This section provides detailed descriptions of antidotes and other therapeutic agents used in the management of a poisoned patient. For each agent, a summary is provided of its pharmacologic effects, clinical indications, adverse effects and contraindications, use in pregnancy, drug or laboratory interactions, and dosage and method of administration.
- Use of antidotes in pregnancy. It is always prudent to avoid or minimize drug exposure during pregnancy, and physicians are often reluctant to use an antidote for fear of fetal harm. This reluctance, however, must be tempered with a case-by-case risk-benefit analysis of the use of the particular therapeutic agent. An acute drug overdose or poisoning during pregnancy may threaten the life of the mother as well as the life of the fetus, and the antidote or therapeutic agent, despite unknown or questionable effects on the fetus, may have a lifesaving benefit. The inherent toxicity and large body burden of the drug or toxic chemical involved in the poisoning may far exceed those of the therapeutic agent or antidote.For most of the agents discussed in this section, little or no information is available about their use in pregnant patients. The Food and Drug Administration (FDA) established five categories (A, B, C, D, and X) of required labeling to indicate the potential for teratogenicity (Table III-1). The distinction between categories depends mainly on the amount and reliability of animal and human data and the risk-benefit assessment for the use of a specific agent. This has led to confusion, with the misbelief that risk increases in a predictable way from Category A to Category X. Note that the categorization may also be based on anticipated chronic or repeated use and may not be relevant to a single use or brief antidotal treatment. Note: In 2015, the Pregnancy and Lactation Labeling Final Rule went into effect, which will eventually replace the FDA A-X pregnancy categories with more detailed narrative sections to include pregnancy and lactation with subsections addressing risk summary, clinical considerations, and data.
- Hospital stocking. The hospital pharmacy should maintain a medical staff-approved stock of antidotes and other emergency drugs. Surveys of hospitals consistently demonstrate inadequate stocks of antidotes. Many antidotes are used infrequently, have short shelf lives, or are expensive. There are also disruptions and delays in the supply of antidotes from manufacturers and the discontinuation of some products (eg, multiple-dose glucagon). The optimal and most cost-effective case management of poisonings, however, requires adequate supplies of readily available antidotes. Fortunately, minimal acquisition and maintenance cost is required to adequately stock many of these drugs. Other cost reduction strategies include employment of an institutional approval and utilization review process, arrangements with suppliers to replace expired and unused antidotes (note that some manufacturers have such a policy), redistribution of soon-to-expire antidotes, and consignment (the hospital has possession of the antidote, but it is owned by the supplier who charges at the time of usage). In addition, some antidotes (eg, Unithiol [DMPS, dimercaptopropanesulfonic acid]) may be available only through compounding pharmacies; therefore, they may not be listed by wholesalers, and additional diligence is needed to ensure the purity of the product (because the drug may be supplied by multiple foreign sources and require extemporaneous preparation).
- We recommend that some antidotes be immediately available and stocked in the emergency department while others be accessible through the hospital pharmacy and available within 60 minutes on a 24-hour basis.
- Larger quantities of a drug may be needed in unusual situations (eg, chemical terrorism), particularly if multiple patients require simultaneous or extended periods of treatment. There are also regional variations and risks (eg, endemic poisonous snakes, industrial chemical facilities, agricultural pesticide use) that need to be factored into stocking strategies. Hospitals in close proximity can explore the practicality of sharing or pooling stocks but should carefully consider the logistics of such arrangements (eg, transferring stocks after hours or on weekends). Hospitals should be linked with regional emergency response plans for hazardous (and nuclear/biological/chemical terrorism) materials, mass casualty incidents, and the mobilization of local and national antidote stockpiles (eg, Strategic National Stockpile).
TABLE III-1. FDA PREGNANCY CATEGORIESa FOR TERATOGENIC EFFECTSFDA Pregnancy Category | Definition |
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A | Adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus in the first trimester, and there is no evidence of a risk later in pregnancy. The possibility of fetal harm appears remote. |
B | Either (1) animal reproduction studies have failed to demonstrate any adverse effect (other than a decrease in fertility) but there are no adequate and well-controlled studies in pregnant women or (2) animal studies that have shown an adverse effect that has not been confirmed by adequate and well-controlled studies in pregnant women. The possibility of fetal harm is probably remote. |
C | Either (1) animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled human studies or (2) there are no animal or human studies. The drug should be given only if the potential benefit outweighs the potential risk to the fetus. |
D | There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or human studies, but the potential risks may be acceptable in light of potential benefits (eg, use in a life-threatening situation for which safer drugs are ineffective or unavailable). |
X | Studies in animals or humans have demonstrated fetal abnormalities, there is positive evidence of fetal risk based on human experience, or both, and the risk of using the drug in a pregnant patient outweighs any possible benefit. The drug in contraindicated in women who are or may become pregnant. |