A Nationwide Survey of mRNA COVID-19 Vaccinee's Experiences on Adverse Events and Its Associated Factors.

BACKGROUND: Although coronavirus disease 2019 (COVID-19) vaccines have been distributed worldwide under emergency use authorization, the real-world safety profiles of mRNA vaccines still need to be clearly defined. We aimed to identify the overall incidence and factors associated with adverse events (AEs) following mRNA COVID-19 vaccination. METHODS: We conducted web-based survey from December 2 to 10 in 2021 with a 2,849 nationwide sampled panel. Study participants were individuals who had elapsed at least two-weeks after completing two dosing schedules of COVID-19 vaccination aged between 18-49 years. We weighted the participants to represent the Korean population. The outcome was the overall incidence of AEs following mRNA COVID-19 vaccination and associated factors. We estimated the weighted odds ratios (ORs) using multivariable logistic regression models to identify the factors associated with AEs. RESULTS: Of the 2,849 participants (median [interquartile range] age, 35 [27-42] years; 51.6% male), 90.8% (n = 2,582) for the first dose and 88.7% (n = 2,849) for the second dose reported AEs, and 3.3% and 4.3% reported severe AEs, respectively. Occurrence of AEs was more prevalent in mRNA-1273 (OR, 2.06; 95% confidence interval [CI], 1.59-2.67 vs. BNT162b2), female sex (1.88; 1.52-2.32), and those with dermatologic diseases (2.51; 1.32-4.77). History of serious allergic reactions (1.96; 1.06-3.64) and anticoagulant medication use (4.72; 1.92-11.6) were associated with severe AEs. CONCLUSION: Approximately 90% of participants reported AEs following mRNA COVID-19 vaccination. Substantial factors, including vaccine type (mRNA-1273), female sex, and dermatologic diseases were associated with AEs. Our findings could aid policymakers in establishing vaccination strategies tailored to those potentially susceptible to AEs.

Ocular Adverse Events after Coronavirus Disease 2019 mRNA Vaccination: Matched Cohort and Self-Controlled Case Series Studies Using a Large Database.

PURPOSE: To investigate the risk of ocular adverse events after Coronavirus Disease 2019 (COVID-19) mRNA vaccination. DESIGN: Matched cohort and self-controlled case series (SCCS) studies. PARTICIPANTS: We used a population-based database of medical claims and vaccination records in a large Japanese city. In the matched cohort study, we identified individuals who received COVID-19 vaccination (BNT162b2) from February 2021 to September 2021. One control was selected from nonvaccinated individuals by matching time, date of birth, sex, Charlson comorbidity index, and the enrollment period for health insurance. In the SCCS study, we analyzed individuals who developed ocular adverse events. METHODS: In the matched cohort study, we applied the Kaplan-Meier estimator to estimate the cumulative incidence of ocular adverse events over 21 days after the first dose and 84 days after the second dose. In the SCCS method, we used conditional Poisson regression to estimate the incidence rate ratio (IRR) of ocular adverse events during the risk periods (0-21 days after the first dose and 0-84 days after the second dose) compared with the remaining periods. MAIN OUTCOME MEASURES: Composite outcome of uveitis, scleritis, retinal vein occlusion (RVO), and optic neuritis. RESULTS: There were 99 718 pairs eligible for the matched cohort study after the first dose (mean age, 69.3 years; male, 44%). The vaccinated and control groups developed 29 and 21 events, respectively, over 21 days after the first dose, and 79 and 28 events, respectively, over 84 days after the second dose. The differences in cumulative incidence (reference, the control group) were 2.9 (95% confidence interval, -14.5 to 19.1) events/100 000 persons and 51.3 (16.2-84.3) events/100 000 persons, respectively, for the first and second doses. The SCCS study showed the IRRs of 0.89 (0.62-1.28) and 0.89 (0.71-1.11) for the first and second doses, respectively. CONCLUSIONS: The matched cohort analysis found an increased risk for the composite outcome after the second dose; however, the SCCS analysis showed no increased risk. Considering that the SCCS can cancel out time-invariant confounders, the current results suggest that COVID-19 vaccination is unlikely to causally increase the risk of ocular adverse events. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Oral side effects of COVID-19 vaccines in 32 European countries: Analysis of EudraVigilance reports.

The recent reports of oral side effects (SEs) following COVID-19 vaccination warrant further investigation into their prevalence, severity, and aetiology. This study was conducted to synthesize the first-ever population-level evidence about oral SEs of COVID-19 vaccines in Europe. The European Union Drug Regulating Authorities Pharmacovigilance (EudraVigilance) database was accessed in August 2022 to extract summary data of all potential oral SEs reported after COVID-19 vaccination. The data were reported descriptively and cross-tabulated to facilitate sub-group analysis per vaccine type, sex, and age group. Dysgeusia was the most commonly reported oral SE (0.381 case per each 100 received reports), followed by oral paraesthesia (0.315%), ageusia (0.296%), lip swelling (0.243%), dry mouth (0.215%), oral hypoaesthesia (0.210%), swollen tongue (0.207%), and taste disorder (0.173%). Females had significantly (Sig. < 0.001) a higher prevalence of all most common (top 20) oral SEs, except for salivary hypersecretion, which was equally prevalent among females and males. The present study revealed a low prevalence of oral SEs, with taste-related, other sensory and anaphylactic SEs being the most common SEs in Europe, similar to what was found earlier among the US population. Future studies should explore the potential risk factors of oral sensory and anaphylactic SEs to verify whether they are causally linked to COVID-19 vaccines.

A severe case of rhabdomyolysis after Moderna mRNA anti-COVID-19 vaccine with a literature review.

The identification of rhabdomyolysis as a potential fatal adverse reaction to recent COVID-19 vaccines is essential. As the symptoms of rhabdomyolysis are not specific, the threshold to actively search for this complication should be low.

Pay attention to the medication safety of patients during the period of coronavirus disease 2019 epidemic prevention.

The coronavirus disease 2019 (COVID-19) epidemic is facing the most critical situation. As of January 11, 2021, there have been nearly 90 million confirmed cases worldwide and nearly 2 million deaths. The local epidemic situation in China is sporadic and locally clustered, and the situation of epidemic prevention is difficult and complicated. In this situation, there are many problems in medication safety of patients, such as safety issues in off-label medication and compassionate medication of COVID-19 treatment, safety problems in the combination use of drugs for COVID-19 and drugs for other diseases, monitoring of adverse drug reactions in COVID-19 treatment, the safety issues in self-purchased drugs for prevention and treatment of COVID-19, and the medication safety in patients with other diseases during the epidemic. Therefore, it is necessary to pay more attention to the medication safety of patients to fight the epidemic scientifically and to win a greater victory in the fight against the COVID-19 epidemic at a smaller price.Copyright © 2021 Chinese Medical Association

Give full play to the role of pharmacists in the safety management of direct oral anticoagulants.

Direct oral anticoagulants (DOACs) are recommended as first-line therapy in patients with atrial fibrillation and venous thromboembolic diseases in relevant guidelines at home and abroad. Compared with warfarin, DOACs have relatively fixed dose, fewer drug interactions, and no need of routine therapeutic drug monitoring in clinic. DOACs bring much convenience to anticoagulant therapy, but they also raise a series of new medication safety challenges. Pharmacists should ensure the safe use of DOAC through improving corresponding pharmaceutical care mechanism, such as assisting doctors to improve the suitability of dose in prescription, standardizing laboratory monitoring process, setting up early warning of potential drug interaction, and strengthening anticoagulant conversion and perioperative anticoagulant therapy management. In the post-coronavirus disease 2019 era, incorporating DOACs into the standardized manage- ment at anticoagulation clinics is an important work extension of the traditional anticoagulation clinics and may reduce the risk of exposure to the novel coronavirus. In addition, considering the limit in labour and work energy of clinical pharmacists, the application of DOAC-related clinical decision support system may help improve the appropriateness of prescription and reduce the adverse drug events.Copyright © 2020 Chinese Medical Journals Publishing House Co.Ltd. All rights reserved.

Incidence and influencing factors of favipiravir-associated serum uric acid elevation in patients with coronavirus disease 2019.

Objective To explore the occurrence and influencing factors of serum uric acid elevation in patients with coronavirus disease 2019 (COVID-19) treated with favipiravir. Methods Medical records of patients with COVID-19 who were hospitalized in Beijing Ditan Hospital between June 1, 2020 and June 30, 2021 and treated with the 5- or 10-day regimen of favipiravir were collected and retrospectively analyzed. After favipiravir withdrawal, if the elevation in serum uric acid was >=30% of baseline level, it was defined as serum uric acid elevation. Then patients were divided into serum uric acid elevation group and non-serum uric acid elevation group. The clinical characteristics such as gender, age, body mass index, comorbidities, smoking and drinking behavior, COVID-19 grade, favipiravir regimen, and serum uric acid level and renal function before treatment in patients between the 2 groups were compared. Influencing factors of favipiravir-associated serum uric acid elevation was analyzed using multivariate logistic regression method. Results A total of 179 patients were included in the analysis, including 104 (58.1%) males and 75 (41.9%) females, aged from 19 to 70 years with a median age of 43 years. The level of serum uric acid in 179 patients after favipiravir treatment was significantly higher than before [(451+/-119) mumol/L vs. (332+/-94) mumol/L, P<0.001]. The change rate of serum uric acid from baseline level ranged from -57.1% to 157.8% with the median of 38.6%. The elevation in serum uric acid of >= 30% of baseline level occurred in 108 (60.3%) patients. The incidences of serum uric acid elevation in patients treated with 5-day and 10-day regi- mens of favipiravir were 46.8% (36/77) and 70.6% (72/102), respectively, and the difference between them was significant (P=0.001). Multivariate logistic regression analysis showed that body mass index 24.0 to <28.0 kg/m2 (OR=3.109, 95%CI: 1.209-7.994, P=0.019) and 10-day regimen of favipiravir (OR=3.017, 95%CI: 1.526-5.964, P=0.001) were independent risk factors for favipiravir-associated serum uric acid elevation. Conclusions More than half of COVID-19 patients treated with favipiravir can develop serum uric acid elevation. Overweight and 10-day regimen of favipiravir are independent risk factors for serum uric acid elevation in patients.Copyright © 2022 Adverse Drug Reactions Journal.

Clinical observation on safety of chloroquine phosphate treatment in patients with novel coronavirus pneumonia.

Objective: To explore the safety of chloroquine phosphate treatment in patients with novel coronavirus pneumonia (COVID-19) and provide references for clinical safety medication. Method(s): Active monitoring for adverse events (AE) was carried out in the Third People's Hospital of Shenzhen from February to March 2020 during the treatment with chloroquine phosphate in patients with COVID-19. The causal relationship between AE and chloroquine phosphate was evaluated. Result(s): A total of 33 patients were entered in the study, including 16 males and 17 females, aged (43+/-13) years. The clinical types of COVID-19 in 26 patients (78.8%) were mild, in 7 patients (21.2%) were common. There were 7 patients (21.2%) with basic diseases, including 6 with hypertension and 1 with hypothyroidism. The treatment course of chloroquine phosphate was (8+/-3) days. During the treatment, a total of 28 cases of AE in 24 (72.7%) of the 33 patients which were probably or possibly related to chloroquine phosphate were detected. The clinical manifestations of AE included abnormal liver function (8/33, 24.2%), gastrointestinal reactions (8/33, 24.2%), neuropsychiatric system reactions (8/33, 24.2%), cardiovascular system reactions (5/33, 15.2%), eye and vision abnormality (2/33, 6.1%), and skin injury (1/33, 3.0%). The severity of AE was grade 1 or grade 2. After drug withdrawal or symptomatic treatments, all the patients' symptoms were improved and the laboratory tests results returned to normal. Conclusion(s): The adverse effects of chloroquine phosphate in the treatment of patients with COVID-19 are mild, but it is still necessary to strengthen the monitoring.Copyright © 2020 by the Chinese Medical Association.

Effectiveness of antithrombotic prophylaxis in hospitalised patients with SARS-CoV-2 infection.

BACKGROUND: Antithrombotic prophylaxis in hospitalised patients with SARS-CoV-2 acute infection has increased. Currently, most of the evidence relates to patients in intensive care units; however, there is little information on patients admitted to hospital wards and there is no consensus protocol on thromboprophylaxis during admission and after discharge. OBJECTIVE: To assess the effectiveness of antithrombotic prophylaxis in patients admitted with COVID-19 and 30 days after discharge. METHOD: A prospective observational study was conducted of patients admitted with COVID-19 in which the hospital thromboprophylaxis protocol was applied, classifying the patients as having a standard or high risk of thrombosis. Pharmacists performed a daily follow-up and actively intervened during admission and at discharge. The main outcome measure was the global incidence of symptomatic venous thromboembolism (VTE) related to hospitalisation. RESULTS: A total of 113 patients were included, 98.23% of whom were admitted to a hospital ward. The incidence of hospital-acquired VTE was 1.77%. In 75.22% of the subjects, thromboprophylaxis was adjusted to the protocol during admission. A total of 23 pharmaceutical interventions were conducted, with an adherence of 52.17%. At discharge, 94.28% of the patients who had no haemorrhage and ≥4 points on the Padua Prediction Score required thromboprophylaxis, aligning with the protocol. The global incidence of haemorrhagic events during the follow-up period was 0.88%. CONCLUSION: The incidence of hospital-acquired VTE was lower than that described in the literature. Although it cannot be certain that it is directly related to the instituted protocol, the data can show that the management of prevention of VTE is being optimally performed at the hospital. Long-term studies are needed to evaluate the incidence after discharge, as well as to agree on a specific protocol in the COVID-19 population for the prevention of these events during hospitalisation and post-discharge.

Treatment of high-risk bleeding with susoctocog alfa in a patient with acquired haemophilia A and a nosocomial severe acute respiratory syndrome coronavirus 2 infection.

We report the case of a man in his early 70s with idiopathic acquired haemophilia A and persistent high-titre type II inhibitors on immunosuppressive treatment to eradicate the inhibitor. As complications, he had a nosocomial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which caused severe pneumonia and an explosive inflammatory reaction that required tocilizumab and remdesivir treatment, and a high-risk retroperitoneal haematoma. Recombinant porcine factor VIII, susoctocog alfa, was requested from the Pharmacy Service in view of the extreme risk of thromboembolism resulting from the concomitant inflammatory storm caused by SARS-CoV-2. Improvement in the SARS-CoV-2 infection made it possible to complete the immunosuppressive treatment with rituximab. The patient was discharged with mycophenolate mofetil as immunosuppressive treatment after 89 days in hospital and 22 days of treatment with susoctocog alfa. His SARS-CoV-2 infection resolved and the haematoma evolved favourably.

Analysis on occurrence and risk factors of drug-induced liver injury in patients with novel coronavirus pneumonia.

Objective: To analyze the occurrence and risk factors of drug-induced liver injury (DILI) in patients with novel coronavirus pneumonia (COVID-19). Method(s): The medical records of patients with COVID-19 who were discharged from the First Hospital of Changsha from January 15 to March 7, 2020 were collected and the patients were divided into the DILI group and the non-DILI group based on DILI diagnostic criteria. Basic information of patients in the 2 groups including gender, age, underlying diseases, classification of COVID-19, liver function test results on admission and after medication, drug use, time to DILI onset after medication, and treatments and outcomes of DILI were recorded and compared. The incidence of DILI in patients with COVID-19 was calculated, and the factors whose P<0.05 in inter-group comparison were included in the multivariate logistic regression analysis to calculate the odds ratio (OR) and95% confidence interval (CI). Result(s): A total of 203 discharged patients with COVID-19 met the inclusion criteria. Of them, 36 patients developed DILI, the incidence was 17.73%. Between the DILI group and the non-DILI group (167 patients), the differences were statistically significant in gender distribution, proportion of patients with underlying diseases such as hypertension, fatty liver, and cholelithiasis, clinical classification of COVID-19, and the kinds of drug use (P<0.05 for all), but not statistically significant in levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBil) on admission (P>0.05 for all). The levels of ALT and AST in patients in the DILI group after medication were higher than those before medication, and the differences were statistically significant (P<0.001 for all). The median time for time to DILI onset after medication was 8 (6, 11) days and none of the patients had obvious clinical signs and symptoms. After the occurrence of DILI, 16 patients stopped the suspicious drugs and received liver-protective treatments, 6 patients only stopped the suspicious drug without additional treatments, and 14 patients received liver-protective treatments without drug withdrawal. Among the 36 patients in the DILI group, liver function were improved in 34 patients but did not returned to normal in 2 patients when they were discharged from the hospital. Multivariate logistic regression analysis showed that male (OR=3.939, 95%CI: 1.426-10.883, P=0.008), being severe and critical in clinical classification (OR=6.433, 95%CI: 2.411-17.162, P<0.001), fatty liver (OR=3.815, 95%CI: 1.298-11.215, P=0.015), cholelithiasis (OR=16.347, 95%CI: 1.267-210.990, P=0.032), and the kinds of drug use >8 (OR=10.181, 95%CI: 3.606-28.744, P<0.001) were the independent risk factors of DILI in patients with COVID-19. Conclusion(s): The incidence of DILI in COVID-19 patients discharged from the First Hospital of Changsha is 17.73%. Male, being severe and critical in clinical classification of COVID-19, fatty liver, cholelithiasis, and the kinds of drug use >8 are the independent risk factors for DILI patients with COVID-19.Copyright © 2020 by the Chinese Medical Association.

Molnupiravir provides little benefit in vaccinated adults with COVID-19.

Overview of: Butler CC, Hobbs FDR, Gbinigie OA, et al Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial. Lancet 2023;401:281-93.

Electronic monitoring of potential adverse drug events related to lopinavir/ritonavir and hydroxychloroquine during the first wave of COVID-19.

During Switzerland's first wave of COVID-19, clinical pharmacy activities during medical rounds in Geneva University Hospitals were replaced by targeted remote interventions. We describe using the electronic PharmaCheck system to screen high-risk situations of adverse drug events (ADEs), particularly targeting prescriptions of lopinavir/ritonavir (LPVr) and hydroxychloroquine (HCQ) in the presence of contraindications or prescriptions outside institutional guidelines. Of 416 patients receiving LPVr and/or HCQ, 182 alerts were triggered for 164 (39.4%) patients. The main associated risk factors of ADEs were drug-drug interactions, QTc interval prolongation, electrolyte disorder and inadequate LPVr dosage. Therapeutic optimisation recommended by a pharmacist or proposals for additional monitoring were accepted in 80% (n=36) of cases. Combined with pharmacist contextualisation to the clinical context, PharmaCheck made it possible to successfully adapt clinical pharmacist activities by switching from a global to a targeted analysis mode in an emergency context.

Signal detection of COVID-19 vaccines adverse events using spontaneous reports from South Korea.

PURPOSE: Studies on the detection of COVID-19 vaccine signals in South Korea are insufficient. Therefore, to investigate adverse events (AEs) that might be associated with COVID-19 vaccines, signals were detected using spontaneous reports from South Korea. We compared the signals with the vaccine insert lists of the regulators in the four countries. METHODS: Spontaneous reports from 62 sites were collected by the National Medical Center between January 2013 and May 2022. A descriptive analysis of AEs associated with COVID-19 vaccines (Pfizer, Moderna, AstraZeneca, and Janssen) was performed, and the proportional reporting ratio, reporting odds ratio, and information component were calculated. We performed five analyses, with five cases and one control group. RESULTS: During the study period, 68 355 cases were reported, of which 12 485 were COVID-19 vaccine AEs. Injection site pain (2198 cases, 17.6%), myalgia (1552 cases, 12.4%), headache (1145 cases, 9.2%), pyrexia (1003 cases, 8.0%), and fatigue (735 cases, 5.9%) were frequently reported. When comparing all COVID-19 vaccines with other viral vaccines, 20 signals were detected, of which cachexia, dyspepsia, abdominal discomfort, and mood swings were not listed on the vaccine inserts in all four countries. Overall, 20, 17, 29, and 9 signals were detected in vaccines developed by Pfizer, Moderna, AstraZeneca, and Janssen, respectively. CONCLUSIONS: Based on a disproportionate analysis of COVID-19 vaccine AEs using spontaneous reports from South Korea, different signals were detected for each vaccine manufacturer.

Complications of COVID-19 Vaccines during Pregnancy; a Systematic Review.

Introduction: Rare serious complications have been documented after COVID-19 vaccination as clinical research proceeded and new target populations, such as children and pregnant women, were included. In this study, we attempted to review the literature relevant to pregnancy complications and maternal outcomes of COVID-19 immunization in pregnant women. . Methods: We searched the databases of PubMed, Scopus, Cochrane, and Web of Science on 31 August 2022. The records were downloaded and underwent a two-step screening; 1) title/abstract and then 2) full-text screening to identify the eligible studies. We included English original studies that evaluated the adverse effects of COVID-19 vaccines during pregnancy. Information such as the type of study, geographical location, type of vaccine injected, gestational age, maternal underlying diseases, and complications following the vaccination were extracted into pre-designed tables. Results: According to the findings of included studies, in most of them vaccination had a positive impact and no negative effects were observed. Also, no medical history was reported in 11 articles, and pregnant women had no underlying diseases. Some serious adverse events were reported after vaccination, including miscarriage, paresthesia, uterine contraction, vaginal bleeding, preterm birth, major congenital anomalies, intrauterine growth restriction, and seizure. . Conclusion: Because of limited data availability and the cross-sectional design of most studies, we could neither infer causation between vaccines and incidence of adverse effects nor comment with certainty about any possible adverse outcome of COVID-19 vaccines in vaccinated pregnant women. Consequently, more longitudinal and experimental studies are needed to define the exact adverse effects of COVID-19 vaccines in pregnant women.

Adverse events following first and second dose COVID-19 vaccination in England, October 2020 to September 2021: a national vaccine surveillance platform self-controlled case series study.

BackgroundPost-authorisation vaccine safety surveillance is well established for reporting common adverse events of interest (AEIs) following influenza vaccines, but not for COVID-19 vaccines.AimTo estimate the incidence of AEIs presenting to primary care following COVID-19 vaccination in England, and report safety profile differences between vaccine brands.MethodsWe used a self-controlled case series design to estimate relative incidence (RI) of AEIs reported to the national sentinel network, the Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub. We compared AEIs (overall and by clinical category) 7 days pre- and post-vaccination to background levels between 1 October 2020 and 12 September 2021.ResultsWithin 7,952,861 records, 781,200 individuals (9.82%) presented to general practice with 1,482,273 AEIs, 4.85% within 7 days post-vaccination. Overall, medically attended AEIs decreased post-vaccination against background levels. There was a 3-7% decrease in incidence within 7 days after both doses of Comirnaty (RI: 0.93; 95% CI: 0.91-0.94 and RI: 0.96; 95% CI: 0.94-0.98, respectively) and Vaxzevria (RI: 0.97; 95% CI: 0.95-0.98). A 20% increase was observed after one dose of Spikevax (RI: 1.20; 95% CI: 1.00-1.44). Fewer AEIs were reported as age increased. Types of AEIs, e.g. increased neurological and psychiatric conditions, varied between brands following two doses of Comirnaty (RI: 1.41; 95% CI: 1.28-1.56) and Vaxzevria (RI: 1.07; 95% CI: 0.97-1.78).ConclusionCOVID-19 vaccines are associated with a small decrease in medically attended AEI incidence. Sentinel networks could routinely report common AEI rates, contributing to reporting vaccine safety.

Management of nirmatrelvir/ritonavir and tacrolimus interaction in kidney transplant recipients infected by COVID-19: a three-case series.

OBJECTIVES: Nirmatrelvir/ritonavir may cause a clinically relevant drug-drug interaction (DDI) with immunosuppressive drugs, such as tacrolimus, which may condition the use of this antiviral in transplant patients. We aimed to describe the management of this interaction. METHODS: Descriptive study in which renal transplant patients in treatment with nirmatrelvir/ritonavir and tacrolimus were included. They suspended tacrolimus the day before starting the antiviral treatment, and the decision to restart it was made based on their tacrolimus blood levels. Main variables studied to measure this DDI were tacrolimus blood concentration, dose adjustment and serum creatinine. RESULTS: Three patients were included. During the study, tacrolimus levels elevation did not have repercussion in the serum creatinine, that remained stable in all patients. No patient required hospitalisation or showed signs of rejection. CONCLUSIONS: Our experience provides further evidence that this interaction should not be a contraindication to treatment with nirmatrelvir/ritonavir, and can be managed with close monitoring of tacrolimus levels.

Neutropenia after the coadministration of clozapine and nirmatrelvir-ritonavir in a patient with SARS-CoV-2 infection: A case report with a literature review.

Background: Schizophrenia is considered one of the major risk factors for mortality from SARS-CoV-2 infection. Early antiviral treatment is important to decrease the risk of mortality. Currently, Paxlovid (nirmatrelvir-ritonavir) has been widely used in SARS-CoV-2 patients with risk factors. However, drug-drug interactions with anti-psychotics are prominent and complicated. Case presentation: We report a clozapine-treated patient with SARS-CoV-2 infection who developed neutropenia after coadministration with Paxlovid. In this case, clozapine was used for over 15 years, without neutropenia development. However, severe neutropenia (absolute neutrophil count = 523/µl) developed 3 days after the coadministration of Paxlovid 2 doses per day, valproic acid 1,000 mg per day and clozapine 100 mg per day. The development of neutropenia may be attributed to the complicated interaction among Paxlovid, SARS-CoV-2 infection, valproic acid, fluvoxamine and clozapine. Conclusions: Neutropenia is a rare but life-threatening event if a concomitant infection occurs. The risk may increase during SARS-CoV-2 infection and the coadministration of clozapine and Paxlovid. Although the exact causes of neutropenia in this patient are not fully clear, the white blood cell count and absolute neutrophil count should be closely monitored during the administration of Paxlovid in clozapine-treated patients with SARS-CoV-2 infection.