Serious Adverse Drug Reactions Research Articles

A PROSPECTIVE STUDY OF ADVERSE DRUG REACTIONS DUE TO PLATINUM ANALOGS - CHEMOTHERAPY IN A TERTIARY CARE HOSPITAL

Objective: The objective of this study was to analyze the types of adverse drug reactions (ADRs) associated with platinum analogs (cisplatin, carboplatin and oxaliplatin) used for cancer chemotherapy in a tertiary care hospital and determine their causal relationship with the offending drug.Methods: This prospective, observational, non-interventional study was conducted in a tertiary care hospital at GSVM Medical College Kanpur, India, for 4 months. Patients of all age and either sex were included in the study. ADRs were reported by the physicians of oncology department of the hospital and ADRs were assessed for different parameters -causality, outcome, and seriousness of ADR as per the World Health Organization (WHO), type of ADRs as per expanded Rawlins and Thompson’s classification, predictability using council for international organization of medical sciences guidelines and severity using modified Hartwig’s scale. Descriptive statistics were used for data analysis.Results: A total of 140 ADRs were reported from platinum analogs following treatment of different types of cancer in hospital. The burden of ADRs in each patient was 2.41. Most of the ADRs were observed in the age group of 40–60 years. Vomiting (27 ADRs) was commonly reported reaction. Among platinum analogs, cisplatin leads to 82 ADRs (58.57%) followed by carboplatin with 53 ADRs (37.86%) and least with oxaliplatin 5 ADRs (3.57%). Most of the ADRs on causality assessment were possible (104, 74.29%) and probable (36, 25.71%) in nature. Type -A ADRs account for 4/5th of the total reported ADRs, followed by Type-B and C. Severity of 90.71% ADRs was found to be mild followed by moderate, with no case of severe and serious nature. Nearly, most of the ADRs were of predictable type (97.14%).Conclusion: The potential of platinum analogs to cause ADRs is high; thus, the need of effective ADRs monitoring is highly emphasized.

Characterization of serious adverse drug reactions as cause of emergency department visit in children: a 5-years active pharmacovigilance study

BackgroundTo describe frequency, preventability and seriousness of adverse drug reactions (ADRs) in children as cause of emergency department (ED) admission and to evaluate the association between specific factors and the reporting of ADRs.MethodsA retrospective analysis based on reports of suspected ADRs collected between January 1st, 2012 and December 31st, 2016 in the ED of Meyer Children’s Hospital (Italy). Demographics, clinical status, suspected drugs, ADR description, and its degree of seriousness were collected. Logistic regression was used to estimate the reporting odds ratios (RORs) with 95% confidence intervals (CIs) of potential predictors of ADR seriousness.ResultsWithin 5 years, we observed 834 ADRs (1100 drug-ADR pairs), of whom 239 were serious; of them, 224 led to hospitalization. Patients were mostly treated with one drug. Among patients treated with more than one drug, 78 ADRs presented a potential interaction. The most frequently reported ADRs involved gastrointestinal system. The most frequently reported medication class was antinfectives. Risk of serious ADR was significantly lower in children and infants compared to adolescents (ROR 0.41 [95% CI: 0.27–0.61] and 0.47 [0.32–0.71], respectively), and it was significantly increased in subjects exposed to more than one drug (ROR 1.87 [1.33–2.62] and 3.01 [2.07–4.37] for subjects exposed to 2 and 3 or more drugs, respectively). Gender, interactions and off-label drug use did not influence the risk of serious ADRs.ConclusionActive surveillance in pharmacovigilance might represent the best strategy to estimate and characterize the clinical burden of ADRs in children.

Assessment of knowledge, attitude and practice of adverse drug reaction reporting among healthcare professionals in secondary and tertiary hospitals in the capital of Pakistan

Adverse Drug Reactions (ADRs) underreporting is a great challenge to pharmacovigilance. Healthcare professionals should consider ADR reporting as their professional obligation because the effective system of ADR reporting is important to improve patient care and safety. This study was designed to assess the knowledge, attitude, practice and factors associated with ADR reporting by healthcare professionals (physicians and pharmacists) in secondary and tertiary hospitals of Islamabad. A pretested questionnaire comprising of 27 questions (knowledge 12, attitude 4, practice 9 and factors influencing ADR reporting 2) was administered to 384 physicians and pharmacists in public and private hospitals. Respondents were evaluated for their knowledge, attitude and practice related to ADR reporting. Additionally, the factors which encourage and discourage respondents to report ADRs were also determined. The data was analysed by using SPSS statistical software. Among 384 respondents, 367 provided responses to questionnaire, giving a response rate of 95.5%. The mean age was 28.3 (SD = 6.7). Most of the respondents indicated poor ADR reporting knowledge (83.1%). The majority of respondents (78.2%) presented a positive attitude towards ADR reporting and only a few (12.3%) hospitals have good ADR reporting practice. The seriousness of ADR, unusualness of reaction, new drug involvement and confidence in the diagnosis of ADR are the factors which encourage respondents to report ADR whereas lack of knowledge regarding where and how to report ADR, lack of access to ADR reporting form, managing patient is more important than reporting ADR legal liability issues were the major factors which discourage respondents to report ADR. The study reveals poor knowledge and practice regarding ADR reporting. However, most of the respondents have shown a positive attitude towards ADR reporting. There is a serious need for educational training as well as sincere and sustained efforts should be made by Government and Hospital Authorities to ensure proper implementation of ADR reporting system in all of the hospitals.

Large-scale surveillance study of the safety and effectiveness of entecavir in Korean patients with chronic hepatitis B

Background/AimsEntecavir (ETV) is effective and safe antiviral agent against hepatitis B virus (HBV) in clinical and real-world setting but, most studies were performed in single institute or have limitation in patient’s number. A large-scale nation-wide real-world surveillance study was carried out to investigate safety, efficacy and clinical effectiveness of ETV in Korean patients with chronic hepatitis B (CHB).MethodsBetween 2006 and 2012, 3,444 patients were enrolled from 132 Korean institutions. For the safety assessment, investigators recorded the occurrence of observed and patient-reported adverse events (AEs), as well as laboratory abnormalities. Efficacy, which consisted of change in HBV DNA and alanine aminotransferase (ALT), was evaluated in patients who had received at least 16 weeks of ETV treatment. Overall clinical effectiveness, based on improvement of ALT, HBV DNA and patient’s symptoms, was evaluated by physicians.ResultsOf the patients, 3,367 were evaluated for safety and 3,115 for efficacy and clinical effectiveness. Three hundred and eighty AEs were reported in 255 cases (7.57%), and 67 adverse drug reactions in 54 cases (1.6%). Serious AEs (SAE) were 19 events in nine cases (0.27%). Serious adverse drug reactions (SADR) were three events in two cases (0.06%), and unexpected SAE/SADR were three events in two cases (0.06%). Medical history and concomitant medications were factors inf luencing incidence rates of AEs. Overall clinical effectiveness rate was 96.53%, which was clinically assessed as marked improved or improved state.ConclusionsThis study showed that ETV was well tolerated and clinically effective in Korean patients with CHB in a real-world nation-wide setting.

The adverse drug reaction reporting assignment for specialist oncology nurses: a preliminary evaluation of quality, relevance and educational value in a prospective cohort study

In a new prescribing qualification course for specialist oncology nurses, we thought that it is important to emphasize pharmacovigilance and adverse drug reaction (ADR) reporting. We aimed to develop and evaluate an ADR reporting assignment for specialist oncology nurses. The quality of report documentation was assessed with the “Clinical Documentation tool to assess Individual Case Safety Reports” (ClinDoc). The relevance of the reports was evaluated in terms of ADR seriousness, the listing for additional monitoring of the drug by European Medicines Agency (EMA), and lack of labelling information about the ADR. Nurses’ opinions of the assignment were evaluated using an E-survey. Thirty-three ADRs were reported, 32 (97%) of which were well documented according to ClinDoc. Thirteen ADRs (39%) were “serious” according to CIOMS criteria. In five cases (15%), the suspect drugs were listed for additional monitoring by EMA and in seven cases (21%), the ADR was not mentioned in the Summary of Product Characteristics. Twenty-five (78.1%) of the 32 enrolled nurses completed the E-survey. Most were > 45 years of age (68%), female (92%) and had extensive clinical experience (6–33 years). All agreed or completely agreed that the reporting assignment was useful, that it fitted in daily practice and that it increased their attention for medication/patient safety. A large majority (84.0%) agreed the assignment changed how they dealt with ADRs. Specialist oncology nurses are capable of reporting ADRs, and they considered the assignment useful. The assignment yielded valuable, relevant, and well-documented ADR reports for pharmacovigilance practice.

Palivizumab Prophylaxis Against Respiratory Syncytial Virus Infection in Children with Immunocompromised Conditions or Down Syndrome: A Multicenter, Post-Marketing Surveillance in Japan.

ObjectiveThe aim of this study was to assess the safety and effectiveness of palivizumab for the prevention of lower respiratory tract infection (LRI) caused by respiratory syncytial virus (RSV) in children with immunocompromised conditions or Down syndrome.MethodsIn this multicenter, post-marketing surveillance study (December 2013 to December 2015), children aged ≤24 months with immunocompromised conditions or Down syndrome (without hemodynamically significant congenital heart disease) receiving palivizumab immunoprophylaxis during two RSV seasons were observed until 30 days after the final palivizumab injection. Safety [adverse events (AEs), serious AEs (SAEs), adverse drug reactions (ADRs), serious ADRs (SADRs)] and effectiveness (frequency, incidence, and duration of hospitalization due to RSV infections) were assessed.ResultsOf 304 patients receiving palivizumab, 167 (54.9%) had immunocompromised conditions, and 138 (45.4%) had Down syndrome; 260 (85.5%) completed palivizumab immunoprophylaxis. The annual mean (±standard deviation) number of doses was 5.3 (±2.4) per season. Overall, 220 AEs occurred in 99 patients (32.6%), including 89 SAEs in 53 patients (17.4%). Of these, 33 AEs in 25 patients (8.22%) were considered ADRs, and 13 ADRs in 11 patients (3.62%) were considered SADRs. In four patients, five SADRs (nephroblastoma and asthma in the same patient, septic shock, device-related infection, and drug-induced liver injury) were previously unreported; however, none were considered drug-related. During the observation period, five RSV infections occurred and two patients required hospitalization.ConclusionPalivizumab was generally safe and effective for the prevention of LRI caused by RSV in newborns, infants, and children with immunocompromised conditions or Down syndrome up to the age of 24 months.Electronic supplementary materialThe online version of this article (doi:10.1007/s40272-017-0264-y) contains supplementary material, which is available to authorized users.

Safety and effectiveness of tadalafil in pediatric patients with pulmonary arterial hypertension: a sub-group analysis based on Japan post-marketing surveillance

Objective: To evaluate the long-term safety and effectiveness of tadalafil in pediatric patients with pulmonary arterial hypertension (PAH) in real-world clinical practice.Methods: This is an observational surveillance of PAH patients receiving tadalafil in the contracted sites. A sub-group analysis was performed of 391 pediatric PAH patients (<18 years) who were included from 1,704 total patients in this surveillance. Safety was assessed from the frequency of adverse drug reactions (ADRs), discontinuations due to adverse events (AEs), and serious adverse drug reactions (SADRs). Effectiveness measurements included change in World Health Organization (WHO) functional classification of PAH, cardiac catheterization (pulmonary arterial pressure: PAP), and echocardiography (tricuspid regurgitation pressure gradient: TRPG). Survival rate was also measured.Results: The mean patient age was 5.7 ± 5.34 years. Associated PAH (APAH) and idiopathic PAH (IPAH) accounted for 76.0% and 17.6%, respectively, of the PAH patients. Patients were followed for up to 2 years. Among 391 patients analyzed for safety, the overall incidence rate of ADRs was 16.6%. The common ADRs (≥ 1%) were headache (2.8%), hepatic function abnormal, platelet count decreased (1.3% each), and epistaxis, (1.0%). Eleven patients (2.8%) reported 16 SADRs. Three patients died secondary to SADRs. For the effectiveness analysis, the incidence of WHO functional class improvement at 3 months, 1 year, and 2 years after the initiation of tadalafil and last observation in pediatric patients were 16.5%, 19.7%, and 16.3%, respectively. Both PAP and TRPG showed a statistically significant reduction at last observation.Conclusion: This manuscript reveals the use of tadalafil in the real-world pediatric population with an acceptable safety profile in Japan.

Effets indésirables « graves » du tramadol : bilan 2011–2015 de pharmacovigilance en France

Tramadol is an opioid and a serotonin reuptake inhibitor drug. It is approved for moderate to severe pain in adults. The aim of this study was to assess tramadol safety through a national pharmacovigilance study in France since dextropropoxyphen withdrawal in 2011. We described all serious adverse drug reactions (SADRs) reported with tramadol in adults in the French National PharmacoVigilance Database from August1st, 2011 to December31st, 2015. We identified 1512SADRs during the study period. The most frequently reported SADRs were neurological (29.4%, including troubles of consciousness [13.2%] and seizures [6.7%]), psychiatric (22.8%, including confusions [14.6%] and hallucinations [7.3%]) and gastrointestinal (17.0%, mostly nausea and vomiting [9.6%]). Unexpected SADRs were also reported: hyponatremia, cholestatic hepatitis, serotonin syndrome. This study demonstrates new unexpected hepatic and metabolic SADRs. Tramadol alone can induce serotonin syndrome in overdose situations.

Pharmacovigilance Training for Specialist Oncology Nurses —A Two Way Evaluation

Background: In a new prescribing qualifcation course for specialist oncology nurses, we thought it important to emphasize pharma-covigilance and adverse drug reaction (ADR)-reporting. To this end, our aim was to develop and evaluate an ADR reporting assignment for specialist oncology nurses. Methods: The quality of report documentation was assessed with the 'Clinical Documentation tool to assess Individual Case Safety Reports' (ClinDoc). The relevance of the reports was evaluated in terms of ADR seriousness, the listing for additional monitoring of the drug by European Medicines Agency (EMA), and lack of labelling information about the ADR. Nurses' opinions of the assignment were evaluated using an E-survey. Results: Thirty-three ADRs were reported, 32 (97%) of which were well documented according to ClinDoc. Thirteen ADRs (39%) were 'serious' according to CIOMS criteria. In 5 cases (15%) the suspect drugs were listed for additional monitoring by EMA and in 7 cases (21%) the ADR was not mentioned in the Summary of Product Characteristics. Twenty-fve (78%) of the 32 enrolled nurses completed the E-survey. Most were > 45 years of age (68%), female (92%), and had extensive clinical experience (6-33 years). All agreed or completely agreed that the reporting assignment was useful, that it ftted in daily practice, and that it increased their attention for medi-cation/patient safety. A large majority (84%) agreed the assignment changed how they dealt with ADRs. Conclusions: Specialist oncology nurses are capable of reporting ADRs, and they considered the assignment useful. The assignment yielded valuable, relevant, and well-documented ADR reports for pharmacovigilance practice.

Long-term safety and effectiveness of adalimumab for the treatment of Japanese patients with rheumatoid arthritis: 3-year results from a postmarketing surveillance of 552 patients

Objectives: To determine the safety and effectiveness of and identify associated factors in long-term adalimumab (ADA) treatment of Japanese patients with rheumatoid arthritis (RA).Methods: Of 7740 patients participating in the all-case postmarketing surveillance study, 552 were enrolled in the present study and observed for 3 years. The safety and effectiveness of ADA were analyzed in 509 and 430 patients, respectively.Results: Adverse drug reactions (ADRs) were reported in 34.2% of patients (23.3/100 person-years [PYs]); serious ADRs (SADRs) were reported in 10.6% (5.9/100 PYs). The most common ADRs and SADRs were infection (16.5%) and serious infection (6.1%), respectively. Seven patients (1.4%) developed malignancies. Multivariate analysis revealed that the risk factors for SADRs were age ≥65 years and respiratory disorder at baseline. The proportion of patients who achieved remission (28-joint count Disease Activity Score based on four erythrocyte sedimentation rates <2.6) increased from 3.3% at baseline to 49.2% at 36 months. Significant predictors of failure to achieve remission were female sex, age ≥65 years, blood disorders and advanced structural change at baseline.Conclusions: Overall, no unknown safety issues were noted during the 3-year treatment with ADA in Japanese patients with RA.

Safety and effectiveness of tadalafil in patients with pulmonary arterial hypertension: Japanese post-marketing surveillance data

Objective: To evaluate the long-term safety and effectiveness of tadalafil in patients with pulmonary arterial hypertension (PAH) in real-world clinical practice.Methods: This prospective, multicenter, noninterventional, post-marketing surveillance included patients with PAH who were observed for up to 2 years after initiation of tadalafil. Safety was assessed by analyzing the frequency of adverse drug reactions (ADRs), discontinuations due to adverse events (AEs), and serious adverse drug reactions (SADRs). Effectiveness measurements included the assessment of the change in World Health Organization (WHO) functional classification of PAH, 6-minute walk test, cardiac catheterization, and echocardiography.Results: Among 1676 patients analyzed for safety, the overall incidence of ADRs was 31.2%. The common ADRs (≥1.0%) were headache (7.0%), diarrhea (1.9%), platelet count decreased (1.8%), anemia, epistaxis, and nausea (1.6% each), flushing (1.3%), hepatic function abnormal (1.1%), hot flush, and myalgia (1.0% each). The common SADRs (≥0.3%) were cardiac failure (0.7%), interstitial lung disease, worsening of PAH, and platelet count decreased (0.3% each). Among 1556 patients analyzed for effectiveness, the percentages of patients with improvement of WHO functional class at 3 months, 1 year, and 2 years after the initiation of tadalafil, and last observation were 17.1%, 24.8%, 28.9%, and 22.5%, respectively. At all observation points (except pulmonary regurgitation pressure gradient at end diastole at 3 months), the mean 6-minute walk distance, cardiac catheterization, and echocardiogram measurements showed statistically significant improvement.Conclusion: This surveillance demonstrated that tadalafil has favorable safety and effectiveness profiles for long-term use in patients with PAH in Japan.

Is safety of childhood growth hormone therapy related to dose? Data from a large observational study.

Concerns have been raised of increased mortality risk in adulthood in certain patients who received growth hormone treatment during childhood. This study evaluated the safety of growth hormone treatment in childhood in everyday practice. NordiNet(®) International Outcome Study (IOS) is a noninterventional, observational study evaluating safety and effectiveness of Norditropin(®) (somatropin; Novo Nordisk A/S, Bagsvaerd, Denmark). Long-term safety data (1998-2013) were collected on 13 834 growth hormone treated pediatric patients with short stature. Incidence rates (IRs) of adverse events (AEs) defined as adverse drug reactions (ADRs), serious ADRs (SADRs), and serious AEs (SAEs) were calculated by mortality risk group (low/intermediate/high). The effect of growth hormone dose on IRs and the occurrence of cerebrovascular AEs were investigated by the risk group. We found that 61.0% of patients were classified as low-risk, 33.9% intermediate-risk, and 5.1% high-risk. Three hundred and two AEs were reported in 261 (1.9%) patients during a mean (s.d.) treatment duration of 3.9 (2.8) years. IRs were significantly higher in the high- vs the low-risk group (high risk vs low risk-ADR: 9.11 vs 3.14; SAE: 13.66 vs 1.85; SADR: 4.97 vs 0.73 events/1000 patient-years of exposure; P < 0.0001 for all). Except for SAEs in the intermediate-risk group (P = 0.0486) in which an inverse relationship was observed, no association between IRs and growth hormone dose was found. No cerebrovascular events were reported. We conclude that safety data from NordiNet(®) IOS do not reveal any new safety signals and confirm a favorable overall safety profile in accordance with other pediatric observational studies. No association between growth hormone dose and the incidence of AEs during growth hormone treatment in childhood was found.

Clinical safety of insulin detemir in patients with Type 2 diabetes in the Gulf countries: The multicenter, noninterventional, open-label LevSafe study.

Aim:To evaluate the safety profile of insulin detemir (IDet) in people with Type 2 diabetes mellitus (T2DM) in the Gulf countries in the 32-week, noninterventional LevSafe study.Methods:People with T2DM whose physicians had opted to start IDet therapy were included in the study. Safety parameters, including serious adverse drug reactions (SADRs) and hypoglycemia, and changes in body weight and glycemic control were evaluated at baseline, week 16 and week 32.Results:A total of 686 patients were exposed to IDet therapy with a mean (±standard deviation) age, body mass index, and diabetes duration of 51.3 ± 11.0 years, 31.3 ± 5.5 kg/m2, and 10.2 ± 6.1 years, respectively. The mean total daily dose of IDet was 32.0 ± 32.8 U at baseline and 44.7 ± 60.7 U at week 32. No SADRs were reported during the study. Total hypoglycemia decreased from 435 events at baseline to 204 events at week 32 (mean change analyzed by Wilcoxon signed rank test: −0.34; P = 0.0115), and no major hypoglycemia was reported at week 32. Over the 32-week treatment period, the mean body weight decreased from 85.7 ± 15.2 kg to 85.4 ± 14.5 kg (P = 0.0203), glycated hemoglobin A1c from 9.9 ± 1.67% to 7.7 ± 1.36% (P < 0.0001), and fasting plasma glucose from 11.9 ± 3.27 mmol/L to 7.4 ± 1.85 mmol/L (P < 0.0001).Conclusion:IDet therapy was well-tolerated and was associated with a decreased number of hypoglycemic events and improved glycemic control after 32 weeks in patients with T2DM in the Gulf countries.

Clinical experience of switching from biphasic human insulin to biphasic insulin aspart 30 in Indian patients with type 2 diabetes in the A1chieve study.

Aim:The aim of the following study is to evaluate the safety and effectiveness of switching from biphasic human insulin (BHI) to biphasic insulin aspart 30 (BIAsp 30) in Indian patients with type 2 diabetes as a sub-analysis of the 24-week, non-interventional A1chieve study.Materials and Methods:Indian patients switching from BHI to BIAsp 30 based on the physicians’ decisions were included. The primary outcome was the incidence of serious adverse drug reactions (SADRs), including major hypoglycemic events; secondary outcomes included changes in hypoglycemia in the 4 weeks preceding baseline and week 24 and changes from baseline to week 24 in glycated hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPPG), body weight and quality of life (QoL).Results:Overall, 1976 patients (mean ± standard deviation age, 55.1 ± 10.6 years and diabetes duration, 10.1 ± 5.3 years) on a mean pre-study BHI dose of 0.44 ± 0.18 U/kg were included. The mean BIAsp 30 dose was 0.43 ± 0.17 U/kg at baseline and 0.44 ± 0.17 U/kg at week 24. No SADRs were reported. The proportion of patients reporting overall hypoglycemic events reduced significantly from baseline to week 24 (15.0% vs. 2.9%, P < 0.0001). The mean HbA1c level improved significantly from 9.1 ± 1.4% at baseline to 7.5 ± 1.0% at week 24, along with improvements in FPG, post-breakfast PPPG and QoL (P < 0.001). The mean body weight decreased from 69.3 ± 10.8 kg at baseline to 69.1 ± 10.4 kg at week 24 (P = 0.003).Conclusion:Switching from BHI to BIAsp 30 therapy was well-tolerated and was associated with improved glycemic control.

An evaluation of adverse drug reactions monitoring at a pharmacovigilance unit under pharmacovigilance program of India in a tertiary care hospital of Haryana

Background: Adverse drug reactions (ADRs) are among top 10 causes of mortality in patients. Pharmacovigilance programme of India (PvPI) is a step towards participation in the WHO programme for International Drug Safety Monitoring. The present article is an evaluation of the incidence and the patterns of ADRs from the reports collected from various clinical departments of this hospital. Methods: A total of 859 suspected ADR reports submitted to the pharmacovigilance unit at Department of Pharmacology under PvPI were evaluated for 6 months with respect to demographics, causative drug, organ system involvement, severity and seriousness of ADRs. The causality assessment was carried out by using WHO assessment method and Naranjo’s scale. Results: Males experienced more (66.33%) ADRs. The highest percentage (45.83%) of ADRs was seen in the age group of 46-60 years (35.33%), followed by 16-30 years (25.5%). The most common drug group causing ADRs was antimicrobials (43.37%), followed by anticancer and immunosuppressive agents (29.02%). The gastrointestinal system (31.43%) was most prone system, followed by generalized body reactions (22.93%) and cutaneous reactions (17.11%). 662 (77%) ADRs were non-serious, 197 (22.9%) were serious. On severity scale, 682 (79.39%) were mild, 168 (19.65%) moderate and only 9 (1.05%) ADRs were severe out of which three were fatal. As per WHO assessment method 66.94% ADRs were probable and 33.06% possible. The probability was comparable with Naranjo’s scale. Conclusion: ADRs to drugs happen commonly, and their reporting is important for the early recognition and prevention of ADRs and will also help in generating signals. ADR monitoring not only acts as an alerting mechanism for physicians, but helps the regulatory authorities in making the policy decision.

Adverse drug reactions associated with asthma medications in children: systematic review of clinical trials

Respiratory medications are frequently prescribed for use in children. Several studies have reported information on the safety of asthma medications in clinical studies in adults, but information about safety in children is scarce. To review published clinical trials on the occurrence and characteristics of adverse drug reactions (ADRs) in children, reported for asthma medications licensed for paediatric use. We systematically reviewed the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines. PubMed, Embase, Cochrane Library, PsycINFO, IPA, and CINAHLs databases were searched from origin until July 2013 for studies reporting ADRs for beta2-receptor agonists, inhaled corticosteroids, leukotriene receptor antagonists and combination products in children from birth to age 17. Information on ADR reporting rates, age and gender, type and seriousness of ADRs, design, setting, observation period, type of assessors, and funding sources was extracted from the articles. Literature searches resulted in 162 potential relevant articles. However only 12 of these studies were included in this review as they reported information about ADR rates from use of salmeterol, formoterol, fluticasone, montelukast, zafirlukast and budesonide/formoterol in children. The total population was approximately 3,000 children; the majority was 6- to 11-year-olds and two thirds of these were boys. The observation period varied from 1 to 22 months. The most frequently reported ADRs were exacerbation of asthma, respiratory tract infection, cough, fever and headache. Only few ADRs were rated as being serious, however a number of children dropped out of the clinical trials due to serious ADRs, and, therefore, the real number of serious ADRs is probably higher. Few clinical trials reporting ADRs from use of asthma medications in children were identified in the literature. These studies reported only a few types of ADRs, the majority being non-serious.

Type 2 Diabetes Mellitus Management and Body Mass Index: Experiences with Initiating Insulin Detemir in the A1chieve Study

IntroductionThis sub-analysis of the A1chieve study aimed to examine the safety and efficacy of insulin detemir (IDet) initiation over 24 weeks in relation to baseline body mass index (BMI) in people with type 2 diabetes mellitus (T2DM).MethodsA1chieve was a 24-week non-interventional study to assess the safety and efficacy of insulin analogs in routine practice. This sub-analysis included insulin-naïve patients who initiated IDet therapy based on their physicians’ decision. Patients were stratified according to baseline BMI (Group I, <25.0 kg/m2; Group II, 25.0 to <30.0 kg/m2; Group III, 30.0 to <35.0 kg/m2; Group IV ≥35.0 kg/m2). Safety and efficacy variables were assessed over 24 weeks.ResultsOverall, 10,650 insulin-naïve patients were included (3,045 patients in Group I, 4,186 patients in Group II, 2,365 patients in Group III, and 1,054 patients in Group IV). Four serious adverse drug reactions (SADRs) were reported. From baseline to Week 24, there was no statistically significant difference in the proportion of patients reporting overall hypoglycemia in Group I (4.0% vs. 4.4%), while a significant decrease in Group II (4.8% vs. 4.0%, p = 0.0335) and significant increases in Groups III and IV (3.3% vs. 5.4% and 3.4% vs. 7.0%, respectively, p < 0.001) were noted. The mean body weight increased from baseline to Week 24 in Group I (60.7 ± 8.4 vs. 61.8 ± 8.5 kg) and reduced in Groups II, III, and IV (74.5 ± 9.2 vs. 74.2 ± 9.2 kg, 87.4 ± 10.3 vs. 86.0 ± 9.8 kg, and 102.2 ± 14.3 vs. 100.1 ± 14.2 kg, respectively; all p < 0.001). Significant improvements were noted in glycemic parameters, systolic blood pressure, and lipids over 24 weeks, irrespective of baseline BMI status.ConclusionIDet therapy was associated with improved glycemic control and a low number of SADRs. Greater weight loss was observed with higher BMI.Electronic supplementary materialThe online version of this article (doi:10.1007/s13300-014-0054-2) contains supplementary material, which is available to authorized users.

Evaluating the effects of combination antiretroviral therapy regimens and the development of adverse drug reactions in Indian human immunodeficiency virus positive patients

Background: In India, adverse drug reactions (ADRs) occur frequently with combination antiretroviral therapy (cART) leading to switching or discontinuing cART intentionally. Objective: The study was conducted to characterize the effects of cART regimen and the development of ADRs in human immunodeficiency virus positive patients (HIV) in a tertiary care teaching hospital. Materials and Methods: A prospective observational study was conducted from August 2009 to May 2012 to characterize the pattern of ADRs to cART at Kasturba Hospital, Manipal in South India. Collection of the data was done by a clinical pharmacist during daily ward rounds to identify the suspected ADRs associated with the use of cART for various parameters which included patient demographics, cART with its adverse reaction characteristics. Assessment was also done for preventability, predictability and seriousness of ADRs, system organ classes affected and causality of the suspected ADRs using the World Health Organization (WHO) Probability Scale. Results: Among 450 patients enrolled, 230 suspected ADRs to cART were reported. By Pearson Chi-square test, higher occurrence of ADRs (P < 0.001) was noted in females, age 41-60 years, CD4 + T-cell counts 350-500 cells/μl, 5 years use of cART. ADRs were highest with zidovudine + lamivudine + nevirapine (42.3%) and tenofovir + emtricitabine + efavirenz (14.2%). On bivariate analysis, (P < 0.001) were identified in 1) Anemia with zidovudine use, 2) Pancytopenia with zidovudine, lamivudine use 3) Hepatotoxicity with nevirapine, efavirenz use, 4) Peripheral neuropathy with stavudine use, 5) Renal failure with tenofovir use and 6) Maculopapular rash with emtricitabine, tenofovir, efavirenz use. The system organ class most affected with ADRs to cART was red blood cell disorders (30.9%) followed by skin and appendages disorders (16.5%). Conclusion: With increasing reports of ADRs in India, clinicians need to select a safe cART regimen with underlying illness, medicines and drug intolerances.

Comparison of serious adverse reactions between thalidomide and lenalidomide: analysis in the French Pharmacovigilance database

Thalidomide and lenalidomide are structural analogs and immunomodulatory drugs. Lenalidomide appears to have a different safety profile than thalidomide and could be less toxic, and as far as we know, we did not found any study comparing their safety profile. The objective of our study was to review and compare serious adverse drug reactions (SADRs) of thalidomide and lenalidomide spontaneously reported to the French Pharmacovigilance database. We extracted all medically confirmed spontaneous reports of SADR for lenalidomide-based regimens and thalidomide-based regimens from the French Pharmacovigilance database. A "serious" adverse drug reaction (ADR) was defined as an ADR that is fatal or life threatening, which causes hospitalization or prolongation of hospitalization, or permanent or significant disability. The study period was between marketing of 2 drugs and January 15, 2012. A total of 392 SADRs related to thalidomide-based regimens were identified in 244 patients and 377 SADRs related to lenalidomide-based regimens in 220 patients. In spite of their structural analogy, this study highlights interesting differences between lenalidomide and thalidomide's safety profile: nervous system and vascular disorders are more frequent with thalidomide-based regimens while hematologic, skin, infectious disorders and secondary primary cancers are more frequent with lenalidomide-based regimens.

Safety and effectiveness of insulin analogues in type 2 diabetic patients from Algeria: a sub-analysis of the A1chieve study

AimTo determine the safety and effectiveness of insulin analogues in type 2 diabetes (T2D) patients in the Algerian cohort of the A1chieve study and to examine the status of T2D management across different regions in Algeria. MethodsPatients starting therapy with biphasic insulin aspart 30, insulin detemir, insulin aspart (IAsp) or IAsp + basal insulin at their physicians' decision were included. The primary outcome was the incidence of serious adverse drug reactions (SADRs), including major hypoglycaemia. Secondary outcomes included changes from baseline to Week 24 in hypoglycaemia, glycated haemoglobin A1c (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPPG), weight and quality of life (QoL, evaluated using the EQ-5D questionnaire). ResultsOverall, 1494 patients (mean±SD age: 60.1±10.3 years; body mass index: 28.1±4.9kg/m2; HbA1c: 9.2±1.8%) were enrolled. Poor baseline glucose control was revealed across the different Algerian regions with mean HbA1c varying from 8.9% to 9.6%. Two SADRs were reported during the study. The proportion of patients reporting major hypoglycaemic events decreased from 1.1% at baseline to 0.2% at Week 24 (p = 0.0017). Significant improvements in mean HbA1c (−1.3±2.0%), FPG (−38.8±79.9 mg/dL) and post-breakfast PPPG (−51.4±97.1 mg/dL) were observed in the entire cohort (all p < 0.001). The mean body weight increased by 0.9±3.8kg, while QoL increased by 9.2±16.7 points after 24 weeks. ConclusionsInsulin analogue therapy was well-tolerated and significantly improved blood glucose control over 24 weeks in the Algerian cohort.