scholarly journals Focus on Clozapine Withdrawal- and Misuse-Related Cases as Reported to the European Medicines Agency (EMA) Pharmacovigilance Database

2020 ◽  
Vol 10 (2) ◽  
pp. 105 ◽  
Author(s):  
Stefania Chiappini ◽  
Fabrizio Schifano ◽  
John Martin Corkery ◽  
Amira Guirguis
Keyword(s):  
Descriptive Analysis ◽  
Drug Misuse ◽  
European Medicines Agency ◽  
Drug Reactions ◽  
Treatment Resistant ◽  
Polydrug Abuse ◽  
Pharmacovigilance Database ◽  
History Of ◽  
Recreational Use ◽  
Clozapine Withdrawal

Background: Clozapine is of high clinical relevance for the management of both treatment-resistant schizophrenia and psychotic disturbances with concurrent drug misuse. Although the molecule presents with a range of well-known side-effects, its discontinuation/withdrawal syndrome has been only anecdotally described. Aims: the 2005–2018 European Medicines Agency (EMA) dataset of Adverse Drug Reactions (ADRs) was analyzed to identify and describe possible clozapine withdrawal- and misuse-/abuse-/dependence-related issues. Method: A descriptive analysis of clozapine-related ADRs was performed when available, data on ADRs’ outcome, dosage, and possible concomitant drug(s) were considered. Results: Out of 11,847 clozapine-related ADRs, some 599 (5.05%) were related to misuse/abuse/dependence/withdrawal issues, including 258 withdrawal-related (43.1%); 241 abuse-related (40.2%); and 80 intentional product misuse-related (13.3%) ADRs. A small number of overdose- and suicide-related ADRs were reported as well. Clozapine was typically (69.2%) identified alone, and most (84.7%) fatalities/high-dosage intake instances were reported in association with a history of substance abuse. Conclusions: Previous suggestions about the possibility of a clozapine discontinuation/withdrawal occurrence are here supported, but further studies are needed. However, the misuse/abuse cases here identified might be difficult to interpret, given the lack of studies highlighting the possible recreational use of clozapine. The high-dosage intake, fatal outcomes and clozapine/polydrug abuse issues reported here may, however, be a reason for concern.

Identification of anticancer drugs associated with atrial fibrillation: analysis of the WHO pharmacovigilance database

2020 ◽  
Author(s):  
Joachim Alexandre ◽  
Joe-Elie Salem ◽  
Javid Moslehi ◽  
Marion Sassier ◽  
Camille Ropert ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Anticancer Drugs ◽  
Kinase Inhibitors ◽  
Descriptive Analysis ◽  
Individual Case ◽  
World Health ◽  
European Medicines Agency ◽  
Individual Case Safety Report ◽  
Pharmacovigilance Database ◽  
Haematologic Malignancies

Abstract Aims The explosion of novel anticancer therapies has meant emergence of cardiotoxicity signals including atrial fibrillation (AF). Reliable data concerning the liability of anticancer drugs in inducing AF are scarce. Using the World Health Organization individual case safety report database, VigiBase®, we aimed to determine the association between anticancer drugs and AF. Methods and results A disproportionality analysis evaluating the multivariable-adjusted reporting odds ratios for AF with their 99.97% confidence intervals was performed for 176 U.S. Food and Drug Administration (FDA)- or European Medicines Agency (EMA)-labelled anticancer drugs in VigiBase®, followed by a descriptive analysis of AF cases for the anticancer drugs identified in VigiBase®. ClinicalTrial registration number: NCT03530215. A total of 11 757 AF cases associated with at least one anticancer drug were identified in VigiBase® of which 95.8% were deemed serious. Nineteen anticancer drugs were significantly associated with AF of which 14 (74%) are used in haematologic malignancies and 9 (45%) represented new AF associations not previously confirmed in literature including immunomodulating agents (lenalidomide, pomalidomide), several kinase inhibitors (nilotinib, ponatinib, midostaurin), antimetabolites (azacytidine, clofarabine), docetaxel (taxane), and obinutuzumab, an anti-CD20 monoclonal antibody. Conclusion Although cancer malignancy itself may generate AF, we identified 19 anticancer drugs significantly associated with a significant increase in AF over-reporting. This pharmacovigilance study provides evidence that anticancer drugs themselves could represent independent risk factors for AF development. Dedicated prospective clinical trials are now required to confirm these 19 associations. This list of suspected anticancer drugs should be known by physicians when confronted to AF in cancer patients, particularly in case of haematologic malignancies.

scholarly journals Beyond the ‘purple drank’: Study of promethazine abuse according to the European Medicines Agency adverse drug reaction reports

2021 ◽  
pp. 026988112095961
Author(s):  
Stefania Chiappini ◽  
Fabrizio Schifano ◽  
John Martin Corkery ◽  
Amira Guirguis
Keyword(s):  
Adverse Drug Reaction ◽  
Drug Reaction ◽  
Drug Abuse ◽  
Adverse Drug Reactions ◽  
Descriptive Analysis ◽  
Public Health Issue ◽  
European Medicines Agency ◽  
Drug Reactions ◽  
Over The Counter ◽  
The University

Background: Promethazine is a medicinal product, available on its own or in combination with other ingredients including dextromethorphan, paracetamol and/or expectorants. Anecdotal reports have however indicated that promethazine may have a misuse potential, especially in adolescents. Objective: We here aimed at studying how this phenomenon has been reported to the European Monitoring Agency Adverse Drug Reactions database. Methods: After a formal request to the European Monitoring Agency, the promethazine-specific dataset has been studied, performing a descriptive analysis of misuse/abuse/dependence-related adverse drug reaction reports. The study was approved by the University of Hertfordshire (LMS/PGR/UH/03234). Results: The analysis of promethazine data showed increasing levels of misuse/abuse/ dependence issues over time (2003–2019). Out of a total number of 1543 cases of adverse drug reactions, the abuse/misuse/dependence-related cases reported were 557, with ‘drug abuse’ (300/557: 53.8%) and ‘intentional product misuse’ (117/557: 21.0%). being the most represented adverse drug reactions. A high number of fatalities were described (310/557: 55.6%), mostly recorded as ‘drug toxicity/drug abuse’ cases, with opiates/opioids having been the most commonly reported concomitant drugs used. Conclusion: Anecdotal promethazine misuse/abuse reports have been confirmed by European Monitoring Agency data. Promethazine misuse/abuse appears to be an alarming issue, being associated with drug-related fatalities. Thus, healthcare professionals should be warned about a possible misuse of promethazine and be vigilant, as in some countries medicinal products containing promethazine can be purchased over the counter. Since promethazine is often available in association with opioids, its abuse may be considered a public health issue, with huge implications for clinical practice.

Diffuse idiopathic skeletal hyperostosis masquerading as asthma: case report

2019 ◽  
Vol 31 (2) ◽  
pp. 261-264
Author(s):  
Karim Mithani ◽  
Ying Meng ◽  
David Pinilla ◽  
Nova Thani ◽  
Kayee Tung ◽  
...  
Keyword(s):  
Pulmonary Function Tests ◽  
Diffuse Idiopathic Skeletal Hyperostosis ◽  
Inhaled Corticosteroid ◽  
Treatment Resistant ◽  
Methacholine Challenge ◽  
Airway Reactivity ◽  
Cervical Osteophytes ◽  
History Of ◽  
Anterior Discectomy And Fusion ◽  
Asthma Case

A 52-year-old man with a 10-year history of treatment-resistant asthma presented with repeated exacerbations over the course of 10 months. His symptoms were not responsive to salbutamol or inhaled corticosteroid agents, and he developed avascular necrosis of his left hip as a result of prolonged steroid therapy. Physical examination and radiography revealed signs consistent with diffuse idiopathic skeletal hyperostosis (DISH), including a C7–T1 osteophyte causing severe tracheal compression. The patient underwent C6–T1 anterior discectomy and fusion, and the compressive osteophyte was removed, which completely resolved his “asthma.” Postoperative pulmonary function tests showed normalization of his FEV1/FVC ratio, and there was no airway reactivity on methacholine challenge. DISH is a systemic, noninflammatory condition characterized by ossification of spinal entheses, and it can present with respiratory disturbances due to airway compression by anterior cervical osteophytes. The authors present, to the best of their knowledge, the first documented case of asthma as a presentation of DISH.

Association of staphylococcal skin infections and swimming

1995 ◽  
Vol 31 (5-6) ◽  
pp. 11-17 ◽  
Author(s):  
N. Charoenca ◽  
R. S. Fujioka
Keyword(s):  
Coastal Waters ◽  
Skin Infection ◽  
Antibiotic Sensitivity ◽  
Control Group ◽  
Skin Infections ◽  
Telephone Interviews ◽  
Phage Types ◽  
History Of ◽  
Staphylococcal Skin Infections ◽  
Recreational Use

An association between using coastal waters for recreation and staphylococcal skin infections has been reported by canoe paddlers and several physicians in Hawaii. A retrospective epidemiological/microbiological monitoring study was undertaken to determine the association between S aureus skin infections in youngsters (4 months to 16 years of age) and their exposure to recreational use of coastal waters. Telephone interviews were conducted of 53 patients with such skin infections and 53 similar (controlled for age and sex) patients with no infection. A significant association between skin infection and water exposure was found, the odds showing that those developing skin infection caused by S aureus were 4 times more likely to have had a history of seawater contact than the control group. Moreover, the antibiotic sensitivity patterns and phage types of S aureus isolated from patients were similar to those isolated from seawater at bathing beaches.

Safety of a Clozapine Trial Following Quetiapine-Induced Leukopenia: A Case Report

2019 ◽  
Vol 14 (1) ◽  
pp. 80-83 ◽  
Author(s):  
Asma H. Almaghrebi
Keyword(s):  
Treatment Options ◽  
Young Female ◽  
Similar Reaction ◽  
Careful Monitoring ◽  
Treatment Resistant ◽  
Blood Cell Count ◽  
Antipsychotic Medications ◽  
Case Presentation ◽  
Clozapine Treatment ◽  
History Of

Background: The clozapine-derivative quetiapine has been shown in some cases to cause leukopenia and neutropenia. Case Presentation: We reported on a case of a young female diagnosed with treatment-resistant schizophrenia. After failed trials of three antipsychotic medications and despite a history of quetiapineinduced leukopenia, clozapine treatment was introduced due to the severity of the patient’s symptoms, the limited effective treatment options, and a lack of guidelines on this issue. Result: Over a ten-week period of clozapine treatment at 700 mg per day, the patient developed agranulocytosis. Her white blood cell count sharply dropped to 1.6 &#215; 10<sup>9</sup> L, and her neutrophils decreased to 0.1 &#215; 10<sup>9</sup> L. There had been no similar reaction to her previous medications (carbamazepine, risperidone, and haloperidol). Conclusion: The safety of clozapine in a patient who has previously experienced leukopenia and neutropenia with quetiapine requires further investigation. Increased attention should be paid to such cases. Careful monitoring and slow titration are advisable.

scholarly journals The Safety of COVID-19 Vaccinations—We Should Rethink the Policy

Vaccines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 693
Author(s):  
Harald Walach ◽  
Rainer J. Klement ◽  
Wouter Aukema
Keyword(s):  
Side Effects ◽  
Confidence Interval ◽  
Field Study ◽  
Adverse Reactions ◽  
Safety Data ◽  
European Medicines Agency ◽  
Point Estimate ◽  
Drug Reactions ◽  
Vaccination Policy ◽  
Risks And Benefits

Background: COVID-19 vaccines have had expedited reviews without sufficient safety data. We wanted to compare risks and benefits. Method: We calculated the number needed to vaccinate (NNTV) from a large Israeli field study to prevent one death. We accessed the Adverse Drug Reactions (ADR) database of the European Medicines Agency and of the Dutch National Register (lareb.nl) to extract the number of cases reporting severe side effects and the number of cases with fatal side effects. Result: The NNTV is between 200–700 to prevent one case of COVID-19 for the mRNA vaccine marketed by Pfizer, while the NNTV to prevent one death is between 9000 and 50,000 (95% confidence interval), with 16,000 as a point estimate. The number of cases experiencing adverse reactions has been reported to be 700 per 100,000 vaccinations. Currently, we see 16 serious side effects per 100,000 vaccinations, and the number of fatal side effects is at 4.11/100,000 vaccinations. For three deaths prevented by vaccination we have to accept two inflicted by vaccination. Conclusions: This lack of clear benefit should cause governments to rethink their vaccination policy.

scholarly journals Automatic Extraction of Adverse Drug Reactions from Summary of Product Characteristics

2021 ◽  
Vol 11 (6) ◽  
pp. 2663
Author(s):  
Zhengru Shen ◽  
Marco Spruit
Keyword(s):  
Natural Language Processing ◽  
Natural Language ◽  
Adverse Drug Reactions ◽  
Language Processing ◽  
European Medicines Agency ◽  
Drug Reactions ◽  
Clinical Practices ◽  
Product Characteristics ◽  
Textual Information ◽  
Summary Of Product Characteristics

The summary of product characteristics from the European Medicines Agency is a reference document on medicines in the EU. It contains textual information for clinical experts on how to safely use medicines, including adverse drug reactions. Using natural language processing (NLP) techniques to automatically extract adverse drug reactions from such unstructured textual information helps clinical experts to effectively and efficiently use them in daily practices. Such techniques have been developed for Structured Product Labels from the Food and Drug Administration (FDA), but there is no research focusing on extracting from the Summary of Product Characteristics. In this work, we built a natural language processing pipeline that automatically scrapes the summary of product characteristics online and then extracts adverse drug reactions from them. Besides, we have made the method and its output publicly available so that it can be reused and further evaluated in clinical practices. In total, we extracted 32,797 common adverse drug reactions for 647 common medicines scraped from the Electronic Medicines Compendium. A manual review of 37 commonly used medicines has indicated a good performance, with a recall and precision of 0.99 and 0.934, respectively.

scholarly journals Psychosocial Risk Factors and Other Than Honorable Military Discharge: Providing Healthcare to Previously Ineligible Veterans

2018 ◽  
Vol 183 (9-10) ◽  
pp. e532-e538 ◽  
Author(s):  
Eric B Elbogen ◽  
H Ryan Wagner ◽  
Mira Brancu ◽  
Nathan A Kimbrel ◽  
Jennifer C Naylor ◽  
...  
Keyword(s):  
Risk Factors ◽  
Sleep Problems ◽  
Healthcare Delivery ◽  
Mental Healthcare ◽  
Drug Misuse ◽  
Social Characteristics ◽  
Research Education ◽  
Military Discharge ◽  
History Of ◽  
Potential Factors

Abstract Introduction In response to a strong focus on suicide prevention for all veterans, the Department of Veterans Affairs (VA) recently revised policy to provide emergency mental healthcare for veterans who received Other Than Honorable (OTH) discharges from the military. This current study takes a preliminary step toward identifying demographic, historic, military, clinical, and social characteristics of veterans with OTH discharges. Materials and Methods N = 1,172 Iraq/Afghanistan-era veterans were evaluated between 2005 and 2016 in the multi-site VA Mid-Atlantic Mental Illness, Research, Education and Clinical Center (MIRECC) Study of Post-Deployment Mental Health (PDMH Study). Results Veterans with OTH discharges constituted 2.7% of our sample, approximating the estimated rate in the overall U.S. veteran population. Compared to veterans discharged under honorable conditions, veterans with OTH discharges were more likely to be younger and have greater odds of reporting family history of drug abuse and depression. Further, veterans with OTH discharges reported a lower level of social support and were more likely to be single, endorse more sleep problems, score higher on measures of drug misuse, have a history of incarceration, and meet diagnostic criteria for major depressive disorder. A subsequent matching analysis provided further evidence of the association between OTH discharge and two risk factors: drug misuse and incarceration. Conclusion These findings elucidate potential factors associated with veterans with OTH discharges, particularly substance abuse and criminal justice involvement. Results also indicate higher incidence of risk factors that often accompany suicidal ideation and should be a highlighted component of healthcare delivery to this vulnerable cohort of veterans.

Lithium use in a patient on haemodialysis with bipolar affective disorder and lithium-induced nephropathy

2021 ◽  
Vol 14 (7) ◽  
pp. e242841
Author(s):  
Sam Topp ◽  
Emma Salisbury
Keyword(s):  
Affective Disorder ◽  
Bipolar Affective Disorder ◽  
Manic Episode ◽  
Dose Titration ◽  
Dialysis Session ◽  
Treatment Resistant ◽  
History Of ◽  
End Stage ◽  
Level Monitoring

Lithium is an effective mood stabiliser used to treat bipolar affective disorder (BPAD); however, it can also adversely affect the kidneys, causing acute toxic effects, nephrogenic diabetes insipidus, chronic renal dysfunction and end-stage kidney disease (ESKD) in a minority of patients. We describe the case of a man with a 34-year history of BPAD type-1 and a 2-year history of ESKD secondary to lithium-induced nephropathy who experienced a manic relapse. He previously responded well to lithium but, following a deterioration in kidney function, was switched to olanzapine and sodium valproate. This precipitated a period of instability, which culminated in a treatment-resistant manic episode requiring hospital admission. After a multidisciplinary team discussion, lithium therapy was restarted and provided remission. This was achieved safely through a reduced dosing schedule of three times a week post dialysis, slow dose titration and blood level monitoring prior to each dialysis session.

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