Direct oral anticoagulants toxicity in children: an overview and practical guide.

INTRODUCTION: By increasing use of direct oral anticoagulants (DOACs) in adults and children, gradual increase in the number of intentional or unintentional DOAC poisonings among children is suspected in the near future. Hence, clinicians and pharmacists need to be familiar with the clinical features and management of DOAC-toxicity among pediatric population. AREAS COVERED: This article provides an overview and practical guide to DOAC-toxicity in pediatrics according to the available clinical evidence. EXPERT OPINION: Based on limited available data, accidental pediatric ingestion of DOACs can be managed by supportive care in most cases. However, serious toxicity may occur following massive overdose, in presence of underlying disorders (renal or hepatic dysfunction) and concurrent anticoagulant therapy. Activated charcoal is recommended for known recent ingestion of DOACs (within 2-4 hours) to reduce the gastrointestinal absorption. Supportive interventions including local hemostatic measures and volume resuscitation are the cornerstone of management of bleeding. Vitamin K and fresh frozen plasma are ineffective for DOAC reversal and thus are not recommended. Currently, safety and efficacy data regarding the use of specific reversal agents (including idarucizumab and andexanet alfa) and 3-factor or 4-factor prothrombin complex concentrate (PCC) or activated PCC (aPCC) among children with DOAC-associated bleeding are lacking.

Bleeding Complication in a Patient with Concomitant Use of Rivaroxaban and Saffron Supplement: a Case Report.

BACKGROUND: Direct oral anticoagulants (DOACs) carry a lower potential risk of food/herb and drug interactions compared with oral vitamin K antagonists. However, as a new class of medications, drug interactions of DOACs have not been fully known. CASE PRESENTATION: We herein present the case of a 64-year old male with the complaint of acute onset epistaxis and bleeding gums following the concomitant use of rivaroxaban and saffron supplement. It seems that coadministration of DOACs and saffron supplements should be avoided due to the potential drug-herbal interactions and possible risk of subsequent bleeding complications. CONCLUSION: However, further larger scale surveillance studies are needed to confirm the findings and assess the clinical significance.

Curcumin supplementation in pediatric patients: A systematic review of current clinical evidence.

This systematic review was designed to determine the clinical efficacy and safety of curcumin supplementation for pediatric patients based on clinical trials in children. We systematically searched electronic databases including PubMed, EMBASE, Web of Science, and Scopus for all studies that investigated curcumin administration in the pediatric population without any time frame limitation. Finally, we identified 16 studies for this review. Clinical efficacy and safety of curcumin were assessed in children with inflammatory and immune disorders (including asthma, inflammatory bowel disease (IBD), and juvenile idiopathic arthritis (JIA)), metabolic disorders, autosomal dominant polycystic kidney disease (ADPKD), cystic fibrosis (CF), tetralogy of Fallot (TOF), and infectious diseases. Curcumin was administered in a wide range of doses (45 mg-4,000 mg daily) and durations (2-48 weeks). Overall, curcumin was well tolerated in all studies and improved the severity of inflammatory and immune disorders and metabolic diseases. However, more studies are needed to clarify the role of curcumin supplementation among children with ADPKD, CF, TOF, and infectious diseases. Because of substantial heterogeneity in methodological quality, design, outcomes, dose, duration of intake, formulations, and study populations across studies, no quantitative analysis was performed. Additional large-scale, randomized, placebo-controlled clinical trials are needed to confirm the results of the conducted studies.

Direct oral anticoagulant safety during breastfeeding: a narrative review.

PURPOSE: There are limited data regarding the safety of direct oral anticoagulants (DOACs) during breastfeeding. The aim of the present study is to investigate the extent of excretion of DOACs into human milk according to the available clinical and experimental studies. METHODS: On 16th January 2021, we systematically searched PubMed, Scopus, Embase, and Web of Science for all studies which investigated DOACs in breastfeeding without any time frame and language limitation. Search keywords were [breastfeeding, breast feeding, breastfed, lactation, milk secretion OR milk] AND [apixaban OR Eliquist OR rivaroxaban OR Xarelto OR edoxaban OR Savaysa OR dabigatran OR Pradaxa OR dabigatran etexilate OR dabigatran etexilate mesylate OR direct oral anticoagulant OR DOAC OR new oral anticoagulant OR NOAC]. Finally, we identified six articles which reported DOAC use during breastfeeding or lactation. RESULTS AND CONCLUSION: According to the available limited data, dabigatran has the least excretion in human breast milk. Rivaroxaban and dabigatran both have acceptable milk excretion cutoffs, whereas apixaban milk excretion is greater than the maximum allowed range. Further well-designed studies with larger sample sizes are required to generate consistent comparable data and clarify benefits and risks of each DOAC during breastfeeding.

Possible Mechanisms and Special Clinical Considerations of Curcumin Supplementation in Patients with COVID-19.

The novel coronavirus outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was recognized in late 2019 in Wuhan, China. Subsequently, the World Health Organization declared coronavirus disease 2019 (COVID-19) as a pandemic on 11 March 2020. The proportion of potentially fatal coronavirus infections may vary by location, age, and underlying risk factors. However, acute respiratory distress syndrome (ARDS) is the most frequent complication and leading cause of death in critically ill patients. Immunomodulatory and anti-inflammatory agents have received great attention as therapeutic strategies against COVID-19. Here, we review potential mechanisms and special clinical considerations of supplementation with curcumin as an anti-inflammatory and antioxidant compound in the setting of COVID-19 clinical research.

Injectable supramolecular hydrogel from insulin-loaded triblock PCL-PEG-PCL copolymer and γ-cyclodextrin with sustained-release property.

Supramolecular hydrogels formed by cyclodextrins and polymers have been widely investigated as a biocompatible, biodegradable and controllable drug delivery system. In this study, a supramolecular hydrogel based on biodegradable poly(caprolactone)-poly(ethylene glycol)-poly(caprolactone) (PCL-PEG-PCL) triblock copolymers and γ-cyclodextrin (γ-CD) was prepared through inclusion complexation as an injectable, sustained-release vehicle for insulin. The triblock copolymer PCL-PEG-PCL was synthesised by the ring-opening polymerisation method, using microwave irradiation. The polymerisation reaction and the copolymer structures were evaluated by nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). The supramolecular hydrogel was prepared in aqueous solution by blending an aqueous γ-CD solution with an aqueous solution of PCL-PEG-PCL triblock copolymer at room temperature. In vitro insulin release through the hydrogel system was studied. The relative surface hydrophobicity of standard and released insulin from the SMGel was estimated using 8-anilino-1-naphthalene sulfonic acid (ANS). Results of (1)HNMR and gel permeation chromatography revealed that microwave irradiation is a simple and reliable method for synthesis of PCL-PEG-PCL copolymer. Gelation occurred within a minute. The supramolecular hydrogel obtained by mixing 10.54% (w/v) γ-CD and 2.5% (w/v) copolymer had an excellent syringeability. Insulin was released up to 80% over a period of 20 days. Insulin kept its initial folding after formulating and releasing from SMGel. A supramolecular hydrogel based on complexation of triblock PCL-PEG-PCL copolymer with γ-cyclodextrin is a suitable system for providing sustained release of therapeutic proteins, with desirable flow behaviour.