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Hydroxychloroquine

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"HCQ" redirects here. For other uses, see HCQ (disambiguation).
Not to be confused with Chloroquine.

Hydroxychloroquine
Hydroxychloroquine freebase molecule
Clinical data
Trade namesPlaquenil, others
Other namesHydroxychloroquine sulfate
AHFS/Drugs.comMonograph
MedlinePlusa601240
License data
Pregnancy
category
Routes of
administration		By mouth (tablets)
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
  • US: ℞-only
  • In general: ℞ (Prescription only)
Pharmacokinetic data
BioavailabilityVariable (74% on average); Tmax = 2–4.5 hours
Protein binding45%
MetabolismLiver
Elimination half-life32–50 days
ExcretionMostly kidney (23–25% as unchanged drug), also biliary (<10%)
Identifiers
  • (RS)-2-[{4-[(7-chloroquinolin-4-yl)amino]pentyl}(ethyl)amino]ethanol
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.003.864 Edit this at Wikidata
Chemical and physical data
FormulaC18H26ClN3O
Molar mass335.872 g·mol−1
3D model (JSmol)
  • Clc1cc2nccc(c2cc1)NC(C)CCCN(CC)CCO
  • InChI=1S/C18H26ClN3O/c1-3-22(11-12-23)10-4-5-14(2)21-17-8-9-20-18-13-15(19)6-7-16(17)18/h6-9,13-14,23H,3-5,10-12H2,1-2H3,(H,20,21) checkY
  • Key:XXSMGPRMXLTPCZ-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Hydroxychloroquine (HCQ), sold under the brand name Plaquenil among others, is a medication used to prevent and treat malaria in areas where malaria remains sensitive to chloroquine.[2] Other uses include treatment of rheumatoid arthritis, lupus, and porphyria cutanea tarda.[2] It is taken by mouth.[2] HCQ is being studied to prevent and treat coronavirus disease 2019 (COVID‑19).[3] High-quality evidence of benefit for such use is lacking, with concerns of potential harms from side effects.[3][4][5]

Common side effects may include vomiting, headache, changes in vision, and muscle weakness.[2] Severe side effects may include allergic reactions, vision problems, and heart problems.[2][6] Although all risk cannot be excluded, it remains a treatment for rheumatic disease during pregnancy.[7] Hydroxychloroquine is in the antimalarial and 4-aminoquinoline families of medication.[2]

Hydroxychloroquine was approved for medical use in the United States in 1955.[2] It is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system.[8] In 2017, it was the 128th most commonly prescribed medication in the United States, with more than five million prescriptions.[9][10] The speculative use of hydroxychloroquine for COVID‑19 threatens its availability for people with established indications.[4]

Medical use

Hydroxychloroquine treats rheumatic disorders such as systemic lupus erythematosus, rheumatoid arthritis, and porphyria cutanea tarda, and certain infections such as Q fever and certain types of malaria.[2] It is considered the first-line treatment for systemic lupus erythematosus.[11] Certain types of malaria, resistant strains, and complicated cases require different or additional medication.[2]

It is widely used to treat primary Sjögren syndrome but does not appear to be effective.[12] Hydroxychloroquine is widely used in the treatment of post-Lyme arthritis. It may have both an anti-spirochete activity and an anti-inflammatory activity, similar to the treatment of rheumatoid arthritis.[13]

Contraindications

The drug label advises that hydroxychloroquine should not be prescribed to individuals with known hypersensitivity to 4-aminoquinoline compounds.[14] There are several other contraindications,[15][16] and caution is required if the person considered for treatment has certain heart conditions, diabetes, or psoriasis.[17]

Adverse effects

The most common adverse effects are nausea, stomach cramps, and diarrhea. Other common adverse effects include itching and headache.[4] The most serious adverse effects affect the eye, with dose-related retinopathy as a concern even after hydroxychloroquine use is discontinued.[2] Serious reported neuropsychiatric adverse effects of hydroxychloroquine use include agitation, mania, difficulty sleeping, hallucinations, psychosis, catatonia, paranoia, depression, and suicidal thoughts.[4] In rare situations, hydroxychloroquine has been implicated in cases of serious skin reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and Drug reaction with eosinophilia and systemic symptoms.[4] Reported blood abnormalities with its use include lymphopenia, eosinophilia, and atypical lymphocytosis.[4]

For short-term treatment of acute malaria, adverse effects can include abdominal cramps, diarrhea, heart problems, reduced appetite, headache, nausea and vomiting.[2] Other adverse effects noted with short-term use of HCQ include low blood sugar and QT interval prolongation.[3] Idiosyncratic hypersensitivity reactions have occurred.[4]

For prolonged treatment of lupus or rheumatoid arthritis, adverse effects include the acute symptoms, plus altered eye pigmentation, acne, anemia, bleaching of hair, blisters in mouth and eyes, blood disorders, cardiomyopathy,[3] convulsions, vision difficulties, diminished reflexes, emotional changes, excessive coloring of the skin, hearing loss, hives, itching, liver problems or liver failure, loss of hair, muscle paralysis, weakness or atrophy, nightmares, psoriasis, reading difficulties, tinnitus, skin inflammation and scaling, skin rash, vertigo, weight loss, and occasionally urinary incontinence.[2] Hydroxychloroquine can worsen existing cases of both psoriasis and porphyria.[2]

Children may be especially vulnerable to developing adverse effects from hydroxychloroquine.[2]

Eyes

Main article: Chloroquine retinopathy

One of the most serious side effects is retinopathy (generally with chronic use).[2][18] People taking 400 mg of hydroxychloroquine or less per day generally have a negligible risk of macular toxicity, whereas the risk begins to increase when a person takes the medication over five years or has a cumulative dose of more than 1000 grams. The daily safe maximum dose for eye toxicity can be computed from a person's height and weight.[19] Macular toxicity is related to the total cumulative dose rather than the daily dose. Regular eye screening, even in the absence of visual symptoms, is recommended to begin when either of these risk factors occurs.[20]

Toxicity from hydroxychloroquine may be seen in two distinct areas of the eye: the cornea and the macula. The cornea may become affected (relatively commonly) by an innocuous cornea verticillata or vortex keratopathy and is characterized by whorl-like corneal epithelial deposits. These changes bear no relationship to dosage and are usually reversible on cessation of hydroxychloroquine.

The macular changes are potentially serious. Advanced retinopathy is characterized by reduction of visual acuity and a "bull's eye" macular lesion which is absent in early involvement.

Overdose

Hydroxychloroquine and chloroquine are extremely toxic in overdose.[4] Serious symptoms of overdose generally occur within an hour of ingestion.[21] These symptoms may include sleepiness, vision changes, seizures, coma, stopping of breathing, and heart problems such as ventricular fibrillation and low blood pressure.[4][21][22] Loss of vision may be permanent.[23] Low blood potassium, to levels of 1 to 2 mmol/L, may also occur.[21][24] Cardiovascular abnormalities such as QRS complex widening and QT interval prolongation may also occur.[4]

Chloroquine has a risk of death in overdose in adults of about 20%, while hydroxychloroquine is estimated to be two or three fold less toxic.[21] While overdoses of hydroxychloroquine have historically been uncommon, one report documented three deaths out of eight cases.[25]

Treatment recommendations include early mechanical ventilation, heart monitoring, and activated charcoal.[21] Supportive treatment with intravenous fluids and vasopressors may be required with epinephrine being the vasopressor of choice.[21] Stomach pumping may also be used.[25] Sodium bicarbonate and hypertonic saline may be used in cases of severe QRS complex widening.[4] Seizures may be treated with benzodiazepines.[21] Intravenous potassium chloride may be required, however this may result in high blood potassium later in the course of the disease.[21] Dialysis does not appear to be useful.[21]

Interactions

The drug transfers into breast milk.[1] There is no evidence that its use during pregnancy is harmful to the developing fetus and its use is not contraindicated in pregnancy.[4]

The concurrent use of HCQ and the antibiotic azithromycin appears to increase the risk for certain serious side effects with short-term use, such as an increased risk of chest pain, congestive heart failure, and mortality from cardiovascular causes.[3] Care should be taken if combined with medication altering liver function as well as aurothioglucose (Solganal), cimetidine (Tagamet) or digoxin (Lanoxin). HCQ can increase plasma concentrations of penicillamine which may contribute to the development of severe side effects. It enhances hypoglycemic effects of insulin and oral hypoglycemic agents. Dose altering is recommended to prevent profound hypoglycemia. Antacids may decrease the absorption of HCQ. Both neostigmine and pyridostigmine antagonize the action of hydroxychloroquine.[26]

While there may be a link between hydroxychloroquine and hemolytic anemia in those with glucose-6-phosphate dehydrogenase deficiency, this risk may be low in those of African descent.[27]

Specifically, the US Food and Drug Administration's (FDA) drug label for hydroxychloroquine lists the following drug interactions:[14]

  • Digoxin (wherein it may result in increased serum digoxin levels)
  • Insulin or anti-diabetic medication (wherein it may enhance the effects of a hypoglycemic treatment)
  • Drugs that prolong QT interval and other arrhythmogenic drugs (as Hydroxychloroquine prolongs the QT interval and may increase the risk of inducing serious abnormal heart rhythms (ventricular arrhythmias) if used concurrently)[6]
  • Mefloquine and other drugs known to lower the seizure threshold (co-administration with other antimalarials known to lower the convulsion threshold may increase risk of convulsions)
  • Antiepileptics (concurrent use may impair the antiepileptic activity)
  • Methotrexate (combined use is unstudied and may increase the frequency of side effects)
  • Cyclosporin (wherein an increased plasma cyclosporin level was reported when used together).

Pharmacology

Pharmacokinetics

Hydroxychloroquine has similar pharmacokinetics to chloroquine, with rapid gastrointestinal absorption, large distribution volume,[28] and elimination by the kidneys. Cytochrome P450 enzymes (CYP2D6, 2C8, 3A4 and 3A5) metabolize hydroxychloroquine to N-desethylhydroxychloroquine.[29] Both agents also inhibit CYP2D6 activity and may interact with other medications that depend on this enzyme.[4]

Pharmacodynamics

Antimalarials are lipophilic weak bases and easily pass plasma membranes. The free base form accumulates in lysosomes (acidic cytoplasmic vesicles) and is then protonated,[30] resulting in concentrations within lysosomes up to 1000 times higher than in culture media. This increases the pH of the lysosome from four to six.[31] Alteration in pH causes inhibition of lysosomal acidic proteases causing a diminished proteolysis effect.[32] Higher pH within lysosomes causes decreased intracellular processing, glycosylation and secretion of proteins with many immunologic and nonimmunologic consequences.[33] These effects are believed to be the cause of a decreased immune cell functioning such as chemotaxis, phagocytosis and superoxide production by neutrophils.[34] HCQ is a weak diprotic base that can pass through the lipid cell membrane and preferentially concentrate in acidic cytoplasmic vesicles. The higher pH of these vesicles in macrophages or other antigen-presenting cells limits the association of autoantigenic (any) peptides with class II MHC molecules in the compartment for peptide loading and/or the subsequent processing and transport of the peptide-MHC complex to the cell membrane.[35]

Mechanism of action

Hydroxychloroquine increases[36] lysosomal pH in antigen-presenting cells.[3] In inflammatory conditions, it blocks toll-like receptors on plasmacytoid dendritic cells (PDCs).[37] Toll-like receptor 9 (TLR 9), which recognizes DNA-containing immune complexes, leads to the production of interferon and causes the dendritic cells to mature and present antigen to T cells. Hydroxychloroquine, by decreasing TLR signaling, reduces the activation of dendritic cells and the inflammatory process.

In 2003, a novel mechanism was described wherein hydroxychloroquine inhibits stimulation of the toll-like receptor (TLR) 9 family receptors. TLRs are cellular receptors for microbial products that induce inflammatory responses through activation of the innate immune system.[38]

As with other quinoline antimalarial drugs, the antimalarial mechanism of action of quinine has not been fully resolved. The most accepted model is based on hydrochloroquinine and involves the inhibition of hemozoin biocrystallization, which facilitates the aggregation of cytotoxic heme. Free cytotoxic heme accumulates in the parasites, causing death.[39]

Hydroxychloroquine increases the risk of low blood sugar through several mechanisms. These include decreased clearance of the hormone insulin from the blood, increased insulin sensitivity, and increased release of insulin from the pancreas.[4]

Society and culture

Cost

The wholesale cost in the developing world was about US$4.65 per month as of 2015, when used for rheumatoid arthritis or lupus.[40] In the United States the wholesale cost of a month of treatment is about US$25 as of 2020.[41] In the United Kingdom this dose costs the National Health Service about £5.15.[42]

Brand names

It is frequently sold as a sulfate salt known as hydroxychloroquine sulfate.[2] 200 mg of the sulfate salt is equal to 155 mg of the base.[2]

Brand names of hydroxychloroquine include Plaquenil, Hydroquin, Axemal (in India), Dolquine, Quensyl, Quinoric.[43]

COVID-19

See also: Chloroquine § COVID-19, Surgisphere § COVID-19, COVID-19 drug development § Hydroxychloroquine, COVID-19 drug repurposing research § Hydroxychloroquine, and Trump administration communication during the COVID-19 pandemic § Chloroquine and hydroxychloroquine

There is no strong scientific evidence to support the use of hydroxychloroquine for preventing or treating coronavirus disease 2019 (COVID‑19).[3][4][44][45] While its use is not approved by the FDA for COVID‑19 treatment, as of April 2020, there is an Emergency Use Authorization for its use,[46] and it has been used off label for potential treatment of the disease.[47] On 24 April 2020, citing the risk of "serious heart rhythm problems", the FDA posted a caution against using the drug for COVID‑19 "outside of the hospital setting or a clinical trial".[48]

On 29 May 2020, the European Medicines Agency (EMA) published a list of references of observational studies of chloroquine and hydroxychloroquine in people with COVID‑19.[49]

A randomized, double-blind, placebo-controlled trial of hydroxychloroquine in 821 participants found that it does not prevent COVID‑19 but the study has some limitations.[50][51]

Timeline

On 17 March 2020, the AIFA Scientific Technical Commission of the Italian Medicines Agency expressed a favorable opinion on including the off-label use of chloroquine and hydroxychloroquine for the treatment of COVID‑19.[52]

During a press briefing on 19 March 2020; Donald Trump, the President of the United States, promoted the drugs chloroquine and hydroxychloroquine as a potential treatment for COVID‑19.[53][54] Trump claimed that chloroquine had been FDA "approved very, very quickly" while discussing treatments for COVID‑19. The FDA later said they had not given approval for the drug to be used in treatment of COVID‑19,[55] but was now allowing chloroquine under compassionate use guidelines.[56][57] Trump's remarks led to a shortage of chloroquine and hydroxychloroquine in the United States and panic-buying in Africa and South Asia.[58][59]

In the US, in March 2020, several state pharmacy boards reported that some doctors and dentists were writing prescriptions for hydroxychloroquine and a related drug, chloroquine, to themselves, family members, and staff.[60][61] Sudden demand spikes caused by hospital use for severely ill COVID‑19 patients and prescriptions for prophylaxis have resulted in shortages; doctors have expressed concern that patients who have long taken hydroxychloroquine for other approved indications, like lupus and rheumatoid arthritis, will be unable to procure needed medicine.[61][62]

News outlets reported on 24 March 2020, that in the state of Arizona, a man had died, leaving his wife in critical condition, as a result of ingesting a product containing chloroquine phosphate designed for treating sick fish. The couple believed the fish treatment could prevent them from contracting COVID‑19.[63] Although chloroquine phosphate is a related compound to hydroxychloroquine, unlike hydroxychloroquine it is used for the treatment of fish parasites and infections. It has a different chemical structure from chloroquine and hydroxychloroquine which, when used in humans and other animals, could result in death.[63][64]

On 28 March 2020, the US Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) to allow hydroxychloroquine sulfate and chloroquine phosphate products donated to the Strategic National Stockpile (SNS) to be distributed and used for certain people who are hospitalized with COVID‑19.[65][66] In anticipation of product shortages, the FDA issued product-specific guidance for chloroquine phosphate and for hydroxychloroquine sulfate for generic drug manufacturers.[67] On 24 April 2020, "due to risk of heart rhythm problems", the FDA cautioned the use of hydroxychloroquine or chloroquine for COVID‑19 outside of the hospital setting or a clinical trial. [68]

On 29 April 2020, based on a preprint retrospective cohort study posted 10 April 2020, on medRxiv of more than 320,000 individuals that were not infected with COVID‑19, but had been treated with a combination of both hydroxychloroquine and azithromycin, an article published in The FASEB Journal cautioned against this combination to treat patients with COVID‑19 outside the context of a clinical trial. This was due to safety concerns with this combination and lack of evidence showing benefit to combining these medications. However the article suggested the combination could be used to treat COVID‑19 patients if new strong scientific evidence showed that combination as beneficial, there is no alternative treatment available, and the patients are counselled and closely monitored. [3]

On 12 May 2020 news outlets reported that NYU hospitals had treated 411 patients hospitalized with COVID-19 using an investigational therapy of hydroxychloroquine, azithromycin and zinc. [69] [70] Only low-level, in-vitro and preprint retrospective cohort study evidence suggests that the addition of zinc with hydroxychloroquine may be beneficial in the treatment of COVID-19 patients. [71]. To obtain high-level evidence if the addition of zinc is beneficial in this combination a Randomized Controlled Trial is currently recruiting and estimated to complete 31 December 2020. [72]

On 18 May 2020, Trump publicly stated that he was taking hydroxychloroquine combined with zinc and an initial dose of azithromycin during the COVID‑19 pandemic. [73]

Based on the results of a study published in The Lancet (which was retracted on 4 June 2020) [17][74][75] the World Health Organization suspended hydroxychloroquine from its global drug trials for COVID‑19 treatments on 26 May 2020, due to safety concerns in that study. It had previously enrolled 3,500 patients from 17 countries in the Solidarity Trial, which was the official name of its study of hydroxychloroquine against COVID‑19.[76] Due to the increased risks described in a subsequently retracted study, France, Italy and Belgium banned the use of hydroxychloroquine as a COVID‑19 treatment.[77][78][79]. None of the results used as the basis of these bans involved outpatient treatment. The first results for outpatient clinical trials of hydroxychloroquine with azithromycin are expected in September 2020.[80]

On 29 May 2020, the EMA issued a public health statement reminding healthcare professionals to closely monitor people with COVID‑19 who are receiving hydroxychloroquine.[81]

On June 3 2020, the WHO announced it would resume its global trial of hydroxychloroquine, after its data safety monitoring committee found there was no increased risk of death for COVID‑19 patients taking it.[82]

On June 4 2020, an article about the treatment of COVID‑19 patients using hydroxychloroquine with or without macrolides that had been published in The Lancet on 22 May 2020, was retracted by its authors. Before its retraction it had provided evidence that hospitalized COVID‑19 patients treated with hydroxychloroquine or chloroquine (with or without a macrolide) did not benefit from the treatment, but instead were at greater risk of death. However since its publication questions were raised about the accuracy of the data used in the article, prompting a third party review which resulted in the retraction of the article from the journal.[17][74][83]

See also

  • Didier Raoult – French physician and controversial advocate for using hydroxychloroquine as prophylaxis and cure of COVID‑19

References

  1. ^ a b c "Hydroxychloroquine Use During Pregnancy". Drugs.com. 28 February 2020. Retrieved 21 March 2020.
  2. ^ a b c d e f g h i j k l m n o p q "Hydroxychloroquine Sulfate Monograph for Professionals". The American Society of Health-System Pharmacists. 20 March 2020. Archived from the original on 20 March 2020. Retrieved 20 March 2020.
  3. ^ a b c d e f g h Meyerowitz EA, Vannier AG, Friesen MG, Schoenfeld S, Gelfand JA, Callahan MV, et al. (May 2020). "Rethinking the role of hydroxychloroquine in the treatment of COVID-19". FASEB Journal. 34 (5): 6027–6037. doi:10.1096/fj.202000919. PMC 7267640. PMID 32350928.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  4. ^ a b c d e f g h i j k l m n o Juurlink DN (April 2020). "Safety considerations with chloroquine, hydroxychloroquine and azithromycin in the management of SARS-CoV-2 infection". CMAJ. 192 (17): E450–E453. doi:10.1503/cmaj.200528. PMC 7207200. PMID 32269021.
  5. ^ Cortegiani A, Ingoglia G, Ippolito M, Giarratano A, Einav S (June 2020). "A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19". Journal of Critical Care. 57: 279–283. doi:10.1016/j.jcrc.2020.03.005. PMID 32173110.
  6. ^ a b "Guidance on patients at risk of drug-induced sudden cardiac death from off-label COVID-19 treatments". newsnetwork.mayoclinic.org. 25 March 2020.
  7. ^ Flint J, Panchal S, Hurrell A, van de Venne M, Gayed M, Schreiber K, et al. (September 2016). "BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding—Part I: standard and biologic disease modifying anti-rheumatic drugs and corticosteroids". Rheumatology. 55 (9): 1693–7. doi:10.1093/rheumatology/kev404. PMID 26750124.
  8. ^ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  9. ^ "The Top 300 of 2020". ClinCalc. Retrieved 18 March 2020.
  10. ^ "Hydroxychloroquine Sulfate – Drug Usage Statistics". ClinCalc. Retrieved 7 April 2020.
  11. ^ Chew CY, Mar A, Nikpour M, Saracino AM (May 2020). "Hydroxychloroquine in dermatology: New perspectives on an old drug". The Australasian Journal of Dermatology. 61 (2): e150–e157. doi:10.1111/ajd.13168. PMID 31612996.
  12. ^ Wang SQ, Zhang LW, Wei P, Hua H (May 2017). "Is hydroxychloroquine effective in treating primary Sjogren's syndrome: a systematic review and meta-analysis". BMC Musculoskeletal Disorders. 18 (1): 186. doi:10.1186/s12891-017-1543-z. PMC 5427554. PMID 28499370.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  13. ^ Steere AC, Angelis SM (October 2006). "Therapy for Lyme arthritis: strategies for the treatment of antibiotic-refractory arthritis". Arthritis and Rheumatism. 54 (10): 3079–86. doi:10.1002/art.22131. PMID 17009226. Free access icon
  14. ^ a b "Plaquenil- hydroxychloroquine sulfate tablet". DailyMed. 3 January 2020. Retrieved 20 March 2020.
  15. ^ "Plaquenil (hydroxychloroquine sulfate) dose, indications, adverse effects, interactions". pdr.net. Retrieved 19 March 2020.
  16. ^ "Drugs & Medications". webmd.com. Retrieved 19 March 2020.
  17. ^ a b c Mehra MR, Desai SS, Ruschitzka F, Patel AN (May 2020). "Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis". Lancet. doi:10.1016/S0140-6736(20)31180-6. PMC 7255293. PMID 32450107. {{cite journal}}: Unknown parameter |lay-url= ignored (help) (Retracted, see  [1])
  18. ^ Flach AJ (2007). "Improving the risk-benefit relationship and informed consent for patients treated with hydroxychloroquine". Transactions of the American Ophthalmological Society. 105: 191–4, discussion 195–7. PMC 2258132. PMID 18427609.
  19. ^ "Plaquenil Risk Calculators". EyeDock. Retrieved 7 April 2020.
  20. ^ Marmor MF, Kellner U, Lai TY, Lyons JS, Mieler WF (February 2011). "Revised recommendations on screening for chloroquine and hydroxychloroquine retinopathy" (PDF). Ophthalmology. 118 (2): 415–22. doi:10.1016/j.ophtha.2010.11.017. PMID 21292109.
  21. ^ a b c d e f g h i Ling Ngan Wong A, Tsz Fung Cheung I, Graham CA (February 2008). "Hydroxychloroquine overdose: case report and recommendations for management". European Journal of Emergency Medicine. 15 (1): 16–8. doi:10.1097/MEJ.0b013e3280adcb56. PMID 18180661.
  22. ^ Smith ER, Klein-Schwartz W (May 2005). "Are 1-2 dangerous? Chloroquine and hydroxychloroquine exposure in toddlers" (PDF). The Journal of Emergency Medicine. 28 (4): 437–43. doi:10.1016/j.jemermed.2004.12.011. PMID 15837026.
  23. ^ Roque MR, Foster CS (23 March 2020). "Chloroquine and Hydroxychloroquine Toxicity: Practice Essentials, Background, Pathophysiology" (Document). {{cite document}}: Cite document requires |publisher= (help); Unknown parameter |access-date= ignored (help); Unknown parameter |archive-date= ignored (help); Unknown parameter |archive-url= ignored (help); Unknown parameter |url-status= ignored (help); Unknown parameter |url= ignored (help); Unknown parameter |work= ignored (help)
  24. ^ Pillay VV (2012). Modern Medical Toxicology (PDF). Jaypee Brothers Publishers. p. 458. ISBN 978-93-5025-965-8.
  25. ^ a b Aronson, Jeffrey K. (2015). Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions. Elsevier. p. 261. ISBN 978-0-444-53716-4. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  26. ^ "Russian Register of Medicines: Plaquenil (hydroxychloroquine) Film-coated Tablets for Oral Use. Prescribing Information". rlsnet.ru (in Russian). Sanofi-Synthelabo. Archived from the original on 16 August 2016. Retrieved 14 July 2016.
  27. ^ Mohammad S, Clowse ME, Eudy AM, Criscione-Schreiber LG (March 2018). "Examination of Hydroxychloroquine Use and Hemolytic Anemia in G6PDH-Deficient Patients". Arthritis Care & Research. 70 (3): 481–485. doi:10.1002/acr.23296. PMID 28556555.
  28. ^ Schrezenmeier E, Dörner T (March 2020). "Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology". Nature Reviews. Rheumatology. 16 (3): 155–166. doi:10.1038/s41584-020-0372-x. PMID 32034323. Free access icon
  29. ^ Kalia S, Dutz JP (2007). "New concepts in antimalarial use and mode of action in dermatology". Dermatologic Therapy. 20 (4): 160–74. doi:10.1111/j.1529-8019.2007.00131.x. PMC 7163426. PMID 17970883. Free access icon
  30. ^ Kaufmann AM, Krise JP (April 2007). "Lysosomal sequestration of amine-containing drugs: analysis and therapeutic implications". Journal of Pharmaceutical Sciences. 96 (4): 729–46. doi:10.1002/jps.20792. PMID 17117426.
  31. ^ Ohkuma S, Poole B (July 1978). "Fluorescence probe measurement of the intralysosomal pH in living cells and the perturbation of pH by various agents". Proceedings of the National Academy of Sciences of the United States of America. 75 (7): 3327–31. Bibcode:1978PNAS...75.3327O. doi:10.1073/pnas.75.7.3327. PMC 392768. PMID 28524.
  32. ^ Ohkuma S, Chudzik J, Poole B (March 1986). "The effects of basic substances and acidic ionophores on the digestion of exogenous and endogenous proteins in mouse peritoneal macrophages". The Journal of Cell Biology. 102 (3): 959–66. doi:10.1083/jcb.102.3.959. PMC 2114118. PMID 3949884.
  33. ^ Oda K, Koriyama Y, Yamada E, Ikehara Y (December 1986). "Effects of weakly basic amines on proteolytic processing and terminal glycosylation of secretory proteins in cultured rat hepatocytes". The Biochemical Journal. 240 (3): 739–45. doi:10.1042/bj2400739. PMC 1147481. PMID 3493770.
  34. ^ Hurst NP, French JK, Gorjatschko L, Betts WH (January 1988). "Chloroquine and hydroxychloroquine inhibit multiple sites in metabolic pathways leading to neutrophil superoxide release". The Journal of Rheumatology. 15 (1): 23–7. PMID 2832600.
  35. ^ Fox R (June 1996). "Anti-malarial drugs: possible mechanisms of action in autoimmune disease and prospects for drug development". Lupus. 5 Suppl 1: S4–10. doi:10.1177/0961203396005001031. PMID 8803903.
  36. ^ Waller, Derek; Sampson, Tony. Medical Pharmacology and Therapeutics (2nd ed.). p. 370. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  37. ^ Schrezenmeier E, Dörner T (March 2020). "Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology". Nature Reviews. Rheumatology. 16 (3): 155–166. doi:10.1038/s41584-020-0372-x. PMID 32034323.
  38. ^ Takeda K, Kaisho T, Akira S (2003). "Toll-like receptors". Annual Review of Immunology. 21: 335–76. doi:10.1146/annurev.immunol.21.120601.141126. PMID 12524386. Free access icon
  39. ^ Sullivan DJ (December 2002). "Theories on malarial pigment formation and quinoline action". International Journal for Parasitology. 32 (13): 1645–53. doi:10.1016/S0020-7519(02)00193-5. PMID 12435449.
  40. ^ "Single Drug Information" (PDF). International Medical Products Price Guide. Retrieved 31 December 2019.
  41. ^ "NADAC as of 2019-08-07". Centers for Medicare and Medicaid Services. Retrieved 19 March 2020. Typical dose is 600mg per day. Costs [$]0.28157 per [daily] dose.…
  42. ^ British national formulary: BNF 69 (PDF) (69 ed.). British Medical Association. 2015. p. 730. ISBN 9780857111562. Archived (PDF) from the original on 16 April 2020. {{cite book}}: |website= ignored (help)
  43. ^ "Hydroxychloroquine trade names". Drugs-About.com. Retrieved 18 June 2019.
  44. ^ "Assessment of Evidence for COVID-19-Related Treatments: Updated 4/3/2020". ASHP. Retrieved 7 April 2020.
  45. ^ Yazdany, J; Kim, AHJ (March 2020). "Use of Hydroxychloroquine and Chloroquine During the COVID-19 Pandemic: What Every Clinician Should Know". Annals of Internal Medicine. 172 (11): M20-1334. doi:10.7326/M20-1334. PMC 7138336. PMID 32232419.
  46. ^ "Coronavirus Disease 2019 (COVID-19)". Centers for Disease Control and Prevention. 11 February 2020. Retrieved 9 April 2020.
  47. ^ Kalil AC (March 2020). "Treating COVID-19-Off-Label Drug Use, Compassionate Use, and Randomized Clinical Trials During Pandemics". JAMA. 323 (19): 1897. doi:10.1001/jama.2020.4742. PMID 32208486.
  48. ^ "FDA cautions against use of hydroxychloroquine or chloroquine for COVID-19 outside of the hospital setting or a clinical trial due to risk of heart rhythm problems". U.S. Food and Drug Administration (FDA). 24 April 2020.
  49. ^ "List of references of observational studies of chloroquine and hydroxychloroquine in COVID-19 patients" (PDF). European Medicines Agency (EMA). 29 May 2020. Retrieved 29 May 2020.
  50. ^ Boulware DR, Pullen MF, Bangdiwala AS, Pastick KA, Lofgren SM, Okafor EC, et al. (June 2020). "A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19". N. Engl. J. Med. doi:10.1056/NEJMoa2016638. PMID 32492293. {{cite journal}}: Unknown parameter |lay-url= ignored (help)
  51. ^ Cohen MS (June 2020). "Hydroxychloroquine for the Prevention of Covid-19 - Searching for Evidence". N. Engl. J. Med. doi:10.1056/NEJMe2020388. PMID 32492298.
  52. ^ "Azioni intraprese per favorire la ricerca e l'accesso ai nuovi farmaci per il trattamento del COVID-19". Italian Medicines Agency (AIFA) (in Italian). 17 March 2020. Retrieved 18 March 2020.
  53. ^ Nisen, Max (19 March 2020). "Trump Is Overhyping Unproven Coronavirus Drugs". The Washington Post. Bloomberg. Retrieved 24 March 2020. {{cite news}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  54. ^ "Remarks by President Trump, Vice President Pence, and Members of the Coronavirus Task Force in Press Briefing". White House. Retrieved 24 March 2020.
  55. ^ Dale, Daniel (20 March 2020). "Fact check: Trump wrongly claims FDA 'approved' drug chloroquine to treat the coronavirus". CNN. Retrieved 29 March 2020. {{cite news}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  56. ^ Naftulin, Julia (20 March 2020). "The FDA is allowing two drugs to be used for 'compassionate use' to treat the coronavirus. Here's what that means". Business Insider. Retrieved 1 April 2020. {{cite news}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  57. ^ Coppock, Kristen (19 March 2020). "FDA Announces Two Drugs Given 'Compassionate Use' Status in Treating COVID-19". Pharmacy Times. Retrieved 1 April 2020. {{cite news}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  58. ^ Rowland, Christopher (23 March 2020). "As Trump touts an unproven coronavirus treatment, supplies evaporate for patients who need those drugs". The Washington Post. Retrieved 24 March 2020. {{cite news}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  59. ^ Parkinson, Joe; Gauthier-Villars, David (23 March 2020). "Trump Claim That Malaria Drugs Treat Coronavirus Sparks Warnings, Shortages". The Wall Street Journal. Retrieved 26 March 2020. {{cite news}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  60. ^ Gabler, Ellen (24 March 2020). "States Say Some Doctors Stockpile Trial Coronavirus Drugs, for Themselves". The New York Times. ISSN 0362-4331. Archived from the original on 24 March 2020. Retrieved 31 March 2020. {{cite news}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  61. ^ a b Rowland, Christopher. "As Trump touts an unproven coronavirus treatment, supplies evaporate for patients who need those drugs". The Washington Post. {{cite web}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  62. ^ Torres, Stacy. "Stop hoarding hydroxychloroquine. Many Americans, including me, need it". The Washington Post. Archived from the original on 25 March 2020. Retrieved 31 March 2020. {{cite web}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  63. ^ a b "A man died after ingesting a substance he thought would protect him from coronavirus". NBC News. Retrieved 22 May 2020.
  64. ^ "FDA Letter to Stakeholders: Do Not Use Chloroquine Phosphate Intended for Fish as Treatment for COVID-19 in Humans". U.S. Food and Drug Administration (FDA). 1 May 2020.
  65. ^ Denise M Hinton (28 March 2020). "Request for Emergency Use Authorization For Use of Chloroquine Phosphate or Hydroxychloroquine Sulfate Supplied From the Strategic National Stockpile for Treatment of 2019 Coronavirus Disease". U.S. Food and Drug Administration (FDA). Retrieved 30 March 2020. Having concluded that the criteria for issuance of this authorization under 564(c) of the Act are met, I am authorizing the emergency use of chloroquine phosphate and hydroxychloroquine sulfate, as described in the Scope of Authorization section of this letter (Section II) for treatment of COVID-19 when clinical trials are not available, or participation is not feasible, subject to the terms of this authorization. Public Domain This article incorporates text from this source, which is in the public domain.
  66. ^ "Emergency Use Authorization". U.S. Food and Drug Administration (FDA). 29 March 2020. Retrieved 30 March 2020. On March 28, 2020, FDA issued an EUA to allow hydroxychloroquine sulfate and chloroquine phosphate products donated to the Stategic National Stockpile (SNS) to be distributed and used for certain hospitalized patients with COVID-19. These drugs will be distributed from the SNS to states for doctors to prescribe to adolescent and adult patients hospitalized with COVID-19, as appropriate, when a clinical trial is not available or feasible. Public Domain This article incorporates text from this source, which is in the public domain.
  67. ^ "Product-Specific Guidances for Chloroquine Phosphate and Hydroxychloro". U.S. Food and Drug Administration (FDA). 13 April 2020. Retrieved 13 April 2020.
  68. ^ "FDA cautions against use of hydroxychloroquine or chloroquine for COVID-19 outside of the hospital setting or a clinical trial due to risk of heart rhythm problems". U.S. Food and Drug Administration (FDA). 24 April 2020.
  69. ^ "Drug Combo with Hydroxychloroquine Promising: NYU Study". NY1. 12 May 2020. Retrieved 6 June 2020.
  70. ^ "Addition of Zinc May Benefit Some Being Treated for COVID-19". Physician's Briefing. 13 May 2020. Retrieved 6 June 2020.
  71. ^ "EVMS CRITICAL CARE COVID-19 MANAGEMENT PROTOCOL" (PDF). evms.edu. 1 May 2020. te Velthuis, AJ; van den Worm, SH; Sims, AC; Baric, RS; Snijder, EJ; van Hemert, MJ (4 November 2010). "Zn(2+) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture". PLoS Pathog. doi:10.1371/journal.ppat.1001176. PMC 2973827. PMID 21079686.{{cite journal}}: CS1 maint: unflagged free DOI (link) Xue, J; Moyer, A; Peng, B; Wu, J; Hannafon, BN; Ding, WQ (1 October 2014). "Chloroquine is a zinc ionophore". PLOS One. doi:10.1371/journal.pone.0109180. PMC 4182877. PMID 25271834.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  72. ^ "Hydroxychloroquine and Zinc With Either Azithromycin or Doxycycline for Treatment of COVID-19 in Outpatient Setting". clinicaltrials.gov. 1 May 2020.
  73. ^ "Trump says he takes unproven hydroxychloroquine to prevent coronavirus infection". CNBC. Retrieved 25 May 2020.
  74. ^ a b Mehra MR, Ruschitzka F, Patel AN (June 2020). "Retraction: "Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis"". Lancet. doi:10.1016/S0140-6736(20)31324-6 (inactive 5 June 2020).{{cite journal}}: CS1 maint: DOI inactive as of June 2020 (link)
  75. ^ Boseley, Sarah; Davey, Melissa (4 June 2020). "Covid-19: Lancet retracts paper that halted hydroxychloroquine trials". The Guardian. Retrieved 4 June 2020. {{cite news}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  76. ^ "Citing safety concerns, the W.H.O. paused tests of a drug Trump said he had taken". The New York Times. 26 May 2020.
  77. ^ "France bans use of hydroxychloroquine, drug touted by Trump, in coronavirus patients". CBS News. 27 May 2020.
  78. ^ Beaubien, Jason (25 May 2020). "WHO Halts Hydroxychloroquine Trial Over Safety Concerns". NPR. Retrieved 27 May 2020. {{cite news}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  79. ^ Chappell, Bill (27 May 2020). "France Bars Use Of Hydroxychloroquine In COVID-19 Cases". NPR. Retrieved 27 May 2020. {{cite news}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  80. ^ Risch, Harvey A. (2020). "Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that Should be Ramped-Up Immediately as Key to the Pandemic Crisis". American Journal of Epidemiology. doi:10.1093/aje/kwaa093. PMID 32458969.
  81. ^ "COVID-19: reminder of the risks chloroquine and hydroxychloroquine". European Medicines Agency (EMA). 29 May 2020. Retrieved 29 May 2020.
  82. ^ Davey, Melissa; Kirchgaessner, Stephanie; Boseley, Sarah (3 June 2020). "Surgisphere: governments and WHO changed Covid-19 policy based on suspect data from tiny US company". The Guardian. Retrieved 4 June 2020. {{cite web}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  83. ^ Boseley, Sarah; Davey, Melissa (4 June 2020). "Covid-19: Lancet retracts paper that halted hydroxychloroquine trials". The Guardian. Retrieved 4 June 2020. {{cite news}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
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