ANTIBIOTIC RECEIVES A NEW WARNING
* Hepatotoxicity induced by telithromycin is suspected.
In response to postmarketing reports of rare cases of serious liver damage and liver failure involving four deaths and one transplantation, the U.S. Food and Drug Administration has requested the revision of the labeling of the ketolide antibiotic telithromycin (Ketek).
Although reports of adverse effects of telithromycin appear to be rare, it's not possible to determine the exact frequency of them. Nurses should instruct patients to discontinue the drug and contact the provider at once for evaluation, including possible tests of liver function, if any signs or symptoms of liver damage-fatigue, malaise, loss of appetite, nausea, jaundice, or dark urine-appear.
U.S. Food and Drug Administration. FDA news: FDA completes safety assessment of Ketek new safety information to be added to product labeling. 2006 Jun 29. http://www.fda.gov/bbs/topics/NEWS/2006/NEW01401.html.
A NEW DRUG TREATS RARE LEUKEMIAS
* Dasatinib is proven effective in chronic myeloid and acute lymphoblastic leukemias.
* Intended for use in patients unresponsive to other drug therapy.
A new drug, dasatinib (Sprycel), has been approved by the U.S. Food and Drug Administration to treat both chronic myeloid leukemia (CML) and Philadelphia-chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL) in adults.
CML is a rare cancer that afflicts about 4,600 people annually in the United States; Ph-positive ALL is a genetically linked, more serious form of the disease. Dasatinib, approved for treatment of CML according to the accelerated approval process and of Ph-positive ALL under the regular one, works by reducing the activity of one or more proteins responsible for the uncontrolled growth of leukemia cells. It's intended for use in patients who either do not respond to or cannot tolerate imatinib (Gleevec).
Dasatinib has been shown to reduce the number of detectable leukemia cells in the blood and bone marrow of patients with CML or, in some cases, to eliminate them. Additional studies will be conducted to determine whether those laboratory changes produce a clinical benefit, such as longer survival or attenuation of symptoms. Initial studies have shown a favorable response in 45% of patients with early-stage CML, response rates among patients with more advanced CML or Ph-positive ALL range from 31% to 59%, and favorable response to the drug therapy was still present in most six months after the start of therapy. The reported adverse effects of dasatinib are fluid retention, bleeding, diarrhea, rash, infection, headache, fatigue, and nausea; anemia, neutropenia, and thrombocytopenia have also been noted frequently. Nurses should monitor patients who receive the drug closely for its adverse effects.
U.S. Food and Drug Administration. FDA news: FDA gives rapid approval for a new treatment for a rare type of leukemia. 2006 Jun 29. http://www.fda.gov/bbs/topics/NEWS/2006/NEW01400.html.
NEW INDICATIONS FOR TWO DRUGS
* An Alzheimer disease therapy is now approved for treatment of Parkinson disease dementia.
* A combination drug is now approved as the first treatment for late-stage cervical cancer in which surgery and radiation are expected to be ineffective.
Rivastigmine (Exelon) is now indicated for the treatment of mild-to-moderate dementia associated with Parkinson disease, in addition to mild-to-moderate dementia of Alzheimer disease, the indication for which it was approved initially. The drug is thought to exert therapeutic effect through the inhibition of acetylcholinesterase, thereby increasing systemic acetylcholine concentration and enhancing cholinergic function.
But because fewer and fewer cholinergic neurons remain functionally intact as Parkinson disease progresses, rivastigmine could lose its effectiveness over time. Significant adverse effects, specifically gastrointestinal (nausea, vomiting, anorexia, weight loss, and dyspepsia), are common. Other adverse effects attributable to greater cholinergic activity include an increase in parkinsonism (extrapyramidal symptoms such as tremor), dizziness, agitation, depression, and chest pain; the frequency of all of these has been observed to decrease with time.
The recommended starting dosage is 1.5 mg twice a day, to be increased to 3 mg, 4.5 mg, and the maximum 6 mg twice a day, as needed, with a minimum of four weeks of treatment at each increment. Because severe gastrointestinal effects can recur if treatment is discontinued for more than several days and restarted at the same dosage, administration should be resumed at the initial dosage and increased incrementally again. Rivastigmine is available in capsules and in an oral solution, the latter of which is dispensed with a syringe.
Nurses should teach patients and their families about the adverse effects of the drug, which should be reported promptly to the prescriber. If the liquid form of the drug is prescribed, nurses should teach the patient's family members how to administer it, instructions for which are found on the drug label.
Topotecan (Hycamtin) and cisplatin. A new combination drug has been approved by the U.S. Food and Drug Administration as the first treatment for late-stage cervical cancer in which surgery or radiation is unlikely to be effective. Topotecan (Hycamtin, previously approved for the treatment of ovarian cancer and small-cell lung cancer), and cisplatin (Platinol-AQ and others, an antineoplastic used in the treatment of cervical cancer, ovarian tumors, testicular tumors, and advanced bladder cancer). In clinical trials conducted in this population the combination drug increased survival by about three months more than did cisplatin alone, but it was associated with a greater incidence of adverse effects, the most serious of which were neutropenia and thrombocytopenia leading to excessive bleeding and anemia; nausea and vomiting, mucositis, rash, and liver toxicity also were noted.
U.S. Food and Drug Administration. FDA news: FDA approves the first treatment for dementia of Parkinson's disease. 2006 Jun 27. http://www.fda.gov/bbs/topics/NEWS/2006/NEW01399.html. U.S. Food and Drug Administration. FDA news: FDA approves first drug treatment for late-stage cervical cancer. 2006 Jun 15. http://www.fda.gov/bbs/topics/NEWS/2006/NEW01391.html. Novartis [Label information: rivastigmine tartrate (Exelon) capsules and oral solution]. 2006 Jun. http://www.fda.gov/cder/foi/label/2006/020823s016,021025s008lbl.pdf.
HIV-PROTEASE INHIBITORS
* Darunavir, a new antiretroviral, should always be given with ritonavir.
* Many drug-drug interactions are associated with darunavir.
* Warning of intracranial hemorrhage added to the labeling of tipranavir.
Darunavir. According to the U.S. Food and Drug Administration accelerated approval process, applied in response to promising results of phase II clinical trials, a new HIV protease inhibitor, darunavir (Prezista), has been approved for use in patients with HIV who have developed resistance to other protease inhibitors. The pharmacodynamics of the drug are comparable to those of other protease inhibitors, and studies have shown that the plasma concentration of darunavir 400 mg once daily increases by approximately 14 times if it's administered with ritonavir 100 mg given twice daily. Darunavir always should be used in combination with ritonavir, never as a single agent. Because food increases the systemic concentration of darunavir, it should be taken with a meal.
Darunavir and ritonavir are both metabolized primarily by the cytochrome P-450 3A (CYP3A) isoenzyme system, and both drugs act as CYP3A inhibitors. Because an increase in CYP3A level increases the metabolism of darunavir, resulting in decreased plasma concentration, drugs and herbs that induce CYP3A are contraindicated. These include the anticonvulsants carbamazepine (Tegretol and others), phenobarbital (Luminal), and phenytoin (Dilantin and others); the antituberculotic rifampin (Rifadin and others); and St. John's wort. Other drugs metabolized primarily by CYP3A that are contraindicated in darunavir-ritonavir therapy are the antihistamine astemizole (Hismanal), cisapride (Propulsid), a drug that increases gastrointestinal motility, and the neuroleptic pimozide (Orap). Concomitant administration of any of these can cause serious or life-threatening cardiac arrhythmias. Ergot derivatives such as dihydroergotamine (Migranal and others), ergonovine (Ergotrate and others), ergotamine (Ergomar and others), and methylergonovine (Methergine) also are contraindicated in darunavir therapy because of possible ergot toxicity characterized by peripheral vasospasm and ischemia. Concurrent use of the lipid-lowering agents lovastatin (Mevacor, Altocor) or simvastatin (Vytorin and Zocor) increases the risk of myopathy and possibly fatal rhabdomyolysis, and concurrent administration of the sedative-hypnotics midazolam (Versed) and triazolam (Xanax) increases the risk of prolonged or heightened sedation and respiratory depression. There are a multitude of other possible drug-drug interactions described in the label. The most commonly observed adverse effects of darunavir are diarrhea, nausea, headache, and nasopharyngitis, and both mild-to-moderate and severe or life-threatening rash have been reported.
Because darunavir was approved according to the accelerated process, the manufacturer must conduct postmarketing trials to verify the clinical benefits of the drug, to study its effects in children, to better define drug interactions, and to evaluate its use in patients with liver impairment in order to identify appropriate dosing.
Nurses should inform patients of the necessity of taking darunavir concurrently with ritonavir and with meals, and that other anti-HIV drugs should be continued. The nurse should carefully check the drug label for specific dosing instructions when other anti-HIV drugs are also used. Nurses should teach patients that if a dose is missed it should be taken as soon as possible, but only within six hours-otherwise, it should be skipped and the next dose taken at the scheduled time. A double dose of darunavir-ritonavir never should be taken. Nurses should obtain a drug history and consult the listing of drug contraindications in the labeling.
Tipranavir. Reports of serious adverse events in 13 patients taking the protease inhibitor tipranavir (Aptivus) have prompted revisions to its labeling, including a new black box warning. Fourteen occurrences of intracranial hemorrhage, eight of which were fatal, were reported in 13 of 6,840 HIV-1-positive patients receiving tipranavir-ritonavir combination treatment in clinical trials at a median interval of 525 days. A direct causal relationship between tipranavir administration and intracranial hemorrhage cannot be assumed; many of the patients had conditions such as central nervous system lesions, head trauma, recent neurosurgery, coagulopathy, hypertension, or alcohol abuse. Others were concomitantly taking other medications such as anticoagulants or antiplatelets, which might have caused or contributed to the hemorrhage. Furthermore, patients with advanced HIV disease are considered to be at greater risk for intracranial hemorrhage. The results of coagulation laboratory testing were normal, until the point at which the event occurred in each of the 13 patients; accordingly, the recommendation to check clotting times routinely in patients taking the drug has not been made. Still, caution should be exercised in patients already at greater risk for bleeding (because of recent trauma, surgery, medical conditions that alter coagulation parameters, or the use of anticoagulants or antiplatelet agents), in whom closer monitoring is warranted.
U.S. Food and Drug Administration. FDA news: FDA approves new HIV treatment for patients who do not respond to existing drugs. 2006 Jun 23. http://www.fda.gov/bbs/topics/NEWS/2006/NEW01395.html. Boehringer Ingelheim Pharmaceuticals. Dear healthcare professional important safety information: intracranial hemorrhage in patients receiving Aptivus (tipranavir) capsules [letter]. 2006 Jun 30. http://www.fda.gov/medwatch/safety/2006/Aptivus-tipranavir_DHCP.pdf. Tibotec. [Label information: darunavir (Prezista) tablets]. 2006 Jun. http://www.fda.gov/cder/foi/label/2006/021976lbl.pdf.
On the Cover
Eudora Welty (1909-2001), in a career spanning more than six decades, achieved international renown for her prize-winning novels and short stories depicting life in the American South. Yet it's as a photographer that her most "merciful" qualities arose, says Reynolds Price, in his introduction to Eudora Welty Photographs: Welty worked, writes Price, "as though the breathing fact of a person who stood before her was a solemn trust that must not be betrayed."
Welty took the cover photograph in the mid-1930s, when she worked as a publicity agent for the Works Progress Administration (WPA), a federally funded "work relief" program that at its peak employed more than 8 million Americans. Welty took hundreds of photographs depicting the lives of rural Mississippians during the Depression, some of which were published in the WPA's guidebook to the state. In this photo, a nurse stands outside her home; the sign reads, "Clara Humes, Obstetric Nurse and Nursing."
Many of Mississippi's health departments had roots in the 1930s with the hiring of WPA nurses. But African American nurses did not benefit from the program. At the time in the rural South, health care reflected the mores of the larger society and was largely segregated, in accordance with the Jim Crow laws. In the first half of the 20th century, very few African Americans were admitted to nursing schools; many trained through apprenticeship.
When asked about the impression her photographs gave of life in her home state in the 1930s, Welty said in an interview published in Eudora Welty Photographs that "poverty in Mississippi, white and black, really didn't have too much to do with the Depression. It was ongoing. Mississippi was long since poor, long devastated. I took the pictures of our poverty because that was reality, and I was recording it. [horizontal ellipsis] The same thing is true of my stories; I didn't announce my view editorially. I tried to show it."
A traveling exhibition, Passionate Observer: Photographs by Eudora Welty, is currently on display at the San Antonio Museum of Art in Texas. For more information on Welty, visit the Eudora Welty House Web site at http://www.mdah.state.ms.us/welty.-Joy Jacobson, managing editor