ACETAMINOPHEN TOXICITY LEADING CAUSE OF LIVER FAILURE
Unintentional overdoses account for one half of cases resulting in encephalopathy.
The excessive use of acetaminophen causes metabolites of the drug to bind to tissue groups in the kidney and liver, causing hepatotoxicity; liver transplantation is often the only treatment to prevent death after hepatic encephalopathy occurs.
N-acetylcysteine, the treatment for acetaminophen toxicity, is not effective unless administered within 12 hours of a single ingestion. Information printed on the labeling of over-the-counter products containing acetaminophen (such as Tylenol) warns against the taking of more than 4 g of the drug daily. It was shown by a recent multicenter prospective research study that acetaminophen hepatotoxicity far exceeds other causes of acute liver failure in the United States and that half of such cases that result in encephalopathy are attributable to unintentional overdoses.
In the study from 1998 to 2003 at 22 academic liver transplant centers, the incidence, risk factors, and outcomes among a cohort of 275 U.S. patients with acetaminophen-related acute liver failure enrolled in the Acute Liver Failure Study Group registry were examined. All of the patients showed evidence of hepatic encephalopathy and had presented-without apparent chronic liver disease-at a transplant center within 26 weeks of its onset. They had taken a median total dose of 24 g of acetaminophen (equivalent to 48 extra-strength tablets), within a range of 1.2 g to 180 g. The patients were nearly equally divided between those who had taken the overdose intentionally (all at once to commit suicide) and those who had taken it unintentionally (over a period of time in the effort to relieve pain or other symptoms). Among cases of intentional and unintentional overdose there were comparable clinical presentations and outcomes in the presence of acute liver failure, and the several factors that appeared to be at play in many of them included repeated dosing in excess of the label recommendations, the concurrent use of more than one product containing the drug, the simultaneous use or abuse of alcohol or narcotics, depression, and chronic pain.
The patients with unintentional overdose were older than those in the intentional-overdose group, used several acetaminophen products at the same time more frequently, and took longer to seek medical care after the onset of symptoms. Two alarming findings are that the annual percentage of acute liver failure cases related to acetaminophen use increased from 28% in 1998 to 51% in 2003, and that the number and percentage of acetaminophen-related acute liver failure cases far exceeded liver failure cases associated with any other cause. Of the 275 patients in the Acute Liver Failure Study Group registry who were considered during the six-year study period, 42% had acetaminophen-related hepatotoxicity, compared with only 12% in whom hepatotoxicity had been caused by the use of other drugs or by the use of herbs. The authors of the study estimate that at least 42% of acute liver failure cases seen at tertiary care centers in the United States and one-third of the consequent deaths are attributable to acetaminophen overdose.
Approximately one-third of people in the United States take an acetaminophen product at least once monthly, and the drug is safe and effective in the great majority of people who take it. However, nurses should educate patients on the risks posed by unintentional acetaminophen overdose, particularly in light of the fact that people tend to believe the dangerous misconception that over-the-counter medications are completely safe at any dose. As stated in the product labeling, doses of acetaminophen exceeding 4 g daily should be avoided. Acetaminophen products come in different concentrations designed for use in patients of different ages, and the use of a formulation created for adults in children or the one created for children in infants can produce an overdose. Also, patients who are unaware that acetaminophen often is an ingredient in combination drug products, such as cold remedies, might take the drug additionally, and nurses should teach those who are prescribed combination narcotics products, such as Vicodin or Tylox, the number of mg of acetaminophen in each dose of the drug, the number that would be taken daily at the full pain-relieving dosage of the prescription, and how many mg of plain acetaminophen, if any, can be safely taken additionally, to treat fever or headache, for example. Further, the present study suggests that patients with chronic pain, depression, or a history of the use or abuse of alcohol or narcotics would benefit from specific, additional warnings of the risk posed by unintentional acetaminophen overdose.
Larson AM, et al. Hepatology 2005;42(6): 1364-72.
NEW DRUG FOR CHRONIC CONSTIPATION
The first in a new class.
Lubiprostone (Amitiza) is a newly approved drug that treats chronic idiopathic constipation in adults, defined as the infrequent and difficult passage of stool, and possibly caused by abnormal colonic motility. Occurring more frequently in women and patients older than age 65, the symptoms of the disorder, one of the most common in the United States, are abdominal pain and discomfort, bloating, straining, and hard or lumpy stools. Lubiprostone works by activating chloride channels in the gastrointestinal epithelium, which then enhances the secretion of intestinal fluid rich in chloride without altering sodium and potassium concentrations in the serum, thereby promoting greater intestinal motility and the passage of stool.
In clinical trials the drug was shown to increase the number of bowel movements within the first week of therapy, and in long-term studies it was shown to decrease the severity of constipation, as well as the attendant bloating and discomfort, over a period of six to 12 months. The most common adverse events are nausea and diarrhea, although other gastrointestinal disorders, such as abdominal pain, distension, and abnormal bowel sounds, can occur. Nausea occurred in almost one-third of patients in the clinical trials and was dose dependent; it was more common when the drug had been taken on an empty stomach, so lubiprostone should be administered with food. Diarrhea does not appear to be a dose-dependent adverse effect of lubiprostone-in 2.2% of patients it was severe enough to necessitate cessation of treatment. Prior to drug treatment, nurses should confirm that all identifiable causes of constipation, including mechanical gastrointestinal obstruction, have been ruled out.
U.S. Food and Drug Administration. FDA news: FDA approves new prescription drug for adults for treatment of chronic "idiopathic" constipation. 2006 Jan. http://www.fda.gov/bbs/topics/news/2006/NEW01305.html; Sucampo Pharmaceuticals. [Label information: lubiprostone (Amitiza) soft gelatin capsules]. 2006 Jan. http://www.fda.gov/cder/foi/label/2006/021908s000lbl.pdf.
REVISIONS TO LABELING OF ANTIBIOTIC
Stronger warning emphasizes risk of altered glucose levels.
The labeling of gatifloxacin (Tequin), a fluoroquinolone antibiotic, has been revised to more strongly emphasize the risks of hypoglycemia and hyperglycemia associated with its use. Since 2002, the drug labeling has warned of those possible adverse effects, but-in response to continuing worldwide postmarketing reports-the language has been strengthened so that health care providers might be more aware of these effects. Diabetes mellitus now is listed as a contraindication for the use of gatifloxacin. While patients with the disease are at greater risk for developing either hyperglycemia or hypoglycemia with the use of the drug, those adverse effects have also been reported in non-diabetic patients. The onset of altered glucose levels generally occurs within three days of the initiation of therapy, and although life-threatening incidents have been rare, some have resulted in fatal outcomes. The administration of gatifloxacin concomitantly with glucose-altering agents, particularly hypoglycemic medications, heightens the risks of both hyperglycemia and hypoglycemia, and older adults are at greater risk of developing either. At the time of gatifloxacin prescription, nurses should educate the patient and family in the signs and symptoms of both hypoglycemia and hyperglycemia.
U.S. Food and Drug Administration. FDA news: stronger warnings for Tequin. 2006 Feb. http://www.fda.gov/bbs/topics/news/2006/NEW01318.html; Bristol-Myers Squibb. Dear healthcare provider [letter: gatifloxacin (Tequin)]. 2006 Feb. http://www.fda.gov/medwatch/safety/2006/tequin_DHCP.pdf.
NEW DRUG APPROVED FOR INFECTIONS CAUSED BY CANDIDA
It can also be used to treat abdominal abscess and peritonitis.
Anidulafungin (Eraxis), a new antifungal agent in the echinocandin class, was recently approved by the U.S. Food and Drug Administration (FDA) for the treatment of various infections caused by the Candida fungi, such as those of the esophagus (candidiasis) and bloodstream (candidemia), as well as other conditions, including abdominal abscess and peritonitis. Administered by IV infusion, the drug is generally tolerated well, although minor adverse effects, including mild diarrhea, slight elevations of liver-enzyme levels, headache, and minor reactions to infusion, have been noted, and serious hepatic abnormalities have occurred in a few patients receiving several medications concomitantly for significant underlying comorbidities.
U.S. Food and Drug Administration. FDA news: FDA approves new treatment for fungal infections. 2006 Feb. http://www.fda.gov/bbs/topics/news/2006/NEW01321.html.
NEW DRUG FOR CHRONIC ANGINA
First in more than 10 years, and a new molecular entity.
Ranolazine (Ranexa) is a new drug available for concomitant administration in patients in whom chronic angina is not well controlled with other drug therapies. Exactly how it decreases incidences of angina is unknown, as it does not significantly lower the heart rate or blood pressure, but in clinical trials involving patients who were taking a calcium channel blocker or a [beta]-blocker for chronic angina there were both significantly fewer episodes and improved exercise tolerance when the drug was added to the daily treatment regimen.
Ranolazine does alter the electrical activity of the heart and prolong the QT interval, an effect that is dose dependent and that has been associated, in the use of other drugs, with the occurrence of torsade de pointes-type arrhythmias and sudden death. In the presence of hepatic dysfunction, the QT interval is prolonged as much as threefold by the use of the drug, which is contraindicated in patients with liver disease of any severity, as well as in those who already have a prolonged QT interval or who are taking other drugs that prolong it or that are potent or moderately potent cytochrome P-450 3A (CYP3A) inhibitors, such as ketoconazole (Nizoral), protease inhibitors, macrolide antibiotics, diltiazem (Cardizem and others), and verapamil (Calan and others), which increase serum levels of ranolazine. Women seem to derive less therapeutic benefit from the drug, and its common adverse effects are dizziness, headache, constipation, and nausea. Nurses should perform a complete drug history to confirm that the patient is not taking any medication that would contraindicate the use of ranolazine, and they should instruct patients to swallow the drug tablets whole--not crush, break, or chew them-and to not drink grapefruit juice, which also inhibits CYP3A. Patients must also be informed that the drug is to be added to the current therapy rather than used to supplant it.
U.S. Food and Drug Administration. FDA news: FDA approves new treatment for chest pain. 2006 Jan. http://www.fda.gov/bbs/topics/news/2006/NEW01306.html; CV Therapeutics. [Label information: ranolazine extended-release tablets (Ranexa)]. 2006 Jan. http://www.fda.gov/cder/foi/label/2006/021526s000lbl.pdf.