What are the common side effects of hydroxychloroquine in patients with a history of eye or heart conditions?

Common Side Effects of Hydroxychloroquine

The most common side effects of hydroxychloroquine are gastrointestinal disturbances (nausea, vomiting, diarrhea), headache, and visual disturbances, with the most serious long-term risk being irreversible retinal toxicity, particularly in patients with pre-existing eye conditions or those on prolonged therapy. 1

Immediate and Short-Term Side Effects (Days to Weeks)

Gastrointestinal Effects

• GI upset is the most frequently reported side effect, including nausea, vomiting, diarrhea, and stomach discomfort 1, 2
• These symptoms are typically mild and can be minimized by taking the medication with food or milk 3

Common Benign Effects

• Headache occurs commonly with oral therapy 1
• Visual disturbances including blurred vision and diplopia may develop but typically reverse with discontinuation 1
• Pruritus and urticaria (itching and hives) are reported 1
• Dizziness may occur 1

Dermatologic Reactions

• Drug eruptions or rashes may appear within days to weeks 2
• Cutaneous hyperpigmentation can develop 2
• Lichenoid skin eruptions and bleaching of hair may occur with prolonged use 1
• Discoloration of nail beds and mucous membranes has been reported 1
• Rare but serious: Stevens-Johnson syndrome and toxic epidermal necrolysis, though these usually resolve with drug discontinuation 2

Critical Concerns for Patients with Pre-existing Conditions

Ocular Toxicity (Major Concern for Eye Disease History)

Retinal toxicity is the most serious dose-limiting adverse effect with long-term use (>2 years), and patients with pre-existing eye conditions require heightened vigilance. 1

• Irreversible retinopathy can result from hydroxychloroquine binding to melanin in the retinal pigment epithelium, causing vision loss 1
• The overall prevalence of retinopathy is 7.5% but varies significantly with dosage and duration 4
• Risk remains <2% within the first 10 years at dosages of 4.0-5.0 mg/kg but rises to almost 20% after 20 years of use 4
• Vortex keratopathy (corneal deposits) can occur; in one study, 7 of 12 patients developed this condition 1
• Retinal toxicity may progress even after drug discontinuation, though some patients show outer retinal regeneration 5

Mandatory monitoring: Ophthalmologic assessment every 6 to 12 months is required for all patients on antimalarial therapy 1

Cardiovascular Toxicity (Major Concern for Heart Disease History)

Patients with pre-existing cardiac conditions face significant risks, as hydroxychloroquine can cause multiple cardiac complications. 1

• Cardiac conduction abnormalities including QRS widening, QT/QTc prolongation, and T-wave changes 1, 2
• Heart block and cardiomyopathy can develop, though chloroquine causes these more frequently than hydroxychloroquine 1
• Cardiovascular effects may progress through vasodilation, hypotension, suppressed myocardial function, cardiac arrhythmia, and cardiac arrest (particularly with parenteral administration or overdose) 1
• Yearly ECGs are performed by some clinicians in asymptomatic patients, especially those on long-term therapy 1
• QT prolongation is of particular concern when combined with azithromycin 2

Other Serious Long-Term Toxicities

Neuromuscular Effects:

• Toxic myopathy, cardiomyopathy, and peripheral neuropathy can occur with prolonged therapy but improve if the drug is promptly withdrawn 1
• Muscle weakness and atrophy have been reported 3
• Rarely: myositis, extremity weakness, and pseudoparkinsonism 2

Neuropsychiatric Reactions:

• CNS effects may progress through confusion, convulsions, and coma (more common in overdose) 1
• Psychosis, disorientation, and hallucinations may occur within 24-48 hours of drug initiation 2
• New or worsening depression and suicidal thoughts require immediate medical attention 3

Ototoxicity:

• Irreversible ototoxicity can develop if oral doses exceed 250 mg/day 1

Hematologic:

• Hemolysis and anemia may occur in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency 2

Metabolic:

• Severe hypoglycemia has been associated with hydroxychloroquine use 3

Critical Dosing Thresholds

To minimize retinal toxicity risk, daily consumption should not exceed 5.0 mg/kg of real body weight (not ideal body weight), as this is associated with low risk for up to 10 years 4. Doses exceeding 250 mg/day increase the risk of irreversible retinopathy and ototoxicity 1.

Additional Risk Factors

• Kidney disease increases risk (odds ratio 2.08) 4
• Concurrent tamoxifen therapy significantly increases risk (odds ratio 4.59) 4
• Duration of use >10 years substantially increases retinopathy risk (odds ratio 3.22) 4
• Renal or hepatic impairment may require dose reduction 3

Common Pitfalls to Avoid

• Do not crush or divide tablets - they must be taken whole with food or milk 3
• Do not assume safety based on short-term use - retinopathy risk increases dramatically after 10 years 4
• Do not use ideal body weight for dosing calculations - real body weight predicts risk better 4
• Do not skip ophthalmologic monitoring - early detection is critical as toxicity can progress after discontinuation 5
• Chloroquine may interfere with intradermal rabies vaccine antibody response 1
• May exacerbate psoriasis 1