Voluntary licensing of long-acting HIV prevention and treatment regimens: using a proven collaboration- and competition-based mechanism to rapidly expand at-scale, sustainable, quality-assured and affordable supplies in LMICs.

INTRODUCTION: Emerging long-acting (LA) prevention and treatment medicines, technologies and regimens could be game-changing for the HIV response, helping reach the ambitious goal of halting the epidemic by 2030. To attain this goal, the rapid expansion of at-scale, sustainable, quality-assured, and affordable supplies of LA HIV prevention and treatment products through accelerated and stronger competition, involving both originator and generic companies, will be essential. To do this, global health stakeholders should take advantage of voluntary licensing of intellectual property (IP) rights, such as through the United Nations-backed, not-for-profit Medicines Patent Pool, as a proven mechanism to support broad access to existing HIV medicines across low- and middle-income countries (LMICs). DISCUSSION: While voluntary licensing may unlock the possibility for generic competition to take place ahead of patent expiry, there are additional elements-of amplified importance for more complex LA HIV medicines-that need to be taken into consideration. This paper discusses 10 enablers of voluntary licensing of IP rights as a model to rapidly expand at-scale, sustainable, quality-assured, and affordable supplies of LA HIV prevention and treatment regimens in LMICs: Identifying promising LA technology platforms and drug formulations at an early developmental stage and engaging with patent holders Consolidating a multidisciplinary network and strengthening early-stage coordination and collaboration to foster innovation Embedding public health considerations in product design and delivery Building innovative partnerships for product development and commercialization Raising awareness of and creating demand for emerging LA products Estimating the market size, ensuring sufficient competition and protecting sustainability Using technology transfer and hands-on technical support to reduce product development timelines and costs Exploring de-risking mechanisms and financial incentives to support generic manufacturers Optimizing strategies for generic product development and regulatory filings Aligning and coordinating efforts of stakeholders across the value chain. CONCLUSIONS: Rapid access to emerging LA prevention and treatment regimens and technologies can be facilitated by voluntary licensing-catalyzed and supplemented by enabling collaborative and non-duplicative efforts of various other stakeholders. This can effectively lead to improved-accelerated and cheaper-access to quality-assured medicines for populations in LMICs.

Important considerations for drugs, nutritional, and herbal supplements in pediatric solid organ transplant recipients.

Pediatric transplant recipients are on multiple prescription and non-prescription drugs. Many patients also use dietary, nutritional, and herbal supplements. This manuscript researched formulations of immunosuppressive drugs currently available and presents information on generic immunosuppressive drugs, commonly used non-prescription medications, dietary supplements, and herbal supplements. Immunosuppressive drugs are available in various formulations. Not all formulations are interchangeable. A number of FDA-approved generic formulations are available commercially in the United States. Generally generic formulations produce similar blood concentration vs time profiles compared to brand name products in adults and are considered to be bioequivalent. NSAID should be avoided in transplant patients due to potential drug interactions and increased risk associated with NSAID use; and appropriate doses of acetaminophen should be used for treatment of pain. Over-the-counter medications, such as guaifenesin and dextromethorphan, antihistamine medications, including diphenhydramine, loratadine, cetirizine, and fexofenadine, can be safely used in pediatric solid organ transplant population. Many safe and effective over-the-counter options exist for stool softening and as laxative. Diarrhea can lead to an increase in calcineurin inhibitor levels. Food can alter the absorption of immunosuppressive drugs. Several herbal products can alter immune status of the patients or alter the blood concentration of immunosuppressive drugs or may produce renal or hepatic toxicities and should be avoided in pediatric transplant recipients. It is important to educate pediatric transplant recipients and their families about not only immunosuppressive drug therapy but also about non-prescription drugs, dietary, and herbal supplement use.

Screening Medications for Association with Progression to Wet Age-Related Macular Degeneration.

PURPOSE: There is an urgent need for treatments that prevent or delay development to advanced age-related macular degeneration (AMD). Drugs already on the market for other conditions could affect progression to neovascular AMD (nAMD). If identified, these drugs could provide insights for drug development targets. The objective of this study was to use a novel data mining method that can simultaneously evaluate thousands of correlated hypotheses, while adjusting for multiple testing, to screen for associations between drugs and delayed progression to nAMD. DESIGN: We applied a nested case-control study to administrative insurance claims data to identify cases with nAMD and risk-set sampled controls that were 1:4 variable ratio matched on age, gender, and recent healthcare use. PARTICIPANTS: The study population included cases with nAMD and risk set matched controls. METHODS: We used a tree-based scanning method to evaluate associations between hierarchical classifications of drugs that patients were exposed to within 6 months, 7 to 24 months, or ever before their index date. The index date was the date of first nAMD diagnosis in cases. Risk-set sampled controls were assigned the same index date as the case to which they were matched. The study was implemented using Medicare data from New Jersey and Pennsylvania, and national data from IBM MarketScan Research Database. We set an a priori threshold for statistical alerting at P ≤ 0.01 and focused on associations with large magnitude (relative risks ≥ 2.0). MAIN OUTCOME MEASURES: Progression to nAMD. RESULTS: Of approximately 4000 generic drugs and drug classes evaluated, the method detected 19 distinct drug exposures with statistically significant, large relative risks indicating that cases were less frequently exposed than controls. These included (1) drugs with prior evidence for a causal relationship (e.g., megestrol); (2) drugs without prior evidence for a causal relationship, but potentially worth further exploration (e.g., donepezil, epoetin alfa); (3) drugs with alternative biologic explanations for the association (e.g., sevelamer); and (4) drugs that may have resulted in statistical alerts due to their correlation with drugs that alerted for other reasons. CONCLUSIONS: This exploratory drug-screening study identified several potential targets for follow-up studies to further evaluate and determine if they may prevent or delay progression to advanced AMD.

Efficacy of generic meropenem products in combination with colistin in carbapenemase-producing Klebsiella pneumoniae experimental osteomyelitis.

Guidelines for the management of carbapenemase-producing Enterobacterales (CPE) infections recommend a combination of two active agents, including meropenem if the minimum inhibitory concentration (MIC) is ≤8 mg/L. The therapeutic equivalence of meropenem generics has been challenged. We compared the bactericidal activity of meropenem innovator (AstraZeneca) and four generic products (Actavis, Kabi, Mylan and Panpharma), both in vitro and in vivo, in association with colistin. In vitro time-kill studies were performed at 4 × MIC. An experimental model of KPC-producing Klebsiella pneumoniae osteomyelitis was induced in rabbits by tibial injection of a sclerosing agent followed by 2 × 108 CFU of K. pneumoniae KPC-99YC (meropenem MIC = 4 mg/L; colistin MIC = 1 mg/L). At 14 days after inoculation, treatment for 7 days started in seven groups of ≥10 rabbits, including a control group, a colistin group, and one group for each meropenem product (i.e. the innovator and four generics), in combination with colistin. In vitro, meropenem + colistin was bactericidal with no viable bacteria after 6 h, and this effect was similar with all meropenem products. In the osteomyelitis model, there was no significant difference between meropenem generics and the innovator when combined with colistin. Colistin-resistant strains were detected after treatment with colistin + meropenem innovator (n = 3) and generics (n = 3). The efficacy of four meropenem generics did not differ from the innovator in vitro and in an experimental rabbit model of KPC-producing K. pneumoniae osteomyelitis in terms of bactericidal activity and the emergence of resistance.

Comparison of In Vivo Pharmacokinetics and Pharmacodynamics of Vancomycin Products Available in Korea.

PURPOSE: Few studies have been investigated the in vivo efficacy of generic vancomycin products available outside of the United States. In this study, we aimed to compare the in vivo pharmacokinetics (PK) and pharmacodynamics (PD) of five generic vancomycin products available in Korea with those of the innovator. MATERIALS AND METHODS: The in vitro vancomycin purity of each product was examined using high-pressure liquid chromatography. Single-dose PK analyses were performed using neutropenic mice. The in vivo efficacy of vancomycin products was compared with that of the innovator in dose-effect experiments (25 to 400 mg/kg per day) using a thigh-infection model with neutropenic mice. RESULTS: Generic products had a lower proportion of vancomycin B (range: 90.3-93.8%) and a higher proportion of impurities (range: 6.2-9.7%) than the innovator (94.5% and 5.5%, respectively). In an in vivo single-dose PK study, the maximum concentration (Cmax) values of each generic were lower than that of the innovator, and the geographic mean area under the curve ratios of four generics were significantly lower than that of the innovator (all p<0.1). In the thigh-infection model, the maximum efficacies of generic products reflected in maximal effect (Emax) values were not significantly different from the innovator. However, the PD profile curves of some generic products differed significantly from that of the innovator in mice injected with a high level of Mu3 (all p≤0.05). CONCLUSION: Some generic vancomycin products available in Korea showed inferior PK and PD profiles, especially in mice infected with hetero-vancomycin-resistant Staphylococcus aureus.

Cancer History, Health Insurance Coverage, and Cost-Related Medication Nonadherence and Medication Cost-Coping Strategies in the United States.

OBJECTIVES: To evaluate the relationship between cancer history and cost-related medication nonadherence (CRN) as well as cost-coping strategies, by health insurance coverage. METHODS: We used the 2013 to 2016 National Health Interview Survey to identify adults aged 18 to 64 years with (n = 3599) and without (n = 56 909) a cancer history. Cost-related changes in medication use included (1) CRN, measured as skipping, taking less, or delaying medication because of cost, and (2) cost-coping strategies, measured as requesting lower cost medication or using alternative therapies to save money. Separate multivariable logistic regressions were used to calculate the adjusted odds ratios (AORs) of CRN and cost-coping strategies associated with cancer history, stratified by insurance. RESULTS: Cancer survivors were more likely than adults without a cancer history to report CRN (AOR 1.26; 95% confidence interval [CI] 1.10-1.43) and cost-coping strategies (AOR 1.10; 95% CI 0.99-1.19). Among the privately insured, the difference in CRN by cancer history was the greatest among those enrolled in high-deductible health plans (HDHPs) without health savings accounts (HSAs) (AOR 1.78; 95% CI 1.30-2.44). Among adults with HDHP and HSA, cancer survivors were less likely to report cost-coping strategies (AOR 0.62; 95% CI 0.42-0.90). Regardless of cancer history, CRN and cost-coping strategies were the highest for those uninsured, enrolled in HDHP without HSA, and without prescription drug coverage under their health plan (all P<.001). CONCLUSIONS: Cancer survivors are prone to CRN and more likely to use cost-coping strategies. Expanding options for health insurance coverage, use of HSAs for those with HDHP, and enhanced prescription drug coverage may effectively address CRN.

Challenges adhering to a medication regimen following first-time percutaneous coronary intervention: A patient perspective.

BACKGROUND: Percutaneous coronary intervention is the most common therapeutic intervention for patients with narrowed coronary arteries due to coronary artery disease. Although it is known that patients with coronary artery disease often do not adhere to their medication regimen, little is known about what patients undergoing percutaneous coronary interventions find challenging in adhering to their medication regimen after hospital discharge. OBJECTIVES: To explore patients' experiences in adhering to medications following early post-discharge after first-time percutaneous coronary intervention. DESIGN: An abductive qualitative approach was used to conduct in-depth interviews of patients undergoing first-time percutaneous coronary intervention. SETTINGS: Participants were recruited from a single tertiary university hospital, which services a large geographical area in western Norway. Patients fulfilling the inclusion criteria were identified through the Norwegian Registry for Invasive Cardiology. PARTICIPANTS: Participants were patients aged 18 years or older who had their first percutaneous coronary intervention six to nine months earlier, were living at home at the time of study inclusion, and were prescribed dual antiplatelet therapy. Patients who were cognitively impaired, had previously undergone cardiac surgery, and/or were prescribed anticoagulation therapy with warfarin or novel oral anticoagulants were excluded. Purposeful sampling was used to include patients of different gender, age, and geographic settings. Twenty-two patients (12 men) were interviewed between December 2016 and April 2017. METHODS: Face-to-face semi-structured interviews were conducted, guided by a set of predetermined open-ended questions to gather patient experiences on factors relating to medication adherence or non-adherence. Transcribed interviews were analysed by qualitative content analysis. FINDINGS: Patients failed to adhere to their medication regimen for several reasons; intentional and unintentional reasons, multifaceted side effects from heart medications, scepticism towards generic drugs, lack of information regarding seriousness of disease after percutaneous coronary intervention, psychological impact of living with coronary artery disease, and these interacted. There were patients who felt that the medication information they received from physicians and nurses was uninformative and inadequate. Side effects from heart medications were common, ranging from minor ones to more disabling side effects, such as severe muscle and joint pain and fatigue. Patients found well established medication taking routines and aids to be necessary, and these improved adherence. CONCLUSION: Patients undergoing first-time percutaneous coronary intervention face multiple, interacting challenges in trying to adhere to prescribed medications following discharge. This study highlights the need for a more structured follow-up care in order to improve medication adherence and to maximise their self-care abilities.

Clinical and Economic Benefits of Pharmacist Involvement in a Community Hospital-Affiliated Patient-Centered Medical Home.

BACKGROUND: The primary goals of an accountable care organization (ACO) are to reduce health care spending and increase quality of care. Within an ACO, pharmacists have a unique opportunity to help carry out these goals within patient-centered medical homes (PCMHs). Pharmacy presence is increasing in these integrated care models, but the pharmacist's role and benefit is still being defined. OBJECTIVE: To exhibit the clinical and economic benefit of pharmacist involvement in ACOs and PCMHs as documented by clinical interventions (CIs) and drug cost reductions. METHODS: This is a retrospective quality improvement study. All interventions made by the pharmacist during the study period were documented using TAV Health. The interventions were then analyzed. Specific identified endpoints included the total number of documented interventions and number of CIs from each category, transition of care (TOC) medication reconciliations performed, discrepancies identified during TOC medication reconciliation, and cost savings generated from generic and therapeutic alternative use. CI categories were collaborative drug therapy management, medication therapy management (MTM), medication reconciliation, patient and provider education, and drug cost management. RESULTS: During the study period (October 2016-March 2017), a pharmacist was in clinic 8 hours per week. Sixty-three patients were included in the study. There were 283 CIs documented, with a majority of the interventions associated with MTM or cost management (94 and 88 CIs, respectively). There were 37 education CIs, 36 TOC medication reconciliations performed, and 28 collaborative drug therapy management CIs. From the 36 TOC medication reconciliations, 240 medication discrepancies were found, with a majority associated with medication omission. A cost savings of $118,409 was gained from generic and therapeutic alternative substitutions. CONCLUSIONS: Clinical benefit of pharmacy services was demonstrated through documented CIs. Pharmacists can have a dramatic and quantitative effect on reducing drug costs by recommending less expensive generic or therapeutic alternatives. Documenting CIs allows pharmacists to provide valuable evidence of avoided drug misadventures and identification of medication discrepancies. Such evidence supports an elevated quality of care. DISCLOSURES: No outside funding supported this study. The authors have nothing to disclose. Study concept and design were contributed by Tate and Hopper, along with Bergeron. Tate collected and interpreted the data, as well wrote the manuscript, which was revised by all the authors.

Comparative Randomized Crossover Clinical Study for the Evaluation of Erectile Dysfunction Medications Via Novel Pentagon System.

INTRODUCTION: Due to the chaos in the legislation in the Middle East, male enhancement nutraceuticals may be sold without any registration or evaluation. These products need to be evaluated with respect to safety and efficacy. Furthermore, cultural and social considerations in the Middle East prevent the use of international evaluations schemes for erectile dysfunction. AIM: Evaluating the safety and efficacy parameters of generic and nutraceutical products for erectile dysfunction in the Middle East through a custom-designed, representable and simple system tailored to the regional culture. METHODS: 74 healthy male volunteers were enrolled into a comparative, simple randomized, single dose, double blind, and crossover clinical study incorporated with a tailored-designed questionnaire. Safety assessment included laboratory analysis for liver functions and measuring blood pressure. MAIN OUTCOME MEASURES: Subjective data regarding safety and efficacy were assessed from the validated questionnaire. Blood pressure was measured. Blood samples were collected to assess the drug/adulterants concentration and liver and kidney functions. RESULTS: All tested nutraceuticals showed undeclared Sildenafil citrate in patients. Questionnaire results showed high inter-patient variability with respect to efficacy and comparable safety profile compared to Viagra®. CONCLUSION: The validated tailored-designed questionnaire effectively assessed the efficacy and safety of male enhancement products. The male enhancement nutraceuticals, sold in Egypt, claimed to be 100% natural are adulterated and of questionable safety profile.

Comparison of the effectiveness of brand-name and generic antipsychotic drugs for treating patients with schizophrenia in Taiwan.

The purpose of this nationwide population-based study is to compare the long-term effectiveness of brand-name antipsychotics with generic antipsychotics for treating schizophrenia. We identified patients with schizophrenia who were prescribed antipsychotics from a random sample of one million records from Taiwan's National Health Insurance database, observed between January 1, 2000 and December 31, 2012. Only those with no prior use of antipsychotics for at least 180days were included. We selected patients who were prescribed brand-name risperidone (N=404), generic risperidone (N=145), brand-name sulpiride (N=334), or generic sulpiride (N=991). The effectiveness of the treatments researched in this study consisted of average daily doses, rates of treatment discontinuation, augmentation therapy, and psychiatric hospitalization. We found that compared to patients treated with generic risperidone, those treated with brand-name risperidone required lower daily doses (2.14mg vs. 2.61mg). However, the two groups demonstrated similar rates of treatment discontinuation, augmentation, and psychiatric hospitalization. On the other hand, in comparison with patients prescribed generic sulpiride, those treated with brand-name sulpiride not only required lower daily doses (302.72mg vs. 340.71mg) but also had lower psychiatric admission rates (adjusted hazard ratio: 0.24, 95% confidence interval: 0.10-0.56). In conclusion, for both risperidone and sulpiride, higher daily doses of the respective generic drugs were prescribed than with brand-name drugs in clinical settings. Furthermore, the brand-name sulpiride is more effective at preventing patients from hospitalization than generic sulpiride. These findings can serve as an important reference for clinical practices and healthcare economics for treating schizophrenic patients.

Systematic screening of generic drugs for progressive multiple sclerosis identifies clomipramine as a promising therapeutic.

The treatment of progressive multiple sclerosis (MS) is unsatisfactory. One reason is that the drivers of disease, which include iron-mediated neurotoxicity, lymphocyte activity, and oxidative stress, are not simultaneously targeted. Here we present a systematic screen to identify generic, orally available medications that target features of progressive MS. Of 249 medications that cross the blood-brain barrier, 35 prevent iron-mediated neurotoxicity in culture. Of these, several antipsychotics and antidepressants strongly reduce T-cell proliferation and oxidative stress. We focus on the antidepressant clomipramine and found that it additionally inhibits B-lymphocyte activity. In mice with experimental autoimmune encephalomyelitis, a model of MS, clomipramine ameliorates clinical signs of acute and chronic phases. Histologically, clomipramine reduces inflammation and microglial activation, and preserves axonal integrity. In summary, we present a systematic approach to identify generic medications for progressive multiple sclerosis with the potential to advance rapidly into clinical trials, and we highlight clomipramine for further development.

Fármacos biosimilares: un nuevo escenario en las terapias biológicas / Biosimilars: a new scenario in biologic therapies

No cabe duda de que los productos biológicos aportan un valor añadido a los sistemas de salud, aunque también plantean grandes interrogantes debido a su especial naturaleza, lo que obliga a ser muy rigurosos y exigentes en su control de calidad y seguimiento. Este hecho se ha visto reforzado por la entrada en escena de los fármacos biosimilares, cuyo menor coste está permitiéndoles alcanzar un mayor protagonismo en el mercado mundial. El propósito de este artículo es revisar en profundidad los principales interrogantes que se plantean en su producción, distribución y control, así como los aspectos más importantes relacionados con su seguridad en la práctica clínica. En este trabajo revisamos lo que representa la farmacovigilancia de estos productos, prestando especial atención a su trazabilidad, como herramienta fundamental para la detección precoz de acontecimientos adversos (AU)

There is no doubt that biologic therapies provide added value for health systems. However, due to their special nature, they also raise some questions that make highly rigorous and demanding quality control and monitoring of their use indispensable. This circumstance is reinforced with the appearance on the scene of biosimilars, which, given their lower cost, are having an increasing impact on the international market. The purpose of this article is to review the major issues posed by their manufacture, distribution and control systems, as well as the most important aspects related to their safety in clinical practice. In this report, we assess the pharmacovigilance of these products, with special attention to traceability, as a key tool to enable earlier detection of adverse events (AU)

Randomized clinical trial comparing efficacy and safety of brand versus generic alendronate (Bonmax®) for osteoporosis treatment.

INTRODUCTION: Although the same efficacy and tolerability are anticipated due to both drugs containing the same active ingredients, comparative studies between brand and generic alendronate are limited. Accordingly, the objective of this study was to compare efficacy and safety between brand alendronate and a recently introduced generic alendronate drug. METHODS: A total of 140 postmenopausal women or men aged older than 50 years who met the indications for osteoporosis treatment were randomized to receive either generic (Bonmax®) or brand alendronate (Fosamax®) 70 mg/week over a 12-month period during the May 2014 to June 2015 study period. Endpoints included bone mineral density (BMD) changes at the lumbar spine, total hip, and femoral neck; percentage of patients with predefined levels of change in total hip and lumbar spine BMD at 12 months; and, changes in biochemical bone markers at 3, 6, and 12 months. Tolerability was evaluated by patient self-reporting of adverse experiences. RESULTS: At 12 months post-treatment, BMD significantly increased at all sites in both groups. There were no differences in BMD percentage changes or the number of patients with stable or increased BMD after 1 year between groups. No significant differences in the amount of biochemical bone marker reduction or incidence of adverse events were observed between groups. CONCLUSIONS: Generic and brand alendronate produced similar gains in BMD and reduction in bone turnover markers. Both medicadoitions were also equally well-tolerated. Based on these findings, generic alendronate (Bonmax®) is a viable alternative to the original brand of alendronate. TRIAL REGISTRATION: ClinicalTrials.gov NCT02371252.

Use of generic medicines by the Brazilian population: an evaluation of PNAUM 2014.

OBJECTIVE: To analyze the existence of differences in the use of generic medicines in Brazil according to demographic and socioeconomic variables and acquisition sources of the medicines. METHODS: Population-based cross-sectional study, conducted with data from the Pesquisa Nacional de Acesso, Utilização e Promoção do Uso Racional de Medicamentos (PNAUM - National Survey on Access, Use and Promotion of Rational Use of Medicines). Data collection took place between September, 2013 and February, 2014 in homes of Brazilian cities (urban area). The use of medicines has been investigated in relation to the treatment of chronic diseases and, in the case of acute events, regarding use over the previous 15 days. Generics were identified by visualization of packaging presented by the users of the medicines. The independent variables used were sex, age, education level, economic class, and region of the Country. The statistical significance of differences between the groups was evaluated by Pearson's Chi-squared test, considering a 5% significance level. RESULTS: The prevalence of generic medicines use was 45.5% (95%CI 43.7-47.3). There was no difference considering education level. The prevalence was higher in females (47.0%; 95%CI 44.9-49.0) than in males (43.1%; 95%CI 40.5-45.8), and were higher with increasing age. Generic medicines were more used in the economic class C (47.0%; 95%CI 44.9-49.1) and in the South (50.6%; 95%CI 46.6-54.6) and Southeast (49.9%; 95%CI 46.8-53.0) regions. Generics accounted for 37.3% of the medicines provided by the Brazilian Unified Health System. CONCLUSIONS: Currently, there is a choice of purchase or free provision by the Brazilian Unified Health System, characterized by quality assurance and reduced price regarding branded medicines considered as reference. In the private market, a considerable part of the population is choosing generic medicines thanks to the availability of this option for virtually all medicines most used by the population. OBJETIVO: Analisar se há diferença no uso de medicamentos genéricos no Brasil segundo variáveis demográficas, socioeconômicas e fontes de obtenção dos medicamentos. MÉTODOS: Estudo transversal de base populacional, conduzido com dados da Pesquisa Nacional de Acesso, Utilização e Promoção do Uso Racional de Medicamentos (PNAUM), com coleta de dados entre setembro de 2013 e fevereiro de 2014 em residências de municípios brasileiros urbanos. O uso dos medicamentos foi investigado em relação ao tratamento de doenças crônicas e, no caso de eventos agudos, quanto ao uso nos últimos 15 dias. Os genéricos foram identificados por visualização das embalagens apresentadas pelos usuários dos medicamentos. As variáveis independentes utilizadas foram sexo, idade, escolaridade, classe econômica e região do País. A avaliação da significância estatística das diferenças entre os grupos foi analisada pelo teste Qui-quadrado de Pearson, considerando nível de significância de 5%. RESULTADOS: A prevalência de uso de genéricos foi de 45,5% (IC95% 43,7-47,3). Não houve diferença por escolaridade, as prevalências foram maiores no sexo feminino (47,0%; IC95% 44,9-49,0) em relação ao masculino (43,1%; IC95% 40,5-45,8) e foram crescentes com o aumento da idade. Maiores usos de genéricos foram encontrados na classe econômica C (47,0%; IC95% 44,9-49,1) e nas regiões Sul (50,6%; IC95% 46,6-54,6) e Sudeste (49,9%; IC95% 46,8-53,0). Observou-se ainda que os genéricos representaram 37,3% dos medicamentos disponibilizados pelo Sistema Único de Saúde . CONCLUSÕES: Pode-se concluir que hoje existe uma alternativa de compra ou fornecimento gratuito pelo Sistema Único de Saúde, caracterizada por garantia de qualidade e preço reduzido em relação aos medicamentos de marca comercial considerados como referência. No mercado privado, boa parte da população está optando pelo uso de medicamentos genéricos, graças à disponibilidade dessa opção para praticamente todos os medicamentos mais utilizados pela população.

Biosimilar monoclonal antibodies: preclinical and clinical development aspects.

Biological drugs and their originated biosimilars are large, highly complex molecules derived from living cells or organisms. Traditional medicines, by contrast, are usually simple molecules of low molecular weight, synthesised by chemical means. The distinct complexities and methods of manufacture create an important difference between biosimilars and conventional generic drugs: while chemical generics can be fully characterised as identical to the originator product, biosimilars cannot. In addition, biological therapies are inherently variable, creating unavoidable differences between even subsequent batches of the same product. An expiring patent does not necessarily mean that the manufacturing process of the originator product becomes available to the biosimilar developers (for instance, the relevant cell line clone and growth medium). Therefore, it cannot be guaranteed that biosimilar products are identical to their reference product on a molecular level. This difference has important implications for the regulation and licensing of biosimilars. While conventional generic drugs require only a limited comparison and demonstration of identical chemical structure to the reference product, biosimilars require far more rigorous testing. In general, there must be a thorough comparison of structural and functional characteristics between biosimilar and originator drug. Stepwise nonclinical in vitro and in vivo approaches are recommended to evaluate the similarity of both drugs and any identified micro-heterogeneities must then be assessed for their impact on safety and clinical performance. Subsequently, clinical pharmacokinetic (PK) studies need to be performed in order to demonstrate a similar PK profile, prior to conducting clinical efficacy trials.

Use of generic medicines by the Brazilian population: an evaluation of PNAUM 2014 / Utilização de medicamentos genéricos na população brasileira: uma avaliação da PNAUM 2014

ABSTRACT OBJECTIVE To analyze the existence of differences in the use of generic medicines in Brazil according to demographic and socioeconomic variables and acquisition sources of the medicines. METHODS Population-based cross-sectional study, conducted with data from the Pesquisa Nacional de Acesso, Utilização e Promoção do Uso Racional de Medicamentos (PNAUM – National Survey on Access, Use and Promotion of Rational Use of Medicines). Data collection took place between September, 2013 and February, 2014 in homes of Brazilian cities (urban area). The use of medicines has been investigated in relation to the treatment of chronic diseases and, in the case of acute events, regarding use over the previous 15 days. Generics were identified by visualization of packaging presented by the users of the medicines. The independent variables used were sex, age, education level, economic class, and region of the Country. The statistical significance of differences between the groups was evaluated by Pearson’s Chi-squared test, considering a 5% significance level. RESULTS The prevalence of generic medicines use was 45.5% (95%CI 43.7–47.3). There was no difference considering education level. The prevalence was higher in females (47.0%; 95%CI 44.9–49.0) than in males (43.1%; 95%CI 40.5–45.8), and were higher with increasing age. Generic medicines were more used in the economic class C (47.0%; 95%CI 44.9–49.1) and in the South (50.6%; 95%CI 46.6–54.6) and Southeast (49.9%; 95%CI 46.8–53.0) regions. Generics accounted for 37.3% of the medicines provided by the Brazilian Unified Health System. CONCLUSIONS Currently, there is a choice of purchase or free provision by the Brazilian Unified Health System, characterized by quality assurance and reduced price regarding branded medicines considered as reference. In the private market, a considerable part of the population is choosing generic medicines thanks to the availability of this option for virtually all medicines most used by the population.

RESUMO OBJETIVO Analisar se há diferença no uso de medicamentos genéricos no Brasil segundo variáveis demográficas, socioeconômicas e fontes de obtenção dos medicamentos. MÉTODOS Estudo transversal de base populacional, conduzido com dados da Pesquisa Nacional de Acesso, Utilização e Promoção do Uso Racional de Medicamentos (PNAUM), com coleta de dados entre setembro de 2013 e fevereiro de 2014 em residências de municípios brasileiros urbanos. O uso dos medicamentos foi investigado em relação ao tratamento de doenças crônicas e, no caso de eventos agudos, quanto ao uso nos últimos 15 dias. Os genéricos foram identificados por visualização das embalagens apresentadas pelos usuários dos medicamentos. As variáveis independentes utilizadas foram sexo, idade, escolaridade, classe econômica e região do País. A avaliação da significância estatística das diferenças entre os grupos foi analisada pelo teste Qui-quadrado de Pearson, considerando nível de significância de 5%. RESULTADOS A prevalência de uso de genéricos foi de 45,5% (IC95% 43,7–47,3). Não houve diferença por escolaridade, as prevalências foram maiores no sexo feminino (47,0%; IC95% 44,9–49,0) em relação ao masculino (43,1%; IC95% 40,5–45,8) e foram crescentes com o aumento da idade. Maiores usos de genéricos foram encontrados na classe econômica C (47,0%; IC95% 44,9–49,1) e nas regiões Sul (50,6%; IC95% 46,6-54,6) e Sudeste (49,9%; IC95% 46,8–53,0). Observou-se ainda que os genéricos representaram 37,3% dos medicamentos disponibilizados pelo Sistema Único de Saúde . CONCLUSÕES Pode-se concluir que hoje existe uma alternativa de compra ou fornecimento gratuito pelo Sistema Único de Saúde, caracterizada por garantia de qualidade e preço reduzido em relação aos medicamentos de marca comercial considerados como referência. No mercado privado, boa parte da população está optando pelo uso de medicamentos genéricos, graças à disponibilidade dessa opção para praticamente todos os medicamentos mais utilizados pela população.

Demonstration of Therapeutic Equivalence of Fluconazole Generic Products in the Neutropenic Mouse Model of Disseminated Candidiasis.

Some generics of antibacterials fail therapeutic equivalence despite being pharmaceutical equivalents of their innovators, but data are scarce with antifungals. We used the neutropenic mice model of disseminated candidiasis to challenge the therapeutic equivalence of three generic products of fluconazole compared with the innovator in terms of concentration of the active pharmaceutical ingredient, analytical chemistry (liquid chromatography/mass spectrometry), in vitro susceptibility testing, single-dose serum pharmacokinetics in infected mice, and in vivo pharmacodynamics. Neutropenic, five week-old, murine pathogen free male mice of the strain Udea:ICR(CD-2) were injected in the tail vein with Candida albicans GRP-0144 (MIC = 0.25 mg/L) or Candida albicans CIB-19177 (MIC = 4 mg/L). Subcutaneous therapy with fluconazole (generics or innovator) and sterile saline (untreated controls) started 2 h after infection and ended 24 h later, with doses ranging from no effect to maximal effect (1 to 128 mg/kg per day) divided every 3 or 6 hours. The Hill's model was fitted to the data by nonlinear regression, and results from each group compared by curve fitting analysis. All products were identical in terms of concentration, chromatographic and spectrographic profiles, MICs, mouse pharmacokinetics, and in vivo pharmacodynamic parameters. In conclusion, the generic products studied were pharmaceutically and therapeutically equivalent to the innovator of fluconazole.

How Do US Gastroenterologists Use Over-the-Counter and Prescription Medications in Patients With Gastroesophageal Reflux and Chronic Constipation?

BACKGROUND: The aim of this study was to assess how US gastroenterologists perceive and utilize over-the-counter (OTC) and prescription medications for gastroesophageal reflux disease (GERD) and chronic constipation (CC). METHODS: A total of 3,600 randomly selected American Gastroenterological Association (AGA) members were mailed a 27-question survey that assessed their perceptions and use of OTC and prescription medications. The χ(2) test and Student's t-test were utilized for bivariate analysis. RESULTS: A total of 830 gastroenterologists (23.1%) completed the survey. For the typical acid reflux patient, 50% of gastroenterologists recommended OTC proton pump inhibitors (PPIs), 13% recommended an OTC histamine2 receptor antagonist, whereas 33% recommended a prescription PPI. However, in the typical CC patient, 97% of gastroenterologists initially utilized OTC treatments. The vast majority of gastroenterologists felt that OTC brand name and store brand PPIs (76%) and polyethylene glycol (PEG 3350; 90%) were equally effective. Despite this, a minority "always" or "very often" directed their patients to purchase a store brand PPI (35%) or laxative (40%). In addition, gastroenterologists tended to underestimate the cost savings associated with store brand medicines and had limited knowledge regarding the regulation of store brands. CONCLUSIONS: Among US gastroenterologists, OTC medications now dominate primary therapy of GERD and CC. Despite feeling that name brand and store brand PPIs and laxatives are equally effective, the majority of gastroenterologists recommend brand name medicines and underestimate the cost savings associated with store brands. In this age of accountable care, greater efforts to help physicians and patients to better utilize their health-care dollars is warranted.

Fármacos biosimilares en psoriasis: informe de posicionamiento / The use of biosimilar drugs in psoriasis: a position paper

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