A case series of three patients presenting with isoniazid induced toxicity and N-acetyl transferase 2 gene mutation: A management conundrum for programmatic therapy of tuberculosis in India.

Indian J Tuberc. 2020 Jul;67(3):407-410

Authors: Shetty P, Panchal F, Munshi R, Sundar U, Darole P

Abstract
Isoniazid is an essential drug in the management of tuberculosis but there is a high degree of variation in the Indian population's capacity to acetylate or inactivate isoniazid to the inactive metabolite acetyl isoniazid, and they can be distinctly characterized phenotypically as being either slow or rapid inactivators (the concentration of the enzyme being higher in rapid inactivators). Several mutations in the N-acetyl transference 2 (NAT2) gene account for majority of the slow acetylator genotypes in the human population (NAT2*5A, NAT2*5B, and NAT2*6A). Such individuals are at a greater risk of drug-induced adverse reactions due to reduced drug elimination, compared to those possessing the wild type allele. Here we discuss two cases of Isoniazid induced peripheral neuropathy and one case of Isoniazid induced hepatotoxicity confirmed as having heterozygous or homozygous NAT2 gene mutation. In all 3 cases, the presence of NAT2 gene mutation was associated with the adverse events and the adverse events subsided on stopping or reducing the dose of isoniazid. However, due to lack of guideline-based management of adverse events occurring due to isoniazid, the drug was either abruptly stopped or dosage lowered based only on clinical expertise, which could potentially lead to further resistance to Mycobacterium tuberculosis (as occurred in one of our cases). Further studies of the relationship between NAT2 genotypes, isoniazid concentrations and adverse drug events are required to make genotyping a helpful tool for optimizing isoniazid's therapeutic response and minimizing adverse drug reactions, particularly in countries with a high burden of tuberculosis.

PMID: 32825881 [PubMed - as supplied by publisher]

Human immunodeficiency virus and intraocular inflammation in the era of highly active anti retroviral therapy - An update.

Indian J Ophthalmol. 2020 Sep;68(9):1787-1798

Authors: Sudharshan S, Nair N, Curi A, Banker A, Kempen JH

Abstract
Intraocular inflammation in patients with human immunodeficiency virus (HIV) infection is commonly due to infectious uveitis. Ocular lesions due to opportunistic infections (OI) are the most common and have been described extensively in the pre highly active antiretroviral therapy (HAART) era. Many eye lesions were classified as acquired immunodeficiency syndrome (AIDS) defining illnesses. HAART-associated improvement in immunity of the individual has changed the pattern of incidence of these hitherto reported known lesions leading to a marked reduction in the occurrence of ocular OI. Newer ocular lesions and newer ocular manifestations of known agents have been noted. Immune recovery uveitis (IRU), the new menace, which occurs as part of immune recovery inflammatory syndrome (IRIS) in the eye, can present with significant ocular inflammation and can pose a diagnostic and therapeutic challenge. Balancing the treatment of inflammation with the risk of reactivation of OI is a task by itself. Ocular involvement in the HAART era can be due to the adverse effects of some systemic drugs used in the management of HIV/AIDS. Drug-associated retinal toxicity and other ocular side effects are being increasingly reported. In this review, we discuss the ocular manifestations in HIV patients and its varied presentations following the introduction of HAART, drug-associated lesions, and the current treatment guidelines.

PMID: 32823395 [PubMed - as supplied by publisher]

aer2vec: Distributed Representations of Adverse Event Reporting System Data as a Means to Identify Drug/Side-Effect Associations.

AMIA Annu Symp Proc. 2019;2019:717-726

Authors: Portanova J, Murray N, Mower J, Subramanian D, Cohen T

Abstract
Adverse event report (AER) data are a key source of signal for post marketing drug surveillance. The standard methodology to analyze AER data applies disproportionality metrics, which estimate the strength of drug/side-effect associations from discrete counts of their occurrence at report level. However, in other domains, improvements in predictive modeling accuracy have been obtained through representation learning, where discrete features are replaced by distributed representations learned from unlabeled data. This paper describes aer2vec, a novel representational approach for AER data in which concept embeddings emerge from neural networks trained to predict drug/side-effect co-occurrence. Trained models are evaluated for their utility in identifying drug/side-effect relationships, with improvements over disproportionality metrics in most cases. In addition, we evaluate the utility of an otherwise-untapped resource in the Food and Drug Administration (FDA) AER system - reporter designations of suspected causality - and find that incorporating this information enhances performance of all models evaluated.

PMID: 32308867 [PubMed - indexed for MEDLINE]

Efficacy and safety of extended-release amantadine in levodopa-induced dyskinesias: a meta-analysis.

Neurodegener Dis Manag. 2019 08;9(4):205-215

Authors: Pajo AT, Espiritu AI, Jamora RDG

Abstract
Aim: To determine the effectiveness and safety of extended-release amantadine (ADS-5102) for levodopa-induced dyskinesias (LID) in patients with Parkinson disease (PD) by conducting a meta-analysis of relevant trials. Methods: The electronic databases were searched on or before March 1, 2019 for relevant trials. Only randomized, double-blind, parallel-group, placebo-controlled trials using ADS-5102 for LID in PD were included. Results: The ADS-5102 showed a reduction in the dyskinesia scores (mean difference: -9.56: CI: -10.05 to -9.07; p < 0.00001) and in the on time without troublesome dyskinesia (mean difference 2.50: CI 2.38 to 2.63; p < 0.00001). The adverse events identified in ADS-5102 were visual hallucinations, constipation, dry mouth and fall. Conclusion: ADS-5102 can be used as an adjunct therapy for LID.

PMID: 31392922 [PubMed - indexed for MEDLINE]

Cryptopharmaceuticals: Increasing the Safety of Medication by a Blockchain of Pharmaceutical Products.

J Pharm Sci. 2019 09;108(9):2838-2841

Authors: Nørfeldt L, Bøtker J, Edinger M, Genina N, Rantanen J

Abstract
The future health-care system will contain an ever expanding number of digital elements. The data stored both at a centralized health-care level and at a local, patient level (e.g., on a smartphone) will be core elements when deciding treatment strategies in a health-care scenario with Internet of things-based elements. The current way of manufacturing pharmaceutical products and related existing logistic solutions is not ready for such a revolution. One of the key challenges is cybersecurity and related robust public key infrastructure solution. This work introduces one element of a potential solution at a prototype level: the concept of cryptopharmaceuticals where pharmaceutical products are connected in a patient-specific blockchain of individual dosage units. This technology is based on the concept where each produced dosage unit has a unique information-rich pattern. A proof-of-concept smartphone application was applied to demonstrate the visualization of this blockchain at different levels. This includes the manufacturing of the individualized dosage unit, the patient view for his/her personal blockchain, and integration of these products into a health Internet of things system. This unbreakable blockchain of personal medication history will provide means to avoid counterfeit products and to enable innovative logistic solutions.

PMID: 31054889 [PubMed - indexed for MEDLINE]

Hypothalamic expression of PD-L1: does it mediate hypothalamitis?

Cell Mol Immunol. 2019 06;16(6):625-626

Authors: Iervasi E, Strangio A, Saverino D

PMID: 30979971 [PubMed - indexed for MEDLINE]

Enhancing the feasibility of outpatient daratumumab administration via a split-dosing strategy with initial doses.

Leuk Lymphoma. 2019 09;60(9):2295-2298

Authors: Arnall JR, Moore DC, Hill HL, Griffin S, Mueller MK, Lavery LA, Voorhees PM, Usmani SZ

PMID: 30848971 [PubMed - indexed for MEDLINE]

Mycobacterium avium Complex: Addressing Gaps in Diagnosis and Management.

J Infect Dis. 2020 Aug 20;222(Supplement_4):S199-S211

Authors: Daley CL, Winthrop KL

Abstract
Nontuberculous mycobacteria (NTM) are ubiquitous in the environment and an important cause of disease. The most common species causing pulmonary disease are members of Mycobacterium avium complex (MAC). MAC pulmonary disease (MAC-PD) can be chronic, debilitating, costly, and associated with a high mortality. However, MAC diagnoses are often delayed due to the nonspecific presentation of MAC-PD and radiological findings that overlap with other pulmonary diseases. Patients with risk factors and who meet the diagnostic criteria-which include clinical, radiological, and microbiologic criteria-should be considered for treatment. Diagnosis requires 2 or more positive sputum cultures or 1 bronchoscopic specimen culture. The recommendation for those who are treated is a 3-drug regimen including macrolide, rifamycin, and ethambutol that is continued for 12 months beyond sputum culture conversion to negative. MAC-PD is difficult to treat, with frequent drug-related side effects and suboptimal treatment outcomes. Refractory and recurrent disease is common, leading to lifelong follow-up of patients. There are limited treatment options for patients with macrolide-resistant or refractory disease. Amikacin liposome inhalation suspension is recommended for treatment-refractory patients whose cultures remain positive after 6 months of guideline-based therapy. Among the research priorities to improve patient outcomes and quality of life are developing new, more rapid diagnostic tests, investigating biomarkers associated with disease progression, and identifying new drugs and routes of administration as well as new, shorter, and better-tolerated regimens.

PMID: 32814943 [PubMed - in process]

Classification of the Severity of Adverse Drugs Reactions.

Stud Health Technol Inform. 2020 Jun 16;270:1227-1228

Authors: Chauvet R, Bousquet C, Lillo-Lelouet A, Zana I, Ben Kimoun I, Jaulent MC

Abstract
This poster presents a non-exhaustive study of machine learning classification algorithms on pharmacovigilance data. In this study, we have taken into account the patient's clinical data such as medical history, medications taken and their indications for prescriptions, and the observed side effects. From these elements we determine whether the patient case is considered serious or not. We show the performances of the different algorithms by their precision, recall and accuracy as well as their learning curves.

PMID: 32570592 [PubMed - indexed for MEDLINE]

Raynaud's Phenomenon Related with Atomoxetine Treatment in a Child with Autism and Attention-Deficit/Hyperactivity Disorder.

J Child Adolesc Psychopharmacol. 2019 10;29(8):649-650

Authors: Gülle ZN, Karayagmurlu A, Coskun M

PMID: 31264893 [PubMed - indexed for MEDLINE]

Implementing a Respiratory Therapist-Driven Continuous Albuterol Weaning Protocol in the Pediatric ICU.

Respir Care. 2019 Nov;64(11):1358-1365

Authors: Maue DK, Tori AJ, Beardsley AL, Krupp NL, Hole AJ, Moser EA, Rowan CM

Abstract
BACKGROUND: Status asthmaticus is one of the most frequent admission diagnoses in the pediatric ICU (PICU). Collaboration between respiratory therapists (RTs) and physicians may help efficiently deliver care to a patient in status asthmaticus. The Pediatric Asthma Severity Score (PASS) is a measure of severity of a patient's asthma exacerbation at a point in time. The aim of this quality improvement initiative was to establish an RT-driven continuous albuterol weaning protocol using the PASS score. We hypothesized that this would decrease the duration of continuous albuterol without increasing adverse events.
METHODS: This was a single-center implementation study in the PICU of a quaternary care children's hospital. Patients with a diagnosis of status asthmaticus who met criteria on continuous albuterol between September 2015 and September 2017 were included. An interdisciplinary team established the protocol, order sets, documentation, and education for involved staff. Qualifying subjects were assessed by an RT per protocol and assigned a PASS score, and the albuterol dose was adjusted on the basis of the PASS score.
RESULTS: We compared 104 subjects studied before the implementation of this protocol (September 2015 to August 2016) to 117 subjects after the implementation of this protocol (September 2016 to October 2017). Median (interquartile range) duration of continuous albuterol in the PICU post-implementation was unchanged compared to pre-implementation: 12.1 (7.2-21.0) h versus 11.1 (6-19) h (P = .22). Median PICU length of stay was also unchanged post-implementation compared to pre-implementation: 19.5 (14.3-29.7) h versus 23.2 (15.2-31.3) h (P = .16). Using control charts, these processes were stable. There was no difference in adverse events.
CONCLUSIONS: An interprofessionally-developed, RT-driven continuous albuterol weaning protocol can be implemented without negatively impacting duration of continuous albuterol or PICU length of stay and without increasing adverse events.

PMID: 30890627 [PubMed - indexed for MEDLINE]

Belgian community pharmacists' pharmacovigilance perspective and practice.

Res Social Adm Pharm. 2019 12;15(12):1446-1452

Authors: De Meestere D, Saevels J

Abstract
BACKGROUND: Pharmacovigilance legislation was introduced back in 2012 with new concepts such as the inverted black triangles and risk minimisation activities. Healthcare professionals need to familiarize themselves with these new notions in order to comply with their obligations such as risk mitigation and reporting of adverse drug reactions.
OBJECTIVE: To measure the magnitude and relevance of these new concepts and the impact on everyday dispensing in Belgian community pharmacies.
METHODS: An inventory database was constructed containing all relevant pharmacovigilance information at product level, and this data was made available within the pharmacy dispensing software. Furthermore, for a typical community pharmacy, the number of concerned products and the number of dispensed products with supplementary pharmacovigilance responsibilities was determined.
RESULTS: The number of available and dispensed medicines with black triangle or additional risk minimisation activities has increased significantly since July 2014. During July 2017, each pharmacy dispensed around 120 packs with risk minimisation obligations and around 70 with a black triangle, clearly illustrating the relevance of having all information at hand.
CONCLUSIONS: With relevant safety information available at the point of dispensing, pharmacists can now focus on complying with their pharmacovigilance responsibilities.

PMID: 30733138 [PubMed - indexed for MEDLINE]

A systematic review of pharmacist-led medicines review services in New Zealand - is there equity for Māori older adults?

Res Social Adm Pharm. 2019 12;15(12):1383-1394

Authors: Hikaka J, Hughes C, Jones R, Connolly MJ, Martini N

Abstract
BACKGROUND: Pharmacist involvement in medicines reviews for older adults can improve prescribing and reduce adverse drug reactions. Māori experience poorer health outcomes than non-Māori resulting, in part, from inequitable access to and quality of medicine-related care. Despite international data showing benefit, it is unclear whether pharmacist-led medicines review services can improve outcomes for Māori older adults.
OBJECTIVE: This systematic review aims to describe pharmacist-led medicines review services for community-dwelling adults in New Zealand, assess effectiveness of these interventions and identify their effect on health equity for Māori and older adults.
METHODS: The review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses - Equity (PRISMA-E 2012). Observational studies were included. The intervention in included studies had to involve a pharmacist, occur in the outpatient setting in New Zealand, and involve review of all medicines for an individual patient. At least one patient-related outcome had to be reported.
RESULTS: The search identified seven observational studies with 542 total participants. Study interventions included adherence-based reviews in community pharmacies and multi-step comprehensive clinical reviews in outpatient haemodialysis units. Medicines reviews identified up to a median of 3 drug-related problems per review. The effect of interventions on medicines adherence and knowledge was not clear. Māori may have been less likely than non-Māori to benefit from improved medicines knowledge as a result of interventions. None of the studies incorporated aspects in study design or delivery to address inequities for Māori.
CONCLUSION: Further investigation is needed to understand whether the development of culturally safe pharmacist-led medicines review services, responsive to community identified needs, can help to achieve equity in health outcomes for Māori older adults.

PMID: 30733137 [PubMed - indexed for MEDLINE]

Double-filtration plasmapheresis combined with immunosuppressive treatment for severe pemphigus: 10 years' experience of a single center in China.

J Clin Apher. 2020 Aug 19;:

Authors: Liu Y, Zhang B, Ma J, Wang H, Fan X, Zheng K, Chen L, Li X, Qin Y, Li L, Li X

Abstract
BACKGROUND: Pemphigus is a group of rare and severe autoimmune blistering disease mediated by pathogenic autoantibodies against desmogleins. Plasmapheresis can directly remove autoantibodies from circulation, which has been applied to the treatment of pemphigus as an adjuvant therapy. But the results of the researches are controversial. This study aims to evaluate the efficacy and safety of double filtration plasmapheresis (DFPP) combined with immunosuppressive treatment for patients with severe pemphigus in our single center.
METHODS: We retrospectively analyzed 17 patients with severe pemphigus who were unresponsive to high-dose corticosteroid and received DFPP treatment between January 2010 and January 2020. The information on demographic characteristics, clinical and laboratory data, treatment regimens, and clinical outcomes were collected.
RESULTS: All the patients were diagnosed as severe pemphigus and had a period of at least 1 week of high-dose prednisone (1-1.5 mg/kg/day), but they were unresponsive to corticosteroid and immunosuppressants treatment. They received DFPP treatment as an adjuvant therapy. After DFPP treatment, the titers of desmogleins antibodies significantly decreased (P < .001), Nikolsky's sign became negative and no new blisters appeared. The dosage of corticosteroid could begin to taper down rapidly in 9 ± 4 days. On discharge, the dosage of prednisone decreased significantly (51 ± 3 mg/day, P < .001). No major adverse events happened that could lead to the termination of DFPP treatment.
CONCLUSION: Double filtration plasmapheresis combined with immunosuppressive treatment is an effective and safe therapeutic regimen for severe pemphigus. DFPP can also contribute to the dosage reduction of steroid to avoid more drug-related side effect.

PMID: 32812668 [PubMed - as supplied by publisher]

The anesthetic bupivacaine induces cardiotoxicity by targeting L-type voltage-dependent calcium channels.

J Int Med Res. 2020 Aug;48(8):300060520942619

Authors: Gao Y, Chen B, Zhang X, Yang R, Hua Q, Li B

Abstract
OBJECTIVE: Bupivacaine is an amide local anesthetic with possible side effects that include an irregular heart rate. However, the mechanism of bupivacaine-induced cardiotoxicity has not been fully elucidated, thus we aimed to examine this mechanism.
METHODS: We performed electrocardiogram recordings to detect action potential waveforms in Sprague Dawley rats after application of bupivacaine, while calcium (Ca2+) currents in neonatal rat ventricular cells were examined by patch clamp recording. Western blot and quantitative real-time polymerase chain reaction assays were used to detect the expression levels of targets of interest.
RESULTS: In the present study, after application of bupivacaine, abnormal action potential waveforms were detected in Sprague Dawley rats by electrocardiogram recordings, while decreased Ca2+ currents were confirmed in neonatal rat ventricular cells by patch clamp recording. These alterations may be attributed to a deficiency of CaV1.3 (L-type) Ca2+ channels, which may be regulated by the multifunctional protein calreticulin.
CONCLUSIONS: The present study identifies a possible role of the calreticulin-CaV1.3 axis in bupivacaine-induced abnormal action potentials and Ca2+ currents, which may lead to a better understanding anesthetic drug-induced cardiotoxicity.

PMID: 32812463 [PubMed - in process]

Reported proton pump inhibitor side effects: what are physician and patient perspectives and behaviour patterns?

Aliment Pharmacol Ther. 2020 01;51(1):121-128

Authors: Ghosh G, Schnoll-Sussman F, Mathews S, Katz PO

Abstract
BACKGROUND: Proton pump inhibitors (PPI) are among the most commonly prescribed medications and studies are reporting potentially harmful PPI-related adverse events. While these studies' findings are controversial, their impact on patients and physicians remains unknown.
AIM: To determine patient and physician awareness of PPI-related adverse events, source of information, and subsequent effect on patient behaviour and physician practice.
METHODS: A 20-item questionnaire was administered to English speaking adult patients and physicians in primary care and specialty clinics about topics including knowledge of PPI-related adverse events, change in behaviour of patients on PPIs and physician management of patients on PPIs.
RESULTS: Of 277 patients surveyed, 45% reported knowledge of side effects related to PPIs. Patients were more likely to hear about PPI side effects from non-physician sources (66%) than physicians (38%). Of patients who had heard about PPI side effects, bone fractures and osteoporosis were the most common concerns, 42% and 44% respectively. Of PPI users, 38% changed their behaviour based upon concerns about PPI-related adverse events. Change in patient behaviour due to concern about PPI side effects was associated with age ≥ 65 years (odds ratio [OR] 4.07 [1.19-13.94]; P = 0.03) and concern about long-term side effects (OR 2.31 [1.03-5.17]; P = 0.04). Of 83 physicians surveyed, 60% reported concern about PPI-related adverse events, with bone fractures (46%) and osteoporosis (49%) being the most frequently reported. Overall, 37% of physicians reported changing their practice based upon their concerns.
CONCLUSIONS: Nearly half of patients reported knowledge of PPI-related adverse events, most often from non-physician sources, and general concern regarding their impact. PPI users are changing their behaviour based upon these concerns, without physician input, and care providers are changing behaviour based on relatively weak evidence.

PMID: 31664732 [PubMed - indexed for MEDLINE]

Characterization of Severe Adverse Drug Reactions at a Free-Standing Children's Hospital.

J Clin Pharmacol. 2019 12;59(12):1569-1572

Authors: Yu D, Sheets J, Suppes S, Goldman J

Abstract
We performed a retrospective chart review on severe adverse drug reactions (ADRs) detected by a pharmacovigilance program at a free-standing pediatric hospital from January 2011 through September 2014. The pharmacist-led program identifies ADRs using electronic medical record triggers. A systematic approach was used to classify ADR type and severity and assure accurate documentation. Data collection included demographics, implicated medication, type of ADR, Naranjo probability scale, ADR-associated International Classification of Diseases, 9th Revision E codes, 30-day mortality, and health care visit cost. One hundred sixty-six severe pediatric ADRs were included, occurring in 163 unique patients. Severe ADRs were commonly associated with antimicrobials (48%), antineoplastics (10%), and antiepileptics (10%). The majority of ADRs were classified by the Naranjo probability scale as probable (59%). One hundred fifty-four patients were admitted to the hospital, with a median length of stay of 3 days; 22 of these patients required admission to the pediatric intensive care unit for a median of 3 days. The median estimated health care cost associated with severe ADRs was $4055.52. No deaths occurred. Nearly 40% of severe ADRs would have gone unidentified using ADR-associated International Classification of Diseases, 9th Revision E codes alone. The impact of pediatric ADRs on the health care system is underestimated. Strategies such as active pharmacovigilance programs enhance the identification, characterization, and documentation of these otherwise unrecognized ADRs.

PMID: 31309572 [PubMed - indexed for MEDLINE]

Safety and efficacy of rifabutin among HIV/TB-coinfected children on lopinavir/ritonavir-based ART.

J Antimicrob Chemother. 2019 09 01;74(9):2707-2715

Authors: Rawizza HE, Darin KM, Oladokun R, Brown B, Ogunbosi B, David N, Akanmu S, Olaitan O, Chang C, Scarsi KK, Okonkwo P, Kanki PJ

Abstract
BACKGROUND: TB is the leading cause of death among HIV-infected children, yet treatment options for those who require PI-based ART are suboptimal. Rifabutin is the preferred rifamycin for adults on PI-based ART; only one study has evaluated its use among children on PIs and two of six children developed treatment-limiting neutropenia.
METHODS: Since 2009, rifabutin has been available for HIV/TB-coinfected children requiring PI-based ART in the Harvard/APIN programme in Nigeria. We retrospectively analysed laboratory and clinical toxicities at baseline and during rifabutin therapy, and examined HIV/TB outcomes.
RESULTS: Between 2009 and 2015, 48 children received rifabutin-containing TB therapy with PI (lopinavir/ritonavir)-based ART: 50% were female with a median (IQR) baseline age of 1.7 (0.9-5.0) years and a median (IQR) CD4+ cell percentage of 15% (9%-25%); 52% were ART experienced. Eighty-five percent completed the 6 month rifabutin course with resolution of TB symptoms and 79% were retained in care at 12 months. Adverse events (grade 1-4) were more common at baseline (27%) than during rifabutin treatment (15%) (P = 0.006). Absolute neutrophil count was lower during rifabutin compared with baseline (median = 1762 versus 2976 cells/mm3, respectively), but only one instance (2%) of grade 3 neutropenia occurred during rifabutin treatment.
CONCLUSIONS: With clinical and laboratory monitoring, our data suggest that rifabutin is a safe option for TB therapy among children on PI-based ART. By contrast with the only other study of this combination in children, severe neutropenia was rare. Furthermore, outcomes from this cohort suggest that rifabutin is effective, and a novel option for children who require PI-based ART. Additional study of rifabutin plus PIs in children is urgently needed.

PMID: 31139825 [PubMed - indexed for MEDLINE]

Does Industry-Conducted All-Case Surveillance of Newly Approved Oncology Drugs Contribute to the Revision of Package Inserts in Japan?

Clin Transl Sci. 2019 09;12(5):505-512

Authors: Suzuki A, Sato H, Sasaki Y

Abstract
In Japan, the Pharmaceuticals and Medical Devices Agency requires all-case surveillance studies (ACSS) for many novel oncology drugs as a condition for approval. However, this is a major burden on the pharmaceutical industry and clinicians. The objective of this analysis was to investigate whether ACSS can contribute essential new information on severe adverse drug reactions, which are necessary to revise the package inserts of drugs. All oncology drugs for which ACSS were required from January 2006-September 2015 found on the Pharmaceuticals and Medical Devices Agency website were reviewed, and the influence of ACSS on the package insert content was evaluated. Most of the package insert revisions regarding serious treatment-related adverse events were based on spontaneous reports from clinicians. The contribution of ACSS results to the revision of package inserts is limited and comes at the cost of financial resources and labor. An alternative, more efficient adverse-event reporting system is necessary.

PMID: 31062933 [PubMed - indexed for MEDLINE]

Thrombocytopenia due to rivaroxaban: A rare adverse effect.

Transfus Apher Sci. 2020 Jul 22;:102883

Authors: Tığlıoğlu M, Akyol P, Sağlam B, Aras MR, Afacan Öztürk HB, Yıldız A, Albayrak M

Abstract
INTRODUCTION: Rivaroxaban is a novel, oral direct acting anticoagulant (DOAC) that is used for both treatment and prevention of thromboembolic diseases. Due to mechanism of action; most common side effect may be seen with hemorrhage. Here in we reported that a patient with chronic atrial fibrillation presented with thrombocytopenia while taking rivaroxaban.
CASE REPORT: A 76-year-old female patient with atrial fibrillation was given rivaroxaban, after lack of dose administration of warfarin and gastrointestinal bleeding. In 12th dayweek of treatment, the patient was admitted to emergency department (ED) with oral mucosal bleeding and petechial spots.The patient diagnosed as Drug-induced Thrombocytopenia (DITP)due to rivaroxaban use, after ruled out most possibilities ofITP (immune thrombocytopenic purpura). After rivaroxaban is discontinued, the patient's bleeding complaints regressed,symptoms were completely resolved, and platelet count rapidly increased towards physiological level in days. The patient is currently in the 6th month of follow-up and is has no bleeding.
CONCLUSION: To the best of our knowledge there are only two cases about rivaroxaban induced thrombocytopenia (RIT). In addition to the well-known side effects ofrivaroxaban treatment, it should be kept in mind that thrombocytopenia may also develop.Naranjo adverse drug reaction probability scale calculated as 7 points.(probable cause for the patient's thrombocytopenia).

PMID: 32807650 [PubMed - as supplied by publisher]