TEXTBOOK AND PUBLICATION ERRATA

Concerns Related to Overdose/Toxicology Information in Some Lexi-Comp Printed Publications

Recent clinical feedback has prompted concern related to the Overdose/Toxicology section of some monographs included in Lexi-Comp’s drug information. These include concerns about whether the information in this section represents the most current standard of clinical practice as well as the quality of some supporting documentation. In addition, there are concerns that this information may be interpreted to represent a treatment algorithm. Although these concerns affect a minority of the monographs, Lexi-Comp has decided to temporarily suspend this content in its electronic resources until these concerns are more fully investigated in consultation with a panel of toxicology experts and/or a new toxicology database is released.

Although the fields have been withdrawn from Lexi-Comp’s online drug databases, as well as other electronic products, this information is presented in past and current print editions of our publications, including the Drug Information Handbook, Geriatric Dosage Handbook, and Drug Information Handbook for Psychiatry. As we have been alerted to this issue, we are also identifying the limits of this information to users of our printed publications. Please be aware that this information should not be considered complete and/or may not reflect current medical-toxicological practice. For these reasons this information should not be the basis of current treatment/management decisions.

It should be noted that some of the information which is a source of concern may also be found in other pharmacology references/databases from other publishers, and even in the FDA-approved product labeling of some products. Because the discipline of toxicology is complex and is constantly evolving, all general pharmacology references should be used cautiously. Consultation of specific toxicological databases, as well as contact with poison control center personnel is preferred. To reach poison control centers in the United States and its territories, individuals may call 1-800-222-1222.

Lexi-Comp is taking extraordinary steps to communicate this message. We are corresponding with recent purchasers of these printed handbooks in order to emphasize these issues. Concerning the most recent edition of the Drug Information Handbook, stock is being recalled from wholesalers for replacement by a book without the current Overdose/Toxicology section. Clients are being offered access to electronic versions of the database to provide the most updated information. Clients who may wish to affix a similar warning sticker to earlier print editions may contact Lexi-Comp.

Letters are also being sent to purchasers of the Pediatric Dosage Handbook. Although this publication does not include an Overdose/Toxicology field, this letter alerts users to three toxicology-related updates regarding the use of physostigmine.

Lexi-Comp has initiated a comprehensive review of the toxicology-related information in our drug monographs. Although the Overdose/Toxicology field has been a long-standing part of our publications, a comprehensive summary of the management of overdose is beyond reasonable limits of this small monograph field. This has prompted an ongoing development process which will create a new, comprehensive toxicology database for release in the Fall of 2008.

Below are descriptions of the specific issues which have prompted this letter. Healthcare practitioners are advised to review/note these changes as soon as possible, and also revise any ancillary documents or protocols derived from this content.

Use of physostigmine

1)  In reference to the Overdose/Toxicology field in all tricyclic antidepressant (TCA) monographs (Amitriptyline, Amoxapine, Clomipramine, Desipramine, Doxepin, Imipramine, Nortriptyline, Protriptyline, Trimipramine) regarding physostigmine’s use in TCA poisonings which appears in Lexi-Comp’s 2008-2009 Drug Information Handbook (16th edition), Geriatric Dosage Handbook (13th edition), Psychotropic Drug Information Handbook (5th edition), and Drug Information Handbook for Psychiatry (5th edition). Please also refer to the physostigmine monograph (p. 1257) in the 2008-09 Pediatric Dosage Handbook (14th edition) monograph.

Physostigmine has been removed as a treatment option in tricyclic antidepressant (TCA) overdose. Previous approaches to the management of TCA overdose events suggested that physostigmine may be effective in the reversal of CNS toxicities and/or vagolytic tachyarrhythmias originating from acute intoxication with agents likely to induce an anticholinergic syndrome. However, current clinical practice acknowledges potential for significant toxicity resulting from this approach, and this is no longer considered a recommended strategy for TCA overdose treatment.

Clinically significant complications, including asystole and seizures, have been reported following the administration of physostigmine in TCA-poisoned patients.  Patients with bradycardia and/or prolonged QRS duration may be at particular risk for physostigmine-associated toxicities.  Therefore, physostigmine is not recommended in the setting of TCA intoxication. Treatment of these patients is complex and requires clinical decisions based upon patient-specific details. Consultation with a poison control center is highly recommended.

2)  In the Pediatric Dosage Handbook, the Use field of the Physostigmine monograph has been revised to the following: Reverse toxic, life threatening delirium caused by atropine, diphenhydramine or dimenhydrinate.

Additional changes affect the Warnings field of the Baclofen monograph. Physostigmine had been previously mentioned in the management of intrathecal baclofen toxicity, and this has been removed due to more recent information.

Treatment of methocarbamol overdose

In reference to the Overdose/Toxicology field regarding the treatment of acute methocarbamol toxicity in Lexi-comp’s 2008-2009 Drug Information Handbook (16th edition) and the Geriatric Dosage Handbook (13th edition):

Dialysis, hemoperfusion and/or osmotic diuresis were previously recommended as possibly efficacious treatment strategies to reduce serum concentrations of excessive methocarbamol ingestion. However, clinical literature does not support diuresis or effective removal of methocarbamol by dialysis in chronic renally impaired patients, so these practices can no longer be recommended. Current labeling of methocarbamol states that the effectiveness of hemodialysis in managing overdose is unknown.