Chloroquine / Hydroxychloroquine: Pharmacological view of an old drug currently used in COVID-19 treatment
Yıl 2020,
Sayı: Special Issue on COVID 19, 204 - 215, 20.03.2020
Berna Terzioğlu Bebitoğlu
,
Elif Oğuz
,
Ajla Hodzic
Nebile Hatiboğlu
Özkan Kam
Öz
Drugs that have been proven to be significantly harmless, and whose pharmacokinetics and optimal dosage are well known are subject to re-research for new indications since drug repositioning studies have been accelerated. Today, clinically proven treatment or vaccine has yet to be established against SARS-CoV-2, which caused the pandemic. In the treatment of COVID-19 disease, the treatment potential of chloroquine and hydroxychloroquine has drawn considerable attention. In this review, pharmacokinetic and pharmacodynamic properties, the information about use and safety in special populations, and particularly data on efficacy and safety in SARS-CoV-2 infection regarding recent studies of chloroquine/hydroxychloroquine, an old drug that is currently used in the treatment of COVID-19 is presented. Although chloroquine / hydroxychloroquine ranks first in the treatment algorithms of COVID-19 disease, more randomized controlled clinical trials are also required.
Kaynakça
- 1. T.C. Sağlık Bakanlığı Halk Sağlığı Genel Müdürlüğü COVID-19(SARS-CoV-2 Enfeksiyonu) Rehberi. Bilim Kurulu Çalışması. Ankara; 14 Nisan 2020.
https://covid19bilgi.saglik.gov.tr/depo/rehberler/COVID-19_Rehberi.pdf
- 2. Zhou P, Yang XL, Wang XG et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270–73.
- 3. Wallace DJ. The history of antimalarials. Lupus. 1996;5(1):2–3.
- 4. Mates M, Nesher G, Zevin S. Quinines—past and present. Harefuah. 2007;146(7): 560–62.
- 5. Shippey EA, Wagler VD, Collamer AN. Hydroxychloroquine: An old drug with new relevance. Cleve Clin J Med. 2018;85(6):459–67.
- 6. Stoughton RB. Treatment of chronic lupus erythematosus with atabrine and chloroquine. Ill Med J. 1955;107(6):299–2.
- 7. Ducharme, J., Farinotti, R. Clinical Pharmacokinetics and Metabolism of Chloroquine. Clin-Pharmacokinet 1996;31:257–74. https://doi.org/10.2165/00003088-199631040-00003
- 8. Rand JH, Wu XX, Quinn AS et al. Hydroxychloroquine directly reduces the binding of antiphospholipid antibody-beta2-glycoprotein I complexes to phospholipid bilayers. Blood. 2008;112(5):1687–95.
- 9. McChesney EW. Animal toxicity and pharmacokinetics of hydroxychloroquine sulfate. Am J Med. 1983;75(1A):11–18.
- 10. Browning DJ. Pharmacology of Chloroquine and Hydroxychloroquine. In: Hydroxychloroquine and Chloroquine Retinopathy. New York:Springer, 2014; p. 35–63.
- 11. Tett SE, Cutler D J, Day RO et al. Bioavailability of hydroxychloroquine tablets in healthy volunteers. Br J Clin Pharmacol. 1989;27(6):771–79.
- 12. Gustafsson LL, Walker D, Alván G et al. Disposition of chloroquine in man after single intravenous and oral doses. Br J Clin Pharmacol. 1983;15(4):471–79.
- 13. FDA Approved Drug Products: Hydroxychloroquine Oral Tablet
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/009768Orig1s051lbl.pdf
- 14. Collins KP, Jackson KM, Gustafson DL. Hydroxychloroquine: A Physiologically-Based Pharmacokinetic Model in the Context of Cancer-Related Autophagy Modulation. J Pharmacol Exp Ther. 2018;365(3):447–59.
- 15. Munster T, Gibbs JP, Shen D et al. Hydroxychloroquine concentration-response relationships in patients with rheumatoid arthritis. Arthritis Rheum. 2002;46(6):1460–69.
- 16. Popert AJ. Chloroquine: a review. Rheumatol Rehabil. 1976;15(3):235–38.
- 17. Laaksonen AL, Koskiahde V, Juva K. Dosage of antimalarial drugs for children with juvenile rheumatoid arthritis and systemic lupus erythematosus. A clinical study with determination of serum concentrations of chloroquine and hydroxychloroquine. Scand J Rheumatol. 1974;3(2):103–8.
- 18. Furst DE, Pharmacokinetics of hydroxychloroquine and chloroquine during treatment of rheumatic diseases. Lupus. 1996; 5(1):11–15.
- 19. Costedoat-Chalumeau N, Amoura Z, Hulot JS et al. Low blood concentration of hydroxychloroquine is a marker for and predictor of disease exacerbations in patients with systemic lupus erythematosus. Arthritis Rheum. 2006;54(10):3284–90.
- 20. Inglot AD. Comparison of the antiviral activity in vitro of some non-steroidal anti-inflammatory drugs. J Gen Virol. 1969;4(2):203–14.
- 21. Shimizu Y, Yamamoto S, Homma M et al. Effect of chloroquine on the growth of animal viruses. Arch Gesamte Virusforsch. 1972;36(1):93–4.
- 22. Schlesinger PH, Krogstad DJ, Herwaldt BL. Antimalarial agents: mechanisms of action. Antimicrob Agents Chemother. 1988;32(6):793–8. doi: 10.1128/aac.32.6.793 .
- 23. Ben-Zvi I, Kivity S, Langevitz P et al. Hydroxychloroquine: from malaria to autoimmunity. Clin Rev Allergy Immunol. 2012;42(2):145–53.
- 24. Plantone D, Koudriavtseva T. Current and Future Use of Chloroquine and Hydroxychloroquine in Infectious, Immune, Neoplastic, and Neurological Diseases: A Mini-Review. Clin Drug Investig. 2018;38(8):653–71.
- 25. Mauthe M, Orhon I, Rocchi C et al. Chloroquine inhibits autophagic flux by decreasing autophagosome- lysosome fusion. Autophagy. 2018;14(8),1435–55.
- 26. Wu SF, Chang CB, Hsu JM et al. Hydroxychloroquine inhibits CD154 expression in CD4(+) T lymphocytes of systemic lupus erythematosus through NFAT, but not STAT5, signaling. Arthritis Res Ther. 2017;19(1),183.
- 27. Rempenault C, Combe B, Barnetche T et al. Metabolic and cardiovascular benefits of hydroxychloroquine in patients with rheumatoid arthritis: a systematic review and meta-analysis. Ann Rheum Dis. 2018;77(1):98–103.
- 28. Al-Bari MA. Chloroquine analogues in drug discovery: New directions of uses, mechanisms of actions and toxic manifestations from malaria to multifarious diseases. J Antimicrob Chemother. 2015;70:1608–21.
- 29. Khan M, Santhosh SR, Tiwari M, Lakshmana Rao PV, Parida M. Assessment of in vitro prophylactic and therapeutic efficacy of chloroquine against Chikungunya virus in vero cells. J Med Virol. 2010;82:817-24.
- 30. Delvecchio R, Higa LM, Pezzuto P et al. Chloroquine, an Endocytosis Blocking Agent, Inhibits Zika Virus Infection in Different Cell Models. Viruses. 2016;29;8(12): pii: E322.
- 31. Dowall SD, Bosworth A, Watson R et al. Chloroquine inhibited Ebola virus replication in vitro but failed to protect against infection and disease in the in vivo guinea pig model. J Gen Virol. 2015;96:3484–92.
- 32. Mizui T, Yamashina S, Tanida I et al. Inhibition of hepatitis C virus replication by chloroquine targeting virus-associated autophagy. J Gastroenterol. 2010;45:195–3.
- 33. Tsai WP, Nara PL, Kung HF, Oroszlan S. Inhibition of human immunodeficiency virus infectivity by chloroquine. AIDS Res Hum Retroviruses. 1990;6:481–89.
- 34. Naarding MA, Baan E, Pollakis G, Paxton WAE. Effect of chloroquine on reducing HIV-1 replication in vitro and the DC-SIGN mediated transfer of virus to CD4+ T-lymphocytes. Retrovirology. 2007;4:6.
- 35. Ooi EE, Chew JS, Loh JP, Chua RC. In vitro inhibition of human influenza A virus replication by chloroquine. Virol J. 2006;3:39.
- 36. Paton NI, Lee L, Xu Y et al. Chloroquine for influenza prevention: A randomised, double-blind, placebo controlled trial. Lancet Infect Dis. 2011;11:677–83.
- 37. Zhou D, Dai SM, Tong Q. COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression. J Antimicrob Chemother. 2020;pii:dkaa114. doi: 10.1093/jac/dkaa114.
- 38. Yao X, Ye F, Zhang M et al. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020;PMID:32150618.
- 39. Biot C, Daher W, Chavain N, Fandeur T, Khalife J, Dive D. Design and synthesis of hydroxyferroquine derivatives with antimalarial and antiviral activities. J Med Chem. 2006;49:2845–49.
- 40. Colson P, Rolain JM, Raoult D. Chloroquine for the 2019 novel coronavirus SARS-CoV-2. Int J Antimicrob Agents. 2020:105923. doi:10.1016/j.ijantimicag.
- 41. Vincent MJ, Bergeron E, Benjannet S, Erickson BR, Rollin PE, Ksiazek TG. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J. 2005;2:69.
- 42. Liu J, Cao R, Xu M, Wang X, Zhang H, Hu H. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov. 2020;6:16.
- 43. Marmor MF, Kellner U, Lai TY, Melles RB, Mieler WF. American Academy of Ophthalmology.Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision) Ophthalmology. 2016;123(6):1386-94
- 44. Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30(3):269-271. doi:10.1038/s41422-020-0282-0.
- 45. Gao J, Tian Z, Yang X. Breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020;14(1):72-73. doi: 10.5582/bst.2020.01047.
- 46. Gautret P, Lagier JC, Parola P et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label nonrandomized clinical trial. Int J Antimicrob Agents. 2020;20:105949. doi: 10.1016/j.ijantimicag.2020.105949.
- 47. Huang C, Wang Y, Li X et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-6.
- 48. Shah S, Das S, Jain A, Misra DP, Negi VS. A systematic review of the prophylactic role of chloroquine and hydroxychloroquine in coronavirus disease-19 (COVID-19). Int J Rheum Dis. 2020;00:1–7. ht tp s://doi.org/10.1111/1756-185X.138427
- 49. Scherbel AL, Schuter SL, Harrison JW. Comparison of effects of two antimalarial agents, hydroxychloroquine sulfate and chloroquine phosphate, in patients with rheumatoid arthritis. Cleve Clin Q 1957;98-4.
- 50. Tett S, Cutler D, Day R. Antimalarials in rheumatic diseases. Baillieres Clin Rheumatol. 1990;4(3):467-89.
- 51. Van Beek MJ, Piette WW. Antimalarials. Dermatol Clin. 2001;19:147–60.
- 52. Kalia S, Dutz JP. New concepts in antimalarial use and mode of action in dermatology. Dermatol Ther. 2007;20:160–74.
- 53. Marmor MF, Kellner U, Lai TY, Lyons JS, Mieler WF; American Academy of Ophthalmology. Revised recommendations on screening for chloroquine and hydroxychloroquine retinopathy. Ophthalmology. 2011;118(2):415-22.
- 54. Melles RB, Marmor MF. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy. JAMA Ophthalmol. 2014;132:1453–60.
- 55. Tonnesmann E, Kandolf R, Lewalter T. Chloroquine cardiomyopathy—a review of the literature. Immunopharmacol Immunotoxicol. 2013;35:434–42.
- 56. Naqvi TZ, Luthringer D, Marchevsky A, Saouf R, Gul K, Buchbinder NA. Chloroquine-induced cardiomyopathy-echocardiographic features. J Am Soc Echocardiogr. 2005;18:383–7.
- 57. Stein M, Bell MJ, Ang LC. Hydroxychloroquine neuromyotoxicity. J Rheumatol. 2000;27:2927–31.
- 58. Teng C. Walter EA, Gaspar DKS, Obodozie-Ofoegbu OO, Frei CR. Torsades de pointes and QT prolongation Associations with Antibiotics: a Pharmacovigilance Study of the FDA Adverse Event Reporting System. Int J Med Sci. 2019;16(7):1018–22.
- 59. Chen CY, Wang FL, Lin CC. Chronic hydroxychloroquine use associated with QT prolongation and refractory ventricular arrhythmia. Clin Toxicol (Phila) 2006;44(2):173–75
- 60. Sarayani A, Cicali B, Henriksen CH, Brown JD. Safety signals for QT prolongation or Torsades de Pointes associated with azithromycin with or without chloroquine or hydroxychloroquine. Res Social Adm Pharm. 2020;S1551-7411(20)30391-0. doi:10.1016/j.sapharm.2020;04.016
- 61. White NJ, Miller KD, Churchill FC et al. Chloroquine treatment of severe malaria in children. Pharmacokinetics, toxicity, and new dosage recommendations. N Engl J Med. 1988;319:1493– 500.
- 62. Schrezenmeier E, Dörner T. Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nat Rev Rheumatol. 2020;16(3):155-66.
- 63. Grondin C, Malleson P, Petty RE. Slow-actingantirheumaticdrugs in chronic arthritis of childhood. Semin Arthritis Rheum. 1988;18:38–47.
- 64. Beukelman T, Patkar NM, Saag KG, et al. American College of Rheumatology Recommendations for the Treatment of Juvenile Idiopathic Arthritis: Initiation and Safety Monitoring of Therapeutic Agents for the Treatment of Arthritis and Systemic Features. Arthritis Care Res. 2011;63:465–82.
- 65. Braun S, Ferner M, Kronfeld K, Griese M. Hydroxychloroquine in children with interstitial (diffuse parenchymal) lung diseases. Pediatr Pulmonol. 2015;50(4):410–19.
- 66. Clement A, Nathan N, Epaud R, Fauroux B, Corvol H. Interstitial lung diseases in children. Orphanet J Rare Dis. 2010;5:22.
- 67. Ke AB, Rostami-Hodjegan A, Zhao P, Unadkat JD. Pharmacometrics in pregnancy: an unmet need. Annu Rev Pharmacol Toxicol. 2014;54:53–69.
- 68. Rainsford KD, Parke AL, Clifford-Rashotte M, Kean WF. Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases. Inflammopharmacology. 2015;23:231–69.
- 69. Janssen N, and Genta M. The effects of immunosuppressive and anti-inflammatory medications on fertility, pregnancy and lactation. Arch Intern Med. 2000; 160:610-19.
- 70. Costedoat-Chalumeau N, Amoura Z, Aymard G et al. Evidence of transplacental passage of hydroxychloroquine in humans. Arthritis Rheum 2002;46:1123–4.
- 71. Bertsias GK, Tektonidou M, Amoura Z et al. Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann Rheumatol Dis. 2012;71:1771–82.
- 72. Bertsias G, Ioannidis JPA, Boletis J, et al. EULAR recommendations for the management of systemic lupus erythematosus. Report of a task force of the EULAR standing committee for international clinical studies including therapeutics. Ann Rheum Dis 2008;67:195-205.
- 73. Levy RA, Vilela VS, Cataldo MJ, et al. Hydroxychloroquine (HCQ) in lupus pregnancy: doubleblind and placebo-controlled study. Lupus 2001;10:401-4.
- 74. Tarfaoui N, Autret-Leca E, Mazjoub S et al. Hydroxychloroquine during pregnancy: a review of retinal toxicity in the newborns. Therapie 2013;68:43–7.
- 75. Centers for Disease Control and Prevention. CDC Yellow Book 2020: Health Information for International Travel. New York: Oxford University Press;2019.
- 76. Breslin N, Baptiste C, Miller R et al. COVID-19 in pregnancy: early lessons, Am J Obstet Gynecol MFM 2020 doi: https://doi.org/10.1016/j.ajogmf.2020.100111
- 77. Karunajeewa HA, Salman S, Mueller I et al. Pharmacokinetics of chloroquine and monodesethylchloroquine in pregnancy. Antimicrob Agents Chemother 2010;54:1186–92.
- 78. Dashraath P, Wong JLJ, Lim MXK et al. Coronavirus disease 2019 (COVID-19) pandemic and pregnancy. Am J Obstet Gynecol. 2020 Mar 23 pii: S0002-9378(20)30343-4. doi: 10.1016/j.ajog.2020.03.021.
- 79. Akintonwa A, Gbajumo SA, Mabadeje AFB. Placental and mild transfer of chloroquine in humans. Ther Drug Monit.1988;10:147–9.
- 80. Cissoko H, Rouger J, Zahr N et al. Breast milk concentrations of hydroxychloroquine. Fundam Clin Pharmacol. 2010;24 (1):420.
- 81. Peng W, Liu R, Zhang L et al. Breast milk concentration of hydroxychloroquine in Chinese lactating women with connective tissue diseases. Eur J Clin Pharmacol. 2019;75:1547–53.
- 82. Tincani A, Faden D, Lojacono A, et al. Hydroxychloroquine in pregnant patients with rheumatic disease. Arthritis Rheum. 2001;44 Supplement S9:S397. Abstract 2065
- 83. Motta M, Tincani A, Faden Dö et al. Follow-up of infants exposed to hydroxychloroquine given to mothers during pregnancy and lactation. J Perinatol. 2005;25:86–9.
- 84. Firestein GF, Budd R. Kelley and Firestein's Textbook of Rheumatology E-Book. Saintt Louis: Elsevier; 2016.
- 85. Mascolo A, Berrino, PM, Gareri P et al. Neuropsychiatric clinical manifestations in elderly. patients treated with hydroxychloroquine: a review article. Inflammopharmacol. 2018;26: 1141–9.
- 86. Choi IA, Park SH, Cha HS et al. Prevalence of co-morbidities and evaluation of their monitoring in Korean patients with rheumatoid arthritis: comparison with the results of an international, cross-sectional study (COMORA). Int J Rheum Dis. 2018;21(7):1414‐22.
- 87. Abdel Galil SM. Hydroxychloroquine-induced toxic hepatitis in a patient with systemic lupus erythematosus: a case report. Lupus. 2015;24(6):638–40.
- 88. Giner Galvañ V, Oltra MR, Rueda D, Esteban MJ, Redón J. Severe acute hepatitis related to hydroxychloroquine in a woman with mixed connective tissue disease. Clin Rheumatol. 2007;26(6):971–2.
- 89. Tett SE. Clinical Pharmacokinetics of Slow-Acting Antirheumatic Drugs. Clin Pharmacokinet. 1993;25(5):392-407.
- 90. Wu CL, Chang CC, Kor CT et al. Hydroxychloroquine Use and Risk of CKD in Patients with Rheumatoid Arthritis. Clin J Am Soc Nephrol. 2018;13(5):702–9.
- 91. Liu LJ, Yang YZ, Shi SF et al. Effects of Hydroxychloroquine on Proteinuria in IgA Nephropathy: A Randomized Controlled Trial. Am J Kidney Dis. 2019;74(1):15–22.
- 92. Bebitoğlu BT, Oğuz E, Nuhoğlu Ç et al. Evaluation of potential drug-drug interactions in a pediatric population. Turk Pediatri Ars. 2020;9:55(1):30-8.
- 93. Masimirembwa CM, Hasler JA, Johansson I. Inhibitory effects of antiparasitic drugs on cytochrome P450 2D6. Eur J Clin Pharmacol 1995;48:35-8.
- 94. Somer Somer M, Kallio J, Pesonen U, Pyykkö K, Huupponen R, Scheinin M. Influence of hydroxychloroquine on the bioavailability of oral metoprolol. Br. J.Clin.Pharmacol. 2000;49:549–54.
- 95. Leden I. Digoxin-Hydroxychloroquine Interaction. Acta Med Scand. 1982;211:411-2.
- 96. Tiberghien F, Loor F. Ranking of P-glycoprotein substrates and inhibitors by a calcein-AM fluorometry screening assay. Anticancer Drugs. 1996;7(5): 568-78.
- 97. Currie GM, Wheat JM, Kiat H. Pharmacokinetic considerations for digoxin in older people. Open Cardiovasc Med J. 2011;5:130‐5.
- 98. Toimela T, Tahti H, Salminen L. Retinal pigmentepithelium cell culture as a model for evaluation of the toxicity of tamoxifen and chloroquine. Ophthalmic Res. 1995;27:150–53.
- 99. Namazi MR. The potential negative impact of proton pump inhibitors on the immunopharmacologic effects of chloroquine and hydroxychloroquine. Lupus 2009;18: 104–5.
- 100. Jallouli M, Galicier L, Zahr N et al. Determinants of hydroxychloroquine blood concentration variations in systemic lupus erythematosus. Arthritis Rheumatol. 2015;67(8):2176-84. doi: 10.1002/art.39194.
Klorokin/Hidroksiklorokin: COVID-19 tedavisi ile gündeme gelen eski bir ilaca farmakolojik bakış
Yıl 2020,
Sayı: Special Issue on COVID 19, 204 - 215, 20.03.2020
Berna Terzioğlu Bebitoğlu
,
Elif Oğuz
,
Ajla Hodzic
Nebile Hatiboğlu
Özkan Kam
Öz
Son yıllarda ilaç yeniden konumlandırma çalışmalarının hız kazanması ile özellikle zararsız olduğu kanıtlanmış, farmakokinetik ve optimal dozu iyi bilinen ilaçlar farklı endikasyonlarda kullanılmak üzere yeniden araştırmalara tabi tutulmaktadır. Günümüzde pandemiye neden olan SARS-CoV-2'ye karşı özellikle klinik olarak etkinliği kanıtlanmış tedavi ya da aşı henüz bulunmamıştır. COVID-19 hastalığının tedavisinde klorokin ve hidroksiklorokinin tedavi potansiyeli büyük ölçüde dikkat çekmiştir. Bu derlemede COVID-19'un tedavisi ile yeniden gündeme gelen eski bir ilaç olan klorokin/hidroksiklorokinin farmakokinetik, farmakodinamik özellikleri, özel popülasyonlardaki kullanımı ve güvenliği ile ilgili mevcut veriler incelenmiş ve literatürdeki güncel araştırmalar doğrultusunda SARS-CoV-2 enfeksiyonundaki etkinlik ve güvenliğine ilişkin veriler sunulmaktadır. Klorokin/Hidroksiklorokinin COVID-19 hastalığının tedavi algoritmalarında ilk sırada yer alması ile birlikte daha fazla randomize kontrollü klinik çalışmanın da gerekli olduğu görülmektedir.
Kaynakça
- 1. T.C. Sağlık Bakanlığı Halk Sağlığı Genel Müdürlüğü COVID-19(SARS-CoV-2 Enfeksiyonu) Rehberi. Bilim Kurulu Çalışması. Ankara; 14 Nisan 2020.
https://covid19bilgi.saglik.gov.tr/depo/rehberler/COVID-19_Rehberi.pdf
- 2. Zhou P, Yang XL, Wang XG et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270–73.
- 3. Wallace DJ. The history of antimalarials. Lupus. 1996;5(1):2–3.
- 4. Mates M, Nesher G, Zevin S. Quinines—past and present. Harefuah. 2007;146(7): 560–62.
- 5. Shippey EA, Wagler VD, Collamer AN. Hydroxychloroquine: An old drug with new relevance. Cleve Clin J Med. 2018;85(6):459–67.
- 6. Stoughton RB. Treatment of chronic lupus erythematosus with atabrine and chloroquine. Ill Med J. 1955;107(6):299–2.
- 7. Ducharme, J., Farinotti, R. Clinical Pharmacokinetics and Metabolism of Chloroquine. Clin-Pharmacokinet 1996;31:257–74. https://doi.org/10.2165/00003088-199631040-00003
- 8. Rand JH, Wu XX, Quinn AS et al. Hydroxychloroquine directly reduces the binding of antiphospholipid antibody-beta2-glycoprotein I complexes to phospholipid bilayers. Blood. 2008;112(5):1687–95.
- 9. McChesney EW. Animal toxicity and pharmacokinetics of hydroxychloroquine sulfate. Am J Med. 1983;75(1A):11–18.
- 10. Browning DJ. Pharmacology of Chloroquine and Hydroxychloroquine. In: Hydroxychloroquine and Chloroquine Retinopathy. New York:Springer, 2014; p. 35–63.
- 11. Tett SE, Cutler D J, Day RO et al. Bioavailability of hydroxychloroquine tablets in healthy volunteers. Br J Clin Pharmacol. 1989;27(6):771–79.
- 12. Gustafsson LL, Walker D, Alván G et al. Disposition of chloroquine in man after single intravenous and oral doses. Br J Clin Pharmacol. 1983;15(4):471–79.
- 13. FDA Approved Drug Products: Hydroxychloroquine Oral Tablet
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/009768Orig1s051lbl.pdf
- 14. Collins KP, Jackson KM, Gustafson DL. Hydroxychloroquine: A Physiologically-Based Pharmacokinetic Model in the Context of Cancer-Related Autophagy Modulation. J Pharmacol Exp Ther. 2018;365(3):447–59.
- 15. Munster T, Gibbs JP, Shen D et al. Hydroxychloroquine concentration-response relationships in patients with rheumatoid arthritis. Arthritis Rheum. 2002;46(6):1460–69.
- 16. Popert AJ. Chloroquine: a review. Rheumatol Rehabil. 1976;15(3):235–38.
- 17. Laaksonen AL, Koskiahde V, Juva K. Dosage of antimalarial drugs for children with juvenile rheumatoid arthritis and systemic lupus erythematosus. A clinical study with determination of serum concentrations of chloroquine and hydroxychloroquine. Scand J Rheumatol. 1974;3(2):103–8.
- 18. Furst DE, Pharmacokinetics of hydroxychloroquine and chloroquine during treatment of rheumatic diseases. Lupus. 1996; 5(1):11–15.
- 19. Costedoat-Chalumeau N, Amoura Z, Hulot JS et al. Low blood concentration of hydroxychloroquine is a marker for and predictor of disease exacerbations in patients with systemic lupus erythematosus. Arthritis Rheum. 2006;54(10):3284–90.
- 20. Inglot AD. Comparison of the antiviral activity in vitro of some non-steroidal anti-inflammatory drugs. J Gen Virol. 1969;4(2):203–14.
- 21. Shimizu Y, Yamamoto S, Homma M et al. Effect of chloroquine on the growth of animal viruses. Arch Gesamte Virusforsch. 1972;36(1):93–4.
- 22. Schlesinger PH, Krogstad DJ, Herwaldt BL. Antimalarial agents: mechanisms of action. Antimicrob Agents Chemother. 1988;32(6):793–8. doi: 10.1128/aac.32.6.793 .
- 23. Ben-Zvi I, Kivity S, Langevitz P et al. Hydroxychloroquine: from malaria to autoimmunity. Clin Rev Allergy Immunol. 2012;42(2):145–53.
- 24. Plantone D, Koudriavtseva T. Current and Future Use of Chloroquine and Hydroxychloroquine in Infectious, Immune, Neoplastic, and Neurological Diseases: A Mini-Review. Clin Drug Investig. 2018;38(8):653–71.
- 25. Mauthe M, Orhon I, Rocchi C et al. Chloroquine inhibits autophagic flux by decreasing autophagosome- lysosome fusion. Autophagy. 2018;14(8),1435–55.
- 26. Wu SF, Chang CB, Hsu JM et al. Hydroxychloroquine inhibits CD154 expression in CD4(+) T lymphocytes of systemic lupus erythematosus through NFAT, but not STAT5, signaling. Arthritis Res Ther. 2017;19(1),183.
- 27. Rempenault C, Combe B, Barnetche T et al. Metabolic and cardiovascular benefits of hydroxychloroquine in patients with rheumatoid arthritis: a systematic review and meta-analysis. Ann Rheum Dis. 2018;77(1):98–103.
- 28. Al-Bari MA. Chloroquine analogues in drug discovery: New directions of uses, mechanisms of actions and toxic manifestations from malaria to multifarious diseases. J Antimicrob Chemother. 2015;70:1608–21.
- 29. Khan M, Santhosh SR, Tiwari M, Lakshmana Rao PV, Parida M. Assessment of in vitro prophylactic and therapeutic efficacy of chloroquine against Chikungunya virus in vero cells. J Med Virol. 2010;82:817-24.
- 30. Delvecchio R, Higa LM, Pezzuto P et al. Chloroquine, an Endocytosis Blocking Agent, Inhibits Zika Virus Infection in Different Cell Models. Viruses. 2016;29;8(12): pii: E322.
- 31. Dowall SD, Bosworth A, Watson R et al. Chloroquine inhibited Ebola virus replication in vitro but failed to protect against infection and disease in the in vivo guinea pig model. J Gen Virol. 2015;96:3484–92.
- 32. Mizui T, Yamashina S, Tanida I et al. Inhibition of hepatitis C virus replication by chloroquine targeting virus-associated autophagy. J Gastroenterol. 2010;45:195–3.
- 33. Tsai WP, Nara PL, Kung HF, Oroszlan S. Inhibition of human immunodeficiency virus infectivity by chloroquine. AIDS Res Hum Retroviruses. 1990;6:481–89.
- 34. Naarding MA, Baan E, Pollakis G, Paxton WAE. Effect of chloroquine on reducing HIV-1 replication in vitro and the DC-SIGN mediated transfer of virus to CD4+ T-lymphocytes. Retrovirology. 2007;4:6.
- 35. Ooi EE, Chew JS, Loh JP, Chua RC. In vitro inhibition of human influenza A virus replication by chloroquine. Virol J. 2006;3:39.
- 36. Paton NI, Lee L, Xu Y et al. Chloroquine for influenza prevention: A randomised, double-blind, placebo controlled trial. Lancet Infect Dis. 2011;11:677–83.
- 37. Zhou D, Dai SM, Tong Q. COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression. J Antimicrob Chemother. 2020;pii:dkaa114. doi: 10.1093/jac/dkaa114.
- 38. Yao X, Ye F, Zhang M et al. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020;PMID:32150618.
- 39. Biot C, Daher W, Chavain N, Fandeur T, Khalife J, Dive D. Design and synthesis of hydroxyferroquine derivatives with antimalarial and antiviral activities. J Med Chem. 2006;49:2845–49.
- 40. Colson P, Rolain JM, Raoult D. Chloroquine for the 2019 novel coronavirus SARS-CoV-2. Int J Antimicrob Agents. 2020:105923. doi:10.1016/j.ijantimicag.
- 41. Vincent MJ, Bergeron E, Benjannet S, Erickson BR, Rollin PE, Ksiazek TG. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J. 2005;2:69.
- 42. Liu J, Cao R, Xu M, Wang X, Zhang H, Hu H. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov. 2020;6:16.
- 43. Marmor MF, Kellner U, Lai TY, Melles RB, Mieler WF. American Academy of Ophthalmology.Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision) Ophthalmology. 2016;123(6):1386-94
- 44. Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30(3):269-271. doi:10.1038/s41422-020-0282-0.
- 45. Gao J, Tian Z, Yang X. Breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020;14(1):72-73. doi: 10.5582/bst.2020.01047.
- 46. Gautret P, Lagier JC, Parola P et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label nonrandomized clinical trial. Int J Antimicrob Agents. 2020;20:105949. doi: 10.1016/j.ijantimicag.2020.105949.
- 47. Huang C, Wang Y, Li X et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-6.
- 48. Shah S, Das S, Jain A, Misra DP, Negi VS. A systematic review of the prophylactic role of chloroquine and hydroxychloroquine in coronavirus disease-19 (COVID-19). Int J Rheum Dis. 2020;00:1–7. ht tp s://doi.org/10.1111/1756-185X.138427
- 49. Scherbel AL, Schuter SL, Harrison JW. Comparison of effects of two antimalarial agents, hydroxychloroquine sulfate and chloroquine phosphate, in patients with rheumatoid arthritis. Cleve Clin Q 1957;98-4.
- 50. Tett S, Cutler D, Day R. Antimalarials in rheumatic diseases. Baillieres Clin Rheumatol. 1990;4(3):467-89.
- 51. Van Beek MJ, Piette WW. Antimalarials. Dermatol Clin. 2001;19:147–60.
- 52. Kalia S, Dutz JP. New concepts in antimalarial use and mode of action in dermatology. Dermatol Ther. 2007;20:160–74.
- 53. Marmor MF, Kellner U, Lai TY, Lyons JS, Mieler WF; American Academy of Ophthalmology. Revised recommendations on screening for chloroquine and hydroxychloroquine retinopathy. Ophthalmology. 2011;118(2):415-22.
- 54. Melles RB, Marmor MF. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy. JAMA Ophthalmol. 2014;132:1453–60.
- 55. Tonnesmann E, Kandolf R, Lewalter T. Chloroquine cardiomyopathy—a review of the literature. Immunopharmacol Immunotoxicol. 2013;35:434–42.
- 56. Naqvi TZ, Luthringer D, Marchevsky A, Saouf R, Gul K, Buchbinder NA. Chloroquine-induced cardiomyopathy-echocardiographic features. J Am Soc Echocardiogr. 2005;18:383–7.
- 57. Stein M, Bell MJ, Ang LC. Hydroxychloroquine neuromyotoxicity. J Rheumatol. 2000;27:2927–31.
- 58. Teng C. Walter EA, Gaspar DKS, Obodozie-Ofoegbu OO, Frei CR. Torsades de pointes and QT prolongation Associations with Antibiotics: a Pharmacovigilance Study of the FDA Adverse Event Reporting System. Int J Med Sci. 2019;16(7):1018–22.
- 59. Chen CY, Wang FL, Lin CC. Chronic hydroxychloroquine use associated with QT prolongation and refractory ventricular arrhythmia. Clin Toxicol (Phila) 2006;44(2):173–75
- 60. Sarayani A, Cicali B, Henriksen CH, Brown JD. Safety signals for QT prolongation or Torsades de Pointes associated with azithromycin with or without chloroquine or hydroxychloroquine. Res Social Adm Pharm. 2020;S1551-7411(20)30391-0. doi:10.1016/j.sapharm.2020;04.016
- 61. White NJ, Miller KD, Churchill FC et al. Chloroquine treatment of severe malaria in children. Pharmacokinetics, toxicity, and new dosage recommendations. N Engl J Med. 1988;319:1493– 500.
- 62. Schrezenmeier E, Dörner T. Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nat Rev Rheumatol. 2020;16(3):155-66.
- 63. Grondin C, Malleson P, Petty RE. Slow-actingantirheumaticdrugs in chronic arthritis of childhood. Semin Arthritis Rheum. 1988;18:38–47.
- 64. Beukelman T, Patkar NM, Saag KG, et al. American College of Rheumatology Recommendations for the Treatment of Juvenile Idiopathic Arthritis: Initiation and Safety Monitoring of Therapeutic Agents for the Treatment of Arthritis and Systemic Features. Arthritis Care Res. 2011;63:465–82.
- 65. Braun S, Ferner M, Kronfeld K, Griese M. Hydroxychloroquine in children with interstitial (diffuse parenchymal) lung diseases. Pediatr Pulmonol. 2015;50(4):410–19.
- 66. Clement A, Nathan N, Epaud R, Fauroux B, Corvol H. Interstitial lung diseases in children. Orphanet J Rare Dis. 2010;5:22.
- 67. Ke AB, Rostami-Hodjegan A, Zhao P, Unadkat JD. Pharmacometrics in pregnancy: an unmet need. Annu Rev Pharmacol Toxicol. 2014;54:53–69.
- 68. Rainsford KD, Parke AL, Clifford-Rashotte M, Kean WF. Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases. Inflammopharmacology. 2015;23:231–69.
- 69. Janssen N, and Genta M. The effects of immunosuppressive and anti-inflammatory medications on fertility, pregnancy and lactation. Arch Intern Med. 2000; 160:610-19.
- 70. Costedoat-Chalumeau N, Amoura Z, Aymard G et al. Evidence of transplacental passage of hydroxychloroquine in humans. Arthritis Rheum 2002;46:1123–4.
- 71. Bertsias GK, Tektonidou M, Amoura Z et al. Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann Rheumatol Dis. 2012;71:1771–82.
- 72. Bertsias G, Ioannidis JPA, Boletis J, et al. EULAR recommendations for the management of systemic lupus erythematosus. Report of a task force of the EULAR standing committee for international clinical studies including therapeutics. Ann Rheum Dis 2008;67:195-205.
- 73. Levy RA, Vilela VS, Cataldo MJ, et al. Hydroxychloroquine (HCQ) in lupus pregnancy: doubleblind and placebo-controlled study. Lupus 2001;10:401-4.
- 74. Tarfaoui N, Autret-Leca E, Mazjoub S et al. Hydroxychloroquine during pregnancy: a review of retinal toxicity in the newborns. Therapie 2013;68:43–7.
- 75. Centers for Disease Control and Prevention. CDC Yellow Book 2020: Health Information for International Travel. New York: Oxford University Press;2019.
- 76. Breslin N, Baptiste C, Miller R et al. COVID-19 in pregnancy: early lessons, Am J Obstet Gynecol MFM 2020 doi: https://doi.org/10.1016/j.ajogmf.2020.100111
- 77. Karunajeewa HA, Salman S, Mueller I et al. Pharmacokinetics of chloroquine and monodesethylchloroquine in pregnancy. Antimicrob Agents Chemother 2010;54:1186–92.
- 78. Dashraath P, Wong JLJ, Lim MXK et al. Coronavirus disease 2019 (COVID-19) pandemic and pregnancy. Am J Obstet Gynecol. 2020 Mar 23 pii: S0002-9378(20)30343-4. doi: 10.1016/j.ajog.2020.03.021.
- 79. Akintonwa A, Gbajumo SA, Mabadeje AFB. Placental and mild transfer of chloroquine in humans. Ther Drug Monit.1988;10:147–9.
- 80. Cissoko H, Rouger J, Zahr N et al. Breast milk concentrations of hydroxychloroquine. Fundam Clin Pharmacol. 2010;24 (1):420.
- 81. Peng W, Liu R, Zhang L et al. Breast milk concentration of hydroxychloroquine in Chinese lactating women with connective tissue diseases. Eur J Clin Pharmacol. 2019;75:1547–53.
- 82. Tincani A, Faden D, Lojacono A, et al. Hydroxychloroquine in pregnant patients with rheumatic disease. Arthritis Rheum. 2001;44 Supplement S9:S397. Abstract 2065
- 83. Motta M, Tincani A, Faden Dö et al. Follow-up of infants exposed to hydroxychloroquine given to mothers during pregnancy and lactation. J Perinatol. 2005;25:86–9.
- 84. Firestein GF, Budd R. Kelley and Firestein's Textbook of Rheumatology E-Book. Saintt Louis: Elsevier; 2016.
- 85. Mascolo A, Berrino, PM, Gareri P et al. Neuropsychiatric clinical manifestations in elderly. patients treated with hydroxychloroquine: a review article. Inflammopharmacol. 2018;26: 1141–9.
- 86. Choi IA, Park SH, Cha HS et al. Prevalence of co-morbidities and evaluation of their monitoring in Korean patients with rheumatoid arthritis: comparison with the results of an international, cross-sectional study (COMORA). Int J Rheum Dis. 2018;21(7):1414‐22.
- 87. Abdel Galil SM. Hydroxychloroquine-induced toxic hepatitis in a patient with systemic lupus erythematosus: a case report. Lupus. 2015;24(6):638–40.
- 88. Giner Galvañ V, Oltra MR, Rueda D, Esteban MJ, Redón J. Severe acute hepatitis related to hydroxychloroquine in a woman with mixed connective tissue disease. Clin Rheumatol. 2007;26(6):971–2.
- 89. Tett SE. Clinical Pharmacokinetics of Slow-Acting Antirheumatic Drugs. Clin Pharmacokinet. 1993;25(5):392-407.
- 90. Wu CL, Chang CC, Kor CT et al. Hydroxychloroquine Use and Risk of CKD in Patients with Rheumatoid Arthritis. Clin J Am Soc Nephrol. 2018;13(5):702–9.
- 91. Liu LJ, Yang YZ, Shi SF et al. Effects of Hydroxychloroquine on Proteinuria in IgA Nephropathy: A Randomized Controlled Trial. Am J Kidney Dis. 2019;74(1):15–22.
- 92. Bebitoğlu BT, Oğuz E, Nuhoğlu Ç et al. Evaluation of potential drug-drug interactions in a pediatric population. Turk Pediatri Ars. 2020;9:55(1):30-8.
- 93. Masimirembwa CM, Hasler JA, Johansson I. Inhibitory effects of antiparasitic drugs on cytochrome P450 2D6. Eur J Clin Pharmacol 1995;48:35-8.
- 94. Somer Somer M, Kallio J, Pesonen U, Pyykkö K, Huupponen R, Scheinin M. Influence of hydroxychloroquine on the bioavailability of oral metoprolol. Br. J.Clin.Pharmacol. 2000;49:549–54.
- 95. Leden I. Digoxin-Hydroxychloroquine Interaction. Acta Med Scand. 1982;211:411-2.
- 96. Tiberghien F, Loor F. Ranking of P-glycoprotein substrates and inhibitors by a calcein-AM fluorometry screening assay. Anticancer Drugs. 1996;7(5): 568-78.
- 97. Currie GM, Wheat JM, Kiat H. Pharmacokinetic considerations for digoxin in older people. Open Cardiovasc Med J. 2011;5:130‐5.
- 98. Toimela T, Tahti H, Salminen L. Retinal pigmentepithelium cell culture as a model for evaluation of the toxicity of tamoxifen and chloroquine. Ophthalmic Res. 1995;27:150–53.
- 99. Namazi MR. The potential negative impact of proton pump inhibitors on the immunopharmacologic effects of chloroquine and hydroxychloroquine. Lupus 2009;18: 104–5.
- 100. Jallouli M, Galicier L, Zahr N et al. Determinants of hydroxychloroquine blood concentration variations in systemic lupus erythematosus. Arthritis Rheumatol. 2015;67(8):2176-84. doi: 10.1002/art.39194.