Estimating the Quantitative Demand of NOAC Antidote Doses on Stroke Units.

BACKGROUND: The first specific antidote for non-vitamin K antagonist oral anticoagulants (NOAC) has recently been approved. NOAC antidotes will allow specific treatment for 2 hitherto problematic patient groups: patients with oral anticoagulant therapy (OAT)-associated intracerebral hemorrhage (ICH) and maybe also thrombolysis candidates presenting on oral anticoagulation (OAT). We aimed to estimate the frequency of these events and hence the quantitative demand of antidote doses on a stroke unit. METHODS: We extracted data of patients with acute ischemic stroke and ICH (<24 h after symptom onset) in the years 2012-2015 from a state-wide prospective stroke inpatient registry. We selected 8 stroke units and determined the mode of OAT upon admission in 2012-2013. In 2015, the mode of OAT became a mandatory item of the inpatient registry. From the number of anticoagulated patients and the NOAC share, we estimated the current and future demand for NOAC antidote doses on stroke units. RESULTS: Eighteen percent of ICH patients within 6 h of symptom onset or an unknown symptom onset were on OAT. Given a NOAC share at admission of 40%, about 7% of all ICH patients may qualify for NOAC reversal therapy. Thirteen percent of ischemic stroke patients admitted within 4 h presented on anticoagulation. Given the availability of an appropriate antidote, a NOAC share of 50% could lead to a 6.1% increase in thrombolysis rate. CONCLUSIONS: Stroke units serving populations with a comparable demographic structure should prepare to treat up to 1% of all acute ischemic stroke patients and 7% of all acute ICH patients with NOAC antidotes. These numbers may increase with the mounting prevalence of atrial fibrillation and an increasing use of NOAC.

Availability of antidotes and key emergency drugs in tertiary care hospitals of Punjab and assessment of the knowledge of health care professionals in the management of poisoning cases.

This study was conducted to evaluate the availability of antidotes/key emergency drugs in tertiary care hospitals of the Punjab province, and to assess the knowledge of health care professionals in the stocking and administration of antidotes in the proper management of poisoning cases. Seventeen (n=17) tertiary care hospitals of Punjab Pakistan were selected. Two performas (A and B) were designed for 26 antidotes/key emergency drugs and given to the hospital pharmacists and physicians respectively. It was observed that Activated Charcoal, being the universal antidote was found only in 6 hospitals (41%). Digoxin Immune Fab, Edentate Calcium disodium and Glucagon were not available in emergency department of any hospital and even not included in the formulary of any hospital. About 80% pharmacists were aware of the method of preparation of Activated Charcoal and 85% physicians were familiar with its route of administration. Data showed that tertiary care hospitals of Punjab do not stock antidotes according to national drug policy. Moreover the study strongly suggests the development of health care centers and professional by organizing antidote awareness programs, continuous education and record keeping of poisonous cases and availability of emergency drugs around the clock.

Drug shortages: Implications for medical toxicology.

CONTEXT: Drug shortages have significantly increased over the past decade. There are limited data describing how shortages impact medical toxicology of drugs. OBJECTIVE: To characterize drug shortages affecting the management of poisoned patients. MATERIALS AND METHODS: Drug shortage data from January 2001 to December 2013 were obtained from the University of Utah Drug Information Service. Shortage data for agents used to treat poisonings were analyzed. Information on drug type, formulation, reason for shortage, shortage duration, marketing, and whether the drug was available from a single source was collected. The availability of a substitute therapy and whether substitutes were in shortage during the study period were also investigated. RESULTS: Of 1,751 shortages, 141 (8.1%) impacted drugs used to treat poisoned patients, and as of December 2013, 21 (14.9%) remained unresolved. New toxicology shortages increased steadily from the mid-2000s, reaching a high of 26 in 2011. Median shortage duration was 164 days (interquartile range: 76-434). Generic drugs were involved in 85.1% of shortages and 41.1% were single-source products. Parenteral formulations were often involved in shortages (89.4%). The most common medications in shortage were sedative/hypnotics (15.6%). An alternative agent was available for 121 (85.8%) drugs; however, 88 (72.7%) alternatives were also affected by shortages at some point during the study period. When present, the most common reasons reported were manufacturing delays (22.0%) and supply/demand issues (17.0%). Shortage reason was not reported for 48.2% of drugs. DISCUSSION: Toxicology drug shortages are becoming increasingly prevalent, which can result in both suboptimal treatment and medication errors from using less familiar alternatives. CONCLUSION: Drug shortages affected a substantial number of critical agents used in the management of poisoned patients. Shortages were often of long duration and for drugs without alternatives. Providers caring for poisoned patients should be aware of current shortages and implement mitigation strategies to safeguard patient care.

Antídotos e medicamentos utilizados para tratar intoxicações no Brasil: necessidades, disponibilidade e oportunidades / Antidotes and medicines used to treat poisoning in Brazil: needs, availability and opportunities / Antídotos y medicamentos utilizados para tratar intoxicaciones en Brasil: necesidades, disponibilidad y oportunidades

Antídotos e determinados medicamentos são essenciais ao tratamento de algumas intoxicações e não podem sofrer falhas no abastecimento, sob o risco de prejudicar a saúde e a segurança da população. O objetivo deste trabalho foi avaliar a disponibilidade de antídotos e medicamentos recomendados para o tratamento de intoxicações no Brasil. A partir de consensos internacionais, foram selecionados 41 antídotos para análise, todos sem patente em vigência. Desses, 27 são registrados, porém 11 estão disponíveis em formas inadequadas ao tratamento de intoxicações, restando 16 medicamentos comercialmente disponíveis. Somente um terço dos medicamentos necessários para o tratamento de intoxicações está incluído na relação de medicamentos essenciais do país. Em adição, é apresentada proposta de suprimento das demandas a um dos antídotos, anticorpo antidigoxina, considerando a capacidade de produção nacional de imunobiológicos. Os resultados demonstram limitação da assistência adequada aos pacientes intoxicados no país e reforçam a necessidade urgente de políticas públicas na área.

Antidotes and certain other drugs are essential for treating some types of poisoning. Failures in their supply can jeopardize the population's health and safety. The current study aimed to assess the availability of antidotes and other drugs used in the treatment of poisonings in Brazil. International guidelines were used as the basis for selecting 41 antidotes for analysis, none of which currently protected by patents. Of these, 27 are registered in Brazil, but 11 of these are available in inadequate forms for treating poisoning, leaving 16 commercially available antidotes. Only one-third of the drugs needed for treating poisoning are included in the country's list of essential drugs. The article also presents a proposal for supplying the demand for one of the antidotes, anti-digoxin antibody, considering Brazil's domestic capacity for manufacturing immunobiologicals. The study's results show the limitations to adequate treatment for poison victims in Brazil and reinforce the urgent need to strengthen public policies in this area.

Los antídotos y determinados medicamentos son esenciales para el tratamiento de algunas intoxicaciones, y su disponibilidad no puede fallar, o la salud y la seguridad de la población se ponen en peligro. Este estudio tuvo como objetivo evaluar la disponibilidad de antídotos y fármacos recomendados para el tratamiento por intoxicaciones en Brasil. Se seleccionaron para el análisis 41 antídotos de reconocido consenso internacional, todos ellos sin patentes en vigor. Veintisiete estaban registrados en Brasil, pero 11 se venden en preparados farmacéuticos, no apropiados para el tratamiento de intoxicaciones, lo que da como resultado 16 medicamentos disponibles en el mercado. Sólo se incluyen en la lista brasileña de medicamentos esenciales un tercio de los medicamentos necesarios para tratar intoxicaciones. Además, se presenta una propuesta para suplir uno de los antídotos, anticuerpo antidigoxina, considerando la capacidad de producción nacional. Los resultados muestran limitaciones en una atención adecuada a los pacientes intoxicados en Brasil y refuerzan la necesidad urgente de fortalecer las políticas públicas en este ámbito.

[Antidotes and medicines used to treat poisoning in Brazil: needs, availability and opportunities]. / Antídotos e medicamentos utilizados para tratar intoxicações no Brasil: necessidades, disponibilidade e oportunidades.

Antidotes and certain other drugs are essential for treating some types of poisoning. Failures in their supply can jeopardize the population's health and safety. The current study aimed to assess the availability of antidotes and other drugs used in the treatment of poisonings in Brazil. International guidelines were used as the basis for selecting 41 antidotes for analysis, none of which currently protected by patents. Of these, 27 are registered in Brazil, but 11 of these are available in inadequate forms for treating poisoning, leaving 16 commercially available antidotes. Only one-third of the drugs needed for treating poisoning are included in the country's list of essential drugs. The article also presents a proposal for supplying the demand for one of the antidotes, anti-digoxin antibody, considering Brazil's domestic capacity for manufacturing immunobiologicals. The study's results show the limitations to adequate treatment for poison victims in Brazil and reinforce the urgent need to strengthen public policies in this area.

[Antidotes--often expensive and not always available]. / Antidootit--usein kalliita eivätkä aina saatavilla.

While there is seldom need for most anti-poisoning agents and antidotes, they should be quickly available, when needed. Local worst-case scenarios, regional staggering of the treatment, and distances must be taken into account at the health care unit level. Hospitals are fairly well equipped with the recommended antidotes. Replenishment of the stocks is complicated by continual disruptions in supply of antidotes. New antidotes in the updated recommendation include calcium folinate (leucovorin) for methanol poisoning and octreotide for the treatment of hypoglycemia caused by intoxications resulting from antidiabetics of the sulfonyl urea group.

Improving antivenom availability and accessibility: science, technology, and beyond.

Snakebite envenomings constitute a serious and neglected public health problem. Despite the fact that effective treatment exists, i.e. administration of animal-derived antivenoms, the availability and accessibility of these life-saving immunobiologicals is deficitary in various parts of the world, particularly in sub-Saharan Africa and some regions of Asia. This article discusses some of the problems that need to be circumvented in order to improve the availability and accessibility of antivenoms. The conglomerate of antivenom manufacturers is highly heterogeneous in terms of technological base, qualification of staff, implementation of Good Manufacturing Practices (GMPs), and volume of production. Therefore, improvements in antivenom quality and availability should be based on strategies tailored to the situation of each region or country; in this context, three different scenarios are discussed. Accessibility of antivenoms demands concerted efforts at multiple levels, including raising the awareness of public health authorities on the relevance of the problem, implementing innovative antivenom purchasing schemes, strengthening national distribution channels on the basis of robust epidemiological information, improving the cold chain and the provision of health services in remote rural settings, supporting the correct use of antivenoms, and promoting the involvement of local community organizations in various aspects of prevention and management. These tasks should be envisaged in terms of synergistic, interprogrammatic and intersectorial interventions, with the participation of many players.

Establishment and first experiences of the National Serum Depot in the Netherlands.

Since 2008, a National Serum Depot is operational in the Netherlands, guaranteeing antivenom supply, 24 h per day, during medical emergencies. In this article the organisation structure, choice of antivenoms, problems encountered during the establishment, and the results from establishment in 2008 till December 2011 are discussed. The Serum Depot is organised by the National Institute for Public Health and the Environment in cooperation with the Dutch National Poisons Information Center. During establishing and maintaining of the Serum Depot several antivenom purchase difficulties were encountered. Some antivenom producers did not respond upon (initial) contact and some antivenoms were (temporarily) unavailable. Good contacts with professional herpetologists are necessary in order to keep the content of the depot up-to-date. At the same time, it is important to remain well informed concerning the safety and efficacy of the currently available antivenoms and development of new antivenoms. During the first four years of the National Serum Depot, the Dutch National Poisons Information Center was consulted on average 10 times a year about exotic venomous bites and stings in which antivenom treatment might play a role. Almost half of these consultations were related to bites by venomous exotic snakes, the other half to scorpion and fish stings. Antivenom was delivered in five cases, all after a bite by an exotic venomous snake, and actually administered twice because of the severity of local effects. To reduce costs and extend coverage of the Serum Depot of antivenoms for more unfamiliar snake species, international cooperation between the various owners of the antivenom Serum Depots in Europe is recommended.

Evaluate the impact of hospital types on the availability of antidotes for the management of acute toxic exposures and poisonings in Malaysia.

INTRODUCTION: The availability of antidotes may be considered essential and lifesaving in the management of certain poisonings. Surveys carried out in a number of countries have demonstrated inadequate availability of a variety of poisoning antidotes. OBJECTIVES: The purpose of this study was to determine the availability of antidote stocking at hospitals, based on published guidelines for antidote stocking, and to evaluate the impact of hospital types on the availability of antidotes for the management of acute toxic exposures and poisonings in Malaysia. METHODS: A questionnaire on the availability of antidotes was sent to all government accident and emergency departments in Malaysia. The list of commonly required antidotes and essential drugs was compiled from published guidelines. Collected data were analysed in SPSS version 16 using descriptive and comparative analysis. RESULTS: The response rate was 59.06%. None of the responding hospitals stocked all of the antidotes on the lists. In relation to hospital type, there was great variability in the availability of antidotes (there were significant differences between hospitals for 13 antidotes). The availabilities of most antidotes were far better in the General Hospitals and the District Hospitals with specialists compared to District Hospitals without specialists. Calcium gluconate, sodium bicarbonate, atropine sulphate, naloxone, flumazenil, vitamin K, and pyridoxine were available at all general hospitals. Atropine sulphate and naloxone were available at all district hospitals with specialists. CONCLUSION: Most Malaysian government hospitals stocked some important antidotes. Raising awareness of the importance of antidotes by education, regular review of antidote storage, distribution plans, and appropriate legislation might provide solutions. Coordination between Malaysian hospitals and the National Poison Centre at Universiti Sains Malaysia is also important.

Problems in the supply of antidotes--a view from the pharmaceutical industry.

Antidotes are drugs and therefore subject to numerous legal requirements. Due to their indication they are usually needed in small quantities. This is to be considered in view of the efforts to comply with the regulatory affairs. The production capacity and the kept in stock quantities in the pharmaceutical industry for economical reasons can only be small. In cases of catastrophic large events large quantities of antidotes are needed within short time. In these cases only a national stockpiling program can secure the supply with the necessary medicaments for the citizens.

[Antidotes availability in Emergency Departments of the Italian National Health System and development of a national data-bank on antidotes]. / Disponibilità di antidoti nei servizi d'urgenza del Sistema Sanitario Nazionale e realizzazione della Banca Dati Nazionale degli Antidoti (BaNdA).

The availability of antidotes in Italian hospitals has been evaluated through the answers to a specific questionnaire sent to all Italian Emergency Departments, Intensive Care Units, 118 emergency response system, and Poison Centres. Five Poison Centres and, approximately, the 30% of the Emergency Departments and Intensive Care Units of all Italian emergency hospitals answered to the questionnaire. The results point out an insufficient availability of antidotes in the Italian emergency hospitals, with an almost total absence of those necessary for the treatment of less frequent and less known poisonings (e.g. digoxin, industrial agents), also when the antidote is a lifesaving drug. To improve the antidotes availability for the toxicological emergencies and to facilitate its supplying, a "national antidotes data-base" (BaNdA) has been realized, freely available to the hospital services which register themselves and make their antidotes stockpile available.

[Antidotes availability in health services of Catalonia, Spain]. / Disponibilidad de antídotos en los ámbitos sanitarios de Cataluña.

BACKGROUND AND OBJECTIVE: Acute poisoning can be treated in different hospital and extrahospital health services. Thus, availability of antidotes in hospital pharmacies, emergency departments and health centres play an important role in poisoning treatment. MATERIAL AND METHOD: This is a descriptive and transversal study of antidotes availability in different health services of Catalonia (Spain). From April to May 2005, a proper questionnaire was sent to 50 different health centres: 28 basic health centres (including medical ambulances) and 22 hospitals with a distinct medical complexity level, to assess the qualitative (QLA) and quantitative availability (QTA) of antidotes. RESULTS: QLA resulted to be 82% in extrahospital health centres and 50% in medical ambulances. QTA was 94% for ambulances, whereas, in health centres, differences were observed between rural (55%) and urban (33%) areas. Regarding basic general hospitals (level 1), reference hospitals (level II) and high technology hospitals (level III) the QLA showed values of 39, 54 and 55%, respectively, and the QTA came about 70, 54 y 54.5%, in that order. Furthermore, lack of adequate stocking was observed for compounded formulations, such as albumin, starch, ipecacuanha syrup or IV ethanol, and for essential antidotes as snake antivenin, digoxin immune Fab or hydroxocobalamine. CONCLUSIONS: There is understocking of poisoning antidotes throughout the health services of Catalonia. Heterogeneity was observed between services with a medical complexity level. The main deficiencies are found in antidotes that, to date, are available as compounded formulations or imported from other countries.

Rapid atropine synthesis for the treatment of massive nerve agent exposure.

STUDY OBJECTIVE: We developed and tested a protocol for compounding a large volume of injectable atropine from powder. The resulting protocol could be used by hospitals to rapidly use large amounts of stockpiled atropine. METHODS: The protocol required 2 g of solid (powdered) atropine and 1 L of normal saline solution. The solution was filtered and mixed. One hundred syringes were filled by using a standard syringe-batching system. Modifications, including hand filling, were studied to reduce the time required to synthesize one hundred 3-mL syringes. RESULTS: A single pharmacist was able to reconstitute one hundred 6-mg atropine syringes in 29 minutes using the batching system. The quickest method for a single pharmacist filling syringes by hand was 34 minutes. The cost to the hospital for 5 g of powdered atropine was 11 dollars versus 5,000 dollars for prefilled syringes. CONCLUSION: Large quantities of atropine syringes can be compounded from a powdered form in a timely manner. Additionally, there is a significant cost advantage to using powdered atropine as a hospital stockpile.

Atropine availability as an antidote for nerve agent casualties: validated rapid reformulation of high-concentration atropine from bulk powder.

STUDY OBJECTIVE: Atropine is the preferred antidote for immediate management of toxicity associated with nerve agents or other cholinergic syndromes. A large-scale exposure to a nerve agent or organophosphate insecticide might result in many victims presenting for care within a short period of time. This situation would require the prompt availability of a large amount of atropine to provide treatment. Antidote stocks at many hospitals are inadequate to meet this demand. Atropine that is commercially available comes supplied at concentrations of either 0.4 mg/mL or 1 mg/mL, thereby requiring intravenous administration because of the volume necessary to administer the commonly recommended initial dose of 2 to 6 mg. Moderately ill victims may not require an intravenous line for other care, and in the setting of overwhelmed resources, intramuscular administration is faster and easier to perform. METHODS: To facilitate the delivery of larger atropine doses, we developed a method of fortifying existing injectable atropine with bulk pharmaceutical-grade atropine powder to a concentration of 2 mg/mL, thereby increasing the amount available and facilitating its intramuscular administration. An independent analysis of the resulting formulation was undertaken to assess its potency, absence of pyrogens, and stability. RESULTS: The amount of atropine initially present varied by less than +/-5%, within the range allowed by the US Pharmacopeia for the original product. The product was pyrogen free and maintained its potency at refrigeration temperature for at least 8 weeks after preparation and at room temperature for 4 weeks. Once all materials were available, the compounding of this preparation required about 1 hour to complete. CONCLUSION: Existing atropine stocks can be readily augmented by fortification with powdered atropine accurately and inexpensively. Common pharmaceutical guidelines recommend refrigeration for compounded products such as this if not completely used within 28 days.

[Antidote availability in Norway]. / Antidotberedskap i Norge.

BACKGROUND: Antidotes are therapeutic substances that are used primarily to counteract the toxic action of poisonous agents and thus have an important role in the treatment of poisoning. Antidote availability is crucial for the poisoned patient; it is important that hospitals keep antidotes in stock to treat these patients. Most antidotes are expensive, infrequently used, and have short shelf-lives. This makes hospital stocking economically difficult. In Norway, there is no national antidote programme. MATERIAL AND METHODS: The National Poisons Information Centre recently made an inquiry about antidote stocking in Norwegian hospitals. RESULTS AND INTERPRETATION: This survey showed that the antidote availability is not satisfactory. The availability of antidotes in Norwegian hospitals is discussed and recommendations are given.