1 selegiline transdermal system (sts) fda psychopharmacologic drugs advisory committee october 26,...

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Selegiline Transdermal Selegiline Transdermal System System (STS)(STS)

FDA Psychopharmacologic Drugs FDA Psychopharmacologic Drugs Advisory CommitteeAdvisory Committee

October 26, 2005October 26, 2005

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IntroductionIntroductionMelissa Goodhead, BSc, RACMelissa Goodhead, BSc, RACGroup Director, Regulatory Affairs / Group Director, Regulatory Affairs / Quality AssuranceQuality AssuranceSomerset PharmaceuticalsSomerset Pharmaceuticals

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FDA QuestionsFDA Questions

Do the available data for the EMSAM 20 mg Do the available data for the EMSAM 20 mg patch support the reasonable safety of this patch support the reasonable safety of this formulation without the need for dietary formulation without the need for dietary restrictions?restrictions?

If the EMSAM 20 mg patch formulation could be If the EMSAM 20 mg patch formulation could be considered reasonably safe for marketing considered reasonably safe for marketing without the need for dietary restrictions, would without the need for dietary restrictions, would it be acceptable to market the 20 mg patch it be acceptable to market the 20 mg patch without dietary restrictions and at the same without dietary restrictions and at the same time require dietary restrictions for the 30 and time require dietary restrictions for the 30 and 40 mg patch strengths?40 mg patch strengths?

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Selegiline – Presentation AgendaSelegiline – Presentation Agenda

OverviewOverview . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . .

Safety Safety –– Tyramine Tyramine . . . . . . . . .. . . . . . . . .

Physician & PatientPhysician & PatientAwareness Program Awareness Program . . . . . . .. . . . . . .

Conclusion Conclusion –– Q&A Q&A. . . . . . . . . . . . . . . . . .

Sheldon Preskorn, MDSheldon Preskorn, MD

Lawrence F. Blob, MDLawrence F. Blob, MD

Chad VanDenBerg, PharmDChad VanDenBerg, PharmD

Melvin Sharoky, MDMelvin Sharoky, MD

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OverviewOverviewSheldon Preskorn, MDSheldon Preskorn, MDChairman, Department of PsychiatryChairman, Department of PsychiatryUniversity of Kansas, WichitaUniversity of Kansas, Wichita

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OverviewOverview

Clinical DepressionClinical Depression

Characteristics of MAOICharacteristics of MAOI

Oral MAOI and tyramineOral MAOI and tyramine

Medical need for MAOI without dietary Medical need for MAOI without dietary modificationsmodifications

Transdermal delivery of MAOITransdermal delivery of MAOI

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Facts About Clinical DepressionFacts About Clinical Depression

High prevalenceHigh prevalence

Significant morbidity and mortalitySignificant morbidity and mortality

Heterogeneous illness: No single antidepressant Heterogeneous illness: No single antidepressant works for every patientworks for every patient

30% do not respond to a series of different 30% do not respond to a series of different antidepressantsantidepressants

Need for additional effective optionsNeed for additional effective options

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Characteristics of Monoamine Oxidase InhibitorsCharacteristics of Monoamine Oxidase Inhibitors

First antidepressantsFirst antidepressants

Established efficacyEstablished efficacy

Affect three neurotransmittersAffect three neurotransmitters

Infrequently used despite their efficacy in Infrequently used despite their efficacy in part because of dietary restrictionspart because of dietary restrictions

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Infrequent MAOI UseInfrequent MAOI Use

IMS 2005 IMS 2005 – 0.1% of all antidepressant – 0.1% of all antidepressant prescriptionsprescriptions

APA guidelines 2000 cite dietary restrictions APA guidelines 2000 cite dietary restrictions as a reason to limit useas a reason to limit use

Surveys have shown dietary restrictions as Surveys have shown dietary restrictions as a major deterrent to MAOI usagea major deterrent to MAOI usage

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MAO in the GutMAO in the Gut

Barrier preventing systemic absorption of Barrier preventing systemic absorption of tyramine tyramine

Virtually impossible to eat enough tyramine Virtually impossible to eat enough tyramine in food to overcome this barrierin food to overcome this barrier

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Oral MAOIs and Dietary TyramineOral MAOIs and Dietary Tyramine

Oral MAOIs substantially inhibit intestinal MAOOral MAOIs substantially inhibit intestinal MAO

Tyramine can enter systemic circulationTyramine can enter systemic circulation

Systemic tyramine causes release of NESystemic tyramine causes release of NE

Large dose of tyramine can cause dramatic Large dose of tyramine can cause dramatic rise in blood pressure via NErise in blood pressure via NE

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Hypertensive CrisisHypertensive Crisis

Not Not chronic or essential hypertensionchronic or essential hypertension

Medical emergency requiring immediate Medical emergency requiring immediate treatmenttreatment

Acute elevation in BP >180/120 mmHg leading Acute elevation in BP >180/120 mmHg leading to end-organ damageto end-organ damage

Tyramine-induced hypertensive crisisTyramine-induced hypertensive crisis

– onset between 10 minutes and 2 hours onset between 10 minutes and 2 hours after mealafter meal

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Current MAOI Diet RecommendationsCurrent MAOI Diet Recommendations

Avoid high tyramine foodsAvoid high tyramine foods

– Aged cheesesAged cheeses

– Fermented or spoiled meats Fermented or spoiled meats

– Some yeast extracts (e.g., marmite) Some yeast extracts (e.g., marmite)

Maximum tyramine content meal: 40 mg tyramineMaximum tyramine content meal: 40 mg tyramine

The need for the diet and the potential risk of The need for the diet and the potential risk of hypertensive crisis discourages MAOI usehypertensive crisis discourages MAOI use

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The Clinical NeedThe Clinical Need

The efficacy of the oral MAOIs without the The efficacy of the oral MAOIs without the need for a tyramine-restrictive dietneed for a tyramine-restrictive diet

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Oral versus Transdermal DeliveryOral versus Transdermal Delivery

20 mg 20 mg patchpatch

skinskin

Oral MAOI Transdermal Selegiline

16Mawhinney et al. Mawhinney et al. J Pharm PharmacolJ Pharm Pharmacol 2003. 2003.

Inhibition of MAO by Selegiline in Guinea Pigs Inhibition of MAO by Selegiline in Guinea Pigs

CortexCortex

Oral SelegilineOral Selegiline Transdermal SelegilineTransdermal Selegiline

DuodenumDuodenum LiverLiver

Per

cen

tag

e in

hib

itio

nP

erce

nta

ge

inh

ibit

ion

Daily dose (mg/kg)Daily dose (mg/kg)

0.10.1 1.01.0 10.010.0 100100

1010

2020

3030

4040

5050

6060

7070

8080

9090

100100

Daily dose (cmDaily dose (cm22/24 h)/24 h)

1010

2020

3030

4040

5050

6060

7070

8080

9090

100100

Per

cen

tag

e in

hib

itio

nP

erce

nta

ge

inh

ibit

ion

0.40.4 0.710.71 1.01.0 1.51.5 2.02.0 2.52.5

Can the 20 mg transdermal delivery system Can the 20 mg transdermal delivery system for selegiline provide antidepressant for selegiline provide antidepressant efficacy without the need for dietary efficacy without the need for dietary modification?modification?

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Positive Placebo-controlled Efficacy TrialsPositive Placebo-controlled Efficacy Trialswith Transdermal Selegilinewith Transdermal Selegiline

E106E106 P0052P0052 P9806P9806

DurationDuration 6 weeks6 weeks 8 weeks8 weeks 52 weeks52 weeks

NN 176176 265265 322322

EMSAM EMSAM DoseDose 20 mg20 mg 20, 30, or 40 20, 30, or 40

mgmg 20 mg20 mg

Primary Primary EndpointEndpoint

HAMD-17HAMD-17p = 0.018p = 0.018

HAMD-28HAMD-28p = 0.033p = 0.033

K-M RelapseK-M Relapse††

p = 0.006p = 0.006

††K-M Relapse = Kaplan Meier time to relapse analysis

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Safety – TyramineSafety – TyramineLawrence Blob, MDLawrence Blob, MDMedical Director, Medical Director, Somerset PharmaceuticalsSomerset Pharmaceuticals

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Safety of Transdermal Selegiline Safety of Transdermal Selegiline

Oral selegiline: 16 years of safe use withOral selegiline: 16 years of safe use withnormal dietnormal diet

Tyramine challenge program shows oral and Tyramine challenge program shows oral and transdermal selegiline have equally low transdermal selegiline have equally low intestinal MAO inhibitionintestinal MAO inhibition

Food challenges demonstrate tyramine safety of Food challenges demonstrate tyramine safety of 20 mg transdermal selegiline20 mg transdermal selegiline

Phase III safety data found no hypertensive Phase III safety data found no hypertensive crises in 2,503 MDD patients at 20, 30, and 40 mgcrises in 2,503 MDD patients at 20, 30, and 40 mg

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10 mg Oral and 20 mg Transdermal Selegiline10 mg Oral and 20 mg Transdermal Selegiline

Same active ingredientSame active ingredient

Unlike oral, transdermal selegiline achieves Unlike oral, transdermal selegiline achieves antidepressant levels in CNS antidepressant levels in CNS

Like oral, transdermal maintains the intestinal Like oral, transdermal maintains the intestinal barrier to tyraminebarrier to tyramine

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Safety of Oral Selegiline (Eldepryl) Safety of Oral Selegiline (Eldepryl)

16 years of safe use in Parkinson’s disease16 years of safe use in Parkinson’s disease

– Approved in 1989Approved in 1989

– No dietary modificationsNo dietary modifications

– 1.5 million patients exposed1.5 million patients exposed

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AERS & IMS Health Records for Oral SelegilineAERS & IMS Health Records for Oral Selegiline

Pharmacovigilance data (1997-2005)Pharmacovigilance data (1997-2005)

Rate of hypertensive crisis per 100,000 Rate of hypertensive crisis per 100,000 exposure-yearsexposure-years

EldeprylEldepryl ParnateParnate

1.561.56 43.3643.36

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AERS: 4 Reports of Hypertensive CrisisAERS: 4 Reports of Hypertensive Crisis

3 determined not related to tyramine3 determined not related to tyramine

– Case 1: tolcapone, levodopa, carbidopa, Case 1: tolcapone, levodopa, carbidopa, bromocriptine, ropinirole bromocriptine, ropinirole

– Case 2: ephedrine, theophylline, Case 2: ephedrine, theophylline, levodopa, carbidopa, lisuride, maprotilinelevodopa, carbidopa, lisuride, maprotiline

– Case 3: levodopa, bromocriptine, Case 3: levodopa, bromocriptine, talipexoletalipexole

One report: no details availableOne report: no details available

– Must consider tyramine-relatedMust consider tyramine-related Tyramine-related hypertensive crisisTyramine-related hypertensive crisis

– <0.4 per 100,000 exposure-years<0.4 per 100,000 exposure-years

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DATATOP: Controlled Safety Data DATATOP: Controlled Safety Data

Study of oral selegiline and Vitamin E for the Study of oral selegiline and Vitamin E for the treatment of Parkinsonismtreatment of Parkinsonism

N = 800N = 800

2,970 patient-years of exposure2,970 patient-years of exposure

No increase in mortality (2.1%) compared to No increase in mortality (2.1%) compared to a matched population (2.7%)a matched population (2.7%)

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DATATOP:DATATOP:Cardiovascular/Cerebrovascular EventsCardiovascular/Cerebrovascular Events

Incidence perIncidence per1000 patient-years1000 patient-years Oral SelegilineOral Selegiline PlaceboPlacebo

MIMI 6.46.4 8.18.1

CVA / TIACVA / TIA 6.76.7 13.013.0

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Food challenges demonstrate tyramine safetyFood challenges demonstrate tyramine safetyof 20 mg transdermal selegilineof 20 mg transdermal selegiline


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Tyramine Challenge StudiesTyramine Challenge Studies

14 tyramine challenge studies (N=214)14 tyramine challenge studies (N=214)

Time of exposure, up to 96 daysTime of exposure, up to 96 days

Dose (20 to 40 mg transdermal selegiline)Dose (20 to 40 mg transdermal selegiline)

Fasting versus fed conditionsFasting versus fed conditions

Comparator drugs Comparator drugs

– Oral selegiline (Eldepryl)Oral selegiline (Eldepryl)

– Fluoxetine (Prozac)Fluoxetine (Prozac)

– Tranylcypromine (Parnate)Tranylcypromine (Parnate)

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Tyramine Pressor Test ModelTyramine Pressor Test Model

Endpoint: 30 mmHg SBPEndpoint: 30 mmHg SBP

BaselineBaselinetyraminetyraminechallengechallenge

Active Active drugdrugtreatmenttreatment

On-drugOn-drugtyramine tyramine challengechallenge

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Model: Minimum Pressor DoseModel: Minimum Pressor Dose

ExampleExampleMinimumMinimumPressorPressordose 200 mgdose 200 mg

MinimumMinimumPressorPressordose 400 mgdose 400 mg

Minimum Pressor Dose:Minimum Pressor Dose: Smallest oral tyramine dose Smallest oral tyramine dose to cause 30 mmHg SBPto cause 30 mmHg SBP




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Model: Tyramine Sensitivity Factor (TSF)Model: Tyramine Sensitivity Factor (TSF)

Example: Drug 1Example: Drug 1

400/200 = TSF of 2400/200 = TSF of 2






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Model: Tyramine Sensitivity Factor (TSF)Model: Tyramine Sensitivity Factor (TSF)

Example: Drug 2Example: Drug 2MinimumMinimumPressorPressordose 10 mgdose 10 mg


400/10 = TSF of 40400/10 = TSF of 40




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Comparator StudiesComparator Studies

Crossover studiesCrossover studies

– Transdermal selegiline 20 mg vs.Transdermal selegiline 20 mg vs.oral selegiline 10 mg (Eldepryl)oral selegiline 10 mg (Eldepryl)

– Transdermal selegiline 20 mg vs. Transdermal selegiline 20 mg vs. tranylcypromine 30 mg (Parnate)tranylcypromine 30 mg (Parnate)

Negative controlNegative control

– Fluoxetine 60 mg (Prozac)Fluoxetine 60 mg (Prozac)

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TSF: Transdermal 20 mg vs. Oral Selegiline 10 mgTSF: Transdermal 20 mg vs. Oral Selegiline 10 mgMean Pressor DoseMean Pressor Dose(mg Tyramine)(mg Tyramine) 338338 385385

1.75 ± 0.54 1.67 ± 1.04

TransdermalSelegiline

20 mg

Oral Selegiline10 mg

Tyramine Sensitivity

Factor

Crossover data

35

0

2

4

6

8

10


Factor

338338 385385

Fluoxetine60 mg

408408

1.43 ± 0.561.75 ± 0.54 1.67 ± 1.04

TSF of Fluoxetine 60 mgTSF of Fluoxetine 60 mg


20 mg

Oral Selegiline10 mg

Mean Pressor DoseMean Pressor Dose(mg Tyramine)(mg Tyramine)

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0

10

20

30

40

50

60

270270 1010

TSF of Tranylcypromine 30 mg (Parnate)TSF of Tranylcypromine 30 mg (Parnate)


20 mg

Tranylcypromine30 mg

40.00 40.00 ± 7.07± 7.07

1.86 1.86 ± ± 0.420.42



Factor

Crossover data

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TSF Stability Over Time (40 mg dose)TSF Stability Over Time (40 mg dose)

0

5

10

15

20

25

30

35

40

45

50

Tyramine Tyramine Sensitivity Sensitivity

FactorFactor

8484 6666 8888 1010

11.45 ± 6.59 (8.17, 14.73)

11.36 ± 5.13 (8.40, 14.33)

9.33 ± 5.20(5.84, 12.82)

40.00 ± 7.07(34.56, 45.44)

Tranylcypromine30 mg/d

Day 8

Transdermal Selegiline40 mgDay 60

40 mgDay 90

40 mgDay 30


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Pharmacodynamic Effect of Food onPharmacodynamic Effect of Food onPressor Dose Pressor Dose

0

50

100

150

200

250

Pressor DosePressor Dose(mg Tyramine)(mg Tyramine)

Transdermal SelegilineTransdermal Selegiline40 mg40 mg

FastingFasting

Transdermal SelegilineTransdermal Selegiline40 mg40 mg

FedFed

6464 172172Mean Pressor DoseMean Pressor Dose

pp = 0.0023 = 0.0023

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Tyramine Content in a High-Tyramine MealTyramine Content in a High-Tyramine Meal

Sample MealSample MealPortionPortion

(g or mL)(g or mL)Tyramine contentTyramine content

(mg/portion)(mg/portion)

Bottled beerBottled beerSauerkrautSauerkrautBoiled potatoesBoiled potatoesGreen and yellow peppers Green and yellow peppers Roast PorkRoast PorkPepper saucePepper sauceCheeseCheese CamembertCamembert Danish blueDanish bluePinot NoirPinot Noir

700700454454454454250250454454150150

30303030

700700

1.01.016.716.71.91.91.81.83.23.23.03.0

1.41.48.88.82.02.0

Total tyramine in mealTotal tyramine in meal 39.839.8

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0

20

40

60

Transdermal Transdermal SelegilineSelegiline

20 mg21 Days

Tranylcypromine30 mg

1010


Factor

Mean Pressor DoseMean Pressor Dose(mg Tyramine) (mg Tyramine)

TransdermalTransdermalSelegilineSelegiline

20 mg30 Days

204204256256

Pressor Dose Range at Steady State Pressor Dose Range at Steady State

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Safety Margin: 20 mg Transdermal, ExtremesSafety Margin: 20 mg Transdermal, Extremes(Calculated for Fed Conditions)(Calculated for Fed Conditions)

0

20

40

60

80

100

120

140


Tranylcypromine High TyramineMeal

20 mgN = 2

N = 10

Minimum = 125 mgMinimum = 125 mg

Minimum = 25 mgMinimum = 25 mg

40 mg40 mg

TyramineTyramine(mg)(mg)

< 5 mg < 5 mg Tyramine Tyramine Typical Typical MealMeal

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Tyramine Challenge Program ConclusionsTyramine Challenge Program Conclusions

20 mg transdermal and oral selegiline and fluoxetine 20 mg transdermal and oral selegiline and fluoxetine all have similar TSF, about 14-20 times less than that all have similar TSF, about 14-20 times less than that of tranylcypromine of tranylcypromine

40 mg transdermal selegiline has a TSF 4 times less 40 mg transdermal selegiline has a TSF 4 times less than tranylcyprominethan tranylcypromine

Patients taking 20 mg transdermal selegiline will be Patients taking 20 mg transdermal selegiline will be unable to eat enough tyramine-rich food to cause a unable to eat enough tyramine-rich food to cause a hypertensive crisishypertensive crisis

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Phase III SafetyPhase III Safety

Exposure in 2500 patientsExposure in 2500 patients

– 20, 30, 40 mg transdermal selegiline20, 30, 40 mg transdermal selegiline

– No dietary modificationNo dietary modification

No serious adverse events of No serious adverse events of hypertensive crisishypertensive crisis

No deathsNo deaths

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Events of Interest Review ProcessEvents of Interest Review ProcessStep I: Comprehensive Computer Term SearchStep I: Comprehensive Computer Term Search

COSTART terms: Amblyopia, arrhythmia, COSTART terms: Amblyopia, arrhythmia, bradycardia, chest pain, coma, headache (severe), bradycardia, chest pain, coma, headache (severe), hypertension, migraine, neck rigidity, palpitation, hypertension, migraine, neck rigidity, palpitation, stupor, tachycardiastupor, tachycardia

Blood Pressure: Occurrence of blood pressure Blood Pressure: Occurrence of blood pressure 160/100 mmHg anytime during the study 160/100 mmHg anytime during the study

Step II: AlgorithmStep II: Algorithm Any patient with AE term hypertension, migraine or Any patient with AE term hypertension, migraine or

severe headachesevere headache Any AE terms judged at least moderate in intensityAny AE terms judged at least moderate in intensity Any AE requiring treatmentAny AE requiring treatment Occurrence of blood pressure Occurrence of blood pressure 160/100 mmHg 160/100 mmHg

anytime during the studyanytime during the study

Results: No events of hypertensive crisisResults: No events of hypertensive crisis

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Analysis of Blood Pressure Increases in Analysis of Blood Pressure Increases in Placebo-Controlled TrialsPlacebo-Controlled Trials

N = 1430 subjects in controlled trialsN = 1430 subjects in controlled trials

↑↑ 20 mmHg over baseline SBP and SBP >16020 mmHg over baseline SBP and SBP >160

Transdermal SelegilineTransdermal Selegiline PlaceboPlacebo

1.4% 1.4% 1.9% 1.9%

Incidence of AE HypertensionIncidence of AE Hypertension

Transdermal SelegilineTransdermal Selegiline PlaceboPlacebo

0.6% 0.6% 0.7% 0.7%

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Safety ConclusionsSafety Conclusions

20 mg transdermal selegiline is effective and 20 mg transdermal selegiline is effective and safe without dietary modificationssafe without dietary modifications

20 mg transdermal selegiline shows a low 20 mg transdermal selegiline shows a low inhibition of intestinal MAOinhibition of intestinal MAO

– Equivalent to 10 mg oral selegiline and Equivalent to 10 mg oral selegiline and 60 mg fluoxetine60 mg fluoxetine

No hypertensive crisis in Phase III programNo hypertensive crisis in Phase III program

Education program will instruct physicians and Education program will instruct physicians and patients on proper use of drugpatients on proper use of drug

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Provider / Patient AwarenessProvider / Patient AwarenessChad VanDenBerg, Pharm.D., BCPPChad VanDenBerg, Pharm.D., BCPPDirector, Clinical Affairs & Product InformationDirector, Clinical Affairs & Product Information

Somerset Pharmaceuticals, Inc.Somerset Pharmaceuticals, Inc.

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FDA Question #2FDA Question #2

If the EMSAM 20 mg patch formulation could be If the EMSAM 20 mg patch formulation could be considered reasonably safe for marketing considered reasonably safe for marketing without the need for dietary restrictions, would without the need for dietary restrictions, would it be acceptable to market the 20 mg patch it be acceptable to market the 20 mg patch without dietary restrictions and at the same without dietary restrictions and at the same time require dietary restrictions for the 30 and time require dietary restrictions for the 30 and 40 mg patch strengths?40 mg patch strengths?

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Education PlanEducation Plan

Goal: 100% awareness of the need for dietaryGoal: 100% awareness of the need for dietarymodifications at the higher strengthsmodifications at the higher strengths(30 and 40 mg patches)(30 and 40 mg patches)

Major elementsMajor elements Multiple education and outreach toolsMultiple education and outreach tools

– PrescribersPrescribers

– PharmacistsPharmacists

– PatientsPatients Uniquely designed packagingUniquely designed packaging

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Objective and ConsiderationsObjective and Considerations

Primary ObjectivePrimary Objective

– Dietary modification instructionsDietary modification instructions

Implementation ConsiderationsImplementation Considerations

– Prevent simultaneous use of multiple Prevent simultaneous use of multiple patchespatches

– Appropriate titration instructionsAppropriate titration instructions

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Study of Physician and Patient Comprehension Study of Physician and Patient Comprehension of the Need for Dietary Modificationsof the Need for Dietary Modifications

MethodologyMethodology

75 Physicians75 Physicians

– Psychiatrists and primary care physiciansPsychiatrists and primary care physicians

70 Patients70 Patients

Results after only one exposure Results after only one exposure

96% of physicians and 94% of patients correctly 96% of physicians and 94% of patients correctly identify the need for dietary modifications at higher identify the need for dietary modifications at higher dosesdoses

Plan calls for multiple exposuresPlan calls for multiple exposures

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Prescriber EducationPrescriber EducationKey ElementsKey Elements

Instructions for appropriate product usage Instructions for appropriate product usage consistent with labelconsistent with label

Patient education materialsPatient education materials Verbally communicateVerbally communicate

– Use as prescribedUse as prescribed

– Apply one patch at a timeApply one patch at a time

– Stay on modified diet for two weeks after Stay on modified diet for two weeks after discontinuationdiscontinuation

Write Write dietary modificationsdietary modifications requiredrequired on prescriptions on prescriptions

Continual Monitoring Continual Monitoring Bi-weekly assessment of awareness and practicesBi-weekly assessment of awareness and practices

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Pharmacist EducationPharmacist Education

Key Elements Key Elements

Educational programs including Educational programs including teleconferences and mailingsteleconferences and mailings

Up-to-date product information available Up-to-date product information available through 3rd party data sourcesthrough 3rd party data sources

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Patient EducationPatient Education

Patient education materialsPatient education materials

Patient information leaflet Patient information leaflet

Patient starter packPatient starter pack

EMSAM websiteEMSAM website

Dietary Modifications RequiredDietary Modifications Required

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Pharmacovigilance ProgramPharmacovigilance Program

Education and outreach program Education and outreach program

Pharmacovigilance procedures and reportingPharmacovigilance procedures and reporting

Targeted follow up on specific adverse eventsTargeted follow up on specific adverse events

– Hypertensive crisis and other CV eventsHypertensive crisis and other CV events

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Provider / Patient Awareness SummaryProvider / Patient Awareness Summary

Multi-faceted planMulti-faceted plan

Enhanced education programEnhanced education program

– PrescribersPrescribers

– PharmacistsPharmacists

– PatientsPatients

Distinctive packagingDistinctive packaging

Enhanced pharmacovigilanceEnhanced pharmacovigilance

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ConclusionsConclusionsMelvin Sharoky, MDMelvin Sharoky, MDCEO and PresidentCEO and President

Somerset Pharmaceuticals, Inc.Somerset Pharmaceuticals, Inc.

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1 selegiline transdermal system (sts) fda psychopharmacologic drugs advisory committee october 26,...

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