What are the side effects of hydroxychloroquine?

Side Effects of Hydroxychloroquine

Hydroxychloroquine has numerous potential side effects, with retinal toxicity being the most serious long-term concern, occurring in up to 8.6% of patients after 15 years of use, particularly at doses exceeding 5 mg/kg/day of actual body weight. 1, 2

Ocular Side Effects

Retinal Toxicity

• Risk factors:

  • Daily dose >5 mg/kg of actual body weight 1
  • Treatment duration >5 years 1, 3
  • Renal impairment 4, 5
  • Concurrent tamoxifen use (increases risk 3-4 times) 4, 5
  • Age >65 years (5.7 times higher risk than those <45 years) 5
  • Female sex (3.8 times higher risk than males) 5
  • Pre-existing macular disease 4

• Manifestations:

  • Initially asymptomatic with subtle changes detectable only on specialized testing
  • Can progress to irreversible vision loss if not detected early
  • Different patterns based on ethnicity: parafoveal damage in European descent, extramacular/pericentral damage in Asian descent 1, 5

• Prevention:

  • Baseline eye examination before starting therapy 1, 4
  • Annual screening after 5 years of use (or earlier with risk factors) 1
  • Keep dose ≤5 mg/kg/day of actual body weight 1

Cardiac Side Effects

Cardiomyopathy and Conduction Abnormalities

• QT interval prolongation with risk of ventricular arrhythmias (including torsades de pointes) 6, 4
• Ventricular hypertrophy and conduction disorders including sick sinus syndrome 4
• Atrioventricular and bundle branch blocks 4

Contraindications

• Congenital or acquired QT prolongation
• Heart failure, history of myocardial infarction
• Bradycardia (<50 bpm)
• History of ventricular dysrhythmias
• Uncorrected electrolyte abnormalities 6, 4

Monitoring

• Baseline ECG and echocardiography in patients with cardiac risk factors
• Regular ECG monitoring (at least yearly) 6

Dermatologic Side Effects

Common

• Maculopapular and erythematous rash (most common, typically within 4 weeks of starting) 7
• Hyperpigmentation 7
• Hair loss 7

Severe (rare but life-threatening)

• Stevens-Johnson syndrome/toxic epidermal necrolysis 4, 7
• Drug reaction with eosinophilia and systemic symptoms (DRESS) 4
• Acute generalized exanthematous pustulosis (AGEP) 4, 7
• Exacerbation of psoriasis 4

Hematologic Side Effects

• Myelosuppression (aplastic anemia, agranulocytosis, leukopenia, thrombocytopenia) 4
• Hemolytic anemia in patients with G6PD deficiency 4

Hepatic Side Effects

• Elevated liver enzymes 4
• Hepatotoxicity, particularly in patients with porphyria cutanea tarda 4

Gastrointestinal Side Effects

• Nausea, vomiting, abdominal pain, diarrhea (among most common extracutaneous effects) 7

Neurological Side Effects

• Headache (common) 7
• Dizziness, vertigo
• Rarely: seizures, psychosis, peripheral neuropathy

Risk Mitigation Strategies

1. Use appropriate weight-based dosing (≤5 mg/kg/day of actual body weight) 1
2. Regular monitoring:
   • Baseline and annual eye exams after 5 years (or earlier with risk factors)
   • Baseline ECG in patients with cardiac risk factors
   • Regular blood work to monitor for hematologic and hepatic effects
3. Immediate evaluation of new symptoms that could indicate toxicity
4. Discontinuation if serious adverse effects develop

Special Considerations

• Asian patients have different patterns of retinal toxicity (pericentral rather than parafoveal) and require different visual field testing protocols 1, 5
• Elderly patients, those with renal impairment, and those on tamoxifen require closer monitoring and potentially lower doses 5

The goal of monitoring is not to unnecessarily stop a valuable medication but to detect toxicity early enough to prevent permanent damage 1.