For the treatment of Covid-19 patients with remdesivir, poor renal- and liver function were both exclusion criteria in randomized clinical trials (RCTs) and contra-indication for treatment. Also, nephrotoxicity and hepatotoxicity are reported as adverse events. We retrospectively reviewed renal- and liver functions of covid-19 patients who received remdesivir in the 15 days after treatment initiation. Approximately 20% of the patient population met RCT exclusion criteria. In total, 11% of the patients had a decrease in estimated glomerular filtration rate larger than 10 ml/min/1.73m2. Also, 25% and 35% had increased alanine transaminase and aspartate transaminase levels, respectively. However, serious adverse events were limited. Therefore, contra-indications based on kidney- and liver function should not be absolute for remdesivir treatment in patients with Covid-19 if these functions are monitored regularly.

COVID-19 has an unpredictable course with substantial percentage of infected patients developing clinical deterioration and increasing health care burden. With no specific treatment or vaccination, the current search is for drugs that can limit the disease progression. Recently Fluvoxamine has been reported to have disease modifying effects in COVID-19. We suggest the hypothesis that short term routine use of Selective Serotonin Reuptake Inhibitors (SSRIs) can prevent clinical deterioration of asymptomatic or mild COVID-19 cases by the following ways: a) anti-inflammatory actions through sigma-1 agonism and reducing release of pro-inflammatory cytokines, b) anti-coagulant action by reducing platelet aggregation, c) specific antiviral and antibacterial effects, d) Immunomodulation through Serotonin pathway and anti-oxidation. The routine short term use of SSRIs can also alleviate the psychological impact of the disease. We hope our hypothesis will encourage future clinical trials to validate the routine use of SSRIs against COVID-19.

Abstract: Aims: The diagnosis of drug-induced liver injury (DILI) is relatively complex, involving a wide variety of drugs. The purpose of this study is to use algorithms to quickly screen DILI patients, count incidence rates and find risk factors. Methods: The Adverse Drug Events Active Surveillance and Assessment System-2 was used to extract the data of hospitalized patients in 2019 according to the set standards, then the RUCAM was used to evaluate patients who meet the standards. A retrospective case-control study was conducted according to suspected drugs, length of hospital stay, height and weight matched controls, and logistic regression was used to find risk factors. Results: Among the 156,570 hospitalized patients, 480 patients (499 cases) of DILI were confirmed, and the incidence of DILI was 0.32%. Anti-infective agents, antineoplastic agents, non-steroidal anti-inflammatory drugs (NASIDs) were the major category of causative drugs causing DILI, and the highest incidence of DILI caused by agent of voriconazole. The latency period and hospital stay of patients with cholestasis was relatively long. Patients with hyperlipidemia (AOR: 1.884), cardiovascular disease (AOR: 1.465), pre-existing liver disease (AOR: 1.827) and surgical history (AOR: 1.312) were likely to be risk factors for DILI. Conclusions: The incidence of DILI in hospitalized patients was uncommon (0.32%), and its pathogenic drugs were widely distributed. LiverTox’s information could assist in the diagnosis of DILI. The incidence of DILI in many drugs was seriously underestimated. It is recommended to focus on patients with hyperlipidemia, cardiovascular disease, pre-existing liver disease, and surgical history.

Anti-tumor necrosis factor alpha (TNFα) agents are effective in diseases including Crohn’s disease (CD) but may cause cytopenias. The mechanisms involved in anti-TNFα agents induced thrombocytopenia are scarce. We report a 73-year-old male with Crohn’s disease for which he currently used adalimumab, an anti-TNFα agent. He had received mesalazine and infliximab before the treatment of adalimumab. No comorbidities were present. Routine laboratory tests revealed a deep thrombocytopenia (thrombocytes 24x10*9/L) after which adalimumab was discontinued. Bleeding symptoms included cutaneous hematomas and mild epistaxis. Direct monoclonal antibody-specific immobilization of platelet antigens (MAIPA assay) revealed autoantibodies specific to glycoprotein IIb/IIIa (GPIIb/IIIa) and glycoprotein V (GPV) platelet receptors. There was no bone marrow suppression. Other causes of the thrombocytopenia were ruled out. The platelet count normalized after adalimumab discontinuation. No further interventions were required. Monitoring thrombocyte levels after initiating anti-TNFα agents is recommended, which could lead to prevention of this potential fatal phenomenon.

Bioequivalence (BE) is established between the brand drug and the generic drug to allow the linking of preclinical and clinical testing conducted on the reference listed drug. Regulatory agencies around the globe have come up with the guidance for locally acting orally inhaled drug products (OIDPs) for bioequivalence approaches. The prime intent of the present article is to compare approaches of different international regulatory authorities such as Health Canada, European Medicines Agency and the US Food and Drug Administration that have published guidance related to locally acting OIDPs. Moreover, the Central Drugs Standard Control Organisation, India, has published guidelines for bioavailability and bioequivalence studies. BE recommendations from global regulatory agencies were based on comparison for different parameters, namely inhaler device, formulation, reference product’s selection, in-vitro as well as in-vivo studies (pharmacokinetics, pharmacodynamics, and clinical studies). In the case of in-vivo studies, details about study design, dose choices, inclusion/ exclusion criteria of the subject, study period, endpoint study, and equivalence acceptance criteria were discussed in the present review article.

COVID-19 is announced as a global pandemic in 2020. The emergent outbreak of COVID-19 prompted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) keeps spreading globally. Its mortality and morbidity rate are rapidly increasing, and medication options are still limited. A patient’s immune response plays a pivotal role in the pathogenesis of COVID-19. Hyperinflammatory state may sparks significant imbalances in transporters and drug metabolizing enzymes, and subsequent alteration of drug pharmacokinetics that may result in unexpected therapeutic response. The present scenario has accounted the requirement for therapeutic opportunities to relive and overcome this pandemic. Despite the fact, the diminishing developments of COVID-19, there is no drug still approved to have significant effects with no side effect. Based on the evidence, many antiviral and anti-inflammatory drugs have been authorized by the Food and Drug Administration (FDA) to treat the COVID-19 patients even though not knowing the possible drug-drug interactions. Hydroxychloroquine is the first medicine chosen for the treatment of disease. Remdesivir, favipiravir, and molnupiravir are deemed the most hopeful antiviral agent; by improving health of infected patients. The dexamethasone saved the lives of seriously ill patients. Many randomized and controlled clinical trials are taking place to further corroborate these agent’s safety and efficacy in handling COVID-19. The current review summarizes the involvement of drug transporters and drug metabolizing enzymes for the existing drugs and gives the opinion on the potential drug-drug interactions in an inflammatory state. This may permit the individualization of these drugs thereby enhancing the safety and efficacy.

Bariatric or weight-loss surgery is a popular option for weight reduction. Depending on the surgical procedure, gastric changes like decreased transit time and volume and increased pH, decreased absorption surface in the small intestine, decreased exposure to bile acids and enterohepatic circulation, and decreased gastrointestinal transit time may be expected. In the years after bariatric surgery, patients will also substantially lose weight. As a result of these changes, the absorption, distribution, metabolism, and/or elimination of drugs may be altered. The purpose of this article is to report the general influence of bariatric surgery on oral drug absorption, and to provide guidance for dosing of commonly used or high-risk drugs in this special population. Upon oral drug administration, the time to maximum concentration is often earlier and this concentration may be higher with less consistent effects on trough concentrations and exposure. Additionally, prescription of liquid formulations to bariatric patients is supported by some reports, even though the high sugar load of these suspensions may be of concern. Studies on extended release medications result in an unaltered exposure for a substantial number of drugs. Also, studies evaluating the influence of timing after surgery show dynamic absorption profiles. Although for this group a specific advice can be proposed for many drugs, we conclude that there is insufficient evidence for general advices for oral drug therapy after bariatric surgery implying that a risk assessment on a case-by-case basis is required for each drug.

Aims To evaluate the effect of severe chronic obstructive pulmonary disease (COPD) on drug metabolism by comparing the pharmacokinetics of patients with severe COPD with healthy volunteers and using the modified ‘Inje’ drug cocktail. Methods This was a single-centre pharmacokinetic study with 12 healthy participants and 7 participants with GOLD D COPD. Midazolam 1 mg, dextromethorphan 30 mg, losartan 25 mg, omeprazole 20 mg, caffeine 130 mg, and paracetamol 1000 mg were simultaneously administered and intensive pharmacokinetic sampling was conducted over 8 hours. Drug metabolism by CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP1A2, UGT1A6 and UGT1A9 in participants with COPD were compared with phenotypes in healthy controls. Results The oral clearance (95% CI) in participants with COPD relative to controls was: midazolam 63% (60-67%), dextromethorphan 72% (40-103%), losartan 53% (52-55%), omeprazole 35% (31-39%), caffeine 52% (50-53%), and paracetamol 73% (72-74%). There was a five-fold increase in AUC for omeprazole and approximately two-fold increases for caffeine, losartan, dextromethorphan, and midazolam. The AUC of paracetamol, which is mostly glucuronidated, was increased by about 60%. Conclusion Severe COPD is associated with a clinically significant reduction in drug clearance. This may be greater for cytochrome P450 substrates than for glucuronidated drugs. This supports reduced starting doses when prescribing for patients with severe COPD.

Glove and stocking distribution rash has previously been reported with viral infections like parvovirus etc. Drug induced glove and stocking distribution rash is very rare. We hereby report such a rsh associated with vancomycin as part of pharmacovigilance.

This themed issue follows a meeting held at the Royal College of Physicians in London in November 2019 entitled “Avoiding harm from overprescribing: how to reduce waste and dependence on prescription drugs.” Here we summarize the existing challenges faced by healthcare professionals and attempt to present solutions to the expanding problem associated with a vast therapeutic arsenal and increasing medical complexity.

Levothyroxine (LT4) is frequently used as thyroid hormone replacement to treat hypothyroidism. Adverse skin reactions are not common. Lichenoid drug eruption is a one such medication-related reaction. the lesion morphology and pathology mimic lichen planus. The current case describes a 47-year-old man who presented to us with a diffuse levothyroxine-induced lichenoid drug eruption. The Naranjo adverse drug reaction probability assessment score suggested this was likely an ADR to levothyroxine. The eruption resolved after discontinuation of the medication. We also reviewed the literature on levothyroxine-associated adverse events.

Background: Bedqauiline (BDQ) is a relatively new agent for multidrug (MDR) and extremely drug resistant (XDR) TB. It is important to look for cardiac safety and the bizarre adverse reactions after initiation of the drugs from the real world studies. Methods: An observational study was conducted on the institutionalized MDR and XDR patients under the conditional access program of BDQ in India. Daily ECG, adverse events and change in laboratory values for first two weeks were recorded with mortality and serious adverse events till first three months of initiation of BDQ containing regimen. Results: Among the total of 49 patients, nausea (n=33) was the most reported side effect. Though a mean rise of QTcF (12%) was noted after 14 days, individually, both prolongations (QTcF >440 ms) and shortening (from baseline values) of QTcF were noted in 95.92% (n=47) and 89.8% (n=44) patients. Three distinct QT patterns noted in ECG were, a) initial rise then fall (n=8), b) initial fall then rise (n=9) and c) rise followed by further rise (32). There was no serious adverse event leading to drug withdrawal or mortality in the first three months. Conclusions: Prolongation of QTcF occurs in alarming numbers during first two weeks of BDQ therapy as well as shortened QT. However, BDQ was otherwise tolerated well by the real world MDR & XDR-TB patients in short term. Intensive ECG and clinical monitoring is recommended to detect possible serious implications of such ECG changes in the long term.

The antidepressant vortioxetine is primarily metabolised by the polymorphic enzyme CYP2D6. The objective of this study was to investigate the effect of CYP2D6 genotype on exposure and therapeutic failure of vortioxetine. The analysis included data from CYP2D6-genotyped patients (N=458) on vortioxetine treatment from a Norwegian therapeutic drug monitoring database. Compared with CYP2D6 normal metabolizers (NMs; N=242), vortioxetine exposure was 3.0-fold (p<0.001) increased in poor metabolizers (PMs; N=35), 1.5-fold (p<0.001) increased in intermediate metabolizers (IMs; N=173), and not significantly changed (p=0.21) in ultra-rapid metabolizers (UMs; N=8). Compared with NMs, treatment switch from vortioxetine to alternative antidepressants was 8.0-fold (95%CI: 2.0-32.3, p=0.001) more frequent among PMs and 12.7-fold (95%CI: 1.1-94.9, p=0.02) more frequent among the CYP2D6 UMs. In conclusion, CYP2D6 genotype was associated with significant changes in vortioxetine exposure and may also be associated with risk of therapeutic failure.

There is growing evidence that the clinical manifestations of COVID-19 are not just respiratory, but also gastrointestinal symptoms. The difference of organ infection should be considered. In addition, as a key molecule mediating viral infection of cells, angiotensin-converting enzyme 2 (ACE2) provides an important intervention means for the exploration of antivirus. This is particularly important as the pandemic intensifies.

Background and Purpose: There is an increasing number of evidence-based indications for pharmacogenetic (PGx) tests and a growing demand for PGx screening. We aimed to evaluate clinical relevance of a 16-gene panel test for PGx-guided pharmacotherapy. Experimental Approach: Observational cohort study of subjects tested with a PGx panel for variants of ABCB1, COMT, CYP1A2, CYP2B6, CYP3A4, CYP3A5, CYP2C9, CYP2C19, CYP2D6, CYP4F2, DPYD, OPRM1, POR, SLCO1B1, TPMT and VKORC1. Specialized clinical pharmacology consultations with PGx-guided pharmacotherapy management were supported by the PGx expert system SONOGEN XP. Study outcomes were PGx-based changes and recommendations regarding current and potential future medication. Key Results: PGx-testing was triggered by specific drug-gene pairs in 102 subjects, whereas screening was performed in 33. Based on PHARMGKB expert guidelines the 16-gene panel identified at least one “actionable” variant relevant for current or potential future medication in all 135 (100%) tested patients. Drugs that triggered PGx-testing were clopidogrel in 60, tamoxifen in 15, polypsychopharmacotherapy in 9, opioids in 7, and other in 11 patients. Among those, PGx variants resulted in clinical recommendations to change PGx-triggering drugs in 33 (32.4 %), and other current pharmacotherapy in 23 (22.5%). Conclusion and Implications: The 16-gene PGx panel detected clinically relevant variants in a high proportion of tested patients, and SONOGEN XP supported their interpretation based on latest evidence. Additional costs of panel vs. single gene tests are moderate, and the efficiency of PGx panel testing challenges traditional cost-benefit calculations for single drug-gene pairs. However, PGx-guided pharmacotherapy requires specialized consultations with interdisciplinary collaborations.

Aim：Chronic subdural hematoma (CSDH) is common in aged people, and minimally invasive surgical interventions such as burr-hole-drainage and twist-drill craniostomy are the first-line therapeutic options for this condition. However, the mortality rate among super-aged patients (over 90 years of age) with CSDH is as high as 38.4% after these surgical procedures. Atorvastatin alone or in combination with dexamethasone has been proven to be effective in eliminating CSDH. In the current study, the researchers evaluated the therapeutic efficacy of atorvastatin with or without dexamethasone on the CSDH patients over 90 years. Methods：The study attempted to treat 12 super-aged patients with primary or post-operative relapsed CSDH by using atorvastatin alone or in combination with dexamethasone. The changes in hematoma volume measured with computed tomography (CT) or magnetic resonance imaging (MRI) and the patients’ neurological improvement were monitored by activities of daily living (ADL) and modified Rankin scale (MRS) scores. Results：Treatment with atorvastatin or atorvastatin combined with low-dose dexamethasone had beneficial effects on hematoma elimination and/or symptom remission within 6 to 24 weeks in 12 super-aged patients. All of them showed complete recovery after 1~4 years of follow-up. Conclusion：The findings in this study indicate that atorvastatin with or without dexamethasone is safe and effective for the treatment for CSDH in super-aged patients.

Obesity and non-alcoholic fatty liver disease (NAFLD) are “lifestyle diseases” related to harmful habits, affecting a large portion of the global population at a steadily increasing prevalence. These disorders are inextricably associated with each other and therapeutic lifestyle changes (TLC) remain the cornerstone of their management. Nevertheless, TLC are difficult to achieve or maintain, and the use of medicines is often suggested. Different categories of medicines have been proposed, many of which are not officially licensed for these conditions. For NAFLD in particular, no drug with official indication exists so far. Thus, it is important that clinicians are aware of the quality of evidence supporting the efficacy of drugs before a decision to treat. To assist rational medical decision, in the present systematic review, we sought to evaluate the quality of evidence from phase III/IV clinical trials of major drugs currently proposed for obesity and NAFLD.

Aim. Polypharmacy may increase the prevalence of potential multidrug interactions (pMDIs), where one drug interacts with two or more other drugs, possibly amplifying the risk of a potential adverse drug event (pADE). The major goal of this study was to estimate the prevalence of amplifying pMDIs in an ambulatory cohort of older patients. Methods. Current medication lists of 22033 randomly chosen outpatients ≥50 years old were extracted from the New York Presbyterian Hospital (NYP) data warehouse. Network analysis identified patients prescribed three or more interacting drugs from their current medication lists. Potentially harmful interactions were identified from the NYP drug-drug interaction alerting system. pMDIs were considered amplifying if the interactions increased the probability of a pADE through pharmacokinetic, pharmacodynamic or conditional mechanisms. Results. pMDIs were identified in 5.1% of the medication lists; 3.4% were three-drug and 1.1% were four-drug pMDIs. The most common drugs involved were psychotropic, comprising 23.3% of the total drugs. The most common pADEs associated with the interactions were serotonin syndrome (17.2%), seizures (14.4%), prolonged QT interval (15.8%) and bleeding (14.4%). pADE amplification risk was identified in 71.8% of three-drug pMDIs when one drug interacted with two others, 97.8% when all three interacted with each other, and 93% for four-drug pMDIs. Conclusion. Our data suggest that approximately 5% of elderly ambulatory patients may be exposed to pMDIs which amplify the probability of associated adverse drug events. The recent and persistent rise in polypharmacy will likely increase the prevalence of pMDIs and potential exposure to serious adverse events.

Second-generation H1-antihistamines are generally considered to be safe. Here we describe a healthy boy who developed left-arm convulsions after repeated exposure to a dry suspension of desloratadine combined with Huatengzi granules. The boy had no family or disease history of epilepsy, convulsions, or any other drug therapy. The Naranjo Adverse Drug Reaction Probability Scale was used to determine that the convulsions were probably related to desloratadine. Our findings suggest that desloratadine (a second-generation H1-antihistamine) can cause epileptic convulsions in healthy children, and so clinicians should be vigilant of the possibility of central side effects.

With the changes of the times and the growth of public demand for medical services, the service objects, service contents and service approaches of hospital pharmacists are also changing and increasing. By summarizing the changes of hospital pharmacists' practice in hospitals and their contributions to the improvement of hospital service quality in the practice of hospital pharmaceutical care, this paper hopes that more doctors, nurses and patients can have a more in-depth understanding of the specific work of pharmacists, which, at the same time, will also provide some reference for pharmacists at home and abroad to optimize the level of pharmaceutical care. Compared with doctors and nurses, hospital pharmacists have a much more systematic and professional drug knowledge system and service concept, which can guarantee that they can undertake the responsibilities of rational use of drugs, control of medical expenditure, guarantee of efficacy, reduction of medical risks, reduction of doctors' workload, improvement of national health and so on. After years of practice and research, pharmacists have gradually realized their own value and established professional needs through hospital pharmaceutical care.

A document by Shivraj Nile, written on Authorea.

Granulocyte colony stimulating factor (G-CSF) has been widely used as a mobilizing agent to rapidly increase peripheral blood stem and progenitor cells. Limited data is available for G-CSF-associated late-onset coronary thrombosis and thrombocytosis. We report a case of a 23-year-old Chinese Han patient who presented with acute myocardial infarction and thrombocytosis after finishing bone marrow harvesting and peripheral blood stem cell collection following G-CSF treatment several days later. By using antiplatelet drugs and undergoing percutaneous transluminal coronary angioplasty, the patient’s symptoms were relieved and his platelet level decreased to normal. This is the first suspected case report of late-onset coronary thrombosis and thrombocytosis related to G-CSF. Caution should be taken for the delayed adverse reactions in patients undergoing G-CSF mobilizing.

Background and purpose: Osteoarthritis (OA) is a chronic and progressive joint disorder characterized by structural damage to one or more joints. However, drugs that could cure or at least stop the progression of this disease are still given no satisfactory outcome. The purpose of this work is to study the potential OA disease-modifying effects of atorvastatin in an experimental model of osteoarthritis and the possible underlining mechanisms if any. Experimental Approach: Seventy-six adult male Sprague-Dawley rats (250-300gms) were used throughout this study. Forty rats were used to assess the effect of atorvastatin in surgically induced OA. While 36 rats were used to assess its anti-inflammatory effect in carrageenan-induced paw edema. In the model of OA; the degree of joint stiffness was assessed by measuring the angle of knee extension besides, the histopathological changes of the OA knee joints and measurement of serum Interleukin-1beta (IL-1β), Matrix metalloproteinase-13 (MMP13), and reduced glutathione (GSH) concentration were biochemically assessed. In the carrageenan-induced paw edema, the paw thickness and pain threshold were assessed in different groups. Key Results: Atorvastatin was found to produce significant improvement of joint stiffness, the histopathological changes, a significant correction in the increased MMP13 and IL1-β, and the decreased GTH in OA rats. Also, atorvastatin showed a significant improvement in both paw thickness and pain threshold. Conclusion and Implications These results present atorvastatin as OA disease-modifying drug worse clinical trials.

COVID-19 pandemic has badly affected the world, having fatality rate ranging from 1 to 10% that differs in various countries. The median time from symptoms to clinical recovery is 6–8 weeks and to death is 2 to 8 weeks. Severity of disease and increasing mortality in COVID 19 is primarily due to presence of comorbidities like cardiovascular disease, pre-existing lungs disease, hypertension, diabetes, obesity and cancer. It is already known to us that humans show difference in drug responses because of their varied genetic make-up. Population genomics furnish an insight about genetic characteristic of a populations and it is critical in determining susceptibility, severity and natural protection against infectious diseases. Therefore, understanding the population genetic makeup may be deemed necessary to identify those who are at risk or protective from disease and develop genomics information, that would be useful in providing insight about COVID‐19 disease severity or outcomes. Some of the proposed genetic gateways in COVID 19 pathogenesis are mentioned in this review including roles of ACE2 gene, HLA gene, Chromosome 3P21.31, ABO locus, genes responsible for cytokine storm, TLR-pathway, Family Mediterranean fever and G6PD deficiency. Significant interindividual variability in response to drug therapy exists in patients. This review also evaluates the current therapeutics in COVID-19 like hydroxycholoroquine, azithromycin, RNA polymerase inhibitors, interleukin inhibitors, antivirals, ivermectin, doxycyclin and their pharmacogenomics viewpoint. Such Pharmacogenomic studies are very helpful for the physicians to choose and give accurate first line therapy for COVID 19 patients.