What are the side effects of Hydrochloroquine (hydroxychloroquine)?

Hydroxychloroquine Side Effects

Hydroxychloroquine can cause a range of side effects from common mild reactions to rare but serious toxicities, with retinal toxicity being the most concerning long-term risk requiring regular monitoring. 1

Common Side Effects

• Gastrointestinal effects: Nausea, vomiting, diarrhea, abdominal discomfort (most frequent adverse effects) 2, 3
• Neurological symptoms: Headache, dizziness, blurred vision 2, 1
• Dermatological reactions: Skin rashes, pruritus, increased skin pigmentation 2, 4

Serious Side Effects

Ocular Toxicity

• Retinopathy: The major dose-limiting toxicity with long-term use 2
  • Risk increases with:
    • Higher daily doses (>5.0 mg/kg of real body weight) 2, 5
    • Longer duration of use (prevalence approaches 20% after 20 years) 5
    • Cumulative dose 2
    • Renal disease (doubles risk) 5
  • Early detection is critical as damage may be irreversible and can progress even after stopping the medication 2
  • Symptoms include difficulty reading, decreased vision, missing central vision, glare, metamorphopsia 6
  • Regular ophthalmologic screening recommended every 6-12 months for long-term users 2, 1

Cardiac Effects

• QT prolongation and risk of arrhythmias 2, 7
• Cardiomyopathy with long-term use 2, 3
• Heart block (more common with chloroquine than hydroxychloroquine) 2
• Torsade de pointes (in overdose or with other QT-prolonging medications) 7

Hematologic Effects

• Hemolytic anemia in patients with G6PD deficiency 2, 3
• Myelosuppression (rare) 1

Neuropsychiatric Effects

• Confusion, disorientation, hallucinations (can occur within 24-48 hours of starting therapy) 3
• Peripheral neuropathy with prolonged therapy 2
• Seizures (rare, more common in overdose) 7, 3

Other Serious Effects

• Hypoglycemia (rare with standard therapeutic use) 1, 3
• Elevated liver enzymes 1
• Skeletal muscle myopathy 2, 1
• Severe cutaneous reactions (rare): Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS syndrome 3, 4

Risk Factors for Toxicity

1. Dosage: Daily dose >5.0 mg/kg real body weight 2, 5
2. Duration: Treatment longer than 5 years 2, 5
3. Renal disease: Impaired clearance increases drug levels 2, 5
4. Concomitant medications:
   • Tamoxifen (increases retinopathy risk 4.6-fold) 5
   • QT-prolonging medications 1, 7
5. Pre-existing conditions:
   • Retinal or macular disease 2
   • G6PD deficiency 2, 3
   • Liver disease 2

Monitoring Recommendations

• Baseline assessment before starting treatment:

  • Complete ophthalmologic examination 2, 1
  • Renal and liver function tests 1
  • Complete blood count 1
  • Consider G6PD screening in at-risk populations 2
  • ECG if cardiac risk factors present 2

• Ongoing monitoring:

  • Ophthalmologic examination every 6-12 months for long-term users 2, 1
  • Regular monitoring of liver function, renal function, and complete blood count 1
  • Consider periodic ECG in patients on long-term therapy, especially with chloroquine 2

Special Populations

• Pregnancy: Generally considered safe; no evidence of retinal toxicity, ototoxicity, cardiotoxicity, or developmental abnormalities in children exposed in utero 1, 7
• Breastfeeding: Present in breast milk at low levels; no adverse reactions reported in breastfed infants 7
• Pediatric patients: Generally considered safe for malaria treatment; limited data for autoimmune conditions 7
• Geriatric patients: May require dose adjustment due to decreased renal function 7

Overdose

Hydroxychloroquine overdose is potentially fatal, with symptoms appearing within 1-3 hours of ingestion 7:

• Cardiovascular collapse and shock
• Severe hypokalemia
• CNS depression, seizures, coma
• Visual disturbances, transient blindness

Immediate medical attention is required for suspected overdose, with monitoring of cardiac function and electrolytes 7.