Definite Adverse Drug Reactions Research Articles

Costs associated with adverse drug reactions in an older population admitted to hospital: a prospective cohort study

PurposeThis study examines healthcare costs associated with adverse drug reactions (ADR) in an older population admitted acutely to an Irish tertiary hospital. MethodsProspective cohort study involving older persons admitted to hospital with and without an ADR. Data was collected at baseline, during hospitalisation and post-discharge. Participants provided information on healthcare resource use three months before admission (baseline) and three months after discharge (follow-up). For each healthcare resource, unit costs were derived and applied. The average cost (standard deviation (SD)) associated with the hospital admission for the ADR and non-ADR are presented. In addition, baseline and follow-up care costs were compared using difference-in-difference analysis and presented with 95% confidence intervals (CI). Costs by preventability and severity of ADR are also presented.ResultsA total of n = 230 participants were included (n = 93 ADR and n = 137 without ADR). The average cost associated with hospital admission for an ADR was €9538 (SD €10442) and €9828 (SD €11770) for non-ADR. The additional follow-up costs (difference-in-difference) associated with the ADR was estimated at €2047 (95% CI: -€889 to €4983). The mean incremental follow-up cost of definite preventable ADRs was estimated at €1648 (95% CI: -€4310 to €7605), possible preventable ADRs €2259 (95 CI: -€1194 to €5712) and unavoidable ADRs €1757 (95% CI: -€3377 to €6890). The mean incremental follow-up cost associated with moderate severe ADRs was estimated at €1922 (95% CI: -€1088 to €4932) and €3580 (95% CI: -€4898 to €12,058) for severe ADRs. ConclusionADRs leading to hospital admission are associated with modest incremental healthcare costs during and three months after admission. Severe and possibly preventable ADRs were associated with higher costs.

Evaluation of Prescribing Pattern, Therapeutic Adherence and Occurrence of Adverse Drug Reactions in Patients with Type 2 Diabetes Mellitus

Background: Persistent hyperglycemia in diabetes mellitus (DM) is considered the leading cause of morbidity and mortality associated with both microvascular and macrovascular complications, having a greater economic impact. This study aimed to assess the impact of socioeconomic status, prescribing patterns, and patient compliance in type 2 diabetes mellitus patients. Method: This study was carried out at the Department of Medicine and Diabetic Clinic of Hakeem Abdul Hameed (HAH) Centenary Hospital at Hamdard University, New Delhi, India. We conducted a prospective observational study on prescribing patterns and monitoring adverse drug reactions (ADRs) in patients with type 2 DM (T2DM) under standard care. We enrolled 150 confirmed cases, and data was obtained from pre-validated questionnaires and then coded and analyzed to observe the association between variables. Results: The glycosylated haemoglobin level in 56% of the cases was between 6.4 to 8.0, and cardiovascular complications were observed as the major comorbidities. 45.33 % of the cases were on mono drug therapy, and metformin (23. 52 %) was the drug of choice, followed by glimepiride (23.52 %). Among the dual drug therapies, sitagliptin with metformin and triple-drug therapy, glimepiride concurrent with metformin and voglibose was the most preferred drug in the treatment of T2DM. Sitagliptin was observed to be a major patient burden (46.213 USD). In only 7.33 % of the cases, we observed definite ADR in T2DM patients. Underprivileged awareness, mainly due to low literacy, was a major concern in the development of new cases of T2DM. Conclusion: We observed better patient compliance; however, a disease awareness program must be implemented. The use of oral hypoglycaemic drugs is still dominant in clinical practice and cardiovascular disorders as comorbidities emerge as a greater challenge in terms of patient outcome and cost burden.

Adverse Drug Reactions at Nonelective Hospital Admission in Children and Adolescents: Comparison of 4 Causality Assessment Methods.

This study aimed to compare assessment methods to determine adverse drug reactions (ADRs) at nonelective hospital admission in pediatric patients, to investigate the interrater reliability of assessment methods in pediatric care, and to analyze symptoms related to ADRs and (suicidal) drug intoxications. For 1 year, the medical records of nonelective patients admitted to a university pediatric department were evaluated for potential ADRs using 4 assessments methods by 1 experienced rater. Krippendorff α was calculated from a sample of 14 patients evaluated by 4 experienced raters to determine interrater reliability. In 1831 nonelective hospital admissions, 63.4% (1161 of 1831) of patients had received at least one drug before admission. We found a potential causal relationship between drugs and symptoms documented at admission and thus potential ADRs according to Naranjo in 23.3% (271 of 1161) of those patients, World Health Organization - Uppsala Monitoring Centre (WHO-UMC) in 22.5% (261 of 1161), Koh in 21.7% (252 of 1161), and Begaud in 16.5% (192 of 1161). The probability rating of the potential causal relationships varied considerably between the methods (Naranjo-Begaud, P < 0.01; Naranjo-Koh, P < 0.001; Koh-Begaud, P < 0.01; Begaud-WHO-UMC, P < 0.01). Acceptable interrater reliability (α ≥ 0.667) was only obtained for WHO-UMC (α = 0.7092). The most frequently identified definite ADR was sedation in 1.5% of all nonelective patients with medication before hospital admission. In 1.2% (22 of 1831) of all nonelective admissions, we found drug intoxications with suicidal intent. The assessment methods showed a high variability in the determination of a potential causal relationship between drug and documented symptom, in the classification of the probability of ADRs, and suboptimal interrater reliability. Thus, their feasibility in pediatric patients is limited.

Hemorrhagic Events in Patients Receiving Heparin or Enoxaparin in Combination With Oral Antithrombotics, NSAIDs, and Antiplatelet Medications: A Multi-Center Case-Series Study

Background: Hemorrhagic events are amongst the significant adverse effects of injectable anticoagulants such as heparin and enoxaparin. This undesirable effect needs close monitoring of their use for clinically relevant drug-drug interactions.&#x0D; Objectives: To study the rate of hemorrhagic events, the anatomical site, and the severity of the bleeding in patients receiving heparin or enoxaparin in combination with clopidogrel, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), and warfarin.&#x0D; Methods: We designed a prospective, multi-center, case-series study. Patients admitted to two teaching hospitals who received either an NSAID, or warfarin, or clopidogrel were evaluated. Any hemorrhagic event was recorded by Yellow Card Scheme. Also, the Naranjo scale was utilized for causality assessment.Results: A total of 123 patients were eligible for inclusion. They were admitted between November 2014 and April 2015. Sixty-five patients (52.5%) received heparin and 58 patients (47.2%) received enoxaparin. Of 123 patients, 115 patients (93.5%) received aspirin, 69 (56.1%) warfarin, 34 (27.6%) an antiplatelet medication, and 121 (98.4%) NSAIDs in combination with heparin or enoxaparin. Overall, 26 cases (21.1%) of the hemorrhagic incident were reported, of whom six cases (4.9%) were categorized as major bleeding. Patients receiving heparin constituted the largest proportion among all 26 hemorrhagic incidents (57.7%). All patients with the hemorrhagic incident had aspirin in their medication regimen, while 19 patients (73.0%) were concomitantly receiving warfarin as well. Hematuria (46.2%), hematoma in the injection site (38.5%), and hematoma (34.6%) were the top three types of hemorrhagic events. In Naranjo scale analysis, 19 patients scored more than 9 points, indicating a definite Adverse Drug Reaction (ADR) causality. Moreover, seven patients scored 5 to 8, affirming a possible association with ADR.&#x0D; Conclusion: The risk of hemorrhagic can be influenced by undesirable drug-drug interactions. Close monitoring of high-risk patients is advised to prevent adverse hemorrhagic reactions. Further studies to detect the explanatory factors associated with the hemorrhagic events are recommended.&#x0D;

Adverse Drug Reactions Study of Antihypertensive Drugs in Primary Care Settings

Hypertension is one of the high-prevalence diseases in primary care. Failure to achieve the target of blood pressure is affected by non-compliance due to the antihypertensive adverse reactions. This study aims to determine adverse drug reaction (ADR) of antihypertensive drugs in primary care settings. A cross sectional study was conducted in “Sibela” Primary Care in Surakarta on March 2019. Investigators interviewed patients directly and observed supporting data from medical records. Hypertension patients with antihypertensive drugs at least for a month were eligible in this study. Then, the data were analyzed by the Liverpool algorithm that interpreted in 4 scales: unlikely, possible, probable, and definite. A total 70 subject were dominated by female (80%). Monotherapy of antihypertensive drugs prescribed to patient in primary care were amlodipine (80%) and captopril (10%). Nine events of ADR were found in hypertension patient. None ADR were doubtful. Possible ADR of amlodipine was drowsiness (5.4%), whereas probable ADR were nausea (3.4%), diuresis (1.8%), and abdominal pain (1.8 %). Definite ADR of captopril was dry mouth (14.3%) and probable ADR was abdominal pain (14.3%). Further investigation regarding the drowsiness, ADR of amlodipine, was needed.

Adverse drug reactions of Yunnan Baiyao capsule: a multi-center intensive monitoring study in China.

Yunnan Baiyao capsule (YBC), a marketed herbal medicine in mainland China, is widely used to control bleeding. This study's aim was to determine the occurrence of YBC-related adverse drug reactions (ADRs) among users of the medicine. This hospital-intensive monitoring study was conducted in 163 hospitals across China. Consumers who used YBC (Z53020799) between June 2015 and December 2016 were included. By face-to-face interview or telephone, the circumstances and experiences of their adverse events (AEs), during drug taking and 14 days after drug withdrawal, were recorded at follow-up and later encoded by International Conference on Harmonisation (ICH) 1997. The Naranjo Adverse Reaction Probability Scale (APS) was used to determine the likelihood of ADRs. A total of 31,556 participants were included (follow-up rate 99.40%). AEs occurred in 742 participants, of which 561 were reported as "not related with drug use" by their physician-in-charge. Based on the remaining 181 cases, the overall ADR incidence was 1.17% (intention to treat) and 0.58% (per protocol), with abnormal findings mainly concentrated in the digestive system, skin and respiratory system. The top 5 frequently reported reactions were nausea and vomiting (0.1785%, 56 cases of 31,367 participants), functional diarrhea (0.1180%, 37 of 31,367 participants), stomach discomfort (0.0893%, 28 of 31,367 participants), rash (0.0574%, 18 of 31,367 participants) and gastro-esophageal reflux (0.0383%, 12 of 31,367 participants). Among them, functional diarrhea and stomach discomfort were judged as definite ADRs of YBC. In this large study, treatment of YBC was found to be associated with ADRs with an incidence of 1.17%, although most were relatively mild and not considered to be life-threatening.

Drug-Induced Pyoderma Gangrenosum: A Review.

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that may be caused by an adverse drug reaction. We discuss the clinical presentation and outcomes of 52 cases of drug-induced PG reported to date in the literature. We conducted our literature search for case reports of drug-induced PG using keywords on PubMed and Medical Subject Heading (MeSH) terms on MEDLINE and EMBASE. To assess the probability that each case of PG was related to drug therapy, we used the Naranjo criteria. We identified 44 studies in the literature, with a total of 52 cases of drug-induced PG. The mean Naranjo score for cocaine-induced PG (n=13) was 9.4, indicating a definite adverse drug reaction, while the mean Naranjo scores for isotretinoin (n=5), propylthiouracil (n=5), and sunitinib (n=5) were 6.2, 6.8, and 7.4, respectively, indicating probable adverse drug reactions. Drugs should be considered as a possible triggering event whenever PG is diagnosed, and clinicians should particularly consider this in patients taking isotretinoin, propylthiouracil, or sunitinib, as well as in patients with a history of cocaine use.

Predicting the Risk of Adverse Drug Reactions in Older Inpatients: External Validation of the GerontoNet ADR Risk Score Using the CRIME Cohort.

Adverse drug reactions (ADRs) in older people are often preventable, indicating that screening and prevention programs aimed at reducing their rate are needed in this population. The aim of this study was to externally validate the GerontoNet ADR risk score and to assess its validity in specific subpopulations of older inpatients. Data from the prospective CRIteria to assess appropriate Medication use among Elderly complex patients (CRIME) cohort were used. Dose-dependent and predictable ADRs were classified as type A, probable or definite ADRs were defined according to the Naranjo algorithm, and diagnostic accuracy was tested using receiver operating characteristic (ROC) analyses. Sensitivity and specificity were calculated for a cut-off point of 4. The mean age of the 1075 patients was 81.4years (standard deviation 7.4) and the median number of drugs was 10 (range 7-13). At least one ADR was observed in 70 patients (6.5%); ADRs were classified as type A in 50 patients (4.7%) and defined as probable or definite in 41 patients (3.8%). Fair diagnostic accuracy to predict both type A and probable or definite ADRs was found in subpopulations aged <70 or ≥80years with heart failure, diabetes, or a previous ADR. Good accuracy to predict type A ADRs was found in patients with a low body mass index (BMI; >18.5kg/m2) and a Mini-Mental State Examination (MMSE) score of >24/30 points, as well as in patients with osteoarthritis. The cut-off point of 4 points yielded very good sensitivity but poor specificity results in these subpopulations. This study suggests that the GerontoNet ADR risk score might represent a pragmatic approach to identifying specific subpopulations of older inpatients at increased risk of an ADR with a fair to good diagnostic accuracy.

Confounding Variables and the Performance of Triggers in Detecting Unreported Adverse Drug Reactions

PurposeThis study explored the performance of trigger in detecting adverse drug reactions (ADRs), the confounding variables impairing the causal association of the ADRs, and the underreporting rate by hospital health professionals. MethodsA 6-month cross-sectional study was conducted in a public general hospital. Data collection was conducted in 2 stages: (1) screening of patient hospitalizations to identify suspected ADRs with 9 triggers developed by the Institute of Healthcare Improvement; and (2) chart review to perform the causality assessment of the suspected ADRs identified, to describe the confounding variables associated with detection of suspected ADRs that were not drug induced, and to analyze the positive predictive value of triggers in recognizing ADRs. To estimate the underreporting rate, ADRs detected by using the tool were compared with ADRs reported by health professionals during the same period. FindingsDuring the study period, 3318 hospitalizations were analyzed. A total of 837 suspected ADRs were identified. However, after causality assessment, 356 were definite ADRs. Confounding variables associated with the detection-suspected ADRs were related to the clinical conditions of inpatients. The use of triggers contributed to increased ADR detection by 10.5%. The performance ranged from 0.00 to 0.75, with an overall positive predictive value of 0.43. Six ADRs were spontaneously reported, of which just 1 was also detected by using the trigger tool. Only 1 of 356 potential ADRs was reported by health professionals. ImplicationsFindings show that the use of triggers contributes to detecting ADRs underreported by health professionals. However, confounding variables impaired the performance of the tool because they underestimated the causal association. Furthermore, both methods are complementary to early recognition of drug-induced harm and should be applied together in health institutions to contribute to policies of risk management, drug safety, and optimization of pharmacotherapy.

Prediction of Hospitalization due to Adverse Drug Reactions in Elderly Community-Dwelling Patients (The PADR-EC Score).

BackgroundAdverse drug reactions (ADRs) are the major cause of medication-related hospital admissions in older patients living in the community. This study aimed to develop and validate a score to predict ADR-related hospitalization in people aged ≥65 years.MethodsADR-related hospitalization and its risk factors were determined using a prospective, cross-sectional study in patients aged ≥65 years admitted to two hospitals. A predictive model was developed in the derivation cohort (n = 768) and the model was applied in the validation cohort (n = 240). ADR-related hospital admission was determined through expert consensus from comprehensive reviews of medical records and patient interviews. The causality and preventability of the ADR were assessed based on the Naranjo algorithm and modified Schumock and Thornton criteria, respectively.ResultsIn the derivation sample (mean [±SD] age, 80.1±7.7 years), 115 (15%) patients were admitted due to a definite or probable ADR; 92.2% of these admissions were deemed preventable. The number of antihypertensives was the strongest predictor of an ADR followed by presence of dementia, renal failure, drug changes in the preceding 3 months and use of anticholinergic medications; these variables were used to derive the ADR prediction score. The predictive ability of the score, assessed from calculation of the area under the receiver operator characteristic (ROC) curve, was 0.70 (95% confidence interval (CI) 0.65–0.75). In the validation sample (mean [±SD] age, 79.6±7.6 years), 30 (12.5%) patients’ admissions were related to definite or probable ADRs; 80% of these admissions were deemed preventable. The area under the ROC curve in this sample was 0.67 (95% CI 0.56–0.78).ConclusionsThis study proposes a practical and simple tool to identify elderly patients who are at an increased risk of preventable ADR-related hospital admission. Further refinement and testing of this tool is necessary to implement the score in clinical practice.

High-dose cytosine arabinoside-induced symptomatic bradycardia

Cardiac complications of high-dose cytosine arabinoside (HiDAC), although rare, predominantly include pericarditis, pericardial effusion and cardiomyopathy (with concurrent use of cyclophosphamide). Clinically significant arrhythmias associated with HiDAC, although reported in the literature, are rare. The following case report has for the first time used the Naranjo Scale to document a high-probability association (definite adverse drug reaction) of cytarabine with symptomatic sinus bradycardia.

ADRIC: Adverse Drug Reactions In Children – a programme of research using mixed methods

AimsTo comprehensively investigate the incidence, nature and risk factors of adverse drug reactions (ADRs) in a hospital-based population of children, with rigorous assessment of causality, severity and avoidability, and to assess the consequent impact on children and families. We aimed to improve the assessment of ADRs by development of new tools to assess causality and avoidability, and to minimise the impact on families by developing better strategies for communication.Review methodsTwo prospective observational studies, each over 1 year, were conducted to assess ADRs in children associated with admission to hospital, and those occurring in children who were in hospital for longer than 48 hours. We conducted a comprehensive systematic review of ADRs in children. We used the findings from these studies to develop and validate tools to assess causality and avoidability of ADRs, and conducted interviews with parents and children who had experienced ADRs, using these findings to develop a leaflet for parents to inform a communication strategy about ADRs.ResultsThe estimated incidence of ADRs detected in children on admission to hospital was 2.9% [95% confidence interval (CI) 2.5% to 3.3%]. Of the reactions, 22.1% (95% CI 17% to 28%) were either definitely or possibly avoidable. Prescriptions originating in the community accounted for 44 out of 249 (17.7%) of ADRs, the remainder originating from hospital. A total of 120 out of 249 (48.2%) reactions resulted from treatment for malignancies. Off-label and/or unlicensed (OLUL) medicines were more likely to be implicated in an ADR than authorised medicines [relative risk (RR) 1.67, 95% CI 1.38 to 2.02;p &lt; 0.001]. When medicines used for the treatment of oncology patients were excluded, OLUL medicines were not more likely to be implicated in an ADR than authorised medicines (RR 1.03, 95% CI 0.72 to 1.48;p = 0.830). For children who had been in hospital for &gt; 48 hours, the overall incidence of definite and probable ADRs based on all admissions was 15.9% (95% CI 15.0 to 16.8). Opiate analgesic drugs and drugs used in general anaesthesia (GA) accounted for &gt; 50% of all drugs implicated in ADRs. The odds ratio of an OLUL drug being implicated in an ADR compared with an authorised drug was 2.25 (95% CI 1.95 to 2.59;p &lt; 0.001). Risk factors identified were exposure to a GA, age, oncology treatment and number of medicines. The systematic review estimated that the incidence rates for ADRs causing hospital admission ranged from 0.4% to 10.3% of all children [pooled estimate of 2.9% (95% CI 2.6% to 3.1%)] and from 0.6% to 16.8% of all children exposed to a drug during hospital stay. New tools to assess causality and avoidability of ADRs have been developed and validated. Many parents described being dissatisfied with clinician communication about ADRs, whereas parents of children with cancer emphasised confidence in clinician management of ADRs and the way clinicians communicated about medicines. The accounts of children and young people largely reflected parents’ accounts. Clinicians described using all of the features of communication that parents wanted to see, but made active decisions about when and what to communicate to families about suspected ADRs, which meant that communication may not always match families’ needs and expectations. We developed a leaflet to assist clinicians in communicating ADRs to parents.ConclusionThe Adverse Drug Reactions In Children (ADRIC) programme has provided the most comprehensive assessment, to date, of the size and nature of ADRs in children presenting to, and cared for in, hospital, and the outputs that have resulted will improve the management and understanding of ADRs in children and adults within the NHS. Recommendations for future research: assess the values that parents and children place on the use of different medicines and the risks that they will find acceptable within these contexts; focusing on high-risk drugs identified in ADRIC, determine the optimum drug dose for children through the development of a gold standard practice for the extrapolation of adult drug doses, alongside targeted pharmacokinetic/pharmacodynamic studies; assess the research and clinical applications of the Liverpool Causality Assessment Tool and the Liverpool Avoidability Assessment Tool; evaluate, in more detail, morbidities associated with anaesthesia and surgery in children, including follow-up in the community and in the home setting and an assessment of the most appropriate treatment regimens to prevent pain, vomiting and other postoperative complications; further evaluate strategies for communication with families, children and young people about ADRs; and quantify ADRs in other settings, for example critical care and neonatology.FundingThe National Institute for Health Research Programme Grants for Applied Research programme.

EPA-0761 – The application of naranjo's adverse drug reaction (ADR) probability scale to elicit the direct correlation between NRG3 consumption and the onset of psychotic symptoms

Background NGR3 substance is usually in the form of a white powder that is consumed by humans to create a legal high; feelings of euphoria and reduce tiredness. It is a GHB analogue and when consumed turns into GHB in the body. A 40year old male patient who ingested NRG3 was admitted thrice with symptoms of hearing voices, hyperactivity, agression and the inability to sleep. Aim and objective To determine the probability of onset of psychotic symptoms as an effect of ingestion of NRG3. Methodology To apply Naranjo's ADR probability scale and on the basis of the weighted questions of the scale, which examine factors such as temporal association of drug administration and event occurrence, alternative causes for the event, drug levels, dose-response relationships and previous patient experience with the substance NRG3. Results Using the scale, the score indicated that there was a definite adverse drug reaction with NRG3. Conclusions A definite adverse drug reaction of psychotic symptoms did occur with the ingestion of NRG3.

Adverse drug reactions and off-label and unlicensed medicines in children: a nested case?control study of inpatients in a pediatric hospital

BackgroundOff-label and unlicensed (OLUL) prescribing has been prevalent in pediatric practice. Using data from a prospective cohort study of adverse drug reactions (ADRs) among pediatric inpatients, we aimed to test the hypothesis that OLUL status is a risk factor for ADRs.MethodsA nested case?control study was conducted within a prospective cohort study. Details of all medicines administered were recorded, including information about OLUL status. The odds ratio for OLUL medicines being implicated in a probable or definite ADR was calculated. A multivariate Cox proportional hazards regression model was fitted to the data to assess the influence that OLUL medicine use had on the hazard of an ADR occurring.ResultsA total of 10,699 medicine courses were administered to 1,388 patients. The odds ratio (OR) of an OLUL medicine being implicated in an ADR compared with an authorized medicine was 2.25 (95% confidence interval (CI) 1.95 to 2.59). Medicines licensed in children but given to a child below the minimum age or weight had the greatest odds of being implicated in an ADR (19% of courses in this category were implicated, OR 3.54 (95% CI 2.82 to 4.44). Each additional OLUL medicine given significantly increased the hazard of an ADR (hazard ratio (HR) 1.3 95% CI 1.2 to 1.3, P <0.001). Each additional authorized medicine given also significantly increased the hazard (HR 1.2 95% CI 1.2 to 1.3, P <0.001).ConclusionsOLUL medicines are more likely to be implicated in an ADR than authorized medicines. The number of medicines administered is a risk factor for ADRs highlighting the need to use the lowest number of medicines, at the lowest dose for the shortest period, with continual vigilance by prescribers, in order to reduce the risk of ADRs.

Dysarthria induced by irinotecan in a patient with colorectal cancer

Successful management and subsequent prevention of a rare adverse drug reaction (ADR) associated with irinotecan chemotherapy are reported. A 49-year-old man with meta-static colon cancer undergoing treatment with i.v. irinotecan (180 mg/m(2) to be infused over 120 minutes) as part of a multidrug chemotherapy regimen developed dysarthria about 90 minutes into irinotecan infusions on two occasions. In both instances, the dysarthric symptoms (numbness of the tongue and difficult speech) resolved after the discontinuation of irinotecan and administration of hydration therapy. Brain imaging studies showed no functional or structural abnormalities; several concomitantly administered medications, including metoclopramide, palonosetron, and other components of the chemotherapy regimen, were deemed unlikely to have played a causal or contributory role in the episodes of dysarthria. Application of the ADR probability scale of Naranjo et al. in this case yielded a score of 9, indicating a definite ADR caused by irinotecan. For subsequently administered chemotherapy cycles, the duration of the patient's irinotecan infusions was increased (to 180 minutes for cycles 3-5 and to 240 minutes for cycles 6-12). Dysarthria did not recur and, with the exception of transient tongue twisting during two of the 180-minute infusions, he completed the full course of irinotecan therapy without a recurrence of dysarthric symptoms. Irinotecan-induced dysarthria in a man being treated for colon cancer resolved with the discontinuation of irinotecan. With increases in the duration of infusion, the man received additional irinotecan treatments with no recurrence of dysarthria.

Association Between Adverse Reactions to Allopurinol and Exposures to High Maintenance Doses

The objective of this study was to estimate the association between adverse drug reactions (ADRs) and exposure to allopurinol maintenance doses higher than those in the 1984 suggested limits of Hande et al. adjusted for level of renal function. We conducted a retrospective review of electronic health records of patients prescribed allopurinol from January 1, 2004, to June 30, 2011, to identify those who had a definite or possible ADR to allopurinol. The associations of ADRs with maintenance doses of allopurinol 1 to 1.5 times and more than 1.5 times the suggested limits of Hande et al. compared with doses within the suggested limits of Hande et al. were estimated using logistic regression models. Of 4755 patients prescribed allopurinol, 2946 had a serum creatinine measured within 6 months of starting allopurinol, and of these, 1268 patients' records were reviewed. Forty-eight patients had a definite ADR to allopurinol, 2 of which were allopurinol hypersensitivity syndrome. The odds ratios of definite ADRs with maintenance doses of allopurinol 1.0 to 1.5 times and more than 1.5 times suggested compared with doses within suggested limits were, respectively, 1.42 (95% confidence interval [CI], 0.66-3.04) and 2.04 (95% CI, 0.87-4.77). Among those with an allopurinol maintenance dose more than 1.5 times suggested limits, the proportion of patients with a definite ADR was 2.6% (95% CI, 1.0%-5.2%). There is no significant association of high maintenance doses of allopurinol with ADRs, and the absolute risk of ADRs at doses higher than 1.5 times the 1984 suggested limits of Hande et al. is low. Cautious, gradual increases in allopurinol maintenance doses above the suggested limits of Hande et al. are warranted if necessary to achieve a serum uric acid level less than 6 mg/dL.

Adverse drug reactions and off-label and unlicensed medicines in children: a nested case-control study of paediatric inpatients

AimsWe examined the impact of off-label and unlicensed (OLUL) prescribing on adverse drug reaction (ADR) risk in paediatric inpatients. We hypothesised that OLUL prescribing may be a risk factor for...

An Algorithm to Detect Adverse Drug Reactions in the Neonatal Intensive Care Unit

Critically ill newborns in neonatal intensive care units (NICUs) are at greater risk of developing adverse drug reactions (ADRs). Differentiation of ADRs from reactions associated with organ dysfunction/immaturity is difficult. Current ADR algorithm scoring was established arbitrarily without validation in infants. The study objective was to develop a valid and reliable algorithm to identify ADRs in the NICU. Algorithm development began with a 24-item questionnaire for data collection on 100 previously suspected ADRs. Five pediatric pharmacologists independently rated cases as definite, probable, possible, and unlikely ADRs. Consensus "gold standard" was reached via teleconference. Logistic regression and iterative C programs were used to derive the scoring system. For validation, 50 prospectively collected ADR cases were assessed by 3 clinicians using the new algorithm and the Naranjo algorithm. Weighted kappa and intraclass correlation coefficient (ICC) were used to compare validity and reliability of algorithms. The new algorithm consists of 13 items. Kappa and ICC of the new algorithm were 0.76 and 0.62 versus 0.31 and 0.43 for the Naranjo algorithm. The new algorithm developed using actual patient data is more valid and reliable than the Naranjo algorithm for identifying ADRs in the NICU population. Because of the relatively small and nonrandom samples, further refinement and additional testing are needed.

1639 Adverse Drug Reactions Associated with Ciprofloxacin in Neonates

BackgroundCiprofloxacin is used in many nurseries in developing countries. Data on drug concentrations and side effects of ciprofloxacin in neonates is limited.AimsTo study adverse drug reactions(ADR) associated with ciprofloxacin in...

Days lost due to disability of diclofenac-induced adverse drug reactions

Disability Adjusted Life Years (DALY) is a widely used measure to quantify the burden of diseases or illness. DALYs for a disease is calculated as the sum of the Years of Life Lost (YLL) due to premature mortality in the population and the equivalent healthy Years Lost due to Disability (YLD). The only difference from the YLD and Days Lost due to Disability (DLD) calculation is that instead of considering the duration of Adverse Drug Reaction (ADR) in years, it is calculated in days. DLD was measured for diclofenac tablets to prepare the ADR profile. The study was done on the patients (18-65 years old) attending the community pharmacy at Kasaragod district, South India, with prescription of diclofenac tablets. Patients reported ADRs on their next visit to the pharmacy or they had called to the provided phone number and reported it. Disability Weight (DW) was calculated in an analogue scale from 0-1. Zero represent complete health and 1 represent death or equivalent condition. DW was multiplied with occurrence and duration of ADRs in days. About 943 patients received diclofenac tablets in 1000 prescriptions were successfully followed up for possible, probable and definite ADRs. A total of 561 reactions reported in 2010 for diclofenac tablet in the study population. There were 34 different types of ADRs under 12 physiological systems/organs. Most common reactions were on gastrointestinal (GI) system (48%), followed by skin (14%), Central Nervous System (10%), renal (7%), and cardiovascular (7%). Abdominal pain, cramps or flatulence was the highest occurring GI ADR (107), followed by 43 rashes, 42 nausea/vomiting, 37 indigestion, 34 peptic ulcers, 31 edema etc. DLD for peptic ulcer was considerably high (0.078) per 1000 of the study population on diclofenac. The most damaging ADR were peptic ulcer with or without perforation, followed by rash 0.036 DLD and edema 0.027 DLD. There was considerable DLD by acute renal failure (0.012) Steven-Johnson syndrome (0.013) even though few cases were reported. Diclofenac has a complex adverse drug profile. Around 34 types of reactions were reported. Diclofenac was widely prescribed because of the experiential belief of comparative safety with other NSAIDs. The study shows the importance of pharmacovigilance even on the most prescribed medicine. Most disabling ADR for the study population was peptic ulcer with or without perforation. YLD or DLD are useful measures of calculating disability caused by ADRs. Future studies could focus on improving the usefulness & precision of DLD.