5/13/2018 Scan 1003

1/7

SUSPECT REACTION REPORT ClaMS FORM

REACTION INFORMATION1. PAnENT INITIALS 11A. COUNTRY

United States 12 AGE YR~:I 3. SEXj a-s , REACTION ONSET

UN1 M J 20117. DESCRIBE REACnON(S)DIABETES MELLITUS; MUSCULAR WSAKNESS; PARAESTHESIAThis is a Non-Interventional Study report from the markl"ting program Pfizer HelpfulAnswers with information provided by a contactable consumer. This report was part ofa post-marketing surveillance program.A male consumer of unknown age and race with cholesterol high, chronic obstructivepulmonary disease and emphysema, started to receive ezetimibe 10 mg for heartcondition (total daily dose not reported). Additional suspect products includedprednisone 40 m e six times a day for emphysema, albuterol sulfate O.83~ of 2.5 mgfor COPD, arforrnoterol tartrate (BROVANA) 15 mcg/2 ml for COPD, budesonide(PULMICORTI 5 mg/2 ml for COPD, fluoxetine hydrochloride (PROZAC) 20 mg for anunknown indication, clonazepam (KLONOPIN) 5 mg for an unknown indication, metoprololsuccinate (TOPROLI 25 mg for heart condition. aspirin 81 mg for heart condition andatorvastatin (LIPITOR) 40 mg daily on an unknown date five years ago for highcholesterol and tiotropium bromide (SPIRIVA) 18 mcg inhalation powder daily in themorning, on an unknown date for chronic obstructive pulmonary disease (COPDI, all

(Conttnued on Additional Paqe)13. RELEVANT TESTM.ASORATORY DATANone

a-n LIST ALL APPROPRIATE RESPONSES (DIED: RESULTEOIN. OR PROlONGED. INPATIENT HOSPITALIZATION: RESULTED IN SEVERE 0R PERMANENT OISABIUTY: LIFE THREATENlNG; NONE Of THE ABOVE.)

10. Resultedn severe orpermanent disability.Other Important Medical Event.

II. SUSPECT DRUG(S) INFORMATION14 . SUSPECT ORUG(S) (INCLUDE GENERIC NAME). 20. DID REAcnON ABATE# 1 TAB ezetimibe M2 TAB atorvastatin calcium AFTER STOPPING ORUG7# 1 UNK #2 UNK(Continued on Additional Page)15.DAILY DOSE(S). 116. ROUTE(S)OF ADMINSTRAnON.#1 Unk #2 4 0 m gJ 1X #1 PO #2 Unk17. INOICAnON(S) fOR USE. 21.010 REACTIONS REAPPEARAFTER REINTROOUCTION?# 1Cardiac disorder #2 Cholesterol high # 1 N/A #2 UNKie. THERAPY OATES (FROMITO) 119. THERAPY DURATION.# 1 Unk -Cant #2 Unk -cont #1 Unk #2 UnkIII. CONCOMITANT DRUG(S) AND HISTORY22. CONCOMITANT DRUG(S) ANO DATE OF AOMlNISTRAnON (EXClUDE THOSE USED TO TREAT REACnON)

None

23 . OTHER RELEVANT HISTORY (E.G. DIAGNOSIS, A lLERGIES. PREGNANCY WITH LAST MONTH OF PERIOD ETC.) SEE ATTACH EOPAGE(S)CONCURRENT CONDITIONS; Cholesterol high; Chronic obstructive pulmonary disease; Emphysema

IV. ONLY FOR REPORTS SUBMITTED BY MANUFACTURER26. NAME AND ADDRESS OF' REPORTERV. INITIAL REPORTER (i n confidence)

24 . MFR Merck Sharp & OohmeDivision of Merck & Co, Inc.West Point, Pa. 19486 Attn: World Wide Product Safety

j 24A. MFR CONTROL NO.WAES 1105USA03728248. .DATE RECV BYMFR

25MAY11 124C. REPORT SOURCEStudy, Consumer

DATE OF THIS REPORT I 25. REPORT TYPE

5/13/2018 Scan 1003

2/7

WAES NUMBER 1105USA03728 PageCONTINUED)

Reaction Information7. Describe Reaction(s)

from an unknown date.There was no medical history or concomitant medications.On an unknown date in 2011, the consumer experienced muscle problems in his legs described as atingling sensation, tiredness and weakness in his legs, and stated he could not walk too much or doexercises. The consumer was not sure which medication was causing him the muscle problem. He statedthat he consulted his physician who mentioned it was due to prednisone, but the consumer was notsure about this. The consumer also mentioned that he developed diabetes due to prednisone on anunknown date and took insulin as a therapeutic measure. The dosage of prednisone was decreased to40 mg two times a day. Therapy was unchanged for remaining suspect products. At the timeof the report, the consumer had not recovered from the eventsMuscle problems in his legs described as a tingling sensation, tiredness and weakness in his legsand diabetes were considered to be disablingMuscle problems in his legs described as a tingling sensation, tiredness and weakness in his legsand diabetes were considered to be other important medical events.The reporting investigator felt that ezetimibe was considered suspect medication for muscleproblems in his legs described as a tingling sensation, tiredness and weakness in his legs anddiabetes.

Additional information has been requested.

Suspect Therapy/Dose14-21. Suspect Drug(s)

#3 POWD tiotropium bromide18 microgm!lXIndication/Start Stop Date DurationChronic obstructive pulmonary diseaselink - Cont UnkEmphysemaUnk - Cant Unkcardiac disorderUnk - Cont UnkChronic obstructive pulmonary diseaseUnk - Cant UnkChronic obstructive pulmonary diseaseUnk - Cont UnkChronic obstructive pulmonary diseaseUnk - Cont UnkUnknownUnk - Cant UnkunknownUnk - Cont UnkCardiac disorderUnk - Cont Unk

RouteINH

#4 prednisone40 mg/link

Unk

#S aspirin81 mg/link link

#6 albuterol sulfatelink link

#7 arformoterol tartratelink link

#8 budesonideUnk link

#9 fluoxetine hcl20 mg/Unk link

#10 clonazepam5 mg/Unk unk

#11 metoprolol succinate25 mg/Unk link

20. Did reaction abate after stopping drug?#3 UNK#4 liNK#5 UNK#6 UNK#7 liNK#8 UNK#9 liNK#10 UNK#11 UNK

2

5/13/2018 Scan 1003

3/7

WAES NUMBER 1105USA03728 (CONTINUED)

21. Did reactions reappear after reintroduction?#3 UNKil4 UNKff5 UNK~6 UNK#7 UNK#8 UNK#9 UNK#1 0 UNK#11 UNK

Page 3

5/13/2018 Scan 1003

4/7

THE DEVELOPMENT SERVICES COMPANY

Drug Safety Services, EuropeCovance Clinical and PeriapprovalServices LtdCompass HouseManor Royal. CrawleyWest Sussex RH10 9PYTel: +44 (D) 1293 58580DFax: +44 (0) 1293585847

cov~Dr. Doina AndreiCentrul Medical de Diagnostic si Tratament Ambulator Neomed SRL, Medicina Internastr. Crisului, Nr. 1, bl 1, sc C. ap.2.Brasov500283Romania20 July 2011Dear Dr. Andrei,MK-0653C-162 : A Randomized, Double-Blind, Active-Controlled, Multicenter Study of Patients with PrimaryHypercholesterolemia and High Cardiovascular Risk Who Are Not Adequately Controlled with Atorvastatin 10mg: A Comparison of the Efficacy and Safety of Switching to Coadministration Ezetimibe and AtorvastatinVersus Doubling the Dose of Atorvastatin or Switching to Rosuvastatin

Covance Drug Safety Services would like to notify you, on behalf of Merck, of the following suspected unexpectedserious adverse reaction(s) which has occurred in a patient receiving the same study medication as patients in a trialconducted at your site.Where required by national legislation, Covance DSS has notified the Central Ethic Committee in your country ofthis/these reports.

Protocol Country of Initial 0,- Date ofNumber Adverse Event PatientID MCN Incidence Follow-Up ReportN/A Myalgia; Hypertension; Thyroid N/A 1107USAO 1344 United States Initial 181ul-11Disorder

The enclosed report{s) should be filed in your Investigator's Brochure.If you have any questions, please contact Damon Hughes, Covance DSS EU Project Manager on +44 (0) 1293585894Yours sincerely,Covance Drug Safety ServicesENC: Dear Doctor letter x 1 (1 pages)

CIOMS x 1 (2 pages)

5/13/2018 Scan 1003

5/7

IS-JuI-20ll Re-'iltr"ict.-dR to c:o.,f"Ki..,t",1~redacce:s-s:e: ezetimibe

Dear Doctor:This letter is to notify you of an adverse experience which has been reported to usconcerning ezetimibe.

In accordance with the International Conference of Harmonization (lCH) Good ClinicalPractice Guidelines, sponsors must notify all concerned investigators (ie, aninvestigators participating in any ongoing study with the drug) of serious, unexpectedadverse experience reports occurring in a clinical study when either the reportinginvestigator or the sponsor believes that there is a reasonable possibility that theexperience may have been drug related or if the drug relationship is unknown.In compliance with these requirements, the enclosed report is provided for yourinformation.Please append this report to the Confidential Investigator's Brochure for the appropriateinvestigational product or to the Product Circular for the appropriate marketed productand retain in your files.Please submit a copy of this report promptly (within less than 30 days of receipt) to yourEthics Review Board(s) even though the report may not involve a patient in your study.This report does not necessarily reflect a conclusion by Merck that the drug caused orcontributed to the adverse experience. If you have any questions, please contact theMerck monitor for your study.

'Serious adverse experiences that may have been drug related or if the drug relationship is unknown:Hypertension, Myalgia, Thyroid disorder

Enclosure(s):WAES# 1107USA01344GENSTUDY#AN#

5/13/2018 Scan 1003

6/7

SUSPECT REACTION REPORT ClaMS FORM

REACTION INFORMATION" PAltoN INI IAlSI lA. COUNTRY

United States 12, AGE YRSI 3, S t1 4-6. REACTION ONSET

65 yrs j r - . 1 _ 1 Unk7. DESCRIBE REACllON(S)MYALGIA; HYPERTENSION; THYROID DISORDERThis report "'asreceived from Pfizer and was assigned manufacturer control#2011138460 for atorvastatin calcium (LIPITOR)_This is a nan interventional study report from the marketing program PfizerAdherence Based Contracting Program (Schedule2), The pharmacist reported for a 65year old male patient who on an unspecified date was prescribed atorvastatin calcium(LIPITOR), 10 mg (daily dose, duration and indication not reported) and withina fewdays developed muscle aches and tiredness, The patient told the doctor about thisand the doctor told patient to stop taking the atorvastatin calcium (LIPITOR) andswitched him to ezetimibe (dose, duration and indication not reported)It was reported that the patient was not able to tolerate that medication as well,At the t.imeof the report, the patient was currently only taking over the counter(arC) fish Oil and garlic and watching his diet, At the time of the report thepatient was still ha.vingmuscle pains in his legs, It: was suggested that the patient

(Continued on Addit ional Pace)13, RELEVANT TESTSJ\..ABORATDRY DATAUnknown

8-12, usr ALL APPROPRIATE RESPONSES (OlEO; RESULTED IN, OR PROLONGED, INPATIENT HOSPITAlIZATION; RESULTEO IN SEVERE 0R PERMANENT DISABILITY; LIFE THREATENING; NONE OFTHE ABOYE.)

Other Importantedical Event.

II SUSPECT DRUG(S) INFORMATION14, SUSPECTDRUG(S) (INClUOE GENERIC NAME), 20, DID REACTION ABATE# 1 T AS ezetimibe # 2 atorvastatin calcium AFTER STOPPING DRUG?# 1 NO .'1 UNK15, DAILY DOSEIS), I 16.ROUTE(S) OF AQMINSTRATION,# 1 10 mglUnk #2 10 mg/Unk #1 PO #2 Unk17, INDICATION(S) FOR USE, 21. DID REACTIONS REAPPEARAFTER REINTRODUCTION?#1 Unknown #2 Unknown # 1 NJA #2 UNK18, THERAPY OATES (FROMfTO) I 19, THEKAJ-'Y DURATION,#1 Unk -Unk #2 Unk -Unk #1 Unk # 2 UnkIII, CONCOMITANT DRUG(S) AND HISTORY22. CONCOMITANT DRUG(S) AND DATE OF ADMINISTRATION (EXCLUOE THOSE USED TO TREAT REACTION)

Unknown

23, OTHER RELEVANT HISTORY (E.G, DIAGNOSIS, AlLERGIES, PREGNANCY WITH LAST MONTH'OF PERIOD ETC.) SEE ATTACHED PAGElS)Unknow'Jl

IV. ONLY FOR REPORTS SUBMITTED BY MANUFACTURER26. NAME AND ADDRESS OF REPORTERV, INITIAL REPORTER (in confidence)

24, MFR Merck Sharp & DohmeDivision of Merck & Co, Inc.West Point, POI, 19486 Attn: World Wide Product Safety

124A . MFR CONTROL NO,

WAES 1107USAOI34424B . DATE REC 'V BY MFR I 24C. REPORT SOURCE

11JUl11 Study, Health ProfDATE OF THIS REPORT 1 2 5 , REPORT TYPE

5/13/2018 Scan 1003

7/7

WAES NUMBER 1107USA01344 PageCONTINUED)

Reaction Information7. Describe Reaction(s)

contacted the doctor and may w2nt to do blood work It was .alsD reported that lhe: p.;tient hadF-atient had thyroid issues and high blood pressure.Muscle pain in legs, high bloDd pressure and thyroid issues were considered to be other impDrtantmedical events and ""ere related to therapy with atorvast.:a.tin calcium (LIPI"IOR) and ezecimibe.No further information is available.

2