What are the side effects of hydroxychloroquine (Plaquenil)?

From the Guidelines

Hydroxychloroquine is associated with several side effects, including nausea, stomach pain, diarrhea, headache, dizziness, and rash, as well as more serious but less common side effects such as vision changes, muscle weakness, abnormal heart rhythms, and blood disorders. The most recent and highest quality study, 1, provides evidence that hydroxychloroquine use in patients with systemic lupus erythematosus (SLE) is associated with a decrease in lupus activity and a satisfactory safety profile in both the mother and the fetus. However, significant side effects can occur, including skin rash, increase in skin pigmentation, muscle weakness, and visual change or loss of vision. The risk of retinal damage increases with higher doses (>5 mg/kg/day based on ideal body weight), longer duration of use (>5 years), kidney disease, and concurrent tamoxifen use. Some key points to consider when prescribing hydroxychloroquine include:

• The daily dose should not exceed 5 mg/kg real body weight to minimize the risk of retinopathy
• Regular eye exams are recommended for patients on long-term therapy, typically every 6-12 months
• Hydroxychloroquine can also cause QT interval prolongation, which may lead to dangerous heart rhythm disturbances, particularly when combined with other QT-prolonging medications
• The medication can cause skin reactions, including sensitivity to sunlight, and neurological side effects, such as anxiety, irritability, nightmares, and rarely psychosis. It is essential to weigh the benefits and risks of hydroxychloroquine therapy and to monitor patients closely for potential side effects, as stated in 1. Additionally, the American College of Rheumatology, American Academy of Dermatology, Rheumatologic Dermatology Society, and American Academy of Ophthalmology emphasize the importance of effective communication between healthcare providers in the management of hydroxychloroquine, as mentioned in 1. Overall, hydroxychloroquine can be a valuable drug for the treatment of rheumatic diseases, but it is crucial to be aware of its potential side effects and to take steps to minimize the risk of retinopathy and other adverse effects, as recommended in 1 and 1.

From the FDA Drug Label

Patients may present with ventricular hypertrophy, pulmonary hypertension and conduction disorders including sick sinus syndrome. ECG findings include atrioventricular, right or left bundle branch block. Hydroxychloroquine sulfate has a potential to prolong the QT interval Ventricular arrhythmias (including torsades de pointes) have been reported in hydroxychloroquine sulfate-treated patients. Irreversible retinal damage was observed in some patients treated with hydroxychloroquine sulfate and it is related to cumulative dosage and treatment duration. Serious adverse reactions have been reported with the use of hydroxychloroquine sulfate including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), acute generalized exanthematous pustulosis (AGEP) Administration of hydroxychloroquine sulfate to patients with psoriasis may precipitate a severe flare-up of psoriasis. Administration of hydroxychloroquine sulfate to patients with porphyria may exacerbate porphyria. Cases of hepatotoxicity have been reported when hydroxychloroquine was used in patients with porphyria cutanea tarda (PCT) Hydroxychloroquine sulfate may cause myelosuppression including aplastic anemia, agranulocytosis, leukopenia, or thrombocytopenia. Hemolysis has been reported in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency.

The side effects of hydroxychloroquine include:

• Cardiac effects: ventricular hypertrophy, pulmonary hypertension, conduction disorders, QT interval prolongation, ventricular arrhythmias
• Retinal toxicity: irreversible retinal damage
• Serious skin reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, acute generalized exanthematous pustulosis
• Psoriasis: severe flare-up of psoriasis
• Porphyria: exacerbation of porphyria
• Hepatotoxicity: liver injury, particularly in patients with porphyria cutanea tarda
• Hematologic toxicity: myelosuppression, aplastic anemia, agranulocytosis, leukopenia, thrombocytopenia
• Hemolytic anemia: particularly in patients with G6PD deficiency 2

From the Research

Hydroxychloroquine Side Effects

• The use of hydroxychloroquine (HCQ) has been associated with various side effects, including cardiac, neuropsychiatric, hematologic, and hepatobiliary manifestations in patients with COVID-19 3.
• In patients with systemic lupus erythematosus (SLE), the daily dose of HCQ associated with the best compromise between efficacy and safety is a matter of debate, with a recommended daily dose of ≤5 mg/kg/day actual body weight to minimize the risk of retinal toxicity 4.
• HCQ has been reported to have a lower incidence of gastrointestinal adverse reactions compared to chloroquine (CQ), and may have a lower risk of ocular adverse reactions 5.
• The use of HCQ during pregnancy does not appear to pose a risk to the baby, and may be beneficial to the mother with SLE by controlling disease activity 5.
• Common side effects of HCQ include:
  • Ocular adverse reactions, such as retinopathy 4, 5, 6
  • Gastrointestinal adverse reactions, such as nausea and diarrhea 5
  • Cardiac adverse reactions, such as QT interval prolongation 3
  • Neuropsychiatric adverse reactions, such as psychosis and hallucinations 3
  • Hematologic adverse reactions, such as anemia and thrombocytopenia 3
  • Hepatobiliary adverse reactions, such as elevated liver enzymes 3
• The mechanisms of action of HCQ are still not completely understood, but it is thought to interfere with lysosomal activity and autophagy, interact with membrane stability, and alter signaling pathways and transcriptional activity, resulting in inhibition of cytokine production and modulation of certain co-stimulatory molecules 7, 6.