Rate Of Adverse Drug Reactions Research Articles

<b>添付文書からみた承認時と再審査終了時における副作用発現率の比較</b>

<b>添付文書からみた承認時と再審査終了時における副作用発現率の比較</b>

The clinical effect of montelukast combined with budesonide aerosol in the treatment of children with cough variant asthma

Objective To observe the clinical efficacy and safety of montelukast combined with budesonide in the treatment of children with cough variant asthma(CVA).Methods 76 cases with CVA were randomly divided into two groups,two groups were treated with terbutaline,discontinuation of the drug after remission of symptoms.38 cases in the observation group were treated with montelukast combined with budesonide,38 cases in the control group were treated with budesonide.All the children were treated for 3 months.The clinical curative effect was compared between the two groups.Follow-up for 6 months,the incidence of adverse reactions and recurrence were observed.Results The total effective rate of observation group was 97.37％,which was higher than that in the control group 86.84％,the difference between the two groups was statistically significant(P＜0.05).The adverse reactions occurred in 2 cases(5.26％)of observation group,5 cases(13.16％)in the control group.The incidence of adverse drug reaction rate was slightly lower than that of control group,but the difference was not significant(P＞0.05).The observation group had 1 case recurrence(2.63％),the control group 2 cases of recurrence(5.26％),the difference between the two groups was not statistically significant(P＞0.05).Conclusion Montelukast combined with budesonide inhalation in treatment of children with CVA has significant efficacy,adverse reactions are mild,low recurrence rate. Key words: Asthma; Montelukast and budesonide; Child

Adverse Drug Reactions to Gabapentin and Pregabalin

Gabapentin and pregabalin are widely used as antineuropathic pain drugs. Their use is also associated with the development of adverse drug reactions (ADRs), mainly neuropsychiatric. The aim of this work was to study 'serious' and/or 'unexpected' adverse reactions associated with pregabalin and gabapentin. We studied ADRs reported to the French Pharmacovigilance System occurring between 1995 and 2009. For each ADR associated with gabapentin or pregabalin, we noted year, patient age and sex, type of adverse reaction, as well as the imputability score. Reporting rate of serious ADRs for gabapentin and pregabalin was estimated with regard to data of use (obtained from the French National Health Insurance Fund) using the defined daily dose. A global and descriptive analysis of the adverse reactions for each drug is presented. Secondly, details of deaths and ADRs with an imputability score of at least 'probable' or 'likely' were presented. Overall, 1333 cases were recorded (725 related to gabapentin, 608 related to pregabalin), mainly neuropsychiatric ADRs. Among the 22 deaths recorded, 8 were related to gabapentin in obstetrical situations. Other less well-documented ADRs were identified, such as hepatitis associated with gabapentin and haematological ADRs associated with pregabalin. This study confirmed the prevalence of neuropsychiatric ADRs associated with gabapentin or pregabalin. A high rate of death occurred with gabapentin in an obstetrical context. New adverse reactions have been noted, such as haematological or hepatic adverse reactions associated with pregabalin and gabapentin, respectively.

Improved Blood Pressure Control with Nifedipine GITS/Valsartan Combination Versus High‐Dose Valsartan Monotherapy in Mild‐to‐Moderate Hypertensive Patients from Asia: Results from the ADVISE Study, a Randomized Trial

ADVISE was a 12-week, multicenter, randomized, prospective, open-label, parallel-group study comparing combination therapy of nifedipine GITS 30 mg plus valsartan 80 mg (N + V) with high-dose valsartan (160 mg) monotherapy (V160) in Asian patients with hypertension. Patients with hypertension inadequately controlled with valsartan 80 mg for at least 4 weeks were randomized. The coprimary endpoints were the mean changes in clinic systolic and diastolic blood pressures (SBP and DBP, respectively) at Week 12. Other endpoints included blood pressure (BP) control rate, response rate, and adverse events. The full analysis set (FAS) comprised 359 patients. Least squares (LS) mean changes in SBP were -18.3 mmHg (N + V; n = 177) and -16.5 mmHg (V160; n = 182) (difference: -1.9 mmHg; P = 0.0998). DBP LS mean changes were -9.8 mmHg (N + V) and -7.4 mmHg (V160) (difference: -2.4 mmHg; P = 0.0011). BP control rates were significantly higher in the N + V group (Week 4: 51.2% vs. 38.4%, P = 0.0138; Week 8: 68.3% vs. 50.3%, P = 0.0004; and Week 12: 71.2% vs. 55.5%, P = 0.0024). Similar findings were observed when patients were stratified according to smoking status, SBP baseline quartiles, and ESC/ESH guideline-defined added-risk category. The BP response rate was also higher in the N + V group compared with the V160 group. Rates of adverse drug reactions (all mild-to-moderate) were similar: 4.5% (N + V) and 4.4% (V160). Although one of the coprimary endpoints did not reach statistical significance, combination treatment with N + V provided a greater early and more consistent BP-lowering effect than monotherapy with V160, including superior reduction in DBP and BP control rates.

Clinical outcomes research of traditional Chinese medicine——introduce registry intensive hospital monitoring study protocol of traditiona Chinese medicine injection's safety

Traditional Chinese medicine (TCM) injection's safety problems has been paid attention for the country and people, TCM injection's labels described the adverse reactions always shows "unclear" or blank, especially the adverse drug reactions(ADR) rates hardly reported. To save the problem, large-scale safety surveillance of TCM injection research is very important. The article introduces the research aim, research type, simple size, outcomes and ethic problem during make the plan. It is a multi-center, large sample size, registry research program about TCM injections safety monitoring. The aim is to get the ADR's rate of TCM injections. According to the "three rules" , each of the TCM injection will be observed for 30 000 cases which are inpatients. The research adopt to using the barcode system and hospital information system(HIS) & laboratory information management system(LIS) to make sure enroll all patients. Case report file (CRF) is used for record patient's information which contained 3 types(A, B, C) tables. Most of people just need to fill table A, and the patient need to fill table B when they have ADR. The outcome of the research is severe ADR. Abide by the international ethical principle to keep the patient's right.

Therapeutic effect of neoadjuvant chemotherapy combined with docetaxel，oxaliplatin and capecitabine in the treatment of advanced gastric cancer

Objective: To investigate the therapeutic effect and adverse drug reactions(ADRs) of neoadjuvant chemotherapy combined with docetaxel,oxaliplatin and capecitabine(DOX regimen) in the treatment of advanced gastric cancer.Methods: One hundred and eighty-six patients with advanced gastric cancer in Department of Gastrointestinal Surgery,Changzheng Hospital,Second Military Medical University from 2008-06-01 to 2011-05-31 received neoadjuvant chemotherapy.Neoadjuvant chemotherapy regimen was as follows:75 mg/m2 docetaxel(iv gtt,on day 1),130 mg/m2 oxaliplatin(iv gtt,on day 2),1 000 mg/m2 capecitabine(bid,po,on days 1-14) with 3 weeks as one treatment course,totalling 2-3 courses.And the patients received surgery,2-3 weeks after termination of chemotherapy.Results: Total response rate was 67.8%,complete response rate was 3.8%(7 patients),partial response rate was 64.0%(119 patients).Total resection rate was 81.5%,R0 resection rate was 80.4%.Main ADRs were myelosuppression,nausea and vomiting.Conclusion: Overall curative resection rate was increased in patients with advanced gastric cancer,after neoadjuvant chemotherapy with docetaxel,oxaliplatin and capecitabine.The ADRs rate of neoadjuvant chemotherapy was within acceptable range.

Workshop- and Telephone-Based Interventions to Improve Adverse Drug Reaction Reporting

Spontaneous reporting of adverse drug reactions (ADRs) is the method most widely used by pharmacovigilance systems, with the principal limitation being the physician's underreporting. This study sought to evaluate the results of workshop and telephone-interview interventions designed to improve the quantity and relevance of ADR reporting by physicians. A cluster-randomized controlled trial was conducted on 6579 physicians in northern Portugal in 2008. Following randomization, we allocated 1034 physicians to a telephone-interview intervention, 438 to a workshop intervention and the remaining 5107 to the control group. At the workshop, a real clinical case was presented and participants were then asked to report on it by completing the relevant form. In the telephone intervention, participants were asked (i) whether they had ever had any suspicion of ADRs; (ii) whether they had experienced any difficulties in reporting; (iii) whether they remembered the different methods that could be used for reporting purposes; and (iv) whether they attached importance to the individual physician's role in reporting. We followed up physicians to assess ADR reporting rates to the Northern Pharmacovigilance Centre. In terms of relevance, adverse reactions were classified as serious or unexpected. Statistical analysis was performed on an intention-to-treat basis, and generalized linear mixed models were applied using the penalized quasi-likelihood method. The physicians studied were followed up over a period of 20 months. Two hundred physicians underwent the educational intervention. Comparison with the control group showed that the workshop intervention increased the spontaneous ADR reporting rate by an average of 4-fold (relative risk [RR] 3.97; 95% CI 3.86, 4.08; p < 0.001) across the 20 months post-intervention. Telephone interviews, in contrast, proved less efficient since they led to no significant difference (p = 0.052) vis-à-vis the control group in ADR reporting (RR 1.02; 95% CI 1.00, 1.04). The effects of the interventions on the reporting rate of serious and high-causality ADRs indicated that the RRs associated with workshops were 6.84 (95% CI 6.69, 6.98; p < 0.001) for serious ADRs and 3.58 (95% CI 3.51, 3.66; p < 0.001) for high-causality ADRs. Whereas telephone interventions only increased spontaneous reporting in the first 4 months of follow-up, workshops significantly increased both the quantity and relevance of spontaneous ADR reporting for more than 1 year.

Safety and effectiveness of adalimumab in Japanese rheumatoid arthritis patients: postmarketing surveillance report of the first 3,000 patients

This interim analysis of postmarketing surveillance data for adalimumab-treated rheumatoid arthritis (RA) patients summarizes safety and effectiveness during the first 24 weeks of therapy for the first 3,000 patients treated in Japan (June 2008–December 2009). Patient eligibility for antitumor necrosis factor therapy was based on the Japanese College of Rheumatology treatment guidelines and Japanese labeling. All patients were screened for tuberculosis. Approximately 50% of the population was biologic naïve, 66% received concomitant methotrexate (MTX), and 72% received concomitant glucocorticoids. The overall incidence rate of adverse events was 31% (5.5% serious) and that of adverse drug reactions (ADRs) was 27% (4.1% serious). Incidence rates of ADRs and serious ADRs were similar regardless of prior biologic therapy or concomitant MTX use but were significantly higher in patients receiving glucocorticoids compared with those not receiving glucocorticoids. Bacterial/bronchial pneumonia occurred in 1.2% of patients; interstitial pneumonia, 0.6%; Pneumocystis jirovecii pneumonia, 0.3%; tuberculosis, 0.13%; and administration-site reactions, 6.1%. Mean 28-joint Disease Activity Scores decreased significantly after 24 weeks from 5.29 to 3.91. All subgroups showed significant improvement, particularly the biologic-naïve patients receiving concomitant MTX. No new safety concerns were identified. ADR Incidence rates were similar to those of other biologic agents approved for RA.

Adverse drug reactions for CAM and conventional drugs detected in a network of physicians certified to prescribe CAM drugs.

Within recent years, the increasing popularity of complementary and alternative medicine (CAM) has led health care authorities to focus on the safety of these drugs. One reason for the low awareness of adverse drug reactions (ADRs) associated with CAM might be that users and physicians believe that there are no risks associated with CAM drugs. Recent studies have shown that ADRs are under-reported and are considered a leading cause of morbidity and mortality. The Evaluation of Anthroposophical Medicine (EvaMed) Pharmacovigilance Network was formed in 2004 at the Havelhoehe Research Institute in Berlin and is composed of 38 CAM physicians located in 12 of the 16 federal states in Germany for the purpose of using EvaMed data to evaluate the prescribing patterns, effectiveness, and safety of CAM therapies. To describe and quantify the volume and severity of ADRs for CAM and conventional (CON) drugs in a proprietary database created from prescriptions and patient data of primary care CAM physicians who participate in the EvaMed Network. This was a prospective, multicenter, observational study based on the ADR reports and electronic prescription data of 38 individual physicians (21 general practitioners, 9 pediatricians, 4 internists, 2 gynecologists, 1 dermatologist, and 1 neurologist) participating in the EvaMed Network. In addition to standard medical education, all physicians had 5 years practical experience and an additional qualification for anthroposophic medicine, which is a subcategory of CAM. All 38 physicians documented ADRs deemed serious, defined as life threatening or resulting in death, disability/incapacity, or inpatient hospital days. Due to the time-consuming nature of documenting ADRs, only a subgroup of 7 physicians (4 in general practice and 1 each in internal medicine, pediatrics, and gynecology) agreed to report both nonserious and serious ADRs. Therefore, the incidence and frequency of ADRs were evaluated in this subgroup. The study period was January 2004 through June 2009. ADRs were documented by the physicians using an electronic case report form in the EvaMed software, which was linked to the physicians' existing electronic medical record (EMR) systems and incorporated into their daily routines to avoid missing data or double entries. The participating physicians were compensated €15 (approximately US$20) for each ADR report. All ADR reports were monitored at the Havelhoehe Research Institute by 2 physicians who evaluated patient characteristics, present visit diagnosis, target drugs, associated drug classes and type of drugs, type of ADR, actions taken for the ADR, and outcome of the ADR. There were 1,018,626 drugs (54.8% CAM) prescribed by the 38 physicians for 88,431 patients, and 412 ADRs reported for 389 patients; 124 (30.1%) ADRs were for CAM drugs. The majority were reported in children (69.2%, n = 285) and females (56.3%, n = 232). All serious ADRs (n = 14) were associated with CON drugs. In the subgroup of 7 physicians who agreed to report all ADRs, a total of 327 serious and nonserious ADRs were reported for 392,243 prescribed drugs (0.08%) and for 308 of 25,966 patients (1.2%). ADRs were reported for 241 of 16,032 children (aged 17 years or younger; 1.5%) versus 67 of 9,934 adults (0.7%). Of the 327 total ADRs, 10 (3.1%) were serious. There were 95 ADRs for 213,900 CAM prescriptions (4.4 per 10,000) versus 232 for 178,343 CON prescriptions (13.0 per 10,000). The CAM drug with the highest frequency of ADRs was Pelargonium sidoides root (0.21%, 4 of 1,940 prescriptions). The most frequently reported ingredient in CAM was ivy leaves with an ADR frequency of 0.17% (n = 11 of 6,575 prescriptions). The most reported drug connected with ADRs was amoxicillin (1.36%, n = 31 of 2,276 prescriptions). The most common ADR medical management was withdrawal of the drug (82.3% overall, 83.9% CAM, 81.6% CON). A sample of 38 CAM physicians reported the occurrence of at least 1 ADR for 0.4% of treated patients in a 5.5-year study period. There were no serious ADRs reported for CAM drugs. In a subsample of 7 physicians who agreed to report all nonserious and serious ADRs, 1.2% of patients experienced at least 1 ADR; rates of ADRs per 10,000 prescriptions were 4.4 for CAM drugs and 13.0 for CON drugs.

The Dual Role of Pharmacogenetics in HIV Treatment: Mutations and Polymorphisms Regulating Antiretroviral Drug Resistance and Disposition

Significant intra- and interindividual variability has been observed in response to use of pharmacological agents in treatment of HIV infection. Treatment of HIV infection is limited by high rates of adverse drug reactions and development of resistance in a significant proportion of patients as a result of suboptimal drug concentrations. The efficacy of antiretroviral therapy is challenged by the emergence of resistant HIV-1 mutants with reduced susceptibility to antiretroviral drugs. Moreover, pharmacotherapy of patients infected with HIV is challenging because a great number of comorbidities increase polypharmacy and the risk for drug-drug interactions. Drug-metabolizing enzymes and drug transporters regulate drug access to the systemic circulation, target cells, and sanctuary sites. These factors, which determine drug exposure, along with the emergence of mutations conferring resistance to HIV medications, could explain variability in efficacy and adverse drug reactions associated with antiretroviral drugs. In this review, the major factors affecting the disposition of antiretroviral drugs, including key drug-metabolizing enzymes and membrane drug transporters, are outlined. Genetic polymorphisms affecting the activity and/or the expression of cytochromes P450 or UGT isozymes and membrane drug transport proteins are highlighted and include such examples as the association of neurotoxicity with efavirenz, nephrotoxicity with tenofovir, hepatotoxicity with nevirapine, and hyperbilirubinemia with indinavir and atazanavir. Mechanisms of drug resistance conferred by specific viral mutations are also reviewed, with particular attention to replicative viral fitness and transmitted HIV drug resistance with the objectives of providing a better understanding of mechanisms involved in HIV drug resistance and helping health care providers to better manage interpatient variability in drug efficacy and toxicity.

A Signal Detection Method to Detect Adverse Drug Reactions Using a Parametric Time-to-Event Model in Simulated Cohort Data

Current quantitative signal detection methods have been primarily developed for the purpose of detecting signals from spontaneous reports. These methods are not always appropriate for cohort data. More recently, parametric time-to-event models have been proposed to model hazard functions with the ultimate aim of detecting adverse drug reactions (ADRs). The rate of occurrence of ADRs after starting a drug will depend upon the causal mechanism and therefore will often vary with time, in contrast to events not associated with the drug, which will tend to occur at a constant background rate. After starting treatment, the onset of ADRs will be rapid for some but delayed for others. A non-constant rate over time may indicate a drug-event relationship. The aim of this study was to propose a simple test to detect signals of ADRs in cohort data and to investigate the power of this test using simulated data. A signal detection tool using the proposed test to improve the power of detection is also described. In order to test for a non-constant hazard (rate of occurrence), the hazard function was estimated using the model shape parameter for the Weibull function. If the shape parameter was found to be significantly different (p < 0.05) from the value one (the value for a constant hazard) a signal was raised. Simulation of background event rates used were 1%, 5% and 10% of the cohort size. The ADR rate was varied in proportion to the background rate; a 10%, 20% and 50% increase in the background rate was explored. The time of occurrence of the ADR will dictate the shape of the hazard function, therefore the ability of the model to detect a signal depending when the highest risk for ADR was also explored. The power of the test was investigated by simulation. The Weibull Shape Parameter (WSP) test was most powerful at detecting signals that occur shortly after starting treatment. These preliminary simulations had low power when the underlying hazard function was symmetrical (e.g. when ADRs occurred in the middle of the study period). The power of the test was improved by censoring the data as this broke the symmetry of the hazard function. A tool that censored the data at regular intervals and repeated the WSP test was found to correctly detect ADR or no ADR around 90% of the time when the sample size was at least 5000. The WSP test is simple to implement using standard statistical software, and can be used to detect non-constant hazards over time in order to raise signals of time-dependent ADRs. When there is no pre-specified event of interest or the time of the ADR is uncertain, the WSP tool should be used instead of the WSP test. These methods do not require any external data for comparative purposes and thus can be implemented in a single cohort of participants exposed to a drug.

Influence of paroxetine combined with Chaihuxiaoyao mixture on life quality of patients with depression

Objective: To evaluate the influence of Chaihuxiaoyao mixture(CXM) on life quality of patients with depression.Methods: One hundred and ninety patients with depression were randomly divided into paroxetine combined with CXM group(trial group) and paroxetine combined with placebo group(control group).The doses of CXM and placebo were 50 ml,bid.The initial dose and recommended dose of paroxetine were 20 mg/d,and the highest dose was 40 mg/d.All of the patients had a 8-week treatment.The therapeutic efficacy was evaluated before and after the treatment by Hamilton depression rating scale(HAMD) and the short form-36 health survey(SF-36),and the adverse drug reactions(ADRs) were evaluated by treatment emergent symptom scale(TESS).Results: One hundred and eighty-two patients completed the trial,89 cases in trial group and 93 cases in control group.Compared with the baseline,significant differences in HAMD scores and the SF-36 scores were observed in both groups after 8-week treatment(P0.01).After 8-week treatment,HAMD scores in trial group were significantly lower than those in control group,and SF-36 scores(vitality,emotional role and mental health) were significantly higher than those in control group(P0.01).There was no statistical difference in ADRs and the TESS scores between two groups(P0.05).Most ADRs were mild and moderate.Conclusion: Paroxetine combined with CXM is more effectiveness and can significantly improve quality of life in patients with depression,and the ADRs rate has no difference compared with placebo control group.

Adverse drug reactions to anthroposophic and homeopathic solutions for injection: a systematic evaluation of German pharmacovigilance databases

Medicinal solutions for injection are frequently applied in anthroposophic medicine and homeopathy. Despite their extensive use, there is little data published on the safety of these products. Therefore, we investigated the safety of anthroposophic and homeopathic solutions for injection through a systematic evaluation of adverse drug reactions (ADRs). ADRs were extracted from the pharmacovigilance databases of eight German manufacturers. Analysed ADRs included case reports in humans only, (spontaneous) case reports from post-marketing surveillance, literature and clinical/safety trials. Between 2000 and 2009, in total, 303 million ampoules for injection were sold, and 486 case reports were identified, corresponding to a total number of 1180 ADRs. Of all case reports, 71.8% (349/486) included ADRs that were listed (e.g. stated in package leaflet), and 9.5% (46/486) of the reports were classified as serious. The most frequently reported ADRs were pruritus, followed by angioedema, diarrhoea and erythema. A total of 27.3% (322/1180) were localized reactions for example; application or injection site erythema, pain, swelling and inflammation. The overall reporting rate of ADRs associated with injections was less than 4 per 1 million sold ampoules and classified as very rare. Our systematic evaluation demonstrated that the reporting rate of ADRs associated with anthroposophic and homeopathic solutions for injection is very low. Most reported ADRs were listed, and one quarter consisted of local reactions. These findings suggest a low risk profile for solutions for injection as therapeutically applied in anthroposophic medicine and homeopathy.

Assessment of hematological adverse drug reactions to antiretroviral therapy in HIV positive patients at Kasturba Hospital Manipal

Background HIV-infected patients have a higher risk of developing hematological adverse drug reactions (ADRs) than the general population and have a significant impact on patients’ current and future care options. The study was to determine the causality, the incidence rate, severity pattern of occurrence of hematological ADRs associated with highly active antiretroviral therapy in HIV positive patients. Methods Prospective observational study conducted at medicine department, Kasturba Hospital over a period of 6 months. Enrolled HIV positive patients were intensively monitored for hematological ADRs associated with fixed dose of highly active antiretroviral therapy. Causality of adverse drug reactions was assessed by using WHO probability scale and also with Naranjo’s algorithm. Results Monitoring of 70 HIV positive patients (58 males and 12 females) with fixed dose drug combinations of antiretroviral therapy by active pharmacovigilance identified 47.3% cases of anemia, 15.7% cases of leucopenia, 21% cases of pancytopenia, 5.2% of eosinophilia, 10.5% cases of bicytopenia. The incidence rate of hematological adverse drug reactions was 37.9% and most of the reported ADR’s were definitely predictable and preventable. Fifty percent of these ADR’s were lead to hospitalization and seventy percent of these ADR’s were of moderate in severity. Hematological ADRs were highest with Zidovudine + Lamivudine + Nevirapine (68.4%) and Zidovudine + Lamivudine + Efavirenz (31.57%) combinations. Conclusion With the increasing access to use of highly active antiretroviral in India, clinician must focus for routine monitoring of hematological investigations for early detection and prevention of adverse effects associated with highly active antiretroviral therapy. Author details 1Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal – 576 104, Karnataka, India. 2Department of Medicine, Kasturba Medical College, Manipal University, Manipal – 576 104, Karnataka, India.

Cost–effectiveness of iodinated contrast media for CT scanning in Spain: a decision-based analysis

Aims: A cost–effectiveness analysis was performed to assess the efficiency of low- and iso-osmolar iodinated contrast media in patients undergoing CT in Spain. Material & methods: The primary outcome measure was the reduction of immediate and delayed adverse drug reactions (ADRs). Deterministic sensitivity analyses according to incidence rates of ADRs and clinical management of ADRs was performed. Results: Low-osmolar contrast media (vs iso-osmolar) showed cost savings of €1682.3 per ADR avoided. Additional cost savings included €799.7 and €2139.5 for each delayed and moderate-to-severe delayed ADR avoided, respectively. For low-osmolar contrast media, moderate-to-severe immediate ADRs accounted for additional costs of €1524.2 and €5781.3, respectively. Conclusion: Low-osmolar contrast media are efficient owing to lower cost and lower risk of delayed ADRs, the treatment of which is more costly.

Iron Dextran Versus Iron Sucrose for Non-Hemodialysis Adult Outpatients with Iron Deficiency Anemia: Assessment of Safety and Feasibility for A Randomized Controlled Trial

Abstract▪2107▪This icon denotes a clinically relevant abstract Introduction:Iron deficiency is the most common cause of anemia worldwide affecting 50% of children under 5 years of age and 25% of women under the age of 50 (11% in the USA) worldwide. Standard treatment is oral iron supplementation, however this route of administration is associated with several adverse drug reactions (ADRs), the most common being epigastralgia and constipation leading to lack of compliance or dose reduction in 30% of patients. Intravenous (IV) iron is an alternative treatment for patients intolerant or non-responsive to oral formulations. Of the two most common formulations available in Canada, IV iron dextran is less expensive but may be associated with more overall ADRs compared to IV iron sucrose. Methods:We conducted a single centre, double-blinded pilot RCT to assess the feasibility of a full RCT to compare ADRs between iron dextran and iron sucrose in non-hemodialysis and IV iron treatment naïve adult patients with iron deficiency anemia. The incidence of immediate (during outpatient hospital visit) and delayed (within 24 hours after patient discharged) ADRs for each iron formulation were compared. Baseline characteristics of participants were analyzed by means of descriptive statistics. Demographic and clinical characteristics of study participants were evaluated by adverse reaction status. They were compared using a two-sample t-test for continuous variables and a two-way contingency table using Chi square or Fisher’s exact test for categorical variables, as appropriate. Patients were contacted 24 hours after discharge to answer a standardized questionnaire. Assessment of ADRs and severe ADRs were done using the standardized World Health Organization and International Conference on Harmonisation definitions. Grading of severity was done independently by three individuals from an independent Drug Safety Monitoring Board. Results:143 adult patients with iron deficiency anemia were were approached and erolled in the study between January 2008 and January 2009 (100% enrolment). Baseline characteristics of patients is depicted in Table 1. All patients received IV iron (73 iron dextran and 70 iron sucrose) and none were lost to follow-up. Immediate ADRs were similar between the two study arms; iron dextran 8/73 (11%) and iron sucrose 5/70 (7%), p=0.568. The average additional nursing time required to manage immediate ADRs was approximately 30 minutes. Delayed ADRs approached statistical significance with a higher rate of ADRs in the iron sucrose group [ iron dextran 9/73 (12%) and iron sucrose 18/70 (26%), p=0.0541]. Details in Table 2. Four patients were considered to have serious adverse reactions (shortness of breath, bronchospasm and diaphoresis). Two form each study arm. [Display omitted] [Display omitted] Conclusions:A RCT to compare adverse drug reaction rates between iron dextran and iron sucrose in non-hemodialysis adult patients with iron deficiency anemia is feasible. In our pilot study we were able to get 100% enrolment rate, in a timely fashion with no patients lost to follow up. The design of the study with a one point in time evaluation and a short follow up that did not require extra hospital visits and blood tests were probably attractive features that maximized patient participation. The incidence and severity of ADRs to both IV iron preparations studied were similar with greater than 25% of patients experiencing either immediate or delayed ADRs. However, a striking higher rate of delayed ADRs, albeit not severe, was slightly more pronounced in patients receiving iron sucrose therapy. The elevated level of ADRs to IV iron suggests the need for alternative formulations and a full RCT to compare the rate of ADRs between iron preparations is warranted. The choice of IV iron formulation in the adult non-hemodialysis population should take into account factors other than cost of the medication such as incidence and severity of ADRs, extra time required by Healthcare professionals, and patient preferences. Disclosures:No relevant conflicts of interest to declare.

High risk of cross-reactivity between vancomycin and sequential teicoplanin therapy

Teicoplanin and vancomycin show similar clinical and bacteriological efficacy in clinical trials. Teicoplanin has been reported to have a lower adverse drug reaction (ADR) rate than vancomycin. Cross-reactivity between these two glycopeptides is controversial. Our aim was to study the cross-reactivity between teicoplanin and vancomycin through an assessment of all the reported ADRs of these drugs in our University hospital. Over a period of 2 years, 170 cases of vancomycin therapy, which were closely monitored by doctors and clinical pharmacists, were used to analyse ADRs. Teicoplanin therapy was used as an alternative in cases of vancomycin intolerance. When an ADR related to vancomycin or teicoplanin was suspected, specialists were consulted to confirm if these were true ADR and to determine whether the implicated drug should be stopped. All ADRs for the two glycopeptides were assessed for causality using the Naranjo probability scale. Thirty-eight of 170 patients (22·4%) treated with vancomycin developed ADRs. Twenty-four patients were switched to teicoplanin. However, 14 of those 24 patients (58·3%) developed ADRs. The time of onset of ADRs involving vancomycin was 12·7 ± 10·9 days (range, 1-46 days). The time of onset of sequential teicoplanin-induced ADRs was 11·7 ± 4·7 days (range, 2-20 days). Of the 14 patients with ADRs related to sequential teicoplanin therapy, six showed cross-reactivity between vancomycin and teicoplanin. The incidence of vancomycin-induced neutropenia was 4·7% (8/170), whereas the incidence of teicoplanin-induced neutropenia subsequent to vancomycin intolerance was as high as 33·3% (8/24). Furthermore, 71·4% (10/14) of the teicoplanin-induced ADRs were associated with haematological abnormalities such as neutropenia, thrombocytopenia or leucopenia. Teicoplanin, used as an alternative in cases of vancomycin intolerance, was associated with a high incidence of ADRs and haematological reactions, most notably neutropenia. This high rate of ADRs suggests cross-reactivity between the two glycopeptides.

Patterns, predictors and preventability of adverse drug reactions in the coronary care unit of a tertiary care hospital

To determine the frequency of occurrence, risk factors, clinical spectrum and drugs associated with adverse drug reactions (ADRs) occurring in the coronary care unit (CCU) of a tertiary care hospital. This was a retrospective cohort study based on evaluation of the medical records of consecutive patients admitted to the CCU between January 2008 and December 2008. Each prescription was monitored for ADRs, and each ADR was assessed for causality, severity, predictability and preventability by two physicians using relevant scales. The chi-square test and independent t test were used to compare the ADR and non-ADR groups. Multiple binary logistic regression was used to identify risk factors for developing ADRs in the CCU. Of 595 patients, 152 (25.5%) developed ADRs, of which 45% were potentially preventable. Severe ADRs constituted 28.6% of the total ADRs. Patients who developed an ADR had a longer duration of stay in the hospital (2.8 extra days) (p < 0.05). Hypokalemia/hyperkalemia (22%), bleeding (11%) and cardiac arrhythmias (11%) were the commonest ADRs. The highest rates of ADRs were seen with streptokinase (59.4%). The predictors for developing an ADR in the CCU included renal dysfunction [odds ratio (OR) 1.66, 95% confidence interval (CI) 1.007-2.72], arrhythmias (OR 1.74, 95% CI 1.052-2.87) and polypharmacy with more than ten drugs (OR 11.3, 95% CI 1.45-87.44). A high frequency of ADR occurrence was identified, with many of the ADRs being potentially preventable. Patients with renal dysfunction or cardiac arrhythmias and those receiving polypharmacy were at an increased risk for developing an ADR in the CCU.

Safety and effectiveness of adalimumab in Japanese rheumatoid arthritis patients: postmarketing surveillance report of the first 3,000 patients

This interim analysis of postmarketing surveillance data for adalimumab-treated rheumatoid arthritis (RA) patients summarizes safety and effectiveness during the first 24weeks of therapy for the first 3,000 patients treated in Japan (June 2008-December 2009). Patient eligibility for antitumor necrosis factor therapy was based on the Japanese College of Rheumatology treatment guidelines and Japanese labeling. All patients were screened for tuberculosis. Approximately 50% of the population was biologic naïve, 66% received concomitant methotrexate (MTX), and 72% received concomitant glucocorticoids. The overall incidence rate of adverse events was 31% (5.5% serious) and that of adverse drug reactions (ADRs) was 27% (4.1% serious). Incidence rates of ADRs and serious ADRs were similar regardless of prior biologic therapy or concomitant MTX use but were significantly higher in patients receiving glucocorticoids compared with those not receiving glucocorticoids. Bacterial/bronchial pneumonia occurred in 1.2% of patients; interstitial pneumonia, 0.6%; Pneumocystis jirovecii pneumonia, 0.3%; tuberculosis, 0.13%; and administration-site reactions, 6.1%. Mean 28-joint Disease Activity Scores decreased significantly after 24weeks from 5.29 to 3.91. All subgroups showed significant improvement, particularly the biologic-naïve patients receiving concomitant MTX. No new safety concerns were identified. ADR Incidence rates were similar to those of other biologic agents approved for RA.

A randomized, double-blind, active-controlled, double-dummy, parallel-group study to determine the safety and efficacy of oxycodone/naloxone prolonged-release tablets in patients with moderate/severe, chronic cancer pain

Objective: An examination of whether oxycodone/naloxone prolonged-release tablets (OXN PR) can improve constipation and maintain analgesia, compared with oxycodone prolonged-release tablets (OxyPR) in patients with moderate/severe cancer pain. Methods: Randomized, double-blind, active-controlled, double-dummy, parallel-group study in which 185 patients were randomized to receive up to 120 mg/day of OXN PR or OxyPR over 4 weeks. Efficacy assessments included Bowel Function Index (BFI), Brief Pain Inventory Short-Form (BPI-SF), laxative and rescue medication use. Quality of life (QoL) and safety assessments were conducted. Results: After 4 weeks, mean BFI score was significantly lower with OXN PR; mean total laxative intake was 20% lower with OXN PR. Mean BPI-SF scores were similar for both treatments and the average rate of analgesic rescue medication use was low and comparable. QoL assessments were stable and comparable with greater improvements in constipation-specific QoL assessments with OXN PR. Overall, rates of adverse drug reactions were similar. Conclusions: OXN PR provides superior bowel function in cancer pain patients, compared with OxyPR, without compromising analgesic efficacy or safety. This study confirms that OXN PR is well tolerated and efficacious in cancer pain patients and results are in line with those seen in non-malignant pain patients.