Aims: The objective of this retrospective cohort study was to provide an overview of the utilization of originator and biosimilar infliximab in the Netherlands. Methods: All infliximab dispensings were selected from the PHARMO In-patient Pharmacy Database from 2002-2018. Descriptive analyses were performed in order to characterise initiators and to describe switching patterns over time. Results: Overall, 3,840 patients with 61,274 infliximab dispensings were identified. 2,496 patients initiated an originator infliximab and 777 patients initiated a biosimilar infliximab. Overall, 57% of the patients was female and mean age was 43.2 years. Both originators and biosimilars were mostly prescribed by gastroenterologists, followed by internists and rheumatologists. After market authorization of the first biosimilar the proportion of new patients initiating the biosimilar increased from 39% in 2015 to 91% in 2018. Out of 704 patients eligible for switching 34% switched. Among switchers, the proportion of females was 60% and mean age at index was 45.1 years. Among non-switchers, 55% was female and mean age was 39.8 years. The median time to switch was 1.7 years and switchers were most frequently initiated on infliximab by a rheumatologist (42%), while non-switchers were most frequently initiated by a gastroenterologist (42%). Conclusions: The results of this large population-based cohort show an increase in biosimilar initiation in daily clinical practice. The number of switchers remains relatively low as non-medical switch is not encouraged in the Netherlands.

Aim: To analyze the appropriateness of DOAC dosing and determinants for under-and overdosing as well as acceptance and implementation rates of interventions by clinical pharmacists. Methods: Cross-sectional study from January 2019-December 2019 in a tertiary hospital in hospitalized patients with atrial fibrillation on DOACs (n=1688). Primary outcome was the proportion of patients with inappropriate DOAC prescribing with identification of determinants for under-and overdosing. Secondary outcomes included acceptance and implementation rates of pharmacists’ advices and determination of reasons for non-acceptance/non-implementation. Results: In 16.9% of patients, inappropriate prescribing was observed. For all DOACs considered together, body weight<60 kg(OR 0.46 [0.27-0.77]), edoxaban use(OR 0.42 [0.24-0.74]), undergoing surgery(OR 0.57 [0.37-0.87]) and being DOAC naïve(OR 0.45 [0.29-0.71]) were associated with a significantly lower odds of underdosing. Bleeding history(OR 1.86 [1.24-2.80]) and narcotic use(OR 1.67 [1.13-2.46]) were associated with a significantly higher odds for underdosing. Determinants with a significantly higher odds of overdosing were renal impairment(OR 11.29 [6.23-20.45]) and body weight<60 kg(OR 2.34 [1.42-3.85]), whereas the use of dabigatran(OR 0.24 [0.08-0.71]) and apixaban(OR 0.18 [0.10-0.32]) were associated with a significantly lower odds of overdosing compared to rivaroxaban. Physicians accepted the pharmacists’ advice in 179 cases (79.2%) consisting of 92 (51.4%) advices for underdosing, 82 (45.8%) for overdosing and 5 (2.8%) for contraindications. The advices were effectively implemented for 75 (81.5%) underdosed, 69 (84.1%) overdosed and 4 (80.0%) contraindicated cases. Conclusion: Inappropriate DOAC prescribing remains common. Clinical services led by pharmacists helps physicians to reduce the number of inadequate prescriptions for high risk medications such as DOACs.

There is a critical skills gap on the African continent in regulatory sciences, and an acknowledged need to develop a long-term strategy for training and professional development of African regulatory personnel. Capacity building programs for African regulators should link education, training and research with career development in an approach that combines an academic base and experiential learning aligned within a competency framework. A regulatory ecosystem that engages with a broad range of stakeholders will mean that expertise in the ever-expanding field of regulatory science filters into teaching and research in a symbiotic way. In this way capacity development interventions will be a collaborative approach between the learning context (academic and training institutions) and the performance context (regulatory agencies and industry), which will ultimately best serve the patients. Monitoring and evaluation of capacity development interventions will be essential to show value of investments and ultimately guide continued funding and sustainability. This paper reviews the skills and human capacity gap and outlines a staged tactical approach for Africa that builds on previous efforts to strengthen African regulatory ecosystems.

Background and Purpose: Surgery remains the first-line treatment of ovarian cancer. However, perioperative risk factors including the choice of anaesthetics may influence its recurrence after surgery. In the current study, it was hypothesised that inhalational anaesthetic sevoflurane and intravenous anaesthetic propofol might affect cancer cellular metabolism and signalling, which might interfere the malignancy of ovarian cancer cells. Experimental Approach: Cultured ovarian cancer cells were exposed to 2.5% sevoflurane or administered with 4 μg/mL propofol for 2 hours followed by 24 hours recovery. Their cell viability, proliferation, migration and invasion were assessed using cell counting kit-8, Ki-67 staining, wound healing and Transwell assay. Cellular signalling biomarkers were measured using immunofluorescent staining and/or Western blot. Cultured media were collected for 1H-NMR spectroscopy-based metabolomics analysis. Key Results: The cell viability, proliferation, migration, and invasion of ovarian cancer cells were enhanced by sevoflurane but suppressed by propofol. Sevoflurane increased the GLUT1, MPC1, GLUD1, p-Erk1/2, and HIF-1α expressions but decreased the PEDF expression. In contrast to the sevoflurane treatment, the “mirror changes” of these cellular markers were observed with propofol. Sevoflurane increased levels of isopropanol but decreased glucose and glutamine levels in the media, but the opposite changes of those metabolites were found after propofol treatment. Conclusion and Implications: These data indicated that unlike propofol, sevoflurane enhanced ovarian cancer cell metabolism and activated PEDF/Erk/HIF-1α cellular signalling pathway, suggesting that sevoflurane might have pro-tumour property but propofol might afford an anti-tumour property. The translational value of this work warrants further study.

Background Thalidomide has been reported as a promising treatment for reducing transfusion volume in adults with β-thalassemia. However, the evidence about the safety and efficacy of thalidomide on children with transfusion dependent β-thalassemia (TDT) is scarce. Methods Seventy-seven children with TDT treated with thalidomide at least for 6 months were included and retrospectively analyzed. Oral dose was started at 2.5 mg•kg-1•d-1 Blood volume for maintenance of hemoglobin above 90 g•L-1 compared with pre-treatment volume is the evaluation index for response. Results After the sixth month treatment, 51/77 (66.2%) maintained Hb over 90 g•L-1 without transfusion. Adverse events were reported in 48 (63.2%) patients.Age, sex, genotype category, dosage and transfusion interval before thalidomide treatment were not correlated to treatment response. The AUC was 0.806 for the HbFat the third month of treatment in predicting probability of major responders at the sixth month treatment. Based on Youden’s index algorithm in the ROC curve, 47.298 g•L-1 was the optimal cut-off value of the HbFat the third month of treatment in predicting major responders at the sixth month treatment, with sensitivity of 67.5%, specificity of 93.3%. Conclusions The dose of thalidomide between 2.5 mg•kg-1•d-1to 3.6 mg•kg-1•d-1 is effective in TDT children. Severe side effects are uncommon. HbF concentration of 47.298 g•L-1 at the third month is recommended as the predictor for further major responders.

There is a lack of transparency about the cost of innovation of the pharmaceutical industry even though these costs are claimed to be the major driver for high prices for medicines. This is reflected by annual reports of the major pharmaceutical firms that contain a low number of pages on innovation and its detailed costs, in comparison to pages about remuneration of executives where the detail is excessive. The Innovation/Remuneration Index (IRI) provides an objective view of the transparency priorities of a company and has the potential to shift this focus in favour of transparent and detailed information on the cost of innovation.

BACKGROUND The use of azoles for antifungal prophylaxis after familial allogeneic stem cell transplantation in children (SCT) is hindered by adverse events and drug interactions especially in children affected by sickle cell disease. Intermittent, higher dose of micafungin could be an alternative. METHODS A prospective, observational, longitudinal, single-center study was conducted between May 2015 and June 2018. The study included 30 patients between 2 and 18 years old who underwent allogeneic SCT and received prophylaxis with micafungin on alternating days after the bone marrow engraftment phase. FINDINGS Fifty transplants performed, 30 included prophylaxis against IFIs, with micafungin in an alternating pattern according to the previously described protocol. The indication for HSCT was hemoglobinopathies in 76.7%, acute leukemia in 20.0% and Fanconi anemia in 3.3%. The prophylaxis duration was 2.33 months (1.53 to 3.98). In our study, 40.0% (12/30) of the patients had acute GVHD, and 6.7% (2/30) had chronic GVHD, which prolonged the duration of alternating prophylaxis. No serious adverse effects of the use of micafungin were observed in any of the patients. There was also no breakthrough Invasive fungal infection (IFI) during alternating prophylaxis. CONCLUSION: In selected patients, micafungin was well tolerated without breakthrough IFI in our study.

Abstract: There is no available data on the secretion and concentration of ketamine and its metabolites in breastmilk. There are statements in the literature made as to the safety of the use of ketamine in lactating women, though these are unsupported. This information is pertinent for the treatment of breastfeeding women who may have depression, PTSD, postpartum depression, and other emotional difficulties and would benefit from ketamine treatment. The objective of this study was to measure the presence and concentration of ketamine in breastmilk and three of its metabolites. We have provided a longitudinal pharmacokinetic analysis of the presence of ketamine and several of its major metabolites (norketamne, dehydronorketamine and hydronorketamine) in 4 women receiving 2 different intramuscular doses of ketamine—0.5mg/kg and 1.0mg/kg. Our results demonstrate the insignificance of ketamine’s presence In breast milk after a 12-hour period of suspension. Given ketamine’s proven record of effectiveness for the treatment of depression, and its intermittent use for this purpose, our data support the safety of its administration for the treatment of postpartum depression (PPD)and other emotional disorders during a woman’s chosen period to provide breast milk to her child without significant interruption or exposure. This provides the necessary data for the study of ketamine assisted psychotherapy as a potential treatment of postpartum emotional disorders without the loss of the relationship between mother and child which breast feeding so vitally provides. We review conventional pharmacologic treatments involved in the treatment of PPD.

There is a need for anti-diabetic agents successfully targeting insulin sensitivity and treating obesity control at the same time. The aim of this first-in-human study was 1) to evaluate safety and tolerability; 2) to evaluate pharmacokinetics and 3) to assess indications of receptor engagement of single ascending doses of KBP-042, a Dual Amylin and Calcitonin Receptor Agonists (DACRA) that has shown promising preclinical data, with superior activity in terms of typical amylin-induced responses including reduction of food intake, weight loss and gluco-regulatory capacities. A randomised double-blind placebo-controlled single ascending dose study was performed with six dose levels of KBP-042 (5, 7.5, 10, 20, 20 evening and 40µg) in healthy male adults. KBP-042 or placebo was administered as a single dose after an overnight fast, followed by a standardized lunch after four hours. KBP-042 was associated with dose-dependent complaints of nausea and vomiting, with a lack of tolerability at doses of 20µg and above. Doses of 5 to 40 μg KBP-042 were behaved according to a linear pharmacokinetic profile. Indications of target receptor engagement were observed at the level of glucose control and lowering of bone resorption, compared to placebo. The results of this study showed that doses up to 40 μg were safe, although tolerability was not present at the highest doses. The study confirmed target receptor engagement at the studied doses.

Emerging data shows pregnant women with COVID-19 are at significantly higher risk of severe outcomes compared to non-pregnant women of similar age. This review discusses the invaluable insight revealed from vaccine clinical trials in women who were vaccinated and inadvertently became pregnant during the trial period. It further explores a number of clinical avenues in their management and proposes a drug development strategy in-line with clinical trials for vaccines and drug treatments for the drug development community. Little is known of the long-term effects of COVID-19 on the mother and the baby. We provide a rationale for our hypothesis that COVID-19 predisposes pregnant women to cardiovascular diseases later in life, in a similar way, to preeclampsia and may increase the risk of preeclampsia in their subsequent pregnancy. This is an ever-evolving landscape and early knowledge for healthcare providers and drug innovators is offered to ensure benefits outweigh the risks.

The use of zolpidem has been driven by the still-widespread false belief among doctors that, since zolpidem is chemically not a benzodiazepine, it cannot lead to addiction and tolerance. We would like to contribute to better highlight certain characteristics of zolpidem and its potential as a substance of abuse due to the fact that our operating unit, which is entirely dedicated to medication abuse, has described among the most numerous cases of addiction to high doses of benzodiazepines and related hypnotics. - Zolpidem was in fourth place among the 29 molecules present on the Italian market; - We believe it’s now time to drop the term “Z-drugs”: zolpidem, zopiclone e zaneplon all have different chemical structures, they bind to different receptors and have completely different abuse potentials3. In our case history, both zopiclon and zaneplon were virtually absent, albeit being commonly used in Italy; - Istvan & colleagues highlight the fact that addiciton and abuse are prevalent in samples suffering from mental illness. In our case history this hasn’t been confirmed: about half of our patients had no history of psychiatric illnesses, nor a history of addiction to illicit substances or alcohol; - Lastly, regarding zolpidem’s hazardousness, we would like to report the fact that the drug was significantly preferred by addicts with a positive ADHD test result. In conclusion, the 2000s saw solid confirmation of the effectiveness of partial agonists in the treatment of some common addictions, such as buprenorphine, varenicline, cytisine. This didn’t happen for BZs

Aims: To optimize the dosing regimen in patients with severe renal impairment based on population pharmacokinetic/pharmacodynamic (PPK/PD) analysis. Methods: The pharmacokinetics and safety of nemonoxacin was evaluated in a single-dose, open-label, nonrandomized, parallel-group study after single oral dose of 0.5 g nemonoxacin capsule in 10 patients with severe renal impairment and 10 healthy controls. Both blood and urine samples were collected within 48 hours after admission and determined the concentrations. A PPK model was built using nonlinear mixed effects modelling. The probability of target attainment (PTA) and the cumulative fraction of response (CFR) against S. Pneumoniae and S. aureus was calculated by Monte Carlo simulation. Results: The data best fitted to a two-compartment model, from which the PPK parameters were estimated, including clearance (8.55 L/h), central compartment volume (80.8 L), and peripheral compartment volume (50.6 L). The accumulative urinary excretion was 23.4±6.5% in severe renal impairment patients and 66.1±16.8% in healthy controls. PPK/PD modeling and simulation of 4 dosage regimens found that nemonoxacin 0.5 g q48h was the optimal dosing regimen in severe renal impairment patients, evidenced by higher PTA (92.7%) and CFR (>99%) at nemonoxacin MIC ≤ 1 mg/L against S. pneumoniae and S. aureus. The alternative regimens (0.25 g q24h; loading dose 0.5 g on Day 1 followed by 0.25 g q24h) were insufficient to cover the pathogens even if MIC ≤ 0.5 mg/L. Conclusion: An extended dosing interval (0.5 g q48h) may be appropriate for optimal efficacy of nemonoxacin in case of severe renal impairment.

Aim To undertake a scoping review of pharmacists’ activities in opioid medicines management in primary care settings, including those developed or led by pharmacists, or in which pharmacists were members of broader multi-disciplinary teams; and to collate the activities, models of care and settings, and reported outcomes. Methods The bibliographic databases MEDLINE, EMBASE, International Pharmaceutical Abstracts, CINAHL, SCOPUS and Web of Science were searched. Studies with quantitative evaluation and published in English were eligible. Participants were patients with any pain category or an opioid use disorder, and healthcare providers. Studies originating in hospitals or involving supply functions were not included. Screening of literature and data charting of results were undertaken by two researchers. Results The 47 studies included in the scooping review occurred in primary care settings collated into four categories: general practice or primary care clinics; healthcare organisations; community pharmacies and outreach services. Studies were primarily of opioid use in chronic, non-cancer pain. Other indications were opioid use disorder, cancer and dental pain. Pharmacist activities targeted risk-mitigation, patient and provider education and broader, strategic approaches. Patient-related outcomes included reduced opioid load, improved functionality and symptom management, enhanced access to services and medication-assisted treatments, and engagement in risk-mitigation strategies. Behaviour change of providers was demonstrated. Conclusion The review has identified the significant contribution that pharmacists working in primary care settings can make to minimise harm from opioids. Strategies implemented in isolation have the potential to further reduce adverse clinical outcomes with greater collaboration and coordination, such as opioid stewardship.

Background and Purpose: Individualized assessment of the activity of cytochrome P450 2D6 (CYP2D6), a highly variable drug-metabolizing enzyme, is performed through phenotyping during which a probe drug is administered to measure the enzyme’s activity. In order to avoid any iatrogenic harm (allergic drug reaction, dosing error) related to the probe drug, the development of non-invasive tools for real-time phenotyping of CYP2D6 could significantly contribute to the expansion of precision medicine in clinical practice. This study focuses on the identification of endogenous markers of the CYP2D6 enzyme in human biofluids using a liquid chromatography (LC)-high-resolution mass spectrometry (HRMS)-based metabolomics approach. Experimental Approach: Data from a control session were compared to data from an inhibition session. Before the latter, healthy volunteers (extensive and ultrarapid metabolizers) received a daily dose of paroxetine 20 mg over seven days. CYP2D6 genotyping and phenotyping, using single oral dose of dextromethorphan 5 mg, were also performed in all participants. Key Results: In CYP2D6 extensive and ultrarapid metabolizers (n = 37), mean relative intensities of five features were significantly reduced during the inhibition session compared to the control session (fold changes ≤ 0.67, FDR-adjusted P < 0.0001). Furthermore, mean relative intensities of these candidates were significantly higher in the CYP2D6 extensive-ultrarapid metabolizer group (n = 37) compared to the poor metabolizer group (n = 6) (fold changes ≤ 0.67, P < 0.0001). Conclusion and Implications: The applied untargeted metabolomics strategy was able to identify five CYP2D6 endogenous metabolites, a promising discovery for non-invasive phenotyping and personalised medicine.

Aim The present study aimed to evaluate the effect of quercetin in COVID-19 treatment. Methods This was a single-centre, prospective randomised controlled cohort study. Routine care versus QCB (quercetin, vitamin C, bromelain) supplementation was compared between 447 patients with at least one chronic disease and moderate-to-severe respiratory symptoms. Demographic features, signs, laboratory results and drug administration data of patients were recorded. The endpoint was that QCB supplementation was continued throughout the follow-up period from study baseline to discharge, intubation, or death. Results The most common complaints at presentation were fatigue (62.4%), cough (61.1%), anorexia (57%), thirst (53.7%), respiratory distress (51%) and chills (48.3%). The decrease in CRP, procalcitonin and ferritin levels was higher in the QCB group (all Ps were <0.05). In the QCB group, an increase in platelet and lymphocyte counts were higher (all Ps were <0.05). QCB did not reduce the risk of events during follow-up. Adjustments for statistically significant parameters, including the lung stage, use of favipiravir and presence of comorbidity did not change the results. While there was no difference between the groups in terms of event frequency, QCB group had more advanced pulmonary findings. QCB supplement is shown to have a positive effect on laboratory recovery. Conclusion We suggest that suboptimal bioavailability of QCB may explain this. So, we conclude that if a stable blood level can be achieved for QCB, it may make a difference in the treatment of COVID-19.

Aims: It is generally accepted that geriatric patients are more sensitive to propofol than adults; thus, a dose-adjusted propofol is recommended for these patients during the induction of anesthesia. However, for patients aged 75 years and over, established guidelines do not provide dose references for the anesthesiologists. To this end, we observed 80 surgical patients (female 39, male 41, American Society of Anesthesiologists physical status score Ⅰ ~ Ⅱ) to access the appropriate dose of propofol for inducing loss of consciousness (LOC). Methods: Patients were subdivided into group A (20 patients, 45~64 yr), group B (20 patients, 65~74 yr), group C (20 patients, 75~84 yr), and group D (20 patients, ≥ 85 yr). All patients received propofol (at a rate of 0.3 mg/kg/min) alone for inducing LOC, which was defined by loss of both eyelash reflex and verbal response. Results: Compared with group A, the propofol requirement for LOC in Group B, C and D decreased by 14.8%, 25.2% and 38.5%, respectively. Bivariate linear correlation analysis showed that propofol requirement was negatively correlated with age. After adjusting for potential confounders, age was still an independent factor affecting propofol requirement. Conclusion: The propofol requirement for inducing LOC decreased significantly in elderly patients. We demonstrated that age was an independent factor impacting propofol requirement for LOC during the induction of general anesthesia, implying that the propofol dose for anesthesia induction should be further reduced in elderly surgical patients, especially those aged 75 years and over.

COVID-19 is a complex disease and many difficulties are faced today especially in the proper choice of pharmacological treatments. The role of antiviral agents for COVID-19 is still being investigated. The evidence for immunomodulatory and anti-inflammatory drugs is quite conflicting, while the use of corticosteroids is supported by robust evidence. The use of heparins in hospitalized critically ill patients is preferred over other anticoagulants. Lastly, conflicting data were found regarding to the use of convalescent plasma and vitamin D. According to data shared by the WHO, many vaccines are under phase 3 clinical trials and some of them already received the marketing approval in EU countries and in the US. In conclusion, drugs repurposing has represented the main approach recently used in the treatment of patients with COVID-19. At this moment, the analysis of efficacy and safety data of drugs and vaccines used in real life context is strongly needed.

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.