Letters
pathway is not applicable for the approval of NBCD follow-on products. Therapeutic equivalence should be evaluated by a “biosimilarlike” approach including nonclinical and clinical tests. The challenge of substitution with NBCD follow-on compounds has been exemplified with comparative clinical and nonclinical data of the originator product iron sucrose (Venofer, American Regent, Shirley, NY), a well-established i.v. iron complex used to treat iron deficiency and anemia, and different follow-on preparations (iron sucrose similars). 2-6 The first clinical evidence showing that iron sucrose similar products are not therapeutically equivalent to the originator product was found in stable, hemodialysis-dependent patients with chronic kidney disease.3 After being switched from the iron sucrose originator to an iron sucrose similar product, patients’ hemoglobin levels decreased rapidly, and anemia medication dosages needed to be increased. Since then, further reports showed a higher risk of adverse reactions to an iron sucrose similar product compared with the originator,4 even in patients who previously tolerated the originator.5 Nonclinical comparisons of originator iron sucrose and different iron sucrose similar products showed significant off-target iron disposition from the similar products as well as associated induction of oxidative stress and inflammation markers that may explain the different tolerability profiles.6 Notably, in two of the abovementioned reports,3,5 iron sucrose preparations were substituted by the pharmacist without informing the prescribing physician. Since substitution is common practice with approved generics, reports citing clinical differences between different iron sucrose preparations confirm the need for comparative clinical tests to prove therapeutic equivalence and safety comparability of follow-on NBCDs with reference products before granting market approval. Driven by the evidence about differences between originator and follow-on products, the European Medicines Agency and the Food and Drug Administra-
1880
tion independently drafted guidance on iron nanoparticles.7,8 Overall, a better understanding of NBCDs and the clinical implications of interchange and substitution is warranted. Substitution of NBCDs without involvement of the prescribing physicians is discouraged. 1. Schellekens H, Klinger E, Mühlebach S et al. The therapeutic equivalence of complex drugs. Regul Toxicol Pharmacol. 2011; 59:176-83. 2. Borchard G, Flühmann B, Mühlebach S. Nanoparticle iron medicinal products— requirements for approval of intended copies of non-biological complex drugs (NBCD) and the importance of clinical comparative studies. Regul Toxicol Pharmacol. 2012; 64:324-8. 3. Rottembourg J, Kadri A, Leonard E et al. Do two intravenous iron sucrose preparations have the same efficacy? Nephrol Dial Transplant. 2011; 26:3262-7. 4. Lee ES, Park BR, Kim JS et al. Comparison of adverse event profile of intravenous iron sucrose and iron sucrose similar in postpartum and gynecologic operative patients. Curr Med Res Opin. 2013; 29:141-7. 5. Stein J, Dignass A, Chow KU. Clinical case reports raise doubts about the therapeutic equivalence of an iron sucrose similar preparation compared with iron sucrose originator. Curr Med Res Opin. 2012; 28:241-3. 6. Toblli JE, Cao G, Oliveri L et al. Differences between original intravenous iron sucrose and iron sucrose similar preparations. Drug Res. 2009; 59:176-90. 7. European Medicines Agency. Reflection paper on non-clinical studies for generic nanoparticle iron medicinal product applications. www.ema.europa.eu/docs/ en_GB/document_library/Scientific_ guideline/2011/04/WC500105048.pdf (accessed 2012 Aug 17). 8. Food and Drug Administration. Draft guidance on iron sucrose (Mar 2012). w w w. f d a . g o v / d ow n l o a d s / D r u g s /
GuidanceComplianceRegulator y Information/Guidances/UCM297630.pdf (accessed 2013 May 20).
Vinod P. Shah, Ph.D., Pharmaceutical Consultant North Potomac, MD Arnold G. Vulto, Ph.D., Professor of Hospital Pharmacy and Practical Therapeutics and Deputy Head, Hospital Pharmacy Erasmus University Medical Center Rotterdam, Netherlands Stefan Mühlebach, Ph.D., Scientific Director Vifor Pharma Ltd. Flughofstrasse 61 P.O. Box CH-8152 Glattbrugg, Switzerland [email protected]
Dr. Shah is Steering Committee Member of the Non-Biological Complex Drugs Working Group, Regulatory Sciences Special Interest Group of the International Pharmaceutical Federation. Dr. Mühlebach is Chair and Steering Committee Member of the Non-Biological Complex Drugs Working Group. Medical writing support by SFL Regulatory Affairs and Scientific Communication, Basel, Switzerland (funded by Vifor Pharma). Dr. Mühlebach is an employee of Vifor Pharma Ltd. The authors have declared no other potential conflicts of interest. DOI 10.2146/ajhp130141
An interdisciplinary approach to determine schistosomiasis prevalence and administer praziquantel to school-age children in Tanzania
F
our students at the James L. Winkle College of Pharmacy, accompanied by a faculty member, traveled to Tanzania on an elective ambulatory care advanced pharmacy practice experience rotation to learn, provide care, and implement
Am J Health-Syst Pharm—Vol 70 Nov 1, 2013
a schistosomiasis project in the village of Burere. We were part of a Village Life Outreach Project team that also included a U.S.-trained physician, an internal medicine resident, two nursing students, a nursing faculty member, and translators.
Letters
Risk Factors and Treatment Status of Children Screened for Schistosomiasis No. Pts Risk Factora
Treated, With No Adverse Event (n = 22)
Treated, With Adverse Event (n = 30)
Untreated (n = 53)
Untreated, With Contraindication (n = 15)
Total No. Pts (%)
Swimming Washing clothes Playing Drinking Bathing Fishing
7 16 8 15 16 2
9 17 9 13 15 3
24 36 14 29 35 6
6 6 4 6 7 0
46 (38) 75 (63) 35 (29) 63 (53) 73 (61) 11 (9)
Risk factors based on potential exposure to infested water; several children had multiple risk factors.
a
School-age children were targeted for this project, in accordance with World Health Organization recommendations, because cyclic treatment in this population may decrease reinfection rates and symptom severity if the child becomes reinfected.1-3 Among school children in the village of Burere, located on the shore of Lake Victoria, the largest identifiable risk factor for schistosomiasis is living close to a freshwater source. Cercariae in the water, when encountering a human host, enter the body and reproduce, causing significant local tissue damage and blood loss by becoming lodged in various tissues and organs. Chronic schistosomiasis infection can lead to hematuria, anemia, decreased fertility, kidney failure, increased risk of bladder cancer, and complications related to liver enlargement.2-5 The aim of current prevention and treatment strategies is to control morbidity associated with chronic schistosomiasis infection and to provide disease-free growth periods to young children.2,6-8 Age-targeted drug delivery, which was the intervention in our project, has been shown to act immediately and have a positive effect on decreasing early and late morbidities of schistosomiasis. In our project, all children who were screened for treatment were asked a series of questions to assess their risk factors for schistosomiasis. Urine samples were also collected from all children before treatment in order to determine the baseline rate of infection. Our analysis revealed that 96% of samples tested positive for schistosomiasis.
The results of our project are presented in the table. The treatment for our project was praziquantel 40 mg/kg orally as a single treatment dose, which will be repeated annually. Praziquantel was used because it is effective as a single dose and has proven to be safe in many patients, including those who are pregnant.2,4 Still, it has adverse effects, which mimic the actual infection, including nausea, abdominal pain, and diarrhea. These adverse
events are transient, related to infection intensity or parasite burden, and more common after the initial treatment.3 If the child assented to the medication, the praziquantel dose was calculated, double-checked for accuracy by a second person, and administered. If the child did not agree, no medication was administered. Due to the known gasContinued on page 1882
Am J Health-Syst Pharm—Vol 70 Nov 1, 2013
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Letters Continued from page 1881
trointestinal adverse events, the children were fed uji (a local food) in the morning before they were screened. The cost to test 124 children and treat all 52 children with informed consent was $329.76. An adverse event occurred in 42% of the treated children, the most common of which was nausea. One child experienced one episode of vomiting. Of those who experienced an adverse event, 82% reported either stomach pain or blood in the urine before medication administration. Data will be tracked in the future to more fully evaluate reinfection rates, treatment-related costs, and adverse events. 1. Norman FF, Perez de Ayala A, PerezMolina JA et al. Neglected tropical diseases outside the tropics. PLoS Negl Trop Dis. 2010; 4:e762. 2. World Health Organization. Preventive chemotherapy in human helminthiasis. http://whqlibdoc.who.int/publications/ 2006/9241547103_eng.pdf (accessed 2012 Aug 9). 3. Croce D, Porazzi E, Foglia E et al. Costeffectiveness of a successful schistosomiasis control programme in Cambodia (1995–2006). Acta Trop. 2010; 113:279-84. 4. Fenwick A, Rollinson D, Southgate V. Implementation of human schistosomia-
sis control: challenges and prospects. Adv Parasitol. 2006; 61:567-622. 5. King CH. Parasites and poverty: the case of schistosomiasis. Acta Trop. 2010; 113:95-104. 6. Garba A, Toure S, Dembele R et al. Present and future schistosomiasis control activities with support from the Schistosomiasis Control Initiative in West Africa. Parasitology. 2009; 136:1731-7. 7. Wang LD, Guo JG, Wu XH et al. China’s new strategy to block Schistosoma japonicum transmission: experiences and impact beyond schistosomiasis. Trop Med Int Health. 2009; 14:1475-83. 8. Utzinger J, Bergquist R, Olveda R et al. Important helminth infections in southeast Asia: diversity, potential for control and prospects for elimination. Adv Parasitol. 2010; 72:1-30.
Andrew Jarrell, Pharm.D., Clinical Pharmacy Specialist, Surgical Intensive Care The Johns Hopkins Hospital 600 North Wolfe Street, Carnegie 180 Baltimore, MD 21287 [email protected] Jaclyn Kawsky, Pharm.D., Pharmacist School of Pharmacy University of Southern California Los Angeles, CA
Sasha Voss, Pharm.D., Night Pharmacist CVS/Caremark Silverton, OH Rajat Madan, M.D., Ph.D., Fellow Department of Infectious Diseases and International Health University of Virginia Charlottesville, VA Tina Weitkamp, M.S.N., RNC, Associate Professor of Clinical Nursing and Director, International Affairs College of Nursing University of Cincinnati Cincinnati, OH Patricia Wigle, Pharm.D., BCPS, Associate Professor Division of Pharmacy Practice and Administrative Sciences James L. Winkle College of Pharmacy University of Cincinnati Cincinnati, OH
The authors have declared no potential conflicts of interest. DOI 10.2146/ajhp120507
Tara Johnson, Pharm.D., Pharmacy Manager CVS Pharmacy Cincinnati, OH
Statement of Ownership, Management and Circulation (Required by 39 U.S.C. 3685) 1. Title of publication, American Journal of HealthSystem Pharmacy. 2. Publication No. 1079-2082. 3. Date of filing, October 1, 2013. 4. Frequency of issue, Twice monthly. 5. No. issues published annually, 24. 6. Annual subscription price, $341.00. 7. Location of known office of publication, 7272 Wisconsin Avenue, Bethesda, Montgomery County, MD 20814-4836. 8. Location of the headquarters or general business offices of publishers, 7272 Wisconsin Avenue, Bethesda, MD 20814-4836. 9. Publisher, American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, MD 20814-4836. Editor in Chief, C. Richard Talley, 7272 Wisconsin Avenue, Bethesda, MD 20814-4836. 10. Owner, American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, MD 20814-4836. 11. Known bondholders, mortgagees, and other security holders owning 1% or more of total amount of bonds, mortgages, and other securities, None. 12. For completion by nonprofit organizations authorized to mail at special rates (Section 132.122, PSM). The purpose, function, and nonprofit status of this organization and the exempt status for federal income tax purposes have not changed during preceding 12 months. 13. Publication name, American Journal of Health-System Pharmacy. 14. Issue date for circulation data below, 9/15/2013. 15. Extent and nature of circulation, A. Total no. copies printed, 35,236/34,140*; B. Paid circulation, 1. Sales through dealers and carriers, street vendors, and counter sales, 300/0. 2. Paid or requested mail subscriptions, 34,135/33,446; C. Total paid or requested circulation, 34,435/33,446; D. Free distribution by mail, 505/181; E. Free distribution outside the mail, 0/0. F. Total free distribution, 474/184. G. Total distribution, 34,909/33,630; H. Copies not distributed, 1. Office use, left over, spoiled, 327/510. 2. Returns from news agents, 0, 0; I. Total, 35,236/34,140. Percent paid circulation, 98.6/99.5. I certify that the statements made by me are correct and complete, signed C. Richard Talley. *First figure, average no. copies of each issue during preceding 12 months; second figure, actual no. copies of single issue published nearest to filing date.
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Am J Health-Syst Pharm—Vol 70 Nov 1, 2013
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.
pathway is not applicable for the approval of NBCD follow-on products. Therapeutic equivalence should be evaluated by a “biosimilarlike” approach including nonclinical and clinical tests. The challenge of substitution with NBCD follow-on compounds has been exemplified with comparative clinical and nonclinical data of the originator product iron sucrose (Venofer, American Regent, Shirley, NY), a well-established i.v. iron complex used to treat iron deficiency and anemia, and different follow-on preparations (iron sucrose similars). 2-6 The first clinical evidence showing that iron sucrose similar products are not therapeutically equivalent to the originator product was found in stable, hemodialysis-dependent patients with chronic kidney disease.3 After being switched from the iron sucrose originator to an iron sucrose similar product, patients’ hemoglobin levels decreased rapidly, and anemia medication dosages needed to be increased. Since then, further reports showed a higher risk of adverse reactions to an iron sucrose similar product compared with the originator,4 even in patients who previously tolerated the originator.5 Nonclinical comparisons of originator iron sucrose and different iron sucrose similar products showed significant off-target iron disposition from the similar products as well as associated induction of oxidative stress and inflammation markers that may explain the different tolerability profiles.6 Notably, in two of the abovementioned reports,3,5 iron sucrose preparations were substituted by the pharmacist without informing the prescribing physician. Since substitution is common practice with approved generics, reports citing clinical differences between different iron sucrose preparations confirm the need for comparative clinical tests to prove therapeutic equivalence and safety comparability of follow-on NBCDs with reference products before granting market approval. Driven by the evidence about differences between originator and follow-on products, the European Medicines Agency and the Food and Drug Administra-
1880
tion independently drafted guidance on iron nanoparticles.7,8 Overall, a better understanding of NBCDs and the clinical implications of interchange and substitution is warranted. Substitution of NBCDs without involvement of the prescribing physicians is discouraged. 1. Schellekens H, Klinger E, Mühlebach S et al. The therapeutic equivalence of complex drugs. Regul Toxicol Pharmacol. 2011; 59:176-83. 2. Borchard G, Flühmann B, Mühlebach S. Nanoparticle iron medicinal products— requirements for approval of intended copies of non-biological complex drugs (NBCD) and the importance of clinical comparative studies. Regul Toxicol Pharmacol. 2012; 64:324-8. 3. Rottembourg J, Kadri A, Leonard E et al. Do two intravenous iron sucrose preparations have the same efficacy? Nephrol Dial Transplant. 2011; 26:3262-7. 4. Lee ES, Park BR, Kim JS et al. Comparison of adverse event profile of intravenous iron sucrose and iron sucrose similar in postpartum and gynecologic operative patients. Curr Med Res Opin. 2013; 29:141-7. 5. Stein J, Dignass A, Chow KU. Clinical case reports raise doubts about the therapeutic equivalence of an iron sucrose similar preparation compared with iron sucrose originator. Curr Med Res Opin. 2012; 28:241-3. 6. Toblli JE, Cao G, Oliveri L et al. Differences between original intravenous iron sucrose and iron sucrose similar preparations. Drug Res. 2009; 59:176-90. 7. European Medicines Agency. Reflection paper on non-clinical studies for generic nanoparticle iron medicinal product applications. www.ema.europa.eu/docs/ en_GB/document_library/Scientific_ guideline/2011/04/WC500105048.pdf (accessed 2012 Aug 17). 8. Food and Drug Administration. Draft guidance on iron sucrose (Mar 2012). w w w. f d a . g o v / d ow n l o a d s / D r u g s /
GuidanceComplianceRegulator y Information/Guidances/UCM297630.pdf (accessed 2013 May 20).
Vinod P. Shah, Ph.D., Pharmaceutical Consultant North Potomac, MD Arnold G. Vulto, Ph.D., Professor of Hospital Pharmacy and Practical Therapeutics and Deputy Head, Hospital Pharmacy Erasmus University Medical Center Rotterdam, Netherlands Stefan Mühlebach, Ph.D., Scientific Director Vifor Pharma Ltd. Flughofstrasse 61 P.O. Box CH-8152 Glattbrugg, Switzerland [email protected]
Dr. Shah is Steering Committee Member of the Non-Biological Complex Drugs Working Group, Regulatory Sciences Special Interest Group of the International Pharmaceutical Federation. Dr. Mühlebach is Chair and Steering Committee Member of the Non-Biological Complex Drugs Working Group. Medical writing support by SFL Regulatory Affairs and Scientific Communication, Basel, Switzerland (funded by Vifor Pharma). Dr. Mühlebach is an employee of Vifor Pharma Ltd. The authors have declared no other potential conflicts of interest. DOI 10.2146/ajhp130141
An interdisciplinary approach to determine schistosomiasis prevalence and administer praziquantel to school-age children in Tanzania
F
our students at the James L. Winkle College of Pharmacy, accompanied by a faculty member, traveled to Tanzania on an elective ambulatory care advanced pharmacy practice experience rotation to learn, provide care, and implement
Am J Health-Syst Pharm—Vol 70 Nov 1, 2013
a schistosomiasis project in the village of Burere. We were part of a Village Life Outreach Project team that also included a U.S.-trained physician, an internal medicine resident, two nursing students, a nursing faculty member, and translators.
Letters
Risk Factors and Treatment Status of Children Screened for Schistosomiasis No. Pts Risk Factora
Treated, With No Adverse Event (n = 22)
Treated, With Adverse Event (n = 30)
Untreated (n = 53)
Untreated, With Contraindication (n = 15)
Total No. Pts (%)
Swimming Washing clothes Playing Drinking Bathing Fishing
7 16 8 15 16 2
9 17 9 13 15 3
24 36 14 29 35 6
6 6 4 6 7 0
46 (38) 75 (63) 35 (29) 63 (53) 73 (61) 11 (9)
Risk factors based on potential exposure to infested water; several children had multiple risk factors.
a
School-age children were targeted for this project, in accordance with World Health Organization recommendations, because cyclic treatment in this population may decrease reinfection rates and symptom severity if the child becomes reinfected.1-3 Among school children in the village of Burere, located on the shore of Lake Victoria, the largest identifiable risk factor for schistosomiasis is living close to a freshwater source. Cercariae in the water, when encountering a human host, enter the body and reproduce, causing significant local tissue damage and blood loss by becoming lodged in various tissues and organs. Chronic schistosomiasis infection can lead to hematuria, anemia, decreased fertility, kidney failure, increased risk of bladder cancer, and complications related to liver enlargement.2-5 The aim of current prevention and treatment strategies is to control morbidity associated with chronic schistosomiasis infection and to provide disease-free growth periods to young children.2,6-8 Age-targeted drug delivery, which was the intervention in our project, has been shown to act immediately and have a positive effect on decreasing early and late morbidities of schistosomiasis. In our project, all children who were screened for treatment were asked a series of questions to assess their risk factors for schistosomiasis. Urine samples were also collected from all children before treatment in order to determine the baseline rate of infection. Our analysis revealed that 96% of samples tested positive for schistosomiasis.
The results of our project are presented in the table. The treatment for our project was praziquantel 40 mg/kg orally as a single treatment dose, which will be repeated annually. Praziquantel was used because it is effective as a single dose and has proven to be safe in many patients, including those who are pregnant.2,4 Still, it has adverse effects, which mimic the actual infection, including nausea, abdominal pain, and diarrhea. These adverse
events are transient, related to infection intensity or parasite burden, and more common after the initial treatment.3 If the child assented to the medication, the praziquantel dose was calculated, double-checked for accuracy by a second person, and administered. If the child did not agree, no medication was administered. Due to the known gasContinued on page 1882
Am J Health-Syst Pharm—Vol 70 Nov 1, 2013
1881
Letters Continued from page 1881
trointestinal adverse events, the children were fed uji (a local food) in the morning before they were screened. The cost to test 124 children and treat all 52 children with informed consent was $329.76. An adverse event occurred in 42% of the treated children, the most common of which was nausea. One child experienced one episode of vomiting. Of those who experienced an adverse event, 82% reported either stomach pain or blood in the urine before medication administration. Data will be tracked in the future to more fully evaluate reinfection rates, treatment-related costs, and adverse events. 1. Norman FF, Perez de Ayala A, PerezMolina JA et al. Neglected tropical diseases outside the tropics. PLoS Negl Trop Dis. 2010; 4:e762. 2. World Health Organization. Preventive chemotherapy in human helminthiasis. http://whqlibdoc.who.int/publications/ 2006/9241547103_eng.pdf (accessed 2012 Aug 9). 3. Croce D, Porazzi E, Foglia E et al. Costeffectiveness of a successful schistosomiasis control programme in Cambodia (1995–2006). Acta Trop. 2010; 113:279-84. 4. Fenwick A, Rollinson D, Southgate V. Implementation of human schistosomia-
sis control: challenges and prospects. Adv Parasitol. 2006; 61:567-622. 5. King CH. Parasites and poverty: the case of schistosomiasis. Acta Trop. 2010; 113:95-104. 6. Garba A, Toure S, Dembele R et al. Present and future schistosomiasis control activities with support from the Schistosomiasis Control Initiative in West Africa. Parasitology. 2009; 136:1731-7. 7. Wang LD, Guo JG, Wu XH et al. China’s new strategy to block Schistosoma japonicum transmission: experiences and impact beyond schistosomiasis. Trop Med Int Health. 2009; 14:1475-83. 8. Utzinger J, Bergquist R, Olveda R et al. Important helminth infections in southeast Asia: diversity, potential for control and prospects for elimination. Adv Parasitol. 2010; 72:1-30.
Andrew Jarrell, Pharm.D., Clinical Pharmacy Specialist, Surgical Intensive Care The Johns Hopkins Hospital 600 North Wolfe Street, Carnegie 180 Baltimore, MD 21287 [email protected] Jaclyn Kawsky, Pharm.D., Pharmacist School of Pharmacy University of Southern California Los Angeles, CA
Sasha Voss, Pharm.D., Night Pharmacist CVS/Caremark Silverton, OH Rajat Madan, M.D., Ph.D., Fellow Department of Infectious Diseases and International Health University of Virginia Charlottesville, VA Tina Weitkamp, M.S.N., RNC, Associate Professor of Clinical Nursing and Director, International Affairs College of Nursing University of Cincinnati Cincinnati, OH Patricia Wigle, Pharm.D., BCPS, Associate Professor Division of Pharmacy Practice and Administrative Sciences James L. Winkle College of Pharmacy University of Cincinnati Cincinnati, OH
The authors have declared no potential conflicts of interest. DOI 10.2146/ajhp120507
Tara Johnson, Pharm.D., Pharmacy Manager CVS Pharmacy Cincinnati, OH
Statement of Ownership, Management and Circulation (Required by 39 U.S.C. 3685) 1. Title of publication, American Journal of HealthSystem Pharmacy. 2. Publication No. 1079-2082. 3. Date of filing, October 1, 2013. 4. Frequency of issue, Twice monthly. 5. No. issues published annually, 24. 6. Annual subscription price, $341.00. 7. Location of known office of publication, 7272 Wisconsin Avenue, Bethesda, Montgomery County, MD 20814-4836. 8. Location of the headquarters or general business offices of publishers, 7272 Wisconsin Avenue, Bethesda, MD 20814-4836. 9. Publisher, American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, MD 20814-4836. Editor in Chief, C. Richard Talley, 7272 Wisconsin Avenue, Bethesda, MD 20814-4836. 10. Owner, American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, MD 20814-4836. 11. Known bondholders, mortgagees, and other security holders owning 1% or more of total amount of bonds, mortgages, and other securities, None. 12. For completion by nonprofit organizations authorized to mail at special rates (Section 132.122, PSM). The purpose, function, and nonprofit status of this organization and the exempt status for federal income tax purposes have not changed during preceding 12 months. 13. Publication name, American Journal of Health-System Pharmacy. 14. Issue date for circulation data below, 9/15/2013. 15. Extent and nature of circulation, A. Total no. copies printed, 35,236/34,140*; B. Paid circulation, 1. Sales through dealers and carriers, street vendors, and counter sales, 300/0. 2. Paid or requested mail subscriptions, 34,135/33,446; C. Total paid or requested circulation, 34,435/33,446; D. Free distribution by mail, 505/181; E. Free distribution outside the mail, 0/0. F. Total free distribution, 474/184. G. Total distribution, 34,909/33,630; H. Copies not distributed, 1. Office use, left over, spoiled, 327/510. 2. Returns from news agents, 0, 0; I. Total, 35,236/34,140. Percent paid circulation, 98.6/99.5. I certify that the statements made by me are correct and complete, signed C. Richard Talley. *First figure, average no. copies of each issue during preceding 12 months; second figure, actual no. copies of single issue published nearest to filing date.
1882
Am J Health-Syst Pharm—Vol 70 Nov 1, 2013
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.
