Acute isoniazid toxicity and the need for adequate pyridoxine supplies.

A 25-year-old, 54-kg Hispanic man who had recently started multidrug therapy for pulmonary tuberculosis presented in status epilepticus after ingesting 9 g of isoniazid in a suicide attempt. Successful management of this patient required collaboration between several institutions to provide the large amount of necessary intravenous pyridoxine. Ultimately, this single overdose depleted the supply of intravenous pyridoxine for a significant region of the state of Nebraska. Isoniazid is commonly used to treat tuberculosis, but it is encountered relatively infrequently as the cause of an acute overdose. Severe isoniazid overdoses may present as seizure activity that is refractory to conventional antiepileptic therapy. Although intravenous pyridoxine is an effective antidote for isoniazid overdoses in patients presenting with status epilepticus, this agent has few indications and is typically stocked in limited quantities. In regions with large populations of patients who receive antituberculosis therapy, collaborative networks must be created to ensure that adequate supplies of intravenous pyridoxine (> or = 20 g) are available for effective treatment of isoniazid poisonings.

Hospital pharmacy and emergency department availability of parenteral pyridoxine.

OBJECTIVES: Pyridoxine is a recommended antidote that should be available in emergency departments (EDs). A pediatric use of this preparation is the treatment of acute seizures secondary to pyridoxine dependency or responsiveness. Two cases of children with pyridoxine-dependent and pyridoxine-responsive seizures whose treatment was affected by the unavailability of pyridoxine in local EDs are presented. These cases prompted the development of a survey to ascertain the availability of parenteral pyridoxine in the pharmacies and EDs of both children's and general hospitals in the United States. METHODS: A survey of 203 pharmacy directors in 100 pediatric hospitals (42 self-governing and 58 within a hospital) and 103 general hospitals was conducted. The questionnaire asked for the number of licensed beds and whether injectable pyridoxine was on the formulary and stocked by the ED. RESULTS: The overall response rate was 73% (83% pediatric and 64% general hospitals). Injectable pyridoxine was on the formulary of 99% of pediatric hospitals and 91% of general hospitals (P = 0.044). Of those hospitals that had pyridoxine on the formulary, the availability of injectable pyridoxine in EDs was low in both pediatric (20.7%) and general hospitals (16.7%). CONCLUSIONS: Given the number of possible uses of parenteral pyridoxine in the ED, it is suggested that there is a case for all pediatric and general hospital pharmacies to have it on the formulary and further for all EDs in these hospitals to have injectable pyridoxine available for immediate use.

Acute isoniazid exposures and antidote availability.

BACKGROUND: Over the past 10 years the reported incidence of acute isoniazid (INH)-related poisonings has increased, with 507 cases reported in 1996. Parenteral pyridoxine is the antidote for INH-induced seizures, but 5-g aliquot recommended to treat an ingestion of unknown quantity of INH is not always readily available to emergency physicians. OBJECTIVE: To determine the hospital availability of pyridoxine. METHODS: One hundred thirty questionnaires were distributed nationwide to the pharmacies and emergency departments (ED) of hospitals containing pediatric emergency medicine (PEM) fellowships and/or emergency medicine (EM) residencies. Questions were posed regarding the availability, quantity, location, and deemed importance of pyridoxine at each institution. RESULTS: Responses were received from 81% of the hospitals with fellowships and 80% of the hospitals with residencies. Half of the former and one third of the latter reported not having the recommended 5-g aliquot available. Eighty percent of the hospitals with PEM programs and 71% with EM residencies with an adequate stock store it in the hospital's pharmacy, as opposed to in the ED. Thirty-four states were represented, 18 of which have experienced an increase in tuberculosis (TB) from 1993 to 1994; 6/18 (33%) of those did not have the pyridoxine available, and 7/18 (39%) did not deem it necessary. CONCLUSIONS: Our results imply that between one third and one half of the respondents would be ill-equipped to treat acute INH neurotoxicity. Establishing regional distribution centers may alleviate this deficiency, specifically in urban areas with a high incidence or a positive percent increase in TB.

The geographic distribution of tuberculosis and pyridoxine supply in Ontario.

Acute poisoning with isoniazid causes generalized convulsions which should be treated with intravenous pyridoxine and a rapidly-acting anticonvulsant. The purpose of this study was to determine the correlation between the distribution of tuberculosis (as a proxy for isoniazid use) and acute care hospital supplies of intravenous pyridoxine (the antidote for isoniazid overdose). The distribution of tuberculosis was based on Ontario public health regions. The study was descriptive using simple linear regression to assess the degree of correlation. Only 15.6% of Ontario acute care hospitals have enough intravenous pyridoxine to treat an average isoniazid overdose. The distribution of tuberculosis and the number of hospitals in the region correlated best with hospital supplies of pyridoxine, although these variables explained only 22% and 23.7%, respectively, of the variation in supply. It does not appear that the distribution of tuberculosis is a major determinant of the availability of the isoniazid antidote, pyridoxine. Acute care hospitals in Ontario should re-evaluate their need for pyridoxine in light of the incidence of tuberculosis in their regions. Each hospital should stock at least 5 Gm of intravenous pyridoxine; additional amounts may be appropriate if there is an increased incidence in the area.

Measuring drug effectiveness by default: the case of Bendectin.

In 1983, Bendectin was voluntarily removed from the market by Merrell Dow Pharmaceuticals Inc. because of the many product liability suits pending. Earlier, 10 to 25% of pregnancies were exposed to Bendectin and over the years the drug was used in as many as 33 million pregnancies. The scientific evidence available pointed to the safety of Bendectin. This article considers some of the effects of the withdrawal of the drug. In 1983, hospital admissions for excessive vomiting in pregnancy per thousand live births rose by 37% over 1980-82 ratios and by 50% in 1984. In the United States, hospitalization rose by similar amounts. A rough estimate of excess hospital costs over the years 1983-87 is $16 million for Canada and $73 million for the U.S. Such estimates do not take into consideration other costs, such as extra physician visits, increased absenteeism from work, and the effect on quality of life of the pregnant woman and her family. No decrease in rates of congenital malformations could be shown to offset this increased cost to society.