The document summarizes the history and requirements of Risk Evaluation and Mitigation Strategy (REMS) programs mandated by the FDA for certain drugs. It focuses on the use of erythropoiesis-stimulating agents (ESAs) in cancer patients. Several meta-analyses found ESAs increased risks of thrombosis, mortality, and decreased survival. The FDA Oncologic Drugs Advisory Committee reviewed these findings and required boxed warnings be added to ESAs about increased risks. The committee later recommended limiting ESA use to palliative patients only after receiving informed consent due to further trials showing adverse outcomes. As of 2010, over 150 drugs had FDA-mandated REMS programs including required medication guides for almost all drugs.
Bioavailability refers to the amount of drug that enters systemic circulation after administration. It is impacted by absorption and first-pass metabolism. Bioequivalence compares the rates and extents of drug absorption between products to determine if they can be expected to have similar effects. Key parameters assessed in bioequivalence studies include Cmax, Tmax, and AUC which are obtained from plasma concentration-time profiles following drug administration. Urinary excretion studies can also be used to assess bioequivalence. The goal is to show that test and reference products have similar pharmacokinetic properties.
Outcomes in Long-term Opioid Tapering and Buprenorphine Transition: A Retrosp...Paul Coelho, MD
This study analyzed outcomes for 240 patients with chronic pain who were prescribed long-term opioid therapy above 90 mg morphine-equivalent daily doses. Patients were offered an outpatient opioid taper or transition to buprenorphine if taper was not tolerated. 44.6% successfully tapered, 18.8% transitioned to buprenorphine, and 36.6% dropped out of treatment. Higher initial opioid doses predicted needing buprenorphine, and benzodiazepine/z-drug use predicted greater dropout. Pain intensity changes after treatment were mixed, with over half of tapered patients reporting increased pain and about half of transitioned patients reporting decreased pain.
This document summarizes the results of a study that evaluated the health care resource utilization and costs of patients with symptomatic multiple myeloma in the United Kingdom. The study found that the average total cost per treatment line was £34,296, with most costs attributed to anti-tumor drugs. The average cost per month of active treatment was £5,168. For patients receiving best supportive care after discontinuing active treatment, the average total cost was £1,444 if they progressed or £2,480 if they did not progress before death.
This study compared the effectiveness of febuxostat and allopurinol in lowering serum urate levels using data from a large U.S. managed care organization. The study included over 16,000 patients taking febuxostat or allopurinol for gout. After matching patients based on demographics, clinical characteristics, and other factors, febuxostat was found to be more effective than allopurinol at reducing serum urate levels and achieving treatment targets. A higher proportion of febuxostat users reached targets of less than 6 mg/dL and less than 5 mg/dL, and they reached the targets faster than allopurinol users. Febuxostat was also more effective in overall
The document describes the System of Objectified Judgement Analysis (SOJA) process for rational drug selection. SOJA involves prospectively defining criteria for drug selection, determining the relative weight of each criterion, and scoring each drug on how well it fulfills the criteria. An expert panel determines the scores and weights based on factors like clinical efficacy, safety, dosing frequency, drug interactions, and cost. The document provides details on how SOJA addresses and scores each selection criterion in a standardized, evidence-based manner to facilitate objective, transparent comparisons among drugs.
C clausura outcomes_strategies_drug_utilization_wright_jz15sefap
The document summarizes strategies implemented in British Columbia to improve prescription drug utilization and their outcomes. It discusses policies such as outcome-based drug coverage, reference-based pricing, restricted access criteria, and therapeutic substitution that were introduced by the Therapeutics Initiative. Evaluations found these policies led to cost savings, changes in prescribing towards preferred drugs, and no increases in adverse health outcomes. However, the initiatives faced opposition from those with conflicts of interest, and changes to governance and funding now threaten the future of the Therapeutics Initiative's role in advising on drug policy in BC.
Do we-have-the-right-dose-dose-adjustments-for-organ-dysfunction-2167-7700.10...science journals
The effect of heat treatment on the activities of three quality related enzymes peroxidase (POD), polyphenol oxidase (PPO), and lipoxygenase (LOX), from edible white yam (Dioscorea rotundata) was studied over a temperature range of 50 to 80°C using mathematical analysis of the kinetic and thermodynamic parameters for the thermoinactivation of the enzymes.
The document summarizes the evolution of prescribing by pharmacists in Alberta, Canada. It describes Alberta's three-category model of pharmacist prescribing which includes: 1) adapting existing prescriptions, 2) emergency prescribing when patients cannot access other care, and 3) additional independent prescribing by pharmacists who complete further training. Over 2800 pharmacists completed orientation to prescribe by adapting or in emergencies by 2007. Fifteen pharmacists obtained additional prescribing privileges after a pilot program. Collaborative efforts among health professionals, regulators, and patients led to developing Alberta's current pharmacist prescribing model.
Bioavailability refers to the amount of drug that enters systemic circulation after administration. It is impacted by absorption and first-pass metabolism. Bioequivalence compares the rates and extents of drug absorption between products to determine if they can be expected to have similar effects. Key parameters assessed in bioequivalence studies include Cmax, Tmax, and AUC which are obtained from plasma concentration-time profiles following drug administration. Urinary excretion studies can also be used to assess bioequivalence. The goal is to show that test and reference products have similar pharmacokinetic properties.
Outcomes in Long-term Opioid Tapering and Buprenorphine Transition: A Retrosp...Paul Coelho, MD
This study analyzed outcomes for 240 patients with chronic pain who were prescribed long-term opioid therapy above 90 mg morphine-equivalent daily doses. Patients were offered an outpatient opioid taper or transition to buprenorphine if taper was not tolerated. 44.6% successfully tapered, 18.8% transitioned to buprenorphine, and 36.6% dropped out of treatment. Higher initial opioid doses predicted needing buprenorphine, and benzodiazepine/z-drug use predicted greater dropout. Pain intensity changes after treatment were mixed, with over half of tapered patients reporting increased pain and about half of transitioned patients reporting decreased pain.
This document summarizes the results of a study that evaluated the health care resource utilization and costs of patients with symptomatic multiple myeloma in the United Kingdom. The study found that the average total cost per treatment line was £34,296, with most costs attributed to anti-tumor drugs. The average cost per month of active treatment was £5,168. For patients receiving best supportive care after discontinuing active treatment, the average total cost was £1,444 if they progressed or £2,480 if they did not progress before death.
This study compared the effectiveness of febuxostat and allopurinol in lowering serum urate levels using data from a large U.S. managed care organization. The study included over 16,000 patients taking febuxostat or allopurinol for gout. After matching patients based on demographics, clinical characteristics, and other factors, febuxostat was found to be more effective than allopurinol at reducing serum urate levels and achieving treatment targets. A higher proportion of febuxostat users reached targets of less than 6 mg/dL and less than 5 mg/dL, and they reached the targets faster than allopurinol users. Febuxostat was also more effective in overall
The document describes the System of Objectified Judgement Analysis (SOJA) process for rational drug selection. SOJA involves prospectively defining criteria for drug selection, determining the relative weight of each criterion, and scoring each drug on how well it fulfills the criteria. An expert panel determines the scores and weights based on factors like clinical efficacy, safety, dosing frequency, drug interactions, and cost. The document provides details on how SOJA addresses and scores each selection criterion in a standardized, evidence-based manner to facilitate objective, transparent comparisons among drugs.
C clausura outcomes_strategies_drug_utilization_wright_jz15sefap
The document summarizes strategies implemented in British Columbia to improve prescription drug utilization and their outcomes. It discusses policies such as outcome-based drug coverage, reference-based pricing, restricted access criteria, and therapeutic substitution that were introduced by the Therapeutics Initiative. Evaluations found these policies led to cost savings, changes in prescribing towards preferred drugs, and no increases in adverse health outcomes. However, the initiatives faced opposition from those with conflicts of interest, and changes to governance and funding now threaten the future of the Therapeutics Initiative's role in advising on drug policy in BC.
Do we-have-the-right-dose-dose-adjustments-for-organ-dysfunction-2167-7700.10...science journals
The effect of heat treatment on the activities of three quality related enzymes peroxidase (POD), polyphenol oxidase (PPO), and lipoxygenase (LOX), from edible white yam (Dioscorea rotundata) was studied over a temperature range of 50 to 80°C using mathematical analysis of the kinetic and thermodynamic parameters for the thermoinactivation of the enzymes.
The document summarizes the evolution of prescribing by pharmacists in Alberta, Canada. It describes Alberta's three-category model of pharmacist prescribing which includes: 1) adapting existing prescriptions, 2) emergency prescribing when patients cannot access other care, and 3) additional independent prescribing by pharmacists who complete further training. Over 2800 pharmacists completed orientation to prescribe by adapting or in emergencies by 2007. Fifteen pharmacists obtained additional prescribing privileges after a pilot program. Collaborative efforts among health professionals, regulators, and patients led to developing Alberta's current pharmacist prescribing model.
This document provides guidance on pharmacokinetic studies for new medicinal products to assist in interpreting EU directives. It discusses studying absorption, distribution, elimination, interactions and adverse reactions. Key factors include determining bioavailability, protein binding, metabolism, excretion routes and changes in special populations. Methodology should use appropriate administration schemes in healthy volunteers and patients, validated analytical methods, and statistical analysis to interpret results. The goal is to understand dose-concentration profiles and establish safe, effective dosing regimens.
The document discusses pharmacometrics and provides examples of its applications in drug development and clinical trials. It begins with definitions of pharmacometrics and related terms. It then provides examples of how pharmacometric modeling and simulation have been used to:
- Support pediatric drug approvals without the need for separate clinical trials by linking exposure to response between adult and pediatric patients.
- Optimize drug doses in clinical trials and make dosing recommendations for specific patient populations.
- Simulate clinical trials to determine trial designs and evaluate outcomes.
adaptive methods are doing with feedback in population pharmacokinetics---- clinical pharmacokinetics and therapeutic drug monitoring-- fifth pharm D notes
Evidence for Cure by Adjuvant Therapy in Colon Cancer: Observations Based on ...alessandrolealmd
This document summarizes a study analyzing individual patient data from 20,898 patients in 18 randomized trials testing fluorouracil-based adjuvant therapy for stage II-III colon cancer. The key findings were:
1) Adjuvant chemotherapy provided a significant and consistent overall survival benefit over 8 years of follow-up, indicating chemotherapy cures some patients rather than just delaying recurrence.
2) Recurrence rates after 5 years were less than 1.5% per year, and after 8 years were less than 0.5% per year for patients treated in clinical trials, demonstrating low long-term recurrence risks.
3) Significant disease-free survival benefit from adjuvant chemotherapy was seen in the first 2 years
This document describes a pilot study comparing three pharmacokinetic (PK)-guided prophylactic dosing tools for hemophilia A: 1) Bayesian analysis using NONMEM software, 2) MyPKFiT, and 3) WAPPS-Hemo portal. Seven patients received factor VIII and had blood levels measured over time. The tools estimated PK parameters like clearance and half-life. MyPKFiT and WAPPS-Hemo estimated higher values than NONMEM for volume of distribution, half-life, and time to a factor level of 0.01 IU/mL. Calculated prophylactic doses based on the estimates differed between the tools. The study concludes larger prospective studies are needed to understand differences between tools and
Premier on Medicinal Fungus as effective Adjuvant & Complementary Agents for ...Chee-Cheow Lee
This document discusses cancer and potential complementary and adjuvant treatments. It summarizes the characteristics and current treatment approaches for cancer. It then discusses various medicinal mushrooms and compounds that show promise as complementary agents, including polysaccharides from Coriolus versicolor and Phellinus linteus, and the compound Antroquinonol isolated from Antrodia camphorata. Antroquinonol in particular has shown safety and efficacy against various cancer types in both in vitro and in vivo studies. The document concludes by discussing how these natural compounds can be applied at different stages of cancer prevention and treatment.
The Potential for Individualization of Neoadjuvant Chemotherapy in Breast Can...CrimsonpublishersCancer
The preoperative, or, as it is often called, neoadjuvant chemotherapy (NAPCT) of operable breast cancer (the breast cancer) with affected regional lymph nodes has in its time replaced preoperative radiotherapy, as it has a number of significant advantages over the latter. The most important advantage of NAPCT is its systemic action, which allows to “catching up” with probable distant micro-metastases or circulating tumor cells, while pre-operative radiotherapy has a local effect, and on the systemic level the tumor continues to develop. Despite of the fact that with operative breast cancer the time of NAPCT (before or after the operation) does not affect to the long-term results of treatment, the latter becomes applicable even for operable breast cancer without affected regional lymph nodes.According to the literature, NAPCT with primary-operative breast cancer allows: 1) make organ saving operations; 2) improve the prognosis in cases of complete morphological regression in patients with triple negative and Her2 / neu positive (non-luminal) subtypes; 3) evaluate the effect of chemotherapy and, in the absence of effect, stop it on time [1].
Pharmacometrics is the science of using mathematical and statistical methods to characterize and predict the pharmacokinetic and pharmacodynamic behavior of drugs. It aims to improve decision making in drug development and pharmacotherapy. Pharmacometric models integrate pharmacokinetic and pharmacodynamic models to describe the relationship between drug concentration, effect, and patient characteristics. Population pharmacometric modeling is useful for characterizing variability in these parameters between individuals.
38 use of drugs in children with impaired renal functionDang Thanh Tuan
The document discusses several key issues regarding drug dosing in pediatric patients with impaired renal function:
1) Most drug studies are performed on adults and two-thirds of drugs are excreted by the kidneys, so dosing children with renal impairment requires careful consideration.
2) Factors like a child's absorption, distribution, and developmental physiology must be accounted for in dosing, as well as the drug's pharmacokinetic properties and metabolism.
3) Guidelines provide recommendations for adjusting drug dosages based on a child's renal function and monitoring drug levels, but balancing specificity and generalizability remains challenging.
This document discusses bioavailability and bioequivalence studies. It provides details on key pharmacokinetic parameters like AUC, Cmax, and Tmax that are evaluated in bioequivalence studies to determine if a generic drug is equivalent to a brand name drug. The document outlines current bioequivalence requirements set by various regulatory agencies like FDA, Health Canada, and others. It also discusses study design considerations, statistical analysis methods, and validation of bioanalytical methods used to evaluate bioequivalence.
1) The study compared real-world outcomes of pomalidomide plus low-dose dexamethasone (POM+LoDEX) to other active treatments for relapsed and refractory multiple myeloma using individual patient data from clinical trials and retrospective analyses.
2) After adjusting for baseline characteristics, POM+LoDEX showed significantly better survival outcomes compared to other active treatments, with a median overall survival of 14.4 months versus 4.6 months for other treatments.
3) There was no significant difference in survival between bendamustine-containing regimens and other standard treatments used in this patient population.
This document discusses advances in monitoring pharmacotherapeutics and drug delivery system design. It begins with definitions of pharmacotherapy and the need for monitoring it to ensure safe and effective use of drugs. It then discusses factors like adverse drug reactions, rational drug use, and improving patient compliance. Recent advances in monitoring discussed include microscopy techniques for examining drug fate and distribution in tissues. The document also discusses trends in pharmaceutical product design like controlled release and targeted delivery systems. Specific advances highlighted include prodrug approaches, nanocarrier systems, and delivery methods like Ocusert inserts and buccal patches.
- The study examined how Medicare Part D enrollment affected out-of-pocket prescription costs and medication use among Medicare beneficiaries with cardiovascular disease. Nearly 49% of these beneficiaries enrolled in Part D plans.
- Those without prior drug coverage reported their monthly out-of-pocket costs decreased the most and were more likely to increase their use of cardiovascular medications after enrolling in Part D.
- Dual-eligible beneficiaries (covered by both Medicare and Medicaid) reported their out-of-pocket costs increased the most and were less likely to use cardiovascular medications after shifting to Part D plans.
Toxicology screening and therapeutic drug monitoring (an introduction) Hossamaldin Alzawawi
Therapeutic drug monitoring (TDM) involves measuring drug concentrations in patients to optimize drug therapy and avoid toxicity. TDM emerged in the 1960s with pharmacokinetic studies linking drug levels to outcomes. Pioneers in the 1970s demonstrated that constructing therapeutic ranges could reduce adverse reactions to drugs like digoxin. TDM utilizes pharmacokinetics and pharmacodynamics to assess medication efficacy and safety. It aims to individualize treatment and tailor it to each patient's needs. Factors like genetics, disease states, and drug interactions cause vast inter-patient variability in how drugs are absorbed, distributed, and eliminated.
1.3.5.1.8 asco 2014 my5 fu poster - final (20-may-2014)DeWayne Davenport
This document summarizes the experience of US oncologists using pharmacokinetic (PK) guided optimization of 5-fluorouracil (5-FU) dosing in colorectal cancer patients. Between 2013-2014, 5-FU plasma levels were measured in 1000 samples from 380 patients treated at over 70 practices. Dose adjustments were recommended based on whether 5-FU exposure was above, within, or below the target range. The majority of initial exposures and doses were outside the target range. Dose adjustments made generally followed recommendations and helped move exposures into the target range. PK-guided dosing showed potential to improve outcomes by achieving optimal 5-FU exposure without increased toxicities.
This document summarizes a study examining risk factors for overdose death from prescription opioids. The study compared 254 decedents who died from prescription opioid overdoses to 1,308 people who used prescription opioids. It found that decedents were more likely to obtain opioids from non-prescription sources, use them more often than prescribed, have chronic pain, smoke daily, have a history of substance abuse or mental illness, and lack social support. The study aims to help clinicians recognize at-risk patients and control opioid exposure to prevent overdoses.
Bioavailability and bioequivalance studies and Regulatory aspectsRumel Dey
This document discusses bioavailability and bioequivalence studies, including definitions, protocols, and regulatory requirements. It defines key terms like bioavailability, bioequivalence, pharmaceutical equivalents, and therapeutic equivalents. It describes the reference and test products used in studies and compares NDA and ANDA review processes. It provides details on the design, conduct, and statistical evaluation of bioavailability and bioequivalence studies. It also discusses biowaiver options and the use of pharmacodynamic and dissolution studies.
Bayesian theory in population pharmacokinetics--
1) INTRODUCTION TO BAYESIAN THEORY
2)BAYESIAN PROBABILITY TO DOSING OF DRUGS
3)APPLICATIONS AND USES OF BAYESIAN THEORY IN APPLIED PHARMACOKINETICS:
therapeutic drug monitoring and clinical pharmacokinetics-fifth pharm d notes
Cehmotherapy Induced Nausea and VomittingAndriUtomo5
This document provides an update to the American Society of Clinical Oncology (ASCO) clinical practice guideline for antiemetics. The update aims to provide recommendations on using dexamethasone as a prophylactic antiemetic in patients receiving checkpoint inhibitors and information on new antiemetics, regimens, and cancer agent emetogenicity. Based on two phase III trials, the guideline recommends that all patients receiving a platinum-based doublet with or without the checkpoint inhibitor pembrolizumab receive dexamethasone as part of antiemetic prophylaxis. Recommendations for adults are largely unchanged, with some modifications for olanzapine use. The guideline adds fosaprepitant to
Thesis_PhD_Improving medication safety in the elderlyHA VO THI
The document discusses medication safety issues for elderly patients, noting that physiological changes with aging increase their risk of adverse drug reactions and interactions from polypharmacy. Polypharmacy, defined as using multiple medications, is common in elderly patients due to multiple chronic conditions but can increase problems with adherence and side effects. Improving medication safety for elderly patients requires addressing polypharmacy issues through individualized treatment reviews that consider life expectancy, treatment goals and targets.
This document provides guidance on pharmacokinetic studies for new medicinal products to assist in interpreting EU directives. It discusses studying absorption, distribution, elimination, interactions and adverse reactions. Key factors include determining bioavailability, protein binding, metabolism, excretion routes and changes in special populations. Methodology should use appropriate administration schemes in healthy volunteers and patients, validated analytical methods, and statistical analysis to interpret results. The goal is to understand dose-concentration profiles and establish safe, effective dosing regimens.
The document discusses pharmacometrics and provides examples of its applications in drug development and clinical trials. It begins with definitions of pharmacometrics and related terms. It then provides examples of how pharmacometric modeling and simulation have been used to:
- Support pediatric drug approvals without the need for separate clinical trials by linking exposure to response between adult and pediatric patients.
- Optimize drug doses in clinical trials and make dosing recommendations for specific patient populations.
- Simulate clinical trials to determine trial designs and evaluate outcomes.
adaptive methods are doing with feedback in population pharmacokinetics---- clinical pharmacokinetics and therapeutic drug monitoring-- fifth pharm D notes
Evidence for Cure by Adjuvant Therapy in Colon Cancer: Observations Based on ...alessandrolealmd
This document summarizes a study analyzing individual patient data from 20,898 patients in 18 randomized trials testing fluorouracil-based adjuvant therapy for stage II-III colon cancer. The key findings were:
1) Adjuvant chemotherapy provided a significant and consistent overall survival benefit over 8 years of follow-up, indicating chemotherapy cures some patients rather than just delaying recurrence.
2) Recurrence rates after 5 years were less than 1.5% per year, and after 8 years were less than 0.5% per year for patients treated in clinical trials, demonstrating low long-term recurrence risks.
3) Significant disease-free survival benefit from adjuvant chemotherapy was seen in the first 2 years
This document describes a pilot study comparing three pharmacokinetic (PK)-guided prophylactic dosing tools for hemophilia A: 1) Bayesian analysis using NONMEM software, 2) MyPKFiT, and 3) WAPPS-Hemo portal. Seven patients received factor VIII and had blood levels measured over time. The tools estimated PK parameters like clearance and half-life. MyPKFiT and WAPPS-Hemo estimated higher values than NONMEM for volume of distribution, half-life, and time to a factor level of 0.01 IU/mL. Calculated prophylactic doses based on the estimates differed between the tools. The study concludes larger prospective studies are needed to understand differences between tools and
Premier on Medicinal Fungus as effective Adjuvant & Complementary Agents for ...Chee-Cheow Lee
This document discusses cancer and potential complementary and adjuvant treatments. It summarizes the characteristics and current treatment approaches for cancer. It then discusses various medicinal mushrooms and compounds that show promise as complementary agents, including polysaccharides from Coriolus versicolor and Phellinus linteus, and the compound Antroquinonol isolated from Antrodia camphorata. Antroquinonol in particular has shown safety and efficacy against various cancer types in both in vitro and in vivo studies. The document concludes by discussing how these natural compounds can be applied at different stages of cancer prevention and treatment.
The Potential for Individualization of Neoadjuvant Chemotherapy in Breast Can...CrimsonpublishersCancer
The preoperative, or, as it is often called, neoadjuvant chemotherapy (NAPCT) of operable breast cancer (the breast cancer) with affected regional lymph nodes has in its time replaced preoperative radiotherapy, as it has a number of significant advantages over the latter. The most important advantage of NAPCT is its systemic action, which allows to “catching up” with probable distant micro-metastases or circulating tumor cells, while pre-operative radiotherapy has a local effect, and on the systemic level the tumor continues to develop. Despite of the fact that with operative breast cancer the time of NAPCT (before or after the operation) does not affect to the long-term results of treatment, the latter becomes applicable even for operable breast cancer without affected regional lymph nodes.According to the literature, NAPCT with primary-operative breast cancer allows: 1) make organ saving operations; 2) improve the prognosis in cases of complete morphological regression in patients with triple negative and Her2 / neu positive (non-luminal) subtypes; 3) evaluate the effect of chemotherapy and, in the absence of effect, stop it on time [1].
Pharmacometrics is the science of using mathematical and statistical methods to characterize and predict the pharmacokinetic and pharmacodynamic behavior of drugs. It aims to improve decision making in drug development and pharmacotherapy. Pharmacometric models integrate pharmacokinetic and pharmacodynamic models to describe the relationship between drug concentration, effect, and patient characteristics. Population pharmacometric modeling is useful for characterizing variability in these parameters between individuals.
38 use of drugs in children with impaired renal functionDang Thanh Tuan
The document discusses several key issues regarding drug dosing in pediatric patients with impaired renal function:
1) Most drug studies are performed on adults and two-thirds of drugs are excreted by the kidneys, so dosing children with renal impairment requires careful consideration.
2) Factors like a child's absorption, distribution, and developmental physiology must be accounted for in dosing, as well as the drug's pharmacokinetic properties and metabolism.
3) Guidelines provide recommendations for adjusting drug dosages based on a child's renal function and monitoring drug levels, but balancing specificity and generalizability remains challenging.
This document discusses bioavailability and bioequivalence studies. It provides details on key pharmacokinetic parameters like AUC, Cmax, and Tmax that are evaluated in bioequivalence studies to determine if a generic drug is equivalent to a brand name drug. The document outlines current bioequivalence requirements set by various regulatory agencies like FDA, Health Canada, and others. It also discusses study design considerations, statistical analysis methods, and validation of bioanalytical methods used to evaluate bioequivalence.
1) The study compared real-world outcomes of pomalidomide plus low-dose dexamethasone (POM+LoDEX) to other active treatments for relapsed and refractory multiple myeloma using individual patient data from clinical trials and retrospective analyses.
2) After adjusting for baseline characteristics, POM+LoDEX showed significantly better survival outcomes compared to other active treatments, with a median overall survival of 14.4 months versus 4.6 months for other treatments.
3) There was no significant difference in survival between bendamustine-containing regimens and other standard treatments used in this patient population.
This document discusses advances in monitoring pharmacotherapeutics and drug delivery system design. It begins with definitions of pharmacotherapy and the need for monitoring it to ensure safe and effective use of drugs. It then discusses factors like adverse drug reactions, rational drug use, and improving patient compliance. Recent advances in monitoring discussed include microscopy techniques for examining drug fate and distribution in tissues. The document also discusses trends in pharmaceutical product design like controlled release and targeted delivery systems. Specific advances highlighted include prodrug approaches, nanocarrier systems, and delivery methods like Ocusert inserts and buccal patches.
- The study examined how Medicare Part D enrollment affected out-of-pocket prescription costs and medication use among Medicare beneficiaries with cardiovascular disease. Nearly 49% of these beneficiaries enrolled in Part D plans.
- Those without prior drug coverage reported their monthly out-of-pocket costs decreased the most and were more likely to increase their use of cardiovascular medications after enrolling in Part D.
- Dual-eligible beneficiaries (covered by both Medicare and Medicaid) reported their out-of-pocket costs increased the most and were less likely to use cardiovascular medications after shifting to Part D plans.
Toxicology screening and therapeutic drug monitoring (an introduction) Hossamaldin Alzawawi
Therapeutic drug monitoring (TDM) involves measuring drug concentrations in patients to optimize drug therapy and avoid toxicity. TDM emerged in the 1960s with pharmacokinetic studies linking drug levels to outcomes. Pioneers in the 1970s demonstrated that constructing therapeutic ranges could reduce adverse reactions to drugs like digoxin. TDM utilizes pharmacokinetics and pharmacodynamics to assess medication efficacy and safety. It aims to individualize treatment and tailor it to each patient's needs. Factors like genetics, disease states, and drug interactions cause vast inter-patient variability in how drugs are absorbed, distributed, and eliminated.
1.3.5.1.8 asco 2014 my5 fu poster - final (20-may-2014)DeWayne Davenport
This document summarizes the experience of US oncologists using pharmacokinetic (PK) guided optimization of 5-fluorouracil (5-FU) dosing in colorectal cancer patients. Between 2013-2014, 5-FU plasma levels were measured in 1000 samples from 380 patients treated at over 70 practices. Dose adjustments were recommended based on whether 5-FU exposure was above, within, or below the target range. The majority of initial exposures and doses were outside the target range. Dose adjustments made generally followed recommendations and helped move exposures into the target range. PK-guided dosing showed potential to improve outcomes by achieving optimal 5-FU exposure without increased toxicities.
This document summarizes a study examining risk factors for overdose death from prescription opioids. The study compared 254 decedents who died from prescription opioid overdoses to 1,308 people who used prescription opioids. It found that decedents were more likely to obtain opioids from non-prescription sources, use them more often than prescribed, have chronic pain, smoke daily, have a history of substance abuse or mental illness, and lack social support. The study aims to help clinicians recognize at-risk patients and control opioid exposure to prevent overdoses.
Bioavailability and bioequivalance studies and Regulatory aspectsRumel Dey
This document discusses bioavailability and bioequivalence studies, including definitions, protocols, and regulatory requirements. It defines key terms like bioavailability, bioequivalence, pharmaceutical equivalents, and therapeutic equivalents. It describes the reference and test products used in studies and compares NDA and ANDA review processes. It provides details on the design, conduct, and statistical evaluation of bioavailability and bioequivalence studies. It also discusses biowaiver options and the use of pharmacodynamic and dissolution studies.
Bayesian theory in population pharmacokinetics--
1) INTRODUCTION TO BAYESIAN THEORY
2)BAYESIAN PROBABILITY TO DOSING OF DRUGS
3)APPLICATIONS AND USES OF BAYESIAN THEORY IN APPLIED PHARMACOKINETICS:
therapeutic drug monitoring and clinical pharmacokinetics-fifth pharm d notes
Cehmotherapy Induced Nausea and VomittingAndriUtomo5
This document provides an update to the American Society of Clinical Oncology (ASCO) clinical practice guideline for antiemetics. The update aims to provide recommendations on using dexamethasone as a prophylactic antiemetic in patients receiving checkpoint inhibitors and information on new antiemetics, regimens, and cancer agent emetogenicity. Based on two phase III trials, the guideline recommends that all patients receiving a platinum-based doublet with or without the checkpoint inhibitor pembrolizumab receive dexamethasone as part of antiemetic prophylaxis. Recommendations for adults are largely unchanged, with some modifications for olanzapine use. The guideline adds fosaprepitant to
Thesis_PhD_Improving medication safety in the elderlyHA VO THI
The document discusses medication safety issues for elderly patients, noting that physiological changes with aging increase their risk of adverse drug reactions and interactions from polypharmacy. Polypharmacy, defined as using multiple medications, is common in elderly patients due to multiple chronic conditions but can increase problems with adherence and side effects. Improving medication safety for elderly patients requires addressing polypharmacy issues through individualized treatment reviews that consider life expectancy, treatment goals and targets.
This document summarizes the results and recommendations from the 2009 Consensus Conference on antiemetics organized by ESMO and MASCC. The conference updated guidelines for preventing chemotherapy- and radiotherapy-induced nausea and vomiting. Key points:
- Chemotherapy agents were classified into four levels of emetogenic potential (high, moderate, low, minimal) based on literature review. This classification guides antiemetic treatment recommendations.
- For prevention of acute nausea/vomiting from highly emetogenic chemo like cisplatin, the addition of the NK1 receptor antagonist aprepitant to ondansetron and dexamethasone was found to significantly improve complete response rates compared to the standard regimen.
APRIL 2018, VOL. 22 NO. 2 CLINICAL JOURNAL OF ONCOLOGY NURSING.docxfestockton
APRIL 2018, VOL. 22 NO. 2 CLINICAL JOURNAL OF ONCOLOGY NURSING 175CJON.ONS.ORG
C
Nephrotoxicity
Evidence in patients receiving cisplatin therapy
Elizabeth A. Duffy, DNP, RN, CPNP, Wendy Fitzgerald, RN, MSN, PPCNP-BC, CPON®, Kelley Boyle, MSN, RN, PCNS-BC, and Radha Rohatgi, PharmD, BCOP
CISPLATIN IS A PLATINUM COMPOUND THAT HAS BEEN USED as a chemotherapeutic
agent for many different cancers, including ovarian, testicular, lung, cervical,
and bladder cancers (Ruggiero, Rizzo, Trombatore, Maurizi, & Riccardi, 2016;
Santoso, Lucci, Coleman, Shafer, & Hannigan, 2003). The primary dose-
limiting toxicity of cisplatin is nephrotoxicity, a well-known side effect
(Jones, Spunt, Green, & Springate, 2008; Miller, Tadagavadi, Ramesh, &
Reeves, 2010). Nephrotoxicity involves glomerular or tubular dysfunction
of the kidneys after exposure to medications, other treatments, or toxins
(Skinner, 2011). Nephrotoxicity associated with cisplatin is related to accu-
mulation of metabolites in the renal proximal tubule cells of the kidneys,
where about 90% of cisplatin undergoes urinary excretion (Ruggiero et al.,
2016). Accumulation of these metabolites causes direct inflammation; the
production of reactive oxygen species, which leads to oxidative cell damage;
and cell death (Miller et al., 2010; Ruggiero et al., 2016). Many methods are
available to measure kidney function and define nephrotoxicity or acute
kidney injury (see Table 1).
Most patients receiving cisplatin experience acute impairment of glo-
merular and tubular function in varying degrees. Toxicity is dependent on
individual cisplatin pharmacokinetics and is usually more severe with high
total cisplatin doses and when other potential nephrotoxic medications are
given concurrently (Skinner, 2011; Womer, Pritchard, & Barratt, 1985). In one
study, children aged 10 years or older at treatment had a lower glomerular
filtration rate 10 years after therapy compared to children aged younger than
10 years at treatment (Skinner et al., 2009).
Nephrotoxicity can be reversible, but for some individuals, it can result
in permanent kidney injury, chronic progressive renal failure, or renal tubule
function impairment (Skinner et al., 2009). Chronic and severe reductions
of renal function have several sequelae. The immediate impact may be dose
reduction or cessation of potentially lifesaving nephrotoxic chemotherapy,
thereby increasing the risk of relapse or progression of the cancer. In the
event of a disease relapse or progression, changes to renal function may limit
enrollment in phase 1 or 2 clinical trials because of inclusion parameters
related to baseline renal function.
Hydration and diuretics have been used in conjunction with cisplatin
administration for decades to improve the excretion of cisplatin and reduce
the incidence of nephrotoxicity. One method of promoting this excretion is
through osmotic diuresis with mannitol (Morgan et al., 2014). However, the
amount ...
This document discusses adverse drug reactions (ADRs), including:
1) Defining ADRs and distinguishing them from adverse drug events. ADRs are unintended effects caused directly by a drug, while adverse events can have other causes.
2) Around 5-10% of hospitalized patients experience an ADR, contributing to increased costs and length of stay. ADRs can reduce quality of life and rarely cause death.
3) Pharmacovigilance aims to detect, understand, and prevent ADRs through monitoring, reporting, and research on drug safety. Pharmacists play a key role in pharmacovigilance.
Drug Information Association Clinical Forum Presentationdneasha
Pharmacoepidemiology studies were performed on YASMIN and CRESTOR to better understand safety risks in real-world use. For YASMIN, a large database study found no increased risks of hyperkalemia or blood clots compared to other oral contraceptives. For CRESTOR, a global program using multiple databases evaluated safety outcomes like rhabdomyolysis. Future directions may include using health databases and electronic records in large simple trials to efficiently answer safety questions.
Drug Information Association Clinical Forum Presentationdneasha
Pharmacoepidemiology studies were performed on YASMIN and CRESTOR to better understand safety risks in real-world use. For YASMIN, a large database study found no increased risks of hyperkalemia or blood clots compared to other oral contraceptives. For CRESTOR, a global program using multiple databases evaluated safety outcomes like rhabdomyolysis. Future directions may include using health databases and electronic records in large simple trials to efficiently answer safety questions.
PAREXEL Early Phase Clinical Research Services experts discuss developing trends in drug development including adaptive trials design, real-world data and biomarkers.
This project report summarizes a quantitative analysis of nursing practices related to medication management at XYZ Hospital in Ludhiana, India. The author observed medication administration practices on the hospital's 4th floor over 50 patient cases. The observation found an 18.75% non-compliance rate with best practices, mostly due to staff negligence. Overall, the analysis showed that nursing staff were well-oriented in medication practices, adhering to patients' medication management plans 81.25% of the time. The report recommends continued focus on reducing errors by strictly following medication administration safety guidelines and policies.
Corticosteroids for sore throat sr ma bmj 2018Mayra Serrano
This systematic review and meta-analysis found that a single low dose of corticosteroids, such as oral dexamethasone up to 10 mg, provides moderate to high quality evidence of pain relief for patients with sore throat. Patients who received corticosteroids were twice as likely to experience pain relief after 24 hours and 1.5 times more likely to have no pain at 48 hours, with no increase in serious adverse effects. The mean time to complete pain resolution was about 11 hours shorter with corticosteroids. Included trials enrolled over 1400 individuals and assessed outcomes up to 48 hours, but did not evaluate risks of repeated corticosteroid use for recurrent sore throats.
The document summarizes a study that evaluated the use of the antibiotic ceftriaxone at a referral hospital in Ethiopia. The study reviewed 127 patient medical records to assess ceftriaxone use based on World Health Organization criteria. It found that ceftriaxone was inappropriately prescribed in 70% of cases, most often due to short treatment durations. Inappropriate antibiotic use contributes to growing antimicrobial resistance, posing a major public health threat. The study concludes that improved antibiotic stewardship programs are needed to promote more prudent ceftriaxone prescribing and preserve its effectiveness.
The medication safety project had two aims: 1) to identify areas of exposure to risk and make recommendations to enhance medication safety, and 2) to inform the development of a medication safety checklist specific to operating rooms. An interdisciplinary team conducted a review of medication use in operating rooms and related areas. They observed environments where medications were prescribed, stored, prepared, dispensed and administered. The team made recommendations in areas like improving documentation of patient medication histories, reducing abbreviations, enhancing pharmacist support, and standardizing medication storage, labeling and carts. Many of the recommendations have been implemented.
This document discusses how drug analytics based on manually extracted semantic relationships in Embase can be useful for drug development, repurposing, and safety. It describes how relationships between drugs, diseases, and adverse reactions that are manually indexed can provide valuable information for drug repurposing, development, and safety. Specific examples are provided to show how the semantic relationships can guide drug repositioning strategies, investigate new combination drugs, identify drug-drug interactions, collect drug comparison data, and help improve risk management.
David Neasham Practical Use Pharmacoepi Drug Devguest41e570
This document summarizes a presentation on practical applications of pharmacoepidemiology in clinical drug development. It provides details on two case studies: a study of Yasmin, an oral contraceptive containing drospirenone, which found no increased risk of adverse events compared to other oral contraceptives. It also describes a large international study program of Crestor, a statin, which evaluated patient characteristics and safety outcomes across multiple databases.
Environmental Risk Assessment for Pharmaceutical DrugsCovance
Understanding the Evaluation and Implications of Findings to the Regulatory Review of Human Medicines in the Environment. Pharmaceutical drugs are intended for the treatment of human disease, therefore the risk of their environmental exposure in clinical use needs to be evaluated. Environmental risk assessment (ERA) is part of the requirements when applying for marketing approval in many geographic regions throughout the world.
Personalized Therapies for OA: Can Biomarkers Get Us There?OARSI
This document discusses the potential for using biomarkers to enable personalized therapies for osteoarthritis (OA). It defines key terms like personalized therapies, biomarkers, phenotypes, and endotypes. The presenter argues that biomarkers could help identify the right treatment for individual OA patients by enabling prognostic and predictive enrichment in clinical trials. However, moving biomarkers from discovery to clinical validation and use involves a long process including assay development, testing biological links and hypotheses, and conducting randomized controlled trials. Several studies are highlighted that have discovered potential new biomarkers and are beginning to test biological links and hypotheses regarding how biomarkers may reflect disease processes and response to treatments.
Presentation: What's trending in medicines regulation? A January 2017 reflectionTGA Australia
This presentation provides a local perspective on recent developments in the medical technology and pharmaceutical landscape, and the future of the TGA in a global context.
This document provides guidelines for conducting bioequivalence studies in ASEAN countries. It adopts guidelines from the European Medicines Agency with some adaptations for ASEAN applications. The guidelines specify the requirements for the design, conduct, and evaluation of bioequivalence studies for immediate release dosage forms. It addresses study designs, subjects, conduct, characteristics to be investigated, strengths to be studied, bioanalytical methodology, evaluation, and special considerations for narrow therapeutic index or highly variable drugs. It also provides guidance on in vitro dissolution testing and requirements for bioequivalence study reports.
Actualización en Fibrilación Auricular: de la evidencia a la práctica clínica.
10 de Junio de 2014, 16:30h
http://www.secardiologia.es/directos/actualizacionFA.html
Introducción: de la investigación a la práctica. ¿Qué cambia en la vida real?
Dr. José Ramón González-Juanatey
Complejo Hospitalario Universitario de Santiago de Compostela. Presidente SEC
Twitter: @JoseJuanatey
One health condition that is becoming more common day by day is diabetes.
According to research conducted by the National Family Health Survey of India, diabetic cases show a projection which might increase to 10.4% by 2030.
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptxHolistified Wellness
We’re talking about Vedic Meditation, a form of meditation that has been around for at least 5,000 years. Back then, the people who lived in the Indus Valley, now known as India and Pakistan, practised meditation as a fundamental part of daily life. This knowledge that has given us yoga and Ayurveda, was known as Veda, hence the name Vedic. And though there are some written records, the practice has been passed down verbally from generation to generation.
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Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
Adhd Medication Shortage Uk - trinexpharmacy.comreignlana06
The UK is currently facing a Adhd Medication Shortage Uk, which has left many patients and their families grappling with uncertainty and frustration. ADHD, or Attention Deficit Hyperactivity Disorder, is a chronic condition that requires consistent medication to manage effectively. This shortage has highlighted the critical role these medications play in the daily lives of those affected by ADHD. Contact : +1 (747) 209 – 3649 E-mail : sales@trinexpharmacy.com
Our backs are like superheroes, holding us up and helping us move around. But sometimes, even superheroes can get hurt. That’s where slip discs come in.
Does Over-Masturbation Contribute to Chronic Prostatitis.pptxwalterHu5
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These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
1. REGULATORY COMPLIANCE
The ESA APPRISE Oncology Program
A History of REMS Requirements, a Review of the Data,
And an Approach to Compliance in the Hospital
David J. Reeves, PharmD, BCOP; Amanda K. Quebe, PharmD; and Ranita Patel, PharmD
History of the REMS Program drugs, including the erythropoiesis-stimulating agents (ESAs),
On September 27, 2007, President George W. Bush signed requires elements to ensure safe use with or without an
into law the Food and Drug Administration Amendments Act implementation system (Table 3, page 425). The FDA seeks
of 2007 (FDAAA), which authorized the FDA to require a Risk input from patients and health care practitioners when devel-
Evaluation and Mitigation Strategy (REMS) program for drugs oping the program design to ensure that it will not be unduly
and biological agents.1 REMS programs are intended to sup- burdensome to patients or the health care system.2
port the safe use of products for which the risks and benefits
need to be carefully weighed in general or in specific patient The Use of Erythropoiesis-Stimulating Agents
populations. The FDA can require a REMS program at the time In Oncology
of a product’s approval. If a safety problem is detected after ESAs have been widely used in cancer patients on the basis
approval, the REMS can be required at any time during a of data showing that they decreased transfusion requirements.
drug’s life cycle. A 2006 meta-analysis of more than 9,000 patients receiving
The decision about whether to require a REMS program is ESAs, with and without concurrent antineoplastic therapy,
based on the estimated patient population likely to be exposed reported a 36% decreased need for red blood cell transfusions.5
to the product, the seriousness of the condition being treated Unfortunately, the authors also found a 67% increase in throm-
by the drug, the expected benefit and duration of treatment, boembolic events (transient ischemic attacks, stroke, pul-
and the safety risk created by use of the drug.2 The results of monar y emboli, deep-vein thrombosis, and myocardial
this analysis determine the need for and the components of the infarction) for those receiving ESAs, conflicting with results of
REMS. a previous publication.6 This earlier analysis, published in
The FDAAA legislation authorized several individual 2005,6 also indicated a trend toward increased survival that was
requirements, one or more of which may be combined to not supported by the subsequent 2006 study.5
make up a product-specific REMS program.2 The require- A meta-analysis, published in 2008 by Bennett et al.,
ments include: reinforced the elevated thromboembolic risk associated with
ESA use compared with a placebo (7.5% vs. 4.9%, respectively).7
• a medication guide. The authors also found an increased mortality risk with
• a communication plan to disseminate risk information to ESAs (hazard ratio [HR], 1.10; 95% confidence interval [CI],
health care professionals (e.g., Dear Healthcare Profes- 1.01–1.20).
sional letters).
• elements to ensure safe use.
Table 1 Elements to Ensure Safe Use
• an implementation system to monitor and evaluate the
program’s success.
A REMS program to ensure safe use incorporates one or more
of the following elements:
Several elements to ensure safe use are outlined in the leg-
islation (Table 1). Products can vary greatly in their REMS • Health care providers who prescribe the drug have
requirements. As of December 10, 2010, more than 150 drug specialized training or experience or are certified in a
products had a REMS program.3 Of those drugs, almost all specific field.
included a medication guide (Table 2). For other products, • Pharmacies, practitioners, or health care settings that
such as antidepressants as a class, a medication guide may be dispense the drug are certified in a specific field.
required outside of a REMS program.4 • The drug is dispensed to patients only in certain health
Many drugs also include a communication plan. A subset of care settings (e.g., hospitals).
• The drug is dispensed to patients with evidence or other
Dr. Reeves is an Oncology Clinical Specialist at St. Vincent Indi- documentation of safe-use conditions (e.g., laboratory
anapolis Hospital and an Assistant Professor of Pharmacy Practice results).
at Butler University in Indianapolis, Ind. Dr. Quebe is Director of • Patients are subjected to certain monitoring requirements.
Clinical Specialists and the Postgraduate Year 1 Residency • Patients are enrolled in a registry.
Program at St. Vincent Indianapolis Hospital in Indianapolis.
Data from FDA Amendments Act of 2007.2
Dr. Patel is a Postgraduate Year 1 Pharmacy Resident at St. Vincent
Indianapolis Hospital in Indianapolis.
Disclosure: The authors report that they have no financial or com-
Approved for publication March 17, 2011. mercial relationships in regard to this article.
Vol. 36 No. 7 • July 2011 • P&T® 423
2. REGULATORY COMPLIANCE: The ESA APPRISE Oncology Program
A 2009 update to the 2006 meta-analysis5 revealed increased warn of the increased risks of thrombosis and tumor promotion.
mortality with the use of ESAs (combined HR, 1.17; 95% CI, In 2007, the ODAC discussed four additional trials that
1.06–1.3) and decreased survival (combined HR, 1.06; 95% CI, showed adverse outcomes: Epoetin Alfa in Advanced Non–
1–1.12) during the active study period.8 There was no statisti- Small Cell Lung Cancer (EPO CAN-20),11 Amgen studies 2001-
cally significant increase in mortality (combined HR, 1.10; 95% 010312 and 2000-0161,13 and the Danish Head and Neck Cancer
CI, 0.98–1.24) or decrease in overall survival (combined HR, Group (DAHANCA 10)14 (see Table 4). This review resulted
1.04; 95% CI, 0.97–1.11) in the subgroup of patients receiving in the addition of a boxed warning to the labeling of ESAs
concomitant chemotherapy and ESAs. regarding an increased risk of death, more rapid tumor pro-
In addition to the meta-analyses of studies investigating gression, and serious cardiovascular and thromboembolic
ESAs, the FDA Oncologic Drugs Advisory Committee (ODAC) events.
met three times to discuss the findings and the future place of In 2008, the ODAC was convened to review the results of two
ESAs in the management of patients with cancer. At the first additional trials: the Gynecologic Oncology Group (GOG-
meeting in 2004, two trials with adverse findings were reviewed 191)15 and the Preoperative Epirubicin Paclitaxel Aranesp
(Table 4, page 426): Evaluation of NeoRecormon on outcome (PREPARE16) study. Based on these trials and the earlier
in Head And Neck Cancer in Europe (ENHANCE)9 and the literature showing adverse outcomes, the ODAC recom-
Breast Cancer Erythropoietin Survival Trial (BEST).10 Based mended limiting the use of ESAs to patients receiving pallia-
on these trials and previous data regarding thromboembolic tive treatment. The ODAC also recommended that the FDA
events, the FDA-approved labeling of ESAs was updated to require informed consent or a patient agreement before ESAs
Table 2 Drug Products With REMS Programs—Medication Guide Only
Antiepileptic drugs, selected Other agents
Carbamazepine (Equetro) Bupropion (Aplenzin, Wellbutrin)
Ethosuximide (Zarontin) Colchicine (Colcrys)
Ethotoin (Peganone) Dabigatran (Pradaxa)
Gabapentin (Neurontin) Diclofenac oral and topical solutions (Cambia, Pennsaid)
Lacosamide (Vimpat) Doxepin (Silenor)
Levetiracetam (Keppra) Fenofibric acid (Trilipix)
Lamotrigine (Lamictal) Mefloquine (Lariam)
Pregabalin (Lyrica) Methsuximide (Celontin)
Primidone (Mysoline) Metoclopramide oral solution and disintegrating tablets
Tiagabine (Gabitril) (Metozolv ODT)
Topiramate (Topamax) Milnacipran (Savella)
Zonisamide (Zonegran) Morphine oral solution
Naltrexone (Vivitrol)
Antiretrovirals, selected Olanzapine (Zyprexa)
Abacavir (Ziagen) Olanzapine/fluoxetine (Symbyax)
Abacavir/lamivudine (Epzicom) Omalizumab (Xolair)
Lopinavir/ritonavir (Kaletra) Oral bowel prep kits
Abacavir/lamivudine/zidovudine (Trizivir) Oxycodone oral solution
Nevirapine (Viramune) Pancrelipase (Creon, Pancreaze, Zenpep)
Didanosine (Videx,Videx EC) Pazopanib (Votrient)
Telbivudine (Tyzeka) Propylthiouracil
Saquinavir (Invirase) Quetiapine (Seroquel)
Ramelteon (Rozerem)
Fluoroquinolones, all Repository corticotropin (HP Acthar Gel)
Ribavirin (Copegus, Rebetol)
Interferon alfa and beta, all Rufinamide (Banzel)
Sirolimus (Rapamune)
Long-acting beta2-agonist combination products, selected Sitagliptin (Januvia, Janumet)
Formoterol/budesonide (Symbicort) Sunitinib (Sutent)
Salmeterol/fluticasone (Advair) Testosterone, topical (AndroGel, Axiron, Testim)
Trazodone extended release (Oleptro)
Thiazolidinediones, all Varenicline (Chantix)
Zolpidem oral spray (ZolpiMist)
Data from FDA, as of December 2010. Information for REMS is updated routinely on the FDA Web site.3
424 P&T® • July 2011 • Vol. 36 No. 7
3. REGULATORY COMPLIANCE: The ESA APPRISE Oncology Program
Table 3 REMS Program Requirements by Drug Product or Class
Medication Communica- Elements of Implementa-
Guide tion Plan Safe Use tion System
Alvimopan (Entereg) X X X
Alglucosidase alfa (Lumizyme) X X X
Alosetron (Lotronex) X X X
Armodafinil (Nuvigil) X X
Botulinum toxin A (Botox, Dysport, Xeomin) and B (Myobloc) X X
Buprenorphine transdermal (Butrans) X X
Buprenorphine/naloxone sublingual film (Suboxone) X X X
Collagenase Clostridium histolyticum (Xiaflex) X X
Dalfampridine (Ampyra) X X
Denosumab (Prolia) X X
Dronedarone (Multaq) X X
Ecallantide (Kalbitor) X X
Eculizumab (Soliris) X X
Electrolyte containing bowel prep tablets (OsmoPrep, Visicol) X X
Eltrombopag (Promacta) X X X
Endothelin receptor antagonists (Letairis, Tracleer) X X X
Erythropoiesis-stimulating agents (Aranesp, Epogen, Procrit) X X X X
Everolimus (Zortress) X X
Fingolimod (Gilenya) X X
Formoterol/mometasone (Dulera) X X
Fentanyl buccal film (Onsolis) X X X X
Glucagon-like peptides (Byetta,Victoza) X X
Hydromorphone extended release (Exalgo) X X
Isotretinoin (Accutane, Amnesteem, Claravis) X X X
Lenalidomide (Revlimid) X X X
Modafinil (Provigil) X X
Morphine/naltrexone (Embeda) X X
Nilotinib (Tasigna) X X
Olanzapine extended release injection (Zyprexa Relprevv) X X X X
Oxycodone extended release X X
Pegloticase (Krystexxa) X X
Prasugrel (Effient) X X
Quinine (Qualaquin) X X
Romiplostim (Nplate) X X X X
Sacrosidase (Sucraid) X X X
Salmeterol (Serevent) X X
Telavancin (Vibativ) X X
Teriparatide (Forteo) X X
Tetrabenazine (Xenazine) X X
Thalidomide (Thalomid) X X X
Tocilizumab (Actemra) X X
Tolvaptan (Samsca) X X
Tumor necrosis factor antagonists: certolizumab (Cimzia), X X
etanercept (Enbrel), adalimumab (Humira), infliximab
(Remicade), golimumab (Simponi)
Ustekinumab (Stelara) X X
Vigabatrin (Sabril) X X X X
Data from FDA, as of December 2010. Information for REMS is updated routinely on the FDA Web site.3
Vol. 36 No. 7 • July 2011 • P&T® 425
4. REGULATORY COMPLIANCE: The ESA APPRISE Oncology Program
Table 4 Summary of Trials of Erythropoiesis-Stimulating Agents (ESAs) Reviewed by the Oncologic
Drugs Advisory Committee
Trial Study Design Selected Results
Reviewed in 2004
ENHANCE9 • Patients with head and neck cancer receiving ESA use was associated with:
radiotherapy • decreased locoregional progression-free survival
• Randomized to receive an ESA or placebo (adjusted relative risk, 1.62; P = 0.0008)
• Target Hb ≤ 14 g/dL for women, ≤ 15 g/dL for • decreased overall survival (relative risk, 1.39;
men P = 0.02)
BEST10 • Women with metastatic breast cancer receiving Study was stopped early; higher mortality rates in the ESA
first-line chemotherapy group than in the placebo group:
• Randomized to receive an ESA or placebo • 12-month overall survival rate 70% vs. 76% (P = 0.01)
• Target Hb 12–14 g/dL • tumor response and time to progression were similar
between groups
Reviewed in 2007
EPO CAN-2011 • Patients with non–small-cell lung cancer not Study was stopped early; higher mortality rates in the ESA
receiving chemotherapy or receiving non– group than in controls:
platinum-based chemotherapy regimens • Median survival, 63 days vs. 129 days (P = 0.04)
• Randomized to receive an ESA or placebo
• Target Hb 12–14 g/dL
Amgen study • Patients with non-myeloid cancers not receiving ESA use was associated with:
2001-010312 chemotherapy • increased cardiovascular and thromboembolic events
• Randomized to receive an ESA or placebo (9.7% vs. 7.7%; P was not reported)
• Target Hb 12–13 g/dL • decreased survival during treatment and long-term
follow-up (HR for overall survival, 1.22; P = 0.022)
Amgen study • Patients with lymphoma or myeloma receiving ESA use was associated with:
2000-016113 chemotherapy • increased quality of life
• Randomized to receive an ESA or placebo • decreased survival (HR for death, 1.37; P = 0.04)
• Target Hb 13–14 g/dL for women, 13–15 g/dL
for men
DAHANCA 1014 • Patients with squamous cell carcinoma of the ESA use was associated with:
head and neck receiving radiotherapy • decreased locoregional control (56% vs. 69%; P = 0.02)
• Randomized to receive an ESA or placebo • decreased disease-free survival (48% vs. 63%; P = 0.004)
• Target Hb ≤ 15.5 g/dL No statistically significant difference in overall survival
Reviewed in 2008
GOG-19115 • Women with cervical cancer receiving Study was stopped early; concerns about an increased rate
chemotherapy and radiation of thromboembolic events with ESAs:
• Randomized to receive an ESA or placebo • 19.2% vs. 7.7%
• Target Hb 12–14 g/dL • fewer than 25% of planned patients enrolled
ESA use was associated with a numerical, but not a
statistically significant, decrease in:
• progression-free survival (58% vs. 66%)
• overall survival (60% vs. 74%)
PREPARE16 • Women with breast cancer receiving neo- An unplanned interim analysis after a median follow-up
adjuvant chemotherapy period of 3 years showed an association of ESA use with:
• Randomized to receive an ESA or a transfusion • decreased overall survival (86% vs. 90%;
• Target Hb 12.5–13 g/dL HR, 1.42; 95% CI, 0.93–2.18)
• decreased progression-free survival (73% vs. 79%;
HR, 1.33; 95% CI, 0.99–1.79)
CI = confidence interval; Hb = hemoglobin; HR = hazard ratio.
Trials: BEST = Breast Cancer Erythropoietin Survival Trial; DAHANCA = Danish Head and Neck Cancer Group; ENHANCE = Evaluation of
NeoRecormon on outcome in Head And Neck Cancer in Europe; EPO CAN-20 = Epoetin Alfa in Advanced Non–Small Cell Lung Cancer;
GOG = Gynecologic Oncology Group; PREPARE = Preoperative Epirubicin Paclitaxel Aranesp.
continued on page 431
426 P&T® • July 2011 • Vol. 36 No. 7
5. REGULATORY COMPLIANCE: The ESA APPRISE Oncology Program
continued from page 426
could be administered. The FDA-approved labels were sub- ESAs, whereas other elements of ESA APPRISE are unique to
sequently revised to state that ESAs were not recommended patients with cancer.)
when the intent of chemotherapy was to cure and when a Some logistical considerations are associated with this
REMS program was initiated. process and must be addressed by each hospital, such as
In response to published data, national guidelines have been which member of the health care team is responsible for
updated. The 2010 American Society of Clinical Oncology/ reviewing the information with the patient (nurse, pharmacist,
American Society of Hematology guideline recommends ESAs or physician) and whether the medication guide must be used
as an option when hemoglobin levels are below 10 g/dL dur- to facilitate discussion. If the guide is used, the process by
ing chemotherapy.17 The guideline does not include a specific which it is stored and retrieved must also be addressed.
hemoglobin target; instead, it recommends maintaining For instance, the medication guides are five pages long,
hemoglobin at the lowest level required to avoid a transfusion. they are not supplied in a 1:1 ratio with the product, and they
Notably, the guideline differs from the FDA-approved labeling are subject to updates. At St. Vincent Indianapolis Hospital, the
by stating that limiting the use of ESAs to palliative chemother- nurse reviews the guide with the patient. The guide is printed
apy regimens is a clinical judgment and not expressly sup- by the pharmacy from the manufacturer’s Web site at the time
ported by the literature. The Centers for Medicare & Medicaid of dispensing, It is then sent with the ESA to ensure that the
Services (CMS) defined the appropriate setting for ESAs to most recent version is used, thereby eliminating the need to
apply only to patients receiving chemotherapy in the palliative store paper copies. The medication guide is distributed with
setting with a hemoglobin level of less than 10 g/dL and fur- each drug administration to each patient so that the content
ther recommend discontinuing ESAs within eight weeks of the provided and the method of dissemination are consistent.
last chemotherapy dose.18
Communication Plan
ESA APPRISE and an Approach to Compliance The responsibility of the communication plan rests with the
In February 2010, based on the ODAC’s recommendations manufacturer. The Dear Healthcare Provider letters and other
and the FDA’s subsequent action, Amgen and Centocor Ortho materials can be accessed at www.esa-apprise.com.20
Biotech announced that the FDA had approved a REMS pro-
gram called Assisting Providers and cancer Patients with Risk Elements to Ensure Safe Use20
Information for the Safe use of ESAs (the ESA APPRISE On- Three of the elements to ensure safe use are incorporated
cology Program).19 This program incorporates a medication into the ESA APPRISE Oncology Program: (1) health care
guide, a communication plan, elements to ensure safe use, and provider training and certification, (2) hospital certification,
an implementation system.20 and (3) dispensing following the documentation of safe-
use conditions. All prescribers who plan to order ESAs for
Medication Guide cancer patients must receive training and must enroll in ESA
The original REMS for ESAs included a requirement that a APPRISE. The manufacturer maintains an on-line list of en-
medication guide be distributed to each patient when an ESA rolled prescribers through an independent third party. The
was to be dispensed.20 There was no specific direction with hospital must appoint a designee to receive training and enroll
regard to the practice setting (i.e., inpatient or outpatient) or in APPRISE on behalf of the institution. At our hospital, the
the frequency with which guides should be distributed (i.e., designee is the director of pharmacy.
upon therapy initiation or with every drug administration). Training, which is available on the manufacturer’s Web site,
In February 2011, the FDA issued a draft guidance ex- includes a review of the risks of using ESAs in cancer patients.
plaining its approach to discretionary enforcement of the Enrollment includes an agreement to conform to the man-
REMS regulations.21 Although not yet formally in effect as of dates of ESA APPRISE. The hospital designee is responsible
this writing, the draft guidance specifies requirements for in- for establishing and overseeing a process that includes verifi-
patient and outpatient sites and when medication guides must cation of prescriber enrollment in the program as well as
be distributed. For hospitalized patients, a guide is not manda- patient and prescriber discussions of risks and benefits before
tory unless the patient or patient’s agent requests it. Instead, ESAs are dispensed.
providing patient information, including appropriate use, po- One of the elements of ESA APPRISE is a formal, docu-
tential side effects, and follow-up by a health care professional mented discussion between a certified prescriber and the
in the course of care, is considered sufficient to meet the reg- patient regarding the risks and benefits of ESA use in cancer.
ulatory intent. In an outpatient setting, in which the ESA is Both parties sign an acknowledgment form. Outside the hos-
dispensed to a health care professional to administer to the pital, these forms are faxed to a central repository and are also
patient, the medication guide must be distributed upon re- maintained in the patient’s medical record. For in-hospital use
quest, at the first time drug is dispensed, and when the guide’s of ESAs, forms are not submitted to a central repository; they
content has been substantively changed. are provided to the hospital designee only to validate that the
The FDA guidance does not affect the duty of the hospital discussion has occurred before an ESA has been dispensed.
to inform a patient of the REMS program. Although distribu- Completion of the form does not constitute patient enrollment
tion of the actual medication guide is not mandated for each in any registry or program; it serves only as documentation of
patient with each drug administration, a review of the infor- the required discussion between prescriber and patient.
mation must still be included for each patient each time. We’ve noted many logistical problems involving the
(Note: Distribution of the guide is required for all uses of acknowledgment form in our institution, which is a community
Vol. 36 No. 7 • July 2011 • P&T® 431
6. REGULATORY COMPLIANCE: The ESA APPRISE Oncology Program
hospital without an integrated electronic health record (EHR) duty of the prescriber to complete the acknowledgment form
system. In the REMS program, a prescriber is required to with the patient. This task cannot be delegated to other mem-
complete the form with the patient for each course of therapy, bers of the health care team. Verification also needs to occur
although many times therapy is initiated in the outpatient set- with each admission, and completed forms must be stored and
ting and continued in the hospital. The hospital could choose retrieved by the pharmacist or must be provided again by the
to require a copy of the acknowledgment form to verify com- office or physician with each admission.
pletion. If so, the form must travel from the office to the hos- Our hospital has opted for a different approach and has
pital, or it must be completed again in the hospital. The office determined that a specific medication order set for ESAs is the
might be unable to provide a copy during off-hours, or the best approach in treating cancer patients (Figure 1). Included
physician might be unavailable to complete it again. in the order set is a physician’s attestation that the medication
According to the ESA APPRISE Oncology Program, it is the guide has been reviewed, the risks and benefits have been
NOTE: Orders for erythropoiesis-stimulating agents IRON REPLACEMENT
(ESAs) will not be honored unless all required infor- I Ferrous Sulfate 325 mg PO t.i.d. on an empty
mation is provided. stomach
I ______________________________
Hgb (g/dL): _________
(Date: ___/___/______) ERYTHROPOIESIS-STIMULATING AGENT
*Hgb must be < 10 g/dL ×
I HOLD darbepoetin if Hgb > 10 g/dL
Inpatient
INDICATION:
I Darbepoetin (Aranesp) 100 mcg subcutaneously
I Chemotherapy-induced anemia
once weekly
* ESAs are indicated only in patients receiving
concomitant chemotherapy. Therapy may be Outpatient
continued for up to 8 weeks after the last dose I Darbepoetin (Aranesp) 500 mcg subcutaneously
of chemotherapy. every three weeks
* ESAs are not indicated in patients receiving I Darbepoetin (Aranesp) ________ mcg
hormonal agents, therapeutic biologic products, (2.25 mcg/kg) subcutaneously weekly
or radiotherapy unless they are also receiving
concomitant myelosuppressive chemotherapy. Centers for Medicare & Medicaid Services (CMS)
I Other (specify): ____________________________ Dose Adjustment Guidelines
• If Hgb increase < 1 g/dL after 4 weeks and Hgb is
*ESAs are not reasonable for AML, CML, or erythroid < 10 g/dL: increase dose by 25%.
cancers; anemia of cancer not related to chemotherapy; • If Hgb increase > 1 g/dL over 2 weeks: hold until
or prophylactic use. Hgb < 10 g/dL: decrease dose by 25%.
LABS:
I CBC prior to each dose ESA APPRISE Program
I Tsat I Ferritin I Serum iron ***REQUIRED FOR ALL ONCOLOGY PATIENTS***
I Serum vitamin B12 (cobalamin) level By signing below I attest that:
I Serum folate level • I have received training and I am enrolled in the ESA
I ________________________________ APPRISE Oncology Program. I have been assigned an
enrollment ID number.
I ________________________________
• I have provided the Medication Guide to the patient
and reviewed it with the patient prior to this course of
therapy.
• I counseled this patient on the risks/benefits of ESAs
prior to this course of therapy.
• I signed the ESA APPRISE Oncology Program Patient
and Healthcare Professional Acknowledgment form
and witnessed the patient sign the same form. I have
retained the archival copy of this form.
Signature:__________________________
Date: ___/___/______
Date ________Time ____________ Signature________________________MD
Figure 1 Sample ESA Oncology Order Set. AML, CML = acute and chronic forms of leukemia; CBC = complete blood count;
Hgb = hemoglobin; PO = orally; t.i.d. = three times daily; Tsat = transferrin saturation.
432 P&T® • July 2011 • Vol. 36 No. 7
7. REGULATORY COMPLIANCE: The ESA APPRISE Oncology Program
discussed, and the prescriber and patient have signed the therapy: A survival study. J Clin Oncol 2005;23:5960–5972.
acknowledgment form. Following confirmation that the pre- 11. Wright JR, Ung YC, Julian JA, et al. Randomized, double-blind,
scriber is registered with the ESA APPRISE Oncology Pro- placebo-controlled trial of erythropoietin in non-small-cell lung
cancer with disease-related anemia. J Clin Oncol 2007;25:1027–
gram, this order set serves as our hospital’s documentation of 1032.
compliance. The patient acknowledgment form, in addition to 12. Smith RE, Aapro MS, Ludwig H, et al. Darbepoetin alfa for the
the medication order set, may be submitted to the pharmacy; treatment of anemia in patients with active cancer not receiving
however, this is not required, because the physician’s attesta- chemotherapy or radiotherapy: Results of a phase III, multicenter,
randomized, double-blind, placebo-controlled study. J Clin Oncol
tion serves as a surrogate. 2008;26:1040–1050.
13. Hedenus M, Adriansson M, San Miguel J, et al. Efficacy and
Implementation safety of darbepoetin alfa in anaemic patients with lympho-
The manufacturer is responsible for confirming compliance proliferative malignancies: A randomized, double-blind, placebo-
with ESA APPRISE. This is achieved through a series of ran- controlled study. Br J Haematol 2003;122:394–403.
14. Overgaard J, Hoff C, Sand Hansen H, et al. Randomized study of
dom on-site audits of enrolled hospitals. Those hospitals that the importance of novel er ythropoiesis stimulating protein
are not enrolled or that are not in compliance may not have (Aranesp) for the effect of radiotherapy in patients with primary
access to ESAs.20 squamous cell carcinoma of the head and neck (HNSCC):
The Danish Head and Neck Cancer Group DAHANCA 10 ran-
Conclusion domized trial. Eur J Cancer Suppl 2007;5:7.
15. Thomas G, Ali S, Hoebers FJP, et al. Phase III trial to evaluate the
REMS programs represent a new facet of drug safety regu- efficacy of maintaining hemoglobin levels above 120 g/dl with ery-
lation. With a growing number of programs and a wide variety thropoietin vs. above 100 g/dl without erythropoietin in anemic
of requirements within the programs, hospitals may be chal- patients receiving concurrent radiation and cisplatin for cervical
lenged to meet the criteria for compliance. The ESA APPRISE cancer: A Gynecologic Oncology Group Study. Gynecol Oncol
2008;108:317–325.
Oncology Program represents a difficult challenge, in that 16. FDA. Background information for the Oncologic Drugs Advisory
ESAs may be high-use agents, and the elements to ensure safe Committee meeting, March 13, 2008. Available at: www.fda.
use present logistical considerations for hospital pharmacy gov/ohrms/DOCKETS/ac/08/briefing/2008-4345b2-05-AMGEN.pdf.
departments. Accessed December 30, 2010.
17. Rizzo JD, Brouwers M, Hurley P, et al. American Society of Clin-
ical Oncology/American Society of Hematology clinical practice
guideline update on the use of epoetin and darbepoetin in adult
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