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hydroxychloroquine (Plaquenil)

Tradename: Plaquenil. (hydroxychloroquine sulfate). Indications: - malaria - malaria prophylaxis - Plasmodium vivax, Plasmodium ovale - rheumatoid arthritis - systemic lupus erythematosus - benefit may exceed risk in pregnancy [6] - safe during pregnancy despite pregnancy category 3 rating [4] - indicated during pregnancy even in stable patients with minimal disease activity [4] - sarcoidosis - porphyria cutanea tarda [10' - cutaneous leukocytoclastic vasculitis - polymorphous light eruption [10] - Coxiella burnetii * uncertain benefit for Sjogren's syndrome [11] Contraindications: - low-dose hydroxychloroquine can be safely used during pregnancy if necessary (see rheumatologic disorders in pregnancy) - off-label use for COVID-19 (no evidence of benefit) [16,17] - appears to have activity against SARS CoV2 (COVID-19) in vitro but is associated with higher in hospital mortality, QT prolongation & ventricular arrhythmias in patients with COVID-19 [19] - no mortality benefit to hospitalized COVID-19 patients [22] - FDA rescinded emergency use authorization of hydroxychloroquine to treat COVID-19 patients [21] - not useful for COVID-19 prophylaxis [20] or post-exposure prophylaxis [24] * also see chloroquine/hydroxychloroquine for COVID-19 Dosage: 1) malaria a) prophylaxis: 400 mg PO weekly (5 mg//kg) b) acute attack: 1] 800 mg (10 mg/kg) loading dose 2] 400 mg (5 mg/kg) in 6 hours 3] 400 mg (5 mg/kg) 18 hours after 2nd dose (day 2) 4] 400 mg (5 mg/kg) day 3 2) rheumatoid arthritis: a) start: 400 mg PO QD b) increase until optimal dose is reached c) after 4-13 weeks, decrease dose by 1/2 d) maintenance 200-400 mg PO QD 3) systemic lupus erythematosus: 200-400 mg PO QD - withdrawal may result in visceral or cutaneous flares take with food or milk Tabs: 200 mg (base 155 mg). Pharmacokinetics: 1) well absorbed after oral administration 2) metabolized by liver 3) metabolites & unchanged drug excreted into the urine 4) may take 6 months for anti-rheumatic or anti-lupus effect Adverse effects: 1) common (> 10%) - ciliary muscle dysfunction, diarrhea, loss of appetite, nausea, stomach cramps, vomiting, headache, itching 2) less common (1-10%) - ocular toxicity, vortex keratopathy*, retinopathy#, bleaching of hair, blue-black discoloration of skin, dizziness, lightheadedness, nervousness, restlessness, rash 3) uncommon (< 1%) - agranulocytosis, aplastic anemia, neutropenia, thrombocytopenia, emotional changes, neuromyopathy, ototoxicity, seizures, visual impairment 4) QT prolongation [14] - ventricular arrhythmias in 6.1% of patients hospitalized for COVID-19 vs 0.3% of controls [17] * binds with cellular lipids in the basement membrane of the cornea leading to deposition & vortex keratopathy (corneal verticillata) # Bull's eye maculopathy (image) [13] Monitor: 1) baseline CBC, LFTs, serum creatinine 2) ophthalmologic examination recommended prior to therapy & annually with continued therapy [4,8,12,25] 3) blood levels > 1.18 mg/mL predict retinopathy 6& vs 1% [15] Drug interactions: - cimetidine may increase hydroxychloroquine levels Mechanism of action: 1) inhibits locomotion of neutrophils 2) inhibits chemotaxis of eosinophils 3) impairs antigen-antibody reactions 4) thought to destabilize lysosomal vacuoles resulting in inhibition of antigen processing [4] 5) interferes with digestive vacuole function within sensitive malarial parasites Clinical trials: - hydroxychloroquine arm within the Solidarity trial for COVID-19 halted by WHO May 25, 2020 due to safety concerns [18] - relative to placebo, hydroxychloroquine did not significantly improve clinical status at hospital day 14 [23]

Interactions

drug interactions drug adverse effects of antimalarials

Related

chloroquine/hydroxychloroquine for COVID-19

General

antimalarial disease-modifying antirheumatic agent (DMARD) quinoline; leucoline; chinoleine; 1-benazazine; benzo[b]pyridine

Properties

MISC-INFO: elimination route LIVER KIDNEY pregnancy-category - C safety in lactation - ?

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  3. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  4. Medical Knowledge Self Assessment Program (MKSAP) 11, 16, 17. American College of Physicians, Philadelphia 1998, 2012, 2015
  5. UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
  6. Clowse MEB, Hydroxychloroquine in lupus pregnancy. Arthritis Rheum 2006, 54:3640 PMID: 17075810
  7. Prescriber's Letter 14(12): 2007 Hydroxychloroquine (Plaquenil) and Systemic Lupus Erythrometosus Detail-Document#: 231201 (subscription needed) http://www.prescribersletter.com
  8. Marmor MF, Kellner U, Lai TY et al Revised recommendations on screening for chloroquine and hydroxychloroquine retinopathy. Ophthalmology. 2011 Feb;118(2):415-22 PMID: 21292109
  9. Ruiz-Irastorza G, Ramos-Casals M, Brito-Zeron P, Khamashta MA. Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review. Ann Rheum Dis. 2010 Jan;69(1):20-8 PMID: 19103632
  10. Deprecated Reference
  11. Gottenberg J-E et al. Effects of hydroxychloroquine on symptomatic improvement in primary Sjogren syndrome: The JOQUER randomized clinical trial. JAMA 2014 Jul 16; 312:249 PMID: 25027140
  12. Geriatric Review Syllabus, 9th edition (GRS9) Medinal-Walpole A, Pacala JT, Porter JF (eds) American Geriatrics Society, 2016 - Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022
  13. Modi YS, Singh RP Bull's-Eye Maculopathy Associated with Hydroxychloroquine. N Engl J Med 2019; 380:1656. April 25, 2019 PMID: 31018071 Free Article https://www.nejm.org/doi/full/10.1056/NEJMicm1412167
  14. Lou N Heart Groups: Clear Risks With HCQ for COVID-19 - AHA/ACC/HRS caution on malaria drug plus antibiotic. MedPage Today April 9, 2020 https://www.medpagetoday.com/infectiousdisease/covid19/85870 - Roden DM, Harrington RA, Poppas A, Russo AM. Considerations for drug interactions on QTc in exploratory COVID-19 (coronarvirus disease 2019) treatment. Circulation 2020. April 8 PMID: 32267732 https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.047521
  15. Petri M, Elkhalifa M, Li J et al. Hydroxychloroquine blood levels predict hydroxychloroquine retinopathy. Arthritis Rheumatol 2020 Mar; 72:448 PMID: 31532077 https://onlinelibrary.wiley.com/doi/abs/10.1002/art.41121
  16. Geleris J, Sun Y, Platt J et al Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19. N Engl J Med. May 7, 2019 PMID: 32379955 https://www.nejm.org/doi/full/10.1056/NEJMoa2012410
  17. Mehra MR, Desai SS, Ruschitzka F, Patel AN Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. Lancet. May 22, 2020 PMID: 32450107 Free PMC article https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31180-6/fulltext * authors associated with Surgisphere implicated in false data * - Cavalcanti AB, Zampieri FG, Rosa RG et al Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19. N Engl J Med. July 23, 2020 PMID: 32706953 https://www.nejm.org/doi/full/10.1056/NEJMoa2019014 - Skipper CP et al. Hydroxychloroquine in nonhospitalized adults with early COVID-19: A randomized trial. Ann Intern Med 2020 Jul 16; PMID: 32673060 Free PMC article. https://www.acpjournals.org/doi/10.7326/M20-4207 - Schluger NW. The saga of hydroxychloroquine and COVID-19: A cautionary tale. Ann Intern Med 2020 Jul 16; [e-pub]. PMID: 32673059 Free PMC article https://www.acpjournals.org/doi/10.7326/M20-5041
  18. Reuters. May 25, 2020 Clinical trial of hydroxychloroquine in COVID-19 patients paused-WHO. https://www.msn.com/en-us/news/world/clinical-trial-of-hydroxychloroquine-in-covid-19-patients-paused-who/ar-BB14zn1l?li=BBnb7Kz
  19. Borba MGS, Val FFA, Sampaio VS et al Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection. A Randomized Clinical Trial. JAMA Netw Open. 2020;3(4.23):e208857 PMID: 32330277 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2765270 - Fihn SD, Perencevich E, Bradley SM Caution Needed on the Use of Chloroquine and Hydroxychloroquine for Coronavirus Disease 2019. JAMA Netw Open. 2020;3(4.23):e209035 PMID: 32330276 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2765269
  20. Boulware DR, Pullen MF, Bangdiwala AS et al A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19. N Engl J Med. June 3, 2020 PMID: 32492293 https://www.nejm.org/doi/full/10.1056/NEJMoa2016638 - Cohen MS Hydroxychloroquine for the Prevention of Covid-19 - Searching for Evidence N Engl J Med. June 3, 2020 PMID: 32492298 https://www.nejm.org/doi/full/10.1056/NEJMe2020388 - Abella BS, Jolkovsky EL, Biney BT et al Efficacy and Safety of Hydroxychloroquine vs Placebo for Pre-exposure SARS-CoV-2 Prophylaxis Among Health Care Workers. A Randomized Clinical Trial. JAMA Intern Med. Published online September 30, 2020 PMID: 33001138 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2771265
  21. Walker M HCQ No Longer Approved Even a Little for COVID-19 - Study after study showed no benefit, and now the FDA has had enough MedPage Today. June 15, 2020 https://www.medpagetoday.com/infectiousdisease/covid19/87066 - FDA News Release June 15, 2020 Coronavirus (COVID-19) Update: FDA Revokes Emergency Use Authorization for Chloroquine and Hydroxychloroquine. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-revokes-emergency-use-authorization-chloroquine-and
  22. Horby P et al for The RECOVERY Collaborative Group Effect of Hydroxychloroquine in Hospitalized Patients with Covid-19. N Engl J Med 2020. Oct 8. PMID: 33031652 https://www.nejm.org/doi/full/10.1056/NEJMoa2022926
  23. Self WH, Semler MW, Leither LM et al Effect of Hydroxychloroquine on Clinical Status at 14 Days in Hospitalized Patients With COVID-19. A Randomized Clinical Trial. JAMA. Published online November 9, 2020 PMID: 33165621 PMCID: PMC7653542 https://jamanetwork.com/journals/jama/fullarticle/2772922
  24. Mitja O, Corbacho-Monne M, Ubals M et al A Cluster-Randomized Trial of Hydroxychloroquine for Prevention of Covid-19. N Engl J Med. 2020. Nov 24. PMID: 32674126 PMCID: PMC7454406 Free PMC article https://www.nejm.org/doi/full/10.1056/NEJMoa2021801
  25. Marmor M, Kellner U, Lai T et al. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision). Ophthalmology. 2016;123(6):1386-1394 PMID: 26992838 https://www.aaojournal.org/article/S0161-6420(16)00201-3/fulltext
  26. Melles RB et al. Hydroxychloroquine dose and risk for incident retinopathy: A cohort study. Ann Intern Med 2023 Jan 17; [e-pub] PMID: 36645889 https://www.acpjournals.org/doi/10.7326/M22-2453