What are the contraindications for hydroxychloroquine?

Hydroxychloroquine Contraindications

Hydroxychloroquine is contraindicated in patients with known hypersensitivity to 4-aminoquinoline compounds, in patients with retinal or visual field deficits, and in those with glucose-6-phosphate dehydrogenase (G6PD) deficiency. 1, 2

Absolute Contraindications

• Hypersensitivity to 4-aminoquinoline compounds 1
• Pre-existing retinopathy or visual field deficits 2
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency 2

Relative Contraindications and Caution Required

Cardiac Conditions

• Congenital or acquired QT prolongation 1
• Cardiac disease (heart failure, myocardial infarction) 1
• Proarrhythmic conditions (bradycardia <50 bpm) 1
• History of ventricular dysrhythmias 1
• Concurrent use of QT-prolonging medications 1

Ocular Conditions

• Significant macular disease 2
• Underlying retinal disease 2
• Central photoreceptor loss 2

Other Medical Conditions

• Renal impairment (increases drug levels and toxicity risk) 2
• Psoriasis (may exacerbate condition) 2, 1
• Porphyria (especially porphyria cutanea tarda) 1
• Liver disease (involved in drug metabolism) 2

Medication Interactions

• Concurrent tamoxifen therapy (increases retinopathy risk 4.59 times) 3
• Other QT interval-prolonging agents 1

Dosing Considerations to Minimize Toxicity Risk

The risk of retinal toxicity is significantly increased with:

• Daily dosage exceeding 5.0 mg/kg of actual body weight 2, 3
• Duration of use greater than 5 years 2, 3
• Cumulative dose (risk increases with higher cumulative exposure) 4

Monitoring Requirements

For patients who must use hydroxychloroquine despite relative contraindications:

1. Baseline assessment before starting treatment:

   • Complete ophthalmologic examination 5
   • ECG (especially with cardiac risk factors) 5
   • Liver function tests 5
   • Complete blood count 5
   • G6PD screening in high-risk populations 5
   • Renal function tests 5

2. Ongoing monitoring:

   • Ophthalmologic examination every 6-12 months 2
   • More frequent monitoring for patients with risk factors 2
   • Monthly monitoring of hydroxychloroquine plasma levels in certain cases (maintain at 0.8–1.2 μg/mL) 2

Clinical Pearls and Pitfalls

• Retinal toxicity from hydroxychloroquine can be irreversible and may progress even after discontinuation 6
• Asian patients may demonstrate an extramacular or pericentral pattern of retinopathy requiring wider field testing 6
• The prevalence of hydroxychloroquine retinopathy is higher than previously recognized (7.5% overall in long-term users, approaching 20% after 20 years of use) 3
• Electrolyte imbalances (hypokalemia, hypomagnesemia) should be corrected before hydroxychloroquine use 1

By carefully screening for contraindications and monitoring patients appropriately, the risk of serious adverse events from hydroxychloroquine can be minimized while maintaining its therapeutic benefits for conditions like rheumatoid arthritis, lupus, and certain other inflammatory disorders.