Clinical and Pharmacoeconomic analysis was extensivley done on Eylea for its placement on a hypothetical health plans formulary for Macular Degeneration. Information was presented to a panel of pharmacy professionals in managed care and industry
Sulfasalazine is a DMARD used to treat rheumatoid arthritis and inflammatory bowel diseases. It consists of sulfapyridine linked to 5-aminosalicylic acid. Its mechanism of action is unknown but it may suppress inflammatory cells. It has low oral bioavailability and is metabolized by intestinal bacteria and the liver. Its metabolites include sulfapyridine, 5-aminosalicylic acid, and N-acetyl-5-aminosalicylic acid. It has a plasma half-life of 7-15 hours and is excreted primarily in urine. Common side effects include nausea, headache and rash. It interacts with digoxin and folic acid. Use in pregnancy requires
This document discusses sulfasalazine, a drug used to treat rheumatoid arthritis, psoriatic arthritis, Crohn's disease, and ulcerative colitis. Sulfasalazine is a prodrug composed of 5-aminosalicylic acid (5-ASA) linked to sulfapyridine through an azo bond. When ingested, it is partially absorbed in the jejunum and the remainder is reduced in the colon by bacteria into sulfapyridine and 5-ASA, its active components. The document also discusses the pharmacology, structure-activity relationships, and use of prodrug approaches of delivering 5-ASA specifically to the colon to treat inflammatory bowel diseases.
This document discusses off-label use of drugs, which refers to prescribing approved medications for indications, populations, doses, or administration routes that are not included in the drug's official approved labeling by regulatory agencies. The document defines off-label use and provides examples. It discusses the frequency, motivations, types based on dose, age, indications, routes of administration. It also discusses perspectives of different stakeholders and regulations governing off-label use in the US, UK, and India. Studies on the prevalence of off-label prescribing in Indian pediatric and psychiatry patients are mentioned.
The document discusses pharmacovigilance, which is defined as monitoring the effects of medicines to detect adverse drug reactions. It describes how pharmacovigilance aims to improve patient safety by contributing to assessments of drug benefit, harm, effectiveness and risk. The World Health Organization (WHO) coordinates global pharmacovigilance efforts through its Uppsala Monitoring Centre. India's Pharmacovigilance Programme of India (PvPI) was launched in 2010 to monitor adverse drug reactions among the Indian population and ensure medicines are used safely and rationally in India. PvPI is coordinated by the National Coordinating Centre and collaborates with WHO and India's drug regulatory authority, CDSCO.
The document outlines the key aspects of Schedule Y, the law in India governing clinical trials. It discusses what Schedule Y is, its purpose, key amendments, and structure. It describes the application process for permission to conduct clinical trials and guidelines around phases of trials, special populations, informed consent, responsibilities of sponsors, investigators and ethics committees, and post-marketing surveillance. Appendices provide more details on required documents, reports, and data.
This document summarizes oral contraceptives, including their mechanism of action, methods of use, and formulation. It discusses how oral contraceptives work by suppressing ovulation through negative feedback inhibition of gonadotropins. It also describes the typical menstrual cycle and hormone levels throughout its phases. Common oral contraceptive formulations include combined estrogen-progesterone pills and sequential pills, which are taken in cycles to prevent pregnancy while allowing withdrawal bleeding. Side effects and precautions are also outlined.
Clinical pharmacokinetics part 1 dr jayesh vaghelajpv2212
This document discusses clinical pharmacokinetics and factors affecting drug absorption and bioavailability. It defines pharmacokinetics as what the body does to a drug, including absorption, distribution, metabolism and excretion. Absorption depends on patient factors like age, gastric emptying time, and presence of food, as well as physicochemical drug properties and pharmaceutical formulation characteristics. Understanding factors influencing absorption can help optimize drug therapy.
This document defines and describes various types of adverse drug reactions and events. It discusses pharmacovigilance, which is the science related to detecting, assessing, understanding, and preventing adverse drug effects. The document categorizes adverse drug effects into side effects, allergy reactions, toxicity, intolerance, idiosyncrasy, photosensitivity, dependence, withdrawal reactions, teratogenicity, mutagenicity, carcinogenicity, and drug-induced diseases. It provides examples and treatments for different types of reactions. Pharmacovigilance helps educate doctors about adverse drug reactions and regulates safe drug use.
Sulfasalazine is a DMARD used to treat rheumatoid arthritis and inflammatory bowel diseases. It consists of sulfapyridine linked to 5-aminosalicylic acid. Its mechanism of action is unknown but it may suppress inflammatory cells. It has low oral bioavailability and is metabolized by intestinal bacteria and the liver. Its metabolites include sulfapyridine, 5-aminosalicylic acid, and N-acetyl-5-aminosalicylic acid. It has a plasma half-life of 7-15 hours and is excreted primarily in urine. Common side effects include nausea, headache and rash. It interacts with digoxin and folic acid. Use in pregnancy requires
This document discusses sulfasalazine, a drug used to treat rheumatoid arthritis, psoriatic arthritis, Crohn's disease, and ulcerative colitis. Sulfasalazine is a prodrug composed of 5-aminosalicylic acid (5-ASA) linked to sulfapyridine through an azo bond. When ingested, it is partially absorbed in the jejunum and the remainder is reduced in the colon by bacteria into sulfapyridine and 5-ASA, its active components. The document also discusses the pharmacology, structure-activity relationships, and use of prodrug approaches of delivering 5-ASA specifically to the colon to treat inflammatory bowel diseases.
This document discusses off-label use of drugs, which refers to prescribing approved medications for indications, populations, doses, or administration routes that are not included in the drug's official approved labeling by regulatory agencies. The document defines off-label use and provides examples. It discusses the frequency, motivations, types based on dose, age, indications, routes of administration. It also discusses perspectives of different stakeholders and regulations governing off-label use in the US, UK, and India. Studies on the prevalence of off-label prescribing in Indian pediatric and psychiatry patients are mentioned.
The document discusses pharmacovigilance, which is defined as monitoring the effects of medicines to detect adverse drug reactions. It describes how pharmacovigilance aims to improve patient safety by contributing to assessments of drug benefit, harm, effectiveness and risk. The World Health Organization (WHO) coordinates global pharmacovigilance efforts through its Uppsala Monitoring Centre. India's Pharmacovigilance Programme of India (PvPI) was launched in 2010 to monitor adverse drug reactions among the Indian population and ensure medicines are used safely and rationally in India. PvPI is coordinated by the National Coordinating Centre and collaborates with WHO and India's drug regulatory authority, CDSCO.
The document outlines the key aspects of Schedule Y, the law in India governing clinical trials. It discusses what Schedule Y is, its purpose, key amendments, and structure. It describes the application process for permission to conduct clinical trials and guidelines around phases of trials, special populations, informed consent, responsibilities of sponsors, investigators and ethics committees, and post-marketing surveillance. Appendices provide more details on required documents, reports, and data.
This document summarizes oral contraceptives, including their mechanism of action, methods of use, and formulation. It discusses how oral contraceptives work by suppressing ovulation through negative feedback inhibition of gonadotropins. It also describes the typical menstrual cycle and hormone levels throughout its phases. Common oral contraceptive formulations include combined estrogen-progesterone pills and sequential pills, which are taken in cycles to prevent pregnancy while allowing withdrawal bleeding. Side effects and precautions are also outlined.
Clinical pharmacokinetics part 1 dr jayesh vaghelajpv2212
This document discusses clinical pharmacokinetics and factors affecting drug absorption and bioavailability. It defines pharmacokinetics as what the body does to a drug, including absorption, distribution, metabolism and excretion. Absorption depends on patient factors like age, gastric emptying time, and presence of food, as well as physicochemical drug properties and pharmaceutical formulation characteristics. Understanding factors influencing absorption can help optimize drug therapy.
This document defines and describes various types of adverse drug reactions and events. It discusses pharmacovigilance, which is the science related to detecting, assessing, understanding, and preventing adverse drug effects. The document categorizes adverse drug effects into side effects, allergy reactions, toxicity, intolerance, idiosyncrasy, photosensitivity, dependence, withdrawal reactions, teratogenicity, mutagenicity, carcinogenicity, and drug-induced diseases. It provides examples and treatments for different types of reactions. Pharmacovigilance helps educate doctors about adverse drug reactions and regulates safe drug use.
A brief description about Pharmacovigilance, aims and scope, need of pharmacovigilance, programs by WHO for international drug safety monitoring, UMC, VIGIBASE, WHO causality assessment scale and specific regulatory bodies of various countries
Drugs affecting on renin angiotensin systemChintan Doshi
The renin-angiotensin system regulates blood pressure and fluid balance. Drugs that affect this system include ACE inhibitors, angiotensin receptor blockers, and direct renin inhibitors. ACE inhibitors work by inhibiting the conversion of angiotensin I to angiotensin II, while ARBs block the effects of angiotensin II by selectively blocking the AT1 receptor. These drugs are used to treat hypertension, congestive heart failure, myocardial infarction, and diabetic nephropathy. Their side effects include hypotension, hyperkalemia, and cough. Direct renin inhibitors such as aliskiren directly inhibit renin's action.
The document summarizes the distribution of drugs in the body. It discusses:
1) Distribution involves the reversible transfer of drugs between blood and tissues, driven by concentration gradients.
2) Factors like tissue permeability, organ size/perfusion, protein binding, and other physiological factors determine the extent of distribution between tissues.
3) Tissue permeability depends on drug properties like size, ionization, and lipid solubility as well as physiological barriers like the blood-brain barrier.
The document discusses the key aspects of an Investigational New Drug (IND) application submitted to the FDA to request permission to conduct clinical trials of an unapproved drug. An IND application contains information on the drug's chemistry, manufacturing, pharmacological and toxicological effects, clinical protocol, and investigators brochure. It allows the FDA to ensure the risks to human subjects are reasonable. The FDA reviews INDs within 30 days to determine if a clinical hold is needed before trials can begin. Annual reports updating trial progress are also required.
This document discusses pharmaceutical dosage forms and their design. It defines key terms like active drug substance, excipients, and dosage forms. It classifies dosage forms based on physical properties into gases, liquids, semisolids, and solids. It also discusses important topics like prescription writing, controlled substances, and requirements for prescriptions of controlled substances.
Mastering Pharmaceutical Interviews- By Santosh Sarnaik.pdfSantosh Sarnaik
This document is an excerpt from a book that provides guidance for job interviews in the pharmaceutical industry, focusing on roles in regulatory affairs, formulation research and development (R&D), and technology transfer. The excerpt discusses formulation R&D, describing the development of oral solid, topical, and parenteral/injectable formulations. It provides an overview of the key areas of formulation R&D and lists common interview questions asked about a candidate's experience and understanding of formulation development, excipient selection, stability testing, bioavailability optimization, and regulatory guidelines.
The document discusses regulatory requirements for bioequivalence studies from the FDA and WHO perspectives. It defines key terms like bioavailability, bioequivalence, reference product and generic products. It also outlines FDA guidelines on bioequivalence documentation for INDs, NDAs and ANDAs. Test procedures for establishing bioequivalence include pharmacokinetic, pharmacodynamic and clinical studies according to FDA regulations. Pharmacokinetic studies are emphasized for directly measuring drug absorption. Study design considerations like single vs multiple dose studies are also covered.
This presentation discusses HMG-CoA reductase inhibitors, also known as statins. It begins with an introduction to hyperlipidemia and its risk factors. It then discusses atorvastatin as the prototype statin drug, and provides examples of other statins. The presentation explains that statins work by inhibiting the HMG-CoA reductase enzyme, which lowers cholesterol synthesis and raises LDL receptor levels, reducing LDL cholesterol. Adverse effects can include increased liver enzymes, myopathy, and interactions with other drugs. The presentation concludes by thanking the audience.
Formulation and evaluation of matrix type rosuvastatin sustained release tabletspharmaindexing
This document describes the formulation and evaluation of matrix-type sustained release tablets of rosuvastatin. Tablets were prepared using polymers like HPMC K15M, HPMC K50M, and ethylcellulose by direct compression technique. The tablets were evaluated for characteristics like hardness, thickness, friability, weight variation, drug content, and floating properties. The best formulation was subjected to kinetic treatment and was found to follow zero order, first order, Peppas, Higuchi, and Hixson-Crowell kinetics. The optimized batches were stable for 2 months at 40°C/75% RH conditions. The document provides details on various sustained release drug delivery systems, techniques for tablet formulation like direct compression
This presentation deals with the in-depth analysis of various cardiac stimulants & depressants both directly & indirectly acting on frog's heart. Also, includes a nice quiz, a good exercise for the grey cells of the brain at the end of the presentation.
The document discusses adverse drug reactions (ADRs), defined as harm caused by a medication at normal doses during normal use. It describes the types of ADRs, including type A reactions which are augmented and predictable, and type B reactions which are bizarre and unpredictable. The mechanisms of ADRs are also explained, including humoral reactions mediated by antibodies and cell-mediated reactions involving T-lymphocytes. Finally, the document outlines some ways to prevent ADRs, such as avoiding inappropriate drug use, considering a patient's history, and watching for potential drug interactions.
Anti-VEGF drugs and HDAC inhibitors are used in cancer treatment. Anti-VEGF drugs inhibit VEGF signaling by blocking the VEGF ligand or receptor and include monoclonal antibodies like bevacizumab and small molecule inhibitors like sunitinib. They are used to treat cancers like colorectal, lung, and kidney cancer. HDAC inhibitors increase histone acetylation, activate tumor suppressor genes, and induce cell cycle arrest. Panobinostat, romidepsin, and vorinostat are examples used for blood cancers and lymphomas. Both classes of drugs can cause side effects like hypertension, bleeding, and fatigue.
Mr. W, a 56-year-old man with risk factors of hypertension and diabetes, presents with chronic chest pain that occurs with exertion such as climbing stairs. His symptoms, location of pain, and risk factors are consistent with stable angina, though gastroesophageal reflux disease and musculoskeletal disorders are also considered. Physical exam is normal except for peripheral neuropathy. Testing shows left ventricular hypertrophy on ECG and hypercholesterolemia on labs. Exercise stress testing surprisingly shows no evidence of ischemia despite reproduced chest pain. Stable angina remains a concern given his risk factors and symptoms.
Sulfasalazine is an anti-inflammatory drug used to treat bowel diseases like ulcerative colitis and rheumatoid arthritis. It works by inhibiting the production of cytokines and inflammatory mediators. Common side effects include gastric distress, headache, and nausea. It is generally considered safe in pregnancy but can cause discoloration of urine or skin. Precautions must be taken with elderly patients or those with allergies or asthma. Drug interactions can also increase risks, so patients should inform their doctors of other medications.
The document discusses targeted drug delivery systems. It begins by introducing the concept of targeted delivery as designed by Paul Ehrlich to specify drug moieties to targeted areas, such as cancer cells or organs. It then discusses the ideal characteristics of targeted delivery systems, including being non-toxic, stable, and providing controlled drug release at the target site. The document outlines different types of targeting approaches, including passive targeting which relies on physiological or pathological differences between target and non-target sites, and active targeting using ligands or antibodies. Liposomes are discussed as a common drug carrier for targeted delivery systems.
This document outlines the requirements and guidelines for conducting clinical trials and obtaining permission to import or manufacture new drugs in India. It discusses the need to frame guidelines for clinical research and regulation of new drugs. Key points include that clinical trials require permission from the licensing authority and approval from ethics committees. Sponsors must submit various data on the drug and trials must be conducted according to Good Clinical Practice guidelines. Informed consent is required from all subjects and safety of subjects must be protected at all stages of the drug development and approval process. Trials generally proceed through Phases I-III to evaluate safety, efficacy, and optimal dosing.
This document discusses drug elimination kinetics. It describes the main routes of drug excretion from the body, including hepatic excretion through bile and renal excretion through glomerular filtration and tubular secretion/reabsorption. The kinetics of drug elimination are explained, including plasma half-life, repeated dosing to achieve steady state concentrations, and target level strategies using loading and maintenance doses. The principles of first-order and zero-order elimination, as well as therapeutic drug monitoring, are also outlined.
This document discusses bioavailability and bioequivalence. It defines bioavailability as the rate and extent to which the active ingredient is absorbed from a drug product and becomes available at the site of action. Bioequivalence denotes that two or more identical dosage forms reach the systemic circulation at the same relative rate and to same relative extent. The document outlines various methods to assess bioavailability, including pharmacokinetic methods like plasma level time studies and urinary excretion studies, as well as pharmacodynamic methods. It also discusses factors that affect bioavailability and the design and statistical analysis of bioequivalence studies.
Using a manufacturer submitted dossier and other clinical data, extensive research was performed to analyze the proper placement of Yervoy on a hypothetical health plan's formulary for treatment of unresectable metastatic melanoma. Pharmacoeconomic benefits and clinical efficacy were weighed heavily in decision making.
Clinical trials established in 2005 the efficacy of Ranibizumab (Lucentis, Genentech) for the treatment of neovascular age-related macular degeneration (wetAMD), the leading cause of legal blindness in the United States.This disease is affecting people over the age of 65 with a prevalence of 1.6 million and 200000 new cases per year in the USA .While awaiting approval for ranibizumab from the Food and Drug Administration, ophthalmologists began treating neovascular AMD with off-label use of bevacizumab (Avastin, Genentech), since the drug had a target specificity similar to that of ranibizumab and was available at low cost for about 50$ per monthly injection Vs 1950$ for Lucentis monthly injection.
Ranibizumab received the FDA approuval in 2006 to treat specifically the wetAMD,there was a huge debate about the cost effectiveness and the reimbursement of Lucentis in comparaison with Avastin for treating the eye disease.
This paper explores the dilemma from different angles.First,it make the emphasize on the need of realizing a head to head comparative study between the two drugs and the means to finance and to launch this study since many roadblocks have been identified.
Then, it explores and analyzes the Genentech reaction facing this problem and their strategy to emphasize on the higher risk of death with Avastin, as compared to Lucentis in one hand and in the other hand their strategy to extend the ophthalmologic indications for Lucentis, including diabetic macula edema (DME).
Finally it explores what value should be put on safety in health technology assessments HTAs by developing that we can’t just consider the dollar value of medicine alone but we need to consider the cost of adverse events caused by the treatment and the cost of living with these adverse events
A brief description about Pharmacovigilance, aims and scope, need of pharmacovigilance, programs by WHO for international drug safety monitoring, UMC, VIGIBASE, WHO causality assessment scale and specific regulatory bodies of various countries
Drugs affecting on renin angiotensin systemChintan Doshi
The renin-angiotensin system regulates blood pressure and fluid balance. Drugs that affect this system include ACE inhibitors, angiotensin receptor blockers, and direct renin inhibitors. ACE inhibitors work by inhibiting the conversion of angiotensin I to angiotensin II, while ARBs block the effects of angiotensin II by selectively blocking the AT1 receptor. These drugs are used to treat hypertension, congestive heart failure, myocardial infarction, and diabetic nephropathy. Their side effects include hypotension, hyperkalemia, and cough. Direct renin inhibitors such as aliskiren directly inhibit renin's action.
The document summarizes the distribution of drugs in the body. It discusses:
1) Distribution involves the reversible transfer of drugs between blood and tissues, driven by concentration gradients.
2) Factors like tissue permeability, organ size/perfusion, protein binding, and other physiological factors determine the extent of distribution between tissues.
3) Tissue permeability depends on drug properties like size, ionization, and lipid solubility as well as physiological barriers like the blood-brain barrier.
The document discusses the key aspects of an Investigational New Drug (IND) application submitted to the FDA to request permission to conduct clinical trials of an unapproved drug. An IND application contains information on the drug's chemistry, manufacturing, pharmacological and toxicological effects, clinical protocol, and investigators brochure. It allows the FDA to ensure the risks to human subjects are reasonable. The FDA reviews INDs within 30 days to determine if a clinical hold is needed before trials can begin. Annual reports updating trial progress are also required.
This document discusses pharmaceutical dosage forms and their design. It defines key terms like active drug substance, excipients, and dosage forms. It classifies dosage forms based on physical properties into gases, liquids, semisolids, and solids. It also discusses important topics like prescription writing, controlled substances, and requirements for prescriptions of controlled substances.
Mastering Pharmaceutical Interviews- By Santosh Sarnaik.pdfSantosh Sarnaik
This document is an excerpt from a book that provides guidance for job interviews in the pharmaceutical industry, focusing on roles in regulatory affairs, formulation research and development (R&D), and technology transfer. The excerpt discusses formulation R&D, describing the development of oral solid, topical, and parenteral/injectable formulations. It provides an overview of the key areas of formulation R&D and lists common interview questions asked about a candidate's experience and understanding of formulation development, excipient selection, stability testing, bioavailability optimization, and regulatory guidelines.
The document discusses regulatory requirements for bioequivalence studies from the FDA and WHO perspectives. It defines key terms like bioavailability, bioequivalence, reference product and generic products. It also outlines FDA guidelines on bioequivalence documentation for INDs, NDAs and ANDAs. Test procedures for establishing bioequivalence include pharmacokinetic, pharmacodynamic and clinical studies according to FDA regulations. Pharmacokinetic studies are emphasized for directly measuring drug absorption. Study design considerations like single vs multiple dose studies are also covered.
This presentation discusses HMG-CoA reductase inhibitors, also known as statins. It begins with an introduction to hyperlipidemia and its risk factors. It then discusses atorvastatin as the prototype statin drug, and provides examples of other statins. The presentation explains that statins work by inhibiting the HMG-CoA reductase enzyme, which lowers cholesterol synthesis and raises LDL receptor levels, reducing LDL cholesterol. Adverse effects can include increased liver enzymes, myopathy, and interactions with other drugs. The presentation concludes by thanking the audience.
Formulation and evaluation of matrix type rosuvastatin sustained release tabletspharmaindexing
This document describes the formulation and evaluation of matrix-type sustained release tablets of rosuvastatin. Tablets were prepared using polymers like HPMC K15M, HPMC K50M, and ethylcellulose by direct compression technique. The tablets were evaluated for characteristics like hardness, thickness, friability, weight variation, drug content, and floating properties. The best formulation was subjected to kinetic treatment and was found to follow zero order, first order, Peppas, Higuchi, and Hixson-Crowell kinetics. The optimized batches were stable for 2 months at 40°C/75% RH conditions. The document provides details on various sustained release drug delivery systems, techniques for tablet formulation like direct compression
This presentation deals with the in-depth analysis of various cardiac stimulants & depressants both directly & indirectly acting on frog's heart. Also, includes a nice quiz, a good exercise for the grey cells of the brain at the end of the presentation.
The document discusses adverse drug reactions (ADRs), defined as harm caused by a medication at normal doses during normal use. It describes the types of ADRs, including type A reactions which are augmented and predictable, and type B reactions which are bizarre and unpredictable. The mechanisms of ADRs are also explained, including humoral reactions mediated by antibodies and cell-mediated reactions involving T-lymphocytes. Finally, the document outlines some ways to prevent ADRs, such as avoiding inappropriate drug use, considering a patient's history, and watching for potential drug interactions.
Anti-VEGF drugs and HDAC inhibitors are used in cancer treatment. Anti-VEGF drugs inhibit VEGF signaling by blocking the VEGF ligand or receptor and include monoclonal antibodies like bevacizumab and small molecule inhibitors like sunitinib. They are used to treat cancers like colorectal, lung, and kidney cancer. HDAC inhibitors increase histone acetylation, activate tumor suppressor genes, and induce cell cycle arrest. Panobinostat, romidepsin, and vorinostat are examples used for blood cancers and lymphomas. Both classes of drugs can cause side effects like hypertension, bleeding, and fatigue.
Mr. W, a 56-year-old man with risk factors of hypertension and diabetes, presents with chronic chest pain that occurs with exertion such as climbing stairs. His symptoms, location of pain, and risk factors are consistent with stable angina, though gastroesophageal reflux disease and musculoskeletal disorders are also considered. Physical exam is normal except for peripheral neuropathy. Testing shows left ventricular hypertrophy on ECG and hypercholesterolemia on labs. Exercise stress testing surprisingly shows no evidence of ischemia despite reproduced chest pain. Stable angina remains a concern given his risk factors and symptoms.
Sulfasalazine is an anti-inflammatory drug used to treat bowel diseases like ulcerative colitis and rheumatoid arthritis. It works by inhibiting the production of cytokines and inflammatory mediators. Common side effects include gastric distress, headache, and nausea. It is generally considered safe in pregnancy but can cause discoloration of urine or skin. Precautions must be taken with elderly patients or those with allergies or asthma. Drug interactions can also increase risks, so patients should inform their doctors of other medications.
The document discusses targeted drug delivery systems. It begins by introducing the concept of targeted delivery as designed by Paul Ehrlich to specify drug moieties to targeted areas, such as cancer cells or organs. It then discusses the ideal characteristics of targeted delivery systems, including being non-toxic, stable, and providing controlled drug release at the target site. The document outlines different types of targeting approaches, including passive targeting which relies on physiological or pathological differences between target and non-target sites, and active targeting using ligands or antibodies. Liposomes are discussed as a common drug carrier for targeted delivery systems.
This document outlines the requirements and guidelines for conducting clinical trials and obtaining permission to import or manufacture new drugs in India. It discusses the need to frame guidelines for clinical research and regulation of new drugs. Key points include that clinical trials require permission from the licensing authority and approval from ethics committees. Sponsors must submit various data on the drug and trials must be conducted according to Good Clinical Practice guidelines. Informed consent is required from all subjects and safety of subjects must be protected at all stages of the drug development and approval process. Trials generally proceed through Phases I-III to evaluate safety, efficacy, and optimal dosing.
This document discusses drug elimination kinetics. It describes the main routes of drug excretion from the body, including hepatic excretion through bile and renal excretion through glomerular filtration and tubular secretion/reabsorption. The kinetics of drug elimination are explained, including plasma half-life, repeated dosing to achieve steady state concentrations, and target level strategies using loading and maintenance doses. The principles of first-order and zero-order elimination, as well as therapeutic drug monitoring, are also outlined.
This document discusses bioavailability and bioequivalence. It defines bioavailability as the rate and extent to which the active ingredient is absorbed from a drug product and becomes available at the site of action. Bioequivalence denotes that two or more identical dosage forms reach the systemic circulation at the same relative rate and to same relative extent. The document outlines various methods to assess bioavailability, including pharmacokinetic methods like plasma level time studies and urinary excretion studies, as well as pharmacodynamic methods. It also discusses factors that affect bioavailability and the design and statistical analysis of bioequivalence studies.
Using a manufacturer submitted dossier and other clinical data, extensive research was performed to analyze the proper placement of Yervoy on a hypothetical health plan's formulary for treatment of unresectable metastatic melanoma. Pharmacoeconomic benefits and clinical efficacy were weighed heavily in decision making.
Clinical trials established in 2005 the efficacy of Ranibizumab (Lucentis, Genentech) for the treatment of neovascular age-related macular degeneration (wetAMD), the leading cause of legal blindness in the United States.This disease is affecting people over the age of 65 with a prevalence of 1.6 million and 200000 new cases per year in the USA .While awaiting approval for ranibizumab from the Food and Drug Administration, ophthalmologists began treating neovascular AMD with off-label use of bevacizumab (Avastin, Genentech), since the drug had a target specificity similar to that of ranibizumab and was available at low cost for about 50$ per monthly injection Vs 1950$ for Lucentis monthly injection.
Ranibizumab received the FDA approuval in 2006 to treat specifically the wetAMD,there was a huge debate about the cost effectiveness and the reimbursement of Lucentis in comparaison with Avastin for treating the eye disease.
This paper explores the dilemma from different angles.First,it make the emphasize on the need of realizing a head to head comparative study between the two drugs and the means to finance and to launch this study since many roadblocks have been identified.
Then, it explores and analyzes the Genentech reaction facing this problem and their strategy to emphasize on the higher risk of death with Avastin, as compared to Lucentis in one hand and in the other hand their strategy to extend the ophthalmologic indications for Lucentis, including diabetic macula edema (DME).
Finally it explores what value should be put on safety in health technology assessments HTAs by developing that we can’t just consider the dollar value of medicine alone but we need to consider the cost of adverse events caused by the treatment and the cost of living with these adverse events
The document summarizes the Lucentis-Avastin Trial for Age-related Macular Degeneration (CATT), a comparative effectiveness trial comparing the drugs Lucentis and Avastin for treating wet AMD. Major challenges for the trial included obtaining drug supplies and payment for Lucentis. After negotiations with CMS and NEI, the trial was able to begin in 2008 with NEI agreeing to pay Lucentis co-pays and masked drug supplies provided. The trial aimed to evaluate efficacy, safety and need for fixed vs variable dosing of Lucentis and Avastin for wet AMD.
This budget impact analysis estimates the costs of treating heterozygous familial hypercholesterolemia (HeFH) patients with alirocumab over one year within a hypothetical commercial health plan. The analysis found that treating an estimated 1,120 HeFH patients with alirocumab would result in a total drug cost of $11.7 million for the health plan, or $0.976 per member per month. Sensitivity analysis showed that the model was most sensitive to changes in the wholesale acquisition cost of alirocumab. While alirocumab is more effective than other options, its high cost needs to be weighed against potential long-term outcomes benefits for formulary decision making.
Eylea (aflibercept) is a treatment for wet age-related macular degeneration (AMD) and central retinal vein occlusion (CRVO). Phase 3 clinical trials found aflibercept to be effective in improving vision for both conditions compared to controls. For wet AMD, VIEW 1 and VIEW 2 trials found aflibercept non-inferior to ranibizumab. For CRVO, Copernicus found aflibercept superior to sham injections and Galileo found it superior to sham injections. Cost analysis found aflibercept increases health plan spending but is cost-effective compared to alternatives. The committee recommends keeping aflibercept non-preferred due to cost but reevaluating as more data is published
Will anti-VEGF injections replace laser photocoagulation in the first line tr...Valon Lasers Oy
The use of anti-VEGF injections for treatment of i.e. diabetic macular edema is a current, ‘hot’ topic. Will the injections replace laser photocoagulation as treatment method?
Crown Medical Research and Pharmaceutical Sciences College of Canada.
Achieve your career goals in a short period of time with a very competitive education and get Canadian experience with the highest quality of supervised training.
Crown Medical Research and Pharmaceutical Sciences College of Canada offers opportunities to expand your experience beyond the classroom and support them with guidance on career opportunities.
Our professors, consultants, and course developers are recognized leaders in professional development and training in the field of pharmaceutical, natural health products, quality assurance and quality control, regulatory affairs and submissions, pharmacovigilance and drug safety reporting, clinical research, cosmetics, food sciences, biopharmaceutical, and health care policy and services management.
We strive to continuously evolve and expand our programs in an attempt to respond effectively to changing technologies and workforce demands in the industry. It is with this strategy that our programs will prepare our learners for their future.
When attending our college, you will be exposed to highly qualified professionals and professors as well as students with diverse backgrounds and proven professional abilities seeking to improve their skill set and employment outlook.
We are located at Richmond Hill, in the Greater Toronto Area, that is one of the 3 biggest financial and social center in North America. This gives learners access to the head quarters of many industries and to be exposed to personal, and professional growth opportunities.
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When you are considering to enroll in a certificate course offered by our college, please explore the program information on the website and contact us for a one-on-one mentoring meeting, to visit the campus, and to get a career consultation at any time. Our intensive courses start every month and our learners can start their program with us at any time during the year.
Presentation by Graybug Vision at OIS@ASRS 2016.
Participant:
Graybug Vision | Jeffrey Cleland, President & CEO
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This document discusses treatments for diabetic retinopathy, including laser treatment and anti-VEGF drugs. It provides details on panretinal laser photocoagulation to treat peripheral retinal ischemia and grid laser photocoagulation to treat macular edema. It also discusses various anti-VEGF drugs like bevacizumab, ranibizumab, and aflibercept that are administered via intravitreal injections to treat diabetic retinopathy. Complications of different treatments and diagnostic tools are also mentioned. Clinical trial results comparing anti-VEGF drugs and laser therapy are summarized.
This document summarizes current treatment options for diabetic macular edema (DME), including laser therapy, anti-VEGF drugs like ranibizumab and aflibercept, and steroid implants. Laser monotherapy is no longer considered the best practice, as evidence shows anti-VEGF drugs alone or with laser provide better visual outcomes than laser alone. While the optimal anti-VEGF injection protocol is still unclear, monthly injections may not be necessary. Newer treatments like dexamethasone and fluocinolone implants provide sustained drug delivery over months and show promise, but more research is still needed on their long-term safety and efficacy.
This document summarizes new and emerging therapies for retinal diseases such as diabetic macular edema (DME), age-related macular degeneration (AMD), and retinal vein occlusion (RVO). For DME, anti-VEGF therapies like ranibizumab and aflibercept as well as corticosteroid implants like fluocinolone and dexamethasone are discussed. For AMD, sustained delivery devices, gene therapy, complement cascade inhibition and other approaches are mentioned. Encapsulated cell technology and nanostructured implants aim to provide longer-lasting drug delivery for retinal conditions.
Manikandan is seeking a position that offers both job satisfaction and professional growth. He has over 4 years of work experience in roles like FTE, DTS, and Senior Associate for companies like Inganam Solutions, Kutumbh Care, Nine Stars Information Technologies, and First Source Solution. He has skills in operating systems, programming languages, databases, and office suites. Manikandan has a diploma in Information Technology and secured 85% marks. He is cooperative with others, self-confident, dedicated, and a hard worker.
This movie poster summarizes a superhero action film. The main characters are enlarged in the center to showcase their importance to the story. Dark colors and fearful facial expressions portray the film as action-packed and involving a hero vs. villain conflict. Various futuristic technologies and weapons displayed in the background images further indicate this is a superhero genre film focused on action.
Profitbomber adalah sebuah sistem yang dirancang untuk membantu anda mendapatkan income cepat setiap hari, berulang - ulang, dengan modal terjangkau dan Potensi Income tanpa batas.
Jennifer Thompson is seeking employment where she can utilize her professional experience and abilities. She has over 10 years of experience in customer service, sales, and event staff roles. Her experience includes setting up conferences, registering attendees, assisting guests, and providing security for VIP guests at events. She is proficient in Microsoft Office, POS systems, cash registers, and metal detectors.
Air monitoring data at the water tower monitor (WTM) in Rhinelander, WI shows SO2 concentrations exceeding the 1-hour SO2 NAAQS and Expera Rhinelander Mill’s 63 m tall cyclone boiler stack is the primary contributor to the monitored exceedance. Making matters more complicated, the AERMOD predicted “design value” concentration at the WTM is in compliance and more than a factor of two lower than observations. Hence, a standard AERMOD modeling approach cannot be used to determine a compliance solution.
After investigating the building geometry, it was noticed that the 38 m high Boiler 7 building corner is directly upwind of the stack when the wind blows toward the WTM. This results in the formation of corner vortices that enhance building downwash, an effect that is not accounted for in AERMOD. To develop a compliance solution, a multi-phased approach was used. First, wind tunnel modeling was conducted to determine an EPA approved 90 m GEP stack height that is taller than the 75 m formula GEP stack height. Next, compliance at the 90 GEP stack height was assessed using two alternate methods. Method 1 employed an alternate model, HYWINMOD, a validated hybrid wind tunnel/numerical model. Method 2 utilized AERMOD in an approved non-standard manner. AERMOD was run without building downwash affects but the results were adjusted to account for building downwash affects using wind tunnel modeling. Both methods provided very similar and manageable compliance solutions.
Visual Basic is a programming tool created by Microsoft to build graphical user interface applications in a user-friendly environment. Programming involves studying computer languages. A flowchart uses graphics to represent step-by-step instructions to solve a problem while an algorithm is a set of instructions. Operators perform logical and mathematical operations on variables, which are memory containers. Loops repeatedly perform an action until a condition is met. Common operators include arithmetic, relational, and logical operators. Flowcharts and algorithms use variables, conditions, and logic to represent the preparation, processing, and output of a program.
The document outlines the openMDM® architecture design. It discusses the driving forces, goals, and components of the openMDM® architecture. The architecture aims to be modular, allow assembly of components, achieve UI independence, and conform to specifications. The business model provides core platform services and allows integration of data from multiple sources through an ODS adapter.
Text Editors (Atom / Sublime)
Apache Server (sftp/ssh/php) – Todd's Server!
CPanel / Wordpress (server side details)
Working with any Web API (Mapping Example)
(facebook, linkedin, twitter, maps, d3.js, jquary)
JSON and HTML <img>
GIT http://www.github.com
1. VEGF is a growth factor that promotes abnormal blood vessel growth in the retina and is responsible for many retinal diseases. Anti-VEGF drugs like ranibizumab (Lucentis), bevacizumab (Avastin), and pegaptanib (Macugen) block VEGF to inhibit this blood vessel growth and treat retinal diseases.
2. While ranibizumab, Avastin, and pegaptanib are all anti-VEGF drugs, they differ in their structure and dosing. Ranibizumab and Avastin are antibodies while pegaptanib is a nucleic acid. Avastin costs $45 per dose while ranibizumab costs over $1500.
3. Clinical trials found ranib
VEGF is a growth factor that promotes abnormal blood vessel growth in the retina and causes vision loss. Anti-VEGF drugs like ranibizumab (Lucentis), bevacizumab (Avastin), and pegaptanib (Macugen) work by blocking VEGF and stopping this blood vessel growth. Ranibizumab was designed specifically for eye injections and has a short half-life, while bevacizumab was designed for cancer but is also used "off-label" in the eye. Clinical trials found that both drugs are effective in treating wet AMD, diabetic retinopathy, and other retinal diseases, but ranibizumab may have a slightly lower risk of rare side effects due to its shorter exposure in
This document analyzes the implications of "not me" drugs like ranibizumab and bevacizumab for treating age-related macular degeneration. While both drugs are effective, ranibizumab is much more expensive. Differing healthcare systems have led to variation in uptake of the drugs between countries. Trials now show similar efficacy and safety, but ranibizumab maintains market dominance where it is fully covered by public drug programs due to regulatory approval and physician reimbursement policies that favor its use. Future policies should promote availability of the cheaper bevacizumab option and ensure accountability, safety, and informed patient choice.
Intraocular safety OF ANTIVEGF INJECTIONS IN THE EYEAjayDudani1
This document provides information about the intraocular safety of anti-VEGF agents:
- Aflibercept has a well-established safety profile across clinical trials and real-world use, with rare rates of intraocular inflammation (IOI), endophthalmitis, and retinal vasculitis reported.
- Recent communications from the American Society of Retina Specialists (ASRS) have reported cases of IOI and occlusive retinal vasculitis following administration of brolucizumab.
- A review of safety data from trials of brolucizumab found higher rates of serious ocular adverse events like IOI compared to aflibercept, raising concerns about its intraocular safety profile
Anti-VEGF drugs like ranibizumab and bevacizumab have revolutionized the treatment of eye diseases like age-related macular degeneration by inhibiting abnormal blood vessel growth, but their long-term safety and high cost remain uncertain, and studies question whether less frequent dosing regimens could achieve similar results with fewer injections. A new anti-VEGF drug, aflibercept, has been approved and may require fewer injections than ranibizumab, but its long-term efficacy and safety also need further evaluation.
Central Retinal Vein OcclUsIon (CRUISE) Study - Cruise trialLaxmi Eye Institute
Ranibizumab injections led to improved visual acuity and resolution of macular edema compared to sham injections in patients with central retinal vein occlusion. At 6 months, patients receiving 0.3 mg or 0.5 mg ranibizumab were twice as likely to have a visual acuity of 20/40 or better compared to the sham group. Ranibizumab also significantly reduced central foveal thickness within 7 days, suggesting retinal edema in CRVO is primarily VEGF-mediated. While ranibizumab was effective, longer term studies are needed to determine optimal duration of treatment and benefits in less severe cases.
This document provides a review of literature on diabetic macular edema (DME). It summarizes key studies on the pathophysiology and treatment of DME, including the Early Treatment Diabetic Retinopathy Study (ETDRS), trials of intravitreal corticosteroids, anti-VEGF drugs, and combination therapies. Major studies discussed include DRCR.net, PACORES, RESOLVE, BOLT, RIDE, and RESTORE trials which evaluated laser photocoagulation, corticosteroids, ranibizumab, bevacizumab, and combination therapies for treating DME. The document concludes anti-VEGF drugs like ranibizumab and bevacizumab
The development & approval of Novoeight, a case studyAllen Che
The FDA approved Novoeight, a recombinant Factor VIII treatment for hemophilia A, in October 2013 based on positive results from clinical trials. Novoeight was found to effectively control and prevent bleeding episodes in adults and children with hemophilia A. The approval process involved reviewing manufacturing, clinical data, and inspections to ensure safety and efficacy. This approval expands treatment options for hemophilia A patients and represents continued innovation in the development of safer recombinant clotting factor therapies.
This document summarizes key details about three anti-VEGF drugs - ranibizumab, aflibercept, and bevacizumab. It provides information on their company, mechanism of action, molecular weight, half-life, licensed indications, formulation, and structure. The drugs are compared in terms of targeting specific VEGF isoforms and receptors. Clinical evidence suggests inhibition of VEGFR-1 provides no additional benefit over inhibition of VEGFR-2 for conditions like wet AMD and DME.
This document discusses a clinical trial evaluating the efficacy of the drug Aricept for the treatment of Alzheimer's disease. It provides details on:
1) The study design which was a 30-week randomized, double-blind, placebo-controlled trial comparing placebo to 5mg or 10mg doses of Aricept.
2) The results which showed a statistically significant improvement in cognitive test scores (ADAS-cog) for both Aricept groups compared to placebo after 24 weeks.
3) That upon stopping Aricept after 24 weeks, cognitive scores returned to placebo levels, indicating the benefits of the drug were temporary and did not change the underlying disease progression.
This document discusses a clinical trial evaluating the efficacy of the drug Aricept for the treatment of Alzheimer's disease. It provides details on:
1) The study design which was a 30-week randomized, double-blind, placebo-controlled trial comparing placebo to 5mg/day or 10mg/day doses of Aricept.
2) The results which showed a statistically significant difference in ADAS-cog scores after 24 weeks between both active drug doses and placebo, indicating improved cognitive performance.
3) After placebo washout, scores returned to placebo levels, suggesting the benefits of Aricept are lost after discontinuing treatment.
The analytical studies that demonstrate biosimilarity to the reference product form the foundation of a biosimilar's development and approval pathway. A biosimilar may directly use information from the reference product's package insert, but will not include clinical studies as these are not designed to independently establish safety and efficacy. The biosimilar label incorporates data from the reference product label but identifies information specific to the biosimilar such as its proprietary name and unique suffix.
The document discusses the risks and considerations around generic substitution of brand name antiepileptic drugs. It notes that while generics may reduce costs, generic AEDs may not be therapeutically equivalent to the brand name versions due to differences in bioavailability and potential problems from changes in drug levels. The document recommends against substituting brand AEDs with generics, especially for patients with well-controlled epilepsy, due to the serious risks of seizure recurrence or increased side effects from changes in drug concentrations.
‘Reports of My Death Are Greatly Exaggerated.’ Signed, Aducanumab _ ALZFORUM.pdffcbmercado
- Biogen announced that aducanumab appears to have worked in one of its two Phase 3 trials, called EMERGE, after a new analysis of more data from both trials was conducted. The identical ENGAGE trial did not meet its primary endpoints.
- In EMERGE, participants receiving the highest dose of aducanumab declined 23% less than those receiving placebo on the primary outcome measure, while in ENGAGE most outcome measures did not show significant slowing of decline except in an exploratory subgroup analysis.
- Biogen will file for regulatory approval of aducanumab in early 2020 based on feedback from the FDA that the new data support a filing, reigniting optimism about disease-modifying treatments for Alzheimer
This document summarizes anti-VEGF drugs used to treat retinal diseases caused by abnormal blood vessel growth. It discusses the role of VEGF in these diseases and introduces several anti-VEGF drugs including pegaptanib, bevacizumab, ranibizumab, and aflibercept. It provides details on the mechanism of action, safety profiles, and costs of these drugs and compares the efficacy and safety of bevacizumab and ranibizumab based on studies like CATT. The document serves as an educational reference on anti-VEGF therapies for retinal specialists.
Alzheimer's Disease Drug Development Aducanumab, Lecanemab & Donanemab.pdfDoriaFang
Alzheimer's disease (AD) is a neurodegenerative disorder marked by cognitive and behavioral impairment. Here we introduce the development of AD drugs (Aducanumab, Lecanemab & Donanemab).
This document provides an overview of newer anti-VEGF therapies for treating retinal diseases involving abnormal blood vessel growth (neovascularization). It discusses the mechanisms and indications of established therapies like bevacizumab, ranibizumab, and aflibercept. It then summarizes several newer anti-VEGF agents currently in clinical trials, including conbercept, brolucizumab, abicipar pegol, and faricimab. These newer therapies aim to provide improved efficacy compared to existing options through mechanisms like inhibiting additional growth factors or requiring less frequent dosing. Ongoing clinical trials are evaluating their safety and ability to improve vision outcomes in conditions like wet age-related macular degeneration and diabetic
My preferred molecule for the management of NEOVASCULAR AMD-DR AJAY DUDANIAjayDudani1
1) Ranibizumab is the preferred molecule for treating neovascular AMD due to the extensive evidence from numerous clinical trials proving its long-term safety and efficacy compared to alternatives like biosimilars which have less data.
2) AMD is a major cause of blindness worldwide, affecting millions of aging individuals, and neovascular AMD can cause severe vision loss without treatment.
3) Landmark clinical trials have established ranibizumab as the standard of care for neovascular AMD, demonstrating long-term vision gains and stability with both fixed and individualized dosing regimens.
Vision Medicines is developing two drug candidates, VM100 and VM200, to treat retinal diseases with high unmet medical need and large market opportunities. VM100 is in Phase 2/3 development for geographic atrophy and intermediate AMD, with a combined $20B market. VM200 is in preclinical development for Stargardt disease, an orphan indication with no approved therapies and a $6B market opportunity. Both drugs address the underlying disease mechanisms and have demonstrated preclinical efficacy in preserving retinal structure and function. Vision Medicines aims to develop these assets and consolidate the fragmented ophthalmology space, which has fewer products per company than other therapeutic areas.
This document discusses Amgen's strategy of innovating beyond molecules in biopharma. It provides examples of Amgen innovating drug delivery systems and digital health tools to better meet patient needs. Specifically, it describes how Neulasta evolved from daily injections to an on-body injector and companion app. The document argues an ecosystem is needed where patients can access and adhere to therapies to achieve full benefits, and healthcare systems cover costs given confirmed outcomes.
Similar to P and T c\Competition 2014 monograph (20)
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
TEST BANK For Community Health Nursing A Canadian Perspective, 5th Edition by...Donc Test
TEST BANK For Community Health Nursing A Canadian Perspective, 5th Edition by Stamler, Verified Chapters 1 - 33, Complete Newest Version Community Health Nursing A Canadian Perspective, 5th Edition by Stamler, Verified Chapters 1 - 33, Complete Newest Version Community Health Nursing A Canadian Perspective, 5th Edition by Stamler Community Health Nursing A Canadian Perspective, 5th Edition TEST BANK by Stamler Test Bank For Community Health Nursing A Canadian Perspective, 5th Edition Pdf Chapters Download Test Bank For Community Health Nursing A Canadian Perspective, 5th Edition Pdf Download Stuvia Test Bank For Community Health Nursing A Canadian Perspective, 5th Edition Study Guide Test Bank For Community Health Nursing A Canadian Perspective, 5th Edition Ebook Download Stuvia Test Bank For Community Health Nursing A Canadian Perspective, 5th Edition Questions and Answers Quizlet Test Bank For Community Health Nursing A Canadian Perspective, 5th Edition Studocu Test Bank For Community Health Nursing A Canadian Perspective, 5th Edition Quizlet Test Bank For Community Health Nursing A Canadian Perspective, 5th Edition Stuvia Community Health Nursing A Canadian Perspective, 5th Edition Pdf Chapters Download Community Health Nursing A Canadian Perspective, 5th Edition Pdf Download Course Hero Community Health Nursing A Canadian Perspective, 5th Edition Answers Quizlet Community Health Nursing A Canadian Perspective, 5th Edition Ebook Download Course hero Community Health Nursing A Canadian Perspective, 5th Edition Questions and Answers Community Health Nursing A Canadian Perspective, 5th Edition Studocu Community Health Nursing A Canadian Perspective, 5th Edition Quizlet Community Health Nursing A Canadian Perspective, 5th Edition Stuvia Community Health Nursing A Canadian Perspective, 5th Edition Test Bank Pdf Chapters Download Community Health Nursing A Canadian Perspective, 5th Edition Test Bank Pdf Download Stuvia Community Health Nursing A Canadian Perspective, 5th Edition Test Bank Study Guide Questions and Answers Community Health Nursing A Canadian Perspective, 5th Edition Test Bank Ebook Download Stuvia Community Health Nursing A Canadian Perspective, 5th Edition Test Bank Questions Quizlet Community Health Nursing A Canadian Perspective, 5th Edition Test Bank Studocu Community Health Nursing A Canadian Perspective, 5th Edition Test Bank Quizlet Community Health Nursing A Canadian Perspective, 5th Edition Test Bank Stuvia
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Kat...rightmanforbloodline
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
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Integrating Ayurveda into Parkinson’s Management: A Holistic ApproachAyurveda ForAll
Explore the benefits of combining Ayurveda with conventional Parkinson's treatments. Learn how a holistic approach can manage symptoms, enhance well-being, and balance body energies. Discover the steps to safely integrate Ayurvedic practices into your Parkinson’s care plan, including expert guidance on diet, herbal remedies, and lifestyle modifications.
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
Muscles of Mastication by Dr. Rabia Inam Gandapore.pptx
P and T c\Competition 2014 monograph
1. 1
Pitt Street Health Plan Formulary Monograph Template
Individual Drug Review
Generic Name: aflibercept for intravitreal injection
Brand Name: Eylea®
Manufacturer: Regeneron Pharmaceuticals, Inc.
Date of Review:
Available Therapeutic Alternatives:
Preferred/Formulary Non-Preferred/Non Formulary
Anti-VEGF Anti-VEGF
ranibizumab (Lucentis®)
bevacizumab (Avastin®) – off label
aflibercept (Eylea®)
pegaptanib (Macugen®)
TABLE OF CONTENTS:
(Click on a link below to view the section.)
Executive Summary
Recommendations
Key Questions/Issues:
Issue 1: Efficacy
Issue 2: Comparative Effectiveness
Issue 3: Safety
Issue 4: Value Proposition
Issue 5: Cost-effective Patient Subgroups
Clinical Evidence Tables
Cost-effectiveness Evidence Tables
Background
Disease Background
Pharmacotherapy
Product Background
Methodology
Authorship
References
Abbreviations used in this monograph:
Vascular endothelial growth factor (VEGF)
Age related macular degeneration (AMD)
Quality adjusted-life year (QALY)
2. 2
REASON FOR REVIEW:
To determine the formulary status for aflibercept for intravitreal injection (EYLEA®
), FDA approved for
treatment of Neovascular (Wet) Age-Related Macular Degeneration (AMD) and Macular Edema
Following Central Retinal Vein Occlusion (CRVO).
EXECUTIVE SUMMARY
Key Questions/Issues and Results of Investigation:
Issue 1: What is the evidence of efficacy from clinical trials?
There is evidence to show that aflibercept is effective in both reducing the macular
thickness, as well as helping to improve vision.1 Both of these were found from the CLEAR
IT 2 trial, a phase 1clinical trial, and the VIEW 1 and 2 trials, both phase 3 clinical trials. The
VIEW 1 trial did find that when compared to Ranibizumab, aflibercept was able to show a
significant improvement in vision. However, in the VIEW 2 trial, the improvement in vision
was not shown to be significantly significant for ranibizumab.2
Issue 2: Is there sufficient evidence to assessreal world comparative effectiveness?
Currently there is real world evidence to assess the effectiveness of aflibercept; however,
more evidence would beneficial to allow for a more complete analysis. Two trials that are
necessary to determine the effectiveness are the VIEW1 and VIEW2 (VEGF Trap-Eye:
Investigation of Efficacy and Safety in Wet Age-Related Macular Degeneration) trials. The
trials each lasted 52 weeks and the endpoints, treatment population, and primary outcome
measures were the same.2 The results of the trials revealed the aflibercept groups were
noninferior to ranibizumab.
Issue 3: What is the evidence of safety?
Evidence of safety can also be found from the VIEW1 and VIEW2 trials. It was
concluded that there was no difference between aflibercept and ranibizumab regarding ocular or
systemic adverse effects.2 In the VIEW trials, ranibizumab was dosed monthly and aflibercept
was administered every two months.
Issue 4: What is the value proposition for this product?
3. 3
Currently, Eylea is a product that is demanded by both patients and physicians. Along
with its noninferiority to Ranibizumab, it has been to have the potential to bring cost savings to
patients affected by wet AMD. According to the National Eye Institute, advanced cases of wet
AMD will rise to nearly 3 million cases by the year 2020.3 When analyzing the cost savings
between Ranibizumab and aflibercept, the yearly cost savings is slightly above $3.5 billion and
the quarterly savings is $884 million. This shows there is a large potential for savings without
sacrificing the quality of therapy provided.4
Issue 5: Are there identifiable patient subgroups in which this treatment will be most cost-effective?
There are certain patient subgroups where this treatment would be most cost-effective.
Treatment with aflibercept would be more cost effective than treatment via ranibizumab over the
course of one year. Due to the decreased dosing schedule, there would be a cost saving of
approximately USD 8,600. It is important to note that bevacizumab is able to be used off-label
for treatment of wet Age-Related Macular Degeneration (AMD).2 If a patient is non-responsive
to ranibizumab therapy, aflibercept would be a cost-effective alternative.
RECOMMENDATIONS TO THE COMMITTEE
Therefore,the following P&T action is recommended:
Based on our findings, we recommend bevacizumab as a first line agent for the
treatment of wet age-related macular degeneration (AMD). This is due to both the current
efficacy and cost versus other drugs, bevacizumab and ranibizumab.1 Moreover, we
recommend adding aflibercept to the formulary to be utilized as a second tier agent due to
the effectiveness against resistant macular degeneration.
By first requiring the use of bevacizumab, there is a great cost savings over the course
of a year. Choosing aflibercept as a second tier agent over ranibizumab was due to the
decreased cost per year and its clinically proven noninferiority; this was accomplished by a
decreased number of injections per year.1 In addition, there are some cases where wet
AMD is resistant both bevacizumab and ranibizumab. Thus, it may be necessary to have
another agent in the event the first line agent, bevacizumab, fails to be effective.
4. 4
ISSUE DETAILS
ISSUE 1: What is the level and quality of evidence for efficacyfrom clinical trials?
The CLEAR IT 2 study showed a reduction in macular thickness of 66% as well as
significant improvement in vision. In the View 1 study those receiving aflibercept had an
improvement of 10.9 letters compared to an improvement of 8.1 letters in those receiving
Ranibuzumab. Also the VIEW 1 showed a reduction in macular thickness that ranged from 218
to 230 micrometers. Although these results are not statistically very different, the results do show
significant increases in visual acuity.5 According to 91.7% of patients achieved stabilized or
reduced intraretinal fluid and an average macular thickness reduction of 65 micrometers, after
just 3 monthly injections.1 Each of these studies show that aflibercept is able to reduce macular
thickness and increase vision acuity in AMD patients.5
ISSUE 2: Is there sufficient evidence to assess real world comparative effectiveness?
Currently there is evidence to assess the real world comparative effectiveness of
aflibercept; however, more evidence would enable a more confident conclusion to be reached.
Unlike both bevacizumab and ranibizumab, aflibercept is able target VEGF by presenting
itself as a receptor for VEGF. Aflibercept is then able to bind to VEGF more tightly than the
native VEGF receptor is. Furthermore, aflibercept is a able to target both VEGF-B and PIGF,
specific subclasses of VEGF, while bevacizumab and ranibizumab are unable to target them
effectively. The ability to target more angiogenic factors makes it possible that aflibercept
may be more effective in treating wet AMD.
When aflibercept was compared to ranibizumab it was found that aflibercept was
considered to be noninferior to ranibizumab. Both the VIEW1 and VIEW2 trials took place
over a 52 week period and each had almost identical results for the primary endpoint.
The one place where real world evidence is lacking is a comparison between aflibercept and
bevacizumab. Although bevacizumab is not FDA indicated for the treatment of wet AMD, it
has been successfully utilized to help patients with the disease. A real world clinical trial of
both bevacizumab and aflibercept would enable a more comprehensive comparison of both
medications.
ISSUE 3: What is the level and quality of evidence for safety?
5. 5
There is ample evidence to be able to assess the quality and level of safety for
aflibercept. Some of the most important information regarding the safety comes from two
phase III trials, VIEW1 and VIEW2. In each trial, the overall safety and efficacy of
aflibercept was monitored. In regards to safety, it was determined that aflibercept was able to
produce similar results as ranibizumab.2
It was able to be determined that over the course of 52 weeks, that both systemic and
ocular side effects were comparable in safety between the treatment and control group.6
Some particular adverse events such as myocardial infarction and stroke produced a slightly
lower incidence than ranibizumab for each disease in each VIEW trial.7 Due to the decreased
number of injections per year, there is a benefit for aflibercept. It is possible to have an
adverse local event in the event there is a problem with the injection.
Based on the each VIEW trial being double-blinded, randomized and there was monthly data
obtained, the level of this trial would be classified as a Level II-3 based on the U.S.
Preventive Services Task Force.
ISSUE 4: What is the value proposition for this product?
Summary of Product Value
Eylea accounted for $1.4 billion in sales in 2013. It is a product patients and doctors are
demanding on a large scale. Eylea saves, as shown below, a substantial amount of money on a
micro and macro type basis. The product has shown non-inferiority to Ranibizumab while
providing the patient with less shots/doctor’s visits, all while being the cheaper alternative to
Ranibizumab.
Manufacturer-Submitted Modeling
Budget Impact Analysis: Approximately 15 million people in the United States have AMD, and
more than 1.7 million Americans have the advanced form of the disease.
About 200,000 new cases of wet AMD are diagnosed each year in North America. Due to
the aging baby boomer population, the National Eye Institute estimates that the prevalence of
advanced AMD will grow to nearly 3 million by 2020.3
Eylea saves $8,000 for a full year’s treatment compared to Ranibizumab per person. That is
a $2,000 dollar saving per person per Fiscal quarter. With 1.7 million people having wet AMD.
In August, BioTrend Research Group surveyed U.S ophthalmologists and found in terms of their
6. 6
total number of wet AMD patients, now they treat 26 % with Eylea, a significant increase from a
year ago where the figure was 21%.4 That is a yearly cost savings $3,536,000,000 on a
nationwide level and a quarterly cost savings of $884,000,000. With the prevalence of wet and
almost doubling by 2020 these savings on a macro level will almost double compared to using
Ranibizumab.
Cost-Utility Analysis: Regeneron has priced Eylea lower than Ranibizumab: just $100 lower on
a per-injection basis, but about $8,000 less for a full year's treatment, if the company's less-
frequent injection schedule holds true. Eylea will run $1,850 per dose, Bloomberg reports,
compared with $2,000 for Ranibizumab, and $16,000 for a full year, compared with $24,000 for
the Roche drug.8
It was indicated an incremental quality adjusted life year (QALY) gain with aflibercept of
0.0107 but a lower cost and thus that aflibercept would be the dominant medicine (lower cost,
more effective).9
ISSUE 5: Are there identifiable patient subgroups in which this treatment will be most
cost-effective?
There are identifiable patient subgroups in which this treatment would be most cost-
effective. When treating wet AMD, the most common forms of therapy include bevacizumab,
ranibizumab, and aflibercept. When considering what therapy to utilize it is important to take
both the cost and effectiveness into consideration. Of all three treatment options, it has been
shown that bevacizumab has the lowest cost, at an estimated USD600 per year. This would
take into account bevacizumab being administered 1 time per month over the course of a
year.2
Patient populations that would benefit from treatment with aflibercept would include
patients who are nonresponsive to bevacizumab therapy or patients who experience an
adverse reaction to bevacizumab therapy. In this case, the choice of therapy would be either
aflibercept or ranibizumab. One distinct difference between the two forms of therapy
involves the frequency of injections. Ranibizumab would need to be administered 12 times
per year, while on the other hand aflibercept would require 8 doses over the course of one
year. Not including costs of injection and physician visits, this would result in an average
savings of approximately USD 8,600.2
7. 7
According to the manufacture of aflibercept, a one-way sensitivity analysis was able to
determine with 100% probability that there would be a cost savings by using aflibercept
compared to ranibizumab. In regards to the incremental cost-effectiveness ratio (ICER), it was
found that £20,000 per quality-adjusted life year (QALY). This would be equivalent to
approximately USD 33,000 per QALY gained.10
Regarding clinical practice, it should be noted that aflibercept does not significantly
differ from current therapies due to the fact that it requires one to visit a doctor’s office for the
medication to be administrated. One benefit over current therapy is that aflibercept requires less
office visits, which could result in greater compliance of therapy.2 Consequently, in patients
where bevacizumab therapy was not found to be appropriate, there is a cost-effective savings by
utilizing aflibercept therapy.
8.
9. 9
Ref. and
Evidence
Grade
Drug Regimens N Time Demographics Design* End Points/Results/Comments NNT
VIEW Studies Aflibercept 2 mgevery8
weeks after 3 initial
monthly loadingdoses, (ii)
aflibercept 2 mgevery4
weeks, (iii) aflibercept 0.5
mgevery 4 weeks, or (iv)
ranibizumab0.5 mgevery
4 weeks
2457
pts
with
neovas
cular
AMD
96 weeks VIEW 1 – NorthAmerica
VIEW 2 – Worldwide
The meanage was 78
years, 41% of patients
were male, and97% of
patients were white. In
VIEW 2, the meanage
was 73-75 years, 45% of
patients were male, and
73% of patients were
white. Thetotal mean
baseline best-corrected
visual acuity score
(definedby Early
Treatment Diabetic
RetinopathyStudy
[ETDRS] scale) ranged
from 54 to56letters in
VIEW 1 andfrom 52 to 54
letters in VIEW 2. Inboth
studies, the distributionof
occult, minimallyclassic
andpredominantlyclassic
lesion types in thestudy
eye was similar across
both treatment arms.
Randomized, double-blindPhase III
trail
1:1:1:1 randomization
Primaryoutcome was identifiedas the percentage ofpatients
who maintainedvisionat week 52. Maintainingvisionwas
definedas losingless than 15letters basedon the best-
correctedvisual acuity scaledcomparedto baseline
measurements. The primaryendpoint showednoninferiority
in all four treatment groups where noninferioritywas defined
in comparison to thestandardof careranibizumaband
concludingthat the three aflibercept groups were noninferior.
The safety analysis in bothVIEW trials foundaflibercept to
be a well-tolerateddrug.
Maintaining
BVCA-
primary end
point-52
weeks- 1/.961-
.944 58 pts
96 weeks
1/.924-.915111
pts
10. 10
CLEAR IT
Studies
3 monthly injections of
aflibercept.
31 pts
with
exudati
ve
AMD
and
choroi
dal
neovas
culariz
ation
(CNV)
in 1 or
both
eyes.
50 weeks The meanage was 79
years (range 60-88),13
male and18 female
patients.
Retrospective observational case
series
After 3 monthly injections ofaflibercept,therewas a
reduction of either subretinal orintraretinal fluidin 18 or36
(50.0%) ofthe treatedeyes; the amount offluidremained
stable in 15 eyes (41.7%)andworsenedin 3 eyes (8.3%). A
significant average decrease was observedfor the central
macular thickness after 3 injections of 65micrometers, with
no significant change in visual acuity.
Not stated.
*Abbreviations usedin this table: AC =active control, CCS= case-control study,DB = double blind, PC = placebo control,PCS= prospective cohort study, PG= parallel group, MA= meta-analysis MC = multicenter,
RCS = retrospective cohort study, RCT = randomizedcontrolledtrial, XO = crossover
11. 11
Table . Clinical evidence summary
Table . Cost-effectiveness evidence summary (Reviewers may change this table format to better fit the economic study methodology)
Ref. and
Sponsor
Study Design and
Treatments Compared
Time Horizon and
Demographics
Model Inputs and Data
Sources
Results:
Base Case, Sensitivity Analysis and Limitations
Regeneron
Pharmaceuticals
Double-masked,
multicenter,parallel-group,
active controlled,
randomizedtrials
Aflibercept 2 mgevery8
weeks after 3 initial
monthly loadingdoses, (ii)
aflibercept 2 mgevery4
weeks, (iii) aflibercept 0.5
mgevery 4 weeks, or (iv)
ranibizumab0.5 mgevery4
weeks
96 Weeks
VIEW 1 – NorthAmerica
VIEW 2 – Worldwide
The meanage was 78
years, 41% of patients
were male, and97% of
patients were white. In
VIEW 2, the meanage
was 73-75 years, 45% of
patients were male, and
73% of patients were
white. Thetotal mean
baseline best-corrected
visual acuity score
(definedby Early
Treatment Diabetic
RetinopathyStudy
[ETDRS] scale) ranged
from 54 to56letters in
VIEW 1 andfrom 52 to 54
letters in VIEW 2. Inboth
studies, the distributionof
occult, minimallyclassic
andpredominantlyclassic
lesion types in thestudy
eye was similar across
both treatment arms.
The VIEW studies showthat a
small percentage of the
patients sawthat Elyea is
effective, but provides no
additional benefit tothe
treatment of wet AMD over
existingtherapies.
Aflibercept 2 mgevery8 weeks after 3 initial monthly loadingdoses, followedby 2 mgevery other
monthresultedin noninferiority in bothefficacyandsafetywhen comparedtoranibizumab0.5mg
administeredevery4 weeks
12. 12
Ref. and
Sponsor
Study Design and
Treatments Compared
Time Horizon and
Demographics
Model Inputs and Data
Sources
Results:
Base Case, Sensitivity Analysis and Limitations
Abbreviations used in this table: LYS = life-years saved, QALY = quality-adjusted life-year, QOL= quality of life.
13. 13
BACKGROUND INFORMATION
DISEASE BACKGROUND
Neovascular age related macualer degeneration is a leading cuase of vision loss in older
populations. Age related macular degeneration accounts for more than 54% of all vision loss in
the white population in the United States.11 The disease is much more common among white
individuals in the population and other people with European decent.11 An estimated 8 million
Americans are affected with early age-related macular degeneration, of whom over 1 million will
develop advanced age-related macular degeneration within the next 5 years.11 Macular
degeneration occurs in 0.2% of the population in those 54-64 and increasing to 13% in those
older than 85 years.11 Neovascualar age-related macular degeneration is the most common cause
of severe central visual loss.11
There are several risk factors associated with the disease. The largest risk factor for age
related macular degeneration with patients over the age of 85 people the biggest group at risk.11
An individual being of the white ethnicity is a risk factor.11 There have been some genetic
factors that have been linked to age related macular degeneration. In addition females have a
greater. A controllable risk factor is cigarette smoking.11
DISEASE BURDEN
The burden on the patient for neovascular age related macular degeneration consists of
decreased eyesight, lifestyle changes, and a financial burden. Patients can lose their vision very
gradually vision loss over months to years or can lose vision within days as a result of subretinal
hemorrhage.11 The patient would also have to make lifestyle changes to decrease the progression
of the disease. For one, the patient would need brighter light to see things and would also need
magnification to read smaller print. There are several lifestyle changes the patient would have to
make. For example, the patient would need to lose weight if they are currently obese, relieve
hypertension if it’s a problem, decrease dietary intake of vegetable fat, and increase consumption
of antioxidants and zinc.12 The quality of life for mild AMD was an average of 17%, a decrease
of an average of 32% decrease among patients with moderate AMD, and a decrease of an
average of 53% among patients with severe AMD. Finally the financial undertaking for the
patient to treat their AMD is quiet substantial.12 The disease also puts burdens on family and
caregivers to make sure the patient stays safe.
14. 14
PATHOPHYSIOLOGY
Neovascular age-related macular degeneration is characterized by the hemorrhagic
detachment of either the retinal pigment epithelium or sensory retina, the presence of subretinal
fibrous tissue, or minimal subretinal fibrosis.11 Neovascularization can develop under the retina,
which can leak fluid or bleed. Onset of vision loss is acute.11 Age related macular degeneration
is characterized by degenerative changes involving the outer portion of the retina, retinal pigment
epithelium, and the Bruch’s membrane.13 A major aspect of the pathophysiology are basal
deposits in the eye.13 The deposits that form can result in the formation of drusen which is are
tiny yellow or white accumulations of extracellular material that build up between Bruch's
membrane and the retinal pigment epithelium of the eye.13 The retinal pigment epithelium cells
can undergo hypotrophy, hypertrophy, hypopigmentation, hyperpigmentation, atrophy,
migration, and the loss of outer retinal cells.13 The outer retinal cells see a 77% reduction in
disease affected eyes compared to non-diseased eyes. Since retinal epithelial cells are
undergoing hypertrophy and hypotrophy, inhibiting vascular endothelial growth factors would be
beneficial to the patient.13
Treatment Alternatives
There are multiple options when treating Neovascular (Wet) Age-Related Macular
Degeneration (AMD). Monotherapy of Anti-VEGF Agents is the gold standard of treatment for
AMD.14 Ranibuzumab (Lucentis) is an Anti-VEGF agent that is a preferred treatment according
to the formulary. The treatment algorithm for Ranibuzumab is the injection of 0.5 mg monthly.
Then based upon the individual patient, after 4 treatments the dosing may be reduced to 0.5 mg
every 3 months. Bevacizumab (Avastin) is a preferred treatment which is used off label. The
treatment algorithm for Bevacizumab is 1.25 mg (0.5mL) monthly for 3 months. Then based
upon the individual patient it is given monthly as needed. A non-preferred medication in the
same category as Eylea is Pegaptanib (Macugen). 0.3 mg of Pegaptanib is injected every 6
weeks to the patient.15
Advanced neovascular AMD has a variety of treatment therapies including Anti-VEGF
injections, photodynamic therapy, as well as laser surgery. Anti-VEGF injections block the
growth of abnormal blood vessels. Photodynamic therapy involves the treatment with the use of
lasers to areas of the retina. Verteporfin is injected intravenously into the patient’s arm.
Verteporfin travels to the newly growing blood vessels. The eye doctor then shines a laser into
the patient’s eye which activates the drug in the newly formed blood vessel. This treatment will
15. 15
not cause harm to normal blood vessels. Verteporfin will close the newly formed blood vessel.
This treatment is less common than Anti-VEGF injections, but can be used as combination
therapy.16 Studies have shown that photodynamic therapy has decreased efficacy with increased
age. Patients over the age of 75 are less likely to benefit from therapy.15 This is important due to
the fact that Age-Related Macular Degeneration most commonly occurs in patients over the age
of sixty. Photodynamic therapy is less efficient in comparison to Anti-VEGF agents unless used
in combination.
Laser surgery is the least common strategy among the different treatments. A laser is
pointed into the abnormal blood vessels in the eye and destroys them. This is most commonly
used when blood vessel growth is centralized in one area of the eye away from the macula. This
can harm healthy tissue and can result in a blind spot where the laser was focused. Immediately
after surgery, vision may be worse than it was prior to surgery, but the vision lost in the future
years will be decreased.
Preferred Existing Therapy
Monotherapy of Anti-VEGF Agents is the gold standard of treatment for AMD.14
Ranibizumab trials with monthly injections are the standard for comparison in most trials.
Researchers have been aiming at increasing the dosing interval. Many of the adverse effects in
regards to patients receiving Age-Related Macular Degeneration treatment are due to the
procedure just as much, if not more than the drug itself. With each injection, there is an
increased risk of error as well as infection which may occur.
The price of Bevacizumab is greatly lower than Ranibizumab. Physicians often prefer
Bevacizumab even though it is used off label for AMD due to cost-savings and the belief that its
efficacy is comparable with that of Ranibizumab. The results of The Complications of Age-
Related Macular Degeneration Treatment Trials (CATT) support this position.5 This trial
showed that monthly Bevacizumab injections had similar vision gains as monthly Ranibizumab
injections. Aflibercept decreases the frequency of injections. Physician preferring Bevacizumab
will now have the option of less frequent treatment with Aflibercept.17
Bevacizumab is the preferred Anti-VEGF treatment agent by nearly sixty percent of physicians
due to its similar efficacy and much lower price than Ranibizumab.5
Other Therapeutic Alternatives
16. 16
Related Macular Degeneration most commonly occurs in patients over the age of sixty.
There have been links found by researchers between Age-Related Macular Degeneration and
multiple lifestyle choices. Researchers have found that smoking abstinence, regular exercise,
healthy blood pressure levels, healthy cholesterol levels, and a diet rich in fish and vegetables
decrease the risk of AMD and also slows the progression.16
Researchers at the National Eye Institute found that nutritional supplements could have
protective properties against AMD in the Age-Related Eye Disease Study (AREDS and
AREDS2 Studies). These supplements were shown to slow the progression of the disease in
patients with intermediate AMD or late AMD in one eye. The first AREDS Trial showed that a
combination of Vitamin C, Vitamin E, beta-carotene, zinc, and copper can reduce the risk of
AMD by twenty-five percent. AREDS2 Trial found that replacing beta-carotene with a five to
one ration of lutein and zeaxanthin may reduce the risk of late AMD. Beta-carotene has also
been linked with an increase in lung cancer prevalence in current and former smokers and thus
should be avoided in patients who are smokers or have a history of smoking.16
There are many supplements available with different ingredients than what was tested in
the AREDS trial. The effective doses tested in the AREDS and AREDS2 study are 500 mg of
Vitamin C, 400 IU of vitamin E, 80 mg of zinc as zinc oxide (25 mg in the AREDS2 Study), 2
mg of copper as cupric oxide, and 15 mg of beta-carotene (or 10 mg lutein and 2mg zeaxanthin).
These supplements should be considered if a patient is at risk for acquiring AMD even if the
patient is taking a multivitamin regularly.16
PRODUCT BACKGROUND
PHARMACOLOGY
Aflibercept works by inhibiting vascular endothelial growth factor (VEGF) by binding to
VEGF with a higher affinity than its native receptor. This trapping prevents VEGF from being
able to carry out its angiogenic effects, effectively rendering VEGF ineffective. Aflibercept is
unique because of its higher affinity for VEGF-A, VEGF-B, and PIGF1; none of the other
current therapies are able to target VEGF-B or PIGF.2
PHARMACOKINETICS
Route of
Administration:
Intravitreal
17. 17
Bioavailability: 1
Time to Peak: 1 to 3 days
Multiple dosing: Once every 4 months for 12, then once every 8 weeks
Clearance: 5 to 6 days
ADVERSE EFFECT PROFILE
The serious adverse effects of aflibercept include Endophthalmitis and Retinal
Detachments (due to administration technique and aseptic technique), increased intraocular
pressure (side effect of VEGF inhibitors), and thromboembolic effects (side effect of VEGF
inhibitors). The common adverse effects include eye pain, conjunctival hemorrhage, increased
intraocular pressure, corneal erosion, vitreous floaters, conjunctival hyperemia, foreign body
sensitation in eyes, vitreous detachment, increased lacrimation, injection site pain, blurry vision,
intraocular inflammation, cataract, eyelid edema, corneal edema, retinal tear, hypersensitivity,
and endophthalmitis.20
The common adverse effects of aflibercept did not significantly vary from the control
(placebo) drug, with the exception of eye pain (13% in aflibercept vs 5% placebo).20 These
adverse effects would therefore be primarily due to the administration technique required to use
the drug and not due to the effects of the drug itself.
Aflibercept is a therapeutic protein and alike all therapeutic proteins there is the potential
for immune response; the production of antibodies that would cause rejection of the agent.
Although the potential for the reaction is there, in both the AMD and CRVO studies there were
no differences in efficacy or safety between patients with or without immunogenecity.20
DRUG INTERACTIONS
There are no known drug interactions.
CONTRACTING AND SITE OF CARE
The National Medicare Physician Fee allowable is $116 for treatment in an outpatient
physician’s office. When the injection is performed in a facility, the reimbursement is $104 due
to site-of-service differential. These do not include the cost of the supply of the stock of Eylea.
The 2 mg vial was assigned the price of $1,961.00 by Medicare.18 The recommended site of
service is an outpatient physician’s office. The patient would remain in the office for a short
18. 18
time after the injection to ensure that the patient’s eye and vision are monitored. Eylea can also
be administered in a hospital outpatient department. According to the Medicare, Eylea is
categorized within the ambulatory payment classification which pays $217 for treatment in a
hospital outpatient department.19
METHODOLOGY OF THIS REVIEW
DATABASES SEARCHED:
Pubmed, Ovid, Google Scholar
SECONDARY SOURCES:
Lexicomp, Drugdex
SEARCH STRATEGY:
In order to be able to successfully research all of the elements necessary to formulate a
recommendation, multiple search strategies were employed. First and foremost, in order to gain
a greater understanding of the medication, aflibercept, databases such as Lexicomp and
Micromedex were searched. By starting with these databases, it enabled us to have a greater
understanding of aflibercept. While the information provided was not sufficient, it gave an idea
of how to direct our future searches.
After getting a foundation, searches were performed in both Pubmed and Ovid. These
databases enabled us to perform more specific searches to target the information vital to making
a recommendation.
INCLUSION CRITERIA:
For the CLEAR IT studies, patients had to be greater than 60 years old and have a diagnosis of
exudative AMD,including presence of dursen, as well as pigment epithelial changes in combination with
choroidal neovascularization, confirmed by fluorescein angiogram and optical coherence tomography.1
Only eyes that had been previously injected with either 1.25 mg bevacizumab or 0.5 mg ranibizumab and
had an initial response, followed by a recurrent increase or persistent subretinal fluid or retinal edema on
OCT.1
Search Results:
Study Type N
Randomized controlled trials (RCT) 3
Meta-analyses 1
Indirect Comparison studies 2
19. 19
Prospective observational studies 1
Retrospective observational studies 2
Economic or QALY modeling studies 1
Case Series 0
RCT abstracts,not peer-reviewed 1
Other abstracts,posters, etc.,not peer-reviewed 6
Articles Excluded from Evidence Synthesis:
Reason for Exclusion N
AUTHORSHIP
Timothy Porter, Kemper May, Scott Borton, Nicolas McCloskey, Gregory
Caspero, Beth Traverse Brian Donahoe
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20. 20
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