Date post: | 23-Dec-2014 |
Category: |
Documents |
Upload: | samueljack |
View: | 1,102 times |
Download: | 9 times |
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
Desvenlafaxine (PristiqDesvenlafaxine (Pristiq®)®)
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
Desvenlafaxine (PristiqDesvenlafaxine (Pristiq®)®)
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
Prestiq (package insert). Philadelphia, PA: Wyeth Pharmaceuticals Inc; February 2009
Desvenlafaxine (PristiqDesvenlafaxine (Pristiq®)®)
PrecautionsPrecautions Mania or hypomaniaMania or hypomania SeizuresSeizures HyponatremiaHyponatremia Narrow angle glaucomaNarrow angle glaucoma
Prestiq (package insert). Philadelphia, PA: Wyeth Pharmaceuticals Inc; February 2009
Desvenlafaxine (PristiqDesvenlafaxine (Pristiq®)®)
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
Prestiq (package insert). Philadelphia, PA: Wyeth Pharmaceuticals Inc; February 2009
Desvenlafaxine (PristiqDesvenlafaxine (Pristiq®)®)
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
Prestiq (package insert). Philadelphia, PA: Wyeth Pharmaceuticals Inc; February 2009
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
Milnacipran (SavellaMilnacipran (Savella®)®)
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
Savella (package insert). St. Louis, MO: Forest Pharmaceuticals Inc; January 2009
Milnacipran (SavellaMilnacipran (Savella®)®)
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
Savella (package insert). St. Louis, MO: Forest Pharmaceuticals Inc; January 2009
Milnacipran (SavellaMilnacipran (Savella®)®)
PrecautionPrecaution Use cautiously in patients with history of Use cautiously in patients with history of
seizures seizures HyponatremiaHyponatremia Abnormal bleedingAbnormal bleeding
Savella (package insert). St. Louis, MO: Forest Pharmaceuticals Inc; January 2009
Milnacipran (SavellaMilnacipran (Savella®)®)
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
Milnacipran (SavellaMilnacipran (Savella®)®)
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
Fesoteridone (ToviazFesoteridone (Toviaz®)®)
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
Toviaz (package insert). New York, NY: Pfizer Labs; November 2008
Fesoteridone (ToviazFesoteridone (Toviaz®)®)
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
Toviaz (package insert). New York, NY: Pfizer Labs; November 2008
Fesoteridone (ToviazFesoteridone (Toviaz®)®)
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
Silodosin (RapafloSilodosin (Rapaflo®®))
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
Rapaflo (package insert). Corona, CA: Watson Labs; October 2008
Silodosin (RapafloSilodosin (Rapaflo®®))
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
Rapaflo (package insert). Corona, CA: Watson Labs; October 2008
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
PDE-5 PDE-5 inhibitorsinhibitors
3A4 inhibitors3A4 inhibitors
P-P-glycoprotein glycoprotein substratesubstrate
PDE-5 PDE-5 inhibitorsinhibitors
PDE-5 PDE-5 inhibitorsinhibitors
PDE-5 PDE-5 inhibitorsinhibitors
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
Lacosamide (VimpatLacosamide (Vimpat®)®)
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
Vimpat (package insert). Smyrna, GA: UCB Inc; October 2008
Lacosamide (VimpatLacosamide (Vimpat®)®)
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
Vimpat (package insert). Smyrna, GA: UCB Inc; October 2008
Lacosamide (VimpatLacosamide (Vimpat®)®)
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
Vimpat (package insert). Smyrna, GA: UCB Inc; October 2008
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
Methylnaltrexone (RelistorMethylnaltrexone (Relistor®)®)
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
Relistor (package insert). Philadelphia, PA: Wyeth Pharmaceuticals Inc; April 2008Guay DRP. Consultant Pharmacist 2009;24:210-26
Methylnaltrexone (RelistorMethylnaltrexone (Relistor®)®)
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
Relistor (package insert). Philadelphia, PA: Wyeth Pharmaceuticals Inc; April 2008Guay DRP. Consultant Pharmacist 2009;24:210-26
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
Tetrabenazine (XenazineTetrabenazine (Xenazine®)®)
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
Tetrabenazine (XenazineTetrabenazine (Xenazine®)®)
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
Tetrabenazine (XenazineTetrabenazine (Xenazine®)®)
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
Tetrabenazine (XenazineTetrabenazine (Xenazine®)®)
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
Febuxostat (UloricFebuxostat (Uloric®)®)
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
Uloric (pakage insert). Deerfield, IL: Takeda Pharmaceuticals America Inc.; February 2009
Febuxostat (UloricFebuxostat (Uloric®)®)
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
Uloric (pakage insert). Deerfield, IL: Takeda Pharmaceuticals America Inc.; February 2009
Febuxostat (UloricFebuxostat (Uloric®)®)
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
Uloric (pakage insert). Deerfield, IL: Takeda Pharmaceuticals America Inc.; February 2009
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
Tapentadol (NucyntaTapentadol (Nucynta®)®)
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
www.clinicalpharmacology.com www.jnj.com/connect/news/all/20080509
Tapentadol (NucyntaTapentadol (Nucynta®)®)
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
www.clinicalpharmacology.com www.jnj.com/connect/news/all/20080509
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
Peaks at 1.5 hrsPeaks at 1.5 hrsInhibits absorption: iron salts, Inhibits absorption: iron salts, ketoconazole; Do not use ketoconazole; Do not use AtazanavirAtazanavir
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
Peaks at 2.5 hrsPeaks at 2.5 hrsInhibits absorption: iron salts, Inhibits absorption: iron salts, ketoconazole; Do not use ketoconazole; Do not use AtazanavirAtazanavir
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
Other New ApprovalsOther New Approvals
DrugDrug FDA FDA CategorCategor
yy
MOAMOA IndicationIndication
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
Other New ApprovalsOther New Approvals
DrugDrug FDA FDA CategorCategor
yy
MOAMOA IndicationIndication
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