hydroxychloroquine (Plaquenil)

see also:

• malaria
• acute hydroxychloroquine or chloroquine overdose / toxicity (Plaquenil)

• hydroxychloroquine is an oral quinine type anti-malarial agent for prophylaxis and Rx of chloroquine-sensitive malaria cases
• it also has uses in Rx of rheumatoid arthritis, systemic lupus erythematosus (SLE), Q fever and porphyria cutanea tarda
• may have a role in Rx of COVID-19 coronavirus (2019-nCoV / SARS-CoV-2) ¹⁾
• first synthesized in 1946 by introducing a hydroxyl group into chloroquine and was demonstrated to be much less (~40%) toxic than chloroquine in animals
• approved by FDA in 1955

• inhibition of hemozoin biocrystallization, which facilitates the aggregation of cytotoxic heme which accumulates in parasites causing their death
• increases lysosomal pH in antigen-presenting cells
• blocks toll-like receptors (TLR) on plasmacytoid dendritic cells (PDCs)
  • by decreasing TLR signaling, reduces the activation of dendritic cells and the inflammatory process
  • inhibits stimulation of the toll-like receptor (TLR) 9 family receptors

• most common:
  • mild anorexia and nausea
  • some abdominal cramps
  • mild diarrhoea
• other acute effects:
  • vomiting
  • headache
  • cardiac
    • prolonged QTc
  • HS reactions
    • anaphylaxis
    • erythema multiforme
    • Stevens-Johnson syndrome
    • toxic epidermal necrolysis
    • drug reaction with eosinophilia and systemic symptoms (DRESS syndrome)
    • photosensitivity
    • acute generalized exanthematous pustulosis (AGEP)
• chronic use effects:
  • serious macular toxicity - especially if cumulative dose exceeds 1000g
  • reversible innocuous cornea verticillata or vortex keratopathy and is characterized by whorl-like corneal epithelial deposits
  • acne
  • cardiomyopathy
  • bleaching of hair
  • mouth and eye blisters
  • blood disorders - anemia, aplastic anemia, agranulocytosis, leukopenia, and thrombocytopenia.
  • convulsions
  • neurologic effects including paralysis, nightmares, decreased reflexes, emotional effects
  • liver toxicity and possibly liver failure
  • alopecia
  • excessive skin coloring
  • vertigo, tinnitus, hearing loss
  • psoriasis and can worsen existing cases of both psoriasis and porphyria
  • weight loss

• HS to 4-Aminoquinoline compounds

• diabetes
• psoriasis
• epilepsy - seizure threshold may be reduced
• cardiac conditions
• pregnancy
• lactation
• concurrent medications which alter liver function (eg. cimetidine, digoxin)
• enhances hypoglycemic effects of insulin and oral hypoglycemic agents
• can increase plasma concentrations of penicillamine which may contribute to the development of severe side effects
• neostigmine and pyridostigmine antagonize the action of hydroxychloroquine
• drugs that prolong QT interval and other arrhythmogenic drugs
• co-administration with other antimalarials such as mefloquine known to lower the convulsion threshold may increase risk of convulsions

• take at least 4hrs before or after taking medications which may bind the drug such as antacids or kaolin
• take with a meal or a glass of milk
• One PLAQUENIL tablet contains 200 mg of hydroxychloroquine sulfate, which is equivalent to 155 mg base.
• Do not crush or divide PLAQUENIL film-coated tablets
• malaria prophylaxis:
  • adults: 400 mg (310 mg base) once weekly on the same day of each week starting 2 weeks prior to exposure, and continued for 4 weeks after leaving the endemic area.
  • children: 6.5 mg/kg (5 mg/kg base), not to exceed 400 mg (310 mg base), once weekly on the same day of the week starting 2 weeks prior to exposure, and continued for 4 weeks after leaving the endemic area.
• uncomplicated malaria Rx:
  • for radical cure of P. vivax and P. malariae infections, concomitant therapy with an 8-aminoquinoline compound is necessary.
  • adults: 800 mg (620 mg base) followed by 400 mg (310 mg base) at 6 hours, 24 hours and 48 hours after the initial dose (total 2000 mg hydroxychloroquine sulfate or 1550 mg base).
  • children: 13 mg/kg (10 mg/kg base), not to exceed 800 mg (620 mg base) followed by 6.5 mg/kg (5 mg/kg base), not to exceed 400 mg (310 mg base), at 6 hours, 24 hours and 48 hours after the initial dose. PLAQUENIL film-coated tablets cannot be divided, therefore they should not be used to treat patients who weigh less than 31 kg.
• systemic lupus erythematosus (SLE):
  • adults: 200 to 400 mg (155 to 310 mg base) daily, administered as a single daily dose or in two divided doses
• rheumatoid arthritis:
  • action of hydroxychloroquine is cumulative and may require weeks to months to achieve the maximum therapeutic effect
  • corticosteroids and salicylates may be used in conjunction with PLAQUENIL, and they can generally be decreased gradually in dosage or eliminated after a maintenance dose of PLAQUENIL has been achieved.
  • Initial adult dosage: 400 mg to 600 mg (310 to 465 mg base) daily, administered as a single daily dose or in two divided doses.
  • Do not exceed 600 mg or 6.5 mg/kg (5 mg/kg base) per day, whichever is lower, as the incidence of retinopathy has been reported to be higher when this maintenance dose is exceeded.