1. Aschenbrenner, Diane S. MS, RN, CS

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Older adults with dementia are at risk for death from a cardiac event or infection.

A review of 17 placebo-controlled clinical trials in which various atypical antipsychotic agents were administered to older adults with dementia has revealed an increase in mortality rates, prompting the U.S. Food and Drug Administration (FDA) to require that black box warnings be placed on the labeling of all such drugs. The drugs studied were olanzapine (Zyprexa), aripiprazole (Abilify), risperidone (Risperdal), and quetiapine (Seroquel); the studies involved 5,106 patients with behavioral disturbances related to dementia, a population in which none of the atypical antipsychotics is approved for use.


During the course of the trials, which averaged 10 weeks, there was a 1.6-to-1.7-times greater incidence of death among patients receiving one of the drugs rather than a placebo, the most frequent causes of death being a cardiac event (such as heart failure or sudden death) and infection (most commonly, pneumonia). Atypical antipsychotics fall into one of three subclasses, according to chemical structure, all of which are represented by the drugs administered in the clinical trials. It would therefore appear that the adverse effect is related to properties common to all atypical antipsychotics. Because of that, the labeling of three others that were not included in the trials-- clozapine (Clozaril), ziprasidone (Geodon), and Symbyax (a combination of olanzapine and fluoxetine used in the treatment of depressive episodes in bipolar disorder)--must also bear the black box warning.


Nurses should be aware that atypical antipsychotic agents are approved and labeled for use in the treatment of schizophrenia but that none of them is approved for the treatment of older adults exhibiting behavioral changes induced by dementia, and that the use of such drugs to treat such changes in that population poses significant risk. Information on the labeling changes is given at the FDA Web site. See and follow the links.


U.S. Food and Drug Administration. FDA talk paper: FDA issues public health advisory for antipsychotic drugs used for treatment of behavioral disorders in elderly patients. 2005. http://www.fda/gov/bbs/topics/ANSWERS/2005/ANS01350.htmlU.S. Food and Drug Administration. Atypical antipsychotic drugs information. 2005.



Interferon beta 1b and oxcarbazepine.

Interferon beta 1b.

Berlex, the manufacturer of interferon beta 1b (Betaseron), used in the treatment of multiple sclerosis to reduce the frequency of clinical exacerbations of the disorder, has issued a letter to remind health care providers that the product bears in its prescribing information a precautionary recommendation concerning liver function, in response to post-marketing data that have indicated rare but serious hepatic injury as an adverse effect of the therapy, including autoimmune hepatitis and severe liver damage resulting in hepatic failure and the necessity of transplantation.


The manufacturer strongly advises that the recommendation that liver function testing be performed in patients one month, three months, and six months after the initiation of therapy be followed. In educating patients with prescriptions for interferon beta 1b, nurses should be certain to emphasize the importance of having the follow-up blood work done and of reading the medication guide that accompanies each refill.



The labeling of oxcarbazepine (Trileptal), an anticonvulsant, has been revised to include a new warning and a new precaution. The warning states that the drug can produce the serious skin disorders Stevens-Johnson syndrome and toxic epidermal necrolysis in both children and adults, disorders that necessitate hospitalization and that, rarely, can be fatal. The median point of onset of the conditions was 19 days after the start of drug therapy, as reported in postmarketing findings that showed much higher rates of occurrence of the conditions when compared with the estimated background incidence rates. If a patient develops a skin reaction while taking oxcarbazepine, discontinuation of the drug and substitution with another anticonvulsant should be considered. Recurrence of the dermatologic reactions after the discontinuance and resumption of oxcarbazepine therapy has also been noted.


The revised precautions section of the oxcarbazepine label states that multiorgan hypersensitivity reactions to the drug have occurred in adults and children; the onset of the reactions ranged from four to 60 days after the initiation of therapy, at a median of 13 days. Some of the patients who suffered that adverse effect needed to be hospitalized; some of the reactions were life threatening.


Multiorgan hypersensitivity presents in several ways, most commonly as a fever and rash associated with other organ system involvement, such as lymphadenopathy, hepatitis, liver function abnormalities, hematologic abnormalities (eosinophilia, thrombocytopenia, and neutropenia), pruritus, nephritis, oliguria, hepatorenal syndrome, arthralgia, and asthenia, and the involvement of still other organ systems should be considered possible. At the initiation of oxcarbazepine therapy, nurses should carefully monitor patients for fever and rash accompanied by other symptoms, bearing in mind the possibility of a multiorgan hypersensitivity reaction to the drug, and if the syndrome is suspected, therapy should be discontinued and an alternative one initiated.


Berlex Incorporated. Dear healthcare professional: Betaseron. 2005. Incorporated. Important drug warning: Trileptal. 2005.



Famotidine and gabapentin.

One lot of famotidine injection (Pepcid), an H2-receptor antagonist used to decrease gastric acidity, has been recalled from the market because sterility cannot be guaranteed. The drug lot in question is that of famotidine injection 20 mg/2mL (NDC 55390-029-10), #609336, bearing the expiration date 04/06. The product was distributed to hospitals in the United States in August 2004, and nurses who come across it should submit it to the hospital pharmacy to be returned to the manufacturer.


One lot of gabapentin (Neurontin), a drug used to control epilepsy, has been recalled from the market because bottles of the medication have been found to contain either empty or only partially filled capsules as a result of a mechanical malfunction in the manufacturing process. The 100-mg denomination of the capsule bearing the lot number 15224V is the only one affected. Because the lot was distributed in the United States in October and November of 2004, nurses should instruct patients to check any prescription for the medication that was filled between October 1, 2004, and March 15, 2005, and advise them that if they have any concerns about it, to take it to the pharmacy where it was purchased.


U.S. Food and Drug Administration. Bedford Laboratories recalls one lot of famotidine injection. 2005. Food and Drug Administration. Pfizer follows up on February, 2005 recall of one lot of epilepsy medicine. 2005.



Drotrecogin alfa (activated) is ineffective in pediatric patients.

Eli Lilly and Company has halted a clinical trial that it had been conducting to determine whether drotrecogin alfa (activated) (Xigris), a recombinant form of human activated protein C that exerts an antithrombotic effect and that is approved for use in adults with sepsis, is safe and effective for use in pediatric patients with severe sepsis. Midtrial analysis of data revealed that the drug wasn't effective and that patients receiving it were four times more likely than those receiving placebo to suffer intracranial hemorrhage.


U.S. Food and Drug Administration. MedWatch: 2005 safety alert: Xigris [drotrecogin alfa (activated)]. 2005.