What are the potential side effects of hydroxychloroquine (Disease-Modifying Antirheumatic Drug - DMARD)?

Hydroxychloroquine Side Effects

Hydroxychloroquine has multiple potential side effects ranging from common gastrointestinal symptoms to rare but serious cardiac, ocular, and dermatologic toxicities that require careful monitoring, especially with long-term use. 1, 2

Common Side Effects

• Gastrointestinal effects: Nausea, vomiting, abdominal pain, and diarrhea are the most frequently reported side effects, though they are generally infrequent at standard doses 1, 3
• Headache, dizziness, blurred vision, and pruritus may occur but usually don't require discontinuation of the medication 1
• Skin reactions: Maculopapular and erythematous rashes are common, typically occurring within 4 weeks of starting treatment and resolving after discontinuation 4

Serious Side Effects

Cardiac Toxicity

• QT interval prolongation and risk of ventricular arrhythmias (including torsades de pointes) 2
• Contraindicated in patients with:
  • Congenital or acquired QT prolongation
  • Cardiac disease (heart failure, myocardial infarction)
  • Bradycardia (<50 bpm)
  • History of ventricular dysrhythmias
  • Uncorrected electrolyte abnormalities 2
• Long-term use has been associated with cardiomyopathy, conduction abnormalities, and valvular disorders 3
• ECG monitoring is recommended, particularly when used with other QT-prolonging medications 1

Ocular Toxicity

• Retinopathy is the major dose-limiting toxicity with long-term use 3
• Risk factors include:
  • Daily doses ≥5 mg/kg of actual body weight
  • Treatment duration >5 years
  • Renal impairment
  • Concomitant use of tamoxifen
  • Concurrent macular disease 2
• In Asian patients, retinal toxicity may first appear outside the macula 2
• Monitoring recommendations:
  • Baseline ocular examination within the first year of treatment
  • Annual examinations for high-risk patients
  • For patients without risk factors, annual exams can be deferred until 5 years of treatment 2
  • Monitoring should include best corrected visual acuity, automated threshold visual field testing, and spectral domain optical coherence tomography 2

Dermatologic Reactions

• Severe skin reactions including:
  • Stevens-Johnson syndrome (SJS)
  • Toxic epidermal necrolysis (TEN)
  • Drug reaction with eosinophilia and systemic symptoms (DRESS)
  • Acute generalized exanthematous pustulosis (AGEP) 2, 5
• Hyperpigmentation of the skin can occur with long-term use 5
• Exacerbation of psoriasis - hydroxychloroquine should be avoided in patients with psoriasis unless benefits outweigh risks 2
• Hair loss has been reported 5

Hematologic Effects

• Myelosuppression including aplastic anemia, agranulocytosis, leukopenia, or thrombocytopenia 2
• Hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency 2
• Regular blood count monitoring is recommended for patients on prolonged therapy 2

Hepatotoxicity

• Hydroxychloroquine is known to concentrate in the liver 1
• Patients with hepatitis or other liver diseases should use with caution 1
• Rare cases of clinically apparent liver injury have been reported 1
• Particularly concerning in patients with porphyria cutanea tarda, where marked elevations in transaminases can occur 2

Neuromuscular Toxicity

• Neuromyotoxicity can present as:
  • Proximal myopathy
  • Peripheral neuropathy
  • Muscle weakness 6
• Symptoms may resolve slowly and incompletely after discontinuation 6
• Caucasian race and concomitant renal failure may be predisposing factors 6

Monitoring Recommendations

• Baseline assessment before starting treatment:

  • Ophthalmologic examination
  • ECG in patients with cardiac risk factors
  • Complete blood count
  • Liver function tests 1, 2

• Ongoing monitoring:

  • Ocular screening every 6-12 months, especially for long-term use 1
  • Periodic blood counts for patients on prolonged therapy 2
  • Monitor for signs of muscle weakness or neuropathy 6
  • ECG monitoring in patients with cardiac risk factors 1

Special Populations

• Pregnancy: Hydroxychloroquine has been used during pregnancy for connective tissue diseases without increased complications compared to untreated pregnancies 1

• Children: Limited information available, though antimalarial agents have been used for rheumatologic diseases in children for many years 1

Drug Interactions

• Caution with drugs that may prolong QT interval 2
• Potential interactions with D-penicillamine and cimetidine, leading to higher drug levels 1
• May interfere with antibody response to human diploid cell rabies vaccine when administered intradermally 1

Hydroxychloroquine is generally well-tolerated when used at appropriate doses with proper monitoring, but awareness of these potential side effects is essential for safe prescribing and patient management.