Gastrointestinal Adverse Drug Reactions Research Articles

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.

Safety Profile of the Trastuzumab-Based ADCs: Analysis of Real-World Data Registered in EudraVigilance.

Trastuzumab (T) and tyrosine kinase inhibitors (TKIs) are among the first-line treatments recommended for HER2-positive breast cancer. More recently, antibody-drug conjugates (ADCs) such as trastuzumab deruxtecan (T-DXd) and trastuzumab emtansine (T-DM1) have been authorized, and they represent the second-line therapy in this type of cancer. The present study aimed to evaluate adverse drug reactions (ADRs) associated with T-based ADCs that were spontaneously reported in EudraVigilance-the European pharmacovigilance database. Out of 42,272 ADRs reported for currently approved ADCs on the market, 24% of ADRs were related to T-DM1, while 12% of ADRs were related to T-DXd. T-DM1 had a higher probability of reporting eye, ear and labyrinth, and cardiac and hepatobiliary ADRs, while T-DXd had a higher probability of reporting respiratory, thoracic and mediastinal, blood and lymphatic system, metabolism and nutrition, and gastrointestinal ADRs. The present research found that in terms of hematological disorders, T-DM1 and T-DXd had a higher probability of reporting ADRs than TKIs. Moreover, the data showed that T-DM1 seemed to have a higher risk of cardiotoxicity than T-DXd, while T-DXd had a higher probability of reporting metabolism and nutrition disorders than T-DM1.

Influence of ABCB1 3435C>T Polymorphism on Methotrexate Safety in Patients with Psoriasis — A Secondary Publication

Background: Methotrexate is a highly effective systemic treatment for moderate to severe psoriasis, but drug toxicity may limit its use. Recent evidence suggests that it is necessary to take into account the individual characteristics of methotrexate pharmacokinetics, which are determined by the presence of polymorphisms of genes encoding methotrexate carrier proteins, to predict the risk of methotrexate-induced toxicity. Aim: The research aims to assess the associations of ABCB1 rs1045642 (3435C>T) polymorphism with methotrexate safety for patients with moderate and severe psoriasis. Methods: The study included 75 psoriasis patients treated with methotrexate with 21 days of follow-up duration. Data on adverse drug reactions (ADR) were collected using a clinically structured questionnaire, and complete and biochemical blood tests, and urinalysis were performed. The severity of ADR was assessed using visual analog scales and the CTCAE toxicity scale. The severity of gastrointestinal ADR was assessed using the GSRS questionnaire. Genotyping was carried out by real-time PCR. Results: Gastrointestinal toxicity was detected in 38 patients (50.67%). The mean GSRS score was 7.97 ± 9.18. Analysis of differences in the ADR incidence showed the presence of statistically significant differences in the frequency of ADR in the gastrointestinal tract: the toxic effect of methotrexate was more often observed in carriers of the T allele of the ABCB1 rs1045642 polymorphism (3435C>T), (CC: 2 (14.3%), TC: 18 (52.9%), TT: 18 (66.7%), P = 0.006). Binomial regression demonstrated the presence of a statistically significant effect of the rs1045642 single-nucleotide polymorphism of the ABCB1 gene on the incidence of ADR from the gastrointestinal tract (OR = 8.64, P = 0.008). Conclusion: An association of ABCB1 rs1045642 single-nucleotide polymorphism with the safety of methotrexate therapy in patients with moderate and severe psoriasis was revealed. The data obtained can be used to personalize the prescription of methotrexate to psoriasis patients.

Adverse drug reaction monitoring of commonly prescribed antimicrobial agents in patients at Rama medical college, hospital and research centre, Kanpur

Background: An adverse drug reaction (ADR) is defined as a harmful or unpleasant reaction due to the use of a drug and may cause different types of effects, such as side effects. The World Health Organization states that adverse drug effects are a response to harmful and unintended medicine and occur at doses normally used in men for the prevention, diagnosis, or therapy of disease or for modifying physiological function. Aims and Objectives: The objective of the study was ADR monitoring of commonly prescribed antimicrobial agents. Materials and Methods: The study was conducted at Rama Hospital and the Research Center Mandhana Kanpur. Data were collected from the patients attending the outpatient and inpatient departments (OPD and IPD) of the medicine departments during the study period at Rama Hospital Mandhana, Kanpur. The sample size was a total of 60 patients. The study duration was conducted for 1 year. Data were collected by analyzing OPDs and IPDs in the Department of Medicine. Results: There are different types of adverse drug effects; we observed only three types of adverse drug effects in this study. The most commonly observed ADR was type A (56.66%). Out of the total ADRs reported in antimicrobial agents, skin ADRs (42.02%) and gastrointestinal tract ADRs (57.97%) are higher. There are also three different types of severity conditions observed in patients prescribed antimicrobial drugs; among them, the most commonly observed severity conditions were mild (58.33%). Conclusion: These study findings suggest that antimicrobial drugs are generally safe for most patients but can cause mild ADRs. It is important to monitor patients for ADRs while taking antimicrobial drugs and to provide appropriate treatment if necessary. Pharmacovigilance programs can help to identify and monitor ADRs, which can lead to improved patient safety.

Association of ABCB1 Polymorphisms with Efficacy and Adverse Drug Reactions of Valproic Acid in Children with Epilepsy.

Genetic polymorphisms in ATP-binding cassette subfamily B member 1 (ABCB1, also known as MDR1) have been reported to be possibly associated with the regulation of response to antiseizure medications. The aim of this study was to investigate the association of ABCB1 polymorphisms with the efficacy of and adverse drug reactions to valproic acid among Chinese children with epilepsy. A total of 170 children from southern China with epilepsy treated with valproic acid for more than one year were recruited, including 61 patients with persistent seizures and 109 patients who were seizure-free. Two single nucleotide polymorphisms of ABCB1, rs1128503 and rs3789243, were genotyped using the Sequenom MassArray system. The two single nucleotide polymorphisms of ABCB1 were found to be significantly associated with treatment outcomes of valproic acid in children with epilepsy. Carriers with the TT genotype of ABCB1 rs1128503 were more inclined to exhibit persistent seizures after treatment with valproic acid (p = 0.013). The CC genotype of rs3789243 was observed to be a potential protective factor for valproic acid-induced gastrointestinal adverse drug reactions (p = 0.018), but possibly increased the risk of valproic acid-induced cutaneous adverse drug reactions (p = 0.011). In contrast, the CT genotype of rs3789243 was associated with a lower risk of valproic acid-induced cutaneous adverse drug reactions (p = 0.011). Haplotype analysis showed that CC haplotype carriers tended to respond better to valproic acid treatment (p = 0.009). Additionally, no significant association was found between ABCB1 polymorphisms and serum concentrations of valproic acid. This study revealed that the polymorphisms and haplotypes of the ABCB1 gene might be associated with the treatment outcomes of valproic acid in Chinese children with epilepsy.

A highlight on carbamazepine-induced adverse drug reactions in Saudi Arabia: a retrospective medical records-based study

The link between human leukocyte antigen (HLA) alleles and carbamazepine-induced cutaneous, respiratory, and gastrointestinal adverse drug reactions (ADR) has created a window of opportunity for preventing certain forms of cutaneous adverse drug reactions (cADRs); however, there is not enough data to make pharmacogenomic recommendations that can be implemented globally. The aim of this study is to assess and document carbamazepine-induced adverse reactions among prescribed Saudi/non-Saudi patients. A retrospective chart review was performed for patients who received carbamazepine (CBZ) in the period between 2016 and 2020, in the Kingdom of Saudi Arabia. Data were gathered and descriptive statistical analyses were performed on the data for the study sample. Comparisons were made using the chi-square test or independent samples’ t-test. Statistical significance was considered at p < .05. All statistical analyses were performed using IBM SPSS 21.0 (Armonk, NY; IBM Corp). Results from multivariate logistic regression analyses showed that higher likelihood of carbamazepine-induced adverse reactions was significantly associated with younger age, OR = 0.82, 95% CI (0.74, 0.90); p < 0.001. Patients who were prescribed CBZ for reasons other than epilepsy or seizures were significantly more likely to develop carbamazepine-induced adverse reactions (epilepsy vs. other; OR = 0.63, p = 0.013; seizures vs. other; OR = 0.59, p = 0.018). Gender or medication duration were not related to carbamazepine-induced adverse reactions (p > 0.05). The findings of this study are comparable with those of other studies assessing carbamazepine-associated adverse reactions in children and adults. Recommendations include genetic prescreening, educating patients and parents on the possibility of adverse reactions, and routine laboratory monitoring.

General medicine and notification of adverse reactions: contributions of health insurance representatives

In order to reduce the under-reporting of adverse drug reactions (ADR) in general practice, the Caen Normandie regional pharmacovigilance center (CRPV) has implemented a training program for the French health insurance representatives (DAM) of the Manche department in order to raise awareness among general practitioners (GPs) to ADR reporting. During quarterly visits of DAM to GPs, the mode of operation and the value of pharmacovigilance reporting was presented. This pilot study presents the impact of these DAM visits to GPs in term of ADRs reporting quantification. Assessment of this first year showed a doubling of ADR reporting by GPs of the Manche department in 2019 compared to 2017 and 2018. This phenomenon was not found in the two control departments (departments of Calvados and Orne) where the information had not been issued. These ADRs first concerned drugs of the renin-angiotensin system, then psychotropic drugs and anti-infectives. These were cutaneous, then neurological and gastrointestinal ADRs, preferentially affecting women. This experimentation should continue on a larger scale. The longer-term evaluation of this tool also requires evaluating its relevance.

Gastrointestinal System Adverse Drug Reactions in Geriatric Patients in Odisha

Gastrointestinal System Adverse Drug Reactions in Geriatric Patients in Odisha

Study of side effect profile of bedaquiline containing regimen among patients with extensively drug-resistant tuberculosis at a nodal drug-resistant center

Background: Extensively drug-resistant tuberculosis (XDR TB) is a type of tuberculosis (TB) characterized by resistance to isoniazid and rifampicin, along with resistance to one of the fluoroquinolones and at least one of the second line injectable drugs. Bedaquiline is a diarylquinoline antimycobacterial agent approved for the treatment of adults with pulmonary multidrug-resistant TB (MDR-TB) and XDR-TB by the food and drug administration. Aim and Objective: The aim of this study was to study the side effect profile of bedaquiline containing regimen among XDR TB patients. Materials and Methods: This study was conducted at outpatient and wards of nodal drug-resistant TB Center, Department of Pulmonary Medicine, SVRRGGH, Tirupati, for a period of 1 year. Forty patients of more than 18 years age and diagnosed with XDR TB were included in the study. Bedaquiline was started and daily monitoring was done with ECG and all organ function tests were repeated every 15 days. Results: All 40 cases were retreatment cases; no new XDR TB case was reported in study period. Most common age group of presentation in our study was 46 to 55 years (32.5%). Gastrointestinal adverse drug reactions were found to be more common (37.5%), cardiovascular QTc changes were observed in 10% of patients, 5% of patients had neurological reactions (Headache), 2.5% of patients had peripheral neuropathy, and 2.5% of patients had arthralgia. Conclusions: Bedaquiline containing regimen is very effective for the treatment of XDR TB cases. The study shows that compliance with this regimen is very good. Bedaquiline has minimal adverse reactions and even these are easily manageable. Bedaquiline has good safety profile and patients have improved quality of life.

Assessing adverse drug reaction reports for antidiabetic medications approved by the food and drug administration between 2012 and 2017: a pharmacovigilance study.

Between 2012 and 2017, the U.S. Food and Drug Administration (FDA) approved 10 antidiabetic indicated therapies. Due to the limited literature on voluntarily reported safety outcomes for recently approved antidiabetic drugs, this study investigated adverse drug reactions (ADRs) reported in the FDA Adverse Event Reporting System (FAERS). A disproportionality analysis of spontaneously reported ADRs was conducted. FAERS reports from January 1, 2012 to March 31, 2022 were compiled, allowing a 5-year buffer following drug approval in 2017. Reporting odds ratios were calculated for the top 10 ADRs, comparing new diabetic agents to the other approved drugs in their therapeutic class. 127,525 reports were identified for newly approved antidiabetic medications listed as the primary suspect (PS). For sodium-glucose co-transporter-2 (SGLT-2) inhibitors, the odds of blood glucose increased, nausea, and dizziness being reported was greater for empagliflozin. Dapagliflozin was associated with greater reports of weight decreased. Canagliflozin was found to have a disproportionally higher number of reports for diabetic ketoacidosis, toe amputation, acute kidney injury, fungal infections, and osteomyelitis. Assessing glucagon-like peptide-1 (GLP-1) receptor agonists, dulaglutide and semaglutide were associated with greater reports of gastrointestinal adverse drug reactions. Exenatide was disproportionally associated with injection site reactions and pancreatic carcinoma reports. Pharmacovigilance studies utilizing a large publicly available dataset allow an essential opportunity to evaluate the safety profile of antidiabetic drugs utilized in clinical practice. Additional research is needed to evaluate these reported safety concerns for recently approved antidiabetic medications to determine causality.

Direct-acting antiviral-related gastrointestinal adverse drug reactions

Direct-acting antiviral-related gastrointestinal adverse drug reactions

Direct-acting antiviral agent use and gastrointestinal safety in patients with chronic hepatitis C: a pharmacovigilance study based on FDAAdverse Event Reporting System.

Gastrointestinal adverse drug reactions (GADRs) of direct-acting antiviral agents (DAAs) in patients with chronic hepatitis C are underestimated. This study aimed to comprehensively evaluate the gastrointestinal safety of DAAs in patients with chronic hepatitis C. The US FDA Adverse Event Reporting System database was searched for GADR cases reported from 01 to 2012 to 30 September 2021. Twelve DAA types used for hepatitis C virus were included. The top 30 GADRs were assessed based on the use of DAAs, number of cases, and clinical features. A case-non-case disproportionality approach was used to confirm pharmacovigilance signals, whereby reporting odds ratios (ROR) with 95% CI were calculated. Nausea (70.01/1000), diarrhoea (39.10/1000), and vomiting (31.68/1000) accounted for the highest number of cases. The pooled median time-to-onset of the top 30 GADRs was 13 days (Q1-Q3: 2-38) and the proportion of drug discontinuation was 19.17%. The highest number of DAA-related cases involved ledipasvir/sofosbuvir (21.86%), sofosbuvir/velpatasvir (21.77%), and sofosbuvir (13.41%). When DAAs were considered as a class drug, after adjusting for age, sex, concomitant diseases and drugs that potentially induced GADRs, significant RORs for specific GADRs were noted, including abdominal discomfort (1.62, 95% CI 1.32-1.99), constipation (1.54, 95% CI 1.26-1.89), dyspepsia (1.25, 95% CI 1.01-1.55), abdominal distension (1.36, 95% CI 1.05-1.75), faeces discoloured (1.77, 95% CI 1.15-2.73), and gastric ulcer (2.37, 95% CI 1.28-4.41). Clinicians should have a deeper understanding of GADRs to improve the gastrointestinal tolerance of patients with chronic hepatitis C.

Anaplastic lymphoma kinase tyrosine kinase inhibitors associated gastrointestinal obstruction, perforation, and ulceration: an analysis of the FDA adverse event reporting system database (FAERS).

BACKGROUND: There have been cases reporting anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) and associated serious gastrointestinal (GI) adverse drug reactions (gastrointestinal obstruction, perforation, and ulceration). These adverse drug reactions are not in the drug package inserts, and the drug relationships are not proven in the literature. AIM: We aimed to examine the potential association between GI obstruction, perforation, and ulceration, and ALK-TKIs by data mining of the US FDA Adverse Event Reporting System (FAERS). METHOD: We conducted a disproportionality analysis of GI obstruction, perforation, and ulceration by estimating the reporting odds ratios (ROR) and the information component (IC) with 95% confidence intervals. RESULTS: A total of 279 cases of ALK-TKI-associated GI obstruction, perforation, and ulceration from January 1, 2011, to December 31, 2020, were identified. GI obstruction, perforation, and ulceration cause 16% of cases of death. A significantly increased reporting rate for GI obstruction [ROR 1.77 (1.45-2.15); IC 0.82 (0.53-2.03)] and perforation [ROR 1.61 (1.28-2.02); IC 0.68 (0.35-1.92)] was observed for ALK-TKIs as a drug class. The signal of GI ulceration was detected only in crizotinib [ROR 1.23 (1.01-1.50); IC 0.29 (0.01-1.51)]. A statistically significant ROR and IC emerged for the site of the esophagus. CONCLUSION: Overall, the pharmacovigilance study of the FAERS indicates slightly increased reporting of GI obstruction and perforation, which may cause severe or even fatal outcomes among ALK-TKIs users.

Five Years of Direct Oral Anticoagulants Use in Italy: Adverse Drug Reactions from the Italian National Pharmacovigilance Network.

Background: Direct oral anticoagulants (DOACs) are the preferred anticoagulant drugs for the prevention of atrial fibrillation (AF)-related thromboembolic complications and for the treatment and the prevention of recurrences of venous thromboembolism (VTE). The evaluation of self-reported adverse drug reactions (ADRs) available from databases of drug-regulatory agencies such as the Italian Medicines Agency (AIFA) pharmacovigilance database represents a novel aid to guide decision making. Objective: To assess the safety profile of DOACs by analyzing ADR rates in the real-world Italian scenario. Methods: Post-marketing surveillance data recorded by the National Pharmacovigilance Network were retrieved for the time period 2017–2021 from the AIFA online site. The following data were collected for each DOAC: total ADR number, serious ADR number, gastrointestinal (GI) ADR, intracranial hemorrhage events (ICH ADR), and more frequently reported ADR for the study year. The safety profile was expressed by the risk index (RI). Results: Rivaroxaban use was associated with consistent and stable low rates of serious ADR, GI ADR, and ICH ADR across the 5-year study period. Rivaroxaban and apixaban showed the lowest RI for serious ADR and GI ADR, while rivaroxaban use was associated with significantly lower ICH events as compared to apixaban. Dabigatran was related to the highest RIs for every ADR class, in particular GI ADRs. Conclusions: DOACs presented an acceptable safety profile in the current post-market analysis. However, rivaroxaban and apixaban were associated with more favorable safety profiles as compared to dabigatran, while rivaroxaban provoked statistically significantly fewer ICH events as compared to apixaban.

Safety of Antibiotics in Hospitalized Children in Romania: A Prospective Observational Study.

Antibiotics are among the most prescribed drugs in pediatric inpatients and are frequently associated with adverse drug reactions (ADRs) in children. This study aimed to assess the frequency and type of ADRs related to the use of antibiotics in pediatric inpatients through a prospective observational study, conducted over 6 months, covering the winter and spring seasons when the incidence of infections peaks in Romania. ADRs were evaluated for causality, avoidability and severity. Among the 266 included children, 25 (9.4%) experienced 30 ADRs. ADR frequency tended to be higher in ≤2-year-olds (13 of 25, 52.0%) than in other age categories. Gastrointestinal and hematological ADRs were most frequently observed. Diarrhea was the most common ADR associated with antibiotics (8 of 30, 26.7%). Ceftriaxone (16 of 30, 53.3%), cefuroxime, ceftazidime and azithromycin (3 of 30, 10.0% each) were most commonly responsible for ADRs. After causality assessment, 2 (6.7%) ADRs were considered definite, 12 (40.0%) probable and 16 (53.3%) possible. One ADR was classified as definitely avoidable and one as possibly avoidable. Seven children required treatment for ADRs. Antibiotic treatment was discontinued in 4 children. Antibiotics frequently caused ADRs in ≤ 2-year-olds and were commonly associated with gastrointestinal symptoms. Close monitoring of antibiotic-associated ADRs remains important in the pediatric population.

Sex-Related Differences in Pharmacological Response to CNS Drugs: A Narrative Review

In the last decades, both animal and human studies have neglected female subjects with the aim of evading a theorized intricacy of feminine hormonal status. However, clinical experience proves that pharmacological response may vary between the two sexes since pathophysiological dissimilarities between men and women significantly influence the pharmacokinetics and pharmacodynamics of drugs. Sex-related differences in central nervous system (CNS) medication are particularly challenging to assess due to the complexity of disease manifestation, drugs’ intricate mechanisms of action, and lack of trustworthy means of evaluating the clinical response to medication. Although many studies showed contrary results, it appears to be a general tendency towards a certain sex-related difference in each pharmacological class. Broadly, opioids seem to produce better analgesia in women especially when they are administered for a prolonged period of time. On the other hand, respiratory and gastrointestinal adverse drug reactions (ADRs) following morphine therapy are more prevalent among female patients. Regarding antidepressants, studies suggest that males might respond better to tricyclic antidepressants (TCAs), whereas females prefer selective serotonin reuptake inhibitors (SSRI), probably due to their tolerance to particular ADRs. In general, studies missed spotting any significant sex-related differences in the therapeutic effect of antiepileptic drugs (AED), but ADRs have sex variations in conjunction with sex hormones’ metabolism. On the subject of antipsychotic therapy, women appear to have a superior response to this pharmacological class, although there are also studies claiming the opposite. However, it seems that reported sex-related differences regarding ADRs are steadier: women are more at risk of developing various side effects, such as metabolic dysfunctions, cardiovascular disorders, and hyperprolactinemia. Taking all of the above into account, it seems that response to CNS drugs might be occasionally influenced by sex as a biological variable. Nonetheless, although for each pharmacological class, studies generally converge to a certain pattern, opposite outcomes are standing in the way of a clear consensus. Hence, the fact that so many studies are yielding conflicting results emphasizes once again the need to address sex-related differences in pharmacological response to drugs.

CYP2C19 slow metabolizer phenotype is associated with lower antidepressant efficacy and tolerability

The inter-individual variability in CYP2C19-mediated metabolism may affect the antidepressant treatment. The aim of this study is to evaluate differences in antidepressant efficacy and tolerability between different CYP2C19 metabolizer categories in inpatients suffering from major depressive disorder. The cohort was divided into experimental groups based on CYP2C19 genotype and it contained 24 slow (SMs), 41 normal (NMs), and 37 fast metabolizers (FMs). Efficacy and tolerability were assessed at baseline, and after two and four weeks as a follow-up. The primary efficacy measurement was the change from baseline in Hamilton's Depression Rating Scale (HAMD), while the primary tolerability measurement was the Toronto Side-Effects Scale (TSES) intensity scores at the last visit. The reduction in HAMD score was 36% less pronounced and response rate was exceedingly less prevalent (75% lower) in SMs, compared with NMs. The TSES intensity score was increased in SMs, compared with NMs, by 43% for central nervous system and by 22% for gastrointestinal adverse drug reactions. No significant differences in measured parameters were observed between NMs and FMs. Compared with NM and RM, lower antidepressant efficacy and tolerability was observed in SMs; this association is likely connected with the lower SM capacity to metabolize antidepressant drugs.

Safety of Non-Steroidal Anti-Inflammatory Drugs in the Elderly: An Analysis of Published Literature and Reports Sent to the Portuguese Pharmacovigilance System.

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most frequently used agents to treat musculoskeletal disorders (principally by the elderly), thus raising the risk of adverse drug reactions (ADRs). This work aims to monitor NSAIDs safety profile in older people by using literature and pharmacovigilance data. Published clinical studies reporting the NSAIDs safety in elderly patients (age ≥ 65) were identified by a literature search and were then deeply analyzed. In addition, suspected ADRs reports submitted to the Portuguese Pharmacovigilance System (PPS) involving patients aged ≥65 with at least one NSAID as suspected drug were explored in detail. Most studies concluded that the risk of gastrointestinal, cardiovascular, and renal ADRs was significantly lower with cyclooxygenase-2 (COX-2)-selective NSAIDs use than with nonselective NSAIDs. The PPS data analysis showed that serious gastrointestinal ADRs occurred mostly in patients taking more than one NSAID and/or another concomitant drug that increases the incidence of these events, in the absence of gastroprotection. The results suggest that while NSAID toxicity is well understood, their safe use needs to be monitored in clinical practice. Furthermore, the pharmacovigilance data analyzed also showed that monitoring NSAIDs use in elderly remains essential to mitigate the associated risks, especially in those with comorbidities and under polytherapy.

Clozapine-induced gastrointestinal hypomotility: presenting features and outcomes, UK pharmacovigilance reports, 1992-2017.

Clozapine-induced gastrointestinal hypomotility (CIGH) affects some 75% of patients treated with clozapine. To document the incidence of potentially harmful CIGH in the UK. We studied spontaneous UK pharmacovigilance reports recorded as clozapine-related gastrointestinal adverse drug reactions, 1992-2017. There were 527 patients reported with potentially harmful CIGH; 33% (n = 172) died. Deaths averaged 1 per year 1992-1999, 5 per year 2000-2009 and 15 per year 2010-2017. Those who died were older (median 52 years v. 49 years) and had been prescribed clozapine for longer than those who recovered (median 11.3 years v. 4.8 years), but there was no difference in prescribed dose. Within the first 4 years of clozapine treatment, there were 169 reports of CIGH, of which 3% (n = 5) were fatal. At 10-14 years there were 63 reports of CIGH, of which 25% (n = 16) were fatal. Among the deaths, males were younger (median 51, range 22-89 v. median 57, range 24-89 years) with higher clozapine doses (median 450, range 100-900 v. median 300, range 12.5-800 mg/d) than females. In non-fatal CIGH, surgery was the most frequent outcome (n = 92). The procedures included appendectomy, ileostomy, total/partial colectomy, colostomy/stoma and proctosigmoidectomy. Clozapine dosage was reduced in 6 patients, stopped and restarted in 23, 'continued' in 6 and discontinued permanently in at least 76 patients. The risk of serious morbidity/mortality from CIGH is substantial. The need to actively monitor bowel function and give laxatives to patients treated with clozapine is clear.

Short-Term Adverse Drug Reactions to Antiretroviral Therapy in Children with HIV: A Cohort Study.

To carry out an active surveillance for adverse drug reactions (ADRs) in children with HIV infection newly initiated on antiretroviral therapy (ART), determine risk factors for their occurrence, and assess their influence on adherence to ART. All children newly initiated on ART from 1st March 2014 to 30th June 2019 at a tertiary care children's hospital in New Delhi, were actively monitored for ADRs to ART for a period of 6 mo after ART initiation. The frequency, spectrum, and severity of ADRs, their influence on adherence, and risk factors for their occurrence were analyzed. Among the 174 enrolled children, ADRs were observed in 78 (44.8%) children during the first 6 mo after ART initiation. Total numbers of episodes of ADR observed were 108 (0.62 episodes of ADR/child). Sixty percent of events were of grade 1 severity, 19.4% events were of grade 2 and 3 each, while 1 (0.9%) event was of grade 4 severity. Adherence to ART was adversely affected in 21.8% of ADRs. Gastrointestinal symptoms (49.1%) were most frequent among all the events observed. Zidovudine, lopinavir/ritonavir, efavirenz and nevirapine based regimes were significantly associated with hematological, gastrointestinal, neurological, and dermatological ADRs, respectively. Children with immunological suppression were at a higher risk of developing ADRs as compared to those without it [RR 1.9 (95% CI (1.1-3.2)]. ADRs to ART are very frequent; most of them are mild and self-limiting. However, they can adversely impact adherence to ART. Anticipatory guidance, ongoing monitoring, and provision of symptomatic treatment will help tide over most ADRs and reduce their adverse impact upon ART adherence.