Preclinical testing of expired antivenoms and its uses in real-world experience: a systematic review.

INTRODUCTION: Limited access to antivenoms is a global challenge in treating snakebite envenoming. In emergency situations where non-expired antivenoms are not readily available, expired antivenoms may be used to save lives with the risk of deteriorating quality, efficacy and safety. Therefore, we aimed to systematically review and summarise the sparse preclinical evidence of neutralising efficacy of expired antivenoms and real-world experience of using expired antivenoms in humans. METHODS: We searched for articles published until 1 March 2023 in PubMed, Scopus, Web of Science and Embase. Studies demonstrating the preclinical studies evaluating expired antivenoms or studies describing the real-world experience of using expired antivenoms were included. Narrative synthesis was applied to summarise the evidence of expired antivenoms. RESULTS: Fifteen studies were included. Ten were preclinical studies and five were real-world experiences of using expired antivenoms in humans. The expired duration of antivenoms in the included studies ranged from 2 months to 20 years. The quality of expired antivenoms was evaluated in one study, and they met the standard quality tests. Five studies demonstrated that the expired antivenoms' immunological concentration and venom-binding activity were comparable to non-expired ones but could gradually deteriorate after expiration. Studies consistently exhibited that expired antivenoms, compared with non-expired antivenoms, were effective when stored in proper storage conditions. The safety profile of using expired antivenoms was reported in two included studies. However, it was inconclusive due to limited information. CONCLUSION: Even though the quality and efficacy of expired antivenoms are comparable to non-expired antivenoms in preclinical studies, the information is limited in terms of real-world experiences of using expired antivenoms and their safety. Therefore, the use of expired antivenoms may be generally inconclusive due to scarce data. Further investigations may be needed to support the extension of antivenoms' expiration date according to their potential efficacy after expiration.

Antivenom preclinical efficacy testing against Asian snakes and their availability in Asia: A systematic review.

BACKGROUND: Cross-neutralizing strategy has been applied to improve access to antivenoms, a key to reducing mortality and disability of snakebite envenoming. However, preclinical studies have been conducted to identify antivenoms' cross-neutralizing ability when clinical studies may not be considered ethical. Therefore, this study aimed to identify and summarize scattered evidence regarding the preclinical efficacy of antivenoms against Asian snakes. METHODOLOGY/PRINCIPLE FINDINGS: In this systematic review, we searched for articles published until May 30, 2022, in PubMed, Scopus, Web of Science, and Embase. Preclinical studies that reported the available antivenoms' neutralizing ability against Asian snake lethality were included. Quality assessment was performed using the Systematic Review Centre for Laboratory animal Experimentation's risk of bias tool and the adapted the Animal Research Reporting In Vivo Experiments guidelines. The availability of effective antivenoms against Asian snakes was analyzed by comparing data from included studies with snakebite-information and data platforms developed by the World Health Organization. Fifty-two studies were included. Most studies assessed the antivenom efficacy against snakes from Southeast Asia (58%), followed by South Asia (35%) and East Asia (19%). Twenty-two (49%) medically important snakes had antivenom(s) with confirmed neutralizing ability. Situation analyses of the availability of effective antivenoms in Asia demonstrated that locally produced antivenoms did not cover all medically important snakes in each country. Among countries without local antivenom production, preclinical studies were conducted only in Bangladesh, Sri Lanka, and Malaysia. Risk of bias assessment was limited in some domains because of unreported data. CONCLUSIONS/SIGNIFICANCE: Cross-neutralizing of antivenoms against some medically important snakes in Asia was confirmed. This strategy may improve access to geographically effective antivenoms and bypass investment in novel antivenom development, especially in countries without local antivenom production. A database should be developed to aid the development of a snakebite-information system.

Drug-Herb Interactions among Thai Herbs and Anticancer Drugs: A Scoping Review.

More than half of Thai patients with cancer take herbal preparations while receiving anticancer therapy. There is no systematic or scoping review on interactions between anticancer drugs and Thai herbs, although several research articles have that Thai herbs inhibit cytochrome P450 (CYP) or efflux transporter. Therefore, we gathered and integrated information related to the interactions between anticancer drugs and Thai herbs. Fifty-two anticancer drugs from the 2020 Thailand National List of Essential Medicines and 75 herbs from the 2020 Thai Herbal Pharmacopoeia were selected to determine potential anticancer drug-herb interactions. The pharmacological profiles of the selected anticancer drugs were reviewed and matched with the herbal pharmacological activities to determine possible interactions. A large number of potential anticancer drug-herb interactions were found; the majority involved CYP inhibition. Efflux transporter inhibition and enzyme induction were also found, which could interfere with the pharmacokinetic profiles of anticancer drugs. However, there is limited knowledge on the pharmacodynamic interactions between anticancer drugs and Thai herbs. Therefore, further research is warranted. Information regarding interactions between anticancer drugs and Thai herbs should provide as a useful resource to healthcare professionals in daily practice. It could enable the prediction of possible anticancer drug-herb interactions and could be used to optimize cancer therapy outcomes.