Incidence Of Adverse Drug Reactions Research Articles

Safety and Effectiveness of Four-Factor Prothrombin Complex Concentrate in Special Populations with INR Below 2: A Post-Marketing Surveillance Study.

We previously conducted a prospective, observational post-marketing surveillance study to assess the safety and effectiveness of four-factor prothrombin complex concentrate (4F-PCC) for rapid vitaminK antagonist (VKA) reversal in Japanese patients. This subgroup analysis compared the safety, especially thromboembolic events (TEEs), and effectiveness of 4F-PCC by stratifying patients into two subgroups according to baseline international normalized ratio (INR) levels with < 2.0 and ≥ 2.0. Of 1271 eligible patients, 215 (17.9%) had INR < 2.0 and 987 (82.1%) had INR ≥ 2.0. Overall baseline characteristics were similar between groups; age (74.0years vs 74.0years), body mass index (22.1kg/m2 vs 21.9kg/m2), ratio of inpatients (90.2% vs 88.7%), manifested atrial fibrillation (46.0% vs 48.8%). Median INRs at baseline were 1.72 (minimum 0.92, maximum 1.99) in the INR < 2.0 group and 2.95 (2.00, 27.11) in the INR ≥ 2.0 group. The most common reason for 4F-PCC administration was intracranial hemorrhage (67.0% vs 59.5%), and lesser gastrointestinal bleeding (0.9% vs 7.5%). After 4F-PCC administration (average doses 24.5IU/kg [INR < 2.0 group] and 29.2IU/kg [INR ≥ 2.0 group]), INRs were significantly reduced to 1.21 (- 28%) and 1.31 (- 68%), respectively, and resulted in hemostasis in a similarly rapid manner. The incidences of adverse drug reactions were 3.7% in each group. TEEs occurred in 4 (1.9%) patients in the INR < 2.0 group and 11 (1.1%) patients in the INR ≥ 2.0 group and were predominantly composed of stroke, while similar rates (67.0% vs 62.9%) of bleeding events post-anticoagulant resumption were observed between groups. This study supports the favorable tolerability and efficacy of 4F-PCC regardless of baseline INR (< 2.0 or ≥ 2.0), with a prompt reduction of INR and substantial hemostatic effectiveness in the real-world setting for patients requiring urgent VKA reversal, although no indicated 4F-PCC dose for VKA reversal exists for INR < 2.0 to date.

A descriptive analysis of drug-drug interactions and corresponding adverse drug reactions in multimorbid older inpatients: findings from the SENATOR trial.

Drug-drug interactions (DDIs) are prevalent among multimorbid and polymedicated older adults and can increase the risk of adverse drug reactions (ADRs), hospital admissions, and mortality. This study describes the incidence and prevalence of 66 clinically relevant DDIs and analyses the occurrence of 12 corresponding predefined ADRs in older inpatients enrolled in the SENATOR trial. The sub-study of the SENATOR trial that involved 1537 multimorbid older inpatients, recruited from 2016 to 2018 in six academic teaching hospitals in Belgium, Iceland, Ireland, Italy, Scotland, and Spain respectively, and analysed 66 potentially clinically significant DDIs. Descriptive analysis determined DDI and corresponding ADR prevalence/incidence. At baseline (median age: 78 [72, 84], 52.8% male), the prevalence of patients with DDIs was high (50.9%), increased during hospitalisation (55.2%) and reduced to 49.7% after 12weeks. The most common DDIs were: ≥ 2potassium reducing drugs (17.1%), ≥ 3centrally acting drugs (9.0%), and SSRI + loop/thiazide diuretic (7.2%). Of all participants, one-third experienced a prevalent (36.6%)/incident (35.8%) ADR. Major serum electrolyte disturbance had the highest incidence (10.7%)/prevalence (11.5%). Incident ADRs were more common in patients with DDIs (p = 0.013). A higher prevalence of new onset falls (p = 0.013), major constipation (p = 0.004), and major serum electrolyte disturbances (p = 0.006) was observed in patients with related and thus potentially causal DDIs. Clinicians should, be aware of DDIs and the involved drug classes that can lead to an increased rate of ADRs in older multimorbid inpatients. Regularly reevaluating the appropriateness of the frequently prescribed drug classesand initiating judicious deprescribing is recommended.

Incidence and Severity of Adverse Drug Reactions in Medical Intensive Care Unit.

Adverse drug reactions (ADRs) curtail patients' quality of life by virtue of increasing therapeutic complexity and rising multimorbidity. In India, the frequency of ADRs for individual drugs and their economic burdens are rarely evaluated. This study aimed at identifying the incidence and severity of ADRs leading to hospitalization (ADRA) and occurring during a hospital stay (ADRH). The objective of this study is to evaluate the incidence the incidence and severity of ADRs in the ICU and their impact on the duration of hospitalization, along with the cost incurred to treat ADRs in the ICU. Demographic, clinical, and pharmacological data on patients admitted to the ICU were collected, analyzed and evaluated for ADRs. According to the setting analyzed, a descriptive analysis of the reactions, suspected medicines, and associated factors was undertaken. A total of 208 patients were admitted to the ICU during the study period, of which ADRA contributed 9.1% of the incidence rate and 8.1% of ADRH in 36 patients. Males had a higher incidence of ADRs than females. Patients who had ADRs had a substantially longer length of stay than those who did not. Electrolyte disturbance was the most commonly found ADR. According to the Hartwig scale and WHO-causality scale, 88.9% were moderate, and 97.2% were possible ADRs, respectively. In this study, a similar incidence rate of ADRA and ADRH was observed. The average cost for treating ADRA was higher than that for treating ADRH. As a result, identifying and preventing these reactions is critical, as they cause the patient greater suffering.

Safety and Tolerability of Initiating Sacubitril-Valsartan With Spironolactone During Hospitalization for Acute Decompensated Heart Failure.

Background: Initiation of sacubitril-valsartan and mineralocorticoid receptor antagonists (MRA) during hospitalization for acute decompensated heart failure (ADHF) may be an ideal time to optimize guideline-directed medical therapy. However, there is limited research assessing the safety of combining these agents in the hospital. Methods: This was a multi-center, retrospective, propensity-score matched cohort study performed at 7 acute-care hospitals within a large health care system. All adult patients admitted with ADHF between January 1, 2019 to December 31, 2021 who received sacubitril-valsartan with MRA (MRA group) or without MRA (non-MRA group) and had a left ventricular ejection fraction (LVEF) < 40% were included in the study. Results: 220 patients were screened during the study time frame with 179 meeting inclusion criteria. Following propensity-score matching, 50 patients in the MRA group were matched to 50 patients in the non-MRA group. The overall incidence of adverse drug reactions (ADRs) was 24% in the non-MRA group compared to 20% in the MRA group (P = .629). There was a significantly greater incidence of hyperkalemia in the MRA group (0% vs 10%; P = .022). None of the patients in the non-MRA group were readmitted within 30 days due to an ADR compared to 6% in the MRA group (P = .079). Conclusion: The addition of spironolactone to sacubitril-valsartan in the hospital setting following stabilization of ADHF did not lead to a significantly greater incidence of overall ADRs, but patients were more likely to develop hyperkalemia and there was a numerically higher incidence of 30-day readmissions due to ADRs.

Effects of pregabalin combined with tramadol/paracetamol on acute pain in patients with CT-guided puncture localization of pulmonary nodules

ObjectiveTo investigate the effects of pregabalin combined with tramadol/paracetamol on acute pain in patients with CT-guided puncture localization of pulmonary nodules. Materials and MethodsIn this randomized, placebo-controlled and single-center study, 120 patients were allocated randomly to four groups: the control group (Group P), the pregabalin-placebo group (Group BP), the tramadol/paracetamol-placebo group (Group AP), and the pregabalin-tramadol/paracetamol group (Group AB). The primary outcome was the NRS (Numerical Rating Scale) score. Other outcomes included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), pulse oxygen saturation (SpO2), the incidence of moderate to severe pain, the analgesia recovery ratio, the incidence of adverse drug reactions and patients’ satisfaction. ResultsNo significant interaction was detected between the interventions (P = 0.752). The NRS score of the Taking pregabalin group and the Taking tramadol/paracetamol group were significantly lower than those of the Not-taking pregabalin group and the Not-taking tramadol/paracetamol group respectively (P < 0.05). There was significant difference in the NRS scores among the four groups (P < 0.001). The NRS score of Group AB was significantly lower than that of Group P (P < 0.001), Group BP (P < 0.001) and Group AP (P = 0.001). At the same time, the NRS scores of Group BP (P < 0.001) and Group AP (P < 0.001) were significantly lower than those of Group P, but there was no significant difference between Group BP and Group AP (P = 1.000). The SBP, DBP, HR, the incidence of moderate to severe pain and the analgesia recovery ratio of Group AB were significantly lower than those of Group P (P < 0.05), while the SpO2 and the number of people who were very satisfied were significantly higher than those of Group P (P < 0.05). There was no significant difference in the incidence of adverse drug reactions among the four groups (P = 0.272). ConclusionsThe combination or single use of pregabalin and tramadol/paracetamol can effectively relieve the acute pain after localization. Pregabalin combined with tramadol/paracetamol has the best analgesic effect and significantly reduces the hemodynamic fluctuations, with high safety and low incidence of adverse drug reactions, which has a certain clinical popularization and application value.

Prevalence of key potentially inappropriate drugs use in pediatrics: a cross-sectional study

BackgroundAppropriate drug prescribing in the pediatric population is challenging, given this age group’s unique pharmacokinetics. This has inevitably led to a high incidence of adverse drug reactions in this population. To address this issue, the Pediatric Pharmacy Association (PPA) compiled a list of 67 drugs that are inappropriately used in the pediatric population called the Key Potentially Inappropriate Drugs “KIDs list”.AimTo estimate the prevalence of potentially inappropriate medications (PIM) use in pediatric wards based on the KIDs list criteria.MethodsA retrospective observational study was conducted and included pediatric patients who were admitted to five pediatric wards during 3 years (2019–2021). The drugs in the KIDs list were matched to the hospital formulary and 11 matched drugs were included in the study. For each individual drug, the patient’s electronic file was reviewed to determine the prescription appropriateness according to the KIDs list criteria.ResultsAmong 3,166 pediatric patients admitted to pediatric wards, a total of 415 patients received a PIM listed in the KIDs list. The mean age was 8.6 (± 4.9) years old, and 60.0% (n = 251/415) were males. The overall prevalence of PIM use was 13.0% (n = 415/3166). Among the prescribed PIM, metoclopramide was the most commonly prescribed PIM 42.8% (n = 178/415), followed by tramadol 37.6% (n = 156/415).ConclusionGiven the high prevalence of inappropriate medication use in the pediatric wards, future research on strategies and interventions should be recommended to limit the use of PIMs and provide safer alternatives for the pediatric population.

Sex differences in patterns of potentially inappropriate prescribing and adverse drug reactions in hospitalized older people: Findings from the SENATOR trial.

Older women experience more adverse drug reactions (ADRs) than older men. However, the underlying basis for this sex difference is unclear. Sex (biological status) and/or gender (sociocultural constructs) influences on patterns of inappropriate prescribing in multimorbid older adults may be one reason for this ADR sex difference. In this secondary analysis, we examined whether incident ADR sex differences could be related to concurrent sex differences in potentially inappropriate prescribing. A retrospective secondary analysis of sex differences in the prevalence of potentially inappropriate medications (PIMs), potential prescribing omissions (PPOs), and ADRs among the 1537 participants (47.2% female, median [IQR] age 78 [72-84] years) was undertaken in the SENATOR clinical trial database, conducted in six large European medical centers. We looked specifically for male/female differences relating to PIMs and PPOs (defined by STOPP/START version 2 criteria) identified within 48 h of acute hospitalization. We also assessed sex differences for ADRs identified at 14 days from admission or discharge, whichever came first. ADRs were assessed by blinded endpoint adjudication panel consensus. During hospitalization, significantly more females experienced ≥1 ADR compared to males (28% and 21%, respectively; odds ratio 1.40, 95% CI 1.10-1.78, p < 0.005). Nine of the 11 STOPP-criteria PIMs showing a significant sex difference occurred more often in females. Of the four START-criteria PPOs showing a significant sex difference, all occurred more often in females. Some sex-associated PIMs reflect higher prevalence of related conditions in older women. We conclude that specific STOPP-criteria PIMs and START-criteria PPOs were identified more frequently in older women than older men during acute hospitalization, possibly contributing to higher ADR incidence in older women. Prescribers should appreciate sex differences in exposure to potentially inappropriate prescribing and ADR risk, given the preponderance of older women over older men in most clinical settings.

Associations between Suspected Adverse Drug Reactions of HMG-CoA Reductase Inhibitors and Polypharmacology Using a National Registry Approach

Aims: The aim of this study was to explore the suspected adverse drug reaction (ADR) data of five licensed statins in the UK: atorvastatin, fluvastatin, pravastatin, rosuvastatin, and simvastatin. A secondary aim was to determine if there are any associations between the polypharmacological properties of the statins and their associated muscle-related side effects. Methods: The chemical database of bioactive molecules with drug-like properties, European Molecular Biology Laboratory (ChEMBL), was used to obtain data on the pharmacological interactions of statins with human proteins. The Medicines and Healthcare Products Regulatory Agency’s (MHRA) Yellow Card scheme was used to obtain reports of suspected ADRs from 2018 to 2022. The OpenPrescribing database was used to obtain the prescribing rates for statistical interpretation. Results: The study found no significant difference between the statins association with suspected ADRs across all organ classes (X2, p &gt; 0.05). Fluvastatin was found to have a higher incidence of ADRs/100,000 Rx across multiple system organ classes. Conclusions: No significant difference was found between the suspected ADR incidence of the statins across all system organ classes.

Polypharmacy, Drug Interaction, and Their Consequences in Terms of Adverse Drug Reaction among Adults Receiving Cancer Chemotherapy in a Tertiary Care Hospital in Central India

Abstract Background: Noncommunicable diseases in India are calculated to account for 63% of total mortality, and cancer is one of the principle causes up to 9% of total deaths. Objective: The objective of the study was t collect and analyze data about drugs taken by patients, which were prescribed by the doctor to combat side effects and to determine the extent of polypharmacy in patients on cancer chemotherapy Materials and Methods: A cross-sectional study in a Tertiary Care Hospital of Central India in the adult population by giving questionnaire forms to assess polypharmacy usage. Necessary statistical tests were applied. Results: A total of 40 indoor patients receiving cancer chemotherapy were included in the study. Many potential interactions between two chemotherapeutic drugs and chemotherapeutic and adjuvant drugs were studied. Positive adverse drug reactions encountered by patients had a strong correlation with these interactions. Conclusion: Drug interactions during chemotherapy are a common occurrence. The judicious use of cancer chemotherapeutic medicines and their combination with adjuvants are required to decrease the incidence of adverse drug reactions and increase the efficacy of chemotherapy.

Global burden of vaccine-associated hepatobiliary and gastrointestinal adverse drug reactions, 1967-2023: A comprehensive analysis of the international pharmacovigilance database.

Although previous studies have focused on hepatobiliary and gastrointestinal adverse drug reactions (ADRs) associated with COVID-19 vaccines, literature on such ADRs with other vaccines is limited, particularly on a global scale. Therefore, we aimed to investigate the global burden of vaccine-associated hepatobiliary and gastrointestinal ADRs and identify the vaccines implicated in these occurrences. This study utilized data from the World Health Organization (WHO) international pharmacovigilance database to extract reports of vaccine-associated hepatobiliary and gastrointestinal ADRs from 1967 to 2023 (total reports = 131 255 418). Through global reporting counts, reported odds ratios (ROR) with 95% confidence interval (CI), and information components (IC) with IC0.25, the study examined the association between 16 vaccines and the incidence of hepatobiliary and gastrointestinal ADRs across 156 countries. Of the 6 842 303 reports in the vaccine-associated ADRs, 10 786 reports of liver injury, 927 870 reports of gastrointestinal symptoms, 2978 reports of pancreas and bile duct injury, and 96 reports of intra-abdominal hemorrhage between 1967 and 2023 were identified. Most hepatobiliary and gastrointestinal ADRs surged after 2020, with the majority of reports attributed to COVID-19 messenger RNA (mRNA) vaccines. Hepatitis A vaccines exhibited the highest association with liver injury (ROR [95% CI]: 10.30 [9.65-10.99]; IC [IC0.25]: 3.33 [3.22]), followed by hepatitis B, typhoid, and rotavirus. Specifically, ischemic hepatitis had a significant association with both Ad5-vectored and mRNA COVID-19 vaccines. Gastrointestinal symptoms were associated with all vaccines except for tuberculosis vaccines, particularly with rotavirus (11.62 [11.45-11.80]; 3.05 [3.03]) and typhoid (11.02 [10.66-11.39]; 3.00 [2.96]). Pancreas and bile duct injury were associated with COVID-19 mRNA (1.99 [1.89-2.09]; 0.90 [0.83]), MMR (measles, mumps, and rubella), and papillomavirus vaccines. For intra-abdominal hemorrhage, inactivated whole-virus COVID-19 vaccines (3.93 [1.86-8.27]; 1.71 [0.41]) had the highest association, followed by COVID-19 mRNA (1.81 [1.42-2.29]; 0.77 [0.39]). Most of these ADRs had a short time to onset, within 1 day, and low mortality rate. Through a global scale database, the majority of ADRs occurred within 1 day, emphasizing the importance of healthcare workers' vigilant monitoring and timely management.

Knowledge, Attitude and Practice of Adverse Drug Reactions Reporting among Health Care Workers at Devdaha Medical College and Research Institute, Bhaluhi, Rupandehi

Background: Adverse drug reactions (ADRs) are unintended and noxious responses of a drug when used at normal doses in human beings. Increased incidence of ADRs is the challenge for the health care workers (HCWs) throughout the world. Therefore, we focused to assess the knowledge, attitude and practice of ADRs among HCWs at tertiary care hospital, Devdaha. Methods: This study is a cross-sectional questionnaire based descriptive study. The validated questionnaire consists of questions that contains scores to categorize knowledge and attitude among HCWs. It also documented practice adopted by the HCWs at the hospital. Out of 50 HCWs approached, 26 gave consent to participate in the study. The collected data were entered in excel and expressed in percentage or frequency. Results: All HCWs, 26 (100%), have heard about pharmacovigilance. However, only 11 (42.31%) participants have adequate knowledge regarding ADRs. In which, 22 (84.62%) expressed desire to report ADRs that they encounter during their medical practice. But, they have not reported any ADRs till date. Moreover, only 12 (46.15%) participants have positive attitude towards ADRs reporting. In case of practice, nine (34.62%) participants mentioned that the main factor that hinders them to practice reporting of ADRs is unavailability of the ADRs reporting form in the institute. Almost all (21) HCWs wanted training in pharmacovigilance. Conclusion: All HCWs are fully aware of ADRs but most of them show inadequate knowledge regarding ADRs. Over half of them lack positive attitude towards ADRs reporting and the practice of ADRs reporting is not satisfactory. Further, proper training of pharmacovigilance and form to report ADRs reporting should be provided in the hospital.

Insights into Anti-Epileptic Drug Therapy: A Cross-Sectional Comparison of Adverse Drug Reactions in Monotherapy vs. Polytherapy at a Tertiary Care Hospital

Epilepsy, a widespread neurological disorder, poses significant challenges to effective treatment, often resulting in a diminished quality of life for affected individuals. Despite its prevalence, managing epilepsy remains a complex task, as many patients experience treatment non-compliance due to adverse effects or perceived lack of efficacy. The conventional approach to treatment involves monotherapy, wherein a single anti-epileptic drug (AED) is prescribed. However, this method often leads to adverse effects necessitating dose escalation, which can ultimately prompt treatment cessation. In recent years, polytherapy has emerged as an alternative strategy for managing epilepsy. Polytherapy involves combining multiple AEDs at reduced doses to mitigate adverse effects and enhance therapeutic efficacy. While monotherapy is favored for its simplicity and historical effectiveness, there is growing interest in exploring the comparative effectiveness and safety between monotherapy and polytherapy.1 Understanding the nuances of these treatment approaches is essential for clinicians and patients alike to make informed decisions regarding epilepsy management, considering factors such as seizure control, adverse effects, and overall quality of life. This review aims to provide a comprehensive analysis of the efficacy and safety profiles of monotherapy and polytherapy in epilepsy treatment. By evaluating existing evidence and clinical outcomes, this study offers valuable insights that can guide clinicians in tailoring treatment regimens to individual patient needs, ultimately improving outcomes and enhancing the overall quality of care for individuals living with epilepsy. Results from our study have established that out of the 563 patients included in our study, about 50% have developed some sort of adverse drug reaction (ADR). Of these 282 patients that have developed an ADR, about 62% of patients were on monotherapy and the remaining 38% were on polytherapy. Establishing the fact that monotherapy is more effective than polytherapy in reducing the incidence of adverse drug reactions.

Comparative efficacy of commercial oral poly-herbal traditional Chinese medicine formulations combined with western medicine in benign prostatic hyperplasia management: a systematic review and network meta-analysis.

Background: Benign prostatic hyperplasia (BPH) is prevalent among the aging male population and often presents with distressing lower urinary tract symptoms. There is emerging evidence that commercial oral poly-herbal traditional Chinese medicine (TCM) formulation combined with Western medicine (WM) may offer enhanced therapeutic effects compared to WM alone in BPH treatment. Nevertheless, determining the optimal formulations for BPH remains controversial. We aimed to employ a network meta-analysis to compare and assess differences among commonly used and recommended poly-herbal TCM formulations outlined in the Chinese guidelines for BPH treatment, providing clinical medication recommendations and guidance. Methods: We extensively searched for RCTs of BPH patients that had oral poly-herbal TCM formulations and WM treatment, covering both English and Chinese databases up to 31 October 2023. The quality of the included studies was evaluated using the Cochrane risk-of-bias tool Version 2 (ROB2). A Bayesian network meta-analysis was performed to assess the effectiveness of various formulations, followed by sensitivity and subgroup analyses. Results: Our meta-analysis included 107 RCTs involving 11,037 patients across 16 oral poly-herbal TCM formulations. The quality of the selected studies was assessed as "Some concerns". Most formulations combined with WM demonstrated superior therapeutic efficacy compared to WM alone. For clinical effective rate, Jingui Shenqi pill (JGSQ) + WM had the highest-ranking probability (87.38%). Concerning International Prostate Symptom Score (IPSS) and maximum flow rate of urine, Guizhi Fuling capsule (GZFL) + WM was most effective (91.10% and 98.55%). Regarding the quality of life score and postvoid residual urine, Pulean tablet (PLA) + WM ranked first (86.71% and 91.81%). In controlling prostate volume, Huange capsule (HE) + WM demonstrated the highest efficacy (95.65%). Additionally, among the interventions, Lingze (LZ) + WM capsule exhibited the lowest incidence of adverse drug reactions (2.32%). Conclusion: Combining oral poly-herbal TCM formulations with WM may provide greater therapeutic benefits in BPH treatment compared to WM alone. JGSQ, GZFL, PLA, and HE emerged as promising treatment options. However, further rigorous empirical studies are essential to substantiate these findings. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=459651, CRD 42023459651.

Clinical impact of medication review and deprescribing in older inpatients: A systematic review and meta-analysis.

Polypharmacy is a primary risk factor for the prescription of potentially inappropriate medications (PIMs), drug-drug interactions (DDIs), and ultimately, adverse drug reactions (ADRs). Medication review and deprescribing represent effective strategies to simplify therapeutic regimens, minimize risks, and reduce PIM prescriptions. This systematic review and meta-analysis of experimental and observational studies aimed to evaluate the impact of different medication review and deprescribing interventions in hospitalized older patients. Experimental and observational prospective cohort studies evaluating the clinical effects of medication review and deprescribing strategies in older hospitalized patients were searched in the bibliographic databases, PubMed, Embase, and Scopus, from inception until January 8, 2024. A narrative synthesis of the results was provided, along with a meta-analysis of dichotomous data (i.e., re-hospitalizations and mortality). Overall, 21 randomized controlled trials, 7 non-randomized interventional studies, and 2 prospective cohort studies were included in the systematic review. Of these, 14 (46.7%) assessed medication appropriateness as the primary outcome, while the remaining evaluated clinical outcomes (e.g., length of hospital stay, hospital readmissions, emergency department visits, and incidence of ADRs) and/or quality of life. The meta-analysis revealed a slight but statistically significant 8% reduction in hospital readmissions (HR: 0.92; 95% CI: 0.85-0.99) following medication review and deprescribing, but no significant impact on mortality (HR: 0.98; 95% CI: 0.96-1.00). Of the 30 included studies, 21 were considered at high risk of bias, mostly due to potential deviations from intended interventions and randomization processes. The remaining nine studies had "some concerns" (eight studies) or were considered at "low" risk of bias (one study). Medication review and deprescribing are associated with potential benefits in reducing hospital readmission rates among hospitalized older patients, particularly through the reduction of PIM prescriptions. The integration of thorough medication review and deprescribing protocols in hospital settings may improve post-discharge outcomes and reduce overall healthcare costs.

Safety and Efficacy of Lemborexant in Insomnia Patients: Results of a Postmarketing Observational Study of Dayvigo® Tablets.

A prospective, postmarketing observational study was conducted to evaluate the safety and efficacy of lemborexant (LEM) tablets in daily clinical practice in Japan. No other studies of a similar size have been conducted since the marketing approval of LEM, making this the first report of its kind. Insomnia patients (n=550) administered LEM (5-10 mg daily) for the first time were enrolled. Adverse events were collected for target events (somnolence, parasomnia, narcolepsy and associated conditions, suicidal ideation and suicidal behavior). Overall improvement of insomnia symptoms was assessed by the investigator based on the patient's complaint. Subjective sleep onset latency (sSOL) and subjective total sleep time (sTST) were investigated as sleep parameters. A case report form was obtained from 539 patients. The incidence of adverse drug reactions (ADRs) was 7.65% for somnolence, 1.76% for nightmares, 0.59% for abnormal dreams, and 0.20% for sleep paralysis. No serious ADRs or ADRs related to suicidal ideation or suicidal behavior were observed. The efficacy rate at the final evaluation was 80.83%. Decreased sSOL and increased sTST were observed as assessed starting from Week 8 of treatment. Based on the results of this study, the safety result was consistent with the safety profile described in the current package insert. Efficacy results also indicated that LEM is clinically useful.

Trastuzumab and pertuzumab in combination with eribulin mesylate or a taxane as first-line chemotherapeutic treatment for HER2-positive, locally advanced or metastatic breast cancer: Results of a multicenter, randomized, non-inferiority phase 3 trial in Japan (JBCRG-M06/EMERALD).

1007 Background: Trastuzumab (H) + pertuzumab (P) + taxane is a current standard first-line therapy for recurrent or metastatic human epidermal growth factor 2–positive (HER2+) breast cancer (BC). However, taxane-induced toxicities, which reduce patient quality of life (QoL), necessitate development of less toxic but at least equally effective taxane alternatives. We investigated the non-inferiority of eribulin to taxane when used in combination with dual HER2 blockade (HP). Methods: The multicenter randomized open-label parallel-group phase 3 EMERALD trial (UMIN000027938, NCT03264547) was carried out to test the non-inferiority of eribulin + HP (study regimen) against docetaxel/paclitaxel + HP (control regimen) as first-line chemotherapeutic treatment in patients with locally advanced or metastatic HER2+ BC. The study design has been published (doi: 10.1186/s13063-020-04341-y). Patients were randomized (1:1) to receive, by intravenous infusion in a 21-day cycle, either (i) eribulin 1.4 mg/m2 on days 1 and 8, or (ii) a taxane (docetaxel 75 mg/m2 on day 1 or paclitaxel 80 mg/m2 on days 1, 8 and 15), each being administered in combination with HP on day 1. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate, overall survival (OS), QoL and safety. Non-inferiority was tested using the Cox proportional hazards model to estimate hazard ratios (HRs) for PFS events. The upper limit of acceptance of non-inferiority HR margins (1.33 and 1.25) was tested in a stepwise manner. Results: Between August 2017 and June 2021, 446 patients (224 and 222 in the study and control groups, respectively) were enrolled: median age was 56.0 (29–70) years, 244 (54.7%) had ER-positive BC, 285 (63.9%) had visceral metastasis. While 247 patients (55.4%) had de novostage 4 disease, 199 (44.6%) underwent radical surgery and 138 (30.9%) received taxanes perioperatively. Both groups’ baseline characteristics were well balanced. Median PFS was 14.0 mos in the study group and 12.9 mos in the control group (HR, 0.96; 95% CI, 0.77–1.20), confirming non-inferiority of the study regimen. Median OS was 65.3 mos in the control group but has not been reached in the study group. Incidences of adverse drug reactions including grade ≥3 febrile neutropenia, edema and diarrhea were numerically lower in the study group than in the control group (4.9% vs 8.7%, 8.5% vs 42.2% and 36.6% vs 54.1%, respectively). Conclusions: This is the first study to show non-inferiority of eribulin to taxane when used in combination with dual HER2 blockade. As a less toxic but equally effective alternative to the taxane-containing regimen, eribulin combined with HP could be first-line treatment of locally advanced or metastatic HER2+ BC. Clinical trial information: UMIN000027938 , jRCTs021180027 .

Isatuximab with pomalidomide-dexamethasone in relapsed/refractory multiple myeloma: post-marketing surveillance in Japan

This post-marketing surveillance assessed the safety and effectiveness of isatuximab plus pomalidomide and dexamethasone (Isa-Pd) for relapsed or refractory multiple myeloma (RRMM) during real-world use in Japan. Data from 211 individuals with RRMM treated with Isa-Pd in Japan between October 2020 and October 2021 were collected, with follow-up for up to 12 months after initiation of Isa-Pd or until treatment discontinuation. The incidence of adverse drug reactions (ADRs), ADRs of special interest (infusion reactions, bone marrow suppression, infections, cardiac disorders, other ADRs of Grade ≥ 3), and serious ADRs was assessed. Best overall response and overall response rate (ORR) were determined. In the safety analysis set (n = 120), ADR incidence was 57.5%. Most ADRs were hematologic, and serious ADRs occurred in 28.3%. Bone marrow suppression occurred in 46.7% of participants (19.2% serious), infusion reactions in 18.3% (6.7% serious), infections in 11.7% (8.3% serious), and a serious cardiac disorder in one participant; other Grade ≥ 3 ADRs were reported in 3.3% (1.7% serious). In the effectiveness analysis set (n = 108), the most common best overall response was very good partial response (24.1%), and ORR was 51.9%. These findings support the safety and effectiveness of Isa-Pd for RRMM in real-life settings in Japan.

Safety of sarilumab in a Japanese population with rheumatoid arthritis by age group: Data from an interim analysis of a post-marketing surveillance study.

Using data from a post-marketing surveillance, this interim subgroup analysis investigated the safety of sarilumab in younger (<65 years) and older patients (≥65 and ≥75 years) with rheumatoid arthritis. During this interim analysis, patients who were treated with sarilumab in Japan were enrolled between June 2018-2021. Data collected by 12 January 2022 were analysed, with adverse drug events monitored over 52 weeks. Of 972 patients with available data, proportion of patients aged <65 years, ≥65 years and ≥75 years were 40.8%, 59.2% and 27.8%, respectively. Most patients (95.5%) received the standard 200 mg dose of sarilumab as the initial dose. Adverse drug reactions were reported in 24.6% of patients, with serious events accounting for 6.4% of cases. No malignancy and low incidences of adverse drug reactions of special interest were reported across all age groups (<65 years, 7.8%; ≥65 years, 8.2%; ≥75 years, 8.5%). When stratified by absolute neutrophil count above and below the lower limit of normal, there were no numerical differences in incidences of serious and non-serious infections between age groups. Regardless of age, sarilumab therapy was well tolerated by patients with rheumatoid arthritis, with no new safety signals reported in this study.

Safety and Effectiveness of Ustekinumab for Crohn's Disease With Perianal Manifestations: Ad hoc Analysis Data From 1-Year Post-Marketing Surveillance Study in Japan.

Crohn's disease (CD) is an immune-mediated inflammatory disorder of the gastrointestinal tract with perianal disease being one of the challenging possible manifestations. Here, we report, an ad hoc analysis of the safety and effectiveness of 1-year use of ustekinumab (UST) for CD in patients with perianal manifestations using post-marketing surveillance (PMS) data in Japan. Among 341 patients enrolled in the PMS, 229 and 224 patients who had baseline Crohn's Disease Activity Index (CDAI) data used for evaluating perianal manifestations were included in the safety and efficacy analysis sets, respectively. Incidence of adverse drug reactions, clinical remission, the mean or its change in CDAI scores, and CDAI items were evaluated through week 52 in the presence or absence of perianal manifestations at baseline. The prevalence of perianal manifestations was also described. Comparing patients with and without baseline perianal manifestations at week 52, there was no difference in ADR incidence (9.1% [n = 66] vs. 15.3% [n = 163]), no difference in clinical remission (68.3% vs. 59.9%; P = 0.269), and decreased mean change of CDAI score (-82.9 [n = 60] vs. -68.8 [n = 137]). The proportion of patients with perianal manifestations decreased after UST treatment in both biologics-naïve patients (23.5% [n = 4/17]) and patients who had received biologics (35.0% [n = 14/40]) at week 52. In Japanese clinical practice, UST is safe and effective in CD patients with and without perianal manifestations. The therapy might be also beneficial in those with manifestations regardless of prior use of other biologics.

CYP1A2 Polymorphism and Drug Co-administration Affect the Blood Levels and Adverse Effects of Pirfenidone

Background: Mutations in metabolic enzymes and co-administration of drugs may affect the blood concentration of pirfenidone effective in pulmonary fibrosis. To provide a basis for the precise clinical use of pirfenidone, the authors analyzed the correlation between steady-state pirfenidone trough concentration and adverse drug reactions (ADRs) and examined the impact of CYP1A2*1C (rs2069514) and *1F (rs762551) variants and co-administration on pirfenidone blood concentrations and ADRs. Methods: Forty-four patients were enrolled. The blood concentration of pirfenidone was determined using high-performance liquid chromatography. CYP1A2*1C and *1F genotypes were determined using direct SNP sequencing. Additional information related to drug associations was collected to screen factors affecting drug metabolism. Results: The highest predictive value of ADRs was observed when the steady-state trough concentration of pirfenidone was 3.18 mcg·mL−1 and the area under the receiver operating characteristic curve was 0.701 (P = 0.024). The pirfenidone concentration-to-dose ratio (C/D) in CYP1A2*1F homozygous AA mutants was lower than that in C carriers (CC+AC) (1.28 ± 0.85 vs. 2.03 ± 1.28 mcg·mL−1; P = 0.036). Adverse drug reaction (ADR) incidence in the homozygous AA mutant group (28.0%) was significantly lower than that in the C carriers (CC+AC) (63.2%; P = 0.020), and ADR incidence in the A carriers (AC+AA) was considerably lower than that in the CC group (85.7%; P = 0.039). The C/D value of the combined lansoprazole/rabeprazole group was lower than that of the noncombination group (P &lt; 0.05). Conclusions: The ADR incidence was positively correlated with pirfenidone blood concentration. The CYP1A2 (rs762551) AA genotype is associated with lower pirfenidone concentrations and fewer ADRs. Lansoprazole/rabeprazole co-administration reduced pirfenidone concentrations. Randomized controlled trials should further explore personalized dosing of pirfenidone and combination therapies.