What are the potential side effects of hydroxychloroquine and how can they be managed?

Hydroxychloroquine Side Effects and Management

Hydroxychloroquine has multiple potential side effects ranging from common mild reactions to rare but serious toxicities, with retinopathy being the most concerning long-term complication requiring regular monitoring. 1

Common Side Effects

Gastrointestinal Effects

• Nausea, vomiting, diarrhea, and abdominal discomfort are the most frequently reported side effects 2, 3
• Management: Taking medication with food, divided doses, or temporary dose reduction 1

Dermatological Effects

• Skin rashes, pruritus, and increased skin pigmentation 2, 4
• More severe reactions include Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS) 5
• Management: Discontinue medication for severe reactions; topical treatments for mild reactions 4

Neurological Effects

• Headache, dizziness, and blurred vision 2
• Rare cases of neuropsychiatric reactions including suicidal ideation 5
• Management: Dose reduction or discontinuation if symptoms are severe 5

Serious Side Effects

Retinopathy

• Most significant dose-limiting toxicity with long-term use 2, 6

• Risk factors:

  • Daily dose >5.0 mg/kg of real body weight 6
  • Duration of use >10 years (prevalence increases to almost 20% after 20 years) 6
  • Age >65 years at initiation (HR 5.68) 7
  • Female sex (HR 3.83) 7
  • Chronic kidney disease stage 3 or greater (HR 1.95) 7
  • Concurrent tamoxifen use (HR 3.43) 7
  • Asian and Black patients have higher risk of pericentral retinopathy pattern 7

• Management:

  • Baseline ophthalmologic examination before starting treatment 1
  • Regular screening every 6-12 months for patients on long-term therapy 2, 1
  • Keep daily dose ≤5.0 mg/kg of real body weight 6
  • Consider more frequent monitoring for high-risk patients 7
  • Discontinue if retinopathy is detected 5

Cardiac Effects

• QT interval prolongation, conduction abnormalities 2
• Rare cases of cardiomyopathy with long-term use 3
• Risk increased when combined with other QT-prolonging medications like azithromycin 2
• Management:
  • Baseline ECG recommended, especially in patients with cardiac risk factors 1
  • Avoid combination with other QT-prolonging medications when possible 2
  • Regular cardiac monitoring for patients on long-term therapy 1

Hematologic Effects

• Hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency 5
• Rare cases of myelosuppression including aplastic anemia, agranulocytosis, leukopenia, or thrombocytopenia 5
• Management:
  • Screen for G6PD deficiency before initiating therapy in high-risk populations 2
  • Regular blood count monitoring for patients on long-term therapy 5
  • Discontinue if unexplained myelosuppression occurs 5

Hepatotoxicity

• Elevated liver enzymes 2
• Increased risk in patients with porphyria cutanea tarda 5
• Management:
  • Baseline and periodic liver function tests 5
  • Prompt investigation of symptoms suggesting liver injury 5
  • Discontinue if significant hepatotoxicity occurs 5

Hypoglycemia

• Can cause severe hypoglycemia, with or without concurrent antidiabetic medications 5
• Management:
  • Blood glucose monitoring, especially in diabetic patients 5
  • Patient education about hypoglycemia symptoms 5
  • Adjustment of antidiabetic medications if needed 5

Neuromuscular Effects

• Skeletal muscle myopathy or neuropathy with prolonged use 5
• Management:
  • Periodic assessment of muscle strength and deep tendon reflexes 5
  • Discontinue if muscle or nerve toxicity is suspected 5

Special Populations

Pregnancy

• Relatively safe during pregnancy 2, 1
• Continuation during pregnancy may be recommended for patients with lupus 2

Patients with Psoriasis

• May precipitate severe flare-ups of psoriasis 2, 5
• Management: Avoid in patients with psoriasis unless benefits outweigh risks 5

Monitoring Recommendations

1. Before Starting Treatment:

   • Complete ophthalmologic examination
   • ECG, especially in patients with cardiac risk factors
   • Liver function tests
   • Complete blood count
   • G6PD screening in high-risk populations
   • Renal function tests

2. During Treatment:

   • Ophthalmologic examination every 6-12 months 2, 1
   • Regular monitoring of liver function, complete blood count, and renal function
   • ECG monitoring if on long-term therapy or with cardiac risk factors
   • More frequent monitoring for patients with risk factors for retinopathy

3. Patient Education:

   • Report visual changes immediately
   • Report new or worsening neuropsychiatric symptoms
   • Monitor for signs of hypoglycemia if diabetic
   • Avoid prolonged sun exposure or use sunscreen

By implementing appropriate monitoring protocols and patient education, many of the serious side effects of hydroxychloroquine can be detected early or prevented, allowing for safe long-term use in most patients.