Chloroquine and hydroxychloroquine: Immunomodulatory effects in autoimmune diseases

Table 1 Clinically relevant drug interactions with chloroquine and hydroxychloroquine

Interacting drug/class	Mechanism of interaction	Clinical implication	Recommendation
Proton pump inhibitors	Reduce lysosomal acidification, affecting HCQ accumulation	Decreased therapeutic efficacy	Consider dose separation or switching to H2 antagonists
Digoxin	Inhibition of P-glycoprotein leads to increased digoxin levels	Risk of digoxin toxicity	Monitor serum digoxin levels
Methotrexate	Overlapping immunosuppression, altered metabolism	Potential increased toxicity	Monitor hepatic and hematologic parameters
Tamoxifen	Additive risk of retinopathy	Increased ocular toxicity	Ophthalmologic monitoring if used long-term
Antacids (e.g., magnesium/aluminum)	Interfere with GI absorption of CQ/HCQ	Reduced drug bioavailability	Separate doses by at least 4 hours
QT-prolonging agents (e.g., azithromycin, amiodarone)	Additive risk of QT prolongation	Increased risk of arrhythmias	Baseline and follow-up ECG monitoring
Cytochrome P450 inhibitors (e.g., ketoconazole)	Impaired metabolism of CQ/HCQ	Elevated plasma drug concentrations	Dose adjustment and monitoring for toxicity
Insulin and antidiabetic agents	HCQ enhances insulin sensitivity and lowers blood glucose	Risk of hypoglycemia	Monitor blood glucose closely

CQ: Chloroquine; HCQ: Hydroxychloroquine; GI: Gastrointestinal; QT: QT interval; ECG: Electrocardiogram.