What are the complications of Plaquenil (hydroxychloroquine)?

Complications of Hydroxychloroquine (Plaquenil)

Hydroxychloroquine can cause serious complications including irreversible retinopathy, cardiac toxicity, and neurological effects that require regular monitoring and prompt discontinuation if detected. 1

Ocular Complications

• Retinal toxicity: The most serious long-term complication
  • Irreversible retinopathy that can progress even after drug discontinuation 2
  • Initially affects photoreceptors before causing retinal pigment epithelium damage
  • Different patterns based on ethnicity:
    • Parafoveal distribution in patients of European descent
    • Peripheral extramacular distribution in Asian patients 2
  • Risk factors:
    • Daily dose exceeding 5 mg/kg real body weight 2
    • Treatment duration >5 years
    • Pre-existing retinal or macular disease
    • Chronic kidney disease 2
  • Early stages often asymptomatic with normal visual acuity
  • Advanced cases may show "bull's eye" maculopathy 2
  • Requires baseline examination and regular screening:
    • Annual screening after 5 years of use (earlier in high-risk patients)
    • Screening should include visual fields and at least one objective test (SD-OCT, mfERG, or FAF) 2

Cardiac Complications

• Cardiotoxicity: Can be fatal or life-threatening 3
  • Cardiomyopathy associated with phospholipidosis
  • Ventricular hypertrophy and pulmonary hypertension
  • Conduction disorders including sick sinus syndrome
  • ECG abnormalities:
    • QT interval prolongation
    • Widening of QRS interval
    • T-wave changes 1
    • Atrioventricular and bundle branch blocks 3
  • Ventricular arrhythmias including torsades de pointes 3
  • Higher risk with:
    • Congenital or acquired QT prolongation
    • Cardiac disease (heart failure, myocardial infarction)
    • Bradycardia (<50 bpm)
    • History of ventricular dysrhythmias
    • Uncorrected electrolyte abnormalities
    • Concomitant QT-prolonging medications 3

Neurological Complications

• Headache and dizziness (common) 2
• Peripheral neuropathy (can improve with drug withdrawal) 1
• Confusion, convulsions in prolonged use 1
• Risk of peripheral neuropathy increased when combined with:
  • Platinum salts
  • Anthracyclines
  • Taxanes
  • Immunomodulators
  • Comorbidities like diabetes or chronic alcohol abuse 1

Gastrointestinal Complications

• Nausea, vomiting, abdominal pain, diarrhea (5-15% of patients) 2, 4
• Hepatotoxicity:
  • Altered liver function 2
  • Can progress to fulminant hepatitis in rare cases 4

Dermatological Complications

• Pruritus (common) 2
• Lichenoid skin eruptions 1
• Hair bleaching 1
• Cutaneous hyperpigmentation 5
• Drug eruptions or rash 5
• Severe reactions (rare):
  • Acute generalized exanthematous pustulosis
  • Stevens-Johnson syndrome
  • Toxic epidermal necrolysis 5
• Hair loss 5

Hematological Complications

• Anemia 2
• Altered platelet counts

Monitoring Recommendations

1. Baseline evaluation before starting treatment:

   • Ophthalmologic examination
   • ECG
   • Liver and kidney function tests 2

2. Ongoing monitoring:

   • Ophthalmologic monitoring:
     • Annual after 5 years of use (earlier in high-risk patients)
   • Cardiac monitoring:
     • Consider periodic ECGs, especially in patients with risk factors
   • Laboratory monitoring:
     • CBC, liver and kidney function tests

3. Drug interactions requiring monitoring:

   • QT-prolonging medications (contraindicated)
   • D-penicillamine and cimetidine (increase hydroxychloroquine levels) 1
   • CYP2D6 substrates like gefitinib and tamoxifen 1

Management of Complications

• For retinal toxicity: Immediate discontinuation is the only effective intervention 2
• For cardiac toxicity: Discontinue if suspected or demonstrated
• For severe skin reactions: Discontinue and provide supportive care
• For GI symptoms: May improve with dose reduction or taking with food 3

Prevention of Complications

• Proper dosing (≤5 mg/kg real body weight daily) 2
• Calculate dose based on real weight rather than ideal weight
• Avoid in patients with pre-existing conditions that increase risk
• Correct electrolyte imbalances before use 3
• Take with food or milk to reduce GI side effects 3

Hydroxychloroquine complications can be serious but are often preventable with appropriate dosing, patient selection, and regular monitoring. Early detection through systematic screening is essential to prevent irreversible damage, particularly to the retina and heart.