hydroxychloroquine (Plaquenil)
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Introduction
Tradename: Plaquenil. (hydroxychloroquine sulfate).
Indications
- malaria
- rheumatoid arthritis
- systemic lupus erythematosus
- 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- FDA rescinded emergency use authorization of hydroxychloroquine to treat COVID-19 patients[21]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
- malaria
- prophylaxis: 400 mg PO weekly (5 mg//kg)
- acute attack:
- 800 mg (10 mg/kg) loading dose
- 400 mg (5 mg/kg) in 6 hours
- 400 mg (5 mg/kg) 18 hours after 2nd dose (day 2)
- 400 mg (5 mg/kg) day 3
- rheumatoid arthritis:
- 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
- well absorbed after oral administration
- metabolized by liver
- metabolites & unchanged drug excreted into the urine
- may take 6 months for anti-rheumatic or anti-lupus effect
elimination via liver
elimination via kidney
Monitor
- baseline CBC, LFTs, serum creatinine
- ophthalmologic examination recommended prior to therapy & annually with continued therapy[4][8][12][25]
- blood levels > 1.18 mg/mL predict retinopathy 6& vs 1%[15]
Adverse effects
- common (> 10%)
- ciliary muscle dysfunction, diarrhea, loss of appetite, nausea, stomach cramps, vomiting, headache, itching
- less common (1-10%)
- ocular toxicity, vortex keratopathy*, retinopathy#, bleaching of hair, blue-black discoloration of skin, dizziness, lightheadedness, nervousness, restlessness, rash
- uncommon (< 1%)
- agranulocytosis, aplastic anemia, neutropenia, thrombocytopenia, emotional changes, neuromyopathy, ototoxicity, seizures, visual impairment
- 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]
Drug interactions
- cimetidine may increase hydroxychloroquine levels
Mechanism of action
- inhibits locomotion of neutrophils
- inhibits chemotaxis of eosinophils
- impairs antigen-antibody reactions
- thought to destabilize lysosomal vacuoles resulting in inhibition of antigen processing[4]
- 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]
More general terms
- quinoline; leucoline; chinoleine; 1-benazazine; benzo[b]pyridine
- disease-modifying antirheumatic agent (DMARD)
- antimalarial
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ 4.0 4.1 4.2 4.3 4.4 Medical Knowledge Self Assessment Program (MKSAP) 11, 16, 17. American College of Physicians, Philadelphia 1998, 2012, 2015
- ↑ UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
- ↑ 6.0 6.1 Clowse MEB, Hydroxychloroquine in lupus pregnancy. Arthritis Rheum 2006, 54:3640 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17075810
- ↑ Prescriber's Letter 14(12): 2007 Hydroxychloroquine (Plaquenil) and Systemic Lupus Erythrometosus Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=231201&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 8.0 8.1 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: https://www.ncbi.nlm.nih.gov/pubmed/21292109
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/19103632
- ↑ 10.0 10.1 Deprecated Reference
- ↑ 11.0 11.1 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: https://www.ncbi.nlm.nih.gov/pubmed/25027140
- ↑ 12.0 12.1 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 - ↑ 13.0 13.1 Modi YS, Singh RP Bull's-Eye Maculopathy Associated with Hydroxychloroquine. N Engl J Med 2019; 380:1656. April 25, 2019 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31018071 Free Article https://www.nejm.org/doi/full/10.1056/NEJMicm1412167
- ↑ 14.0 14.1 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: https://www.ncbi.nlm.nih.gov/pubmed/32267732 https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.047521 - ↑ 15.0 15.1 Petri M, Elkhalifa M, Li J et al. Hydroxychloroquine blood levels predict hydroxychloroquine retinopathy. Arthritis Rheumatol 2020 Mar; 72:448 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31532077 https://onlinelibrary.wiley.com/doi/abs/10.1002/art.41121
- ↑ 16.0 16.1 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: https://www.ncbi.nlm.nih.gov/pubmed/32379955 https://www.nejm.org/doi/full/10.1056/NEJMoa2012410
- ↑ 17.0 17.1 17.2 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: https://www.ncbi.nlm.nih.gov/pubmed/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: https://www.ncbi.nlm.nih.gov/pubmed/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: https://www.ncbi.nlm.nih.gov/pubmed/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: https://www.ncbi.nlm.nih.gov/pubmed/32673059 Free PMC article https://www.acpjournals.org/doi/10.7326/M20-5041 - ↑ 18.0 18.1 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
- ↑ 19.0 19.1 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: https://www.ncbi.nlm.nih.gov/pubmed/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: https://www.ncbi.nlm.nih.gov/pubmed/32330276 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2765269 - ↑ 20.0 20.1 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: https://www.ncbi.nlm.nih.gov/pubmed/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: https://www.ncbi.nlm.nih.gov/pubmed/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: https://www.ncbi.nlm.nih.gov/pubmed/33001138 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2771265 - ↑ 21.0 21.1 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 - ↑ 22.0 22.1 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: https://www.ncbi.nlm.nih.gov/pubmed/33031652 https://www.nejm.org/doi/full/10.1056/NEJMoa2022926
- ↑ 23.0 23.1 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: https://www.ncbi.nlm.nih.gov/pubmed/33165621 PMCID: PMC7653542 https://jamanetwork.com/journals/jama/fullarticle/2772922
- ↑ 24.0 24.1 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: https://www.ncbi.nlm.nih.gov/pubmed/32674126 PMCID: PMC7454406 Free PMC article https://www.nejm.org/doi/full/10.1056/NEJMoa2021801
- ↑ 25.0 25.1 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: https://www.ncbi.nlm.nih.gov/pubmed/26992838 https://www.aaojournal.org/article/S0161-6420(16)00201-3/fulltext
- ↑ Melles RB et al. Hydroxychloroquine dose and risk for incident retinopathy: A cohort study. Ann Intern Med 2023 Jan 17; [e-pub] PMID: https://www.ncbi.nlm.nih.gov/pubmed/36645889 https://www.acpjournals.org/doi/10.7326/M22-2453
Patient information
hydroxychloroquine patient information