Hydroxychloroquine (Plaquenil)

Saara Rawn MD/PhD, Raj Carmona MBBS FRCPC

INDICATIONS (including off-label uses)

Off-label use: Rheumatoid arthritis, Systemic Lupus Erythematosus, primary Sjögren’s Syndrome (extraglandular manifestations), inflammatory osteoarthritis


ADULT DOSING

200-400 mg PO daily in a single or divided dose (tablets are 200 mg).

To reduce risk of retinopathy, do not exceed 5 mg/kg/day or 400 mg PO daily.


DOSE ADJUSTMENT

Hepatic Impairment: No dose adjustments; caution advised.

Renal Impairment: No dose adjustments; caution advised.


MONITORING

Baseline:  CBC, lytes, Cr, BUN, AST, ALT. Baseline major eye exam.

Every year, repeat basic labs described above and ensure repeat major eye exam to look for retinopathy due to this medication.


CONTRAINDICATIONS

Hypersensitivity to hydroxychloroquine. Caution in patients with previous retinal or visual field changes.


SIDE EFFECTS AND ADVERSE REACTIONS

Hydroxychloroquine is generally considered to be the safest DMARD, and a “go to” drug for pregnancy.

Retinal pigment changes and retinal toxicity can occur with prolonged use.  Early changes tend to be reversible, but may progress despite discontinuation if advanced.  In the short term, it can cause accommodation disturbance, blurred vision, halos, photophobia [reversible on discontinuation.

Very rarely, Stevens-Johnson syndrome/toxic epidermal necrolysis can occur. Very rarely, the skin and mucosa can change to a black-blue color in a process called dyschromia. Hydroxychloroquine can also exacerbate psoriasis.

 In patients with glucose-6-phosphate deficiency, hemolysis can occur.  Rare cases of cardiomyopathy and myopathy have been reported.


PREGNANCY AND LACTATION

Hydroxychloroquine is considered safe in all trimesters of pregnancy. Due to the high risk of flare in systemic lupus erythematosus when discontinuing this medication, continued Plaquenil use is advised in these patients during pregnancy.

Small amounts of hydroxychloroquine can be found in breastmilk, but international experts indicate this medication is acceptable while breastfeeding.


MECHANISM OF ACTION

Plaquenil increases the pH of lysosomes and impairs complement-dependent antigen-antibody reactions. It also inhibits the chemotaxis of eosinophils and locomotion of neutrophils.


SUMMARY OF EVIDENCE (in development)

Ponticelli C et al. 2017 “Hydroxycholoroquine in systemic lupus eyrthematosis (SLE)” Expert Opin Drug Saf. Mar; 16(3)411-419.

O’Dell JR et al. 2002 “Treatment of rheumatoid arthritis with methotrexate and hydroxychloroquine, methotrexate and sulfasalazine, or a combination of the three medications: results of a two-year, randomized, double-blind, placebo-controlled trial” Arthritis Rheum May;46(5):1164-70.

Sharma TS et al. 2016 “Hydroxychloroquine use is associated with decreased incident cardiovascular events in rheumatoid arthritis patients” J Am Heart Assoc Jan;4;5(1)