Watch

COMBINATION LIPID-LOWERING wasn’t designed to look at cancer the data from SHARP and espe - DRUGS AND CANCER RISK risk, the analysis “was performed cially IMPROVE-IT become after the fact and without statis - known. • There is no evidence that the tical correction to account for combination cholestero l- lowering multiple comparisons. Therefore, A REMINDER ABOUT TERATOGENIC drug Vytorin (simvastatin plus the true statistical significance RISK WITH VALPROATE ezetimibe ) increases the risk of of the cancer imbalance is un- cancer or cancer-related death. known ,” said the FDA. • The antiepileptic valproate sodium • Patients taking Vytorin should and its derivatives are increas - continue to do so. Further bolstering the FDA’s conclusion are interim data from ingly being used to treat condi - two ongoing, large-scale clinical tions other than epilepsy. • Providers are reminded by the he Food and Drug Admin- trials involving the combination FDA about the risks of major birth Tistration (FDA) has con - of simvastatin and ezetimibe, the defects in babies born to women cluded that, at this time, there’s Study of Heart and Renal Pro tec- who take these medications. no evidence that the combination tion (SHARP) and the IMProved • Risks include neural tube defects, lipid- lowering drug Vytorin (the Reduction of Outcomes: Vytorin craniofacial defects, and cardi o- cholesterol-lowering statin sim- Efficacy International Trial vascular malformations. va statin plus the cholesterol (IMPROVE-IT), although results absorption inhibitor ezetimibe) from IMPROVE-IT, which isn’t linicians have known for increases the risk of cancer or due to conclude until 2012, could Cyears that use of the anti- cancer-related death. ultimately shed more light on any epileptic drug valproate sodium The FDA had issued a warning association between use of the (Depacon) and its derivatives in August of last year that the combination drug and cancer. increases the risk of major birth Simvastatin and Ezetimibe in In March 2008 preliminary defects in fetuses exposed in Aortic Stenosis (SEAS) trial had results of the Ezetimibe and utero. As these drugs are increas - ingly being prescribed for other conditions, the Food and Drug Nurses should tell patients to Administration (FDA) has issued a reminder (http://bit.ly/8JRHOr ) continue using their prescribed to all prescribers of the risks to fetuses of neural tube defects, cholesterol-lowering drugs. such as spina bifida and anen - cephaly; craniofacial defects, such as cleft lip and cleft palate; and revealed a greater incidence of Simvastatin in Hypercholesterol- cardiovascular malformations. cancer in the treatment group than emia Enhances Atherosclerosis Originally used as antiepilep - in the placebo group. Its most re - Regression (ENHANCE) trial tics, these drugs have more re- cent announcement comes on showed the combination drug to cently been approved for use in the heels of a follow-up analysis be no more effective than sim - the treatment of bipolar disorder showing that the higher rate in vastatin alone in reducing carotid and migraine headache; the labels the treatment group was likely artery–plaque formation (see on the drugs have always in- the result of all cancers having Drug Watch , May 2009). Because cluded information on terato - been combined for analysis. “It the two ongoing trials are much genic risks, but the FDA fears is biologically less likely that a larger than the ENHANCE trial, that not all practitioners will be single drug increases the risk of the FDA doesn’t recommend any cognizant of those risks. The re- a wide variety of cancer types,” changes in use of the drugs at minder covers valproate sodium wrote the FDA ( http://bit.ly/ this time. Nurses should tell pa- and its related products, such 4uA1XC ), which concluded that tients to continue using their pre - as valproic acid (Depakene and neither the combination drug nor scribed cholesterol-lowering drugs. Stavzor) and divalproex sodium ezetimibe (Zetia) alone increases Nurses should also be alert to (Depakote, Depakote CP, and cancer risk. Because the SEAS trial any changes in FDA guidance as Depakote ER).

24 AJN M May 2010 M Vol. 110, No. 5 ajnonline.com By Diane S. Aschenbrenner, MS, APRN-BC

Additional information on the be weaned off of them before tachycardia, strokes, and acute risks of valproate products during they attempt to do so, if at all myocardial infarction, the label pregnancy has emerged from possible. Because suddenly stop - had already warned prescribers to data gathered in the Antiepileptic ping an antiepileptic drug can use extreme caution when giving Drug Pregnancy Registry, which precipitate seizures or a flare- the drug to patients with a history was created by Massachusetts up of bipolar disease, women of cardiovascular disease . Now General Hospital in Boston . shouldn ’t just stop drug therapy the scope of the warning has been Women taking any antiepileptic but should work with their health broadened to include patients drug (for any indication) during care provider to make the transi - with a family history of sudden pregnancy can voluntarily enroll tion to an alternative therapy; death, cardiac arrhythmias, or in the registry, allowing data failure to treat epilepsy or bipo - cardiac conduction distur bances. about their pregnancy and their lar disorder can also result in Another new warning is that baby’s health to be recorded and poor fetal outcomes or create desipramine must be used with analyzed. pregnancy complications. extreme caution in patients with Pregnancy registries are an im - Women who wish to become a history of seizure disorder be- portant source of information on pregnant should take a folic acid cause the drug can lower the sei- how drugs actually affect preg - supplement before becoming preg- zure threshold, precipitating nant women, a group about nant , as well as during pregnancy , seizures; some patients have had whom little is known because which decreases the risk of neu - seizures that preceded cardiac they ’re usually excluded from ral tube defects in the baby. Some arrhythmias and death. clinical drug trials. According to women won’t be able to switch Further, according to the the FDA, registry data on 149 from valproate sodium to another manufacturer, overdoses of women with epilepsy who used medication. Women who become desipramine are more likely to valproate alone revealed a rate pregnant while tak ing valproate cause death than are overdoses of major malformations of almost sodium or any other antiepileptic of other tri cyclic antidepressants. 12%, nearly four times that of drug should be encouraged to en- Electrocar diographic changes women taking other antiepileptic roll in the Anti epileptic Drug Preg- can occur in overdosage , includ - drugs. nancy Registry . They can do so by ing a widening of the QRS com - The FDA will revise the labels calling the toll- free number , (888) plex, the presence of a terminal of these drugs to more clearly in- 233-2334, or by going to www. S wave seen in lead I and aVL, dicate the increased risk of major aedpregnancyregistry. org . and an R wave seen in aVR. birth defects. A medication guide, Nurses should assess patients which explains the possible risks REVISED WARNING FOR THE carefully for these risk factors if from a drug and accompanies ANTIDEPRESSANT DESIPRAMINE they ’re to begin therapy with each prescription, will be devel - desipramine and teach patients oped. Nurses should tell female • Desipramine (Norpramin) should and their families about possible patients of childbearing age who be used with great caution in adverse effects. Because all anti - are receiving valproate sodium patients with a family history of depressants carry a warning of or any of its related products sudden death, cardiac arrhyth - an increased risk of suicidality or mias, or cardiac conduction about the risk of fetal defects. disturbances . suicide, families should be aware They should also tell patients to • It should also be used with cau - of the signs of depression and thoroughly read the medication tion in patients with a history of notify the physician or NP if guide that comes with each dis - seizure disorder. depression occurs or worsens. pensed prescription because the • An overdose of desipramine is The patient may take an over - information can change. It’s more likely to cause death than dose as a suicide attempt, and important that women taking an overdose of other tricyclic the cardiovascular adverse ef- antidepressants. valproate sodium and related fects from overdosage may be medications be taught to use an fatal. M effective contraceptive because he warnings on the label of many of the adverse effects occur Tdesipramine (Norpramin) , a Diane S. Aschenbrenner is the course in the early weeks of a pregnancy, tricyclic antidepressant, have been coordinator for undergraduate pharma - before the pregnancy is confirmed. revised (go to http://bit.ly/d064qf ). cology at Johns Hopkins University School of Nursing in Baltimore, MD. Patients taking these drugs who Because the drug can produce She also coordinates Drug Watch: wish to become pregnant should conduction defects, arrhythmias, [email protected]. [email protected] AJN M May 2010 M Vol. 110, No. 5 25