News
N e ws Droxidopa approved for neurogenic orthostatic hypotension
D
roxidopa, a synthetic amino acid precursor of norepinephrine, has been approved as oral therapy for the treatment of neurogenic orthostatic hypotension, FDA and Chelsea Therapeutics announced on February 18. The company expects the drug to be available during the second half of this year under the brand name Northera. Labeling for droxidopa states that it is indicated for the treatment of orthostatic dizziness, lightheadedness, or the sensation of impending fainting in adults with symptomatic neurogenic orthostatic hypotension caused by primary autonomic failure, dopamine β-hydroxylase deficiency, or nondiabetic autonomic neuropathy. The recommended starting dosage of droxidopa is 100 mg taken three times daily—when arising in the morning, at
New drugs and dosage forms Elosulfase alfa injection (Vimizim, BioMarin): The enzyme, produced by recombinant DNA technology, is indicated as replacement therapy for the treatment of patients with Morquio syndrome type A. Indomethacin capsules (Tivorbex, Iroko Pharmaceuticals): The nonsteroidal antiinflammatory drug is indicated for the treatment of mild–to–moderate acute pain in adults. The drug is subject to FDA Medication Guide requirements. Metreleptin for injection (Myalept, Bristol-Myers Squibb): The leptin analog is indicated as an adjunct to diet as replacement therapy for the treatment of the complications of leptin deficiency in patients with generalized lipodystrophy. The product has a risk evaluation and mitigation strategy and is subject to FDA Medication Guide requirements.
520
midday, and late in the afternoon, at least three hours before bedtime. The capsules should be taken consistently with or without food and swallowed whole. Each dose can be increased in 100-mg increments every 48 hours to a maximum of 600 mg per dose, or 1800 mg per day, depending on the patient’s symptomatic response. The effectiveness of droxidopa has not been evaluated in clinical studies of greater than two weeks’ duration. The labeling recommends periodic assessment of the patient’s response to therapy to ensure its continued effectiveness. A boxed warning in the labeling for droxidopa emphasizes the need to avoid supine hypertension, which increases a patient’s risk for cardiovascular events and can be caused or worsened by droxidopa therapy. The warning recommends monitoring supine blood pressure and elevating the head of the bed to reduce the patient’s risk of supine hypertension. If elevating the head of the bed does not
control the condition, then the clinician should reduce the dosage of droxidopa or discontinue therapy. According to the labeling, postmarketing reports in Japan describe patients with symptoms of neuroleptic malignancy syndrome—including fever, muscle rigidity, involuntary movements, altered consciousness, and mental status changes—after taking droxidopa. Patients should be carefully observed for the occurrence of these symptoms after droxidopa dosage changes and also if there is abrupt discontinuation or a reduction in the dosage of concomitant levodopa therapy, especially if the patient is also taking neuroleptic drugs. In clinical trials, the most frequently reported adverse events reported by patients taking droxidopa were headache, dizziness, nausea, hypertension, and fatigue. Droxidopa will be supplied as 100-, 200-, and 300-mg capsules in bottles of 90 each. The bottles should be stored at controlled room temperature. —Kate Traynor DOI 10.2146/news140024
Saline shortage prompts conservation efforts
D
rug shortages have been a part of daily pharmacy practice for years, but the recent national shortage of 0.9% sodium chloride injection is garnering unusual attention. “This is one that’s really hitting every patient across the board,” said Jennifer Brandt, clinical specialist pharmacist at
Am J Health-Syst Pharm—Vol 71 Apr 1, 2014
MedStar Washington Hospital Center in Washington, D.C. “There’s rarely a patient that comes into the hospital that doesn’t need i.v. fluids for a procedure, for surgery, for hydration,” Brandt said. “With a lot of Jennifer Brandt
News
the other shortages, it’s been a really narrow patient population that is affected.” Three out of four pharmacy directors who responded to a recent ASHP online survey said i.v. sodium chloride products are in short supply at their institutions. In all, 29% of respondents said they had insufficient supplies of the i.v. solutions to meet patient needs. Conservation efforts reported by the survey respondents included using alternative products when appropriate, changing doses, prioritizing i.v. saline use in patients on the basis of clinical factors, and, rarely, delaying treatments. Bona Benjamin, ASHP’s director of medication-use quality improvement, said ASHP conducted the survey to assess the effects of the shortage on patient care and communicate the urgency of the problem to Bona Benjamin FDA and the health care community. “We have also used this information to notify the Centers for Disease Control and Prevention of the potential for a public health risk and to update the assistant secretary for preparedness and response,” Benjamin said. “We are in daily contact with the FDA drug shortage staff, who has said locating additional supplies is their priority issue right now.” FDA stated in January that the agency was working with Baxter Healthcare Corp., B. Braun Medical Inc., and Hospira Inc., to preserve the U.S. supply of sodium chloride injection. According to FDA, the shortage is related to an increased demand for i.v. saline solution that may be related, in part, to the treatment of patients with influenza. Brandt said the shortage hasn’t greatly affected her health system. “We’ve been really lucky,” she said. “MedStar, as a whole, has worked really hard to mitigate the shortage. And they tried to do that as early in the process as possible. So we were able to conserve what we had and use it wisely.” She said MedStar’s saline conservation practices include using smaller-sized bags, oral replacement fluids, and alternative i.v. solutions, when appropriate.
Information about the shortage and mitigation practices is communicated through e-mail, newsletters, and messages embedded in the computerized prescriber-order-entry system. “We have 1500 prescribers and more than 2000 nurses, and getting the message across to all of them has been difficult,” she said. She said another important practice has been to reemphasize an existing policy to keep bags of i.v. saline hanging for 96 hours during administration to a patient instead of replacing them every 24 hours. The Centers for Disease Control and Prevention (CDC) recommends changing infusion administration sets no sooner than 72–96 hours in patients who are not receiving i.v. blood, blood products, or fat emulsions. That policy does not include an official recommendation for so-called hang times for i.v. fluids. But the Institute for Safe Medication Practices (ISMP), in response to the i.v. saline shortage, found that at least one study supports extending hang times beyond 24 hours, which ISMP said hospitals are now doing or considering. William Greene, chief pharmaceutical officer for St. Jude Children’s Research Hospital in Memphis, Tennessee, said his hospital has doubled i.v. bag hang times in response to the William Greene shortage. He said the nursing staff, when told about the shortage, let him know that they were routinely discarding saline bags with substantial volume remaining in them. “In a child, you might send up, say, 500 cc’s or a liter of fluid, and you only use 200 or 250 cc’s and throw away the rest,” he said. “So the first step we did to improve our utilization and reduce our waste was simply to allow those fluids to continue to stay on and running for up to 48 hours.” Greene said the additional hang time applies only to “preprepared and lowrisk fluids,” not i.v. solutions that contain
medications or are otherwise unsuitable for the extension. He said no one could recall a valid clinical justification for the previous practice of changing i.v. bags after 24 hours, and the infection-control staff supported the doubling of the hang time. Greene characterized the shortage as mostly administrative in nature and said it is having a moderate effect on the hospital. He said a dedicated purchaser for St. Jude networks with manufacturers and wholesalers to meet patients’ needs, and the pharmacy staff hand count the hospital’s supply of i.v. saline solutions at least three times per week to keep track of what’s on hand. “We’re spending the time and effort to go and count, and that means that we’re worried about it,” Greene said. He said St. Jude probably has less need for saline than, for example, hospitals that treat adults or burn victims. Nevertheless, he said, the hospital is taking the shortage seriously. In addition to increasing hang times, saline conservation largely involves communicating with clinicians and asking them to select alternatives to i.v. saline, when appropriate. “Our clinical pharmacists are engaged in a lot of nutrition-support and hydration decisions,” Greene said. “They know when it’s possible to select a different kind of hydration fluid.” Greene said clinicians at St. Jude are mindful, when considering dextrosebased i.v. solutions, of the need to avoid changes in osmolality that can cause serious neurologic problems, especially in small children. John Armitstead, system director of pharmacy services for Lee Memorial Health System in Fort Myers and Cape Coral, Florida, said the shortage has led to greaterthan-normal use of lacJohn Armitstead tated Ringer’s injection and a more moderate increase in the use of dextrose solutions. Armitstead said dextrose solutions can be used safely in patients with diabetes, especially in conjunction with the blood
Am J Health-Syst Pharm—Vol 71 Apr 1, 2014
521
News
glucose monitoring that hospital patients undergo. “It sounds counterintuitive, but all you need to do is compensate for the calories that you’re delivering,” he said. “In a diabetic patient, it’s preferred not to dominate the diet with carbohydrate calories, but dextrose solution contains small-tomoderate amounts of carbohydrates.” Armitstead said establishing and maintaining i.v. line access accounts for the vast majority of i.v. solution use at Lee Memorial, with far less going toward
fluid replacement. He said the hospital uses alerts in the electronic health record system to remind prescribers about the shortage and ask them to select another fluid, if appropriate. The multihospital system typically maintains a three- to four-week supply of i.v. saline and had about three weeks’ worth on hand when news of the shortage broke, Armitstead said. “Through our conservation, we projected that we’d turn that three-week supply into, in essence, a six-week supply,” he
Specialization key to evolving health care environment
A
s health care models evolve, so do pharmacy practices, and the profession’s increased emphasis on specialized training has a vital role to play in the process. “We’re in what I believe is the era of accountability for health care . . . and that has demanded the expansion of clinical knowledge and competence of all pharmacists,” said William Ellis, executive director William Ellis of the Board of Pharmacy Specialties (BPS). “We’re truly moving beyond a distribution model to being directly involved in affecting patient outcomes.” John Clark, director of pharmacy services at the University of Michigan Hospitals and Health Centers, said that from his perspective as an employer, specialized training helps guide hiring John Clark decisions. “One of the things that specialization and board certification allows us is an opportunity to look at practitioners that are beyond residency-trained individuals,” Clark said. “There are fewer
522
positions available than there were a few years ago. And this allows us to be more selective as employers.” And from the profession’s standpoint, specialization and credentialing are viewed as keystones of so-called provider status—the recognition of the pharmacy profession as health care providers under Medicare. “While we believe that all pharmacists should be recognized as providers, we also realize that . . . decision-makers will want to know that the pharmacists who are providing care possess the requisite knowledge and skills to provide that care competently,” said ASHP Chief Operating Officer David Witmer David Witmer. Witmer said that through its work with the Council on Credentialing in Pharmacy, a collaborative effort involving 10 national pharmacy organizations, ASHP “strives to create a framework for credentialing and privileging that empowers pharmacists to assume a more significant role in patient care.” Specialization today. BPS today awards credentials in six specialty areas
Am J Health-Syst Pharm—Vol 71 Apr 1, 2014
said, adding that his group purchasing organization has been able to consistently supply the health system. “We’re still under conservation mode, but we never ran out and we don’t expect that we will,” Armitstead said in late February. “So we are not directly impacted in patient care needs situations.” —Kate Traynor DOI 10.2146/news140025
and next year will allow pharmacists to take examinations for two additional areas—pediatric pharmacy and critical care pharmacy. But that’s a tiny fraction of the more than 150 specialty and subspecialty areas in which physicians can be credentialed through the Board of Medical Specialties. “Pharmacy is probably behind the curve in specialization,” Ellis said. “Our colleagues in medicine and nursing have had board certifications and specialties for probably a good 30 or 40 years prior to pharmacy.” Ellis said the needs of patients and the health care system will ultimately determine the appropriate number of specialty areas for the pharmacy profession— presumably, a much smaller number than for physicians. He said one reason fewer specialty areas are needed is that pharmacists’ knowledge encompasses a broad range of patient care situations, whereas physicians, especially those who are board certified, tend to have a narrow practice focus. “Pharmacists . . . understand overall medication therapy beyond a specialty area. And that can be a very valuable addition to the health care team,” Ellis said. Witmer noted that hospitals and payers expect physicians to undergo credentialing and privileging in order to care for
Copyright of American Journal of Health-System Pharmacy is the property of American Society of Health System Pharmacists and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
N e ws Droxidopa approved for neurogenic orthostatic hypotension
D
roxidopa, a synthetic amino acid precursor of norepinephrine, has been approved as oral therapy for the treatment of neurogenic orthostatic hypotension, FDA and Chelsea Therapeutics announced on February 18. The company expects the drug to be available during the second half of this year under the brand name Northera. Labeling for droxidopa states that it is indicated for the treatment of orthostatic dizziness, lightheadedness, or the sensation of impending fainting in adults with symptomatic neurogenic orthostatic hypotension caused by primary autonomic failure, dopamine β-hydroxylase deficiency, or nondiabetic autonomic neuropathy. The recommended starting dosage of droxidopa is 100 mg taken three times daily—when arising in the morning, at
New drugs and dosage forms Elosulfase alfa injection (Vimizim, BioMarin): The enzyme, produced by recombinant DNA technology, is indicated as replacement therapy for the treatment of patients with Morquio syndrome type A. Indomethacin capsules (Tivorbex, Iroko Pharmaceuticals): The nonsteroidal antiinflammatory drug is indicated for the treatment of mild–to–moderate acute pain in adults. The drug is subject to FDA Medication Guide requirements. Metreleptin for injection (Myalept, Bristol-Myers Squibb): The leptin analog is indicated as an adjunct to diet as replacement therapy for the treatment of the complications of leptin deficiency in patients with generalized lipodystrophy. The product has a risk evaluation and mitigation strategy and is subject to FDA Medication Guide requirements.
520
midday, and late in the afternoon, at least three hours before bedtime. The capsules should be taken consistently with or without food and swallowed whole. Each dose can be increased in 100-mg increments every 48 hours to a maximum of 600 mg per dose, or 1800 mg per day, depending on the patient’s symptomatic response. The effectiveness of droxidopa has not been evaluated in clinical studies of greater than two weeks’ duration. The labeling recommends periodic assessment of the patient’s response to therapy to ensure its continued effectiveness. A boxed warning in the labeling for droxidopa emphasizes the need to avoid supine hypertension, which increases a patient’s risk for cardiovascular events and can be caused or worsened by droxidopa therapy. The warning recommends monitoring supine blood pressure and elevating the head of the bed to reduce the patient’s risk of supine hypertension. If elevating the head of the bed does not
control the condition, then the clinician should reduce the dosage of droxidopa or discontinue therapy. According to the labeling, postmarketing reports in Japan describe patients with symptoms of neuroleptic malignancy syndrome—including fever, muscle rigidity, involuntary movements, altered consciousness, and mental status changes—after taking droxidopa. Patients should be carefully observed for the occurrence of these symptoms after droxidopa dosage changes and also if there is abrupt discontinuation or a reduction in the dosage of concomitant levodopa therapy, especially if the patient is also taking neuroleptic drugs. In clinical trials, the most frequently reported adverse events reported by patients taking droxidopa were headache, dizziness, nausea, hypertension, and fatigue. Droxidopa will be supplied as 100-, 200-, and 300-mg capsules in bottles of 90 each. The bottles should be stored at controlled room temperature. —Kate Traynor DOI 10.2146/news140024
Saline shortage prompts conservation efforts
D
rug shortages have been a part of daily pharmacy practice for years, but the recent national shortage of 0.9% sodium chloride injection is garnering unusual attention. “This is one that’s really hitting every patient across the board,” said Jennifer Brandt, clinical specialist pharmacist at
Am J Health-Syst Pharm—Vol 71 Apr 1, 2014
MedStar Washington Hospital Center in Washington, D.C. “There’s rarely a patient that comes into the hospital that doesn’t need i.v. fluids for a procedure, for surgery, for hydration,” Brandt said. “With a lot of Jennifer Brandt
News
the other shortages, it’s been a really narrow patient population that is affected.” Three out of four pharmacy directors who responded to a recent ASHP online survey said i.v. sodium chloride products are in short supply at their institutions. In all, 29% of respondents said they had insufficient supplies of the i.v. solutions to meet patient needs. Conservation efforts reported by the survey respondents included using alternative products when appropriate, changing doses, prioritizing i.v. saline use in patients on the basis of clinical factors, and, rarely, delaying treatments. Bona Benjamin, ASHP’s director of medication-use quality improvement, said ASHP conducted the survey to assess the effects of the shortage on patient care and communicate the urgency of the problem to Bona Benjamin FDA and the health care community. “We have also used this information to notify the Centers for Disease Control and Prevention of the potential for a public health risk and to update the assistant secretary for preparedness and response,” Benjamin said. “We are in daily contact with the FDA drug shortage staff, who has said locating additional supplies is their priority issue right now.” FDA stated in January that the agency was working with Baxter Healthcare Corp., B. Braun Medical Inc., and Hospira Inc., to preserve the U.S. supply of sodium chloride injection. According to FDA, the shortage is related to an increased demand for i.v. saline solution that may be related, in part, to the treatment of patients with influenza. Brandt said the shortage hasn’t greatly affected her health system. “We’ve been really lucky,” she said. “MedStar, as a whole, has worked really hard to mitigate the shortage. And they tried to do that as early in the process as possible. So we were able to conserve what we had and use it wisely.” She said MedStar’s saline conservation practices include using smaller-sized bags, oral replacement fluids, and alternative i.v. solutions, when appropriate.
Information about the shortage and mitigation practices is communicated through e-mail, newsletters, and messages embedded in the computerized prescriber-order-entry system. “We have 1500 prescribers and more than 2000 nurses, and getting the message across to all of them has been difficult,” she said. She said another important practice has been to reemphasize an existing policy to keep bags of i.v. saline hanging for 96 hours during administration to a patient instead of replacing them every 24 hours. The Centers for Disease Control and Prevention (CDC) recommends changing infusion administration sets no sooner than 72–96 hours in patients who are not receiving i.v. blood, blood products, or fat emulsions. That policy does not include an official recommendation for so-called hang times for i.v. fluids. But the Institute for Safe Medication Practices (ISMP), in response to the i.v. saline shortage, found that at least one study supports extending hang times beyond 24 hours, which ISMP said hospitals are now doing or considering. William Greene, chief pharmaceutical officer for St. Jude Children’s Research Hospital in Memphis, Tennessee, said his hospital has doubled i.v. bag hang times in response to the William Greene shortage. He said the nursing staff, when told about the shortage, let him know that they were routinely discarding saline bags with substantial volume remaining in them. “In a child, you might send up, say, 500 cc’s or a liter of fluid, and you only use 200 or 250 cc’s and throw away the rest,” he said. “So the first step we did to improve our utilization and reduce our waste was simply to allow those fluids to continue to stay on and running for up to 48 hours.” Greene said the additional hang time applies only to “preprepared and lowrisk fluids,” not i.v. solutions that contain
medications or are otherwise unsuitable for the extension. He said no one could recall a valid clinical justification for the previous practice of changing i.v. bags after 24 hours, and the infection-control staff supported the doubling of the hang time. Greene characterized the shortage as mostly administrative in nature and said it is having a moderate effect on the hospital. He said a dedicated purchaser for St. Jude networks with manufacturers and wholesalers to meet patients’ needs, and the pharmacy staff hand count the hospital’s supply of i.v. saline solutions at least three times per week to keep track of what’s on hand. “We’re spending the time and effort to go and count, and that means that we’re worried about it,” Greene said. He said St. Jude probably has less need for saline than, for example, hospitals that treat adults or burn victims. Nevertheless, he said, the hospital is taking the shortage seriously. In addition to increasing hang times, saline conservation largely involves communicating with clinicians and asking them to select alternatives to i.v. saline, when appropriate. “Our clinical pharmacists are engaged in a lot of nutrition-support and hydration decisions,” Greene said. “They know when it’s possible to select a different kind of hydration fluid.” Greene said clinicians at St. Jude are mindful, when considering dextrosebased i.v. solutions, of the need to avoid changes in osmolality that can cause serious neurologic problems, especially in small children. John Armitstead, system director of pharmacy services for Lee Memorial Health System in Fort Myers and Cape Coral, Florida, said the shortage has led to greaterthan-normal use of lacJohn Armitstead tated Ringer’s injection and a more moderate increase in the use of dextrose solutions. Armitstead said dextrose solutions can be used safely in patients with diabetes, especially in conjunction with the blood
Am J Health-Syst Pharm—Vol 71 Apr 1, 2014
521
News
glucose monitoring that hospital patients undergo. “It sounds counterintuitive, but all you need to do is compensate for the calories that you’re delivering,” he said. “In a diabetic patient, it’s preferred not to dominate the diet with carbohydrate calories, but dextrose solution contains small-tomoderate amounts of carbohydrates.” Armitstead said establishing and maintaining i.v. line access accounts for the vast majority of i.v. solution use at Lee Memorial, with far less going toward
fluid replacement. He said the hospital uses alerts in the electronic health record system to remind prescribers about the shortage and ask them to select another fluid, if appropriate. The multihospital system typically maintains a three- to four-week supply of i.v. saline and had about three weeks’ worth on hand when news of the shortage broke, Armitstead said. “Through our conservation, we projected that we’d turn that three-week supply into, in essence, a six-week supply,” he
Specialization key to evolving health care environment
A
s health care models evolve, so do pharmacy practices, and the profession’s increased emphasis on specialized training has a vital role to play in the process. “We’re in what I believe is the era of accountability for health care . . . and that has demanded the expansion of clinical knowledge and competence of all pharmacists,” said William Ellis, executive director William Ellis of the Board of Pharmacy Specialties (BPS). “We’re truly moving beyond a distribution model to being directly involved in affecting patient outcomes.” John Clark, director of pharmacy services at the University of Michigan Hospitals and Health Centers, said that from his perspective as an employer, specialized training helps guide hiring John Clark decisions. “One of the things that specialization and board certification allows us is an opportunity to look at practitioners that are beyond residency-trained individuals,” Clark said. “There are fewer
522
positions available than there were a few years ago. And this allows us to be more selective as employers.” And from the profession’s standpoint, specialization and credentialing are viewed as keystones of so-called provider status—the recognition of the pharmacy profession as health care providers under Medicare. “While we believe that all pharmacists should be recognized as providers, we also realize that . . . decision-makers will want to know that the pharmacists who are providing care possess the requisite knowledge and skills to provide that care competently,” said ASHP Chief Operating Officer David Witmer David Witmer. Witmer said that through its work with the Council on Credentialing in Pharmacy, a collaborative effort involving 10 national pharmacy organizations, ASHP “strives to create a framework for credentialing and privileging that empowers pharmacists to assume a more significant role in patient care.” Specialization today. BPS today awards credentials in six specialty areas
Am J Health-Syst Pharm—Vol 71 Apr 1, 2014
said, adding that his group purchasing organization has been able to consistently supply the health system. “We’re still under conservation mode, but we never ran out and we don’t expect that we will,” Armitstead said in late February. “So we are not directly impacted in patient care needs situations.” —Kate Traynor DOI 10.2146/news140025
and next year will allow pharmacists to take examinations for two additional areas—pediatric pharmacy and critical care pharmacy. But that’s a tiny fraction of the more than 150 specialty and subspecialty areas in which physicians can be credentialed through the Board of Medical Specialties. “Pharmacy is probably behind the curve in specialization,” Ellis said. “Our colleagues in medicine and nursing have had board certifications and specialties for probably a good 30 or 40 years prior to pharmacy.” Ellis said the needs of patients and the health care system will ultimately determine the appropriate number of specialty areas for the pharmacy profession— presumably, a much smaller number than for physicians. He said one reason fewer specialty areas are needed is that pharmacists’ knowledge encompasses a broad range of patient care situations, whereas physicians, especially those who are board certified, tend to have a narrow practice focus. “Pharmacists . . . understand overall medication therapy beyond a specialty area. And that can be a very valuable addition to the health care team,” Ellis said. Witmer noted that hospitals and payers expect physicians to undergo credentialing and privileging in order to care for
Copyright of American Journal of Health-System Pharmacy is the property of American Society of Health System Pharmacists and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
