokinetics MetabolizedMetabolized

Conjugation by uridine diphosphate Conjugation by uridine diphosphate glucuronosyltransferaseglucuronosyltransferase

CYP1A2, 2C8, and 2C9CYP1A2, 2C8, and 2C9

Adverse EffectsAdverse Effects Liver function abnormalities, arthralgia Liver function abnormalities, arthralgia

(joint pain), and rash(joint pain), and rash



PrecautionsPrecautions Gout flaresGout flares Cardiovascular thromboembolic eventsCardiovascular thromboembolic events

Compared to allopurinol and febuxostat 80 Compared to allopurinol and febuxostat 80 mgmg

Increase in liver enzymesIncrease in liver enzymes Contraindicated in patients being Contraindicated in patients being

treated with azathioprine, treated with azathioprine, mercaptopurine, or theophyllinemercaptopurine, or theophylline



Dosage: recommended at 40 to 80 Dosage: recommended at 40 to 80 mg dailymg daily Start at 40 mg tablet dailyStart at 40 mg tablet daily Patients not achieving a serum uric acid Patients not achieving a serum uric acid

less than 6 mg/dL after 2 weeks with 40 less than 6 mg/dL after 2 weeks with 40 mg increase to 80 mg dailymg increase to 80 mg daily

Caution in patients with CrCl < 30 Caution in patients with CrCl < 30 ml/minml/min


Comparison: Allopurinol and Comparison: Allopurinol and FebuxostatFebuxostat

AllopurinolAllopurinol FebuxostatFebuxostat

MOAMOA Inhibits xanthine oxidaseInhibits xanthine oxidase Inhibits xanthine oxidaseInhibits xanthine oxidase

(more selective)(more selective)

Cost (month)Cost (month) < $16.00< $16.00 $160$160

Uric acid < 6 Uric acid < 6 mg/dLmg/dL

36% - 42% (300 mg)36% - 42% (300 mg) 45% (40mg)45% (40mg)

67% - 74% (80 mg)67% - 74% (80 mg)

Renal adjustmentRenal adjustment YesYes

CrCl 10-20 ml/min; CrCl 10-20 ml/min; 200mg200mg

CrCl < 10 ml/min; CrCl < 10 ml/min; 100mg100mg

NoNo

(caution in CrCl <30 ml/min)(caution in CrCl <30 ml/min)

CommentsComments 600mg reduced uric acid 600mg reduced uric acid (< 6mg/dL) by 85%(< 6mg/dL) by 85%

Offers an alternative to Offers an alternative to allopurinolallopurinol

Discontinuation due to LFTs Discontinuation due to LFTs greater than allopurinolgreater than allopurinol

Febuxostat 40mg (1.8%), Febuxostat 40mg (1.8%), 80mg (1.2%) vs Allopurinol 80mg (1.2%) vs Allopurinol (0.9%)(0.9%)

Uloric (pakage insert). Deerfield, IL: Takeda Pharmaceuticals America Inc.; February 2009Pharmacist’s letter/Prescriber’s Letter. April 2009: Volume 25; Number 250413

Tapentadol (NucyntaTapentadol (Nucynta®)®)

FDA rating: 1 SFDA rating: 1 S MOA: two mechanisms of actionMOA: two mechanisms of action

Binds to and activates mu-opioid Binds to and activates mu-opioid receptors in the CNSreceptors in the CNS

Norepinephrine reuptake inhibitor; Norepinephrine reuptake inhibitor; inhibits transmission of pain from spinal inhibits transmission of pain from spinal cord and affect activity at parts of the cord and affect activity at parts of the brain that control how pain is perceivedbrain that control how pain is perceived

Indication: relief of moderate to Indication: relief of moderate to severe pain in adults 18 yrs or oldersevere pain in adults 18 yrs or older

www.clinicalpharmacology.com www.jnj.com/connect/news/all/20080509


PharmacokineticsPharmacokinetics No active metabolites; metabolized by No active metabolites; metabolized by

glucuronidationglucuronidation 3% renally excreted unchanged3% renally excreted unchanged 69% renally excreted as conjugates69% renally excreted as conjugates

Adverse effectsAdverse effects Nausea, vomiting, dizziness, Nausea, vomiting, dizziness,

somnolence somnolence



PrecautionsPrecautions ElderlyElderly COPD, sleep apneaCOPD, sleep apnea Patients with head injuryPatients with head injury Patients with biliary tract diseasePatients with biliary tract disease

Drug InteractionsDrug Interactions Serotonergic drugs: Serotonin syndromeSerotonergic drugs: Serotonin syndrome

Available: 50 mg, 75 mg, 100 mg doseAvailable: 50 mg, 75 mg, 100 mg dose


Degarilex (No Trade Name)Degarilex (No Trade Name)

FDA rating: 1 SFDA rating: 1 S MOA: GnRH receptor antagonistsMOA: GnRH receptor antagonists

It binds reversibly to the pituitary GnRH It binds reversibly to the pituitary GnRH receptors, thereby reducing the release receptors, thereby reducing the release of gonadotropins and consequently of gonadotropins and consequently testosteronetestosterone

Indication: Treatment of patients Indication: Treatment of patients with advanced prostate cancerwith advanced prostate cancer

Pharmacokinetics: not a substrate, Pharmacokinetics: not a substrate, inducer, or inhibitor of CYP450inducer, or inhibitor of CYP450

Degarilex (pakage insert). Saint-Prex, Switzerland : Ferring Pharmaceuticals Inc.; December 2008

DegarilexDegarilex

Adverse effectsAdverse effects Injection site reactionsInjection site reactions Hot flashesHot flashes Increased weightIncreased weight Increase LFTs and gamma-Increase LFTs and gamma-

glutamyltranferaseglutamyltranferase Drug interactions: unlikelyDrug interactions: unlikely Precautions:Precautions:

QT prolongationQT prolongationDegarilex (pakage insert). Saint-Prex, Switzerland : Ferring Pharmaceuticals Inc.; December 2008

DegarilexDegarilex

Dosage: Treatment started with Dosage: Treatment started with 240mg given as two subcutaneous 240mg given as two subcutaneous injections of 120mg eachinjections of 120mg each Followed by 80 mg administered every Followed by 80 mg administered every

28 days28 days Available in 80 mg/vial and 120mg/vialAvailable in 80 mg/vial and 120mg/vial

Degarilex (pakage insert). Saint-Prex, Switzerland : Ferring Pharmaceuticals Inc.; December 2008

Other GnRH Antagonists and Other GnRH Antagonists and Agonist used for Prostate CancerAgonist used for Prostate Cancer

Aberilex (PlenaxisAberilex (Plenaxis®): antagonists®): antagonists Leuprolide: agonistLeuprolide: agonist Goserelin (Zoladex®): agonistGoserelin (Zoladex®): agonist Advantage of these agents over Advantage of these agents over

GnRH agonists (goserelin, leuprolide) GnRH agonists (goserelin, leuprolide) would be they lack initial flare would be they lack initial flare stimulation and induce quickly a stimulation and induce quickly a hypogonadal situation hypogonadal situation

Degarelix vs LeuprolideDegarelix vs Leuprolide

Degarelix Degarelix

(240/160 mg)(240/160 mg)

N=202N=202

Degarelix Degarelix

(240/160 mg)(240/160 mg)

N=207N=207

LeuprolideLeuprolide

(7.5 mg )(7.5 mg )

N=201N=201

Day 1Day 1 44%44% 52%52% 0%0%

Day 3Day 3 96%96% 96%96% 0%0%

Day 7Day 7 99%99% 99%99% 1%1%

Day 14Day 14 99%99% 99%99% 18%18%

Day 28Day 28 99%99% 100%100% 100%100%

Percentage Attaining Testosterone Percentage Attaining Testosterone << 50 ng/dL within the First 50 ng/dL within the First 28 Days28 Days

Klotz L, et al. BJU Int. 2008. 102:1531-8

Dexlansoprazole (KapidexDexlansoprazole (Kapidex®®):):Comparison to Other Proton Pump InhibitorsComparison to Other Proton Pump Inhibitors

DrugDrug FormulationFormulation Drug InteractionsDrug Interactions

DexlansoprazDexlansoprazoleole

Dual Delayed ReleaseDual Delayed Release

(1(1stst peak 1 to 2 hrs after peak 1 to 2 hrs after and 2and 2ndnd peak within 4 to 5 peak within 4 to 5 hrs)hrs)

Inhibits absorption: iron salts, Inhibits absorption: iron salts, ketoconazole; Do not use ketoconazole; Do not use Atazanavir Atazanavir

LansoprazoleLansoprazole Delayed ReleaseDelayed Release

Peaks at 1.7 hrsPeaks at 1.7 hrsInhibits absorption: iron salts, Inhibits absorption: iron salts, ketoconazole; Do not use ketoconazole; Do not use AtazanavirAtazanavir

EsomeprazoleEsomeprazole Delayed ReleaseDelayed Release


OmeprazoleOmeprazole

ZegeridZegeridDelayed Release 0.5 – 3 Delayed Release 0.5 – 3 hrshrs

Peaks 10 – 90 min (30 Peaks 10 – 90 min (30 min)min)

Inhibits absorption: iron salts, Inhibits absorption: iron salts, ketoconazole, Atazanavir (do not ketoconazole, Atazanavir (do not use)use)

Inhibits metabolism: DiazepamInhibits metabolism: Diazepam

PantoprazolePantoprazole Delayed ReleaseDelayed Release


RabeprazoleRabeprazole Delayed ReleaseDelayed Release

Peaks 2 – 5 hrsPeaks 2 – 5 hrsInhibits absorption: iron salts, Inhibits absorption: iron salts, ketoconazole; Do not use ketoconazole; Do not use AtazanavirAtazanavir

Patients treated with proton pump inhibitors and warfarin concomitantlymay need to be monitored for increases in INR and prothrombin time

Comparison of Clevidipine vs Other Comparison of Clevidipine vs Other IV Agents to Lower Blood PressureIV Agents to Lower Blood Pressure

CharacteristiCharacteristicscs

ClevidipiClevidipinene

NicardipinNicardipinee

NTGNTG EsmololEsmolol LabetalolLabetalol

MOAMOA DHP CCBDHP CCB DHP CCBDHP CCB VasodilatorVasodilator B-BlockerB-Blocker B-blocker B-blocker and alpha-and alpha-

blockerblocker

Onset of Onset of ActionAction

2-4 min2-4 min 5-10 min5-10 min 1-5 min1-5 min 1-2 min1-2 min 5-10 min5-10 min

Duration of Duration of ActionAction

5-15 min5-15 min 1-4 h1-4 h 3-5 min3-5 min 10-20 min10-20 min 3-6 h3-6 h

Adverse Adverse EffectsEffects

HA, HA, tachycarditachycardi

aa

hypotensihypotensionon

N & VN & V

HA, N & V HA, N & V edema, edema,

tachycarditachycardiaa

flushingflushing

HA, vomiting, HA, vomiting, tachycardiatachycardia

MethemoglobiMethemoglobin-emian-emia

BronchospasBronchospasm, m,

bradycardia,bradycardia,

hypotensionhypotension

BronchospasBronchospasmbradycardimbradycardi

a, a, hypotensionhypotension

Phung OJ, et al. Formulary 2009;44:102-7

Other New ApprovalsOther New Approvals

DrugDrug FDA FDA CategorCategor

yy

MOAMOA IndicationIndication

Alvimopan* Alvimopan* (Entereg)(Entereg)

* Hospital use * Hospital use onlyonly

1S1S Peripheral acting mu-Peripheral acting mu-opioid receptor opioid receptor antagonistantagonist

Acceleration of the time Acceleration of the time to upper and lower GI to upper and lower GI recovery following partial recovery following partial large or small bowel large or small bowel resection with primary resection with primary anastomosis anastomosis

BendamustineBendamustine

(Treanda)(Treanda)1P,O1P,O Akylating agentAkylating agent Chronic lymphocytic Chronic lymphocytic

leukemialeukemia

ClevidipineClevidipine

Cleviprex)Cleviprex)1S1S Dihydropyrydine Dihydropyrydine

calcium channel calcium channel blockerblocker

Hypertension when oral Hypertension when oral therapy is not possible or therapy is not possible or desirabledesirable

DifluprednateDifluprednate

(Durezol)(Durezol)1P1P Topical corticosteroidTopical corticosteroid

Inhibits inflammationInhibits inflammationTreatment of Treatment of inflammation and inflammation and painpain associated with ocular associated with ocular surgerysurgery

Drugs@FDA: Information about FDA-approved prescription, over-the-counter, and discontinued drug products

www.accessdata.fda.gov/scripts/cder/drugsatfda



yy


EltrombopagEltrombopag

(Promact)(Promact)1P, O1P, O Thrombopoietin Thrombopoietin

receptor agonist, receptor agonist, stimulates platelet stimulates platelet productionproduction

Treatment of chronic Treatment of chronic immune immune thrombocytopenia thrombocytopenia purpura (ITP) in patients purpura (ITP) in patients with insufficient response with insufficient response to corticosteroids, to corticosteroids, immunoglobulins, or immunoglobulins, or splenectomy splenectomy

RomiplostimRomiplostim

(Nplate)(Nplate)1P, O1P, O Thrombopoietin Thrombopoietin

receptor agonist, receptor agonist, stimulates platelet stimulates platelet productionproduction

Treatment of chronic Treatment of chronic immune immune thrombocytopenia thrombocytopenia purpura (ITP) in patients purpura (ITP) in patients with insufficient response with insufficient response to corticosteroids, to corticosteroids, immunoglobulins, or immunoglobulins, or splenectomy splenectomy Drugs@FDA: Information about FDA-approved prescription, over-the-counter, and discontinued drug products

www.accessdata.fda.gov/scripts/cder/drugsatfda



yy


EtravirineEtravirine 1P1P Non-nucleoside Non-nucleoside reverse transciptasereverse transciptase

In combination with other In combination with other antiretovirals for HIV-1 antiretovirals for HIV-1 among treatment among treatment experienced adults who experienced adults who have evidence of have evidence of resistanceresistance

Certolizum Certolizum PegolPegol

(Cimzia)(Cimzia)

1S1S Humanized Humanized monoclonal antibiody monoclonal antibiody Fab’ fragment that Fab’ fragment that binds and neutralizes binds and neutralizes TNF-alphaTNF-alpha

Reducing signs and Reducing signs and symptoms of Crohn’s symptoms of Crohn’s disease and maintaining disease and maintaining clinical response in clinical response in moderate to severe moderate to severe disease when disease when conventional therapy fails conventional therapy fails

Rufinamide Rufinamide

(Banzel)(Banzel)1S1S Modulates sodium Modulates sodium

channels, prolonging channels, prolonging the inactive state of the inactive state of the channelthe channel

Adjunctive treatment of Adjunctive treatment of seizures associated with seizures associated with Lennox-Gastaut Lennox-Gastaut syndromesyndrome

Drugs@FDA: Information about FDA-approved prescription, over-the-counter, and discontinued drug productswww.accessdata.fda.gov/scripts/cder/drugsatfda

Questions or Comments

2008-2009 new drug approvals

Documents

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urine prestiq package

milnacipran savella

milnacipran savella

desvenlafaxine pristiq

daily day

new ester