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Valsartan, losartan, and irbesartan, are widely used in the treatment strategies of cardiovascular medicine diseases, including hypertension and heart failure. Recently, many formulations for the aforementioned diseases contained active pharmaceutical ingredients and had been abruptly recalled from the market due to safety concerns mainly associated with unwanted impurities - nitrosamines, which are highly carcinogenic substances accidentally produced during manufacturing. Along with cardiovascular medications, formulations containing ranitidine were also recalled from the market. This poses a particular threat to public health due to the non-prescription status of these drugs. Regulatory authorities, including the Food and Drug Administration and European Medicines Agency among others, have taken action to minimize patient risk and improve the manufacturing quality as well as re-checking current guidelines and recommendations. While these steps are necessary to avoid further recalls, authorities should remember the growing concerns of patients regarding the safety and efficacy of pharmacotherapy. Apart from the genuine manufacturing mistakes mentioned above, falsified and counterfeit medications should be at the heart of global attention. The lack of a well-accepted definition of falsified/counterfeit medications has impeded political and scientific efforts to mitigate risk of this phenomenon. Falsified Medicines Directive should be considered the most pivotal legislation recently enacted to harmonize international cooperation. In summary, one should remember that only international and direct collaboration between patients, stakeholders, and authorities be considered a remedy for a pandemic of falsified medicines and plague of unexpected recalls due to safety concerns.

This Viewpoint discusses the controversy surrounding the FDA’s efforts to withdraw Makena from the market and the broader implications for the accelerated approval pathway.

Background: The manufacture of medicinal products for human use in the European Economic Area is governed by European Directives and Regulations stipulating the relevant principles and guidelines of Good Manufacturing Practice, describing the minimum standard to be fulfilled in the production processes. Aim: To present analysis of the deficiencies reported following Good Manufacturing Practice inspections in Bulgaria in two consecutive years (2016, 2017) and to compare them with results from similar inspections reported by other EU member states. Materials and methods: A retrospective study was carried out by reviewing the complete Good Manufacturing Practice inspection reports of all manufacturers conducted by the Bulgarian Drug Agency in 2016 and 2017, according to relevant requirements and applicable local legislation. The items reviewed were scope of inspection, type of companies, classification of deficiencies – ‘critical’, ‘major’ and ‘other significant deficiencies’, their nature and reference to EU Good Manufacturing Practice. Results: The analyzed data included 55 inspections, revealing 460 various deficiencies, of which 2 were critical and 102 – major. Twenty inspections were performed in 2016 vs. 35 inspections in 2017. The pattern of deficiencies was similar to the findings of other EU regulatory agencies, showing that equivalent requirements were applied. Our analysis showed that Bulgarian Drug Agency inspectors rarely raised deficiencies related to Computer Systems, Qualification/Validation, Personnel and Qualification of Suppliers unlike other EU regulators agents. Conclusions: Our analysis of Good Manufacturing Practice inspection findings in 2016 and 2017 showed that the Bulgarian Drug Agency demonstrated its ability to detect non-compliances and take necessary regulatory actions. Quality related issues constitute the main reasons for non-compliances with the requirements. Publishing the results from the inspections performed by the national competent authorities enhances the regulatory transparency that can be useful for industry to improve its Good Manufacturing Practice compliance.

Losartan was the ninth most prescribed drug in the United States in 2016, and several other angiotensin-II receptor blockers (ARBs) are widely prescribed. Since July 2018, >2 dozen specific ARB products have been recalled owing to the presence of potentially carcinogenic nitrosamine impurities in selected lots. As is the case with all U.S. drug recalls, the ARB recalls have been voluntary on the part of the companies involved. In April 2019, the Food and Drug Administration categorized marketed ARB products with respect to nitrosamine impurities: (1) not present, (2) to be determined with no prior lots removed from the market (TBD), or (3) to be determined in the context of prior lots having been removed from the market (TBD*). The data were structured as hundreds of rows of products. Owing to the complexity of these data, more than a year into the recalls, it remains difficult for clinicians to understand which ARB products are free of impurities.

Background: Drug shortages represent a growing global problem, with potentially serious consequences to patients and the health care system. Our study investigates the impacts of a major recall and shortage of valsartan, an angiotensin receptor blocker (ARB), in July 2018 in Canada. Methods: We conducted a time-series analysis of antihypertensive drugs dispensed in Canada between 2015 and 2019 using commercially available retail prescription data. Using autoregressive integrated moving average (ARIMA) modelling, we evaluated the change in valsartan use after the recall. We also measured the overall use of ARBs, angiotensin-converting-enzyme (ACE) inhibitors and other antihypertensive drug classes for the same period. Results: After the recall in July 2018, valsartan use decreased 57.8%, from 362 231 prescriptions dispensed in June 2018 to 152 892 in September 2018 (difference = 209 339, p < 0.0001). Overall use of the ARB drug class decreased 2.0%, from 1 577 509 prescriptions dispensed in June 2018 to 1 545 591 in September 2018 (difference = 31 918, p = 0.0003), but use of non-valsartan ARBs increased 14.6%, from 1 215 278 to 1 392 699 prescriptions dispensed (difference = 177 421, p < 0.0001) in the same time frame. Although use of ACE inhibitors initially declined, this reduction was not sustained. The valsartan recall was not associated with a significant impact on use of other antihypertensive drug classes. Interpretation: Our findings illustrate the impact of a major drug shortage, with the immediate and substantial reduction of valsartan dispensed and cascading effects on other ARBs, though future research is warranted to understand the consequences of such extensive shortages on clinical outcomes and health system costs. Improved policy strategies are needed to address the underlying causes of drug shortages and to mitigate their effects.

Ensuring the quality and safety of the pharmaceutical supply chain is a key policy focus vital to protecting the public from harmful or potentially harmful medications. Although the Food and Drug Administration (FDA) reports the number of recalled products per fiscal year and categorizes recalls based on product type and recall classification, these reports do not distinguish between manufactured and compounded products.This research aims to categorize drug recalls based on the reason for recall and then to compare this reason between manufacturers and compounders.All publicly available drug recall data were downloaded from the FDA Data Dashboard website on January 24, 2021. Two reviewers independently categorized the recalling firm, distribution pattern, and reason for recall, and a third reviewer resolved all conflicts. Descriptive statistics were reported for recall event classification, distribution, and recall reason for the full sample. Chi-square test of independence was used to assess categorical variables by facility type (manufacturer or compounder) as well as by event classification (class I, II, or III). A subgroup analysis was performed focusing on class I level recalls only, representing the most serious recall, and similar statistical procedures were performed.From June 8, 2012, to January 24, 2021, there were 12,343 drug products recalled; 6771 were from a manufacturer, and 5572 were from a compounder. Most recalls from both compounders and manufacturers were class II recalls with products being distributed to multiple states. Sterility assurance was the predominant reason for recall among compounders, whereas product quality was the most frequent recall reason for manufacturers. There were statistically significant differences in class I recalls between compounders and manufacturers and recall reason compared across recall classification.There was a statistically significant difference in the reason for a drug to be recalled, the distribution level, and the product class for manufactured and compounded products.

Cilj istraživanja: U ovom radu pregledom dostupne literature napravljena je analiza prijava neispravnosti u kakvoći i povlačenja lijeka s hrvatskog tržišta u vremenskom razdoblju od 1.1.2015. do 31.12.2019. godine. Materijali i metode: Podaci o prijavama neispravnosti u kakvoći dobiveni su iz godišnjih Izvješća o izvršenju poslovnog plana HALMED-a, dok su detaljniji podaci dobiveni izravno iz baza podataka HALMED-a. Podaci o prijavama neispravnosti i povlačenjima lijekova odobrenih centraliziranim postupkom preuzeti su iz Godišnjih izvješća Europske agencije za lijekove. Od dobivenih podataka analizirani su godina prijave, godina povlačenja, prijavitelj, klasa neispravnosti, provjere OMCL-a, negativni nalazi i povlačenja uslijed negativnih nalaza. Rezultati: U promatranom vremenskom razdoblju HALMED je zaprimio 783 validne prijave neispravnosti u kakvoći. Najviše prijava neispravnosti u kakvoći zaprimljeno je 2018. godine (202). Najviše prijava podnijeli su nositelji odobrenja za stavljanje lijeka na tržište (67,4 %). U prijavama neispravnosti u kakvoći prijavitelji su neispravnost najčešće pripisali klasi neispravnosti III (62,6 %). Povučeni lijekovi odobreni centraliziranim postupkom najrjeđe su pripadali klasi neispravnosti I (13,3 %). Rezultati ovog istraživanja pokazuju da nema razlike u učestalosti povlačenja lijeka s hrvatskog tržišta u odnosu na povlačenje lijeka s europskog tržišta odobrenog centraliziranim postupkom. Zaključak: Učestalost prijavljivanja neispravnosti u kakvoći u RH je u porastu. Nositelj odobrenja za stavljanje lijeka na tržište najčešće prijavljuje neispravnost u kakvoći. Prijava neispravnosti u kakvoći najčešće pripada klasi neispravnosti III. Lijekovi odobreni centraliziranim postupkom koji se povlače s tržišta najrjeđe pripadaju klasi neispravnosti I. Povlačenje lijekova s hrvatskog tržišta zbog neispravnosti u kakvoći nije češće od povlačenja lijekova s europskog tržišta odobrenih centraliziranim postupkom., Objective: In this paper, by reviewing the available literature, an analysis of reports on medicines quality defects and recalls from the Croatian market in the period from January 1st 2015 to December 31st 2019 was made. Materials and methods: Reports on medicines quality defects data are obtained from HALMED's (Agency for Medicinal Products and Medical Devices of Croatia) annual Reports on Business Plan Performance while more detailed data are summoned directly from HALMED's database. The data on quality defect reports and recalls of centrally authorised medicines are obtained from the European Medicines Agency. The reporting year, the year of the recall, the reporter, classification of quality defect, OMCL quality control and negative results and recalls due to the latter are analyzed in the paper. Results: In the observed time period, HALMED received 783 valid quality defect reports. Most of the quality defect reports were received in 2018 (202). Marketing authorization holders were the ones who reported most quality defects (67.4 %). In the reports, the reporters attributed quality defects mainly to class III defects (62.6 %). The recalled centrally authorised medicinal products were rarely connected to class I defects (13.3 %). The results of this study show that there is no difference in incidence of medicinal product recall from the Croatian market in relation to incidence of centrally authorized medicinal product recall from the European market. Conclusion: The reporting of quality defects in Croatia is on the rise. Marketing authorization holders most frequently report quality defects. The class III defect is the most common. Centrally authorized medicines being recalled from the market are rarely connected to class I defects. Medicine recall from Croatian market is not more frequent than centrally authorized medicine recall from European market.

Ranitidine has been the topic of recent media reports. Current findings, confirmed by the US Food and Drug Administration, indicate that some ranitidine products contain a substance that may be carcinogenic. Providers and patients require additional information on the risks of continuing therapy vs. the benefits of the medication. This article comments on what is currently known about the evolving situation of elevated N-nitrosodimethylamine levels in ranitidine and the limits of the existing information to assess best practices.

Atropinic drugs are known to potentially induce physical and/or mental impairments in the elderly. The aim of this study was to investigate trends of atropinic exposure in patients ≥65 years in France between 2006 and 2015. A repeated cross-sectional study was performed quarterly from January 1, 2006 to December 31, 2015, in the 'Echantillon Generaliste des Beneficiaires (EGB)', a representative sample of the French population. Exposed patients were identified using the Anticholinergic Duran's list. Outcomes were rate of patients exposed to at least one atropinic drug (atropinic prevalence rate) and atropinic burden per patient (sum of atropinic burden scores). Interrupted time series were used to analyze the impact of market withdrawal of some drugs with atropinic properties during the period of the study. The number of patients ≥65 years registered in the EGB ranged from 75 611 in 2006 to 95 389 in 2015. Atropinic prevalence rate decreased significantly from 45.6% in 2006 to 33.2% in 2015 (-12.4%, slope significance P < 0.05). Subjects aged ≥85 years were the most exposed. Total atropinic burden decreased significantly between 2006 and 2015 (2.2 ± 1.7 in 2006; 2.0 ± 1.5 in 2015; slope significance P < 0.05), especially in patients ≥85 years. Market withdrawals for safety reasons of some atropinic drugs were significantly associated with a decrease in the atropinic prevalence rate (P < 0.05) and atropinic burden per patient (P < 0.05). In conclusion, atropinic drug exposure in the elderly significantly decreased in France between 2006 and 2015. This decrease can be partly explained by regulatory measures against some atropinic drugs.

Effective doctor–patient communication is critical for disease management, especially when considering genetic information. We studied patient-provider communications after implementing a point-of-care pharmacogenomic results delivery system to understand whether pharmacogenomic results are discussed and whether medication recall is impacted. Outpatients undergoing preemptive pharmacogenomic testing (cases), non-genotyped controls, and study providers were surveyed from October 2012–May 2017. Patient responses were compared between visits where pharmacogenomic results guided prescribing versus visits where pharmacogenomics did not guide prescribing. Provider knowledge of pharmacogenomics, before and during study participation, was also analyzed. Both providers and case patients frequently reported discussions of genetic results after visits where pharmacogenomic information guided prescribing. Importantly, medication changes from visits where pharmacogenomics influenced prescribing were more often recalled than non-pharmacogenomic guided medication changes (OR = 3.3 [1.6–6.7], p = 0.001). Case patients who had separate visits where pharmacogenomics did and did not, respectively, influence prescribing more often remembered medication changes from visits where genomic-based guidance was used (OR = 3.4 [1.2–9.3], p = 0.02). Providers also displayed dramatic increases in personal genomic understanding through program participation (94% felt at least somewhat informed about pharmacogenomics post-participation, compared to 61% at baseline, p = 0.04). Using genomic information during prescribing increases patient-provider communications, patient medication recall, and provider understanding of genomics, important ancillary benefits to clinical use of pharmacogenomics.

This study examines the frequency of product recalls and the presence of FDA-prohibited drugs in supplements after FDA warning letters.

ObjectivesTo evaluate the pattern of substandard and falsified pharmaceutical products recall in Nepal.SettingWe analysed drug recall notices issued by the Department of Drug Administration (DDA), Nepal, and systematically reviewed peer-reviewed research articles during January 2010 to December 2020.ParticipantsThis study did not include human participants. However, data were collected from 72 drug recall notices issued by DDA and four research papers.ResultsA total of 346 pharmaceutical products were recalled during the reported period. The number of recalled pharmaceutical products has increased significantly over the past decade in Nepal. The most frequently recalled drugs were antimicrobials followed by gastrointestinal medicines, vitamins and supplements and pain and palliative medicines among others. Number of imported recalled drugs were slightly higher (42.2%) than domestic recalled drugs (40.7%). Sixty-two percentage of recalled drugs were substandard, 11% were falsified and remaining 27% were not registered at the DDA. Similarly, higher number of modern drugs (62%) were recalled than traditional ones (35%). Hand sanitisers used to minimise COVID-19 transmission contributed significantly to the list of recalled pharmaceutical products in 2020. Most of these sanitisers contained significant amounts of methanol (as high as 75% v/v) instead of appropriate amount of ethyl or isopropyl alcohol. The peer-reviewed research papers reported issues with labelling, unregistered drugs and drugs failed in several laboratory testing.ConclusionOur analysis showed that number of recalls of substandard and falsified drugs are increasing in Nepal. Since the recall data in this paper did not include number of samples tested and location of samples collected, more studies to understand the prevalence of substandard and falsified drugs in Nepal is recommended.

Ranitidine was one of the most commonly used medications for the treatment of gastroesophageal reflux disease. On 1 April 2020, the US Food and Drug Administration requested all manufacturers to immediately withdraw ranitidine from the market because of concern of higher than acceptable levels of N-nitrosodimethylamine, a potential carcinogen. Herein, we highlight the reason for this recall, along with the effects of this recall on both the patients and healthcare practitioners, and offer insights on management strategies.

Pharmaceutical companies use the quality by design (QbD) approach to build high-quality drug products. A thorough understanding of risk factors is required to successfully employ QbD. In order to better understand risk factors that potentially impact drug product quality and inform future QbD approaches, we hypothesized root causes of drug product recalls based on publicly available data and a retroactive analysis of drug products recalled by the United States Food and Drug Administration (USFDA) from 2012 to 2018. We focused on two categories of drug products that pose unique regulatory challenges and an increased risk of shortage that could hinder the adequate supply of quality medicine to the patient. Knowing the significant risk factors from previous drug product recalls can help inform QbD and avoid future recalls. Quality recall reasons were studied individually to find risk factors associated with each recall category. Logistical regression statistical tests were done in R using a significance level of 0.05 to find correlations between a recalled product and its manufacturing information such as excipients and manufacturing steps. The results showed significant positive and negative correlations, such as products containing magnesium stearate are more likely to be recalled for impurities and degradation. This information could be used in the future to inform the design and manufacturing of drug products, ensuring consumers receive high-quality products with a low risk of recall.

A product recall is the outcome of a careful pharmacovigilance; and it is an integral part of drug regulation. Among various reasons for product recall, the detection of unacceptable levels of carcinogenic impurities is one of the most serious concerns. The genotoxic and carcinogenic potential of N-nitrosamines raises a serious safety concern, and in September 2020, the FDA issued guidance for the pharmaceutical industry regarding the control of nitrosamines in drug products. The FDA database shows that >1400 product lots have been recalled from the market due to the presence of carcinogenic N-nitrosamine impurities at levels beyond the acceptable intake limit of 26.5 ng/day. The drugs that were present in recalled products include valsartan, irbesartan, losartan, metformin, ranitidine, and nizatidine. This perspective provides a critical account of these product recalls with an emphasis on the source and mechanism for the formation of N-nitrosamines in these products.

Background and Aims: Chemical impurities discovered in angiotensin receptor blocker (ARB) products in late 2018–2019 resulted in recalls of various products and has likely had downstream effects for patients and prescribers. The purpose of this study is to determine how the valsartan recall impacted clinical endpoints and prescribing of antihypertensives. Methods: This was a retrospective, single-center, cohort study including patients receiving recalled valsartan with essential hypertension who were mailed a recall letter on 12 March 2019. Mean blood pressure endpoints were collected 6 months before (pre-recall) and after the recall letter was mailed (post-recall). Antihypertensive medication changes and titrations were also characterized post-recall. Results: A total of 300 patients meeting eligibility criteria were included. There was no statistically significant difference in mean systolic blood pressure (SBP) or diastolic blood pressure (DBP) when pre- and post-recall blood pressures were compared (SBP: 137.2 mmHg versus 135.8 mmHg, p = 0.125; DBP: 78.6 mmHg versus 78.5 mmHg, p = 0.900). In addition, the percentage of patients with controlled blood pressure readings was similar in the pre- and post-recall timeframes (28% versus 27%, p = 0.72). A total of 33 medication changes involving valsartan occurred, with approximately one-third being changed to another ARB ( n = 11) or drug class ( n = 12). In total, 11 valsartan medication changes were specifically documented to be related to the valsartan recall. Conclusion: The results of this study indicate the valsartan recalls that occurred in 2019 did not significantly impact the clinical outcomes of the studied population. Plain Language Summary Impact of a medication recall on Veterans’ outcomes Background: Chemical impurities discovered in a class of blood pressure medications known as angiotensin receptor blockers (ARBs) occurred in late 2018–2019. This resulted in recalls of various products and has likely had downstream effects for patients and prescribers. Objective: The purpose of this study is to determine how the recall of valsartan, which is a medication in the ARB class, impacted clinical endpoints and prescribing of medications for blood pressure. Methods: This was a retrospective, single-center, cohort study including patients receiving recalled valsartan with high blood pressure who were mailed a recall letter on 12 March 2019. Blood pressure endpoints were collected 6 months before (pre-recall) and after the recall letter was mailed (post-recall). Medication changes and titrations were also characterized post-recall. Results: Three hundred patients meeting eligibility criteria were included. There was no difference found in systolic blood pressure (SBP) or diastolic blood pressure (DBP) when pre- and post-recall blood pressures were compared (SBP: 137.2 mmHg versus 135.8 mmHg; DBP: 78.6 mmHg versus 78.5 mmHg). In addition, the percent of patients with controlled blood pressure readings was similar in the pre- and post-recall timeframes (28% versus 27%). A total of 33 medication changes involving valsartan occurred, with approximately one-third being changed to another ARB ( n = 11) or drug class ( n = 12). Eleven valsartan medication changes were specifically documented to be related to the valsartan recall. Conclusions: The results of this study indicate the valsartan recalls that occurred in 2019 did not significantly impact the clinical outcomes of the studied population.

Background Information provided in an interactive way is believed to be engaging because users can actively explore the information. Yet empirical findings often contradict this assumption. Consequently, there is still little known about whether and how interactivity affects communication outcomes such as recall. Objective The aim of this study was to investigate mechanisms through which interactivity affects recall of online health information. We tested whether and how cognitive involvement, perceived active control, and cognitive load mediate the effects of interactivity on recall. In addition, we examined need for cognition and health literacy as potential moderators of the mediation effects. Given the increasing popularity of dietary supplement use, our health website focused on this topic. Methods In an online between-subjects experiment (n=983), participants were randomly assigned to control condition (no interactive features), moderate interactivity (dropdown menus), and high interactivity (dropdown menus and responsive infographics). Two weeks before the experiment, background characteristics and moderating variables were measured. During website visit, data on users’ online behavior were collected. Recall was measured postexposure. Results Participants recalled significantly less information in the moderate (mean 3.48 [SD 2.71]) and high (mean 3.52 [SD 2.64]) interactivity conditions compared with the control condition (mean 5.63 [SD 2.18]). In the mediation analysis, we found direct, negative effects of moderate (b=–2.25, 95% CI –2.59 to –1.90) and high (b=–2.16, 95% CI –2.51 to –1.81) levels of interactivity on recall as well. In the relationship between interactivity and recall, cognitive involvement had a partial negative mediation effect (moderate interactivity: b=–.20; 95% CI –0.31 to –0.10; high interactivity: b=–.21, 95% CI –0.33 to –0.10) and perceived active control had a partial positive mediation effect (moderate interactivity: b=.28, 95% CI 0.18 to 0.40; high interactivity: b=.27, 95% CI 0.16 to 0.40). Conclusions Interactivity decreased recall. In addition, through interactivity participants were less involved with the content of the information, yet they felt they had more control over the information. These effects were stronger in the high need for cognition and high health literate groups compared with their counterparts.

High numbers of drug recalls persist despite the tremendous time and effort invested by pharmaceutical organizations and regulatory bodies such as the Food and Drug Administration (FDA) to ensure the quality of safe and effective medicines for the patient. It is imperative to better understand the underlying risk factors of drug formulation-based recalls to best protect the patient from poor quality drugs. Increased knowledge of underlying factors of formulation risk can also help inform the future design and development of drugs. In this study, we used a text mining technique with Python to parse the data and examine drug recalls from the aspect of administration route, dosage form, release mechanism, market type, pharmacologic class, and excipients. Observational analysis of the recalls revealed both high- and low-risk factors for the formulation-based recalls. Higher risk, or an increased probability of a formulation-based recall, was associated with factors such as extended release mechanism, capsule dosage form, oral route of administration, and an increased number of excipients, while lower risk of formulation-based recalls was associated with other factors including the new drug application market type, immediate release mechanism, and solution dosage form. In addition, the factors did not work independently, and we observed interactions among variables. For example, the release mechanism modified the effect of market type, administration route, and dosage form. This study will help inform the future design of quality drug products by pharmaceutical organizations and assist risk-based oversight by regulatory organizations, such as FDA, to ensure patient safety.

Nitrosamines are known carcinogens which have been recently discovered in several angiotensin receptor blockers (ARBs). This led to the recall of valsartan in the United States in 2018, and afterward, the recall of other ARBs as well as unrelated medications (e.g., ranitidine). The presence of nitrosamine in ARBs was likely a result of changes in the manufacturing process, although nitrosamine contamination is believed to occur by different mechanisms with other medications. The United States Food and Drug Administration has since taken steps to identify products affected by nitrosamine contamination and mitigate this concern going forward. Despite the contamination of some drug products, studies estimate that the overall risk to patients is low enough to not necessitate changes in prescribing patterns at this time.

Beginning in July of 2018, the FDA issued a voluntary recall regarding the presence of a contaminant found in the manufacturing of valsartan. What would ensue has become a largely unprecedented sequence of alarming events since the FDA began reporting public recalls, withdrawals and safety alerts on their website in 2016. Since then, the United States has been significantly impacted by drug recalls affecting angiotensin receptor blockers. This report arms clinicians with additional guidance and provides a framework for responding appropriately to future similar incidents and includes an overview of the angiotensin receptor blockers, and their effects and safety profiles.This report includes a review of data from all pertinent clinical and scientific sources including information from the FDA's inspection documents and recall website. Additional information is provided on the specific bottles including all lot numbers, expiration dates, etc. RESULTS: The recalls/withdrawals are attributable to the presence of cancer-causing contaminants identified during the manufacturing process from drug manufacturers abroad. The root causes behind the recalls and subsequent shortage appear multifactorial, and stem to a certain extent from the outsourcing of medication manufacturing overseas and lack of quality checks and appropriate oversight.This inherent issue is not likely to resolve soon and has eroded the public trust of/in the healthcare system and the pharmaceutical industry. Patients and healthcare providers are significantly affected and should have a full understanding of the matter in order to guide appropriate response and actions.

The purpose of this review is to familiarize readers with issues surrounding angiotensin receptor blockers (ARBs) and the risk of cancer, both from the perspective of clinical trial data and the more recent concerns about impurities in certain ARB products. Approximately 45.6% of adults in the USA have hypertension. ARB-containing medications are widely used in the USA, with tens of millions of prescriptions written yearly. Whether exposure to certain ARB drug products contributes to the development of cancer has been the topic of a series of publications. Nonetheless, ARBs’ link to cancer, if any, remains inconclusive. Any mechanistic link between ARBs and cancer is poorly understood, with a variety of basic science studies suggesting that ARBs should exert a protective effect. Due to the presence of potentially carcinogenic nitrosamine impurities in certain ARB products, a series of large recalls in the USA and in countries around the world has occurred since 2018. These recalls have occurred in the context of two recent trends affecting antihypertensive drugs: nearly ubiquitous reliance on generic drugs and increased use of manufacturing facilities in China and India to supply the USA. Despite substantial efforts directed toward understanding whether ARBs have the potential to cause cancer, the available studies do not provide a consistent answer, and a causal link remains speculative. The principal conclusion must be that there is not a definitive signal for cancer associated with ARB exposure, although the possibility has not been fully excluded. The problem of nitrosamine impurities in certain ARB products (and some other drug products) is in need of further investigation, so that the risks can be mitigated by eliminating these impurities from the drug supply chain.

After N-nitrosodimethylamine, a potential carcinogen, was detected in valsartan supplied by Zhejiang Huahai Pharmaceuticals (Zhejiang, China), Health Canada issued a voluntary recall notice on July 9, 2018, for 28 generic valsartan preparations ([1][1]). The impact of drug recalls on health services

Purpose of review The current review examines the success and failures of the development of new hypnotic compounds for the human market. One of the important aspects is that one of the key present agents, propofol, is considered by many anaesthesiologists as 'the ideal'. However, all drugs have adverse or side-effects. Recent findings The last 30 years since the introduction of propofol has seen many new compounds evaluated; but as at the present time, only three agents may achieve a pivotal position in the market - fospropofol (a sedative agent which may have a role in endoscopic surgery); remimazolam (a short-acting benzodiazepine) whose development is also being focused on the sedation rather than anaesthesia market; and the pregnane steroid, alfaxalone (an anaesthetic agent first introduced in 1972, but withdrawn in 1984 because of adverse allergic reactions to the solvent, Cremophor EL) now solvented in a cyclodextrin. Summary Studies of these three agents thus far have shown that none of them has any major adverse side-effects; all have properties which warrant further clinical evaluation.

Hypertension Hot Potato A spate of recalls of angiotensin-receptor blockers highlights several issues related to the readiness of our health systems to respond to drug recalls, trust between patients and providers, uncertain drug-dose equivalences, and the regulation of drug manufacturing in the global marketplace.