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Hydroxychloroquine response

MedGen UID:
980610
Concept ID:
CN296780
Sign or Symptom
Drug:
hydroxychloroquine
MedGen UID:
5673
Concept ID:
C0020336
Pharmacologic Substance
A 4-aminoquinoline with immunosuppressive, antiautophagy, and antimalarial activities. Although the precise mechanism of action is unknown, hydroxychloroquine may suppress immune function by interfering with the processing and presentation of antigens and the production of cytokines. As a lysosomotropic agent, hydroxychloroquine raises intralysosomal pH, impairing autophagic protein degradation; hydroxychloroquine-mediated accumulation of ineffective autophagosomes may result in cell death in tumor cells reliant on autophagy for survival. In addition, this agent is highly active against the erythrocytic forms of P. vivax and malariae and most strains of P. falciparum but not the gametocytes of P. falciparum. [from NCI]

Definition

Hydroxychloroquine, which is closely related to chloroquine, can be used for the prevention and treatment of some forms of malaria and rheumatic conditions such as systemic lupus erythematosus (SLE) and rheumatoid arthritis. Malaria is an infection caused by the Plasmodium parasite, transmitted via mosquito bites. Hydroxychloroquine sulfate is indicated for the prevention and treatment of uncomplicated malaria due to sensitive strains of Plasmodium falciparum (P. falciparum), Plasmodium vivax (P. vivax), Plasmodium malariae (P. malariae), Plasmodium ovale (P. ovale), and Plasmodium knowlesi (P. knowlesi) by both the US Centers for Disease Control (CDC) and World Health Organization (WHO). Resistance to chloroquine and hydroxychloroquine has been reported in Plasmodium species, thus hydroxychloroquine therapy is not recommended if the infection arose in a region with known resistance. Most P. falciparum infections are resistant to the 4-aminoquinolines (chloroquine and hydroxychloroquine), and as such these drugs are no longer used widely for these infections. Hydroxychloroquine must be co-administered with an 8-aminoquinoline compound for the radical cure of P. vivax or P. ovale infection to eliminate the hypnozoite forms of these parasites. Additionally, hydroxychloroquine is indicated for the treatment of many rheumatoid conditions in adults, including chronic discoid lupus erythematosus, systemic lupus erythematosus, as well as acute and chronic rheumatoid arthritis. Hydroxychloroquine has also been used in an off-label capacity for the management of Sjögren syndrome. Hydroxychloroquine accumulates in cellular acidic compartments such as the parasitic food vacuole and mammalian lysosomes, leading to alkalinization of these structures. Among antimalarial medications, hydroxychloroquine is less likely than other medicines to cause hemolysis in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals; however, the U.S. FDA-approved drug label states there is still a risk of acute hemolytic anemia (AHA). In contrast, the Clinical Pharmacogenetics Implementation Consortium (CPIC) performed a systematic review of the available clinical literature and found low-to-no risk of AHA for individuals with G6PD deficiency who take hydroxychloroquine. It should be noted that G6PD deficiency has a range of severity; CPIC advises caution for all medications when used by an individual with a severe G6PD deficiency with chronic non-spherocytic hemolytic anemia (CNSHA). Regardless of G6PD phenotype, chronic use of hydroxychloroquine can cause irreversible retinal damage and regular visual exams are recommended by the FDA. [from Medical Genetics Summaries]

Professional guidelines

PubMed

Fanouriakis A, Kostopoulou M, Andersen J, Aringer M, Arnaud L, Bae SC, Boletis J, Bruce IN, Cervera R, Doria A, Dörner T, Furie RA, Gladman DD, Houssiau FA, Inês LS, Jayne D, Kouloumas M, Kovács L, Mok CC, Morand EF, Moroni G, Mosca M, Mucke J, Mukhtyar CB, Nagy G, Navarra S, Parodis I, Pego-Reigosa JM, Petri M, Pons-Estel BA, Schneider M, Smolen JS, Svenungsson E, Tanaka Y, Tektonidou MG, Teng YO, Tincani A, Vital EM, van Vollenhoven RF, Wincup C, Bertsias G, Boumpas DT
Ann Rheum Dis 2024 Jan 2;83(1):15-29. doi: 10.1136/ard-2023-224762. PMID: 37827694
Ramos-Casals M, Brito-Zerón P, Bombardieri S, Bootsma H, De Vita S, Dörner T, Fisher BA, Gottenberg JE, Hernandez-Molina G, Kocher A, Kostov B, Kruize AA, Mandl T, Ng WF, Retamozo S, Seror R, Shoenfeld Y, Sisó-Almirall A, Tzioufas AG, Vitali C, Bowman S, Mariette X; EULAR-Sjögren Syndrome Task Force Group
Ann Rheum Dis 2020 Jan;79(1):3-18. Epub 2019 Oct 31 doi: 10.1136/annrheumdis-2019-216114. PMID: 31672775
Fava A, Petri M
J Autoimmun 2019 Jan;96:1-13. Epub 2018 Nov 16 doi: 10.1016/j.jaut.2018.11.001. PMID: 30448290Free PMC Article

Curated

DailyMed Drug Label, hydroxychloroquine, 2022

Gammal et al, Expanded Clinical Pharmacogenetics Implementation Consortium Guideline for Medication Use in the Context of G6PD Genotype. 2 Sept 2022. Clin Pharmacol Ther.

Recent clinical studies

Etiology

Englert KA, Dyduch G, Kłosowicz A, Spałkowska M, Jaworek AK, Migacz-Gruszka K, Jarosz-Chudek A, Mercuri SR, Szpor J, Mazzoccoli G, Damiani G, Wojas-Pelc A
Medicina (Kaunas) 2023 Nov 17;59(11) doi: 10.3390/medicina59112022. PMID: 38004071Free PMC Article

Therapy

Englert KA, Dyduch G, Kłosowicz A, Spałkowska M, Jaworek AK, Migacz-Gruszka K, Jarosz-Chudek A, Mercuri SR, Szpor J, Mazzoccoli G, Damiani G, Wojas-Pelc A
Medicina (Kaunas) 2023 Nov 17;59(11) doi: 10.3390/medicina59112022. PMID: 38004071Free PMC Article
Tarek M, Savarino A
Eur J Drug Metab Pharmacokinet 2020 Dec;45(6):715-723. doi: 10.1007/s13318-020-00640-6. PMID: 32780273Free PMC Article

Prognosis

Englert KA, Dyduch G, Kłosowicz A, Spałkowska M, Jaworek AK, Migacz-Gruszka K, Jarosz-Chudek A, Mercuri SR, Szpor J, Mazzoccoli G, Damiani G, Wojas-Pelc A
Medicina (Kaunas) 2023 Nov 17;59(11) doi: 10.3390/medicina59112022. PMID: 38004071Free PMC Article

Clinical prediction guides

Englert KA, Dyduch G, Kłosowicz A, Spałkowska M, Jaworek AK, Migacz-Gruszka K, Jarosz-Chudek A, Mercuri SR, Szpor J, Mazzoccoli G, Damiani G, Wojas-Pelc A
Medicina (Kaunas) 2023 Nov 17;59(11) doi: 10.3390/medicina59112022. PMID: 38004071Free PMC Article

Therapeutic recommendations

From Medical Genetics Summaries

This section contains excerpted 1 information on gene-based dosing recommendations. Neither this section nor other parts of this review contain the complete recommendations from the sources.

2022 Statement from the US Food and Drug Administration (FDA):

Hemolysis has been reported in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Monitor for hemolytic anemia as this can occur, particularly in association with other drugs that cause hemolysis.

Please review the complete therapeutic recommendations that are located here: (3)

1 The FDA labels specific drug formulations. We have substituted the generic names for any drug labels in this excerpt. The FDA may not have labeled all formulations containing the generic drug. Certain terms, genes and genetic variants may be corrected in accordance to nomenclature standards, where necessary. We have given the full name of abbreviations, shown in square brackets, where necessary.

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • DailyMed Drug Label, 2022
      DailyMed Drug Label, hydroxychloroquine, 2022
    • CPIC, 2022
      Gammal et al, Expanded Clinical Pharmacogenetics Implementation Consortium Guideline for Medication Use in the Context of G6PD Genotype. 2 Sept 2022. Clin Pharmacol Ther.

    Consumer resources

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