Submit Search
Upload
Stability of active ingredients in lon expired prescription medications
•
1 like
•
98 views
M
mack2286
Follow
Stability of active ingredients in lon expired prescription medications
Read less
Read more
Health & Medicine
Report
Share
Report
Share
1 of 3
Download now
Download to read offline
Recommended
Prescription pattern of drugs in pregnancy induced hypertension in a tertiar...
Prescription pattern of drugs in pregnancy induced hypertension in a tertiar...
Naser Tadvi
Estimating the Maximum Safe Starting Dose for First-in-Human Clinical Trials
Estimating the Maximum Safe Starting Dose for First-in-Human Clinical Trials
MaRS Discovery District
Population pharmacokinetics
Population pharmacokinetics
Krishna Shriram.D
Population pharmacokinetics
Population pharmacokinetics
Dr. Ramesh Bhandari
Dose determination in preclinical and clinical studies
Dose determination in preclinical and clinical studies
DrSahilKumar
Dose selection
Dose selection
pp_shivgunde
zhe_CRI2015_drug_v2
zhe_CRI2015_drug_v2
Zhe (Henry) He
1. Introduction to clinical pharmacokinetics
1. Introduction to clinical pharmacokinetics
Dr. Ramesh Bhandari
Recommended
Prescription pattern of drugs in pregnancy induced hypertension in a tertiar...
Prescription pattern of drugs in pregnancy induced hypertension in a tertiar...
Naser Tadvi
Estimating the Maximum Safe Starting Dose for First-in-Human Clinical Trials
Estimating the Maximum Safe Starting Dose for First-in-Human Clinical Trials
MaRS Discovery District
Population pharmacokinetics
Population pharmacokinetics
Krishna Shriram.D
Population pharmacokinetics
Population pharmacokinetics
Dr. Ramesh Bhandari
Dose determination in preclinical and clinical studies
Dose determination in preclinical and clinical studies
DrSahilKumar
Dose selection
Dose selection
pp_shivgunde
zhe_CRI2015_drug_v2
zhe_CRI2015_drug_v2
Zhe (Henry) He
1. Introduction to clinical pharmacokinetics
1. Introduction to clinical pharmacokinetics
Dr. Ramesh Bhandari
Patterns of Prescription Writing in Psychiatric Clinics
Patterns of Prescription Writing in Psychiatric Clinics
Hafiz Saad Salman
Bayesian theory
Bayesian theory
pavithra vinayak
Genetics of antipsychotic drug outcome and implications for the clinician in...
Genetics of antipsychotic drug outcome and implications for the clinician in...
BARRY STANLEY 2 fasd
Hyperkalemia JC
Hyperkalemia JC
Elmira Darvish
Therapeutic drug monitoring
Therapeutic drug monitoring
Urmila Aswar
Characteristics of efficacy evidence supporting approval of supplemental indi...
Characteristics of efficacy evidence supporting approval of supplemental indi...
Sandeepkumar Balabbigari, PharmD, RPh
First in Human dose
First in Human dose
Ramakanth Gadepalli
Analysis of kinetic data
Analysis of kinetic data
Vineetha Menon
PROs and Patient Preference Studies
PROs and Patient Preference Studies
Sheily Kamra
Pharmacometrics
Pharmacometrics
Animesh Mandal
Tapering Meta-Analysis Erin Krebs
Tapering Meta-Analysis Erin Krebs
Paul Coelho, MD
COPD Journal Club
COPD Journal Club
Jade Abudia
Population pharamacokinetics
Population pharamacokinetics
Dr. Ramesh Bhandari
Interpreting population pharmacokinetic pharmacodynamic analyses – a clinical...
Interpreting population pharmacokinetic pharmacodynamic analyses – a clinical...
Ming Chia Lee
Nocebo In FMS
Nocebo In FMS
Paul Coelho, MD
Analysis of pk data- Pop PK analysis
Analysis of pk data- Pop PK analysis
Gayathri Ravi
BCATSfinal
BCATSfinal
Shruti Marwaha
Daptomycin MUE Jun to Oct 2014
Daptomycin MUE Jun to Oct 2014
Hang Truong-McDaniel
Adaptive method OR dosing with feedback
Adaptive method OR dosing with feedback
pavithra vinayak
Senior philosophy graded
Senior philosophy graded
Casey Burritt
Health Presentation
Health Presentation
ampellegrino
5 Grand Rounds
5 Grand Rounds
Casey Burritt
More Related Content
What's hot
Patterns of Prescription Writing in Psychiatric Clinics
Patterns of Prescription Writing in Psychiatric Clinics
Hafiz Saad Salman
Bayesian theory
Bayesian theory
pavithra vinayak
Genetics of antipsychotic drug outcome and implications for the clinician in...
Genetics of antipsychotic drug outcome and implications for the clinician in...
BARRY STANLEY 2 fasd
Hyperkalemia JC
Hyperkalemia JC
Elmira Darvish
Therapeutic drug monitoring
Therapeutic drug monitoring
Urmila Aswar
Characteristics of efficacy evidence supporting approval of supplemental indi...
Characteristics of efficacy evidence supporting approval of supplemental indi...
Sandeepkumar Balabbigari, PharmD, RPh
First in Human dose
First in Human dose
Ramakanth Gadepalli
Analysis of kinetic data
Analysis of kinetic data
Vineetha Menon
PROs and Patient Preference Studies
PROs and Patient Preference Studies
Sheily Kamra
Pharmacometrics
Pharmacometrics
Animesh Mandal
Tapering Meta-Analysis Erin Krebs
Tapering Meta-Analysis Erin Krebs
Paul Coelho, MD
COPD Journal Club
COPD Journal Club
Jade Abudia
Population pharamacokinetics
Population pharamacokinetics
Dr. Ramesh Bhandari
Interpreting population pharmacokinetic pharmacodynamic analyses – a clinical...
Interpreting population pharmacokinetic pharmacodynamic analyses – a clinical...
Ming Chia Lee
Nocebo In FMS
Nocebo In FMS
Paul Coelho, MD
Analysis of pk data- Pop PK analysis
Analysis of pk data- Pop PK analysis
Gayathri Ravi
BCATSfinal
BCATSfinal
Shruti Marwaha
Daptomycin MUE Jun to Oct 2014
Daptomycin MUE Jun to Oct 2014
Hang Truong-McDaniel
Adaptive method OR dosing with feedback
Adaptive method OR dosing with feedback
pavithra vinayak
What's hot
(19)
Patterns of Prescription Writing in Psychiatric Clinics
Patterns of Prescription Writing in Psychiatric Clinics
Bayesian theory
Bayesian theory
Genetics of antipsychotic drug outcome and implications for the clinician in...
Genetics of antipsychotic drug outcome and implications for the clinician in...
Hyperkalemia JC
Hyperkalemia JC
Therapeutic drug monitoring
Therapeutic drug monitoring
Characteristics of efficacy evidence supporting approval of supplemental indi...
Characteristics of efficacy evidence supporting approval of supplemental indi...
First in Human dose
First in Human dose
Analysis of kinetic data
Analysis of kinetic data
PROs and Patient Preference Studies
PROs and Patient Preference Studies
Pharmacometrics
Pharmacometrics
Tapering Meta-Analysis Erin Krebs
Tapering Meta-Analysis Erin Krebs
COPD Journal Club
COPD Journal Club
Population pharamacokinetics
Population pharamacokinetics
Interpreting population pharmacokinetic pharmacodynamic analyses – a clinical...
Interpreting population pharmacokinetic pharmacodynamic analyses – a clinical...
Nocebo In FMS
Nocebo In FMS
Analysis of pk data- Pop PK analysis
Analysis of pk data- Pop PK analysis
BCATSfinal
BCATSfinal
Daptomycin MUE Jun to Oct 2014
Daptomycin MUE Jun to Oct 2014
Adaptive method OR dosing with feedback
Adaptive method OR dosing with feedback
Viewers also liked
Senior philosophy graded
Senior philosophy graded
Casey Burritt
Health Presentation
Health Presentation
ampellegrino
5 Grand Rounds
5 Grand Rounds
Casey Burritt
喚起國文教學的熱情
喚起國文教學的熱情
wooder
Community hlth planning_project_final 2
Community hlth planning_project_final 2
Casey Burritt
Burritt cc casestudy
Burritt cc casestudy
Casey Burritt
Heart attacksmartattack
Heart attacksmartattack
Casey Burritt
Grand rounds
Grand rounds
Casey Burritt
Pediatric issues paper
Pediatric issues paper
Casey Burritt
Progress summary paper
Progress summary paper
Casey Burritt
Stability of active ingredients in lon expired prescription medications
Stability of active ingredients in lon expired prescription medications
mack2286
從袪魅到返魅
從袪魅到返魅
wooder
Activism paper
Activism paper
Casey Burritt
Bonfire Night
Bonfire Night
annitaguai
Sophomore philosophy
Sophomore philosophy
Casey Burritt
Transplant paper
Transplant paper
Casey Burritt
從袪魅到返魅
從袪魅到返魅
wooder
Kertas kerja bengkel teknik menjawab soalan 2014
Kertas kerja bengkel teknik menjawab soalan 2014
remz21
DeadLock Preventer
DeadLock Preventer
Teodor Madan
Viewers also liked
(19)
Senior philosophy graded
Senior philosophy graded
Health Presentation
Health Presentation
5 Grand Rounds
5 Grand Rounds
喚起國文教學的熱情
喚起國文教學的熱情
Community hlth planning_project_final 2
Community hlth planning_project_final 2
Burritt cc casestudy
Burritt cc casestudy
Heart attacksmartattack
Heart attacksmartattack
Grand rounds
Grand rounds
Pediatric issues paper
Pediatric issues paper
Progress summary paper
Progress summary paper
Stability of active ingredients in lon expired prescription medications
Stability of active ingredients in lon expired prescription medications
從袪魅到返魅
從袪魅到返魅
Activism paper
Activism paper
Bonfire Night
Bonfire Night
Sophomore philosophy
Sophomore philosophy
Transplant paper
Transplant paper
從袪魅到返魅
從袪魅到返魅
Kertas kerja bengkel teknik menjawab soalan 2014
Kertas kerja bengkel teknik menjawab soalan 2014
DeadLock Preventer
DeadLock Preventer
Similar to Stability of active ingredients in lon expired prescription medications
P&T Newsletter February 2015
P&T Newsletter February 2015
Florentina Eller
Pharmacoepidemiology
Pharmacoepidemiology
Ravilla Jyothsna Naidu
Drug risk assessment 23 4-2010
Drug risk assessment 23 4-2010
RobHeerdink
Cytisine, the world’s oldest smoking cessation aid Growing evidence for its u...
Cytisine, the world’s oldest smoking cessation aid Growing evidence for its u...
Georgi Daskalov
Tabex 2013 nai vajnototootot (2014 10_24 15_22_48 utc)
Tabex 2013 nai vajnototootot (2014 10_24 15_22_48 utc)
Georgi Daskalov
Cytisine, the world’s oldest smoking cessation aid Growing evidence for its u...
Cytisine, the world’s oldest smoking cessation aid Growing evidence for its u...
Georgi Daskalov
Tabex 2013 (2014 10_24 15_22_48 utc)
Tabex 2013 (2014 10_24 15_22_48 utc)
Georgi Daskalov
Homeopathy And Cancer
Homeopathy And Cancer
drstevenmoore
The-Case-for-Practice-Integration[1]
The-Case-for-Practice-Integration[1]
Amy Williams
Finding promiscuous old drugs for new uses
Finding promiscuous old drugs for new uses
US Environmental Protection Agency (EPA), Center for Computational Toxicology and Exposure
For this Discussion, review the case Learning Resources and the .docx
For this Discussion, review the case Learning Resources and the .docx
evonnehoggarth79783
DOES METHYLPHENIDATE STIMULANT MEDICATION OR AMPHETAMINE STIMULANT MEDICATION...
DOES METHYLPHENIDATE STIMULANT MEDICATION OR AMPHETAMINE STIMULANT MEDICATION...
Colin MacKichan
WHMS PGx Presentation
WHMS PGx Presentation
Orion Cuffe
Thesis_PhD_Improving medication safety in the elderly
Thesis_PhD_Improving medication safety in the elderly
HA VO THI
Nada Alkis' Master Thesis, Novo Nordisk & University of Copenhagen
Nada Alkis' Master Thesis, Novo Nordisk & University of Copenhagen
Nada Alkis
Evaluating the efficacy of different platelet rich plasma regimens for manage...
Evaluating the efficacy of different platelet rich plasma regimens for manage...
anestesiaudec
20091109 Biol1010 Personalized Medicine
20091109 Biol1010 Personalized Medicine
Michel Dumontier
Copyright 2016 American Medical Association. All rights reserv.docx
Copyright 2016 American Medical Association. All rights reserv.docx
vanesaburnand
provide recommendations for alternative drug treatments to address.docx
provide recommendations for alternative drug treatments to address.docx
simonlbentley59018
Reduction-in-Methadone-letter-size
Reduction-in-Methadone-letter-size
Adolfo Gonzalez
Similar to Stability of active ingredients in lon expired prescription medications
(20)
P&T Newsletter February 2015
P&T Newsletter February 2015
Pharmacoepidemiology
Pharmacoepidemiology
Drug risk assessment 23 4-2010
Drug risk assessment 23 4-2010
Cytisine, the world’s oldest smoking cessation aid Growing evidence for its u...
Cytisine, the world’s oldest smoking cessation aid Growing evidence for its u...
Tabex 2013 nai vajnototootot (2014 10_24 15_22_48 utc)
Tabex 2013 nai vajnototootot (2014 10_24 15_22_48 utc)
Cytisine, the world’s oldest smoking cessation aid Growing evidence for its u...
Cytisine, the world’s oldest smoking cessation aid Growing evidence for its u...
Tabex 2013 (2014 10_24 15_22_48 utc)
Tabex 2013 (2014 10_24 15_22_48 utc)
Homeopathy And Cancer
Homeopathy And Cancer
The-Case-for-Practice-Integration[1]
The-Case-for-Practice-Integration[1]
Finding promiscuous old drugs for new uses
Finding promiscuous old drugs for new uses
For this Discussion, review the case Learning Resources and the .docx
For this Discussion, review the case Learning Resources and the .docx
DOES METHYLPHENIDATE STIMULANT MEDICATION OR AMPHETAMINE STIMULANT MEDICATION...
DOES METHYLPHENIDATE STIMULANT MEDICATION OR AMPHETAMINE STIMULANT MEDICATION...
WHMS PGx Presentation
WHMS PGx Presentation
Thesis_PhD_Improving medication safety in the elderly
Thesis_PhD_Improving medication safety in the elderly
Nada Alkis' Master Thesis, Novo Nordisk & University of Copenhagen
Nada Alkis' Master Thesis, Novo Nordisk & University of Copenhagen
Evaluating the efficacy of different platelet rich plasma regimens for manage...
Evaluating the efficacy of different platelet rich plasma regimens for manage...
20091109 Biol1010 Personalized Medicine
20091109 Biol1010 Personalized Medicine
Copyright 2016 American Medical Association. All rights reserv.docx
Copyright 2016 American Medical Association. All rights reserv.docx
provide recommendations for alternative drug treatments to address.docx
provide recommendations for alternative drug treatments to address.docx
Reduction-in-Methadone-letter-size
Reduction-in-Methadone-letter-size
Recently uploaded
(👑VVIP ISHAAN ) Russian Call Girls Service Navi Mumbai🖕9920874524🖕Independent...
(👑VVIP ISHAAN ) Russian Call Girls Service Navi Mumbai🖕9920874524🖕Independent...
Taniya Sharma
Bangalore Call Girls Majestic 📞 9907093804 High Profile Service 100% Safe
Bangalore Call Girls Majestic 📞 9907093804 High Profile Service 100% Safe
narwatsonia7
Russian Call Girls in Pune Tanvi 9907093804 Short 1500 Night 6000 Best call g...
Russian Call Girls in Pune Tanvi 9907093804 Short 1500 Night 6000 Best call g...
Miss joya
CALL ON ➥9907093804 🔝 Call Girls Baramati ( Pune) Girls Service
CALL ON ➥9907093804 🔝 Call Girls Baramati ( Pune) Girls Service
Miss joya
Call Girls Service In Shyam Nagar Whatsapp 8445551418 Independent Escort Service
Call Girls Service In Shyam Nagar Whatsapp 8445551418 Independent Escort Service
parulsinha
sauth delhi call girls in Bhajanpura 🔝 9953056974 🔝 escort Service
sauth delhi call girls in Bhajanpura 🔝 9953056974 🔝 escort Service
9953056974 Low Rate Call Girls In Saket, Delhi NCR
Bangalore Call Girls Hebbal Kempapura Number 7001035870 Meetin With Bangalor...
Bangalore Call Girls Hebbal Kempapura Number 7001035870 Meetin With Bangalor...
narwatsonia7
VIP Call Girls Indore Kirti 💚😋 9256729539 🚀 Indore Escorts
VIP Call Girls Indore Kirti 💚😋 9256729539 🚀 Indore Escorts
aditipandeya
Artifacts in Nuclear Medicine with Identifying and resolving artifacts.
Artifacts in Nuclear Medicine with Identifying and resolving artifacts.
MiadAlsulami
Call Girls Horamavu WhatsApp Number 7001035870 Meeting With Bangalore Escorts
Call Girls Horamavu WhatsApp Number 7001035870 Meeting With Bangalore Escorts
vidya singh
VIP Call Girls Pune Vani 9907093804 Short 1500 Night 6000 Best call girls Ser...
VIP Call Girls Pune Vani 9907093804 Short 1500 Night 6000 Best call girls Ser...
Miss joya
Call Girls Service Pune Vaishnavi 9907093804 Short 1500 Night 6000 Best call ...
Call Girls Service Pune Vaishnavi 9907093804 Short 1500 Night 6000 Best call ...
Miss joya
Call Girls Cuttack Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Cuttack Just Call 9907093804 Top Class Call Girl Service Available
Dipal Arora
♛VVIP Hyderabad Call Girls Chintalkunta🖕7001035870🖕Riya Kappor Top Call Girl ...
♛VVIP Hyderabad Call Girls Chintalkunta🖕7001035870🖕Riya Kappor Top Call Girl ...
astropune
Call Girls Ludhiana Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Ludhiana Just Call 9907093804 Top Class Call Girl Service Available
Dipal Arora
VIP Call Girls Tirunelveli Aaradhya 8250192130 Independent Escort Service Tir...
VIP Call Girls Tirunelveli Aaradhya 8250192130 Independent Escort Service Tir...
narwatsonia7
💎VVIP Kolkata Call Girls Parganas🩱7001035870🩱Independent Girl ( Ac Rooms Avai...
💎VVIP Kolkata Call Girls Parganas🩱7001035870🩱Independent Girl ( Ac Rooms Avai...
Taniya Sharma
Call Girl Coimbatore Prisha☎️ 8250192130 Independent Escort Service Coimbatore
Call Girl Coimbatore Prisha☎️ 8250192130 Independent Escort Service Coimbatore
narwatsonia7
Call Girl Number in Vashi Mumbai📲 9833363713 💞 Full Night Enjoy
Call Girl Number in Vashi Mumbai📲 9833363713 💞 Full Night Enjoy
babeytanya
Lucknow Call girls - 8800925952 - 24x7 service with hotel room
Lucknow Call girls - 8800925952 - 24x7 service with hotel room
discovermytutordmt
Recently uploaded
(20)
(👑VVIP ISHAAN ) Russian Call Girls Service Navi Mumbai🖕9920874524🖕Independent...
(👑VVIP ISHAAN ) Russian Call Girls Service Navi Mumbai🖕9920874524🖕Independent...
Bangalore Call Girls Majestic 📞 9907093804 High Profile Service 100% Safe
Bangalore Call Girls Majestic 📞 9907093804 High Profile Service 100% Safe
Russian Call Girls in Pune Tanvi 9907093804 Short 1500 Night 6000 Best call g...
Russian Call Girls in Pune Tanvi 9907093804 Short 1500 Night 6000 Best call g...
CALL ON ➥9907093804 🔝 Call Girls Baramati ( Pune) Girls Service
CALL ON ➥9907093804 🔝 Call Girls Baramati ( Pune) Girls Service
Call Girls Service In Shyam Nagar Whatsapp 8445551418 Independent Escort Service
Call Girls Service In Shyam Nagar Whatsapp 8445551418 Independent Escort Service
sauth delhi call girls in Bhajanpura 🔝 9953056974 🔝 escort Service
sauth delhi call girls in Bhajanpura 🔝 9953056974 🔝 escort Service
Bangalore Call Girls Hebbal Kempapura Number 7001035870 Meetin With Bangalor...
Bangalore Call Girls Hebbal Kempapura Number 7001035870 Meetin With Bangalor...
VIP Call Girls Indore Kirti 💚😋 9256729539 🚀 Indore Escorts
VIP Call Girls Indore Kirti 💚😋 9256729539 🚀 Indore Escorts
Artifacts in Nuclear Medicine with Identifying and resolving artifacts.
Artifacts in Nuclear Medicine with Identifying and resolving artifacts.
Call Girls Horamavu WhatsApp Number 7001035870 Meeting With Bangalore Escorts
Call Girls Horamavu WhatsApp Number 7001035870 Meeting With Bangalore Escorts
VIP Call Girls Pune Vani 9907093804 Short 1500 Night 6000 Best call girls Ser...
VIP Call Girls Pune Vani 9907093804 Short 1500 Night 6000 Best call girls Ser...
Call Girls Service Pune Vaishnavi 9907093804 Short 1500 Night 6000 Best call ...
Call Girls Service Pune Vaishnavi 9907093804 Short 1500 Night 6000 Best call ...
Call Girls Cuttack Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Cuttack Just Call 9907093804 Top Class Call Girl Service Available
♛VVIP Hyderabad Call Girls Chintalkunta🖕7001035870🖕Riya Kappor Top Call Girl ...
♛VVIP Hyderabad Call Girls Chintalkunta🖕7001035870🖕Riya Kappor Top Call Girl ...
Call Girls Ludhiana Just Call 9907093804 Top Class Call Girl Service Available
Call Girls Ludhiana Just Call 9907093804 Top Class Call Girl Service Available
VIP Call Girls Tirunelveli Aaradhya 8250192130 Independent Escort Service Tir...
VIP Call Girls Tirunelveli Aaradhya 8250192130 Independent Escort Service Tir...
💎VVIP Kolkata Call Girls Parganas🩱7001035870🩱Independent Girl ( Ac Rooms Avai...
💎VVIP Kolkata Call Girls Parganas🩱7001035870🩱Independent Girl ( Ac Rooms Avai...
Call Girl Coimbatore Prisha☎️ 8250192130 Independent Escort Service Coimbatore
Call Girl Coimbatore Prisha☎️ 8250192130 Independent Escort Service Coimbatore
Call Girl Number in Vashi Mumbai📲 9833363713 💞 Full Night Enjoy
Call Girl Number in Vashi Mumbai📲 9833363713 💞 Full Night Enjoy
Lucknow Call girls - 8800925952 - 24x7 service with hotel room
Lucknow Call girls - 8800925952 - 24x7 service with hotel room
Stability of active ingredients in lon expired prescription medications
1.
sess its effect
on major adverse cardiac events.1 Rates of any cardiac hospitalization were 5% in the intervention group vs 16% in the usual care group. The approxi- mately 70% relative risk reduction and 11% absolute risk reduction in hospitalization for major adverse cardiac events or heart failure are much higher than would be expected for even the most potent intervention or treat- ment in this setting. In the Myocardial Ischemia Reduc- tion with Aggressive Cholesterol Lowering (MIRACL) study, for example, 3086 almost exclusively statin- naı¨ve patients were randomized to receive high-dose ator- vastatin (80 mg/d) or placebo.8 Even one of the most im- pressive treatments in our therapeutic armamentarium, which, in the MIRACL study, lowered low-density lipo- protein cholesterol level by 40%, led to far more modest risk reductions in cardiac events requiring hospitaliza- tion than the reductions reported for enhanced depres- sion care in the COPES trial. Indeed, most of the effect of high-dose statin treatment in the MIRACL study was due to a 26% relative risk reduction and 2% absolute risk reduction in hospitalization for myocardial ischemia. Thus, while the results of the COPES trial are provoca- tive and exciting, they must be replicated in larger, ap- propriately powered trials before the promising reduc- tion in hospitalizations can be used to calculate potential cost savings. Ladapo et al2 should be congratulated for addressing the economicimpactoftheirfindingsandforconductingaran- domized controlled trial in patients with ACS, a difficult enough task in and of itself. However, the task before medi- cal professionals when interpreting studies like this is also challenging. Coping with rising health care costs requires us to carefully examine all the resources that would be in- volved in implementing “more health care” and then, equally, to carefully determine whether this would actu- ally lead to “better health” by evaluating the net gain to pa- tients and society. Whether the COPES trial is good value for the money remains unclear. Published Online: October 15, 2012. doi:10.1001/2013 .jamainternmed.114 Author Affiliations: Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Mary- land (Dr Ziegelstein); Departments of Psychiatry, Coun- seling and Educational Psychology, Epidemiology, Bio- statistics, and Occupational Health, and Medicine and School of Nursing, McGill University, and Lady Davis In- stitute for Medical Research, Jewish General Hospital (Dr Thombs), Montreal, Quebec, Canada. Correspondence: Dr Ziegelstein, Department of Medi- cine, The Johns Hopkins Bayview Center, Mason F. Lord Building, Center Tower, 5200 Eastern Ave, Third Floor, Room 320, Baltimore, MD 21224 (rziegel2@jhmi.edu). Financial Disclosure: None reported. Funding/Support: Dr Ziegelstein is supported by the Miller Family Scholar Program of the Johns Hopkins Cen- ter for Innovative Medicine. Dr Thombs is supported by a New Investigator Award from the Canadian Institutes of Health Research. 1. Davidson KW, Rieckmann N, Clemow L, et al. Enhanced depression care for patients with acute coronary syndrome and persistent depressive symptoms: coronary psychosocial evaluation studies randomized controlled trial. Arch Intern Med. 2010;170(7):600-608. 2. Ladapo JA, Shaffer JA, Fang Y, Ye S, Davidson KW. Cost-effectiveness of en- hanced depression care after acute coronary syndrome: results from the Coro- nary Psychosocial Evaluation Studies randomized controlled trial [pub- lished online October 15, 2012]. Arch Intern Med. 2012;172(21):1682-1684. 3. Frasure-Smith N, Lespe´rance F, Talajic M. Depression following myocardial infarction: impact on 6-month survival. JAMA. 1993;270(15):1819-1825. 4. Czarny MJ, Arthurs E, Coffie DF, et al. Prevalence of antidepressant prescrip- tion or use in patients with acute coronary syndrome: a systematic review. PLoS One. 2011;6(11):e27671. 5. Cassel CK, Guest JA. Choosing wisely: helping physicians and patients make smart decisions about their care. JAMA. 2012;307(17):1801-1802. 6. Grady D, Redberg RF. Less is more: how less health care can result in better health. Arch Intern Med. 2010;170(9):749-750. 7. Unu¨tzer J, Katon W, Callahan CM, et al; IMPACT Investigators. Collabora- tive care management of late-life depression in the primary care setting: a ran- domized controlled trial. JAMA. 2002;288(22):2836-2845. 8. Schwartz GG, Olsson AG, Ezekowitz MD, et al; Myocardial Ischemia Reduc- tion with Aggressive Cholesterol Lowering (MIRACL) Study Investigators. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA. 2001; 285(13):1711-1718. RESEARCH LETTERS Stability of Active Ingredients in Long-Expired Prescription Medications Debate exists regarding the relative potency of medications beyond their labeled expiration dates. Expired medications have not necessar- ily lost potency, since the expiration date is only an as- surance that the labeled potency will last at least until that time.1 Clinical situations may arise in which ex- pired drugs might be considered owing to lack of viable alternatives2 or financial concerns.3 Ongoing studies show that many medications retain their potency years after their initially labeled expiration dates.4 We sought to char- acterize the potency of some prescription medications that had expired decades ago. Methods. Eight long-expired medications with 15 dif- ferent active ingredients were discovered in a retail phar- macy in their original, unopened containers. All had ex- pired 28 to 40 years prior to analysis. Three tablets or capsules of each medication were analyzed, with each sample tested 3 times for each labeled active ingredient. No analytical standard for homatropine could be found, so that ingredient was not tested. Tablets or capsule contents were dissolved and soni- cated in methanol, reconstituted in analysis buffer (10% methanol) and analyzed with Liquid Chromatograph (Agi- lent Technologies) Time-of-Flight Mass Spectrometer (Agilent) using electrospray ionization in negative and positive polarities. Chromatography was run with gra- dient elution using Eclipse Plus C18 column (Agilent). Data analysis was performed using Mass Hunter Quali- tative and Quantitative Analysis (Agilent). Quantifica- tion was performed by isotope dilution method with a 6-point calibration curve. Roy C. Ziegelstein, MD Brett D. Thombs, PhD ARCH INTERN MED/VOL 172 (NO. 21), NOV 26, 2012 WWW.ARCHINTERNMED.COM 1685 ©2012 American Medical Association. All rights reserved. Downloaded From: http://archinte.jamanetwork.com/ by Andres Lopez on 04/19/2015
2.
Results. Twelve of
the 14 drug compounds tested (86%) were present in concentrations at least 90% of the la- beled amounts, the generally recognized minimum ac- ceptable potency. Three of these compounds were present at greater than 110% of the labeled content. Two com- pounds (aspirin and amphetamine) were present in amounts of less than 90% of labeled content. One com- pound (phenacetin) was present at greater than 90% of labeled amounts from 1 medication tested, but less than 90% in another medication that contained that drug (Table). Comment. The US Food and Drug Administration (FDA) permits “reasonable variation,” such that most medica- tions marketed in the United States contain 90% to 110% of the amount of the active ingredient claimed on the la- bel.5 Drug expiration dates typically range from 12 to 60 months after their production.4 However, FDA regula- tions do not require determination of how long medica- tions remain potent after that, allowing manufacturers to arbitrarily establish expiration dates without deter- mining actual long-term drug stability. The Shelf-Life Extension Program (SLEP) checks long- term stability of federal drug stockpiles. Eighty-eight per- cent of 122 different drugs stored under ideal environ- mental conditions had their expiration dates extended more than 1 year, with an average extension of 66 months and a maximum extension of 278 months.4 In our data set, 12 of 14 medications retained full potency for at least 336 months, and 8 of these for at least 480 months. Given our inability to confirm ideal storage conditions for our samples, our results support the effectiveness of broadly extending expiration dates for many drugs, the efficacy of which has been demonstrated by SLEP in a more con- trolled fashion. The 3 drugs found with less than 90% of their la- beled potency were amphetamine and aspirin in both samples tested and phenacetin in 1 of 2 samples tested. Aspirin is known to degrade in vitro,6 but there are no such published data regarding amphetamine. For phen- acetin, the difference in recovery between the 2 samples could be due to differences in packaging or storage of the containers. Aside from aspirin, all drugs in Fiorinal (butal- bital, aspirin, caffeine, and codeine phosphate) had al- most 100% of labeled concentrations, while those of Co- dempiral No. 3 (phenacetin with codeine phosphate) were all less than 95%. Since the codeine measured in Codem- piral No. 3 was also lower than that of Fiorinal (90% vs 99%), this suggests that Codempiral’s packaging was less intact, allowing moisture to penetrate, which can pro- mote hydrolysis. Because phenacetin has an amide func- tional group, it is more prone to this type of degradation than codeine. Three drugs were unexpectedly found in our samples at potencies greater than 110% of the labeled amounts. Some samples may have been produced prior to 1963, when FDA-mandated quality control measures were in- stituted (Paula R. Katz, Regulatory Counsel, FDA, Cen- ter for Drug Evaluation and Research, Division of Manu- facturing and Product Quality, Guidance and Policy; e-mail communication, May 23, 2011); however, exact dating of all our samples was not possible. Alternately, these drugs could have come from lots untested by the manufacturer, or the accuracy between analytical meth- ods used in this study compared with those used de- cades ago could be questioned. The most important implication of our study involves the potential cost savings resulting from lengthier prod- uct expiration dating. Each dollar spent on SLEP to dem- onstrate longer than labeled drug stability results in $13 to $94 saved on reacquisition costs.4 Given that Ameri- cans currently spend more than $300 billion annually on prescription medications,7 extending drug expiration dates could yield enormous health care expenditure savings. In conclusion, this study provides additional evi- dence that many prescription pharmaceuticals retain their full potency for decades beyond their manufacturer- ascribed expiration dates. Given the potential cost- savings, we suggest the current practices of drug expi- ration dating be reconsidered. Published Online: October 8, 2012. doi:10.1001 /archinternmed.2012.4501 Author Affiliations: California Poison Control System, San Diego Division, University of California San Fran- cisco School of Pharmacy, San Diego (Dr Cantrell); De- partment of Emergency Medicine, University of Califor- Table. Declared and Measured Amounts in Drugs Drug Trade Name With Active Ingredients Declared Amount, mg Measured Amount, Mean (SD), mg Somnafac Methaqualone 200.0 240.3 (20.6) Fiorinal with codeine No. 1 Codeine 7.5 7.4 (0.3) Butalbital 50.0 51.1 (1.6) Aspirin 200.0 2.28 (0.10) Phenacetin 130.0 142.8 (7.1) Caffeine 40.0 51.2 (4.8) Codempiral No. 3 Codeine 32.4 29.3 (2.6) Phenobarbital 16.2 15.2 (0.2) Aspirin 226.8 1.53 (0.04) Phenacetin 162.0 87.8 (2.7) Bamadex Meprobamate 300.0 390.8 (44.9) Amphetamine 15.0 8.1 (0.9) Obocell Amphetamine 5.0 2.2 (0.1) Nebralin Pentobarbital 90.0 105.1 (7.4) Seconal Secobarbital 100.0 90.5 (7.1) Hycomine Hydrocodone 5.0 5.2 (0.4) Homatropine 1.5 Not tested Chlorpheniramine 2.0 6.1 (0.2) Acetaminophen 250.0 249.2 (38.3) Caffeine 30.0 30.3 (1.8) Lee Cantrell, PharmD Jeffrey R. Suchard, MD Alan Wu, PhD Roy R. Gerona, PhD ARCH INTERN MED/VOL 172 (NO. 21), NOV 26, 2012 WWW.ARCHINTERNMED.COM 1686 ©2012 American Medical Association. All rights reserved. Downloaded From: http://archinte.jamanetwork.com/ by Andres Lopez on 04/19/2015
3.
nia, Irvine Medical
Center, Orange (Dr Suchard); and Department of Laboratory Medicine, San Francisco Gen- eral Hospital/University of California San Francisco, San Francisco (Drs Wu and Gerona). Correspondence: Dr Cantrell, California Poison Con- trol System, San Diego Division, University of Califor- nia San Francisco School of Pharmacy, 200 W Arbor Dr, San Diego, CA 92103-8925 (lcantrell@calpoison.org). Author Contributions: Study concept and design: Cantrell, Suchard, Wu, and Gerona. Acquisition of data: Gerona. Analysis and interpretation of data: Cantrell, Wu, and Gerona. Drafting of the manuscript: Cantrell, Suchard, Wu, and Gerona. Critical revision of the manuscript for impor- tant intellectual content: Cantrell, Suchard, Wu, and Gerona. Statistical analysis: Gerona. Obtained funding: Wu. Administrative, technical, and material support: Cantrell and Wu. Study supervision: Cantrell and Wu. Financial Disclosure: None reported. Previous Presentation: This study was an oral presen- tation at the 2011 North American Congress of Clinical Toxicology; September 23, 2011; Washington, DC. 1. Title 21 CFR 211.166(a) and (b). Current good manufacturing practice in manufacturing for finished pharmaceuticals and expiration dating (2012). 2. Sandford-Smith J. Outdated drugs may be useful. BMJ. 2003;326(7379):51. 3. Consumer Reports. Risky prescription drug practices are on the rise in a grim economy. http://news.consumerreports.org/health/2011/09/risky -prescription-drug-practices-are-on-the-rise-in-a-grim-economy.html. Accessed October 11, 2011. 4. Courtney B, Easton J, Inglesby TV, SooHoo C. Maximizing state and local medi- cal countermeasure stockpile investments through the Shelf-Life Extension Program. Biosecur Bioterror. 2009;7(1):101-107. 5. US Food and Drug Administration. Questions and answers on levothyroxine sodium products. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrug SafetyInformationforPatientsandProviders/ucm161266.htm?utm_source =fdaSearch&utm_medium=website&utm_term=. Accessed April 18, 2012. 6. Martin BK. The formulation of aspirin. Adv Pharm Sci. 1971;3:107-171. 7. The White House. We can’t wait: Obama administration takes action to re- duce prescription drug shortages, fight price gouging. http://www.whitehouse .gov/the-press-office/2011/10/31/we-can-t-wait-obama-administration -takes-action-reduce-prescription-drug. Accessed January 18, 2012. Persistence With Therapy Among Patients Treated With Warfarin for Atrial Fibrillation The major challenges of warfarin therapy relate to poor adherence and persistence, the need for regular monitoring, and the risk of hemor- rhage. In clinical trials, persistence with warfarin treat- ment ranges from 75% to 79% at 1 year,1,2 but persis- tence in clinical practice is thought to be poorer. Small observational studies suggest that approximately one- quarter of patients cease warfarin treatment within a year of initiation.3,4 To our knowledge, there are currently no large studies offering real-world estimates of persis- tence among warfarin users. The objective of this study was to examine persistence with warfarin therapy in a large population-based cohort of newly treated patients with atrial fibrillation (AF). Methods. We conducted a population-based cohort study among residents of Ontario, Canada, 66 years and older, who commenced treatment with warfarin between April 1, 1997, and March 31, 2008. We used multiple linked administrative data sets from Ontario, the most popu- lous province in Canada, to identify outpatient prescrip- tion records, hospitalizations, emergency department vis- its, physician services, patient demographics, and comorbidities. Details of these databases are given in the eAppendix (http://www.archinternmed.com). The data were held securely in a linked, deidentified form and ana- lyzed at the Institute for Clinical Evaluative Sciences. For each study subject, we identified a period of con- tinuous warfarin use beginning with the first prescrip- tion dispensed after their 66th birthday and defined by successive prescription refills within 180 days, thereby allowing for periodic dose adjustments, brief lapses in adherence, and variable timing of prescription refills. To create an inception cohort of patients with AF, patients with any prescription for warfarin in the preceding year were excluded, and the analysis was restricted to pa- tients who had a physician visit, emergency department assessment, or hospital admission for AF or flutter in the 100 days preceding the first prescription for warfarin. We followed patients from their cohort entry date until the first instance of discontinuation of warfarin therapy, death, or the end of the study period (March 31, 2010), with a maximum follow-up of 5 years. We constructed Kaplan-Meier curves to characterize drug therapy discontinuation. Secondary analyses de- scribed persistence with warfarin therapy according to age (66 to 75 years, 76 to 85 years, and Ն86 years), sex, CHADS2 (congestive heart failure, hypertension, age Ն75 years, diabetes mellitus, and prior stroke or transient is- chemic attack) score,5 and date of warfarin therapy ini- tiation (before or after April 1, 2003; presuming progres- sive improvements in anticoagulation management over time).6,7 The log-rank test was used to examine differ- ences in persistence among patient subgroups. This re- search was approved by the research ethics board of Sun- nybrook Health Sciences Centre, Toronto, Ontario. Results. Over the 13-year study period, we identified 125 195 new users of warfarin in Ontario 66 years or older with a recent diagnosis of AF. Of these, 86 432 (69.0%) had a CHADS2 score of 2 or higher at the outset of therapy, and 62 851 (50.2%) initiated treatment within a week of their AF diagnosis. Of 125 195 patients who started warfarin therapy for AF, 8.9% did not fill a second warfarin prescription dur- ing follow-up, 31.8% discontinued therapy within 1 year, 43.2% discontinued therapy within 2 years, and 61.3% discontinued therapy within 5 years (Figure). The me- dian time to discontinuation (MTD) was 2.9 years. Men discontinued warfarin therapy earlier than women (MTD, 2.6 years vs 3.2 years, respectively; PϽ.001), while pa- tients aged 66 to 75 years were more likely to discon- tinue therapy compared with older patient groups (MTD, 2.7 years vs 3.1 years for patients Ͼ85 years; PϽ.001). Persistence with warfarin therapy increased with stroke risk, as reflected by the CHADS2 score (MTD, 2.3 years, 2.9 years, and 3.3 years among people with a CHADS2 See Invited Commentary at end of letter ARCH INTERN MED/VOL 172 (NO. 21), NOV 26, 2012 WWW.ARCHINTERNMED.COM 1687 ©2012 American Medical Association. All rights reserved. Downloaded From: http://archinte.jamanetwork.com/ by Andres Lopez on 04/19/2015
Download now