Post-marketing Surveillance Reports Research Articles

Empagliflozin-A Sodium Glucose Co-transporter-2 Inhibitor: Overview of Its Chemistry, Pharmacology, and Toxicology.

Empagliflozin is a sodium glucose co-transporter-2 (SGLT2) inhibitor that has gained significant attention in the treatment of type 2 diabetes mellitus. Understanding its chemistry, pharmacology, and toxicology is crucial for the safe and effective use of this medication. This review aims to provide a comprehensive overview of the chemistry, pharmacology, and toxicology of empagliflozin, synthesizing the available literature to present a concise summary of its properties and implications for clinical practice. A systematic search of relevant databases was conducted to identify studies and articles related to the chemistry, pharmacology, and toxicology of empagliflozin. Data from preclinical and clinical studies, as well as post-marketing surveillance reports, were reviewed to provide a comprehensive understanding of the topic. Empagliflozin is a selective SGLT2 inhibitor that works by constraining glucose reabsorption in the kidneys, causing increased urinary glucose elimination. Its unique mechanism of action provides glycemic control, weight reduction, and blood pressure reduction. The drug's chemistry is characterized by its chemical structure, solubility, and stability. Pharmacologically, empagliflozin exhibits favorable pharmacokinetic properties with rapid absorption, extensive protein binding, and renal elimination. Clinical studies have demonstrated its efficacy in improving glycemic control, reducing cardiovascular risks, and preserving renal function. However, adverse effects, for instance, urinary tract infections, genital infections, and diabetic ketoacidosis have been reported. Toxicological studies indicate low potential for organ toxicity, mutagenicity, or carcinogenicity. Empagliflozin is a promising SGLT2 inhibitor that offers an innovative approach to the treatment of type 2 diabetes mellitus. Its unique action mechanism and favorable pharmacokinetic profile contribute to its efficacy in improving glycemic control and reducing cardiovascular risks. While the drug's safety profile is generally favorable, clinicians should be aware of potential adverse effects and monitor patients closely. More study is required to determine the longterm safety and explore potential benefits in other patient populations. Overall, empagliflozin represents a valuable addition to the armamentarium of antidiabetic medications, offering significant benefits to patients suffering from type 2 diabetes mellitus. This study covers all aspects of empagliflozin, including its history, chemistry, pharmacology, and various clinical studies, case reports, and case series.

Post-Marketing Surveillance Report of Rupatadine Fumarate for the Treatment of Allergic Rhinitis

Post-Marketing Surveillance Report of Rupatadine Fumarate for the Treatment of Allergic Rhinitis

The integrity of the antimicrobial supply chain in Bangladesh: assessing the regulatory environment and contextual challenges.

Most low- and middle-income countries lack theregulatory capacity to contain substandard and falsified (SF) medicines. Innovations for strengthening regulatory systems are needed to protect public health. We assessed the integrity of the antimicrobial supply chain in Bangladesh. We employed qualitative methods comprising policy content analysis, and literature and database reviews. Using a framework modified from the World Health Organization's and the United States Pharmacopoeia's, the Bangladesh National Drug Policy (BNDP), was evaluated forprovisions on medicinesquality assurance mechanisms. We used newspaper, peer-reviewed, and post-marketing surveillance reports to assess prevalence of SF antimicrobials. The BNDP contains provisions for quality assurance. Newspaper reports identified circulation of substandard antimicrobials. We identified only six peer-review studies testing antimicrobial product quality with three studies reporting out-of-specifications products. We suggest three strategies for strengthening the regulatory system: community-based surveillance, task shifting, and technology-enabled consumer participation.

Post-Marketing Surveillance Report of Rupatadine Fumarate for the Treatment of Urticaria and Pruritus Associated with Skin Diseases

目的：蕁麻疹，皮膚疾患（湿疹・皮膚炎，皮膚そう痒症）に伴うそう痒に対するルパタジンフマル酸塩（以下，ルパタジン）の使用実態下における安全性および有効性を検討した。

Innovative Nutraceutical Effectively Manages Canine Atopy

Like people, dogs may be allergic to numerous substances that their bodies touch or are found in the air or in food. These allergens enter the body by inhalation, direct contact or absorption, i.e., through the skin or respiratory or gastrointestinal tracts. Recognized as foreign entities, the canine response is the release of inflammatory cells and the regulation of histamine levels as defence mechanisms. Innumerable prescription and over-the-counter treatments have been advanced in attempts to relieve the clinical signs associated with canine seasonal allergies. The primary aim of this multisite, prospective open label trial was to support anecdotal postmarketing surveillance reports that the non-prescription canine chew under study provided significant benefits for the treatment of canine allergic dermatitis. A secondary aim was to elicit responses from groomers and pet parents who used the product for their dogs. Animals presented at random with lesions consistent with a diagnosis of allergic dermatitis were enrolled during the normal course of business at the veterinary hospital and groomers’ shops. Pet parents, groomers and veterinarians reported that a twice-a-day treatment regimen resulted in the reduction or alleviation of one or more cardinal signs of canine allergic dermatitis in 83.3% of the enrolled dogs. These findings warrant the use of Dermabliss Seasonal Allergy Chews alone or in conjunction with other treatments) for dogs with allergic dermatitis.

Effectiveness of BNT162b2 mRNA Vaccine Against Infection and COVID-19 Vaccine Coverage in Healthcare Workers in England, Multicentre Prospective Cohort Study (the SIREN Study)

Background: BNT162b2 mRNA and ChAdOx1 nCOV-19 adenoviral vector vaccines have been rapidly rolled out in the UK. We determined the factors associated with vaccine coverage for both vaccines and documented the vaccine effectiveness of the BNT162b2 mRNA vaccine in our healthcare worker (HCW) cohort study of staff undergoing regular asymptomatic testing.Methods: The SIREN study is a prospective cohort study among staff working in publicly funded hospitals. Baseline risk factors, vaccination status (from 8/12/2020-5/2/2021), and symptoms are recorded at 2 weekly intervals and all SARS-CoV-2 polymerase chain reaction (PCR) and antibody test results documented. A mixed effect proportional hazards frailty model using a Poisson distribution was used to calculate hazard ratios to compare time to infection in unvaccinated and vaccinated participants to estimate the impact of the BNT162b2 vaccine on all (asymptomatic and symptomatic) infection.Findings: Vaccine coverage was 89% on 5/2/2021. Significantly lower coverage was associated with prior infection (aOR 0.59 95% confidence interval [CI] 0.54-0.64), female (aOR 0.72, 95% CI 0.63-0.82), aged under 35 years, being from minority ethnic groups (especially Black, aOR 0.26, 95% CI 0.21-0.32), porters/security guards (aOR 0.61, 95% CI 0.42-0.90),or midwife (aOR 0.74, 95% CI 0.57-0.97), and living in more deprived neighbourhoods (IMD 1 (most) vs. 5 (least) (aOR 0.75, 95% CI 0.65-0.87). A single dose of BNT162b2 vaccine demonstrated vaccine effectiveness of 72% (95% CI 58-86) 21 days after first dose and 86% (95% CI 76-97) seven days after two doses in the antibody negative cohort.Conclusion: Our study demonstrates that the BNT162b2 vaccine effectively prevents both symptomatic and asymptomatic infection in working age adults; this cohort was vaccinated when the dominant variant in circulation was B1.1.7 and demonstrates effectiveness against this variant.Trial Registration: IRAS ID 284460, REC reference 20/SC/0230 Berkshire Research Ethics Committee, Health Research Authority and Health and Care Research Wales approval granted 22 May 2020. Trial registered with ISRCTN, Trial ID: ISRCTN11041050. https://www.isrctn.com/ISRCTN11041050Funding: The study is funded by the United Kingdom’s Department of Health and Social Care and Public Health England, with contributions from the Scottish, Welsh and Northern Irish governments. Funding is also provided by the National Institute for Health Research (NIHR) as an Urgent Public Health Priority Study (UPHP). SH, VH are supported by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Healthcare Associated Infections and Antimicrobial Resistance at the University of Oxford in partnership with Public Health England (PHE) (NIHR200915). AC is supported by NIHR HealthProtection Research Unit in Behavioural Science and Evaluation at University of Bristol in partnership with Public Health England. MR, NA, AC are supported by NIHR HealthProtection Research Unit in Immunisation at the London School of Hygiene and Tropical Medicine in partnership with Public Health England.Conflict of Interest: The Immunisation and Countermeasures Division has provided vaccine manufacturers(including Pfizer) with post-marketing surveillance reports on pneumococcal andmeningococcal infection which the companies are required to submit to the UK Licensing authority in compliance with their Risk Management Strategy. A cost recovery charge is made for these reports.Ethical Approval: The study was approved by the Berkshire Research Ethics Committee, Health Research Authority (IRAS ID 284460, REC reference 20/SC/0230) on 22 May 2020; the vaccine amendment was approved on 12/1/2021.

Safety of Gliadel Implant for Malignant Glioma: Report of Postmarketing Surveillance in Japan.

Clinical trial data of Carmustine implant (Gliadel Wafer) in Japanese patients with malignant glioma are limited; thus, we conducted a postmarketing surveillance study to evaluate the safety of Gliadel in real-world clinical practice in Japan. In this postmarketing surveillance study, all patients who received Gliadel placement for malignant glioma surgeries from its market launch (January 9, 2013) to July 10, 2013 were enrolled from 229 institutions using a central registration system. Up to eight wafers of Gliadel (containing 61.6 mg of carmustine) were used to cover the site of brain tumor resection intraoperatively according to the size and shape of the tumor resection cavity. The observation period lasted 3 months after Gliadel placement. Patients were followed up for 1 year postoperatively. Safety was assessed by the incidence of adverse events (AEs) and adverse drug reactions (ADRs). In total, 558 patients were included. Most patients (66.7%) received eight Gliadel wafers. The percentage of patients with ADRs was 35.7% (365 ADR episodes in 199 patients). Of the AEs of special interest, the most common were cerebral edema (22.2%, 124/558 patients), convulsion (9.9%, 55/558 patients), impaired healing (4.8%, 27/558 patients), and infection (3.4%, 19/558 patients). This first all-case postmarketing surveillance report of the safety of Gliadel in real-world clinical practice in Japan suggests that the risk of toxicity with Gliadel placement is relatively tolerable. The survival benefits of Gliadel placement should be evaluated and considered carefully by the clinician taking into account possible toxicities.

The Impact of the COVID-19 Pandemic on Invasive Pneumococcal Disease and the Risk of Pneumococcal Coinfection with SARS-CoV-2: Prospective National Cohort Surveillance, England

Background: Streptococcus pneumoniae coinfection with seasonal and pandemic influenza results in synergistic lethality, but there are limited data on pneumococcal coinfection with SARS-CoV-2 during the current COVID-19 pandemic.Methods: Public Health England conducts invasive pneumococcal disease (IPD) and COVID-19 surveillance in England. IPD trends from 2000/01 to 2019/20 were analysed and cases between 01 February and 30 June 2020 were linked with laboratory-confirmed SARS-CoV-2 infections.Findings: IPD incidence in 2019/20 (7.6/100,000; 3,964 cases) was 30% (IRR 0.70, 95%CI, 0.18-2.67) lower compared to 2018/19 (10.9/100,000, 3,964 cases) with large reductions observed across all age-groups during March-June 2020. The serotypes responsible for IPD during 2019/20 were similar to previous years. There were 160,886 SARS-CoV-2 infections and 1,159 IPD cases between February and June 2020, including 40 IPD/SARS-CoV-2 coinfections (0.025% [95%CI, 0.018-0.034] of SARS-CoV-2 infections; 3.5% [95%CI, 2.5-4.8] of IPD cases), 21 with COVID-19 diagnosed 3-28 days after IPD and 27 who developed COVID-19 >28 days after IPD. Case fatality was 63.2% (25/40) in the coinfection group compared to 47.6% (10/21) in those who developed COVID-19 3-14 days after IPD, and 33.3% (9/27) in patients who developed IPD and COVID-19 more than 28 days apart (pInterpretation: The COVID-19 pandemic and the consequent lockdown was associated with large declines in IPD across all age groups. IPD/SARS-CoV-2 confections were rare but associated with high case-fatality, mainly in older adults. The rarity, age distribution and serotype distribution of IPD/SARS-CoV-2 coinfections does not support wider extension of pneumococcal vaccination during the COVID-19 pandemicFunding: PHEDeclaration of Interests: SNL performs contract research for vaccine manufacturers (including GSK, Pfizer, and Sanofi Pasteur) on behalf of St George’s University of London and Public Health England but receives no personal remuneration. The Immunisation and Countermeasures Division at PHE has provided pharmaceutical companies with post-marketing surveillance reports on vaccine-preventable infections, which the companies are required to submit to the UK Licensing Authority in compliance with their Risk Management Strategy. A cost recovery charge is made for these reports. All other authors declare no competing interests.Ethics Approval Statement: PHE has legal permission, provided by Regulation 3 of The Health Service (Control of Patient Information) Regulations 2002, to process patient confidential information for national surveillance of communicable diseases. This includes PHE’s responsibility to monitor the safety and effectiveness of vaccines, and as such, individual patient consent is not required.

Invasive Pneumococcal Disease in People with HIV in England, 1999-2017

Background: The 7-valent and 13-valent pneumococcal conjugate vaccines (PCVs) were introduced into the United Kingdom childhood immunisation programme in 2006 and 2010 respectively, with high effectiveness and resulting in both direct and indirect protection. We describe the epidemiology of invasive pneumococcal disease (IPD) in adults with HIV in England following the introduction of both PCVs. Methods: Data on a national cohort of people with HIV were linked to confirmed IPD cases in adults aged ≥15 years during 1999-2017. Date of HIV infection was estimated using a CD4 slope decline algorithm. Findings: Among 133,994 adults with HIV, 1,453 developed IPD during 1999-2017, with 70% (1,016/1,453) developing IPD ≥3 months after their HIV diagnosis. IPD and HIV were co-diagnosed within 90 days in 345 (24%) individuals. A missed opportunity for earlier HIV diagnosis was identified in 6% (89/1,453), mostly in earlier years. IPD incidence in people with HIV increased from 147/100,000 in 1999 to 284/100,000 in 2007 before declining and stabilising between 92-113/100,000 during 2014-2017. Mean annual IPD incidence was lower among those receiving ART during 2014-17 (720 vs. 68/100,000; IRR 9.3; 95%CI, 7.3-11.8; P<0.001) and was markedly lower in those with a suppressed viral load (523 vs. 50/100,000; IRR 10.4; 95%CI, 7.6-14.1; P<0.001). The latter group still had 4.5-fold higher (95%CI, 3.8-5.3; P<0.001) IPD incidence compared to the general population (11.2/100,000). Interpretation: IPD incidence among people with HIV reduced after PCV13 introduction and has remained stable. Adults presenting with IPD should continue to be tested for HIV infection. Funding Statement: The authors are employed by PHE. There was no additional funding for this study. Declaration of Interests: PDK, ZAC, SEC, CS, NF and VCD declare no conflicts of interest. SNL performs contract research on behalf of St. George’s University of London (SGUL) and Public Health England (PHE) for vaccine manufacturers but receives no personal remuneration. The Immunisation Department has provided vaccine manufacturers with post-marketing surveillance reports on pneumococcal and meningococcal infection which the companies are required to submit to the UK Licensing authority in compliance with their Risk Management Strategy. A cost recovery charge is made for these reports. Ethics Approval Statement: PHE has legal permission, provided by Regulation 3 of The Health Service (Control of Patient Information) Regulations 2002, to process patient confidential information for national surveillance of communicable diseases (http://www.legislation.gov.uk/uksi/2002/1438/regulation/3/made). This includes PHE’s responsibility to monitor the safety and effectiveness of vaccines.

A comprehensive safety profile of tafamidis in patients with transthyretin amyloid polyneuropathy

Background: Tafamidis is approved in over 40 countries to delay neurologic progression in patients with transthyretin amyloid polyneuropathy (ATTR-PN). A comprehensive, integrated analysis of safety data from interventional, observational and surveillance studies of tafamidis in ATTR-PN patients was conducted.Methods: Safety data from all sponsored, completed, or ongoing, Phase 2/3 studies of tafamidis in ATTR-PN patients as of 3 January 2017 were pooled. Also assessed were safety data from the ongoing Transthyretin Amyloidosis Outcomes Survey (THAOS) as of 3 January 2017 and post-marketing surveillance reports as of 31 March 2017.Results: There were 137 patients in Phase 2/3 studies (mean duration of tafamidis exposure, 44.2 months), with 134 (97.8%) experiencing ≥1 treatment-emergent adverse event (TEAE) and 46 (33.6%) ≥1 treatment-emergent serious adverse event (TESAE). The most common TEAEs were diarrhoea (26.3%), urinary tract infection (UTI; 25.5%) and influenza (21.2%). In THAOS, 661 subjects had tafamidis exposure (mean duration, 27.6 months), with 250 (37.8%) experiencing ≥1 TEAE and 96 (14.5%) ≥1 TESAE. The most common TEAE was UTI (6.1%). Post-marketing surveillance reports generally reflected the known safety profile of tafamidis.Conclusions: This analysis did not reveal any significant new safety findings; tafamidis was generally safe and well tolerated in ATTR-PN patients. Trial registration: ClinicalTrials.gov identifier: NCT00409175.Trial registration: ClinicalTrials.gov identifier: NCT00791492.Trial registration: ClinicalTrials.gov identifier: NCT00630864.Trial registration: ClinicalTrials.gov identifier: NCT01435655.Trial registration: ClinicalTrials.gov identifier: NCT00925002.Trial registration: ClinicalTrials.gov identifier: NCT00628745.

Safety and effectiveness of high-dose methotrexate (over 8 mg/week) in 2838 Japanese patients with rheumatoid arthritis: a postmarketing surveillance report

Objectives: To confirm the safety and effectiveness of high-dose (>8 mg/week) methotrexate (MTX) for the treatment of rheumatoid arthritis in Japan.Methods: A postmarketing surveillance program enrolled Japanese patients with rheumatoid arthritis starting on high-dose MTX followed up for 24 or 52 weeks. Analyses for safety, risk factors affecting safety, and effectiveness were conducted.Results: The safety/effectiveness analysis sets included 2838/2779 and 335/326 patients in the 24 and 52-week follow-up groups, respectively. Incidence of adverse drug reactions (ADRs) and serious ADRs was 21.42 and 1.66% in the 24-week and 35.52 and 2.69% in the 52-week groups, respectively. The Disease Activity Score in 28 Joints (DAS28) was significantly decreased as early as four weeks from the start of high-dose MTX; after 24-week (4.09–3.21) and 52-week treatment (3.91–2.80; both p < .001). In a majority of patients at baseline who had high-to-moderate disease activity, the remission rate (defined as DAS28-4ESR <2.6) increased three-fold from 10.6% (baseline) to 33.0% (24-week) compared to patients with low disease activity whose remission rate increased two-fold from 24.0% (baseline) to 53.6% (24 weeks).Conclusion: High-dose MTX was well tolerated in Japanese patients, resulted in improved disease control, and can be considered a step forward in achieving treat-to-target goals.

CASE REPORT ON DOCETAXEL-INDUCED INTERSTITIAL LUNG DISEASE

Docetaxel belongs to taxane family of antineoplastic agents that are indicated for the treatment of locally advanced or metastatic non-small-cell lung cancer. Docetaxel is associated with many adverse effects, and pulmonary reaction has an incidence of 41%. However, interstitial pulmonary disease is found to occur only in &lt;1% of the population as per the post-marketing surveillance reports. Here, we report a case of docetaxel-induced interstitial lung disease (ILD). The patient information and details were collected using the hospital information system. The adverse drug reaction (ADR) of ILD occurred after 5 cycles of chemotherapy with docetaxel at a dose of 60 mg/m2 that is 80 mg IV. The causality of the event in our case was assessed using the Naranjo ADR probability scale which marked a score of 7 (probable). It is necessary that all physicians be aware of the reaction and to closely monitor clinicoradiological and functional status of the patients at regular intervals after administration of docetaxel.

RETRACTED ARTICLE: Safety and effectiveness of high-dose methotrexate (over 8 mg/week) in 2838 Japanese patients with rheumatoid arthritis: A postmarketing surveillance report

The following article is being retracted from publication in Modern Rheumatology:“Safety and effectiveness of high-dose methotrexate (over 8 mg/week) in 2838 Japanese patients with rheumatoid arthr...

Fatal adverse drug reactions of anticancer drugs detected by all-case post-marketing surveillance in Japan.

All-case post-marketing surveillance of newly approved anticancer drugs is usually conducted on all patients in Japan. The present study investigates whether all-case post-marketing surveillance identifies fatal adverse drug reactions undetected before market entry. We examined fatal adverse drug reactions identified via all-case post-marketing surveillance by reviewing the disclosed post-marketing surveillance results, and determined the time points in which the fatal adverse drug reactions were initially reported by reviewing drug labels. We additionally scanned emergency alerts on the Japanese regulatory authority website to assess the relationship between all-case post-marketing surveillance and regulatory action. Twenty-five all-case post-marketing surveillances were performed between January 1999 and December 2009. Eight all-case post-marketing surveillances with final results included information on all fatal cases. Of these, the median number of patients was 1287 (range: 106-4998), the median number of fatal adverse drug reactions was 14.5 (range: 4-23). Of the 111 fatal adverse drug reactions detected in the eight post-marketing surveillances, only 28 (25.0%) and 22 (19.6%) were described on the initial global and the initial Japanese drug label, respectively, and 58 (52.3%) fatal adverse drug reactions were first described in the all-case post-marketing surveillance reports. Despite this, the regulatory authority issued only four warning letters, and two of these were prompted by case reports from the all-case post-marketing surveillance. All-case post-marketing surveillance of newly approved anticancer drugs in Japan was useful for the rigorous compilation of non-specific adverse drug reactions, but it rarely detected clinically significant fatal adverse drug reactions.

Adverse events following immunization in Ontario's female school-based HPV program

BackgroundIn September 2007, a school-based human papillomavirus (HPV) vaccination program targeting grade 8 girls (approximately 13 years old) and delivered by public health was implemented in Ontario, Canada. We assessed reports of adverse events following immunization (AEFI) from the school-based program as part of quadrivalent HPV (HPV4) vaccine safety surveillance and to contribute to a comprehensive HPV vaccine program evaluation. MethodsAEFIs following HPV4 vaccine (Gardasil®) administered between September 1, 2007 and December 31, 2011 were extracted from the province's reportable disease system. Confirmed AEFI reports among females 12–15 years old (i.e. assumed to have received vaccine through the program) were included. Events were grouped according to provincial AEFI case definitions. Rates were calculated using doses distributed as the denominator. ResultsBetween 2007 and 2011, 133 confirmed AEFIs were reported while 691,994 HPV4 vaccine doses were distributed in the school-based program. The overall reporting rate was 19.2 HPV4 AEFI per 100,000 doses distributed. Annual reporting rates decreased from 30.0 to 18.3 per 100,000 doses distributed. Frequently reported events included ‘allergic reaction—dermatologic/mucosa’ (25%), ‘rash’ (22%), and ‘local/injection site reaction’ (20%); 26% of reports had a non-specific event of ‘other severe/unusual events’ selected. Ten serious AEFIs were reported (7.5% of reports) including 2 anaphylaxis, 2 seizures, 1 thrombocytopenia and 1 death. Further review found that the reports of anaphylaxis did not meet the Brighton anaphylaxis definition and the death was attributed to a preexisting cardiac condition. ConclusionsOverall these findings are consistent with the safety profile of HPV4 vaccine from pre-licensure clinical trials and post-marketing surveillance reports and importantly, no new safety signals were identified, especially no reports of VTE in this younger female population. Continued assessment of HPV4 AEFI surveillance data may be important to detect and investigate safety signals.

Safety and effectiveness of adalimumab in Japanese rheumatoid arthritis patients: Postmarketing surveillance report of 7740 patients

Objectives. To confirm the safety and effectiveness of adalimumab and to evaluate the influence of the concomitant use of methotrexate (MTX).Methods. Postmarketing surveillance of 7740 Japanese rheumatoid arthritis (RA) patients was performed. All patients who received adalimumab in the registration period were followed for 28 weeks after starting treatment for safety and 24 weeks for effectiveness. Effectiveness was measured by duration of morning stiffness, swollen and tender joint counts (28 joints), patient global assessment of disease activity, erythrocyte sedimentation rate and serum C-reactive protein.Results. Comparable rates of adverse drug reactions (ADRs) were reported in this study and in the interim analysis. Age, pulmonary disease history or comorbidity, co-existing diabetes mellitus, concomitant MTX at doses of > 8 mg/week and concomitant glucocorticoids at doses of > 5 mg/day were risk factors for infections. All mean values of effectiveness measurements improved. Relatively lower disease activity at baseline, biologic-naïve, concomitant MTX use and early RA stage/low functional class were background factors contributing to the effectiveness. The combination of adalimumab with MTX improved the response to adalimumab treatment.Conclusion. Adalimumab, especially with concomitant use of MTX, provided significant improvement in disease activity, without any unexpected ADRs in Japanese RA patients.

The toxicology and comorbidities of fatal cases involving quetiapine

The use of quetiapine in Australia has increased rapidly in recent years. Anecdotal and post-marketing surveillance reports indicate an increase in quetiapine misuse in prisons as well as an increase in its availability on the black-market. This study examined a cohort of quetiapine-associated deaths occurring in Victoria, Australia, between 2001 and 2009, to determine the prevalence of deaths associated with this drug and to determine whether misuse represents a legitimate concern. Case details were extracted from the National Coronial Information System. There were 224 cases with an average age of 43years of age (range 15-87years). The cause of death was mostly drug toxicity (n=114, 51%), followed by natural disease (n=60, 27%), external injury (n=31, 14%) and unascertained causes (n=19, 8%). Depression and/or anxiety were common, observed in over a third of the cohort (80 cases, 36%). About 20% of cases did not mention a psychiatric diagnosis at all which raises the question of whether quetiapine had been prescribed correctly in these cases. Cardiovascular disease was the most commonly reported illness after mental disease. Quetiapine ranged in concentration from the limit of reporting (0.01mg/L) to 110mg/L. The median concentration of quetiapine was much lower in the natural disease deaths (0.25mg/L) compared with drug caused deaths (0.7mg/L). The most commonly co-administered drug was diazepam in 81 (36%) cases. There were a small number of cases where quetiapine contributed to a death where it had not apparently been prescribed, including the death of a 15year old boy and one of a 34year old female. Overall, misuse of quetiapine did not appear to be a significant issue in this cohort; use of the drug only occasionally led to fatalities when used in excess or concomitantly with interacting drugs. However, considering that it is a recent social concern, it is possible that analysis of cases post 2009 would reveal more cases of quetiapine abuse. Close monitoring of quetiapine is therefore advised to prevent adverse outcomes, particularly in vulnerable populations such as substance abusers.

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.

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.

Varenicline: No Harm, but Little Benefit

Varenicline, a partial agonist of the nicotinic acetylcholine receptor, is a widely advertised smoking-cessation drug that some postmarketing surveillance reports have linked to adverse neuropsychiatric events. These researchers randomized 110 highly dependent smokers (of 857 initially screened) without psychiatric histories to receive varenicline (1 mg) or placebo twice daily for 12 weeks. The manufacturer funded the trial, which was conducted at a commercial site, …