Prof. Dr.
F. Cankat Tulunay
President of Turkish ISPOR and Clinical Pharmacological Society
Honorary President of EACPT
20...
LEVENT KAMACIK’IN
ANISINA
WHAT IS CHANGED
1969-2009
2009
Türkiye
İlaç Çöplüğü oldu
Çalışma ve Sosyal Güvenlik Bakanı
Ömer Dinçer
• İlaç sektörü pahalı ilaç veriyor
Sağlık hizmetlerindeki miktarların ciddi ...
Sağlıkta 3 milyarlık tasarruf yapılacak
(İlaç Sektörünün Gözü Aydın!!)
Dinçer,alınacak önlemlerin toplamının 3 milyar TL o...
2009
Türkiyede halen
Antidotlar yok,
tiyazit diüretik bile
Türkiyede yetim kaldı!!
9.12.2001, Milliyet
NO COMMENT!
Eşdeğer ilaçlar!!!!
ÖRNEKLER GELİYOR!!!
Medication error
• Medication errors affecting
at least 1.5 million people
every year
• In USA 98.000death/year
due to med...
Nonprescription drug-related problems and pharmacy
interventions
LO. Westerlund ve ark., Ann Pharmacother, 35: 1343-1349, ...
Principles of Conservative Prescribing
When you start one, choose wisely
Beware of indication creep!!!!
Lyrica® Diabetic n...
MOH
DRUG
COMPANIES
PATIENTSACADEMICIANS
SOCIAL
SECURIT
AGENCY
PHARMACISTS
DOCTORS
F.C. Tulunay, 2009
Drug expenditure
European avarage
200 USD / Person
Turkey
40 USD / Person
Reality...
logical expenditure
Waste
With permis...
Waste
TURKISH MARKET
2
BİLLİON
DOLLAR
12
BİLLİON DOLLAR
ARAŞTIRMACI-KLİNİSYEN FARKI
KLİNİK FARMAKOLOG
• Kontrollu kinik çalışmaları
değerlendirir
• Geniş araştırma
yapar,İstatist...
GSK: Allen ROSES
• VICE PRESIDENT OF GSK,
HAS ADMITTED THAT MOST
PRESCRIPTION MEDICINES
DO NOT WORK ON MOST
PEOPLE WHO TAK...
• DRUGS FOR ALZHEIMER'S DISEASE
WORK IN FEWER THAN ONE IN THREE
PATIENTS,
• WHEREAS THOSE FOR CANCER ARE
ONLY EFFECTIVE IN...
Corrupt drug company GlaxoSmithKline...
http://littlemountainhomeopathy.wordpress.com/2009/10/22/corrupt-drug-company-glax...
YABANCI İLAÇ FİRMALARI NE
KADAR DÜRÜST? (Multinational companies: How honest?)
0
10
20
30
40
50
60
ÇOK
DÜRÜST
ORTA
DÜRÜST
...
15.10.2009, RX MEDIA
Efficacy, safety, and cost of new anticancer drugs
Silvio Garattini, director and Vittorio Bertele', head, regulatory poli...
Critical Drug Evaluation of New Cancer
Drugs
The Scottish Experience
Prof Ken Paterson
Chair – Scottish Medicines Consorti...
SMC and Anti-Cancer Medicines
• 61 cancer medicines reviewed
– 36 for advanced/metastatic cancer
– 25 for earlier/adjuvant...
What does this Mean?
• Median health gain
– 6 months with quality of life 70% of normal
• Mean health gain
– 8-9 months wi...
Is There No Good News- 1?
• Some of the greatest health-gains are with
really innovative drugs –
– Trastuzumab – 2.4 QALYs...
Is There No Good News – 2?
• Anti-cancer drugs are much like other
drugs
– Musculoskeletal (11) – 0.66 QALY
– Infections (...
How Good are New Drugs?
• 22% offer no health gain (=me too!)
28% offer >0 – 0.1 QALY
25% offer >0.1 – 0.5 QALY
13% off...
FOLOTYN
• FOLOTYN is a folate analogue metabolic inhibitor indicated for the treatment of
patients with relapsed or refrac...
• U.K. rejected NEXAVAR for
liver cancer
• Nexavar was estimated to
cost 65,900 pounds
($102,000) for every “quality
adjus...
NEXAVAR?? (1month cost is 8.270 TL=5.500 USD)
Which one is wright!!??
• Bayer, Onyx Pill Doesn’t Slow Breast
Cancer in Stu...
SUTENT
• Costs
• Sunitinib is marketed by Pfizer as Sutent, and is subject to patents and
market exclusivity as a new chem...
39
Wall Street Journal
Oct. 4, 2008
 A prominent Emory University psychiatrist
failed to tell the school about $500,000 he
r...
Dr. Nemeroff served from 2003 until this
past summer as the primary investigator on
a collaborative grant between Emory, G...
Pfizer Paid for Doc's Helicopter in Off-
Label Geodon (ZELDOX) Push, Suit Claims
• Mark R. Westlock (worked for Pfizer) al...
GSK
n COURT EXPOSED GSK/RESEARCHERS FRAUD
The court documents released as a result of one of the
lawsuits in October 2008 ...
Drugs Giants GlaxoSmithKline In
Iraq Probe
• Pharmaceutical companies
GlaxoSmithKline and AstraZeneca have
been linked to ...
10.000 USD/18 months
REGULATORY AGENCIES
PHYSICIANS
INDUSTRY
PHARMACYST
PATIENTS
RATIONAL DRUG USE
Hastaların klinik ihtiyaçlarına
göre, ihtiyaç duyduğu dozda,
sürede ve kendisi ve toplum
için en ucuz ma...
WHO advocates 12 key interventions to
promote more rational use:
1 Establishment of a multidisciplinary national body to c...
Is there an EVİDENECE-BASED
pharmacotherapy?
PHARMACOTHERAPY
EVIDENCE BASED
PHARMACOTHERAPY
OR
FRAUD BASED
PAHARMACOTHERPY?
STAR
MİLLİYET
FEAR BASED MARKETING !!!
Sadece 25 milyon!
Domuz gribi için Türkiye’ye 25 milyon aşı geliyor.
Sağlık Bakanlı...
• H1N1 Pandemic Vaccine
• “It’s unethical to recommend a vaccine
which hasn’t even received the usual
minimal safety testi...
H1N1 Vaccine To Cost Countries
$2.50 - $20 Per Dose
The H1N1 (swine) flu vaccine will cost countries
between $2.50 and $20...
Urgent lawsuit filed against FDA to
halt swine flu vaccines; claims FDA
violated federal law (October 09, 2009 )
Health fr...
Another
GARDASİL.... 806 TL
CERVARIX.... 734 TL
!
Gardasil & Merck
 For Immediate Release, May 23, 2007; Contact: Press Office
202-646-5188
 There have been 3,461 reports...
8 October 2009, BMJ 2009;339:b3884
Cost effectiveness analysis of including boys in a human
papillomavirus vaccination pro...
Hysteria over genital warts?
New York Times,2008
•
In a New York Times article published last year, Dr. Harper spoke about...
Top researcher who worked on cervical
cancer vaccine warns about its dangers
8.10.2009 www.NaturalNews.com
• One of the ke...
Press Release For immediate release
9th October 2009
ALLIANCE FOR NATURAL HEALTH CALLS FOR AN URGENT
SCIENTIFIC INQUIRY IN...
Merck Paid for Medical ‘Journal’ Without
Disclosure, May 14, 2009.....
Merck published fake journal 30th April 2009 ...
Fr...
New Merck Allegations: A Fake Journal;
Ghostwritten Studies; Vioxx Pop Songs; PR Execs
Harass Reporters
New Merck Allegations: A Fake Journal;
Ghostwritten Studies; Vioxx Pop Songs; PR Execs
Harass Reporters
 Baystate Tıp Merkezi Ağrı merkezinin önde gelen
isimlerden olan Dr. Scott S. Reuben’in 2002-2008
arasında yayınladığı 21...
Do Not Use : Generic drug name: montelukast
Brand name: SINGULAIR (Merck)
Do Not Use : Generic drug name: zafirlukast
Bran...
• Aspects of ordinary life, such as menopause, being medicalised;
• Mild problems portrayed as serious illnesses, as has o...
The making of a disease: female sexual
dysfunction
Ray Moynihan, BMJ 326 4 JANUARY 2003
Is a new disorder being identified...
SELLING SICKNESS: THE PHARMACEUTICAL INDUSTRY AND DISEASE
MONGERING
RAY MOYNIHAN, IONA HEATH, DAVID HENRY, BMJ 2002;324:88...
GIVING LEGS TO RESTLESS LEGS: A CASE STUDY OF HOW THE MEDIA HELPS
MAKE PEOPLE SICK
STEVEN WOLOSHIN, LISA M. SCHWARTZ, PLOS...
Medical journals and pharmaceutical companies: uneasy bedfellows
Richard Smith, editor
BMJ 2003;326:1202-1205 (31 May)
• F...
Senator Moves to Block Medical
Ghostwriting
A growing body of evidence suggests that doctors at some of
the nation’s top m...
Senator Moves to Block Medical
Ghostwriting
The documents offer a look at the inner workings of DesignWrite, a
medical wri...
Definitions:
Guest and Ghost writers
In their earlier survey, published in JAMA in 1998, the authors
spell out their defin...
WYETH “PROJECT ASSIGNMENT FORM”
NAME: Steven W. Gutkin
PROJECT: #8231: Manuscript on "Can a Healthy Endothelium Influence ...
October 13, 2000
Steven W. Gutkin
22 Monhegan Avenue, Oakland, NJ 07436-4025
Dear Steve:
Thank you for tackling the Koh pa...
Ghostwriter Budget
Preclinical manuscript………. $10,000
Clinical manuscript…………… $16,000
Review article………………….. $20,000
Pos...
Pfizer Pays $2.3 Billion to
Settle Marketing Case
• WASHINGTON — The pharmaceutical
giant Pfizer agreed to pay $2.3 billio...
PFIZER AND FRAUD
 Pfizer to pay record $2.3 billion settlement for illegal drug promotion - (ABC
News)
 Pfizer completes...
AKIL
ALMAZ İŞLER..????
PARANTERAL MELOXICAM
Only reimbursable in Turkey
Treatment of OA symptoms?
It is not analgesic!
Symptomatic treatment of p...
Dr. Frank DEGNER
Medical Department, Boehringer Ingelheim, Germany,
COX concept: MELISSA and SELECT report,
1998
15 mg Mel...
ETOL, NOBEL
ETODİN, ULKAR (NOBEL)
400 mg etodolac
PFIZER
ETODOLAC USA !
Lodine, may cause serious CV side
effects, such as MI or stroke, which
may result in hospitalization and ev...
Indication: Skin
and complicated
intraabdominal
infections
560 EURO
MİGREN PROFLAKSİSİ
TOPAMAX
100 mg/gün
DEPAKİN
500 mg/gün
DİDERAL
40 mg/gün
Kutu 184.321.000 16.392.000 3.827.000
1 aylık t...
Topiramate in migraine prophylaxis--results from a placebo-
controlled trial with propranolol as an active control.
Diener...
FDA Talk Paper
T05-13 April 11, 2005FDA Issues Public Health Advisory for Antipsychotic Drugs used for Treatment of Behavi...
NİDAZOL-M VAJİNAL TABLET
10. GÜN
Units
Year/08
TL
Year/08
US$
Year/08
NIDAZOL M 273.034 741.164 579.309
Ruhsat tarihi:20.7.1999
Acaba o tarihte komisyonda
...
KETEK & SANOFI-AVENTIS
 Hearing on Deadly Drug Tomorrow: Panel Features Drug Maker Sanofi-
Aventis Official, GAP Client w...
5.8 4.1
Times more expencive
Treatment of upper respiratory
infections...
FDA: Ketek (telithromycin)
[UPDATE 03/26/2007] Sanofi-Aventis issued a "Dear Healthcare Professional" letter.
• [Posted 02...
KETEK?????
FDA Restricts The Future Use Of Sanofi-Aventis SA's Antibiotic Ketek
New Package Insert, Or Label, For Ketek Wi...
WHO IS STUPID?!!!!
American patients or Turkish bacterias???
If KETEK doesn’t have any effect on US patients’ acute exacer...
22.29TL 22.29TL
TURKISH TYPE
PHARMACOECONOMY
No comment!
=
42.57 TL
100 puffs
80.82 TL
120 puffs???
+ = 129.37 TL
Is it really equal?
Who is paying for waste of 20 puf...
EMEA, FACTIVE (gemifloksazin)
için negatif fikir beyan etti
Mennarini ruhsat müracaatını geri çekti. Hafif ve orta şiddett...
11.7 x
LYRICA, FDA
• 5.4 Suicidal Behavior and Ideation
• LYRICA, increase the risk of suicidal thoughts or behavior in patients ...
TURKEY
KİLO ARTIŞI, 9% OF PATIENTS,USA
sss
SSRIs
SSRIs= KILLER DRUGS
FULLY REIMBURSIBLE!!
 34 cases of bizarre behavior,
 28 school shootings/incidents,
 46 road rage t...
February
2008
The Physicians' Desk Reference
2009
•
The Physicians' Desk Reference lists the following adverse reactions (side effects) ...
Selective Serotonin Reuptake Inhibitor
(SSRI) Drugs:
More Risks Than Benefits?
Joel M. Kauffman,
Journal of American Physi...
Selective Publication of
Antidepressant Trials and Its
Influence on Apparent
Efficacy
E H. Turner, AM. Matthews, E Linarda...
NICE, 2007
donepezil, galantamine,
rivastigmine for mild to
moderately severe
Alzheimer’s disease
memantine for
moderate...
BIG PHARMA COULD NOT
BUY NICE! 2009
Since May 2006, NICE has refused to fund three drugs – Aricept, Exelon
and Reminyl – f...
Cholinesterase Inhibitors in Mild Cognitive
Impairment: A Systematic Review of
Randomised Trials
Roberto Raschetti1*, Emil...
Vitamin E and Donepezil for the Treatment
of Mild Cognitive Impairment
Ronald C. Petersen, Ph.D., M.D., Ronald G. Thomas, ...
Cholinesterase Inhibitors Linked to Serious Adverse Events in
Older Adults With Dementia
Laurie Barclay, Charles Vega,
CME...
FDA Talk Paper
T05-13 April 11, 2005
FDA Issues Public Health Advisory for Antipsychotic Drugs used for
Treatment of Behav...
NHS National Institute for Health and Clinical Excellence
Issue date: November 2006
(amended September 2007)
Review date: ...
Recently released internal documents
and e-mails show that AstraZeneca,
knew a decade ago that its drug
Seroquel caused di...
Real world side effects of
Seroquel (quetiapine fumarate)
On May, 30, 2009: 29,764 related reports are studied
 Overall r...
Selective Publication of Antidepressant Trials and Its
Influence on Apparent Efficacy
E H. Turner, AM. Matthews, E Linarda...
STATINs
Vital Roles of Cholesterol
 Cholesterol acts as a cell to interconnect "lipid molecules". A
lipid molecule is needed to s...
Vital Roles of Cholesterol
 Cholesterol is produced by almost every cell in the body.
 Cholesterol is essential for many...
STATINs
• March 2010: The FDA issued a safety
announcement about the risk of muscle
injury in people taking the 80mg/day
d...
VYTORIN “INEGY”
=
THE MOST
EXPENCIVE PLACEBO
SCHERING PLOUGH & MERCK
PRESENTS....
F. Cankat Tulunay, 2008
Simvastatin with or without Ezetimibe in Familial
Hypercholesterolemia
John J.P. Kastelein, M.D., ...
Systematic Review: Comparative Effectiveness and Harms of
Combinations of Lipid-Modifying Agents and High-Dose Statin
Mono...
Simvastatin with or without Ezetimibe in Familial Hypercholesterolemia
John J.P. Kastelein, M.D., Ph.D., Fatima Akdim, M.D...
Merck/Schering-Plough Pharmaceuticals. ENHANCE
trial results. January 14, 2008.
ENHANCE: Primary end point
End point Ezeti...
ENHANCE: CV events
Merck/Schering-Plough Pharmaceuticals. ENHANCE
trial results. January 14, 2008.
Event Ezetimibe plus
si...
The Vytorin on Carotid Intima-Media Thickness
and Overall Arterial Rigidity (VYCTOR) Study
Alejandra Meaney,Guillermo Ceba...
FENOFİBRAT
Statins and erectile dysfunction: results of a case/non-case
study using the French Pharmacovigilance System Database.
Do ...
Lipitor And Impotence: Unfortunately, Side
Effects Include Experiencing Erectile
Dysfunction
• A Close Relation Exists Bet...
Simvastatin and impotence
G Jackson, BMJ 1997;315:31
• Five men with coronary artery disease developed impotence within
on...
 Muscle pain
The most common statin side effect is muscle pain. You may feel this pain as a soreness, tiredness or
weakne...
 Taking multiple medications to lower your
cholesterol
 Being female
 Having a smaller body frame
 Being age 65 and ol...
 A retrospective cohort analysis of 284 158 consecutive patients in
Ontario aged 65 years and older who were admitted for...
Copyright ©2008 Canadian Medical Association or its licensors
Redelmeier, D. A. et al. CMAJ 2008;179:645-652
Table 1
Copyright ©2008 Canadian Medical Association or its licensors
Redelmeier, D. A. et al. CMAJ 2008;179:645-652
Figure 1: Ris...
Copyright ©2008 Canadian Medical Association or its licensors
Redelmeier, D. A. et al. CMAJ 2008;179:645-652
Figure 2: Rel...
Copyright ©2008 Canadian Medical Association or its licensors
Redelmeier, D. A. et al. CMAJ 2008;179:645-652
Table 2
Copyright ©2008 Canadian Medical Association or its licensors
Redelmeier, D. A. et al. CMAJ 2008;179:645-652
Table 3
Copyright ©2008 Canadian Medical Association or its licensors
Redelmeier, D. A. et al. CMAJ 2008;179:645-652
Table 4
I'm trying to get pregnant, can I take Crestor?
No. Pregnant, breastfeeding, or women trying to get pregnant should not be...
Trends in Serum Lipids and Lipoproteins of Adults, 1960-2002 Margaret D.
Carroll, MSPH; David A. Lacher, MD; Paul D. Sorli...
 Some people experience memory loss, report an inability to concentrate as well, and feel
that they are developing Alzhei...
Statins and risk of incident diabetes: a collaborative meta-analysis of
randomised statin trials
Naveed Sattar, David Prei...
Association between statins and
development of diabetes
Statin Odds ratio (95% CI)
Overall (n=91 140) 1.09 (1.02-1.17)
Ato...
JUPITER Cholesterol Drug Trial: Marketing Tactics Threaten
Public Health and Wealth
Vera Hassner Sharav, Alliance for Huma...
JUPITER (Justification for the Use of Statins in Prevention: an
Intervention Trial Evaluating Rosuvastatin , NEJM, 2008
 ...
Conclusions In this trial of apparently healthy persons
without hyperlipidemia but with elevated high-sensitivity C-
react...
EDITORIAL
Expanding the Orbit of Primary Prevention — Moving beyond JUPITER
Mark A. Hlatky, M.D. NEJM, 359:2280-2282, 2008...
EDITORIAL
Expanding the Orbit of Primary Prevention — Moving beyond JUPITER
Mark A. Hlatky, M.D. NEJM, 359:2280-2282, 2008...
EDITORIAL
Expanding the Orbit of Primary Prevention — Moving beyond JUPITER
Mark A. Hlatky, M.D. NEJM, 359:2280-2282, 2008...
Henry C. Ginsberg, MD
College of Physicians & Surgeons , Columbia University, New York
For The ACCORD Study Group
Dr. Ginsberg reports receiving
◦ Consulting fees from Merck, Merck Schering Plough,
Bristol-Myers Squibb, AstraZeneca, Abb...
ACCORD Study Design
• Designed to independently test three medical strategies to reduce
cardiovascular disease in diabetic...
ACCORD Study Design
• Overall ACCORD Glycemia Trial: 10,251 participants
• Lipid Trial: 5,518 in Lipid Trial
• 2765 random...
 All participants on open-labeled simvastatin, 20 to 40 mg/day
◦ Simvastatin dose complied with lipid guidelines
 Patien...
140
150
160
170
180
190
200
0 1 2 3 4 5 6 7
mg/dl
Years Post-
Randomization
Mean Total Cholesterol
Feno
Placebo
N = 5483 5...
Primary Outcome
Rate Rate
(%/yr) (%/yr) HR (95% CI) P Value
Primary Outcome:
Major Fatal or Nonfatal
Cardiovascular Event
...
Prespecified Secondary Outcomes
Rate Rate
(%/yr) (%/yr) HR (95% CI) P Value
Primary + Revasc +
hospitalized CHF
641 5.35 6...
Conclusion
• ACCORD Lipid does not support use of the
combination of fenofibrate and simvastatin
compared to simvastatin a...
HYPERTENSION
Centre for Evidence-Based Medicine
Telmisartan, ramipril, or both in patients at high risk for
vascular events.
Yusuf S, et al for the ONTARGET investigators...
Yusuf S et al. N Engl J Med 2008: 358:1547-1559.
ONTARGET: Key results
Outcome Ramipril,
n=8576 (%)
Telmisartan,
n=8542 (%...
Effects of Telmisartan, Ramipril, and Their Combination on Left Ventricular Hypertrophy in
Individuals at High Vascular Ri...
WHY????
Effect of Telmisartan on Renal
Outcomes: A Randomized Trial.
Mann JF, Schmieder RE, Dyal L, McQueen MJ, Schumacher H, Pogu...
Telmisartan to Prevent Recurrent Stroke and Cardiovascular
Events
Salim Yusuf, M.B., B.S., D.Phil., Hans-Christoph Diener,...
Telmisartan, ramipril, or both in patients at high risk for
vascular events.
Yusuf S, et al for the ONTARGET investigators...
40 mg is registered in Turkey,
but not in the market! Only
maximum dose (80 mg) is in
the market!
WHY???..
DOSAGE AND ADMI...
BU YANLIZ
TÜRKİYEDE
OLUR!!
TEK BAŞINA 80 Mg TELMİSARTAN
80 Mg TELMİSARTAN+12.5 Mg HİDROKLOROTİYAZİTTEN
20 Tl DAHA PAHALI
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy
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F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy

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Can we trust to big pharma? How can we use drugs rationally? What is the impact of irrational drug use on economy?

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F. Cankat Tulunay M.D., Ph.D: Rational Drug Use and Pharmacoeconomy

  1. 1. Prof. Dr. F. Cankat Tulunay President of Turkish ISPOR and Clinical Pharmacological Society Honorary President of EACPT 2009
  2. 2. LEVENT KAMACIK’IN ANISINA
  3. 3. WHAT IS CHANGED 1969-2009
  4. 4. 2009 Türkiye İlaç Çöplüğü oldu
  5. 5. Çalışma ve Sosyal Güvenlik Bakanı Ömer Dinçer • İlaç sektörü pahalı ilaç veriyor Sağlık hizmetlerindeki miktarların ciddi ölçüde arttığını kaydeden Dinçer, daha önceden kişi başına ortalama 2,8 olan sağlık hizmeti miktarının 6'ya çıktığını ve bunun da yılda 420 milyon muayene-tedavi anlamına geldiğini belirtti. • İlaç harcamalarında 2008'in ilk 6 ayıyla 2009 yılının aynı dönemini karşılaştıran Dinçer bu dönemde reçete sayısında yüzde 8'lik artış olduğunu, fatura tutarında ise yüzde 26'lık artış olduğunu belirtti. Dinçer, "İlaç sektörü bize pahalı ilaç vermeye başlamış. Reçete başına maliyetlerimiz de 43 liradan 48 liraya çıkmış. Bir başka deyişle ucuz ilaçlar yavaş yavaş piyasadan çekiliyor" dedi. • Türkiye'de kişi başına ortalama 140 lira ilaç harcaması yapıldığını belirten Dinçer, kronik hastalar hariç bu rakamın üstündeki harcamalarla ilgili önlem alabileceğini söyledi. Dinçer "Belki 140-150 liranın üstündeki ilaç harcamalarında katkı payı oranlarını artıracağım" dedi. Basın: 28.9.2009
  6. 6. Sağlıkta 3 milyarlık tasarruf yapılacak (İlaç Sektörünün Gözü Aydın!!) Dinçer,alınacak önlemlerin toplamının 3 milyar TL olduğunu söyyledi. Dinçer sağlık hizmeti kapsamı ve erişimi ile ilgili bir kısıtlama yapmayı planlamadıklarını söylerken, ilaç sektörüne yönelik alınacak tedbirler ile fiyatların düşmesini planladıklarını kaydetti. Bakan Ömer Dinçer, şunları söyledi: “Kaliteli hizmet sunumuyla ilgili idari tedbir alacağız. Bu alandaki tasarruflar, harcamaların hizmet, ilaç ve benzeri ürün tedarik ettiğimiz firmalarla olan ilişkilerimizde ortaya çıkacak. İlaç sektörüyle ilgili alınacak terbirle fiyatların düşürülmesini planlıyoruz. Grip olan hastanın, sadece ilaç yazdırmak için hastaneye gitmesinin maliyeti yüksek. 3 liralık ilaç için maliyet 15 lira oluyor. Hastanede maliyet 30 liraya çkıyor. Özel hastane ve üniversite hastanesinde 40 liraya çıkıyor.” (Radikal, 17,9.2009)
  7. 7. 2009 Türkiyede halen Antidotlar yok, tiyazit diüretik bile Türkiyede yetim kaldı!!
  8. 8. 9.12.2001, Milliyet NO COMMENT! Eşdeğer ilaçlar!!!!
  9. 9. ÖRNEKLER GELİYOR!!!
  10. 10. Medication error • Medication errors affecting at least 1.5 million people every year • In USA 98.000death/year due to medication errors • Medication errors 5th death cause in USA • Costing the health-care system between $77 billion and $177 billion annually,
  11. 11. Nonprescription drug-related problems and pharmacy interventions LO. Westerlund ve ark., Ann Pharmacother, 35: 1343-1349, 2001 ERRORS (Delivered from pharmacies) % Wrong indication 31.9 Low dose 5.9 Over dose 5.1 Other dosage problems 6.1 Containdications, drug interactions 8.0 Treatment error 16.9 Side effect 6.8 Other practical problems 3.0 Language difficulties 2.8 Other 9.6
  12. 12. Principles of Conservative Prescribing When you start one, choose wisely Beware of indication creep!!!! Lyrica® Diabetic neuropathy Partial Seizures adjunct Post-herpatic Neuralgia HIV neuropathy Sciatica Partial Seizures primary Fibromyalgia migraines Back Pain DJD Headaches Any Pain Headaches any neuropathy Likely little or no data Some data
  13. 13. MOH DRUG COMPANIES PATIENTSACADEMICIANS SOCIAL SECURIT AGENCY PHARMACISTS DOCTORS F.C. Tulunay, 2009
  14. 14. Drug expenditure European avarage 200 USD / Person Turkey 40 USD / Person Reality... logical expenditure Waste With permission of Dr.Altan Demirdere, President of AİFD, 2006
  15. 15. Waste TURKISH MARKET 2 BİLLİON DOLLAR 12 BİLLİON DOLLAR
  16. 16. ARAŞTIRMACI-KLİNİSYEN FARKI KLİNİK FARMAKOLOG • Kontrollu kinik çalışmaları değerlendirir • Geniş araştırma yapar,İstatistik yöntemler kullanır • Hastaları uzun süreli takip eder • Hastayı değil hastaları düşünür • Yanlız uygun ilaçların kullanımını ister • İlaç firmalarının baskısı daha azdır (?) • Mevcut finansman kaynaklarını tüm hastalar için adil kullanılmasına çalışır • Çok yönlü değerlendirme yapar KLİNİSYEN • Hastayı değerlendirir • Gözlemleri önemlidir • Toplumu değil, hastasını düşünür • Hastayı çoğu kısa süre takip eder, bazen sonuçları göremez • Mevcut tüm ilaçları ve her yeni çıkan ilacı kullanmak ister • İlaç firmalarının etkisi çoktur • Mevcut tüm kaynakları hastası için kullanmak ister • Tek yönlü (hasta merkezli) değerlendirme yapar FC Tulunay, 2010
  17. 17. GSK: Allen ROSES • VICE PRESIDENT OF GSK, HAS ADMITTED THAT MOST PRESCRIPTION MEDICINES DO NOT WORK ON MOST PEOPLE WHO TAKE THEM.
  18. 18. • DRUGS FOR ALZHEIMER'S DISEASE WORK IN FEWER THAN ONE IN THREE PATIENTS, • WHEREAS THOSE FOR CANCER ARE ONLY EFFECTIVE IN A QUARTER OF PATIENTS. • DRUGS FOR MIGRAINES, FOR OSTEOPOROSIS, AND ARTHRITIS WORK IN ABOUT HALF THE PATIENTS, , Dr. ROSES
  19. 19. Corrupt drug company GlaxoSmithKline... http://littlemountainhomeopathy.wordpress.com/2009/10/22/corrupt-drug-company-glaxosmithkline-to-distribute-canadian-swine-flu-vaccine/ ...an executive of the drug company talked about burying negative studies of Paxil. A company memo was presented as evidence during the trial. In 2000, GSK pulled a drug for irritable bowel syndrome, Lotronex, off the market because it was linked to severe side effects and several deaths. I t had only been on the market for 8 months, and in that time had caused 4 deaths and nearly 200 serious gastrointestinal events. In 2001, an article in Bio-Medicine links GSK’s anti-smoking medication Zyban with 5000 adverse reactions and 40 deaths. In 2003, the Italian branch of GlaxoSmithKline faced fraud and bribery charges for providing financial incentives to physicians to favour their products. In 2005, the drug company was forced by the FDA to put new warnings on the labels of three of their asthma medications: Advair, Serevent, and Foradil. These asthma medications all contain long-acting beta 2-adrenergic agonists (LABA), which are linked to an increased risk of severe asthma episodes and death. Also in 2005, GSK paid over $150 million dollars in a drug pricing fraud case. It was alleged that the company was engaged in a scheme to set and maintain fraudulent and inflated prices for anti-emetic drugs Zofran and Kytril. In 2007 the FDA issued a warning about the GlaxoSmithKline diabetes drug Avandia
  20. 20. YABANCI İLAÇ FİRMALARI NE KADAR DÜRÜST? (Multinational companies: How honest?) 0 10 20 30 40 50 60 ÇOK DÜRÜST ORTA DÜRÜST DEĞİL FİKRİ YOK www.kfd.org.tr anket,2009
  21. 21. 15.10.2009, RX MEDIA
  22. 22. Efficacy, safety, and cost of new anticancer drugs Silvio Garattini, director and Vittorio Bertele', head, regulatory policy laboratory Mario Negri Institute for Pharmacological Research, 20157 Milan, Italy Correspondence to: S Garattini sgarattini@marionegri.it BMJ. 2002 August 3; 325(7358): 269–271 • New anticancer drugs reaching the European market in 1995-2000 offered few or no substantial advantages over existing preparations, yet cost several times—in one case 350 times—as much • The greatest changes have been 4500 fewer deaths from childhood tumours and 4000 fewer from lymphomas (Hodgkin's disease) each year over the past four decades. • Among solid tumours, advances have been made in treating breast cancer, in which tamoxifen increases 10 year survival by 6% for node negative and 11% for node positive tumours, and chemotherapy increases survival by 7% and 11%, respectively. • For most other common solid tumours such as those of lung, oesophagus, stomach, or pancreas, only limited survival gains have been achieved. COST
  23. 23. Critical Drug Evaluation of New Cancer Drugs The Scottish Experience Prof Ken Paterson Chair – Scottish Medicines Consortium Berlin – 18 February 2010
  24. 24. SMC and Anti-Cancer Medicines • 61 cancer medicines reviewed – 36 for advanced/metastatic cancer – 25 for earlier/adjuvant treatment • Median QALY gain (over current treatment) – 0.38 for advanced cancer – 0.30 for earlier/adjuvant treatment • Mean QALY gain (over current treatment) – 0.52 for both groups
  25. 25. What does this Mean? • Median health gain – 6 months with quality of life 70% of normal • Mean health gain – 8-9 months with QoL 70% • Only 6 drugs (10%) offered ≥1 QALY • 22 drugs (36%) offered ≤0.2 QALY – = ≤3 months at 70% of normal QoL – Note NICE ‘end-of-life’ decision-making
  26. 26. Is There No Good News- 1? • Some of the greatest health-gains are with really innovative drugs – – Trastuzumab – 2.4 QALYs – Nilotinib – 2.1 QALYs – Bortezomib – 1.1 QALYs • Even if these are expensive, they offer good ‘value-for-money’
  27. 27. Is There No Good News – 2? • Anti-cancer drugs are much like other drugs – Musculoskeletal (11) – 0.66 QALY – Infections (33) – 0.11 QALY – Endocrine (24) – 0.07 QALY – Cardiovascular (33) – 0.05 QALY – CNS and pain (55) – 0.04 QALY • New drugs in general are not as valuable as many would like to think!
  28. 28. How Good are New Drugs? • 22% offer no health gain (=me too!) 28% offer >0 – 0.1 QALY 25% offer >0.1 – 0.5 QALY 13% offer >0.5 – 1.0 QALY 12% offer >1 QALY Median health gain (n = 281) = 0.1 QALY!!
  29. 29. FOLOTYN • FOLOTYN is a folate analogue metabolic inhibitor indicated for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). This indication is based on overall response rate. Clinical benefit such as improvement in progression free survival or overall survival has not been demonstrated. (FDA Prospektüs) • The drug was approved by the Food and Drug Administration in late September as a treatment for peripheral T-cell lymphoma, 30.000 dolar/month • In the clinical trial, the median duration of use was 70 days, which would cost roughly $70,000 to $80,000. But some patients used the drug for many months. • Folotyn has not yet shown an effect on longevity. In the clinical trial that led to approval of the drug, 27 percent of the 109 patients experienced a reduction in tumor size. The reductions lasted a median of 9.4 months. • But considering all the patients in the trial, only 12 percent had a reduction in tumor size that lasted for more than 14 weeks. The trial did not compare Folotyn to another drug or a placebo. • Genzyme’s Clolar for pediatric leukemia costs about $34,000 a week, though the company says that only two weeks of treatment are typically needed. • GlaxoSmithKline is charging up to $98,000 for a six-month treatment course of Arzerra, a drug approved in late October for chronic lymphocytic leukemia • The colon cancer drug Erbitux, for instance, costs $10,000 a month and the drug Avastin about $8,800 when used to treat lung cancer.
  30. 30. • U.K. rejected NEXAVAR for liver cancer • Nexavar was estimated to cost 65,900 pounds ($102,000) for every “quality adjusted year of life,” Not: • NEXAVAR: 200 mg 112 tab: 8.270 TL ödenmez (SGK)
  31. 31. NEXAVAR?? (1month cost is 8.270 TL=5.500 USD) Which one is wright!!?? • Bayer, Onyx Pill Doesn’t Slow Breast Cancer in Study Sept. 30 (Bloomberg) -- Bayer AG and Onyx Pharmaceuticals Inc.’s Nexavar cancer drug failed to slow the progression of breast cancer in the second of four studies that combine the medicine with different types of chemotherapy. • September 30, 2009 Mid-stage breast cancer trial of Bayer, Onyx's Nexavar misses primary endpoint Last Updated:September 30, 2009 00:30 Preliminary results showed that a Phase II trial of Bayer and Onyx’s Nexavar (sorafenib) in combination with paclitaxel in patients with advanced breast cancer did not meet its primary endpoint of progression-free survival, the companies announced on Wednesday. Dimitris Voliotis, vice president of global clinical development oncology at Bayer, said the “data require further analysis and interpretation before we determine the appropriate path forward." • • Wednesday - September 23, 2009 Phase II Study in Advanced Breast Cancer: • Nexavar® in Combination with Chemotherapy Demonstrates 74 Percent Improvement in Progression-Free Survival • First presentation of results at joint ECCO- ESMO congress in Berlin, Germany • Abstract # 3LBA Berlin, September 23, 2009 – Bayer HealthCare AG and Onyx Pharmaceuticals, Inc. today announced the full results from their first collaborative group-sponsored randomized, double-blind, placebo controlled Phase II trial showing that Nexavar® (sorafenib tablets) in combination with the oral chemotherapeutic agent, capecitabine, significantly extended progression-free survival in patients with advanced breast cancer by 74 percent. The data were presented at the joint 15th European CanCer Organisation (ECCO) and 34th European Society for Medical Oncology (ESMO) Multidisciplinary Congress in Berlin, Germany. Bayer
  32. 32. SUTENT • Costs • Sunitinib is marketed by Pfizer as Sutent, and is subject to patents and market exclusivity as a new chemical entity until February 15, 2021 • Sutent is one of the most expensive drugs widely marketed. Doctors and editorials have criticized the high cost, for a drug that doesn't cure cancer but only prolongs life. • In the U.S., insurance companies have refused to pay for all or part of the costs of Sutent. • In the UK NICE refused (late 2008) to recommend sunitinib for late stage renal cancer (kidney cancer) due to the high cost per QALY, estimated by NICE at £72,000/QALY and by Pfizer at £29,000/QALY.[21] It was also refused by NICE in 2008 for the treatment of kidney cancer.[22] This refusal/guidance was updated Feb 2009 after negotiations on price for the first course of treatment will be paid by Pfizer. • TÜRKİYEDE BİR SİKLÜS İLAÇ GİDERİ: 17.346 TL
  33. 33. 39
  34. 34. Wall Street Journal Oct. 4, 2008  A prominent Emory University psychiatrist failed to tell the school about $500,000 he received from drug maker GlaxoSmithKline ...  The payments to Charles Nemeroff, chairman of the Atlanta university's psychiatry department, compensated him for making presentations to doctors about Glaxo drugs, including its big-selling antidepressant Paxil
  35. 35. Dr. Nemeroff served from 2003 until this past summer as the primary investigator on a collaborative grant between Emory, Glaxo and the National Institute of Mental Health, a federal agency. The research effort, called the Emory-GSK-NIMH Collaborative Mood Disorders Initiative, had a $3.95 billion budget from the government, and examined five Glaxo drugs considered for use as possible antidepressants.
  36. 36. Pfizer Paid for Doc's Helicopter in Off- Label Geodon (ZELDOX) Push, Suit Claims • Mark R. Westlock (worked for Pfizer) alleges that Dr. Neil S. Kaye of Wilmington, Del., an assistant clinical professor of psychiatry at Jefferson Medical College, received $4,000 a day in speaker fees to talk to other doctors about “the off label use of Geodon® in adolescents,” among other issues. He was used so frequently by Pfizer that he was flown by ‘copter to some of his gigs. • Among the tactics they allegedly used were recommending the antidepressant Zoloft for girls who failed to make the cheerleading squad; and staging talks in which doctors recommended prescribing Viagra for women who had difficulty reaching orgasm.
  37. 37. GSK n COURT EXPOSED GSK/RESEARCHERS FRAUD The court documents released as a result of one of the lawsuits in October 2008 indicated that GSK "and/or researchers may have suppress n MISLEADING PUBLIC For 10 years, GlaxoSmithKline's marketing of the drug (PAXIL) stated that it was "not habit forming". In 2002, the U.S. Food and Drug Administration published a new product warning about the drug, and the International Federation of Pharmaceutical Manufacturers Associations (IFPMA) declared GSK guilty of misleading the public about paroxetine on US television. ed or obscured suicide risk data during clinical trials"
  38. 38. Drugs Giants GlaxoSmithKline In Iraq Probe • Pharmaceutical companies GlaxoSmithKline and AstraZeneca have been linked to an investigation into bribes allegedly paid to Saddam Hussein's former regime. • The oil-for-food programme was supposed to allow the Iraqi government to sell limited amounts of oil to buy foreign food and medicines.
  39. 39. 10.000 USD/18 months
  40. 40. REGULATORY AGENCIES PHYSICIANS INDUSTRY PHARMACYST PATIENTS
  41. 41. RATIONAL DRUG USE Hastaların klinik ihtiyaçlarına göre, ihtiyaç duyduğu dozda, sürede ve kendisi ve toplum için en ucuz maliyette ilaç bulabilmesidir. (WHO 1985)  Right indication  Right drug  Right route, dosage, duration  Right patient  Right patient information  Rigtht evaluation  Right price  Uygun endikasyon  Uygun ilaç  Uygun yol, doz ve süre  Uygun hasta  Uygun hasta bilgilendirilmesi  Uygun değerlendirme  Uygun fiyat 7U 7R “Patients receive medications appropriate to their clinical needs, in doses that meet their own individual requirements, for an adequate period of time, and at the lowest cost to them and their community.” (WHO, 1985).
  42. 42. WHO advocates 12 key interventions to promote more rational use: 1 Establishment of a multidisciplinary national body to coordinate policies on medicine use.....NO 2. Use of clinical guidelines.....NO 3. Development and use of national essential medicines list...NO 4. Establishment of drug and therapeutics committees in districts and hospitals...NO 5. Inclusion of problem-based pharmacotherapy training in undergraduate curricula...NO 6. Continuing in-service medical education as a licensure requirement: 7. Supervision, audit and feedback...NO 8. Use of independent information on medicines...NO 9. Public education about medicines...NO 10. Avoidance of perverse financial incentives...NO 11. Use of appropriate and enforced regulation...NO 12. Sufficient government expenditure to ensure availability of medicines and staff...NO
  43. 43. Is there an EVİDENECE-BASED pharmacotherapy? PHARMACOTHERAPY
  44. 44. EVIDENCE BASED PHARMACOTHERAPY OR FRAUD BASED PAHARMACOTHERPY?
  45. 45. STAR MİLLİYET FEAR BASED MARKETING !!! Sadece 25 milyon! Domuz gribi için Türkiye’ye 25 milyon aşı geliyor. Sağlık Bakanlığı, salgına yol açan H1N1 virüsüne (domuz gribi) karşı aşı geliştiren GlaxoSmithKline (GSK) ile Türkiye’ye 25 milyon doz HNN1 aşısı sağlanması için anlaşma imzaladı. GSK yetkililerinin verdiği bilgiye göre, Türkiye’ye aşı en geç Kasım ayı ortasında ulaştırılmış olacak.
  46. 46. • H1N1 Pandemic Vaccine • “It’s unethical to recommend a vaccine which hasn’t even received the usual minimal safety testing let alone long term testing.” • Numerous doctors have remarked that it has been no more deadly or disabling than seasonal influenza virus that circulates yearly.
  47. 47. H1N1 Vaccine To Cost Countries $2.50 - $20 Per Dose The H1N1 (swine) flu vaccine will cost countries between $2.50 and $20 per dose, based on their ability to pay, according to the director of the Initiative for Vaccine Research at the WHO, Marie-Paule Kieny. Akdağ aşının maliyetine ilişkin de bilgi verdi. Tek doz aşının maliyetinin 5,2 Euro+KDV (8 $) olduğunu belirten Akdağ, “Yaklaşık 500 milyon TL’nin üstünde bir maliyet olacak” dedi. Not: 25 milyon kişi X 8 $=300.000.000 TL eder
  48. 48. Urgent lawsuit filed against FDA to halt swine flu vaccines; claims FDA violated federal law (October 09, 2009 ) Health freedom attorney Jim Turner is filing a lawsuit in Washington D.C. mid-day Friday in an urgent effort to halt the distribution of the swine flu vaccine in America. On behalf of plaintiffs Dr. Gary Null and other licensed health care workers of New York State, the lawsuit charges that the FDA violated the law in its hasty approval of four swine flu vaccines by failing to scientifically determine neither the safety nor efficacy of the vaccines. "The FDA is required by law to establish that a vaccine is safe and effective before it can be given to the public," said Turner. "We are arguing that they did not establish that the vaccine was effective, and did not establish that it was safe. They are trying to get it on the market by a waiver."
  49. 49. Another GARDASİL.... 806 TL CERVARIX.... 734 TL !
  50. 50. Gardasil & Merck  For Immediate Release, May 23, 2007; Contact: Press Office 202-646-5188  There have been 3,461 reports of adverse events, including a maximum of 11 deaths, in patients receiving Merck’s cervical cancer vaccine Gardasil, public interest group Judicial Watch said.  Judicial Watch Uncovers New FDA Records Detailing Deaths in 1,824 Adverse Reaction Reports Related to HPV Vaccine  FDAnews Drug Daily Bulletin, Oct. 11, 2007 | Vol. 4 No. 200 : Gardasil Adverse Events Include Deaths, Seizures,..
  51. 51. 8 October 2009, BMJ 2009;339:b3884 Cost effectiveness analysis of including boys in a human papillomavirus vaccination programme in the United States Jane J Kim, assistant professor, Sue J Goldie, professor 1 Harvard School of Public Health, Department of Health Policy and Management, Center for Health Decision Science, 718 Huntington Avenue, Boston, MA 02115, USA • Given currently available information, including boys in an HPV vaccination programme generally exceeds conventional thresholds (QALY over 100.000$) of good value for money, even under favourable conditions of vaccine protection and health benefits
  52. 52. Hysteria over genital warts? New York Times,2008 • In a New York Times article published last year, Dr. Harper spoke about the fear-based marketing of Gardasil by Merck: "'Merck lobbied every opinion leader, women's group, medical society, politicians, and went directly to the people -- it created a sense of panic that says you have to have this vaccine now..." This behavior by drug companies -- using fear tactics to promote a particular disease in order to sell the "treatment" -- is called disease mongering. Most of the pharmaceutical profits generated today are based on precisely this tactic: Spread the fear, then sell the treatment. Why is disease mongering so important to the profits of the drug companies? They figured out many years ago that selling drugs only to those people who are sick was a very limited income opportunity. To rake in the real profits, they needed to devise a way to sell drugs to healthy people (i.e. people who don't need them). That's what cervical cancer vaccines really are: A scheme to sell vaccines to people who aren't suffering from any disease at all. That one of the industry's own researchers is willing to speak out against this is not just highly unusual; it's also highly courageous. It makes you wonder: Who, exactly, is this Dr. Harper? Dr. Diane Harper • Dr. Harper is a graduate of the Massachusetts Institute of Technology. She studied additional courses at Stanford and received her medical degree from the University of Kansas. She was a key researcher in both Gardasil and Cervarix vaccines, and she's one of the most experienced researchers in the world on HPV-related diseases. She's done work for both Merck and GlaxoSmithKline.
  53. 53. Top researcher who worked on cervical cancer vaccine warns about its dangers 8.10.2009 www.NaturalNews.com • One of the key researchers involved in the clinical trials for both Gardasil and Cevarix cervical cancer vaccines has gone public with warnings about their safety and effectiveness. Dr. Diane Harper openly admitted the vaccine doesn't even prevent cervical cancer, stating, "[The vaccine] will not decrease cervical cancer rates at all." Dr. Harper also warned that the cervical cancer vaccine was being "over-marketed" and that parents should be warned about the possible risk of severe side effects from the vaccine. She even concluded that the vaccine itself is more dangerous than the cervical cancer it claims to prevent! Dr. Harper's warnings about cervical cancer vaccines are especially relevant considering her expertise in the cost/benefit analysis of vaccines. Her conclusion is that cervical cancer vaccines aren't worth the risks, nor are they worth all the effort being put into hyping them to the public. "This may not be the best use of our resources at this time," she said in a Washington Post article. So why do cervical cancer vaccines continue to be pushed by doctors and health authorities across the US, UK and other first-world nations? Because Big Pharma is the great corporate puppeteer that's pulling the strings of legislators. With enough money and lobbyists, you can always overcome scientific thinking with fear-based marketing and under-the-table deal-making. Science-based medicine has no place in a world where disease is big business.
  54. 54. Press Release For immediate release 9th October 2009 ALLIANCE FOR NATURAL HEALTH CALLS FOR AN URGENT SCIENTIFIC INQUIRY INTO THE HPV VACCINE USED IN THE UK The Alliance for Natural Health (ANH) today calls for an independent Inquiry into the safety of HPV vaccine, and appeals to all Members of Parliament to press for this. • Reports of serious and even lethal adverse reactions to the Human Papilloma Virus (HPV) vaccine, Cervarix, manufactured by GlaxoSmithKline, raises grave concern over the safety of the vaccine. While its closely related vaccine, Gardasil, manufactured by Merck, is recognised by the US Centers for Disease Control (CDC) to trigger severe reactions, namely hospitalisation, permanent disability, life-threatening illness or death, equivalent data in the UK appears not to be publicly available.
  55. 55. Merck Paid for Medical ‘Journal’ Without Disclosure, May 14, 2009..... Merck published fake journal 30th April 2009 ... From 2002 through 2005, the Australian affiliate of Merck paid the Australian office of Elsevier, an academic publisher, to publish eight compilations of scientific articles under the title Australasian Journal of Bone and Joint Medicine, a spokesman for Elsevier said. Nine of 29 articles in the second issue of the journal referred positively to Vioxx, and an additional 12 articles referred positively to another Merck drug, Fosamax, a bone treatment, An Australian physician, Dr. James V. Bertouch, testified on May 8 that he had been surprised to find his name listed in the first issue without his permission as a member of the journal’s editorial board, and had asked to have his named removed from the publication. A company spokesman said Elsevier believed that one of the Merck issues was distributed to 20,000 doctors in Australia while other issues went to about 10,000 doctors.
  56. 56. New Merck Allegations: A Fake Journal; Ghostwritten Studies; Vioxx Pop Songs; PR Execs Harass Reporters
  57. 57. New Merck Allegations: A Fake Journal; Ghostwritten Studies; Vioxx Pop Songs; PR Execs Harass Reporters
  58. 58.  Baystate Tıp Merkezi Ağrı merkezinin önde gelen isimlerden olan Dr. Scott S. Reuben’in 2002-2008 arasında yayınladığı 21 makalenin sahte olduğu ortaya çıktı. Bu tıp tarihindeki en büyük ve en uzun sahtekarlık olayı idi. Yayınların çoğu “multimodal” analjezi, post-operatif analjezi ve analjezik kombinasyonları gibi konularla ilgiliydi.  Reuben’in Pfizer’in paralı konuşmacılar listesinde olduğu ve Pfizer için birçok konuşma yaparak Pfizer’in ilaçlarını meth ettiği, ayrıca yalan araştırmaların bir kısmının (Pfizer’den 5 grant almış, özellikle post- operatif ağrıda Celebrex ve Lyryca kullanım gibi) Pfizer tarafından maddi olarak desteklendiği ortaya çıktı.
  59. 59. Do Not Use : Generic drug name: montelukast Brand name: SINGULAIR (Merck) Do Not Use : Generic drug name: zafirlukast Brand name: ACCOLATE (AstraZeneca) Leukotriene inhibitors are not as effective or as safe as inhaled steroids (beclomethasone), the currently recommended drugs for treatment and prevention of asthma.3 Montelukast was compared to an active antihistamine, loratadine (CLARITIN). In this trial, loratadine was found to work better than montelukast.13 The Medical Letter on Drugs and Therapeutics reviewed studies on montelukast. The studies showed that fluticasone (FLONASE) was better than both montelukast and loratadine for hay fever May 2009
  60. 60. • Aspects of ordinary life, such as menopause, being medicalised; • Mild problems portrayed as serious illnesses, as has occurred in the drug-company-sponsored promotion of irritable bowel syndrome • Risk factors, such as high cholesterol and osteoporosis, being framed as diseases. • Drug companies are by no means the only players in this drama. Through the work of investigative journalists, we have learned how informal alliances of pharmaceutical corporations, public relations companies, doctors' groups, and patient advocates promote these ideas to the public and policymakers—often using mass media to push a certain view of a particular health problem. • Currently, these alliances are working with the media to popularize little-known conditions, such as restless legs syndrome and female sexual dysfunction [7], • The Eli Lilly–sponsored promotion of premenstrual dysphoric disorder to help sell a re-branded version of fluoxetine (rebranded from Prozac to Sarafem)
  61. 61. The making of a disease: female sexual dysfunction Ray Moynihan, BMJ 326 4 JANUARY 2003 Is a new disorder being identified to meet unmet needs or to build markets for new medications?  Researchers with close ties to drug companies are defining and classifying a new medical disorder at company sponsored meetings  The corporate sponsored definitions of “female sexual dysfunction” are being criticized as misleading and potentially dangerous  Commonly cited prevalence estimates, which indicate that 43% of women have “female sexual dysfunction,” are described as exaggerated and are being questioned by leading researchers  The role of drug companies in the construction of new conditions, disorders, and diseases needs more public scrutiny
  62. 62. SELLING SICKNESS: THE PHARMACEUTICAL INDUSTRY AND DISEASE MONGERING RAY MOYNIHAN, IONA HEATH, DAVID HENRY, BMJ 2002;324:886-891  Pharmaceutical companies sponsor diseases and promote them to prescribers and consumers.  There's a lot of money to be made from telling healthy people they're sick.  Pharmaceutical companies are actively involved in sponsoring the definition of diseases and promoting them to both prescribers and consumers.  “Disease awareness" campaigns are commonly linked to companies' marketing strategies, they operate to expand markets for new pharmaceutical products  Groups and/or campaigns are orchestrated, funded, and facilitated by corporate interests, often via their public relations and marketing infrastructure.
  63. 63. GIVING LEGS TO RESTLESS LEGS: A CASE STUDY OF HOW THE MEDIA HELPS MAKE PEOPLE SICK STEVEN WOLOSHIN, LISA M. SCHWARTZ, PLOS MED 3(4): E170. DOI:10.1371/JOURNAL.PMED.0030170  What Is Restless Legs Syndrome?  The diagnosis of restless legs syndrome requires the presence of the following four criteria [4]:  An urge to move the legs due to an unpleasant feeling in the legs.  Onset or worsening of symptoms when at rest or not moving around frequently.  Partial or complete relief by movement (e.g., walking) for as long as the movement continues.  Symptoms that occur primarily at night and that can interfere with sleep or rest.  The severity of disease is judged by the frequency of these symptoms, which can range from less than once a month to many times a day. Recommended treatments include stretching exercises and less caffeine for intermittent disease and various prescription drugs (e.g., benzodiazepines and dopamine agonists) for daily symptoms [5].  “[Restless legs syndrome] is quite a serious sleep disorder that affects a lot of people….Their sleep is disturbed and, unless they are really awake, they will not be aware of it” [1].
  64. 64. Medical journals and pharmaceutical companies: uneasy bedfellows Richard Smith, editor BMJ 2003;326:1202-1205 (31 May) • Free newspapers for doctors depend completely on income from pharmaceutical advertising, but many journals also depend heavily on such advertising • The advertising is often misleading • Editorial coverage is much more valuable to drug companies than advertising, and scientific studies can be manipulated in many ways to give results favourable to companies • Many medical journals have a substantial income from supplements and reprints paid for by drug companies • In one sense, all journals are bought by the pharmaceutical industry. The industry dominates health care, and most doctors have been wined and dined by it. HADİ RICHARD...BİZ BİRBİRİMİZE MUHTAÇIZ
  65. 65. Senator Moves to Block Medical Ghostwriting A growing body of evidence suggests that doctors at some of the nation’s top medical schools have been attaching their names and lending their reputations to scientific papers that were drafted by ghostwriters working for drug companies — articles that were carefully calibrated to help the manufacturers sell more products. By NATASHA SINGER Published: August 18, 2009
  66. 66. Senator Moves to Block Medical Ghostwriting The documents offer a look at the inner workings of DesignWrite, a medical writing company hired by Wyeth to prepare an estimated 60 articles favorable to its hormone drugs. The articles were published in medical journals between 1998 and 2005 — continuing even though a big federal study was suspended in 2002 after researchers found that menopausal women who took certain hormones had an increased risk of invasive breast cancer and heart disease. By NATASHA SINGER Published: August 18, 2009
  67. 67. Definitions: Guest and Ghost writers In their earlier survey, published in JAMA in 1998, the authors spell out their definition of honorary author in depth, pointing out that an "honorary" or "guest" author is often something "bestowed as a tribute to a department chair or to the person who acquired funding for the study." By contrast, a "ghost" author refers to someone who is not named as an author, despite having made substantial contributions to the research or writing of the article.
  68. 68. WYETH “PROJECT ASSIGNMENT FORM” NAME: Steven W. Gutkin PROJECT: #8231: Manuscript on "Can a Healthy Endothelium Influence the Cardiovascular Effects of HRT?" for submission to Journal of the American College of Cardiology. DESCRIPTION: Write 8- to 10-page manuscript (not including references) based on the approved outline. Points to Include Generally points to be covered include: the controversy over the increase in cardiovascular events with hormone replacement therapy in women with CHD. Stress the importance of primary prevention vs. secondary prevention. Include evidence and mechanisms for why a healthy endothelium may be necessary for the maximal effect of estrogens (ERT) with or without progestins (HRT). WRITER'S FEE: $3,500. One-third may be invoiced upon commencement of work; the second third may be invoiced upon acceptance of the manuscript by DesignWrite; onethird may be invoiced upon submission of the paper to the target journal or 90 days from when the manuscript was approved. Out-of-pocket expenses for telephone calls, faxes, and mailings will be reimbursed following submission of proper receipts. ASSIGNED BY: Karen D. Mittleman, Ph.D. Date: January 18, 2005 ( ASSIGNMENT ACCEPTED BY: Steven W. Gutkin Date:
  69. 69. October 13, 2000 Steven W. Gutkin 22 Monhegan Avenue, Oakland, NJ 07436-4025 Dear Steve: Thank you for tackling the Koh paper again. According to Karen, anything that doesn't bolster the main message that early intervention with estrogen in order to maintain a healthy endothelium in postmenopausal women can go. However, as we agreed on the phone, Koh's own additions will probably have to stay no matter what. We can always leave the extra cutting to him, so anything you can do toward the goal of 5.000 words will be appreciated. Let me know if I can assist with references or other questions. Sincerely, Stephen M. Parker Medical Editor Cc: Karen D. Mittleman, PhD, Senior Medical Writer
  70. 70. Ghostwriter Budget Preclinical manuscript………. $10,000 Clinical manuscript…………… $16,000 Review article………………….. $20,000 Poster presentation…………… $6,000 Journal supplement………….. $175,000
  71. 71. Pfizer Pays $2.3 Billion to Settle Marketing Case • WASHINGTON — The pharmaceutical giant Pfizer agreed to pay $2.3 billion to settle civil and criminal allegations that it had illegally marketed its BEXTRA, GEODON, LYRICA and ZYVOX • • It was the largest health care fraud settlement and the largest criminal fine of any kind ever.
  72. 72. PFIZER AND FRAUD  Pfizer to pay record $2.3 billion settlement for illegal drug promotion - (ABC News)  Pfizer completes $2.3 billion settlement of US drug claims - (Bloomberg)  Pfizer fined $2.3B in record fraud settlement - (CNN Money)  Justice Department announces largest health care fraud settlement in its history - (HHS)  Pfizer settles drug-promotion case for $2.3 billion - (MarketWatch)  Pfizer concludes previously disclosed settlement agreement with US Department Of Justice regarding past promotional practices - (Pfizer)  Pfizer to pay $2.3 billion to settle case on drug marketing - (SmartMoney)  Pfizer pays $2.3 billion to settle marketing case - (The New York Times)  Pfizer to pay $2.3 billion to settle marketing charges - (The Washington Post)  Justice department announces largest health care fraud settlement in its history - (US Department of Justice)
  73. 73. AKIL ALMAZ İŞLER..????
  74. 74. PARANTERAL MELOXICAM Only reimbursable in Turkey Treatment of OA symptoms? It is not analgesic! Symptomatic treatment of painful osteoarthritis (arthrosis, degenerative joint disease) Symptomatic treatment of rheumatoid arthritis Symptomatic treatment of ankylosing spondylitis Paranteral 1 month drug cost= 198 TL + injection cost + side effects 3 X15 mg=3.14 TL Melox 30X15 mg=11.96 1 ay Melox+Lansor= 27 TL
  75. 75. Dr. Frank DEGNER Medical Department, Boehringer Ingelheim, Germany, COX concept: MELISSA and SELECT report, 1998 15 mg Meloxicam highly significantly differnt than 7.5 mg. 15 mg Meloksikam is equipotent with 20 mg Piroksicam.
  76. 76. ETOL, NOBEL ETODİN, ULKAR (NOBEL) 400 mg etodolac PFIZER
  77. 77. ETODOLAC USA ! Lodine, may cause serious CV side effects, such as MI or stroke, which may result in hospitalization and even death. Although serious CV events can occur without warning symptoms, patients should be alert for the signs and symptoms of chest pain, shortness of breath, weakness, slurring of speech, and should ask for medical advice when observing any indicative sign or symptoms. Patients should be apprised of the importance of this follow-up (see WARNINGS, Cardiovascular Effects).
  78. 78. Indication: Skin and complicated intraabdominal infections 560 EURO
  79. 79. MİGREN PROFLAKSİSİ TOPAMAX 100 mg/gün DEPAKİN 500 mg/gün DİDERAL 40 mg/gün Kutu 184.321.000 16.392.000 3.827.000 1 aylık tedavi 184.321.000 16.293.000 4.600.000 6 aylık tedavi 1.140.000.000 98.352.000 27.600.00 10.000 kişi/sene 11 TRİLYON 980 MİLYAR 276 MİLYAR 2.6.2004
  80. 80. Topiramate in migraine prophylaxis--results from a placebo- controlled trial with propranolol as an active control. Diener HC, Tfelt-Hansen P, Dahlof C, Lainez MJ, Sandrini G, Wang SJ, Neto W, Vijapurkar U, Doyle A, Jacobs D; MIGR-003 Study Group. J Neurol. 2004 Aug;251(8):943-50 • 13 Ülke, 61 merkez, 575 hasta • TOPAMAX 100 mg/gün ve PROPRANOLOL 160 mg/gün ayni etkinlikte bulundu. • Her iki ilaçtada: migren sıklığı, cevap veren oranı, migrenli gün sayısı ve günlük analjezik ihtiyacı ayni bulunmuş • TOPAMAX çok PAHALI!
  81. 81. FDA Talk Paper T05-13 April 11, 2005FDA Issues Public Health Advisory for Antipsychotic Drugs used for Treatment of Behavioral Disorders in Elderly Patients The Food and Drug Administration (FDA) today issued a public health advisory to alert health care providers, patients, and patient caregivers to new safety information concerning an unapproved (i.e., “off-label”) use of certain drugs called “atypical antipsychotic drugs.” These drugs are approved for the treatment of schizophrenia and mania, but clinical studies of these drugs to treat behavioral disorders in elderly patients with dementia have shown a higher death rate associated with their use compared to patients receiving a placebo (sugar pill). Today’s advisory applies to such antipsychotic drugs as Abilify (aripiprazole), Zyprexa (olanzapine), Seroquel (quetiapine), Risperdal (risperidone), Clozaril (clozapine) and Geodon (ziprasidone). Symbyax, which is approved for treatment of depressive episodes associated with bipolar disorder is also included in the agency’s advisory. FDA is requesting that the manufacturers of all of these kinds of drugs add a boxed warning to their drug labeling describing this risk and noting that these drugs are not approved for the treatment of behavioral symptoms in elderly patients with dementia. Patients receiving these drugs for treatment of behavioral disorders associated with dementia should have their treatment reviewed by their health care providers. In analyses of seventeen placebo-controlled studies of four drugs in this class, the rate of death for those elderly patients with dementia was about 1.6 to 1.7 times that of placebo. Although the causes of death were varied, most seemed to be either heart-related (such as heart failure or sudden death) or from infections (pneumonia). The atypical antipsychotics fall into three drug classes based on their chemical structure. Because the increase in mortality was seen with atypical antipsychotic medications in all three chemical classes, the agency has concluded that the effect is probably related to the common pharmacologic effects of all atypical antipsychotic medications, including those that have not been studied in the dementia population. The agency is considering adding a warning to the labeling of older antipsychotic medications because limited data also suggest a similar increase in mortality for these drugs. The review of the data on these older drugs, however, is still on-going. • Second generation anti-psychotics causes 4.5% mortality among elderly patients. Antipsychotics can not be use in demantia. • It is reimburseble in Turkey for the treatment of demantia in elderly and AD.
  82. 82. NİDAZOL-M VAJİNAL TABLET 10. GÜN
  83. 83. Units Year/08 TL Year/08 US$ Year/08 NIDAZOL M 273.034 741.164 579.309 Ruhsat tarihi:20.7.1999 Acaba o tarihte komisyonda farmasötik teknolog yokmu idi??
  84. 84. KETEK & SANOFI-AVENTIS  Hearing on Deadly Drug Tomorrow: Panel Features Drug Maker Sanofi- Aventis Official, GAP Client who Discovered Company Knew of Fraudulent Trails, Feb.11, 2008  HHS secretary could be held in contempt for withholding information  Integrity of Drug Approvals in Doubt, Lawmakers Say  Congress accuses HHS and FDA of contempt in Ketek case 13 February 2008  SUBCOMMITTEE ON OVERSIGHT AND INVESTIGATIONS HEARING ENTITLED, “KETEK CLINICAL STUDY FRAUD: WHAT AVENTIS KNEW” February 12, 2008  Bush administration has failed to comply with a subpoena for documents used to prepare testimony from FDA Commissioner Andrew von Eschenbach about the antibiotic Ketek, manufactured by Sanofi-Aventis,  A U.S. government investigator said Sanofi-Aventis had evidence that a safety study of its antibiotic contained fake data, but submitted it to the Food and Drug Administration anyway.
  85. 85. 5.8 4.1 Times more expencive Treatment of upper respiratory infections...
  86. 86. FDA: Ketek (telithromycin) [UPDATE 03/26/2007] Sanofi-Aventis issued a "Dear Healthcare Professional" letter. • [Posted 02/12/2007] FDA and Sanofi-Aventis notified healthcare professionals of revisions to the prescribing information, including a BOXED WARNING and a new Patient Medication Guide, for the antibiotic Ketek. Two of the three previously approved indications, acute bacterial sinusitis and acute bacterial exacerbations of chronic bronchitis, were removed from the prescribing information because the balance of benefits and risks no longer support approval of the drug for these indications. Ketek will remain on the market for the treatment of community acquired pneumonia of mild to moderate severity. In addition, warnings were strengthened for hepatotoxicity (liver injury), loss of consciousness, and visual disturbances. The BOXED WARNING states that Ketek is contraindicated in patients with myasthenia gravis. The Patient Medication Guide, which must be distributed to all patients, informs them about the risks of the drug and how to use it safely. • [March 2007 – Letter – Sanofi-Aventis] [February 12, 2007 – Press Release – FDA] [February 12, 2007 – Label –Sanofi-Aventis] [February 12, 2007 – Drug Information Page – FDA]
  87. 87. KETEK????? FDA Restricts The Future Use Of Sanofi-Aventis SA's Antibiotic Ketek New Package Insert, Or Label, For Ketek Will Get Black-box Warning And Medication Guide For Patients, Also Sanofi-Aventis Sends "Dear Doctor" Letter Regarding Antibiotic Ketek In Late March 2007 The Letter Concerns Black-Box Warning, Prescribing Changes, And Patient Medication Guide Announced Back In Mid-February 2007 EMEA: Section 4.1 of the SPC was updated to restrict the indications acute exacerbation of chronic bronchitis and acute sinusitis to infections caused by known or suspected beta-lactam and/or macrolide resistant strains covered by the antibacterial spectrum of telithromycin. The indication tonsilitis/pharyngitis was restricted to infections with Streptococcus pyogenes when beta-lactam antibiotics are not appropriate in countries/regions with a significant prevalence of resistant
  88. 88. WHO IS STUPID?!!!! American patients or Turkish bacterias??? If KETEK doesn’t have any effect on US patients’ acute exacerbations of chronic bronchitis (AECB) and acute bacterial sinusitis... How it kills Turkish bacterias of AECB and sinusitis?????????????????
  89. 89. 22.29TL 22.29TL
  90. 90. TURKISH TYPE PHARMACOECONOMY
  91. 91. No comment! = 42.57 TL 100 puffs 80.82 TL 120 puffs??? + = 129.37 TL Is it really equal? Who is paying for waste of 20 puffs (25.9 TL)? Only available in TURKEY! Original company doesn’t have it!! 123.39 TL
  92. 92. EMEA, FACTIVE (gemifloksazin) için negatif fikir beyan etti Mennarini ruhsat müracaatını geri çekti. Hafif ve orta şiddette toplumda kazanılmış pnömoni ve kronik bronşitin akut hecmelerinde kullanılması planlanan florokinolin grubu ilaçlardan, 320 mg gemifloksazin (FACTİVE) ruhsat müracatından Menarini International vazgeçti. EMEA, Factive’in genotoksik olduğunu ve diğer florokinolonlardan daha fazla DNA hasarına sebep olduğunu, ve pnömonideki 5 günlük tedavi etkenliğinin şüpheli olduğunu, 7 günlük tedavide ise ciddi yan etki oluştuğunu belirtti. ayrıca ilacın kronik bronşitteki etkinliğinin yeteri klinik çalışma ile desteklenmediğini ve diğer ilaçlardan herhangi bir üstünlüğü olmadığını belirterek, negatif fikir beyan etti. Yazar Bulut , 9.8.2009
  93. 93. 11.7 x
  94. 94. LYRICA, FDA • 5.4 Suicidal Behavior and Ideation • LYRICA, increase the risk of suicidal thoughts or behavior in patients taking for any indication. • Pooled analyses of 199 placebo-controlled clinical trials of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks (27,863 AED-treated patients, 6,029 placebo-treated patients). Representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. • The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed. There is no head to head study with LYRICA and Neurontin!
  95. 95. TURKEY KİLO ARTIŞI, 9% OF PATIENTS,USA
  96. 96. sss
  97. 97. SSRIs
  98. 98. SSRIs= KILLER DRUGS FULLY REIMBURSIBLE!!  34 cases of bizarre behavior,  28 school shootings/incidents,  46 road rage tragedies,  10 air rage incidents,  32 postpartum depression cases,  over 500 murders (homicides),  over 180 murder-suicides and other acts of violence including workplace violence
  99. 99. February 2008
  100. 100. The Physicians' Desk Reference 2009 • The Physicians' Desk Reference lists the following adverse reactions (side effects) to antidepressants among a host of other physical and neuropsychiatric effects: • Manic Reaction (Mania, e.g., Kleptomania, Pyromania, Dipsomania) • Abnormal Thinking • Hallucinations • Personality Disorder • Amnesia • Agitation • Psychosis • Abnormal Dreams • Emotional Lability (Or Instability) • Alcohol Abuse and/or Craving • Hostility • Paranoid Reactions • Confusion • Delusions • Sleep Disorders • Akathisia (Severe Inner Restlessness) • Discontinuation (Withdrawal) Syndrome • Adverse reactions are most likely to occur when starting or discontinuing the drug, increasing or lowering the dose or when switching from one SSRI to another. Adverse reactions are often diagnosed as bipolar disorder when the symptoms may be entirely iatrogenic (treatment induced). Withdrawal, especially abrupt withdrawal, from any of these medications can cause severe neuropsychiatric and physical symptoms. It is important to withdraw extremely slowly from these drugs, often over a period of a year or more, under the supervision of a qualified and experienced specialist, if available.
  101. 101. Selective Serotonin Reuptake Inhibitor (SSRI) Drugs: More Risks Than Benefits? Joel M. Kauffman, Journal of American Physicians and Surgeons 14: 7-12, 2009 Adverse effects are common, occurring in up to 75% of subjects. Severe adverse effects may be underreported. Meta-analyses of controlled trials did not include any actual suicides or murders, but only suicidality, some finding, in 1991 and 2007, no evidence even of suicidality. Other meta-analyses using many of the same trials found that suicidality doubled to 1 in 500 on SSRIs compared with placebo or non-SSRI antidepressants, but did not include any actual suicides or murders. The trial designs were devised by SSRI makers to prevent reports of suicides, by eliminating subjects with the slightest trace of suicidal tendencies. Retrospective studies by others showed actual suicides on SSRIs with a relative risk (RR) of 2– 3 compared with non-SSRI antidepressants, with an increased incidence of 123/100,000.
  102. 102. Selective Publication of Antidepressant Trials and Its Influence on Apparent Efficacy E H. Turner, AM. Matthews, E Linardatos, R A. Tell, R Rosenthal, n engl j med 358;3 , 2008 Lustral Paksil, GSK
  103. 103. NICE, 2007 donepezil, galantamine, rivastigmine for mild to moderately severe Alzheimer’s disease memantine for moderately severe to severe Alzheimer’s disease. Issue date: November 2006 (amended September 2007) Review date: September 2009 Donepezil, galantamine, rivastigmine (review) and memantine for the treatment of Alzheimer’s disease (amended)
  104. 104. BIG PHARMA COULD NOT BUY NICE! 2009 Since May 2006, NICE has refused to fund three drugs – Aricept, Exelon and Reminyl – for those with mild or severe forms of the disease. In April 2008, the Court of Appeal ruled that NICE should release a fully executable version of the economic model used in preparing ‘Donepezil, galantamine, rivastigmine (review) and memantine for the treatment of Alzheimer’s disease (amended)’ and reconsider the guidance in light of any comments received on the model. Andrew Dillon, NICE's chief executive, said its independent advisory committee these treatments a cost-effective use of NHS resources in the mild stages of the disease'.
  105. 105. Cholinesterase Inhibitors in Mild Cognitive Impairment: A Systematic Review of Randomised Trials Roberto Raschetti1*, Emiliano Albanese1,2, Nicola Vanacore1, Marina Maggini1 PLoS Medicine, November 2007 | Volume 4 | Issue 11 | e338 Conclusions  The use of ChEIs in MCI was not associated with any delay in the onset of AD or dementia.  Moreover, the safety profile showed that the risks associated with ChEIs are not negligible.  The uncertainty regarding MCI as a clinical entity raises the question as to the scientific validity of these trials.
  106. 106. Vitamin E and Donepezil for the Treatment of Mild Cognitive Impairment Ronald C. Petersen, Ph.D., M.D., Ronald G. Thomas, Ph.D., Michael Grundman, M.D., M.P.H.,David Bennett, M.D., Rachelle Doody, M.D., Ph.D., Steven Ferris, Ph.D., Douglas Galasko, M.D.,Shelia Jin, M.D., M.P.H., Jeffrey Kaye, M.D., Allan Levey, M.D., Ph.D., Eric Pfeiffer, M.D., Mary Sano, Ph.D.,Christopher H. van Dyck, M.D., and Leon J. Thal, M.D., for the Alzheimer’s Disease Cooperative Study Group* N Engl J Med 2005;352.1 (13 Nisan 2005) • As compared with the placebo group, there were no significant differences in the probability of progression to Alzheimer's disease in the vitamin E group or the donepezil group during the three years of treatment. • The rate of progression to Alzheimer's disease after three years was not lower among patients treated with donepezil than among those given placebo. • Severe side effecs are significantly higher in Donepezil group.
  107. 107. Cholinesterase Inhibitors Linked to Serious Adverse Events in Older Adults With Dementia Laurie Barclay, Charles Vega, CME/CE Released: 05/20/2009; Medscape • Cholinesterase inhibitors are associated with previously underrecognized serious adverse events in older adults with dementia, which must be carefully balanced against the generally modest benefits of these drugs, according to the results of a population-based cohort study reported in the May 11 issue of the Archives of Internal Medicine. • The study cohort consisted of 19,803 community-dwelling older adults with dementia who were prescribed cholinesterase inhibitors and 61,499 control subjects who were not using these medications. • Compared with control subjects, patients who were prescribed cholinesterase inhibitors had more frequent hospital visits for syncope (31.5 vs 18.6 events per 1000 person-years; adjusted hazard ratio [HR], 1.76. Participants receiving cholinesterase inhibitors also had a higher frequency of other syncope-related events vs control subjects. • These events included hospital visits for bradycardia (6.9 vs 4.4 events per 1000 person-years; HR, 1.69; 95% CI, 1.32 - 2.15), permanent pacemaker insertion (4.7 vs 3.3 events per 1000 person-years; HR, 1.49; and hip fracture (22.4 vs 19.8 events per 1000 person-years; HR, 1.18; .
  108. 108. FDA Talk Paper T05-13 April 11, 2005 FDA Issues Public Health Advisory for Antipsychotic Drugs used for Treatment of Behavioral Disorders in Elderly Patients The Food and Drug Administration (FDA) today issued a public health advisory to alert health care providers, patients, and patient caregivers to new safety information concerning an unapproved (i.e., “off-label”) use of certain drugs called “atypical antipsychotic drugs.” These drugs are approved for the treatment of schizophrenia and mania, but clinical studies of these drugs to treat behavioral disorders in elderly patients with dementia have shown a higher death rate associated with their use compared to patients receiving a placebo (sugar pill). Today’s advisory applies to such antipsychotic drugs as Abilify (aripiprazole), Zyprexa (olanzapine), Seroquel (quetiapine), Risperdal (risperidone), Clozaril (clozapine) and Geodon (ziprasidone). Symbyax, which is approved for treatment of depressive episodes associated with bipolar disorder is also included in the agency’s advisory. FDA is requesting that the manufacturers of all of these kinds of drugs add a boxed warning to their drug labeling describing this risk and noting that these drugs are not approved for the treatment of behavioral symptoms in elderly patients with dementia. Patients receiving these drugs for treatment of behavioral disorders associated with dementia should have their treatment reviewed by their health care providers. In analyses of seventeen placebo-controlled studies of four drugs in this class, the rate of death for those elderly patients with dementia was about 1.6 to 1.7 times that of placebo. Although the causes of death were varied, most seemed to be either heart-related (such as heart failure or sudden death) or from infections (pneumonia). The atypical antipsychotics fall into three drug classes based on their chemical structure. Because the increase in mortality was seen with atypical antipsychotic medications in all three chemical classes, the agency has concluded that the effect is probably related to the common pharmacologic effects of all atypical antipsychotic medications, including those that have not been studied in the dementia population. The agency is considering adding a warning to the labeling of older antipsychotic medications because limited data also suggest a similar increase in mortality for these drugs. The review of the data on these older drugs, however, is still on-going. • Second generation anti-psychotics causes 4.5% mortality among elderly patients. Antipsychotics can not be use in demantia.
  109. 109. NHS National Institute for Health and Clinical Excellence Issue date: November 2006 (amended September 2007) Review date: September 2009  Donepezil, galantamine, rivastigmine (review) and memantine for the treatment of Alzheimer’s disease (amended)  The three acetylcholinesterase inhibitors donepezil, galantamine and rivastigmine are recommended as options in the management of patients with Alzheimer’s disease of moderate severity only those with a Mini Mental State Examination [MMSE] score of between 10 and 20 points), and under the following conditions.  Patients who continue on the drug should be reviewed every 6 months by MMSE score and global, functional and behavioural assessment.  The drug should only be continued while the patient’s MMSE score remains at or above 10 points and their global, functional and behavioural condition remains at a level where the drug is considered to be having a worthwhile effect. Any review involving MMSE assessment should be undertaken by an appropriate specialist team, unless there are locally agreed protocols for shared care.
  110. 110. Recently released internal documents and e-mails show that AstraZeneca, knew a decade ago that its drug Seroquel caused diabetes and significant weight gain. May 26, 2009 Blizzard, McCarthy & Nabers announces the release of AstraZeneca internal documents showing the drug maker knew SEROQUEL caused diabetes and significant weight gain.
  111. 111. Real world side effects of Seroquel (quetiapine fumarate) On May, 30, 2009: 29,764 related reports are studied  Overall results of Seroquel:  Top drug interactions, adverse side effects of Seroquel:  NameCount (% of total incidents)  Diabetes mellitus 4,888 (16.54%)  Pancreatitis 1,844 (6.24%)  Weight increased 1,217 (4.12%)  Death 1,169 (3.96%)  Ill-defined disorder 1,152 (3.90%)  Polytraumatism 1,001 (3.39%)  Diabetic ketoacidosis 983 (3.33%)  Depression 975 (3.30%)  Somnolence 879 (2.97%)  Nausea 860 (2.91%)
  112. 112. Selective Publication of Antidepressant Trials and Its Influence on Apparent Efficacy E H. Turner, AM. Matthews, E Linardatos, R A. Tell, R Rosenthal n engl j med 358;3 , 2008  Among 74 FDA-registered studies, 31%, accounting for 3449 study participants, were not published. Whether and how the studies were published were associated with the study outcome. A total of 37 studies viewed by the FDA as having positive results were published; 1 study viewed as positive was not published. Studies viewed by the FDA as having negative or questionable results were, with 3 exceptions, either not published (22 studies) or published in a way that, in our opinion, conveyed a positive outcome (11 studies). According to the published literature, it appeared that 94% of the trials conducted were positive. By contrast, the FDA analysis showed that 51% were positive.
  113. 113. STATINs
  114. 114. Vital Roles of Cholesterol  Cholesterol acts as a cell to interconnect "lipid molecules". A lipid molecule is needed to stabilize our cell membranes. Without cholesterol, our bodies ruins.  Cholesterol is an important part of the myelin sheath which is a neuron consists of fat-containing cells that insulate the axon from electrical activity. It is to ensure our brain functions properly by aiding route of electrical impulses. Without it, our brain would be difficult to focus and might lose of memory.  Cholesterol has lots of beneficial on the human body immune system.  Cholesterol in cell membranes makes cells waterproof so there can be a different chemistry on the inside and the outside of the cell.  Cholesterol is nature’s repair substance, used to repair wounds, including tears and irritations in the arteries.
  115. 115. Vital Roles of Cholesterol  Cholesterol is produced by almost every cell in the body.  Cholesterol is essential for many important hormones, including hormones that regulate mineral metabolism and blood sugar, hormones that help us deal with stress, and all the sex hormones, such as testosterone, estrogen and progesterone.  Cholesterol is vital to the function of the brain and nervous system.  Cholesterol protects us against depression; it plays a role in the utilization of serotonin, the body’s “feel-good” chemical.  Cholesterol is necessary for the bile salts, needed for the digestion of fats.  Cholesterol is the precursor of vitamin D, which is formed by the action of ultra-violet (UV-B) light on cholesterol in the skin.  Cholesterol is a powerful antioxidant that protects us against free radicals and therefore against cancer.  Cholesterol, especially LDL-cholesterol (the so-called bad cholesterol), helps fight infection.
  116. 116. STATINs • March 2010: The FDA issued a safety announcement about the risk of muscle injury in people taking the 80mg/day dosage of simvastatin. Most statin users are not affected as this is the highest authorized dosage and most people take a lower dosage. Myopathy has long been known as a potential side effect of statins. The FDA based its new warning on a review of a large clinical trial. Consult your doctor if you are concerned
  117. 117. VYTORIN “INEGY” = THE MOST EXPENCIVE PLACEBO SCHERING PLOUGH & MERCK PRESENTS....
  118. 118. F. Cankat Tulunay, 2008 Simvastatin with or without Ezetimibe in Familial Hypercholesterolemia John J.P. Kastelein, M.D., Ph.D., Fatima Akdim, M.D., Erik S.G. Stroes, M.D., Ph.D., Aeilko H. Zwinderman, Ph.D., Michiel L. Bots, M.D., Ph.D., Anton F.H. Stalenhoef, M.D., Ph.D., F.R.C.P., Frank L.J. Visseren, M.D., Ph.D., Eric J.G. Sijbrands, M.D., Ph.D., Mieke D. Trip, M.D., Ph.D., Evan A. Stein, M.D., Ph.D., Daniel Gaudet, M.D., Ph.D., Raphael Duivenvoorden, M.D., Enrico P. Veltri, M.D., A. David Marais, M.D., Ph.D., Eric de Groot, M.D., Ph.D., for the ENHANCE Investigators Published at www.nejm.org March 30, 2008 (10.1056/NEJMoa0800742) • Supported by Merck and Schering-Plough. • Dr. Kastelein reports receiving consulting and lecture fees from Pfizer, Roche, AstraZeneca, Merck, and Schering-Plough and grant support from AstraZeneca, Merck, and Schering-Plough; Dr. Stroes, receiving consulting fees from Novartis, Isis Pharmaceuticals, AstraZeneca, and Roche and lecture fees from AstraZeneca, Merck, and Isis Pharmaceuticals; Dr. Bots, receiving consulting fees from Pfizer and AstraZeneca and lecture fees from Pfizer, AstraZeneca, and Organon; Dr. Stalenhoef, receiving grant support from Merck and Pfizer; Dr. Veltri, being an employee of, receiving royalties for coinventions with, and having an equity interest in Schering-Plough; Dr. Marais, receiving consulting and lecture fees from Abbott, AstraZeneca, Pfizer, and Merck; and Dr. de Groot, receiving consulting fees from Wyeth and lecture fees from Merck. No other potential conflict of interest relevant to this article was reported.
  119. 119. Systematic Review: Comparative Effectiveness and Harms of Combinations of Lipid-Modifying Agents and High-Dose Statin Monotherapy. Sharma M, Ansari MT, Abou-Setta AM, Soares-Weiser K, Ooi TC, Sears M, Yazdi F, Tsertsvadze A, Moher D. Ann Intern Med. 2009 Aug 31 . DATA SOURCES: English-language records from MEDLINE (1966- 2009), EMBASE (1980-2009), and the Cochrane Library (third quarter of 2008). Studies that were longer than 24 weeks and reported clinical and harms outcomes. 102 studies met eligibility criteria. CONCLUSION: Limited evidence suggests that combinations of lipid-lowering agents do not improve clinical outcomes more than high- dose statin monotherapy. Very-low-quality evidence favors statin-ezetimibe treatment for attainment of low-density lipoprotein cholesterol goals.
  120. 120. Simvastatin with or without Ezetimibe in Familial Hypercholesterolemia John J.P. Kastelein, M.D., Ph.D., Fatima Akdim, M.D., Erik S.G. Stroes, M.D., Ph.D., Aeilko H. Zwinderman, Ph.D., Michiel L. Bots, M.D., Ph.D., Anton F.H. Stalenhoef, M.D., Ph.D., F.R.C.P., Frank L.J. Visseren, M.D., Ph.D., Eric J.G. Sijbrands, M.D., Ph.D., Mieke D. Trip, M.D., Ph.D., Evan A. Stein, M.D., Ph.D., Daniel Gaudet, M.D., Ph.D., Raphael Duivenvoorden, M.D., Enrico P. Veltri, M.D., A. David Marais, M.D., Ph.D., Eric de Groot, M.D., Ph.D., for the ENHANCE Investigators www.nejm.org March 30, 2008  Results The primary outcome, the mean (±SE) change in the carotid-artery intima–media thickness, was 0.0058±0.0037 mm in the simvastatin-only group and 0.0111±0.0038 mm in the simvastatin-plus- ezetimibe (combined-therapy) group (P=0.29). Secondary outcomes (consisting of other variables regarding the intima– media thickness of the carotid and femoral arteries) did not differ significantly between the two groups.
  121. 121. Merck/Schering-Plough Pharmaceuticals. ENHANCE trial results. January 14, 2008. ENHANCE: Primary end point End point Ezetimibe plus simvastatin Simvastatin alone p Change in mean carotid IMT after 2-y treatment (mm) 0.0111 0.0058 0.29
  122. 122. ENHANCE: CV events Merck/Schering-Plough Pharmaceuticals. ENHANCE trial results. January 14, 2008. Event Ezetimibe plus simvastatin, n Simvastatin alone, n CV death 2/357 1/363 Nonfatal MI 3/357 2/263 Nonfatal stroke 1/357 1/363 Revascularization 6/357 5/363
  123. 123. The Vytorin on Carotid Intima-Media Thickness and Overall Arterial Rigidity (VYCTOR) Study Alejandra Meaney,Guillermo Ceballos,Juan Asbun,Gustavo Solache,Emma Mendoza,Agustín Vela,and Eduardo Meaney, J Clin Pharm OnlineFirst, published on May 14, 2009 This study is one of the first providing evidence that dual therapy has a beneficial effect on a surrogate marker of atherosclerosis!!!. Pravastatin+Ezetimibe Simvastatin Simvastatin+Ezetimibe
  124. 124. FENOFİBRAT
  125. 125. Statins and erectile dysfunction: results of a case/non-case study using the French Pharmacovigilance System Database. Do C, Huyghe E, Lapeyre-Mestre M, Montastruc JL, Bagheri H., Drug Saf. 2009;32(7):591-7. METHODS:. The study period was from 1 January 1985 to 31 December 2006, limited to males aged 13-80 years. RESULTS: Among the total of spontaneous reports selected (110 685), exposure to statins was identified in 4471 cases (4%), of which 51 reports (1.1%) concerned ED, whereas 431 (0.4%) cases of ED were found in the 106 214 reports without exposure to statins (p < 0.0001). The mean delay of onset of ED after starting statins, was 62 days (median 29 days). In 56.9% of cases, recovery occurred after withdrawal of statin, and rechallenge was positive in five cases. The association was statistically significant for all statins (adjusted ROR = 2.4; 95% CI 1.8, 3.3), simvastatin (aROR = 2.6; 1.6, 4.1), atorvastatin (aROR = 3.4; 2.1, 5.4) and rosuvastatin (aROR = 7.1; 2.6, 19.4) [p < 0.001 for all] but not for pravastatin and fluvastatin. We did not find any relationship between the occurrence of ED and the daily dose or the duration of exposure to statins . Assessment of the association between drugs other than statins known to be at risk of ED confirmed a significant association for finasteride (aROR = 14.5; 95% CI 8.3, 25.4), fibrates (aROR = 3.6; 2.6, 5.1), beta-adrenergic receptor antagonists (aROR = 1.5; 1.01, 2.1) and tricyclic antidepressants (aROR = 2.0; 1.2, 3.4) [all p < 0.05]. CONCLUSION: Despite some methodological limitations, the present study suggests that statins may induce or worsen ED in accordance with other data
  126. 126. Lipitor And Impotence: Unfortunately, Side Effects Include Experiencing Erectile Dysfunction • A Close Relation Exists Between Lipitor And Impotence • Cholesterol is the precursor for a whole class of hormones known as the steroid hormones that are absolutely critical for life, as we know it. These hormones determine our sexuality, control the reproductive process, and regulate blood sugar levels and mineral metabolism.
  127. 127. Simvastatin and impotence G Jackson, BMJ 1997;315:31 • Five men with coronary artery disease developed impotence within one week of starting treatment with simvastatin 10 mg or having the dose increased to 20 mg (three men); they also had profound lethargy and inertia. Drug treatment for heart disease (aspirin alone in two patients) was not changed. Within one week of stopping simvastatin sexual function was restored. Two patients were rechallenged with simvastatin and impotence recurred and was resolved within a week. • Adverse effects on sexual function are not reported in the major trials of simvastatin or in the drug's data sheets. The Australian Adverse Drug Reactions Committee has reported 42 cases of impotence associated with simvastatin, the onset being from 48 hours to 27 months after starting treatment.3 Simvastatin was the only drug implicated in 35 cases, with four developing impotence on rechallenge. • Simvastatin may affect the central nervous system directly by passing through the blood-brain barrier or it may interact with other agents that might cause impotence. However, two of these five patients and 35 in Australia were not receiving any other drugs, which suggests an effect on the central nervous system.
  128. 128.  Muscle pain The most common statin side effect is muscle pain. You may feel this pain as a soreness, tiredness or weakness in your muscles. The pain can be a mild discomfort, or it can be severe enough to make your daily activities difficult.  Statins can cause life-threatening muscle damage called rhabdomyolysis . Rhabdomyolysis can cause liver damage, kidney failure and death.  Liver damage Statin use could cause your liver to increase its production of enzymes. If the increase is severe, you may need to stop taking the drug, which usually reverses the problem. If left unchecked, increased liver enzymes may lead to permanent liver damage. Certain other cholesterol-lowering drugs, such as gemfibrozil (Lopid) and niacin, increase the risk of liver problems even more in people who take statins. Because liver problems may develop without symptoms, people who take statins should have their liver function tested about six weeks after they start taking a statin, and then again every three to six months for the first year of treatment, particularly if their statin dose is increased.  Digestive problems Some people taking a statin may develop nausea, diarrhea or constipation after taking a statin. Taking your statin medication in the evening with a meal can reduce digestive side effects.  Rash or flushing You could develop a rash or flushing after you start taking a statin. If you take a statin and niacin, either in a combination pill such as Simcor or as two separate medications, you're more likely to have this side effect. Taking aspirin before taking your statin medication may help, but talk to your doctor first.  Neurological side effects Statins could be linked to memory loss or amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. Some people experience memory loss, report an inability to concentrate as well, and feel that they are developing Alzheimer’s disease when taking statin drugs. A systematic review of the cases reported to the FDA determined that approximately half of the memory loss problems occurred within 60 days of starting on statin therapy, although memory problems were reported after taking a statin drug for just 5 days. Fortunately most people return to normal after discontinuing the statin drug.
  129. 129.  Taking multiple medications to lower your cholesterol  Being female  Having a smaller body frame  Being age 65 and older  Having kidney or liver disease  Having type 1 or 2 diabetes
  130. 130.  A retrospective cohort analysis of 284 158 consecutive patients in Ontario aged 65 years and older who were admitted for elective surgery  About 7% (n = 19 501) of the patients were taking statins. Overall, 3195 patients experienced postoperative delirium; the rate was significantly higher among patients taking statins (14 per 1000).  Use of statins during the perioperative period may increase the risk of postoperative delirium by about 30%.  The relative risk associated with statin use was somewhat higher among patients who had noncardiac surgery than among those who had cardiac surgery (adjusted OR 1.33, 95% CI 1.16–1.53), and extended to more complicated cases of delirium. We did not observe an increased risk of delirium with 20 other cardiac or noncardiac medications.
  131. 131. Copyright ©2008 Canadian Medical Association or its licensors Redelmeier, D. A. et al. CMAJ 2008;179:645-652 Table 1
  132. 132. Copyright ©2008 Canadian Medical Association or its licensors Redelmeier, D. A. et al. CMAJ 2008;179:645-652 Figure 1: Risk of postoperative delirium with use of statins among elderly patients
  133. 133. Copyright ©2008 Canadian Medical Association or its licensors Redelmeier, D. A. et al. CMAJ 2008;179:645-652 Figure 2: Relative risk of postoperative delirium associated with the use of statins among elderly patients, by type of medication and surgery
  134. 134. Copyright ©2008 Canadian Medical Association or its licensors Redelmeier, D. A. et al. CMAJ 2008;179:645-652 Table 2
  135. 135. Copyright ©2008 Canadian Medical Association or its licensors Redelmeier, D. A. et al. CMAJ 2008;179:645-652 Table 3
  136. 136. Copyright ©2008 Canadian Medical Association or its licensors Redelmeier, D. A. et al. CMAJ 2008;179:645-652 Table 4
  137. 137. I'm trying to get pregnant, can I take Crestor? No. Pregnant, breastfeeding, or women trying to get pregnant should not be taking any kind of cholesterol lowering drugs because statins may cause birth defects.
  138. 138. Trends in Serum Lipids and Lipoproteins of Adults, 1960-2002 Margaret D. Carroll, MSPH; David A. Lacher, MD; Paul D. Sorlie, PhD; James I. Cleeman, MD; David J. Gordon, MD, PhD; Michael Wolz, MS; Scott M. Grundy, MD, PhD; Clifford L. Johnson, MSPH JAMA. 2005;294:1773-1781  Objective To examine trends in serum lipid levels among US adults between 1960 and 2002, with a particular focus on changes since the 1988-1994 NHANES survey.  Main Outcome Measures Mean serum total cholesterol, LDL cholesterol, high-density lipoprotein (HDL) cholesterol, and geometric mean serum triglyceride levels, and the percentage of adults with a serum total cholesterol level of at least 240 mg/dL (6.22 mmol/L).  Results Between 1988-1994 and 1999-2002, total serum cholesterol level of adults aged 20 years or older decreased from 206 mg/dL (5.34 mmol/L) to 203 mg/dL (5.26 mmol/L) (P=.009) and LDL cholesterol levels decreased from 129 mg/dL (3.34 mmol/L) to 123 mg/dL (3.19 mmol/L) (P<.001). Greater and significant decreases were observed in men 60 years or older and in women 50 years or older. The percentage of adults with a total cholesterol level of at least 240 mg/dL (6.22 mmol/L) decreased from 20% during 1988-1994 to 17% during 1999-2002 (P<.001). There was no change in mean HDL cholesterol levels and a nonsignificant increase in geometric mean serum triglyceride levels (P = .06).  Conclusions The decrease in total cholesterol level observed during 1960-1994 and LDL cholesterol level observed during 1976-1994 has continued during 1999-2002 in men 60 to 74 years and women 50 to 74 years. The target value of no more than 17% of US adults with a total cholesterol level of at least 240 mg/dL (6.22 mmol/L), an objective of Healthy People 2010, has been attained. The increase in the proportion of adults using lipid-lowering medication, particularly in older age groups, likely contributed to the decreases in total and LDL cholesterol levels observed. The increased prevalence of obesity in the US population may have contributed to the increase in mean serum triglyceride levels.
  139. 139.  Some people experience memory loss, report an inability to concentrate as well, and feel that they are developing Alzheimer’s disease when taking statin drugs. This memory loss may be so extreme as to be amnesia that lasts for 6 to 12 hours.  A systematic review of the cases reported to the FDA determined that approximately half of the memory loss problems occurred within 60 days of starting on statin therapy, although memory problems were reported after taking a statin drug for just 5 days. Fortunately most people return to normal after discontinuing the statin drug. The time until recovery appears to be related to the amount of time before the cognitive symptoms appeared; that is, the longer it took for the symptoms to appear, the longer it took for the person to recover. However, a small group may continue to suffer with cognitive problems, perhaps indefinitely. The risk of experiencing memory problems while taking statins did show up in the first clinical trials of statins but memory loss occurred in less than half of one percent of the people in the clinical trials.  Meanwhile, about 2 percent of the cases of side effects of statins reported to the FDA at the time these cases were studied concerned cognitive problems including memory loss.  It may be impossible to measure how many people who are taking statins simply ignore smaller lapses of memory or lack of attention. At this point in time, current research does not have an estimate of the incidence of memory loss associated with statin use in the general population.
  140. 140. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials Naveed Sattar, David Preiss, Heather M Murray, Paul Welsh, Brendan M Buckley, Anton J M de Craen, Sreenivasa Rao Kondapally Seshasai, John J McMurray, Dilys J Freeman, J Wouter Jukema, Peter W Macfarlane, Chris J Packard, David J Stott, Rudi G Westendorp, James Shepherd, Barry R Davis, Sara L Pressel, Roberto Marchioli, Rosa Maria Marfi si, Aldo P Maggioni, Luigi Tavazzi, Gianni Tognoni, John Kjekshus, Terje R Pedersen, Thomas J Cook, Antonio M Gotto, Michael B Clearfi eld, John R Downs, Haruo Nakamura, Yasuo Ohashi, Kyoichi Mizuno, Kausik K Ray, Ian Ford  Findings: We identifi ed 13 statin trials with 91 140 participants, of whom 4278 (2226 assigned statins and 2052 assigned control treatment) developed diabetes during a mean of 4 years. Statin therapy was associated with a 9% increased risk for incident diabetes (odds ratio [OR] 1·09; 95% CI 1·02–1·17), with little heterogeneity (I²=11%) between trials. Meta-regression showed that risk of development of diabetes with statins was highest in trials with older participants, but neither baseline body-mass index nor change in LDL-cholesterol concentrations accounted for residual variation in risk. Treatment of 255 (95% CI 150– 852) patients with statins for 4 years resulted in one extra case of diabetes.
  141. 141. Association between statins and development of diabetes Statin Odds ratio (95% CI) Overall (n=91 140) 1.09 (1.02-1.17) Atorvastatin only (n=7773) 1.14 (0.89-1.46) Simvastatin only (n=18 815) 1.11 (0.97-1.26) Rosuvastatin only (n=24 714) 1.18 (1.04-1.33) Pravastatin (n=33 627) 1.03 (0.90-1.19) Lovastatin (n=6211) 0.98 (0.70-1.38)
  142. 142. JUPITER Cholesterol Drug Trial: Marketing Tactics Threaten Public Health and Wealth Vera Hassner Sharav, Alliance for Human Research Protection , 2008  A recent study seems to suggest that cholesterol lowering medication should perhaps be given to everyone, regardless of their level of cholesterol, to prevent future heart attacks. This is big money. At present, sales of cholesterol lowering medications are worth tens of billions of dollars, on a much more limited set of prescribing guidelines. Yet, there are huge numbers of people suffering from the side effects of statins, which include severe muscle pains, cognitive trouble and even Amyotrophic Lateral Sclerosis and Alzheimer's disease.
  143. 143. JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin , NEJM, 2008  "In this trial of apparently healthy persons without hyperlipidemia but with elevated high-sensitivity C- reactive protein levels, rosuvastatin [Crestor] significantly reduced the incidence of major cardiovascular events."  Current treatment algorithms for the prevention of myocardial infarction, stroke, and death from cardiovascular causes recommend statin therapy for patients with established vascular disease, diabetes, and overt hyperlipidemia. Last year Statins commanded a $34 billion market share.
  144. 144. Conclusions In this trial of apparently healthy persons without hyperlipidemia but with elevated high-sensitivity C- reactive protein levels, rosuvastatin significantly reduced the incidence of major cardiovascular events.
  145. 145. EDITORIAL Expanding the Orbit of Primary Prevention — Moving beyond JUPITER Mark A. Hlatky, M.D. NEJM, 359:2280-2282, 2008  JUPITER study might push the orbit of statin therapy outward to include even more of the general population. The JUPITER trial enrolled healthy subjects who did not have high cholesterol levels, according to conventional benchmarks.  The trial of nearly 18,000 patients was stopped, with only 1.9 of its proposed 4 years of follow-up concluded,  On the other side of the balance, of concern are the significantly higher glycated hemoglobin levels and incidence of diabetes in the rosuvastatin group in JUPITER (3.0%, vs. 2.4% in the placebo group; P=0.01). There are also no data on the long-term safety of lowering LDL cholesterol to the level of 55 mg per deciliter (1.4 mmol per liter), as was attained with rosuvastatin in JUPITER, which is lower than in previously reported trials. Long-term safety is clearly important in considering committing low-risk subjects without clinical disease to 20 years or more of drug treatment. Finally, the cost of rosuvastatin (roughly $3.45 per day) is much higher than that of generic statins.
  146. 146. EDITORIAL Expanding the Orbit of Primary Prevention — Moving beyond JUPITER Mark A. Hlatky, M.D. NEJM, 359:2280-2282, 2008  The measurement of high-sensitivity C-reactive protein has been shown to improve the estimation of the risk of coronary events.4 An elevated high-sensitivity C-reactive protein level was an entry criterion for JUPITER, but coronary disease is affected by multiple factors, and high-sensitivity C-reactive protein was just one of several indicators of participants' cardiovascular risk. Ridker et al. suggest, from their meta- regression analysis, that the risk reduction observed in JUPITER was greater than that expected on the basis of previous trials. Meta-regression is not a reliable technique, however, and the early termination of JUPITER owing to the efficacy data probably exaggerated the results to some degree.5  The design of JUPITER means that the study provides only limited and indirect information about the role of high-sensitivity C-reactive protein testing in clinical management, since the trial did not compare subjects with and those without high- sensitivity C-reactive protein measurements, nor did it compare the use of high- sensitivity C-reactive protein with the use of other markers of cardiovascular risk. It also did not ascertain whether subjects with a high-sensitivity C-reactive protein level of less than 2.0 mg per liter would benefit from treatment.
  147. 147. EDITORIAL Expanding the Orbit of Primary Prevention — Moving beyond JUPITER Mark A. Hlatky, M.D. NEJM, 359:2280-2282, 2008  In evaluating how to use high-sensitivity C-reactive protein testing in practice, it is important to understand how the participants in JUPITER were selected. The 89,890 subjects who attended a clinic visit appear to have been prescreened to exclude those who had previous lipid-lowering therapy, diabetes, elevated serum creatinine levels, or poorly controlled hypertension. At the screening visit, approximately 80% of the remaining subjects were excluded, most because of LDL cholesterol or high-sensitivity C-reactive protein levels.  There is increasing recognition that laboratory and screening tests need to be evaluated according to their effects on clinical management and outcomes, not just risk levels. Randomized trials have shown that performing mammography,6 screening for abdominal aortic aneurysm,7 and performing coronary angiography after acute myocardial infarction8 improve outcomes. However, JUPITER was a trial of statin therapy, not high-sensitivity C-reactive protein testing  Guidelines for primary prevention will surely be reassessed on the basis of the JUPITER results, but the appropriate size of the orbit of statin therapy depends on the balance between the benefits of treatment and its long-term safety and cost.
  148. 148. Henry C. Ginsberg, MD College of Physicians & Surgeons , Columbia University, New York For The ACCORD Study Group
  149. 149. Dr. Ginsberg reports receiving ◦ Consulting fees from Merck, Merck Schering Plough, Bristol-Myers Squibb, AstraZeneca, Abbott, Roche, Isis/Genzyme, GlaxoSmithKline, Novartis, Pfizer, and Regeneron/ SanofiAventis. ◦ Grant support from Merck, ISIS/Genzyme, Roche, and AstraZeneca.
  150. 150. ACCORD Study Design • Designed to independently test three medical strategies to reduce cardiovascular disease in diabetic patients • Lipid Trial question: whether combination therapy with a statin plus a fibrate would reduce cardiovascular disease compared to statin monotherapy in people with type 2 diabetes mellitus at high risk for cardiovascular disease. • Randomized, placebo-controlled, double-blind clinical trial conducted in 77 clinical sites in the U.S. and Canada
  151. 151. ACCORD Study Design • Overall ACCORD Glycemia Trial: 10,251 participants • Lipid Trial: 5,518 in Lipid Trial • 2765 randomized to fenofibrate • 2753 randomized to placebo • Primary Outcome: First occurrence of a major cardiovascular event (nonfatal MI, nonfatal stroke, cardiovascular death) • 87% power to detect a 20% reduction in event rate, assuming placebo rate of 2.4%/yr and 5.6 yrs follow-up in participants without events.
  152. 152.  All participants on open-labeled simvastatin, 20 to 40 mg/day ◦ Simvastatin dose complied with lipid guidelines  Patients randomized to double-blind placebo or fenofibrate, 54 to 160mg/day ◦ Dosing based upon eGFR level  Only blinded ACCORD trial  Observed Follow-up: 4 to 8 years (mean 4.7 years)
  153. 153. 140 150 160 170 180 190 200 0 1 2 3 4 5 6 7 mg/dl Years Post- Randomization Mean Total Cholesterol Feno Placebo N = 5483 5180 4988 4783 5250 3377 1668 491 60 70 80 90 100 110 120 0 1 2 3 4 5 6 7 mg/dl Years Post- Randomization Mean LDL-C Feno Placebo N = 5483 5180 4988 4783 5250 3377 1668 491N = 5483 5180 4988 4783 5250 3377 1668 491N = 5483 5180 4988 4783 5250 3377 1668 491 37 38 39 40 41 42 0 1 2 3 4 5 6 7 mg/dl Years Post- Randomization Mean HDL-C Feno Placebo N = 5483 5180 4988 4783 5250 3377 1668 491N = 5483 5180 4988 4783 5250 3377 1668 491 110 120 130 140 150 160 170 0 1 2 3 4 5 6 7 mg/dl Years Post- Randomization Median Triglycerides Feno Placebo N = 5432 5180 4988 4783 5250 3377 1668 491
  154. 154. Primary Outcome Rate Rate (%/yr) (%/yr) HR (95% CI) P Value Primary Outcome: Major Fatal or Nonfatal Cardiovascular Event 291 2.24 310 2.41 0.92 (0.79 - 1.08) 0.32 Fenofibrate Placebo (N=2765) (N=2753) N of Events N of Events
  155. 155. Prespecified Secondary Outcomes Rate Rate (%/yr) (%/yr) HR (95% CI) P Value Primary + Revasc + hospitalized CHF 641 5.35 667 5.64 0.94 (0.85-1.05) 0.30 Major Coronary Event 332 2.58 353 2.79 0.92 (0.79-1.07) 0.26 Nonfatal MI 173 1.32 186 1.44 0.91 (0.74 - 1.12) 0.39 Total Stroke 51 0.38 48 0.36 1.05 (0.71 - 1.56) 0.80 Nonfatal Stroke 47 0.35 40 0.30 1.17 (0.76 - 1.78) 0.48 Total Mortality 203 1.47 221 1.61 0.91 (0.75 - 1.10) 0.33 Cardiovascular Death 99 0.72 114 0.83 0.86 (0.66 - 1.12) 0.26 Fatal/Nonfatal CHF 120 0.90 143 1.09 0.82 (0.65 - 1.05) 0.10 Fenofibrate Placebo Outcome (N=2765) (N=2753) N of Events N of Events
  156. 156. Conclusion • ACCORD Lipid does not support use of the combination of fenofibrate and simvastatin compared to simvastatin alone to reduce CVD events in the majority of patients with T2DM who have HDL- C and TG levels that are close to the normal range
  157. 157. HYPERTENSION
  158. 158. Centre for Evidence-Based Medicine
  159. 159. Telmisartan, ramipril, or both in patients at high risk for vascular events. Yusuf S, et al for the ONTARGET investigators. N Engl J Med 2008: 358:1547-1559.  The angiotensin receptor blocker (ARB) telmisartan (Micardis, Boehringer Ingelheim) was "noninferior" to the ACE inhibitor ramipril in patients with vascular disease or high-risk diabetes in the landmark ONTARGET trial. However, the combination of the two drugs was associated with more adverse events without an increase in benefit.  Dr John McMurray (University of Glasgow, Scotland) comments: "As the fourth and largest comparative trial, the ONTARGET study confirms, beyond doubt, that angiotensin receptor blockers are not better than ACE inhibitors at reducing fatal and nonfatal cardiovascular events.“  But he says the ONTARGET trial was a "high-quality noninferiority trial" and shows that telmisartan provides a similar benefit to that of a proven ACE inhibitor, a result that was also found with valsartan (Diovan, Novartis) vs captopril in the VALIANT trial in MI patients.
  160. 160. Yusuf S et al. N Engl J Med 2008: 358:1547-1559. ONTARGET: Key results Outcome Ramipril, n=8576 (%) Telmisartan, n=8542 (%) Combination, n=8502 (%) CV death/MI/ stroke/ CHF hospitalizationa 16.5 16.7 16.3 CV death/MI/strokeb 14.1 13.9 14.1 MI 4.8 5.2 5.2 Stroke 4.7 4.3 4.4 CHF hospitalization 4.1 4.6 3.9 CV death 7.0 7.0 7.3 Any death 11.8 11.6 12.5 Renal impairment 10.2 10.6 13.5 a. Primary end point b. Primary end point in the HOPE trial
  161. 161. Effects of Telmisartan, Ramipril, and Their Combination on Left Ventricular Hypertrophy in Individuals at High Vascular Risk in the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial and the Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease Circulation, September 21, 2009 Paolo Verdecchia MD*, Peter Sleight MD, Giuseppe Mancia MD, Robert Fagard MD, PhD, Bruno Trimarco MD, Roland E. Schmieder MD, Jae-Hyung Kim MD, Garry Jennings MBBS, PhD, Petr Jansky MD, Jyh-Hong Chen MD, Lisheng Liu MD, Peggy Gao MSc, Jeffrey Probstfield MD, Koon Teo MD, Salim Yusuf MD, DPhil, FRCPC, for the ONTARGET/TRANSCEND Investigators From the Hospital S. Maria della Misericordia, Clinical Research Unit Preventive Cardiology, Perugia, Italy (P.V.); Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada (P.V., P.G., K.T., S.Y.); Cardiovascular Medicine, John Radcliffe Hospital, Oxford, UK (P.S.); University of Milano-Bicocca, Milano, Italy (G.M.); Hypertension Unit, Catholic University of Leuven, Leuven, Belgium (R.F.); Department of Clinical Medicine and Cardiovascular and Immunological Sciences, University Federico II, Naples, Italy (B.T.); Department of Nephrology and Hypertension, Friedrich Alexander University, Erlangen, Germany (R.E.S.); Department of Cardiology, St Paul's Hospital, Catholic University of Korea, Division of Cardiology, Seoul, South Korea (J.-H.K.); Baker IDI Heart and Diabetes Institute, Melbourne, Australia (G.J.); University Hospital Motol, Department of Cardiovascular Surgery, Prague, Czech Republic (P.J.); National Cheng Kung University Medical College, Division of Cardiology, Department of Medicine, Tainan, Taiwan (J.-H.C.); Chinese Academy of Medical Sciences, Department of Hypertension, Fu Wai Hospital, Beijing, China (L.L.); and University of Washington, School of Public Health, Seattle (J.P.). Conclusions—In patients at high vascular risk, telmisartan is more effective than placebo in reducing LVH. New-onset LVH is reduced by 37%. The effect of combination of the 2 drugs on LVH is similar to that of ramipril alone.
  162. 162. WHY????
  163. 163. Effect of Telmisartan on Renal Outcomes: A Randomized Trial. Mann JF, Schmieder RE, Dyal L, McQueen MJ, Schumacher H, Pogue J, Wang X, Probstfield JL, Avezum A, Cardona-Munoz E, Dagenais GR, Diaz R, Fodor G, Maillon JM, Rydén L, Yu CM, Teo KK, Yusuf S; for the TRANSCEND (Telmisartan Randomised Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease) Investigators. Ann Intern Med. 2009 May 18. RESULTS: No important difference was found in the composite renal outcome with telmisartan versus placebo. CONCLUSION: In adults with vascular disease but without macroalbuminuria, telmisartan's effects on major renal outcomes were similar to those of placebo.
  164. 164. Telmisartan to Prevent Recurrent Stroke and Cardiovascular Events Salim Yusuf, M.B., B.S., D.Phil., Hans-Christoph Diener, M.D., Ph.D., Ralph L. Sacco, M.D., Daniel Cotton, M.S., Stephanie Ôunpuu, Ph.D., William A. Lawton, B.A., Yuko Palesch, Ph.D., Reneé H. Martin, Ph.D., Gregory W. Albers, M.D., Philip Bath, F.R.C.P., Natan Bornstein, M.D., Bernard P.L. Chan, M.D., Sien-Tsong Chen, M.D., Luis Cunha, M.D., Ph.D., Björn Dahlöf, M.D., Ph.D., Jacques De Keyser, M.D., Ph.D., Geoffrey A. Donnan, M.D., Conrado Estol, M.D., Ph.D., Philip Gorelick, M.D., Vivian Gu, M.D., Karin Hermansson, D.M.Sc., Lutz Hilbrich, M.D., Markku Kaste, M.D., Ph.D., Chuanzhen Lu, M.D., Thomas Machnig, M.D., Prem Pais, M.D., Robin Roberts, M.Tech., Veronika Skvortsova, M.D., Philip Teal, M.D., Danilo Toni, M.D., Cam VanderMaelen, Ph.D., Thor Voigt, M.D., Michael Weber, M.D., Byung-Woo Yoon, M.D., Ph.D., for the PRoFESS Study Group NEJM, 359:1225-1237, 2008 We evaluated the effects of therapy with an angiotensin-receptor blocker, telmisartan, initiated early after a stroke. Methods In a multicenter trial involving 20,332 patients who recently had an ischemic stroke, we randomly assigned 10,146 to receive telmisartan (80 mg daily) and 10,186 to receive placebo.The primary outcome was recurrent stroke. Secondary outcomes were major cardiovascular events (death from cardiovascularcauses, recurrent stroke, myocardial infarction, or new or worsening heart failure) and new-onset diabetes. Results. During a mean follow-up of 2.5 years, the mean blood pressure was 3.8/2.0 mm Hg lower in the telmisartan group than in the placebo group. A total of 880 patients (8.7%) in the telmisartan group and 934 patients (9.2%) in the placebo group had a subsequent stroke. Major cardiovascular events occurred in 1367 patients (13.5%) in the telmisartan group and 1463 patients (14.4%) in the placebo group. Conclusions Therapy with telmisartan initiated soon after an ischemic stroke and continued for 2.5 years did not significantly lower the rate of recurrent stroke, major cardiovascular events, or diabetes.
  165. 165. Telmisartan, ramipril, or both in patients at high risk for vascular events. Yusuf S, et al for the ONTARGET investigators. N Engl J Med 2008: 358:1547-1559. 1.41 TL/GÜN 0.46 TL/GÜN ACEI
  166. 166. 40 mg is registered in Turkey, but not in the market! Only maximum dose (80 mg) is in the market! WHY???.. DOSAGE AND ADMINISTRATION Dosage must be individualized. The usual starting dose of MICARDIS (telmisartan) tablets is 40 mg once a day. Blood pressure response is dose related over the range of 20-80 mg. Micardis® (telmisartan) Tablets, 20 mg, 40 mg and 80 mg
  167. 167. BU YANLIZ TÜRKİYEDE OLUR!! TEK BAŞINA 80 Mg TELMİSARTAN 80 Mg TELMİSARTAN+12.5 Mg HİDROKLOROTİYAZİTTEN 20 Tl DAHA PAHALI

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