Adverse Drug Reactions In Group Research Articles

Risk factors for adverse drug reactions to sulfamethoxazole-trimethoprim prophylaxis in patients with rheumatic and musculoskeletal diseases.

Risk factors for adverse drug reactions (ADRs) associated with prophylactic sulfamethoxazole-trimethoprim (SMX/TMP) in patients with rheumatic and musculoskeletal diseases undergoing immunosuppressive therapy remain unclear, we aimed to identify the risk factors associated with ADRs. Consecutive patients with rheumatic and musculoskeletal diseases, who were admitted to Keio University Hospital and received prophylactic administration of SMX/TMP, were included. Data regarding ADRs to SMX/TMP were collected to identify associated risk factors using multivariable analysis. Of 438 patients included in the analysis, 82 (18.7%) experienced ADRs. Patients in the ADRs group were significantly older, had chronic kidney disease, and exhibited lower lymphocyte and platelet counts, lower albumin levels, lower estimated glomerular filtration rates, higher aspartate aminotransferase levels, and higher ferritin levels than those in the non-ADR group. Regarding underlying rheumatic and musculoskeletal diseases, adult-onset Still's disease (ASD) was associated with a significantly higher incidence of ADRs (67%) than other diseases. Multivariable analysis identified the presence of ASD and low lymphocyte counts as independent risk factors for allergic ADRs, and older age and use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers for non-allergic ADRs. Risk factors for ADRs associated with prophylactic SMX/TMP treatment in patients with rheumatic and musculoskeletal diseases were identified.

Evaluation of adverse reactions induced by anti-tuberculosis drugs among hospitalized patients in Wuhan, China: A retrospective study.

The study aims to estimate the incidence and risk factors of adverse drug reactions (ADRs) induced by anti-tuberculosis (TB) drugs. A single center retrospective analysis of patients taking anti-TB therapy from January 2016 to December 2018 in the hospital was conducted. Univariate and multivariate logistic regression analysis were used to identify these risk factors of ADRs induced by anti-TB drugs. Among 1430 patients receiving anti-TB therapy, 440 (30.77%) patients showed at least 1 ADR induced by anti-TB drugs. Hyperuricemia was the most common ADR, followed by hepatic function test abnormality, liver damage and gastrointestinal reactions. Significant differences (P < .05) were also seen in diabetes, age, treatment duration, type of TB (extrapulmonary) and some therapeutic regimens between ADR group and non-ADR group, respectively. Multivariate logistic regression analysis showed that treatment duration (OR = 1.029, 95%CI[1.018-1.040], P = .000), type of TB (extrapulmonary, OR = 1.487, 95%CI[1.134-1.952], P = .004) and some therapeutic regimens (HREZ, OR = 1.425, 95%CI[0.922-2.903], P = .001; HRZS, OR = 2.063, 95% CI[1.234-3.449], P = .006; HRZ, OR = 3.623, 95%CI[2.289-5.736], P = .000) were risk factors for ADRs induced by anti-TB drugs. Anti-TB drugs usually induced the occurrence of severe and frequent adverse effects, such as hyperuricemia. Treatment duration, HREZ, HRZS and HRZ regimens, and type of TB (extrapulmonary) should be considered as high-risk factors. Thus, it should be recommended to consider optimum management during anti-TB therapy, particularly hyperuricemia monitoring and hepatic function test.

Clinical profile of medication-related emergencies among patients presenting to the emergency department: An observational study

Objective: To determine the clinical profile of patients presenting with medication-related emergencies to the Emergency Department of our institute. Methods: This was an observational study conducted between November 2018 and September 2020 at Bangalore Baptist Hospital, Karnataka. A total of 138 subjects who satisfied the inclusion criteria were included in the study. The severity of adverse drug reactions (ADR) is assessed based on the Hurwitz severity assessment scale of ADR. Glasgow coma scale at the time of presentation and source of medication were noted. The type of drug overdose, requirement of advanced airway and vasopressors, and the outcome were also assessed. Results: Among medication-related emergencies (n=138) in our study, ADR contributed to 70.3% (n=97) of the study population, and drug overdose accounted for 29.7% (n=41). One-third of the ADR occurred in patients aged above 60 years. Most patients were hemodynamically stable and did not require vasopressors, or advanced airway in both groups. Most patients had Glasgow coma scale ranging from 13-15 in both groups. Nonsteroidal anti-inflammatory drugs were the most used medicine (17/41, 41.5%) and most medications were over the counter drugs (25/41, 61.0%) in the drug overdose group; meanwhile in the ADR group, anti-diabetic medication was the most used medicine (34/97, 35.1%) and most medications were prescribed in the ADR group (93/97, 95.9%). Conclusions: Our study shows that ADR is the most common type of medication-related emergency.

A RETROSPECTIVE ANALYSIS OF SPONTANEOUSLY REPORTED ADVERSE DRUG REACTIONS TO ANTIRETROVIRAL THERAPY DURING AND POST-TRANSITIONAL PHASE OF DOLUTEGRAVIR

Objectives: The main objective of this study was to analyze the pattern of reported adverse drug reaction (ADRs) in people receiving antiretroviral therapy (ART) mainly during and post-transitional phase of dolutegravir-based regimens. Methods: This is a retrospective observational study initiated after the approval of the Institutional Ethics Committee and from the ART Center. Sources of data are spontaneously reported ADR data of human immunodeficiency virus (HIV) persons to the ADR monitoring center (AMC). Results: A total of 190 patients who are on ART reported at AMC from April 2020 to June 2022 had a total of 204 ADRs. Among them, 108 (57%) were females and had a higher prevalence than 82 (43%) males. ADRs were higher among the age group of 41–50 years (33.68%) followed by 31–40 years (32.10%). Among dolutegravir-based regimens, tenofovir, lamivudine, and dolutegravir were given to more patients (118). The most common ADRs encountered were peripheral neuropathy 16.66%, followed by hyperglycemia (14.21%), renal toxicity (10.29%), hyperbilirubinemia (9.31%), and anemia (7.84%) of all ADRs. Conclusion: In this study, it has been observed that HIV patients on dolutegravir-based regimens are associated with more ADRs. Nervous system disorders were the most commonly observed group of ADRs, followed by metabolism and nutritional disorders, the others being skin diseases and renal toxicity. This incidence of ADRs to ART calls for efficient pharmacovigilance surveillance to improve patient care and drug safety.

POSA21 An In-Hospital Study to Trace the Risk Factors Associated with Adverse Drug Reactions during the Second Wave of COVID-19 in a Secondary Care Hospital in India

To characterize the adverse drug reactions (ADRs) and the risk factors associated with COVID -19 treatment in a secondary care hospital in South India. A prospective observational study was carried out on 327 patients admitted between April 1 and May 15, 2021, using an in-person surveillance system. The demographic characters of all the patients including the time of admission, comorbid diseases, length of stay, history of drug allergies, and the number of medications used during hospitalization were collected. After identification of an adverse drug event, the causality, suspicious drugs, and prognosis of ADRs were also recorded. Descriptive statistics and multivariate logistic regressions were carried out to analyze the risk factors of ADRs. Out of the 327 patients, 194 (59.3%) were men and the mean age was 45.7± 16.6 years. 122 ADRs were reported among 87 patients with an incidence rate of 26.6%. Most of the reactions were associated with dexamethasone (31.9%), remdesivir (18%), and favipiravir (14.7%) with dexamethasone-induced hyperglycemia being most prominent. The majority of the suspected ADR cases were categorized as probable (61.8%) according to the WHO-UMC causality assessment. When compared with the No ADRs group, the length of stay (p=0.004), history of drug allergies (p<0.001), number of drugs used in treatment (p<0.001) were significantly higher in the ADRs group. Multivariable analysis revealed that length of stay (OR: 2.03; 95% CI 1.02–3.98; P = 0.04), comorbidities (OR: 2.08; 95% CI 1.05–4.18; P = 0.04), number of drugs used for treatment (OR: 3.17; 95% CI 1.60–6.27; P = 0.001) and were independent risk factor for ADRs in the patients. Active surveillance measures are important in case of all drugs used for COVID treatment to keep the living guidelines the most live one.

Diagnosis and treatment of drug-induced interstitial lung disease

Drug-induced interstitial lung disease (DILD) is a group of adverse drug reactions that is rare but fatally toxic. Pulmonary toxicity causes inflammation and subsequent interstitial fibrosis. As novel drugs with a variety of purposes are introduced into the medical field, the number of culprit medications that are suspected to cause lung complications is accordingly increasing. In this review, DILD will be discussed from several aspects such as causality by numerous drugs, check points for a timely diagnosis, alongside some contemporary treatment options. The exact mechanism of DILD has not been elucidated, and a useful clinical, radiological, or pathological confirmation process is still lacking. Common drugs which casue DILD include bleomycin, amiodarone, epidermal growth factor receptor-targeted agents, and immune checkpoint inhibitors. Diagnosis is based on a suspicious drug administration history, somewhat inconsistent clinical symptoms and signs, radiological hints, and histopathological assistance, together with the exclusion of other lung-injuring etiologies. Cessation of the suspected drug, meticulous corticosteroid usage, and ancillary supportive management are the mainstay therapeutic strategy for DILD. Most cases of DILD respond to these countermeasures and reductions, but in some cases the fibrotic process worsens, leading to irreversible sequelae on the affected lung.

Drug-Induced Fatty Liver Disease

Drug-induced fatty liver disease (DIFLD) covers a group of adverse drug reactions whose prevalence accounts for about 10% of all adverse reactions. The aim of this review was to analyse and summarise data on medicines that can potentially lead to the development of DIFLD, as well as on the pathophysiological mechanisms of its development, methods of its diagnosis, treatment, and prevention. The analysis of scientifi c literature showed that most often this complication occurred following the use of amiodarone, methotrexate, tamoxifen, valproic acid, and some other medicines. It was demonstrated that the main risk factors for developing DIFLD are comorbidity/polymorbidity and mitochondrial dysfunction. Due to the lack of pathognomonic clinical manifestations of DIFLD the best approach to making diagnosis is to obtain a thorough medical history, including medication history, to use RUCAM and Naranjo scales, to analyse a number of blood chemistry parameters (alanine transaminase, aspartate transaminase, bilirubin, alkaline phosphatase), and, if necessary, to perform liver biopsy. Whenever DIFLD is observed in a patient, it is necessary, if possible, to discontinue the use of the medicine that caused the adverse reaction, or to lower its dose and to exclude the factors that may potentially aff ect the patient’s condition. The following measures will help healthcare professionals to prevent and detect DIFLD in a timely manner: observing the requirements of the patient information leafl et, taking into account any comorbidity and potential adverse drug interactions, as well as regular monitoring of the condition of patients taking medicines with known hepatotoxic eff ects.

The Necessity of Anti-Tuberculosis Therapy after Resection of Pulmonary Tuberculous Nodules: A Single Center Retrospective Study.

Purpose: To discuss the necessity of anti-tuberculosis therapy after resection of asymptomatic pulmonary tuberculous nodules: is postoperative anti-tuberculosis therapy is over-treatment?Methods: This is a single-center retrospective study. Patients with solitary pulmonary nodule (SPN) and diagnosed as tuberculosis by pathology were included. Clinical features are collected. The primary end point is tuberculosis relapse and the secondary is adverse drug reactions. Patients are divided into two groups according to the acceptance of anti-tuberculosis treatment after operation (A: treated; B: untreated). Recurrence is diagnosed by multi-disciplinary discussion. The difference of recurrence rate will be compared and the incidence of adverse drug reactions in Group A will be calculated.Results: A total of 98 patients were enrolled, 66 in Group A and 32 in Group B. No significant difference between two groups was found in the past history of tuberculosis, erythrocyte sedimentation rate (ESR), T-spot positive rate, and the uptake value of 18F-glucose. No relapse of tuberculosis was found in both groups. The incidence of adverse drug reactions in Group A was 61% (40/66), and the rate of severe adverse reaction was 14% (9/66).Conclusions: Postoperative recurrence of tuberculosis is rare, anti-tuberculosis treatment seems unnecessary for asymptomatic pulmonary tuberculous nodules. Adverse drug reactions should not be ignored.

Evaluation of Adverse Drug Reaction Profile of Drugs Used as First-Line Antiretroviral Therapy.

Background and Objectives The objective was to study the adverse drug reaction (ADR) profile in HIV patients receiving first-line antiretroviral therapy. Methods This was a prospective, observational study that included 171 HIV patients with a follow-up at six months. Demographic details, medical history, details of HIV infection including most recent CD4 count, details of antiretroviral therapy, and other concomitant medication were recorded. Adverse drug reactions were elicited by reviewing patient records and also by interviewing the patient/attendants directly. Results 171 patients completed the study out of which 88 (51.5%) were males and 83 (48.5%) were females. The study subjects included HIV-positive, treatment naïve patients who were started on treatment regimens recommended by the NACO guidelines. The ADRs observed were a fall in haemoglobin or absolute anaemia in response to zidovudine, nonspecific symptoms like headache, and a nonspecific feeling of being unwell in response to tenofovir, stavudine, and efavirenz; dyslipidaemia, pancreatitis, peripheral neuropathy, and lactic acidosis in response to stavudine; generalised rash in response to nevirapine and one case of nephrotoxicity to efavirenz. Majority of the ADRs satisfied the ‘probable' category (60.1%), and the rest were “possible”. ADRs to zidovudine and nevirapine superseded all others. Interpretation and Conclusion Gastrointestinal effects were the most commonly observed group of ADRs, with nausea being the most common ADR, the others being gastritis and diarrhoea. The other ADRs included rash, hepatotoxicity, blood dyscrasias like anaemia, neutropenia, and thrombocytopenia, and fatigue. Few cases of lactic acidosis, peripheral neuropathy, headache, lipoatrophy, and pancreatitis were reported.

Pharmacokinetic patterns of risperidone-associated adverse drug reactions.

The aim of the study was to investigate a correlation between plasma concentrations of risperidone (RIS), its active metabolite 9-hydroxyrisperidone (9-OH-RIS) and the active moiety (AM) (RIS + 9-OH-RIS), and adverse drug reactions (ADRs) in a naturalistic sample. Plasma concentrations of RIS, 9-OH-RIS, and AM in patients out of a therapeutic drug monitoring (TDM) database complaining ADRs were categorized according to the Udvalg for Kliniske Undersogelser side effect rating scales (UKU) (n=97) and compared to patients without ADRs (n=398). Patients in the ADR group received a significantly lower daily dosage of risperidone (trimmed mean 3.64mg/day) than patients without ADRs (4.40mg/day). No differences were found for active moiety plasma concentrations between the groups (p=0.454). Differences were detected only in the case of dose-adjusted plasma concentration values (concentration-by-dose, C/D) for 9-OH-RIS, being higher in patients reporting ADRs (4.78ng/mL/mg) than in patients without ADRs (4.3ng/mL/mg) (p=0.037 for Mann-Whitney U test). Note that differences for non-adjusted 9-OH-RIS plasma levels between groups failed to reach significance (p=0.697). Our findings are consistent with previous data supporting a prominent role of 9-hydroxyrisperidone, but not of risperidone with regard to ADRs. When studying the various subgroups of reported ADRs separately, the size of these subsamples offers some plausible limitations by reducing the power of the analysis.

Adverse Drug Reaction Reporting Pattern in Turkey: Analysis of the National Database in the Context of the First Pharmacovigilance Legislation.

IntroductionIn Turkey, pharmacovigilance began in 1985. A fully structured adverse drug reaction (ADR)-reporting system was established with the publication of the first pharmacovigilance regulation in 2005. Subsequent regulation published in 2014 brought further improvements to the system.ObjectiveIn this study, we aimed to analyse the ADR-reporting pattern in the context of the first pharmacovigilance legislation in Turkey.MethodsWe analysed ADR reports submitted to the Turkish Pharmacovigilance Center (TUFAM) from 2005 to 2014 with respect to reporting rate (RR), patient characteristics, type of the ADRs, suspected drugs, source of the report and the profession of the reporter.ResultsThe annual RR increased gradually over the study period. RRs for females were greater than those for males. RRs were highly correlated with age. Most commonly reported ADRs were skin and subcutaneous tissue disorders. Most commonly suspected drugs were antineoplastic and immunomodulating agents. There was no remarkable change in reporting pattern of ADRs, patient characteristics or classes of suspected drugs over the years. The most common source of reports was spontaneous reporting. Contribution of the reports from studies increased gradually. Most of the reports were reported by physicians. RRs by pharmacists increased substantially over the years.ConclusionThis study showed that the annual RR increased gradually over the 9-year study period. This increase was neither due to an increased reporting of a specific group of ADRs or drugs, nor to an increased reporting in a specific group of patients. There was a general increase in RR in parallel to pharmacovigilance activities.Electronic supplementary materialThe online version of this article (doi:10.1007/s40801-015-0054-1) contains supplementary material, which is available to authorized users.

Genetics of psychotropic medication induced side effects in two independent samples of bipolar patients.

The treatment of bipolar disorder (BD) usually requires combination therapies, with the critical issue of the emergence of adverse drug reactions (ADRs) and the possibility of low treatment adherence. Genetic polymorphisms are hypothesized to modulate the pharmacodynamics of psychotropic drugs, representing potential biological markers of ADRs. This study investigated genes involved in the regulation of neuroplasticity (BDNF, ST8SIA2), second messenger cascades (GSK3B, MAPK1, and CREB1), circadian rhythms (RORA), transcription (SP4, ZNF804A), and monoaminergic system (HTR2A and COMT) in the risk of neurological, psychic, autonomic, and other ADRs. Two independent samples of BD patients naturalistically treated were included (COPE-BD n=147; STEP-BD n=659). In the COPE-BD 34 SNPs were genotyped, while in the STEP-BD polymorphisms in the selected genes were extracted from the genome-wide dataset. Each ADRs group was categorized as absent-mild or moderate-severe and logistic regression with appropriate covariates was applied to identify possible risk genotypes/alleles. 58.5 and 93.5% of patients were treated with mood stabilizers, 44.2 and 50.7% were treated with antipsychotics, and 69.4 and 46.1% were treated with antidepressants in the COPE-BD and STEP-BD, respectively. Our findings suggested that ST8SIA2 may be associated with psychic ADRs, as shown in the COPE-BD (rs4777989 p=0.0017) and STEP-BD (rs56027313, rs13379489 and rs10852173). A cluster of RORA SNPs around rs2083074 showed an effect on psychic ADRs in the STEP-BD. Trends supporting the association between HTR2A and autonomic ADRs were found in both samples. Confirmations are needed particularly for ST8SIA2 and RORA since the few available data regarding their role in relation to psychotropic ADRs.

Genetic predictors of antidepressant side effects: A grouped candidate gene approach in the Genome-Based Therapeutic Drugs for Depression (GENDEP) study

The unwanted side effects associated with antidepressants are key determinants of treatment adherence in depression; propensity to experience these adverse drug reactions (ADRs) may be influenced by genetic variation. However, previous work attempting to ascertain the genetic variants involved has had limited success, in part due to the range of ADRs reported with antidepressants. ADRs reported with antidepressant treatment were categorised using their likely pharmacological basis; adrenergic, cholinergic, serotonergic and histaminergic. To identify genetic predictors of susceptibility to each group of ADRs, a candidate gene analysis was performed with data from 431 depressed patients (from a total sample size of 811 patients) enrolled in the Genome-Based Therapeutic Drugs for Depression (GENDEP) project, who were randomly allocated to receive treatment with escitalopram or nortriptyline. Data from 474 patients treated with citalopram or reboxetine in the GenPod project (total sample of 601 patients) were used for replication of significant findings. We found no significant predictors of presumed adrenergic, cholinergic and histaminergic ADRs. Putative serotonergic ADRs were significantly associated with variation in the gene encoding the serotonin 2C receptor (HTR2C, rs6644093, odds ratio (OR)=1.72, 95% confidence interval (CI)=1.31-2.25, p=7.43×10(-5)) in GENDEP. However, this finding was not replicated in GenPod. The association between serotonergic side effects and variation in the HTR2C gene in the GENDEP sample supports the hypothesis that serotonin receptor-mediated mechanisms underlie these adverse reactions, however this finding was not replicated in GenPod.

Adverse Drug Reactions in Ophthalmology - are they a Myth?

Sometimes ocular (and systemic) therapeutics may cause ocular (and systemic) diseases, namely adverse drug reactions (ADRs). The Journal of Ocular Diseases and Therapeutics is therefore doubly adequate for discussion of the theme of ADRs in Ophthalmology. Many terms are utilized as synonyms but the correct definition of ADR (according to the World Health Organization, WHO) is: "any noxious, unintended and undesired effect of a drug, which occurs at doses used in humans for prophylaxis, diagnosis, or therapy". Ophthalmology is one of the medical specialties in which there is a high difficulty in continuous diagnosis, assessment and treatment. Additionally, the specific and delicate anatomy and physiology of the eye may easily be disrupted by an ADR, with possible irreversible consequences. Ocular ADRs may be frequent (such as cornea verticillata caused by amiodarone) or specific. On the other hand, systemic ADRs may occur after ocular treatments (such as hypotension after instillation of a beta-blocker drop). The timely detection and recognition of ADRs is therefore critical. Several methods exist for the detection of ADRs, but few are specific or apply to ADRs in Ophthalmology. Spontaneous reporting is a low-resource method for detection of ADRs but has flaws, namely under-detection and risk of bias. The literature can be confusing or incomplete, with several case reports and case series about ocular ADRs lacking a causality assessment (such as Naranjo's or WHO's). In conclusion, ADRs in Ophthalmology are a heterogeneous group of ADRs that lack detection, assessment and systematization. Studies about ADRs should increase their quality for further clarification. Each ophthalmologist should know the specific ocular ADRs to systemic medication, the specific systemic ADRs to ocular medication, and to detect and treat them adequately for good clinical practice.

Evaluation of adverse drug reactions in medical intensive care units

Patterns of adverse drug reactions (ADRs) in the medical intensive care unit (MICU) were analysed, and signals for detecting ADRs were developed from the analysis. A retrospective study was conducted in MICU wards at a tertiary care teaching hospital in Seoul, Korea. The areas included one general MICU and one cancer centre MICU. Two pharmacists evaluated ADRs in terms of length of stay, causality, severity, preventability, types, related organs, and incidence. Differences in ADR perception rates between physicians and pharmacists were also evaluated. ADR cases detected through the evaluation were reviewed to develop specific alerting signals for ICU ADRs. The study group included 346 patients admitted to the ICU over 4 months. The overall incidence of ADRs was 32%. ICU length of stay is closely related to ADRs (p = 0.014). Most ADR cases were mild, temporary, and harmful to the patient. Twenty percent of ADRs were preventable, and 74% were type A. Of the ADRs, 70% were noted by physicians; 80% required intervention. The most commonly implicated drug was amphotericin B, and the clinical presentation was a haematologic reaction. Data on the time required for pharmacists to identify ADRs indicated that they were not slower than physicians. Six signals for early detection of the ADRs were developed. The overall ADR incidence in the MICU was about one-third, and the length of stay of the ADR group was longer than that of those without this experience. Automated signal generation was developed. It seemed to be a valuable tool for faster and more efficient patient management, and possibly prevention of ADRs. A future study should scientifically evaluate the clinical relevance of this tool.

Intensive monitoring of adverse drug reactions in hospitalized patients of two medical units at a tertiary care teaching hospital

Objective:To detect incidence of adverse drug reactions (ADRs) in hospitalized patients and to assess their causality, seriousness, preventability, and the possible economic impact.Materials and Methods:This was a prospective study carried out in two medical units at a tertiary care, teaching hospital, for about 18 months. All the admitted patients who developed an ADR after admission (group A) or who were admitted primarily for the treatment of an ADR (group B) were included. Descriptive statistics with 95% CI, χ2, χ2 for the trend and kappa test were used.Results:Out of 6601 patients, 140 patients developed 154 ADRs with an incidence of 2.12%. Causality of the majority of the ADRs in group A was ‘possible’ while those in group B was ‘probable’. Among 109 ADRs (34 serious) in group A, 38 were preventable. On the other hand, out of 45 serious ADRs in group B, 19 were preventable. The total cost of 154 ADRs in 140 patients was Rs. 1,49,803 with an average of Rs. 1070 per patient. The preventable cost for 57/154 ADR was Rs. 96,310.Conclusion:Around 2% of the hospital patients develop ADRs. A large number of these ADRs were preventable. A substantial saving can be made if adequate caution is exerted.

Adverse Drug Reactions and Impaired Renal Function in Elderly Patients Admitted to the Emergency Department

Adverse drug reactions (ADRs) are common in elderly patients. There are various reasons for this, including age- and disease-related alterations in pharmacokinetics and pharmacodynamics as well as the common practice of polypharmacy. The decline in renal function in elderly patients may also predispose them to pharmacological ADRs (type A, augmented). Patients receiving home healthcare may be at even higher risk. To study ADRs as a cause of acute hospital admissions in a defined cohort of elderly patients (aged >or=65 years) registered to receive home healthcare services, with special reference to impaired renal function as a possible risk factor. This was a retrospective study of 154 elderly patients aged >or=65 years admitted to the emergency department of a university hospital in Stockholm, Sweden, in October-November 2002. Estimated creatinine clearance (eCL(CR)) was calculated from the Cockcroft-Gault formula, and estimated glomerular filtration rate (eGFR) by the Modification of Diet in Renal Disease (MDRD) equation. ADRs were defined according to WHO criteria. All medications administered to patients at admission and at discharge were collated. These and other data were collected from computerized hospital records. ADRs were judged to contribute to or be the primary cause of hospitalization in 22 patients, i.e. 14% of 154 patients registered to receive home healthcare. Eleven of the 22 patients were women. All but one ADR were type A. Excessive doses or drugs unsuitable in renal insufficiency were present in seven patients in the ADR group compared with only four patients in the group without ADRs (p = 0.0001). Patients with ADRs did not differ significantly from those without ADRs in relation to age, plasma creatinine, eCL(CR), weight or number of drugs prescribed at admission. However, women with ADRs were significantly older than women without ADRs (mean +/- SD age 88.8 +/- 5.7 years vs 82.5 +/- 8.0 years, respectively; p = 0.014) and had significantly lower mean +/- SD eCL(CR) values (25.5 +/- 10.8 and 37.1 +/- 17.1 mL/min, respectively; p = 0.035). Median MDRD eGFR was significantly higher than median eCL(CR) (59 [range 6-172] mL/min/1.73 m2 vs 38 [range 5-117] mL/min, respectively; p = 0.0001). In elderly patients registered to receive home healthcare, 14% of hospital admissions were primarily caused by ADRs. One-third of these ADRs were related to impaired renal function, generally in very old women. These ADRs may be avoided by close monitoring of renal function and adjustments to pharmacotherapy (drug selection and dose), particularly in very elderly women.

Children and Adolescent Exposures to Atomoxetine Hydrochloride Reported to a Poison Control Center

Background. Atomoxetine hydrochloride, a selective norepinephrine reuptake inhibitor was FDA approved for patients with attention-deficit/hyperactivity disorder. Little is known about adverse drug reactions of atomoxetine following an overdose among children. The objective of our study was to evaluate the type of atomoxetine adverse drug reactions in relation to dose. Methods. We evaluated children exposed to atomoxetine reported to a poison center from January-December 2004. Results. Sixty-four cases met all inclusion criteria. Twenty-one patients had an adverse drug reaction (15 at dosage range 0.52–6.25 mg/kg): agitation, headache, erythema, rash, elevated blood pressure and heart rate, nausea, emesis, and lethargy. In 51 patients, weights were known: group 1 (n = 43) received higher than maximum recommended doses >1.4 mg/kg and group 2 (n = 8) received ≤1.4 mg/kg. There were no differences in adverse drug reactions in group 1 versus 2. Eight patients were admitted to a healthcare facility and all were discharged without any sequelae. Hypertension occurred in 3 of 9 patients for whom blood pressure was recorded. Conclusion. At the doses reported, adverse drug reactions did not correlate with atomoxetine dose. Hypertension may occur in some patients following atomoxetine overdose.

The role of common variants of ABCB1, CYP3A4, and CYP3A5 genes in lipid-lowering efficacy and safety of simvastatin treatment

Our objective was to investigate the interactions between common polymorphisms in ABCB1, CYP3A4, and CYP3A5 genes and the lipid-lowering efficacy and safety of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor simvastatin. One hundred sixteen hypercholesterolemic patients were prospectively screened by physical examination, medical history, and clinical laboratory evaluation and were included in this study. Subjects entering the study were treated with 20 mg/d simvastatin. Plasma lipid and lipoprotein levels were measured before treatment, after 2 months of treatment, and after 6 months of treatment. Ninety-nine patients completed the 6-month follow-up and were included in the association analysis for treatment efficacy. Seventeen subjects who had adverse drug reactions (ADRs) to simvastatin (ADR group) could not complete the 6-month follow-up and were included in the association analyses for safety. Myalgia was observed in 15 of 17 subjects and was the only ADR included in the association analyses, but other common ADRs were also observed. Myalgia was defined as proximal or diffuse muscle pain, tenderness, or weakness, or both pain and weakness, with normal or slightly increased serum creatine phosphokinase levels. ABCB1 (1236C>T, 2677G>A/T, and 3435C>T), CYP3A4 (-392A>G), and CYP3A5 (6986A>G) allele variants were determined by polymerase chain reaction and restriction mapping. After adjustment for covariates, carriers of the ABCB1 1236T variant allele had a greater reduction in total cholesterol and low-density lipoprotein cholesterol with simvastatin treatment, as compared with homozygotes with the wild-type allele (-29.0% [95% confidence interval (CI), -25.9 to -32.5] versus -24.2% [95% CI, -19.0 to -29.3] [P = .042] and -39.6% [95% CI, -35.8 to -44.0] versus -33.8% [95% CI, -27.4 to -40.2] [P = .042], respectively). Similar results were observed for the 2677G>A/T polymorphism and haplotype data. The 1236T, 2677non-G, and 3435T alleles were less frequent in ADR cases than in the non-ADR group (P < .05 for all single-nucleotide polymorphisms). Haplotype analyses also demonstrated a reduction of the T-non-G-T haplotype frequency (20%) in patients in whom myalgia developed during simvastatin treatment, as compared with the non-ADR group (41.4%) (P = .03). No significant associations were observed between the CYP3A4 -392A>G and CYP3A5*3 allele variants and the efficacy or tolerability of simvastatin. Our data suggest an association of ABCB1 gene polymorphisms and the efficacy and safety of simvastatin.

Influenza prophylaxis in the long-term care facility: a case-control study of the risk factors for adverse drug reactions to amantadine

Background Amantadine hydrochloride remains an inexpensive means of influenza A prophylaxis, but it is reported to have a high incidence of adverse drug reactions (ADRs) in residents of long-term care facilities (LTCFs) compared with newer, more expensive drugs. Objective This study attempted to determine the effects of poor renal function on the rate of ADRs and any other variables on the tolerability of prophylaxis in this population. This would allow a high-risk subset of LTCF residents to be identified before prophylaxis, thus decreasing the risk for ADRs from amantadine. Methods In this retrospective case-control study, a course of standardized low-dose (100-mg/d tablets) amantadine prophylaxis was ordered for all 242 residents of Ten Broeck Commons LTCF in Lake Katrine, New York, without influenza A for 14 days. Chart data of residents who developed ADRs (ADR group) were compared with those of a selected group who did not (control group). Residents’ age, sex, renal function (blood urea nitrogen, serum creatinine, and creatinine clearance), dementia diagnosis, and number and classes of medications were compared. Results The ADR group comprised 25 residents (21 women, 4 men; mean [SD] age, 84.8 [8.4] years); the control group, 29 residents (23 women, 6 men; mean [SD] age, 85.7 [7.5] years). The development of ADRs was not associated with differences in age, sex, renal function, or any medical condition, including measured, preexisting mental status changes between the groups. The overall risk for ADRs in the 242 residents was highest between days 8 and 14 of prophylaxis (17 residents [7.0%]) compared with the first 7 days (8 residents [3.3%]). Acute confusion was the most common ADR. All ADRs resolved on cessation of treatment. Conclusions No preexisting medical condition was statistically associated with an increased risk for ADRs, but an association with the number of days of prophylaxis was observed. By shortening prophylaxis to 7 days, the ADR risk may be lowered to be commensurate with more expensive medications.