Alendronato de sódio, levotiroxina e inibidores da bomba de prótons: há interação entre eles?

Camila Tavares de  Sousa; Gabrielle Kéfrem Alves  Gomes; Janaina de Sousa Dias  Pichitelli; Marlon Silva Tinoco; Leonardo Régis Leira Pereira; Mariana Linhares  Pereira; André de Oliveira  Baldoni

doi:10.5712/rbmfc16(43)2486

Authors

Camila Tavares de Sousa Federal University of São João del Rei https://orcid.org/0000-0001-8946-1820
Gabrielle Kéfrem Alves Gomes Universidade Federal de São João del Rei
Janaina de Sousa Dias Pichitelli Universidade Federal de São João del Rei https://orcid.org/0000-0002-5219-5706
Marlon Silva Tinoco Universidade Federal de São João del-Rei https://orcid.org/0000-0002-5658-4434
Leonardo Régis Leira Pereira Faculdade de Ciências Farmacêuticas de Ribeirão Preto - Universidade de São Paulo (FCFRP-USP). Ribeirã Preto, São Paulo https://orcid.org/0000-0002-8609-1390
Mariana Linhares Pereira Universidade Federal de São João Del Rei https://orcid.org/0000-0002-3214-2789
André de Oliveira Baldoni Universidade Federal de São João Del Rei https://orcid.org/0000-0001-6379-0415

DOI:

https://doi.org/10.5712/rbmfc16(43)2486

Keywords:

Alendronate, Thyroxine, Proton Pump Inhibitors, Drug Development.

Abstract

Introduction: Drug interactions can alter safety and/or effectiveness in the treatment of diseases. Some medications need to be used on an empty stomach and the literature presents divergent information about the real clinical impact of using them at the same time. Objectives: To analyze the evidence on the clinical relevance of potential interactions between proton pump inhibitors, levothyroxine and sodium alendronate. Methods: A narrative review of articles available in the PubMed database was carried out, in addition to consulting potential drug interactions in sources of information on drugs available on the World Wide Web. Results: In only three of the 17 information sources consulted, a report was reported possible reduction in plasma levels and the effectiveness of levothyroxine, when administered concomitantly with omeprazole or another in the class. Only one source reports a slight reduction in plasma sodium alendronate levels due to interaction with levothyroxine, and only two sources show a possible reduction in the therapeutic effect of sodium alendronate through interaction with PPIs. Only two studies report significant results related to the existence of an interaction between levothyroxine or alendronate in concomitant use of PPIs. In all sources consulted, interactions are described as minor, mild, moderate or of unknown significance. All sources of information suggest the continuity of therapy to manage the interaction. Conclusion: To date, there is no robust evidence demonstrating that it is impossible to use proton pump inhibitors, levothyroxine and sodium alendronate at the same time, and it is essential to monitor clinical and laboratory parameters.

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References

(1) Tornio A, Filppula AM, Niemi M, Backman JT. Clinical studies on drug–drug interactions involving metabolism and transport: methodology, pitfalls, and interpretation. Clin Pharmacol Ther. 2019 Jun;105(6):1345-61. PMID: 30916389 DOI: https://doi.org/10.1002/cpt.1435

(2) Chong E, Kalia V, Willsie S, Winkle P. Drug-drug interactions between sucroferric oxyhydroxide and losartan, furosemide, omeprazole, digoxin and warfarin in healthy subjects. J Nephrol. 2014 Dez;27(6):659-66. DOI: https://doi.org/10.1007/s40620-014-0080-1

(3) Guidoni CM, Obreli-Neto PR, Régis L, Pereira L. Fontes de informações sobre interações medicamentosas: há concordância entre elas? Rev Univ Vale do Rio Verde. 2011 Ago/Dez;9(2):84-91. DOI: https://doi.org/10.5892/ruvrv.2011.92.8491

(4) Shamliyan TA, Middleton M, Borst C. Patient-centered outcomes with concomitant use of proton pump inhibitors and other drugs. Clin Ther. 2017 Fev;39(2):404-27. DOI: http://dx.doi.org/10.1016/j.clinthera.2017.01.011

(5) IBM Micromedex 2.0 (US). Web Applications Access [Internet]. Ann Arbor (MI): Truven Health Analytics Inc.; 2018. Available from: http://www.micromedexsolutions.com

(6) Drugs.com (US). Drugs interacrions checker [Internet]. Ann Arbor (MI): Drugs.com; 2021. Available from: https://www.drugs.com/drug_interactions.html

(7) Medscape (US). Drug interaction checker [Internet]. New York (NY): Medscape; 2021. Available from: https://reference.medscape.com/drug-interactionchecker

(8) P.R. Vade-mécum (BR). A nova era da prescrição médica [Internet]. São Paulo (SP): P.R. Vade-mécum; 2018. Available from: https://br.prvademecum.com/

(9) Wolters Kluwer Health (US). Homepage [Internet]. Waltham (MA): UpToDate, Inc.; 2020. Available from: https://www.uptodate.com/

(10) Agência Nacional de Vigilância Sanitária (ANVISA). Bulário eletrônico [Internet]. Brasília (DF): ANVISA; 2007. Available from: https://www.anvisa.gov.br/datavisa/fila_bula/index.asp

(11) U.S. Food and Drug Administration (FDA). Medication guides [Internet]. Silver Spring (MD): FDA; 2020. Available from: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=medguide.page

(12) Alendronate: drug information [Internet]. UpToDate. 2020. Available from: https://www.uptodate.com/

(13) Omeprazole: drug information [Internet]. UpToDate. 2020. Available from: https://www.uptodate.com/

(14) Synthroid: levothyroxine sodium [bula de remédio da Internet]. Chicago (IL): ABBOTT Laboratories; 2005. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021402s011lbl.pdf

(15) Synthroid [bula de remédio]. São Paulo (SP): ABBOTT Laboratório do Brasil Ltda.; 2019.

(16) Victrix: omeprazol [bula de remédio]. Nova York: FARMASA; 2014.

(17) Pantozol: pantoprazol [bula de remédio]. Oranienburg: Takeda GmbH; 2018.

(18) Nexium: esomeprazol [bula de remédio]. Södertälje: AstraZeneca; 2009.

(19) Prazol: lansoprazol [bula de remédio]. Campinas (SP): Medley; 2005.

(20) Fosamax: alendronato de sódio [bula de remédio]. México (DF): Merck Sharp & Dohme Farmacêutica; 2012.

(21) Prilosec: omeprazole [bula de remédio da Internet]. Wilmington (DE): AstraZeneca Pharmaceuticals LP; 2012. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019810s096lbl.pdf PMID: 25721889

(22) Protonix: pantoprazole sodium [bula de remédio da Internet]. Konstanz: Pfizer; 2012. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020987s045lbl.pdf

(23) Nexium: ezomeprazole magnesium [bula de remédio da Internet]. Wilmington (DE): AstraZeneca Pharmaceuticals LP; 2014. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022101s014021957s017021153s050lbl.pdf

(24) Prevacid: ianzoprazol [bula de remédio da Internet]. Deerfield (IL): Takeda Pharmaceuticals America, Inc.; 2012. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020406s078-021428s025lbl.pdf

(25) Fosamax: alendronate sodium [bula de remédio da Internet]. México (DF): Merck Sharp & Dohme; 2012. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021575s017lbl.pdf

(26) Ananthakrishnan S, Braverman LE, Levin RM, Magnani B, Pearce EN. The effect of famotidine, esomeprazole, and ezetimibe on levothyroxine absorption. Thyroid. 2008 Mai;18(5):493-8. DOI: https://doi.org/10.1089/thy.2007.0381

(27) Dietrich JW, Gieselbrecht K, Holl RW, Boehm BO. Absorption kinetics of levothyroxine is not altered by proton-pump inhibitor therapy. Horm Metab Res [Internet]. 2006; [citado ANO Mês dia]; 38(1):57-9. Available from: https://pubmed.ncbi.nlm.nih.gov/16477543/ DOI: https://doi.org/10.1055/s-2006-924980

(28) Sachmechi I, Reich DM, Aninyei M, Wibowo F, Gupta G, Kim PJ. Effect of proton pump inhibitors on serum thyroid-stimulating hormone level in euthyroid patients treated with levothyroxine for hypothyroidism. Endocr Pract. 2007 Jul/Ago;13(4):345-9. DOI: https://doi.org/10.4158/EP.13.4.345

(29) Abi-Abib RC, Vaisman M. Is it necessary to increase the dose of levothyroxine in patients with hypothyroidism who use omeprazole?. Arq Bras Endocrinol Metabol. 2014;58(7):731-6. DOI: https://doi.org/10.1590/0004-2730000002997

(30) Bone HG, Walter MA, Hurley ME, Epstein S. Pharmacokinetics of coadministration of levothyroxine sodium and alendronate sodium new effervescent formulation. Osteoporos Int. 2017 Mai;28(5):1745-52. DOI: https://doi.org/10.1007/s00198-017-3941-331. Panico A, Lupoli GA, Fonderico F, Marciello F, Martinelli A, Assante R, et al. Osteoporosis and thyrotropin-suppressive therapy: reduced effectiveness of alendronate. Thyroid. 2019 Mai;19(5):437-42.

(31) Panico A, Lupoli GA, Fonderico F, Marciello F, Martinelli A, Assante R, et al. Osteoporosis and thyrotropin-suppressive therapy: reduced effectiveness of alendronate. Thyroid. 2019 Mai;19(5):437-42. DOI: https://doi.org/10.1089/thy.2008.0428

(32) Abrahamsen B, Eiken P, Eastell R. Proton pump inhibitor use and the antifracture efficacy of alendronate. Arch Intern Med. 2011 Jun;171(11):998-1004. PMID: 21321287 DOI: https://doi.org/10.1001/archinternmed.2011.20

(33) Pytlik M, Cegiela U, Nowiska B, Folwarczna J, Åliwiski L, Kaczmarczyk-Sedlak I, et al. Bone remodeling after administration of proton pump (H+/K+ -ATPase) inhibitors and alendronate in ovariectomized rats. Acta Pol Pharm. 2012 Jan/Fev;69(1):113-20.

(34) Cegieł U, Pytlik M, Folwarczna J, Miozga R, Piskorz S, Nowak D. Exercise prevented the lansoprazole-induced reduction of anti-osteoporotic efficacy of alendronate in androgen deficiency rats. Acta Pol Pharm. 2014 Mai/Jun;71(3):485-95.

(35) Pytlik M, Cegieła U, Folwarczna J, Nowińska B. Proton pump (H+/K+-ATPase) inhibitors weaken the protective effect of alendronate on bone mechanical properties in estrogen-deficient rats. Pharmacol Reports. 2012;64(3):625-34. DOI: https://doi.org/10.1016/S1734-1140(12)70858-7

(36) Roux C, Goldstein JL, Zhou X, Klemes A, Lindsay R. Vertebral fracture efficacy during risedronate therapy in patients using proton pump inhibitors. Osteoporos Int. 2012 Jan;23(1):277-84. PMID: 21365461 DOI: https://doi.org/10.1007/s00198-011-1574-5

(37) Hall SF, Wright NC, Wolinsky FD, Lou Y, Edmonds S, Roblin D, et al. The prevalence of overtreatment of osteoporosis: results from the PAADRN trial. Arch Osteoporos. 2018 Set;13(1):103. DOI: https://doi.org/10.1007/s11657-018-0517-

(38) Sanfélix-Gimeno G, Hurtado I, Sanfélix-Genovés J, Baixauli-Pérez C, Rodríguez-Bernal CL, Peiró S. Overuse and underuse of antiosteoporotic treatments according to highly influential osteoporosis guidelines: apopulation-based cross-sectional study in Spain. PLoS One. 2015 Ago;10(8):e135475. DOI: https://doi.org/10.1371/journal.pone.0135475

(39) Bach-Huynh TG, Nayak B, Loh J, Soldin S, Jonklaas J. Timing of levothyroxine administration affects serum thyrotropin concentration. J Clin Endocrinol Metab. 2009 Out;94(10):3905-12. DOI: https://doi.org/10.1210/jc.2009-0860

(40) Leite MOR. Tratamento da osteoporose pós-menopausa. Arq Bras Endocrinol Metabol. 1999 Dez;43(6):442-5. DOI: https://doi.org/10.1590/S0004-27301999000600009

(41) Rang HP, Ritter JM, Flower RJ, Henderson G. Rang & Dale - Farmacologia. 6a ed. São Paulo: Elsevier; 2008.

(42) Silva P. Farmacologia. 7ª ed. Rio de Janeiro: Guanabara; 2006.

(43) Heringa M, Van Der Heide A, Floor-Schreudering A, Smet PAGM, Bouvy ML. Better specification of triggers to reduce the number of drug interaction alerts in primary care. Int J Med Inform. 2018 Jan;109:96-102. DOI: https://doi.org/10.1016/j.ijmedinf.2017.11.005 PMID: 29195711