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

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Changes are made to the labeling of several drugs.


Because of two case reports submitted to the U.S. Food and Drug Administration (FDA), the labeling of atomoxetine (Strattera), a drug approved for the treatment of attention deficit-hyperactivity disorder in adults and children, has been revised to carry a boldfaced warning of the possibility of severe liver injury, which can progress to liver failure either necessitating transplantation or causing death. The risk of serious liver damage as an adverse effect of atomoxetine is extremely slight-hepatotoxicity was not identified as a risk during clinical trials involving 6,000 patients. Nevertheless, a description of the signs and symptoms of liver problems has been added to the package insert, and they should be addressed during patient education in the drug therapy. Nurses should be sure that patients and families understand that if pruritus, jaundice, dark urine, abdominal pain or tenderness in the upper right quadrant, or unexplained flulike symptoms develop, the prescriber should be contacted.



The labeling of nevirapine (Viramune), a nonnucleoside reverse-transcriptase inhibitor used to treat HIV infection, has been revised to reflect the higher risk of liver toxicity in patients who have CD4+ cell counts higher than 250/mm3 at the initiation of therapy with the drug, a risk that is also higher among women. Liver toxicity can be either asymptomatic or clinically symptomatic; signs and symptoms can range from elevated liver enzyme levels with at least one other symptom (such as rash, flulike symptoms, or fever) to rapidly progressing liver failure and death. There is a threefold higher risk of symptomatic liver toxicity among women, and women with CD4+ cell counts higher than 250/mm3 have a twelvefold greater risk of developing it, compared with women with lower counts. The revised treatment recommendation now states that women with high CD4+ cell counts should not begin nevirapine therapy unless the benefits clearly outweigh the risks. The revised label does not state that nevirapine should not be prescribed to women - some medical circumstances do not carry the higher risk of liver toxicity. There have been no reports of liver toxicity (in either mother or child) when the drug has been used in a single dose for the prevention of perinatal HIV infection, for example, nor has it been reported in children infected with HIV-a fortunate circumstance because nevirapine, unlike many other HIV drugs, is available in the liquid form that is easily administered to children. In addition to the revisions made to its labeling, the FDA now requires that the drug be dispensed with a medication guide providing additional information on its possible serious adverse effects. Nurses and physicians should be aware of the nevirapine labeling revisions and should be certain to assess the patient's CD4+ cell count prior to initiating therapy with the drug; counts lower than 250/mm3 are associated with a lower risk of liver toxicity. Patients and families should be taught the signs and symptoms of liver failure and instructed to read the nevirapine medication guide thoroughly each time a prescription for the drug is filled, as it may have been revised according to new information on adverse effects.



The labeling of darbepoetin alfa (Aranesp), a drug used to raise the low red blood cell count associated with chemotherapy-induced anemia in patients with nonmyeloid malignancies, also has been recently revised. Studies of other hematopoietic drugs (epoetin alfa and epoetin beta) investigated the effects of raising the hemoglobin levels above 12 g/dL in cancer patients with anemia; results indicated a greater incidence of adverse effects, including thrombotic vascular events and death, when the levels were raised that high. Although the darbepoetin alfa labeling has borne the recommendation that the hemoglobin level should not exceed 12 g/dL, the findings of the other trials have been added to it to more strongly emphasize the risk. Nurses should closely monitor the patient's response to darbepoetin alfa therapy to confirm that the hemoglobin level is not excessively high.



Changes also have been made to the labeling of two forms of penicillin, penicillin G benzathine with penicillin G procaine injectable suspension (Bicillin C-R), and penicillin G benzathine injectable suspension (Bicillin L-A); changes entail boxed warnings stating that neither drug is to be administered intravenously and precautionary statements that Bicillin C-R is not to be used as treatment of syphilis, Bicillin L-A being the form recommended for that purpose. As an additional warning to professionals and to prevent medication errors, the words "Warning: Not For Intravenous Use" have been added in bold red capital letters to the cartons and syringe labels of both drugs, because intravascular administration has been found to result in serious adverse effects, including cardiopulmonary arrest and death. The packaging has been modified further so that the background on the cartons of Bicillin C-R is colored-that of the Bicillin L-A cartons remaining white-and the words "Not for the Treatment of Syphilis" have been added in red to the Bicillin C-R syringe labels.


U.S. Food and Drug Administration. FDA talk paper: new warning for Strattera. 2004.; U.S. Food and Drug Administration. FDA public health advisory for nevirapine (Viramune). 2005.; Amgen. Aranesp: dear health care professional. 2005.; Amgen. Aranesp product information. 2003.; U.S. Food and Drug Administration. FDA talk paper: FDA strengthens labels of two specific types of antibiotics to ensure proper use. 2004.



An effort to minimize adverse effects.

A new Food and Drug Administration medication guide has been created for distribution with amiodarone (Cordarone), a class III antiarrhythmic drug used to treat life-threatening ventricular arrhythmias that have not responded to other drug therapy. The drug has always been recognized to have significant adverse effects, including pulmonary toxicity (fairly common and possibly fatal), liver toxicity (usually mild but occasionally fatal), and either the exacerbation of the cardiac arrhythmia or the induction of a different, additional one. The effects of amiodarone vary greatly among individuals, possibly because of differences in metabolism within the cytochrome P-450 enzyme system, and probably for the same reason, appropriate dosing with the drug is difficult to achieve because of its exceptionally long half-life and the several drug interactions that can occur. The new medication guide provides patients with detailed information on those risks (as well as on other possible adverse effects), how to minimize them, and when to contact the physician. Nurses should instruct patients and their families to read the guide thoroughly each time the prescription is filled, in the event that the information in it has been revised. Patients and their families should also be made aware that while it states that amiodarone is used only for the treatment of certain ventricular arrhythmias (the only approved use of the drug), it's now being prescribed fairly often as an off-label treatment of atrial fibrillation. If it's used for atrial fibrillation, education in the appropriate off-label usage of drugs should be provided to allay any concern about receiving an erroneous prescription. If the reason that amiodarone has been prescribed is ever unclear, the nurse should consult the prescriber.


U.S. Food and Drug Administration. 2005 safety alert: Cordarone (amiodarone HCl). 2004.; Wyeth Pharmaceuticals. Medication guide: Cordarone tablets (amiodarone HCl). 2004.



Effective in patients treated for hematologic malignancy.

Palifermin (Kepivance), a new drug produced by recombinant DNA technology, is a synthetic form of human keratinocyte growth factor, an endogenous protein that promotes the production of epithelial cells in the skin and on the surface layers of the mouth, stomach, and colon. The drug has been shown to reduce the incidence of mucositis in patients who have cancer and are undergoing chemotherapy and radiation therapy prior to bone marrow transplantation. It appears to induce more rapid replacement of the cells in the mouth and gastrointestinal tract. And if mucositis does develop after the administration of palifermin, its duration is much shorter, at an average of three days, compared with the usually expected average duration of nine days. The drug is administered daily by IV bolus for three consecutive days prior to chemotherapy and three consecutive days after it (a total of six doses). The prechemotherapy doses should be timed so that the third one is given between 24 and 48 hours before the administration of chemotherapy, and the first postchemotherapy dose (the fourth one in all) should be given on the day of administration. The most common adverse effects are skin rash, unusual oral symptoms (such as tingling in the mouth, thickening and discoloration of the tongue, alteration in taste, or dysesthesia), joint pain, unusual sensations in the skin (such as numbness, tingling, burning, or itching), and edema. Mild, transient hypertension is also possible, as are asymptomatic elevations of serum lipase and serum amylase levels, neither of which has been found to be of significance, and proteinuria. Because of its effect on epithelial cell growth, palifermin may stimulate the growth of epithelial tumors. The drug has not yet been tested for efficacy in patients with other types of cancer.


U.S. Food and Drug Administration. FDA talk paper: new biotechnology drug approved to treat mucositis associated with cancer treatments. 2004.; Amgen. Kepivance (palifermin) product information.; U.S. Food and Drug Administration. Questions and answers on palifermin (keratinocyte growth factor). 2004.