News
N e ws Changes coming to pregnancy labeling
F
DA officials say this year’s rollout of new requirements for pregnancy, lactation, and reproductive risk information in the labeling of prescription drugs is a major advance in public health. The so-called pregnancy and lactation labeling rule, which was proposed in 2008 and finalized this past December, requires that labeling reflect current knowledge about pregnancy, lactation, and reproductive risks associated with the drug’s use. The labeling will also direct women to pregnancy registries that have been established for specific drugs. “Clinicians will . . . be able to rely on FDA-approved drug labeling for comprehensive, clinically relevant, and user-friendly information in this part of labeling—something that has been missing for many years,” said Sandra Kweder, deputy director of the Office of New Drugs in FDA’s Center for Drug Evaluation and Research. Kweder said during a December 3 media briefing that drug manufacturers won’t be required to conduct new studies to assess pregnancy-related risks. But the rule requires manufacturers to evaluate medical literature that describes these risks and revise drug labeling accordingly. Kweder said most of the information will come from postmarketing studies. The rule mandates the creation of new sections and subsections in drug labeling that describe current information on pregnancy, lactation, and reproductive risks. This information will eventually replace the A, B, C, D, and X pregnancy category designations that FDA established in 1979. Under that system, drugs in category A are generally considered well studied and safe throughout pregnancy,
and drugs in category X are contraindicated during pregnancy. For drugs in the other categories, animal or human studies describe some potential for fetal harm, and clinicians should weigh this data when considering whether to prescribe the drugs. FDA now says these designations are confusing, overly simplistic, and ineffective at communicating risk information to pregnant women. Kweder said these limitations apply even to drugs assigned to pregnancy category X. For example, she said, many hormonal contraceptives were designated as category X drugs not because they cause birth defects but because there is no reason for a pregnant woman to use a hormonal contraceptive. Philip Anderson, health sciences clinical professor of pharmacy at the University of California, San Diego (UCSD), Skaggs School of Pharmacy and Pharmaceutical Sciences, said the letterbased system doesn’t differentiate among adverse effects during different stages of pregnancy or consider why a woman wants information about a drug’s reproductive effects. For example, he said, does the woman want to know whether to continue to take a medication during pregnancy, or does she want information about the effects of exposure before she knew she was pregnant? Anderson called the pregnancy category letters “really useless.” “I tell my students to just ignore them,” he said. Anderson said the pregnancy category for a drug is generally decided during the approval process for the drug product and not changed afterward. For newer drugs, the pregnancy category may be based on
postmarketing information from an older drug in the class—information that was never incorporated into the older drug’s labeling. This can result in inconsistent use of the pregnancy categories. The benzodiazepine triazolam, for example, is classified into pregnancy category X on the basis of studies that found an increased risk of birth defects after fetal exposure to diazepam and chlordiazepoxide. But diazepam is in pregnancy category D, and labeling for chlordiazepoxide, a decades-old drug, doesn’t include a pregnancy category. Teratology organizations have recommended for decades that FDA scrap the lettered pregnancy categories in favor of narrative summaries of risk information gleaned from clinical research. Lynn Martinez, senior teratogen information specialist with MotherToBaby Utah, a service of the nonprofit Organization of Teratology Information Specialists, said that the C, D, and X designations are overused. “At least 80% of [medications] should be A’s or B’s, since they’re well studied and they don’t cause birth defects. But they don’t get upgraded,” she said. She suggested that categorizing drugs as C, D, or X agents provides “legal coverage” for companies if they are later faced with a lawsuit related to a birth defect. Martinez said FDA’s new system for providing pregnancy information should better serve clinicians and patients and could, through the inclusion of pregnancy registry information, result in better data on medication use during pregnancy. “We would really like to see as much research as possible in this area,” Martinez said. “The vast majority of research that’s done in teratology is still done in animal models, and it tends not to be very helpful for us, because animal models have
Am J Health-Syst Pharm—Vol 72 Feb 1, 2015
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News
very rarely predicted human experience as far as teratogenicity is concerned.” Martinez noted that students at the University of Utah College of Pharmacy can learn about teratology and issues of concern to pregnant and breastfeeding women by completing a six-week rotation at MotherToBaby Utah. About 30 students participate in the rotation each year, she said. UCSD’s Anderson, the author of the monographs in the National Library of Medicine’s online Drugs and Lactation Database (LactMed), said the new labeling format should provide “a lot more information” about lactation. He noted that women are interested not just in whether a drug is found in breast milk but also how a drug affects the milk supply; both issues are addressed in the final rule. The lactation section of the labeling also requires manufacturers to evaluate information about how exposure to a drug in breast milk affects infants of different ages. “Something like 80% of adverse reactions occur in infants two months or younger, and most of those are in the first month,” Anderson said. “A drug that could be a problem for a newborn could be not a problem at all for a fourmonth-old or a six-month-old. And then it all depends, too, on if she’s exclusively breastfeeding her infant or is partially formula feeding, because that will de-
Appointments FDA made the following appointments to its Pharmacy Compounding Advisory Committee: Gigi S. Davidson, B.S.Pharm., DICVP, Robert DeChristoforo, M.S., FASHP, William A. Humphrey, B.S.Pharm., and Allen J. Vaida, Pharm.D., FASHP. Davidson is the director of clinical pharmacy services at North Carolina State University College of Veterinary Medicine in Raleigh. DeChristoforo is chief of the Clinical Center pharmacy department at the National Institutes of Health in Bethesda, Maryland. Humphrey is the director of pharmacy operations at St. Jude Children’s Research Hospital in Memphis. Vaida is executive vice president of the Institute for Safe Medication Practices in Horsham, Pennsylvania.
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crease the dose of the drug that the baby’s getting.” The rule goes into effect June 30, and labeling for all drugs and biologicals whose application for approval is filed with FDA after that date must use the new format. Manufacturers of drugs and biologicals whose applications are filed before June 30 have four years to develop labeling that meets the new requirements. For drugs approved since June 30, 2001, manufacturers have three to five
years to revise the content and format of the labeling to include new sections on pregnancy, lactation, and reproductive risks. Manufacturers of products that were approved before June 30, 2001, have three years from the rule’s effective date to remove the pregnancy category designations from product labeling. —Kate Traynor DOI 10.2146/news150008
Know what’s in airplane’s emergency medical kit, two pharmacists say
A
s two pharmacists learned on a recent trip, domestic passengercarrying airplanes with a flight attendant also have onboard an emergency medical kit with a small assortment of medications and supplies. The Federal Aviation Administration (FAA) has required such a kit since 1986. Since 2004, this kit (see sidebar on page 178) at a minimum has contained several medications in addition to the originally required 50% dextrose injection, epinephrine injection 1 mg/mL, diphenhydramine injection, and nitroglycerin tablets. That was also the year by which airplanes with a capacity of at least 30 passengers had to start carrying an automated external defibrillator (AED). FAA in addition requires the airlines to ensure that each crewmember receives training for in-flight medical events. Some of that training was put to the test this past December, after a passenger lost consciousness on a United Airlines flight from Houston to Los Angeles. DeeDee Hu, a clinical specialist in critical care at Memorial Hermann Memorial City Medical Center in DeeDee Hu
Am J Health-Syst Pharm—Vol 72 Feb 1, 2015
Houston, said she reached the man ahead of the flight attendants, did not detect a pulse, and repositioned him across the row of coach-class seats in preparation for chest compressions. When he suddenly regained consciousness, albeit temporarily, Hu said she further assessed him and asked about his medical history. The flight attendants “immediately pulled out the AED,” said Sapana Desai, a clinical pharmacy specialist in emergency medicine at Memorial Hermann who, like Hu, happened to be Sapana Desai seated near the ill passenger. But the emergency medical kit did not surface until a physician asked for an i.v. set to infuse fluid, she said. The family practice physician and a nurse had responded to the overhead page for medical personnel. Before the physician arrived, however, Hu had called out for aspirin in case the man was having a myocardial infarction. “I didn’t know that they had this kit,” she said, “so my first thought was, let’s find someone on the plane with aspirin.” A passenger did provide a tablet of low-dose aspirin, Desai said, and the Continued on page 178
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 Changes coming to pregnancy labeling
F
DA officials say this year’s rollout of new requirements for pregnancy, lactation, and reproductive risk information in the labeling of prescription drugs is a major advance in public health. The so-called pregnancy and lactation labeling rule, which was proposed in 2008 and finalized this past December, requires that labeling reflect current knowledge about pregnancy, lactation, and reproductive risks associated with the drug’s use. The labeling will also direct women to pregnancy registries that have been established for specific drugs. “Clinicians will . . . be able to rely on FDA-approved drug labeling for comprehensive, clinically relevant, and user-friendly information in this part of labeling—something that has been missing for many years,” said Sandra Kweder, deputy director of the Office of New Drugs in FDA’s Center for Drug Evaluation and Research. Kweder said during a December 3 media briefing that drug manufacturers won’t be required to conduct new studies to assess pregnancy-related risks. But the rule requires manufacturers to evaluate medical literature that describes these risks and revise drug labeling accordingly. Kweder said most of the information will come from postmarketing studies. The rule mandates the creation of new sections and subsections in drug labeling that describe current information on pregnancy, lactation, and reproductive risks. This information will eventually replace the A, B, C, D, and X pregnancy category designations that FDA established in 1979. Under that system, drugs in category A are generally considered well studied and safe throughout pregnancy,
and drugs in category X are contraindicated during pregnancy. For drugs in the other categories, animal or human studies describe some potential for fetal harm, and clinicians should weigh this data when considering whether to prescribe the drugs. FDA now says these designations are confusing, overly simplistic, and ineffective at communicating risk information to pregnant women. Kweder said these limitations apply even to drugs assigned to pregnancy category X. For example, she said, many hormonal contraceptives were designated as category X drugs not because they cause birth defects but because there is no reason for a pregnant woman to use a hormonal contraceptive. Philip Anderson, health sciences clinical professor of pharmacy at the University of California, San Diego (UCSD), Skaggs School of Pharmacy and Pharmaceutical Sciences, said the letterbased system doesn’t differentiate among adverse effects during different stages of pregnancy or consider why a woman wants information about a drug’s reproductive effects. For example, he said, does the woman want to know whether to continue to take a medication during pregnancy, or does she want information about the effects of exposure before she knew she was pregnant? Anderson called the pregnancy category letters “really useless.” “I tell my students to just ignore them,” he said. Anderson said the pregnancy category for a drug is generally decided during the approval process for the drug product and not changed afterward. For newer drugs, the pregnancy category may be based on
postmarketing information from an older drug in the class—information that was never incorporated into the older drug’s labeling. This can result in inconsistent use of the pregnancy categories. The benzodiazepine triazolam, for example, is classified into pregnancy category X on the basis of studies that found an increased risk of birth defects after fetal exposure to diazepam and chlordiazepoxide. But diazepam is in pregnancy category D, and labeling for chlordiazepoxide, a decades-old drug, doesn’t include a pregnancy category. Teratology organizations have recommended for decades that FDA scrap the lettered pregnancy categories in favor of narrative summaries of risk information gleaned from clinical research. Lynn Martinez, senior teratogen information specialist with MotherToBaby Utah, a service of the nonprofit Organization of Teratology Information Specialists, said that the C, D, and X designations are overused. “At least 80% of [medications] should be A’s or B’s, since they’re well studied and they don’t cause birth defects. But they don’t get upgraded,” she said. She suggested that categorizing drugs as C, D, or X agents provides “legal coverage” for companies if they are later faced with a lawsuit related to a birth defect. Martinez said FDA’s new system for providing pregnancy information should better serve clinicians and patients and could, through the inclusion of pregnancy registry information, result in better data on medication use during pregnancy. “We would really like to see as much research as possible in this area,” Martinez said. “The vast majority of research that’s done in teratology is still done in animal models, and it tends not to be very helpful for us, because animal models have
Am J Health-Syst Pharm—Vol 72 Feb 1, 2015
175
News
very rarely predicted human experience as far as teratogenicity is concerned.” Martinez noted that students at the University of Utah College of Pharmacy can learn about teratology and issues of concern to pregnant and breastfeeding women by completing a six-week rotation at MotherToBaby Utah. About 30 students participate in the rotation each year, she said. UCSD’s Anderson, the author of the monographs in the National Library of Medicine’s online Drugs and Lactation Database (LactMed), said the new labeling format should provide “a lot more information” about lactation. He noted that women are interested not just in whether a drug is found in breast milk but also how a drug affects the milk supply; both issues are addressed in the final rule. The lactation section of the labeling also requires manufacturers to evaluate information about how exposure to a drug in breast milk affects infants of different ages. “Something like 80% of adverse reactions occur in infants two months or younger, and most of those are in the first month,” Anderson said. “A drug that could be a problem for a newborn could be not a problem at all for a fourmonth-old or a six-month-old. And then it all depends, too, on if she’s exclusively breastfeeding her infant or is partially formula feeding, because that will de-
Appointments FDA made the following appointments to its Pharmacy Compounding Advisory Committee: Gigi S. Davidson, B.S.Pharm., DICVP, Robert DeChristoforo, M.S., FASHP, William A. Humphrey, B.S.Pharm., and Allen J. Vaida, Pharm.D., FASHP. Davidson is the director of clinical pharmacy services at North Carolina State University College of Veterinary Medicine in Raleigh. DeChristoforo is chief of the Clinical Center pharmacy department at the National Institutes of Health in Bethesda, Maryland. Humphrey is the director of pharmacy operations at St. Jude Children’s Research Hospital in Memphis. Vaida is executive vice president of the Institute for Safe Medication Practices in Horsham, Pennsylvania.
176
crease the dose of the drug that the baby’s getting.” The rule goes into effect June 30, and labeling for all drugs and biologicals whose application for approval is filed with FDA after that date must use the new format. Manufacturers of drugs and biologicals whose applications are filed before June 30 have four years to develop labeling that meets the new requirements. For drugs approved since June 30, 2001, manufacturers have three to five
years to revise the content and format of the labeling to include new sections on pregnancy, lactation, and reproductive risks. Manufacturers of products that were approved before June 30, 2001, have three years from the rule’s effective date to remove the pregnancy category designations from product labeling. —Kate Traynor DOI 10.2146/news150008
Know what’s in airplane’s emergency medical kit, two pharmacists say
A
s two pharmacists learned on a recent trip, domestic passengercarrying airplanes with a flight attendant also have onboard an emergency medical kit with a small assortment of medications and supplies. The Federal Aviation Administration (FAA) has required such a kit since 1986. Since 2004, this kit (see sidebar on page 178) at a minimum has contained several medications in addition to the originally required 50% dextrose injection, epinephrine injection 1 mg/mL, diphenhydramine injection, and nitroglycerin tablets. That was also the year by which airplanes with a capacity of at least 30 passengers had to start carrying an automated external defibrillator (AED). FAA in addition requires the airlines to ensure that each crewmember receives training for in-flight medical events. Some of that training was put to the test this past December, after a passenger lost consciousness on a United Airlines flight from Houston to Los Angeles. DeeDee Hu, a clinical specialist in critical care at Memorial Hermann Memorial City Medical Center in DeeDee Hu
Am J Health-Syst Pharm—Vol 72 Feb 1, 2015
Houston, said she reached the man ahead of the flight attendants, did not detect a pulse, and repositioned him across the row of coach-class seats in preparation for chest compressions. When he suddenly regained consciousness, albeit temporarily, Hu said she further assessed him and asked about his medical history. The flight attendants “immediately pulled out the AED,” said Sapana Desai, a clinical pharmacy specialist in emergency medicine at Memorial Hermann who, like Hu, happened to be Sapana Desai seated near the ill passenger. But the emergency medical kit did not surface until a physician asked for an i.v. set to infuse fluid, she said. The family practice physician and a nurse had responded to the overhead page for medical personnel. Before the physician arrived, however, Hu had called out for aspirin in case the man was having a myocardial infarction. “I didn’t know that they had this kit,” she said, “so my first thought was, let’s find someone on the plane with aspirin.” A passenger did provide a tablet of low-dose aspirin, Desai said, and the Continued on page 178
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.
