Quality of Vancomycin for Injection Formulations in Brazil

Author(s): Gabriela Secco, Cristiane Sachetti, Luciana Grazziotin Rossato-Grando, Siomara Regina Hahn, Lidiane Riva Pagnussat, Paula Maria Façanha da Cruz Fresco, Charise Dallazem Bertol*

Journal Name: Current Pharmaceutical Analysis

Volume 15 , Issue 3 , 2019

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Graphical Abstract:


Background: The presence of impurities in vancomycin compromised the safety and contributed to decrease of its use for years. In Brazil, vancomycin generic drug represents an option to reduce hospital costs. However, the controversy over the quality of these formulations and their relationship to effectiveness and safety raised concerns.

Objective and Methods: To assess in vitro quality of vancomycin injections through uniformity of weight, pH, clarity of solution, microbiological assay and impurities determination by High Performance Liquid Chromatography (HPLC).

Results: The samples were approved in the tests.

Conclusion: The injectable formulations of vancomycin proved to be safe for use in hospital environment. This work contributes to increase health professionals’ confidence on generic vancomycin.

Keywords: Generic, impurities, HPLC, injections, quality control, vancomycin.

Siddiqui, M.R.; AlOthman, Z.A.; Rahman, N. Analytical techniques in pharmaceutical analysis: A review. Arab. J. Chem., 2017, 10, S1409-S1421.
Rahman, N.; Azmi, S.N.H.; Wu, H.F. The importance of impurity analysis in pharmaceutical products: An integrated approach. Accredit. Qual. Assur., 2006, 11(1-2), 69-74.
Levine, D.P.. Vancomycin: A History. Clin. Infect. Dis., 2006, 42(Suppl. 1), S5-S12.
Moellering , Jr, R.C. Vancomycin: a 50-year reassessment. . Clin. Infect. Dis., 2006, 42( Suppl 1(Suppl 1)), S3-4.
Rodriguez, C.A.; Agudelo, M.; Cataño, J.C.; Zuluaga, A.F.; Vesga, O. Potential therapeutic failure of generic vancomycin in a liver transplant patient with MRSA peritonitis and bacteremia. J. Infect., 2009, 59(4), 277-280.
Vesga, O.; Agudelo, M.; Salazar, B.E.; Rodriguez, C.A.; Zuluaga, A.F. Generic vancomycin products fail in vivo despite being pharmaceutical equivalents of the innovator. Antimicrob. Agents Chemother., 2010, 54(8), 3271-3279.
Rodriguez, C.A.; Agudelo, M.; Zuluaga, A.F.; Vesga, O. Generic vancomycin enriches resistant subpopulations of Staphylococcus aureus after exposure in a neutropenic mouse thigh infection model. Antimicrob. Agents Chemother., 2012, 56(1), 243-247.
Jones, R.N.; Watters, A.A.; Flamm, R.K.; Sader, H.S. Comparative potencies of contemporary generic vancomycin lot: In vitro assay results from nine products and a reference reagent-grade sample. Diagn. Microbiol. Infect. Dis., 2013, 76(2), 237-238.
Monnier, A.; Malbranche, C.; Fagnoni, P.; Serge Aho, L.; Guerard, P.; Sgro, C.; Guignard, M.H.; Croisier-Bertin, D.; Chavanet, P.; Chrétien, M.L.; Caillot, D.; Boulin, M. Generic vancomycin products: Analysis of serum concentrations in patients with acute myeloid leukemia. Ann. Pharm. Françaises., 2014, 72(3), 178-183.
Sutton, J.D.; Mynatt, R.P.; Kaye, K.S.; Murray, K.P.; Rybak, M.J.; Pogue, J.M. Nephrotoxicity comparison of two commercially available generic vancomycin products. Antimicrob. Agents Chemother., 2015, 59(9), 5470-5474.
Nambiar, S.; Madurawe, R.D.; Zuk, S.M.; Khan, S.R.; Ellison, C.D.; Faustino, P.J.; Mans, D.J.; Trehy, M.L.; Hadwiger, M.E.; Boyne, M.T.; Biswas, K.; Cox, E.M. Product quality of parenteral vancomycin products in the United States. Antimicrob. Agents Chemother., 2012, 56(6), 2819-2823.
Hadwiger, M.E.; Sommers, C.D.; Mans, D.J.; Patel, V.; Boyne, M.T. Quality assessment of U.S. marketplace vancomycin for injection products using high-resolution liquid chromatography-mass spectrometry and potency assays. Antimicrob. Agents Chemother., 2012, 56(6), 2824-2830.
BRASIL. Ministério das Saúde. Agência Nacional de Vigilância Sanitária. Alerta ANVISA sobre a vancomicina carta circular no 06 GFARM/NUVIG/ANVISA/MS. http://www.saude.mt.gov.br/
upload/controle-infeccoes/pasta3/alerta_anvisa_vancomicina.pdf (Accessed on: Mar 12, 2015)
BRASIL. Ministério das Saúde. Agência Nacional de Vigilância Sanitária. Lista de Medicamentos Genéricos. http://portal.anvisa.gov.br/medicamentos-genericos-registrados (Accessed on: Jun 3, 2016).
WHO. How to Develop and Implement a Nacional Drug Policy, 2nd ed; Organization, W.H., Ed.; Geneva, 2001.
Midha, K.K.; Shah, V.P.; Amidon, G.; Barends, D.; Dressman, J.; Hubbard, J.; Junginger, H.; Patnaik, R.; Polli, J.; Stavchansky, S. Multisource (generic) pharmaceutical products: guidelines on registration requirements to establish interchangeability draft. WHO - World Health Organization Organisation Mondiale De La Sante. http://www.who.int/medicines/services/expertcommittees/pharmprep/QAS04_093Rev4_final.pdf [Accessed on: Jan 25, 2017].
BRASIL. Lei No 9.787, De 10 De Fevereiro De 1999, estabelece o medicamento genérico, dispõe sobre a utilização de nomes genéricos em produtos farmacêuticos e dá outras providências. http://www.camara.gov.br/sileg/integras/642202.pdf [Accessed on: Dec 12, 2016].
Fonseca, E.M. da; Shadlen, K.C. Promoting and regulating generic medicines: Brazil in comparative perspective. Rev. Panam. Salud Publica, 2017, 41, 1-6.
Bertoldi, A.D.; Arrais, P.S.D.; Tavares, N.U.L.; Ramos, L.R.; Luiza, V.L.; Mengue, S.S.; Dal-Pizzol, T. da S.; Farias, M.R.; Oliveira, M.A. Utilização de medicamentos genéricos na população brasileira: uma avaliação da PNAUM 2014. Rev. Saude Publica, 2016, 50(Suppl. 2), 1-11.
BRASIL Ministério das Saúde. Agência Nacional de Vigilância Sanitária. Farmacopéia Brasileira5th ed.; Anvisa, Ed.; Brasília, 2010, Vol. 1., .
The United States Pharmacopoeia. USP- UNITED STATES PHARMACOPOEIA NF 31 36th ed.; United States Pharmacopeia Convention, Ed.; Rockville, 2013.
Bailie, G.R.; Neal, D. Vancomycin ototoxicity and nephrotoxicity. A review. Med. Toxicol.Adverse Drug Exp., 1988, 3, 376-386.
Darko, W.; Medicis, J.J.; Smith, A.; Guharoy, R.; Lehmann, D.E. Mississippi mud no more: cost-effectiveness of pharmacokinetic dosage adjustment of vancomycin to prevent nephrotoxicity. Pharmacotherapy, 2003, 23(5), 643-650.
Elting, L.S.; Rubenstein, E.B.; Kurtin, D.; Rolston, K.V.; Fangtang, J.; Martin, C.; Raad, I.; Whimbey, E.; Manzullo, E.; Bodey, G.P. Mississippi mud in the 1990s: risks and outcomes of vancomycin-associated toxicity in general oncology practice. Cancer, 1988, 83(12), 2597-2607.
Rybak, M.; Lomaestro, B.; Rotschafer, J.C.; Moellering, Jr , R.; Craig, W.; Billeter, M.; Dalovisio, J.R.; Levine, D.P. Therapeutic monitoring of vancomycin in adult patients: A consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am. J. Heal. Pharm., 2009, 66(1), 82-98.
Esmerino, L.A.; Pereira, A.V.; Adamowicz, T.; Borges, D.M.; Talacimon, E.A.; Schelesky, M.E. Método microbiológico para determinação da potência de antimicrobianos. Publ. UEPG Ciênc. Biol. Saúde, 2004, 10(1), 53-60.

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Article Details

Year: 2019
Published on: 11 February, 2019
Page: [280 - 285]
Pages: 6
DOI: 10.2174/1573412914666180116143232
Price: $65

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