Package inserts for hydroxychloroquine (Plaquenil) report side effects that may be seen in patients taking hydroxychloroquine at recommended doses for rheumatoid arthritis (RA) or systemic lupus erythematosus.1,2 In available studies, the frequency of reported side effects has been low, and are usually mild.3 Many side effects are transient, but the frequency of these events is not specified in the package inserts. It is important to note that while these side effects have been reported in people taking hydroxychloroquine, it is not possible from these reports to determine if they were caused by the hydroxychloroquine, the disease process, or an unrelated cause. They include:
- Gastrointestinal: Nausea, vomiting, diarrhea, and abdominal pain
- Skin: Rash, pruritus, pigmentation disorders in skin and mucous membranes, hair color changes, alopecia. Dermatitis eruptions including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), photosensitivity, dermatitis exfoliative, acute generalized exanthematous pustulosis (AGEP), psoriasis
- Nervous system: Headache, dizziness, seizure, ataxia, dystonia, dyskinesia, convulsions, tremor
- Ocular: retinopathy and corneal deposits
- Musculoskeletal: Skeletal muscle myopathy, neuromyopathy
- Ear or labyrinth: Vertigo, tinnitus, nystagmus, nerve deafness, deafness
- Blood and lymphatic: Bone marrow failure, anemia, aplastic anemia, agranulocytosis, leukopenia, and thrombocytopenia. Hemolysis reported in individuals with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency
- Cardiac: Cardiomyopathy, prolonged QT interval, ventricular arrhythmias, and torsade de pointes
- General: Fatigue
- Liver: Liver function tests abnormal, acute hepatic failure
- Immune system: Urticaria, angioedema, bronchospasm
- Metabolic: Loss of appetite, hypoglycemia, porphyria, weight loss
- Psychiatric disorders: Affect/emotional lability, nervousness, irritability, nightmares, psychosis, suicidal behavior
An uncommon, but serious, side effect that has been attributed to hydroxychloroquine is retinopathy that can cause visual field deficits, visual disturbances, macular degeneration, decreased dark adaptation, and color vision abnormalities.1,2 This effect is dose related and if not identified in its early stages, may be irreversible. Estimates of the frequency of retinopathy vary across studies. The risk of toxicity is estimated to be less than one percent in people taking hydroxychloroquine for under five years.4 In one study, retinopathy was reported in 7.5% or more of people taking it for five years or more and 30% or higher in patients taking it for 20 years or more.5 Because of the frequency of this adverse event, the American Academy of Ophthalmology recommends optimal dosing of hydroxychloroquine based on total body weight (maximum daily dose not to exceed 5 mg/kg actual weight), dose reduction after long-term use, and intensified screening with techniques including optical coherence tomography after five years.4,6 The Royal Academy of Ophthalmology of the United Kingdom suggests that the standard dose of hydroxychloroquine for long term use should be 200 mg rather than 400 mg daily. They also recommend screening for retinopathy annually for individual on long-term therapy and more frequently if risk factors, such as concomitant tamoxifen treatment or renal impairment, are present.7
Hydroxychloroquine has also been reported to cause severe hypoglycemia in some patients with diabetes who are also taking hypoglycemic drugs and rarely to cause bone marrow suppression.8
- Plaquenil [package insert]. St Michael, Barbados, BBI: Concordia Pharmaceuticals, Inc; 2017.
- Plaquenil (Hydroxychloroquine) [package insert]. Bridgewater, NJ: Sanofi-Aventis U.S. LLC; 2006.
- Ruiz-Irastorza G, Ramos-Cassals M, Brito-Zeron P, Khamashta MA. Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review. Ann Rheum Dis 2010; 69 : 20-28.
- Marmor MF, Kellner U, Lai TYY, Melles RB. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 Revision). Ophthalmology 2016; 123 (6): 1386-1394.
- Melles R, Marmor M. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy. JAMA Ophthalmol 2014; 132 (12): 1453-1460.
- Abdulaziz N, Shah AR, Mccune WJ. Hydroxychloroquine: balancing the need to maintain therapeutic levels with ocular safety: an update. Curr Opin Rheumatol 2018; 30 : 249-255.
- Hughes GR V. Hydroxychloroquine: an update. Lupus 2018; 27 : 1402-1403.
- Yusuf IH, Sharma S, Luqmani R, Downes SM. Hydroxychloroquine retinopathy. Eye 2017; 31 (6): 828-845.