A NEW FORMAT FOR DRUG LABELS
Preventing errors, improving patient safety.
For the first time in 25 years, the U.S. Food and Drug Administration (FDA) has announced a significantly revised format for prescription drug labeling, which will be required on all new drugs beginning June 30, 2006. There is a separate schedule for drugs approved within the five years preceding that date, and drugs approved more than five years ago are not required to reflect the changes, although manufacturers may revise the labeling "voluntarily at any time."
"Each year," according to the FDA, "approximately 300,000 preventable adverse events occur in hospitals in this country, many as a result of confusing medical information. Research shows that prioritizing the warning information has a greater impact on reducing such events." Accordingly, the new format includes an introductory section entitled "Highlights," which presents a summary of key information on the label, including boxed warnings, drug indications and usage, dosing and administration information, dosage forms and strengths, and any substantive changes made to it in the past year. A table of contents is also included.
Other elements of the revised format are the date of the drug's initial approval, a toll-free number and Internet information for reporting suspected adverse events, and a section with patient-counseling information, which emphasizes information that the prescriber should share with the patient to ensure safe use of the drug. Any information approved by the FDA to be directed toward patients will either be printed at the end of the label directly after the patient-counseling section, or will accompany the prescription as an insert. Other revisions have been made to streamline and better organize the information presented.
To view a sample of the revised label format please see the FDA Web site at http://www.fda.gov/oc/initiatives/2VRX1219_files/800x600/index.html.
U.S. Food and Drug Administration. FDA news: FDA announces new prescription drug information format to improve patient safety. 2006 Jan 18. http://www.fda.gov/bbs/topics/news/2005/NEW01272.html.
NEW DRUGS
Inhaled insulin and a treatment for both gastrointestinal and kidney cancer.
Exubera (recombinant human insulin [rDNA origin]), a rapidly-acting insulin powder inhaled by means of a special administration device, is the first inhaled insulin product approved by the U.S. Food and Drug Administration (FDA).
Representing the first insulin delivery option in 80 years, the product can be used in either type 1 or type 2 diabetes. It reaches a peak concentration more quickly than regular insulin administered subcutaneously (30 to 90 minutes, compared with 60 to 240 minutes) and should be taken no more than 10 minutes before a meal. Because of its unique means of administration, Exubera has been found to produce some adverse effects on respiratory function, specifically decreased pulmonary function as evidenced by forced expiratory volume in one second and carbon monoxide diffusing capacity, effects that were noted within the first several weeks of treatment in clinical trials. Because of this, patients should undergo pulmonary function testing before starting therapy with Exubera, and follow-up studies should be performed after six months of therapy and then annually thereafter, even in the absence of pulmonary symptoms.
The drug is contraindicated in smokers. The systemic levels of insulin in smokers using Exubera are two to five times higher than those in nonsmokers, placing them at a much higher risk for hypoglycemia. Patients should stop smoking at least six months before starting therapy, and if they resume smoking, they should quit taking Exubera immediately. Exubera is also contraindicated in patients with unstable or poorly controlled underlying lung disease because of the significant variation in lung function that might alter absorption of the drug. Respiratory adverse effects, such as cough shortly after administration, dyspnea, pharyngitis, greater sputum production, and epistaxis, which appear to be mild and sometimes transient, are possible.
Exubera comes in blisters of insulin denominated in milligrams (mg) rather than in international units (IU), the 1-mg blister equaling approximately 3 IU of regular insulin, and the 3-mg blister equaling approximately 8 IU. Patients should be instructed to use the fewest possible blisters that provide the prescribed dosage, that is, for example, one 3-mg blister rather than three 1-mg blisters, as the latter might provide more medication than prescribed. A medication guide for patients will provide information on how to administer the drug; close adherence to the directions will be necessary to achieve full therapeutic effect. Instructions in the use of the medication are given at the end of the drug label and can be viewed online at http://www.fda.gov/cder/foi/label/2006/021868lbl.pdf.
A new cancer drug holds the distinction of being the first one approved simultaneously for the treatment of two different cancers. Sunitinib (Sutent) is a "targeted" therapy for gastrointestinal stromal tumors (GIST), a rare stomach cancer, and for advanced renal cell carcinoma. Targeted therapy differs from conventional therapy in that it pinpoints cancerous cells, rather than affecting both healthy cells and cancer cells; because of this, the systemic adverse effects that can occur in chemotherapy are minimized. Specifically, sunitinib is a tyrosine kinase inhibitor that deprives tumor cells of the blood and nutrients necessary for their growth. Interim analysis of clinical trial data showed that the drug increased the time it takes for tumors or new lesions to grow in patients with GIST. The medication is approved for use in patients with GIST who have not responded to or are unable to tolerate treatment with imatinib (Gleevec, also a tyrosine kinase inhibitor and the current approved treatment for the cancer).
In advanced renal cell carcinoma, sunitinib appears to work differently, in that it reduces the size of the tumor; a response rate of 26% to 37% was seen in patients with metastatic disease. Sunitinib was approved by the U.S. Food and Drug Administration through the accelerated process used for drugs considered to have demonstrated the potential to save or extend lives in cases of serious disease. Additional data regarding the drug will be collected and reviewed in the postmarketing period.
U.S. Food and Drug Administration. FDA news: FDA approves first ever inhaled insulin combination product for treatment of diabetes. 2006 Jan 27. http://www.fda.gov/bbs/topics/news/2006/NEW01304.html; U.S. Food and Drug Administration. FDA news: FDA approves new treatment for gastrointestinal and kidney cancer. 2006 Jan 26. http://www.fda.gov/bbs/topics/news/2006/NEW01302.html; Pfizer Inc. [Label information: insulin human (rDNA origin) inhalation powder (Exubera)]. 2006. http://www.fda.gov/cder/foi/label/2006/021868lbl.pdf.
NEW WARNINGS ON ECZEMA DRUG LABELING
Possible risk of cancer is highlighted.
New boxed warnings have been added to the labeling of two immunosuppressants used as topical treatments for eczema, in response to data of studies in animals and some case reports. Pimecrolimus cream (Elidel) and tacrolimus (Protopic Ointment) both suppress the immune system by inhibiting the activation of T lymphocytes. Animal studies of the drugs have demonstrated the development of lymphoma or follicular cell adenoma of the thyroid (the former dose dependent), and case reports (10 concerning pimecrolimus and 19 concerning tacrolimus) received by the U.S. Food and Drug Administration (FDA) describe the development of cutaneous tumors, a lymph node-cutaneous tumor, lymphomas, squamous cell carcinoma, malignant melanoma, and other types of tumor in patients who used the products. The labeling of the oral and IV forms of tacrolimus (Prograf), used to prevent rejection after organ transplantation, has always borne a boxed warning of the possible development of lymphoma.
The FDA's recommendations for practitioners are as follows:
* Use the drugs only as second-line agents after other therapy has failed.
* Use the drugs for short periods of time only, not continuously.
* Use the minimum dosage necessary to control symptoms.
* Avoid use in children younger than two years of age.
* Avoid use in patients with weakened or compromised immune systems.
Additionally, the medication guide distributed with each prescription filled will explain the possible risks, and nurses should instruct patients to read it upon each refilling, as new information may have been added to it.
U.S. Food and Drug Administration. FDA alert for healthcare professionals: pimecrolimus (marketed as Elidel). 2005 Mar. http://www.fda.gov/cder/drug/InfoSheets/HC P/ElidelHCP.pdf; U.S. Food and Drug Administration. FDA alert for healthcare professionals: tacrolimus (marketed as Protopic). 2005 Mar. http://www.fda.gov/cder/drug/InfoSheets/HCP/ProtopicHCP.pdf; U.S. Food and Drug Administration. FDA news: FDA approves updated labeling with boxed warning and medication guide for two eczema drugs, Elidel and Protopic. 2006 Jan. http://www.fda.gov/bbs/topics/news/2006/NEW01299.html.
SAFETY UPDATES
New warnings for three drugs.
The manufacturer of rosiglitazone (Avandia, Avandamet, Avandaryl), an oral type 2 diabetes drug, is revising the precautions section of the product label in response to postmarketing reports of new-onset or worsening diabetic macular edema associated with use of the product (most patients also developed peripheral edema). Generally, the macular edema either resolved or improved after discontinuation of the drug therapy, and the manufacturer asserts that the adverse event are rare. The symptoms of macular edema, which usually occurs in association with diabetic retinopathy, include blurred vision, distorted vision, diminished sensitivity to color, and diminished ability to adapt to the dark.
Clozapine (Clozaril), an atypical antipsychotic agent used in the treatment of severely ill schizophrenic patients who have not responded to therapy with other such agents, is associated with the risk of agranulocytosis, and its distribution is limited through a special system that ensures that the white blood cell count and the absolute neutrophil count are monitored throughout therapy. Now there are further requirements regarding the frequency of monitoring and the parameters that must be met. Nurses providing care to patients receiving clozapine can review them at http://www.fda.gov/medwatch/SAFETY/2006/Clozaril_chart_letter_final12-2005.pdf. Other changes to clozapine's label include the new boxed warning (applicable to all atypical antipsychotics) that among older adults with psychosis related to dementia, there is a greater risk of death associated with use of the drug. Further, a new contraindication to the use of clozapine is paralytic ileus, and newly identified adverse effects are hypercholesterolemia or hypertriglyceridemia, or both, the laboratory values of which should be monitored by the nurse.
Also, new warnings have been added to the labeling of hydroxyurea (Hydrea and Droxia), a chemotherapeutic agent. Use of the drug, which is believed to achieve its effect by inhibiting an enzyme crucial to DNA synthesis, has been associated with cutaneous vasculitic toxicities, such as vasculitic ulcerations and gangrene, in patients with myeloproliferative disorders. Most often, it affects patients who have previously received or are currently receiving interferon drug therapy. The labeling of the Hydrea formulation of the drug bears an additional new warning regarding its use in older adults, in whom impaired renal function is more common; because toxicity occurs more often in patients with impaired renal function, a lower-dosage regimen may be necessary in that population.
On the labeling of both formulations of hydroxyurea, warnings about the safe handling of the drug have been strengthened--anyone not taking the drug who handles either it or the bottle it's in should wear impervious disposable gloves and wash his hands before and after any such contact, including that occurring in pharmacy stocking, transport within a facility, and dose preparation and administration. Nurses should discuss the precautions with the appropriate staff members, patients, and patients' families.
GlaxoSmithKline. Dear health care provider [letter; rosiglitazone (Avandia, Avandamet, and coming soon in some markets, Avandaryl)]. 2005 Dec. http://www.fda.gov/medwatch/safety/2006/Avandia_DHCPletter.pdf; Novartis Pharmaceuticals Corp. Dear health care provider [letter; clozapine (Clozaril)]. 2005 Dec. http://www.fda.gov/medwatch/safety/2006/Clozaril_chart_letter_final12-2005.pdf; Bristol-Myers Squibb Co. [letter; hydroxyurea capsules (Hydrea)]. 2006 Jan. http://www.fda.gov/medwatch/safety/2006/HydreaDearDrLtr.pdf; Bristol-Myers Squibb Co. Dear healthcare provider [letter; hydroxyurea capsules, USP (Droxia)]. 2006 Jan. http://www.fda.gov/medwatch/safety/2006/DroxiaDearDrLtr.pdf.
PUBLIC HEALTH ADVISORY
Case reports of liver toxicity from an antibiotic.
Case reports have indicated an association between use of the antibiotic telithromycin (Ketek) and possibly fatal liver toxicity. The antibiotic is indicated for the treatment of bacterial infections such as community-acquired pneumonia of mild-to-moderate severity (including multi-drug-resistant Streptococcus pneumoniae), acute bacterial sinusitis, and acute bacterial exacerbation of chronic bronchitis.
The drug was approved for use in the United States in April 2004, and nearly 4 million prescriptions had been written prior to that time in Europe and Japan. Currently, there are three reported cases (one patient recovered, one underwent transplantation, and one died), and the U.S. Food and Drug Administration does not believe that the risk of liver toxicity posed by telithromycin is any greater than that posed by erythromycin (E-Mycin and others) or amoxicillin (Amoxil and others). The agency has stated that it's working with regulatory agencies in other countries to determine whether case reports of liver failure associated with the use of telithromycin have been reported there. Nurses should monitor patients taking telithromycin for signs and symptoms of liver toxicity and see that the drug therapy is discontinued if they are noted, and patients should be instructed to be on the lookout for yellowing of the eyes or skin and to contact the prescriber immediately if either is present.
U.S. Food and Drug Administration. FDA public health advisory: Ketek (telithromycin) tablets. 2006 Jan. http://www.fda.gov/cder/drug/advisory/telithromycin.htm; U.S. Food and Drug Administration. Questions and answers on telithromycin (marketed as Ketek). 2006 Jan. http://www.fda.gov/cder/drug/infopage/telithromycin/qa.htm.