News diarrhea-predominant irritable bowel events, some fatal, had occurred in us- of 48, 544 patients have taken alosetron syndrome(IBS-D)for whom the ben- ers. At the time, the product's labeled from 2002 through March 2013 efits of therapy exceed the risks, and indication was the treatment of IBS-D in An FDA review of the agency's Ad- Communicate the risks of ischemic women; the recommended dosage was 1 verse Event Reporting System for 2002 colitis and serious complications of mg twice daily through 2012 revealed one case in which constipation to patients, pharmacists, The product returned to the market a patient died, and her gastroenterologist and prescribers in 2002 with a risk management plan, reported that the small-intestine perfora- a boxed warning in the labeling, and a tion, which led to sepsis, was"possibly Both FDa and prometheus, in their narrower indication: women with severe due to alosetron. Two additional alos briefing documents for the committee's IBS-D who have chronic symptoms, no etron users underwent or were scheduled meeting, state that the rEMs is meeting anatomic or biochemical abnormali- to undergo intestinal surgery. both goals ties of the gastrointestinal tract, and no The Prometheus-supported adjudi But the requirements for the prescriber- response to conventional therapy. The cated review of adverse-event reports verification sticker and patient signature labeling recommended an initial dos- from 2002 through 2012 found no deaths on the"Patient Acknowledgement Form" age of 1 mg once daily; a higher dosage, related to alosetron use and one intesti- pose logistical burdens that do not further 1 mg twice daily, could be taken after nal surgery for a"probable/possible"case those goals, according to the company, four weeks if the initial dosage was well of ischemic colon which proposed eliminating both require- tolerated but insufficient to adequately In 2000 alone, according to the com- ments but not the medication guide ontrol a patient's symptoms pany's report on GlaxoSmithKline's data Committee member Brian Erstad, a In 2008, after Prometheus acquired 11 alosetron users died of causes related College of Pharmacy in Tuscon, voted dosage was changed to 0.5 mg twice to gastrointestinal events. professor at the University of Arizona the product, the initial recommended in favor of updating the prescriber- daily verification requirement According to Prometheus, which re DOI10.2146/news130057 And he spoke in favor of continuing to lied on an IMS Health database, a total have patients, after a discussion with the they understand the risks of alosetron ther py and know the appropriate responses to No one. erstad said. could "ease out L the effective elements" from the whole REMS. Thus, FDA should make only one TB care poses challenges, opportunities is already considered effective he pharmacist-managed tubercu T. Mark Woods, clinical coordinator losis(TB) compliance clinic at the giving that supply of the medications for pharmacy at St. Luke's Hospital in University of Southern California(USC) as the students come in. They check Kansas City, Missouri, likewise voted in fa- serves students with latent TB infec- to make sure how much they've taken vor of updating the prescriber-verification tion and also showcases what could be a of the medication, "Goad said. Phar growing health care role for pharmacists. maoists also monitor the students for Drugs we put REMS on have serious, Clinical pharmacist Jeffrey Goad said medication-related adverse events and serious problems, he said. that before the pharmacy staff began for signs and symptoms of active tB Yet the committee consistently hears managing the program, less than 5% which requires more extensive care than about workarounds for elements in the of the students who came to the clinic the clinic offers REMS Programs, he added. completed the then-standard six-month The Centers for Disease Control and With alosetron, Woods said, the sticker course of isoniazid therapy for latent TB. Prevention(CDC)has recommended on prescriptions signals the dispensing We came in about 12 years ago and three drugs--isoniazid, rifampin, and pharmacist to give the situation extra told [administration] that pharmacists rifapentine--for the treatment of latent attention can do a better job. We took it over, and TB. Treatment courses last for three, four Alosetron, a serotonin type 3-receptor we got the rate up to about 66%, Goad six, or nine months and require patients antagonist, first entered the U.S. market said to take one or two medications daily in early 2000 and left later that year. Six pharmacists participate in weekly, or twice weekly. Glaxo SmithKline withdrew the product clinic, which is part of the university because serious adverse gastrointestinal outpatient pharmacy services Continued on page 1370 1366 Am J Health-Syst Pharm--Vol 70 Aug 15, 2013
News 1366 Am J Health-Syst Pharm—Vol 70 Aug 15, 2013 diarrhea-predominant irritable bowel syndrome (IBS-D) for whom the benefits of therapy exceed the risks, and • Communicate the risks of ischemic colitis and serious complications of constipation to patients, pharmacists, and prescribers. Both FDA and Prometheus, in their briefing documents for the committee’s meeting, state that the REMS is meeting both goals. But the requirements for the prescriberverification sticker and patient signature on the “Patient Acknowledgement Form” pose logistical burdens that do not further those goals, according to the company, which proposed eliminating both requirements but not the medication guide. Committee member Brian Erstad, a professor at the University of Arizona College of Pharmacy in Tuscon, voted in favor of updating the prescriberverification requirement. And he spoke in favor of continuing to have patients, after a discussion with the prescriber, sign the form acknowledging they understand the risks of alosetron therapy and know the appropriate responses to certain symptoms. No one, Erstad said, could “tease out the effective elements” from the whole REMS. Thus, FDA should make only one major change at a time to a strategy that is already considered effective. T. Mark Woods, clinical coordinator for pharmacy at St. Luke’s Hospital in Kansas City, Missouri, likewise voted in favor of updating the prescriber-verification requirement. “Drugs we put REMS on have serious, serious problems,” he said. Yet the committee consistently hears about workarounds for elements in the REMS programs, he added. With alosetron, Woods said, the sticker on prescriptions signals the dispensing pharmacist to give the situation extra attention. Alosetron, a serotonin type 3-receptor antagonist, first entered the U.S. market in early 2000 and left later that year. GlaxoSmithKline withdrew the product because serious adverse gastrointestinal of 48,544 patients have taken alosetron from 2002 through March 2013. An FDA review of the agency’s Adverse Event Reporting System for 2002 through 2012 revealed one case in which a patient died, and her gastroenterologist reported that the small-intestine perforation, which led to sepsis, was “possibly” due to alosetron. Two additional alosetron users underwent or were scheduled to undergo intestinal surgery. The Prometheus-supported adjudicated review of adverse-event reports from 2002 through 2012 found no deaths related to alosetron use and one intestinal surgery for a “probable/possible” case of ischemic colon. In 2000 alone, according to the company’s report on GlaxoSmithKline’s data, 11 alosetron users died of causes related to gastrointestinal events. —Cheryl A. Thompson DOI 10.2146/news130057 events, some fatal, had occurred in users. At the time, the product’s labeled indication was the treatment of IBS-D in women; the recommended dosage was 1 mg twice daily. The product returned to the market in 2002 with a risk management plan, a boxed warning in the labeling, and a narrower indication: women with severe IBS-D who have chronic symptoms, no anatomic or biochemical abnormalities of the gastrointestinal tract, and no response to conventional therapy. The labeling recommended an initial dosage of 1 mg once daily; a higher dosage, 1 mg twice daily, could be taken after four weeks if the initial dosage was well tolerated but insufficient to adequately control a patient’s symptoms. In 2008, after Prometheus acquired the product, the initial recommended dosage was changed to 0.5 mg twice daily. According to Prometheus, which relied on an IMS Health database, a total TB care poses challenges, opportunities The pharmacist-managed tuberculosis (TB) compliance clinic at the University of Southern California (USC) serves students with latent TB infection and also showcases what could be a growing health care role for pharmacists. Clinical pharmacist Jeffrey Goad said that before the pharmacy staff began managing the program, less than 5% of the students who came to the clinic completed the then-standard six-month course of isoniazid therapy for latent TB. “We came in about 12 years ago and told [administration] that pharmacists can do a better job. We took it over, and we got the rate up to about 66%,” Goad said. Six pharmacists participate in the clinic, which is part of the university’s outpatient pharmacy services. “The pharmacists are in charge of giving that supply of the medications as the students come in. They check to make sure how much they’ve taken of the medication,” Goad said. Pharmacists also monitor the students for medication-related adverse events and for signs and symptoms of active TB, which requires more extensive care than the clinic offers. The Centers for Disease Control and Prevention (CDC) has recommended three drugs—isoniazid, rifampin, and rifapentine—for the treatment of latent TB. Treatment courses last for three, four, six, or nine months and require patients to take one or two medications daily, weekly, or twice weekly. Continued on page 1370
News Continued from page 1366 countries, it,'s only active TB that they re man is infected with a strain of Mycobac eally concerned about, because of re- terium tuberculosis that is resistant to at The once- and twice-weekly regimens source constraints, Goad said. ast eight first-line anti-TB drugs require directly observed therapy, mean- According to CDC, the annual TB Goad said the issue of drug resistance ing that the patient comes to the clinic case rate for U.S. -born persons is 1.5 per is"a little tricky in his TB clinic because and a pharmacist observes the patient 100,000 population. The burden is higher students are identified on the basis of a taking the dose to ensure compliance. nong some ethnic and racial groups, positive skin-test result and a negative more and more therapy moves to such as Native Americans, whose annual chest x-ray. He said cultures aren't done short course, we're going to have more TB case rate is 5.6 per 100,000 population. because people with latent TB don't pro- need for directly observed therapy, "Goad Kai Chiu, director of the pharmacist- duce sputum to test for the presence of said. "It's a perfect service for pharmacists managed latent TB clinic at the Phoenix the organism for adherence, disease progression, Indian Medical Center, said pharmacists"For all practical purposes, we treat d side-effect monitoring. make treatment recommendations and all patients as if they have a susceptible Tuberculosis typically affects the lungs monitor therapy for Native Americans infection,"Goad said. but can involve any part of the body. In who are referred to the clinic. Goad said he is concerned about the its active form, TB can be transmitted to The clinic works with local public public health implications of MDR-TI others through airborne droplets when an health officials who treat patients with and the lack of new therapies for the infected person coughs, sneezes, or speaks. active TB infection, and the staff par- disease According to the World Health Or- ticipates in the treatment of people who aquiline late last year became the ganization(WHO), more than 9 million have been exposed to active TB and are at first anti-TB drug with a new mechanism new TB cases occur each year, and nearly high risk for infection. of action that FDA has approved in 40 2 million people die of the disease annu- Chiu said he is moderately concerned years. The drug is indicated for the treat ally. about a third of the world s popula- about drug-resistant TB in his practice ment of MDR-TB for which no other tion is estimated to be infected with TB, setting, because people come to Phoenix treatment options exist. most with the latent form of the disease. from all over the world Other than bedaquiline, which isnt Without drug therapy, about 5-10% of Of particular concern is multidrug- used at USCs clinic, "were dealing with these people will eventually progress to resistant (MDR) TB, which constitutes old drugs, and the mycobacterium has active TB, which requires up to two years about 7% of new and 20% of previously had plenty of years to get used to them, of drug therapy. treated TB cases worldwide, according to Goad said. Most U.S. cases of TB occur in non-US. WHO nationals who acquired the infection in MDR-TB is resistant to, at least, iso- DOI10.2146/news130058 their home country, according to CDC. niazid and rifampin. Extensively USC's student population included resistant(XDR) TB is a subset of MDR 8,000 international students during TB that is resistant to isoniazid, rifampin, the 2012-13 academic year, including any fluoroquinolone, and amikacin, about 3,000 from China and 1, 300 from kanamycin, or capreomycin or another India. According to WHO, China and second-line injectable drug News briefs India account for about 40% of TB cases A total of 98 U.S. cases of MDR-TB worldwide including 6 cases of XDR-TB, were re-. The Annals of Pharmacotherapy and Goad said it's challenging to treat ported to CDC in 2011, the most recent The Journal of Pharmacy Technology latent TB in international students who year for which full data are available In (PT) are now published by Sage Pub- leed to leave USC before completing all, MDR-TB accounted for 1.3% of all lications. Milap C. Nahata remains the heir drug regimen TB cases reported to CDC, a slight uptick editor-in-chief of Annals of pharmace For our students who are graduating, from the previous year apy. Eugene M. Sorkin, previously the or who are only there for a short pro-"Despite the fact that tuberculosis.. is associate editor of both journals, is now gram, we have to send them back[home] currently at an all time low in the United the managing editor of Annals of pharma and instruct them to follow up, which States, as long as TB remains a otherapy and editor of JPT. The new pub probably wont happen, he said. problem, [resistance] will always lisher was announced in both journals He said that's because latent TB isn't a great concern, "Chiu said July-August issue. Harvey A K Whitney, viewed as an urgent problem in many News reports in March described an Jr, is the journals'former publisher immigrant from Nepal with XDR-TB America's Essential Hospitals is the In the United States, we have a larger who is under quarantine in Texas. Ac- new name for the National Association problem with latent infections than we cording to The Wall Street Journal which of Public Hospitals and Health Systems, have with active infections. And in other first reported on the case, the Nepalese which was founded in 1981 1370 J Health-Syst Pharm-vol 70 Aug 15, 2013
News 1370 Am J Health-Syst Pharm—Vol 70 Aug 15, 2013 The once- and twice-weekly regimens require directly observed therapy, meaning that the patient comes to the clinic and a pharmacist observes the patient taking the dose to ensure compliance. “As more and more therapy moves to short course, we’re going to have more need for directly observed therapy,” Goad said. “It’s a perfect service for pharmacists . . . for adherence, disease progression, and side-effect monitoring.” Tuberculosis typically affects the lungs but can involve any part of the body. In its active form, TB can be transmitted to others through airborne droplets when an infected person coughs, sneezes, or speaks. According to the World Health Organization (WHO), more than 9 million new TB cases occur each year, and nearly 2 million people die of the disease annually. About a third of the world’s population is estimated to be infected with TB, most with the latent form of the disease. Without drug therapy, about 5–10% of these people will eventually progress to active TB, which requires up to two years of drug therapy. Most U.S. cases of TB occur in non-U.S. nationals who acquired the infection in their home country, according to CDC. USC’s student population included 8,000 international students during the 2012–13 academic year, including about 3,000 from China and 1,300 from India. According to WHO, China and India account for about 40% of TB cases worldwide. Goad said it’s challenging to treat latent TB in international students who need to leave USC before completing their drug regimen. “For our students who are graduating, or who are only there for a short program, we have to send them back [home] and instruct them to follow up, which probably won’t happen,” he said. He said that’s because latent TB isn’t viewed as an urgent problem in many countries. “In the United States, we have a larger problem with latent infections than we have with active infections. And in other countries, it’s only active TB that they’re really concerned about,” because of resource constraints, Goad said. According to CDC, the annual TB case rate for U.S.-born persons is 1.5 per 100,000 population. The burden is higher among some ethnic and racial groups, such as Native Americans, whose annual TB case rate is 5.6 per 100,000 population. Kai Chiu, director of the pharmacistmanaged latent TB clinic at the Phoenix Indian Medical Center, said pharmacists make treatment recommendations and monitor therapy for Native Americans who are referred to the clinic. The clinic works with local public health officials who treat patients with active TB infection, and the staff participates in the treatment of people who have been exposed to active TB and are at high risk for infection. Chiu said he is moderately concerned about drug-resistant TB in his practice setting, because people come to Phoenix from all over the world. Of particular concern is multidrugresistant (MDR) TB, which constitutes about 7% of new and 20% of previously treated TB cases worldwide, according to WHO. MDR-TB is resistant to, at least, isoniazid and rifampin. Extensively drugresistant (XDR) TB is a subset of MDRTB that is resistant to isoniazid, rifampin, any fluoroquinolone, and amikacin, kanamycin, or capreomycin or another second-line injectable drug. A total of 98 U.S. cases of MDR-TB, including 6 cases of XDR-TB, were reported to CDC in 2011, the most recent year for which full data are available. In all, MDR-TB accounted for 1.3% of all TB cases reported to CDC, a slight uptick from the previous year. “Despite the fact that tuberculosis . . . is currently at an all time low in the United States, as long as TB remains a global problem, [resistance] will always remain a great concern,” Chiu said. News reports in March described an immigrant from Nepal with XDR-TB who is under quarantine in Texas. According to The Wall Street Journal, which first reported on the case, the Nepalese man is infected with a strain of Mycobacterium tuberculosis that is resistant to at least eight first-line anti-TB drugs. Goad said the issue of drug resistance is “a little tricky” in his TB clinic because students are identified on the basis of a positive skin-test result and a negative chest x-ray. He said cultures aren’t done because people with latent TB don’t produce sputum to test for the presence of the organism. “For all practical purposes, we treat all patients as if they have a susceptible infection,” Goad said. Goad said he is concerned about the public health implications of MDR-TB and the lack of new therapies for the disease. Bedaquiline late last year became the first anti-TB drug with a new mechanism of action that FDA has approved in 40 years. The drug is indicated for the treatment of MDR-TB for which no other treatment options exist. Other than bedaquiline, which isn’t used at USC’s clinic, “we’re dealing with old drugs, and the mycobacterium has had plenty of years to get used to them,” Goad said. —Kate Traynor DOI 10.2146/news130058 News Briefs • The Annals of Pharmacotherapy and The Journal of Pharmacy Technology (JPT) are now published by Sage Publications. Milap C. Nahata remains the editor-in-chief of Annals of Pharmacotherapy. Eugene M. Sorkin, previously the associate editor of both journals, is now the managing editor of Annals of Pharmacotherapy and editor of JPT. The new publisher was announced in both journals’ July–August issue. Harvey A. K. Whitney, Jr., is the journals’ former publisher. • America’s Essential Hospitals is the new name for the National Association of Public Hospitals and Health Systems, which was founded in 1981. Continued from page 1366
