HYDROXYCHLOROQUINE SULFATE
Clinical safety rating: safe
Can cause retinal toxicity requiring regular ophthalmologic exams Can cause retinal toxicity and QT prolongation.
Antimalarial and immunosuppressive agent. Accumulates in lysosomes, raising pH, impairing antigen processing and presentation. Inhibits toll-like receptor signaling and cytokine production (e.g., IL-6, TNF-α). Interferes with quinone reductase activity and heme polymerization in plasmodia.
| Metabolism | Partially metabolized by cytochrome P450 enzymes (CYP2D6, CYP3A4, CYP2C8, CYP2C9) and flavin-containing monooxygenase (FMO). N-desethylation is the major metabolic pathway. |
| Excretion | Renal: ~50% unchanged; Hepatic metabolism: ~50% (desethylchloroquine, desethylhydroxychloroquine); Fecal: minimal (<5%). |
| Half-life | Terminal half-life: ~40–50 days (range 30–60 days) due to extensive tissue distribution. Steady-state reached after 4–6 months. |
| Protein binding | ~50% bound to plasma proteins (albumin). |
| Volume of Distribution | ~800 L/kg (very large, extensive tissue binding, especially melanin-rich tissues). |
| Bioavailability | Oral: ~74% (range 67–91%); Food increases absorption. |
| Onset of Action | Oral: Antimalarial: 2–3 days; Rheumatic disease: 4–12 weeks (slow). |
| Duration of Action | Antimalarial: ~7 days; Rheumatic disease: persists for weeks to months after discontinuation due to long half-life. |
200-400 mg orally once daily or divided twice daily; maximum 600 mg/day or 6.5 mg/kg/day (whichever is lower). For malaria: 800 mg loading dose, then 400 mg at 6, 24, and 48 hours.
| Dosage form | TABLET |
| Renal impairment | CrCl >=30 mL/min: no adjustment. CrCl <30 mL/min or on dialysis: reduce dose by 50% or extend interval to every 48-72 hours. Not removed by hemodialysis. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 25-50%. Child-Pugh C: contraindicated or use with extreme caution, dose not established. |
| Pediatric use | Malaria: 6.5 mg/kg (base) orally loading dose, then 3.25 mg/kg at 6, 24, 48 hours. Lupus/RA: 3-6.5 mg/kg/day orally once daily; maximum 400 mg/day (or 6.5 mg/kg/day). |
| Geriatric use | No specific dose adjustment but start at low end of dosing range (200 mg orally once daily) due to increased risk of QT prolongation, hypoglycemia, and retinal toxicity. Monitor renal function and cardiac status. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Can cause retinal toxicity requiring regular ophthalmologic exams Can cause retinal toxicity and QT prolongation.
| FDA category | Human |
| Breastfeeding | Hydroxychloroquine is excreted into human breast milk in low concentrations. The milk-to-plasma ratio is approximately 0.6. The estimated daily infant dose is about 2% of the maternal weight-adjusted dose, which is below levels expected to cause toxicity. The American Academy of Pediatrics considers hydroxychloroquine compatible with breastfeeding. However, caution is advised in infants with G6PD deficiency due to theoretical risk of hemolysis. |
■ FDA Black Box Warning
Hydroxychloroquine can cause retinal toxicity (irreversible retinopathy) with prolonged use. Dose-related and cumulative. Baseline and annual ophthalmic examinations are mandatory. Risk increased with daily dose >5.0 mg/kg actual body weight, cumulative dose >1000 grams, and concomitant use of tamoxifen.
| Common Effects | lupus |
| Serious Effects |
["Hypersensitivity to hydroxychloroquine or any component of the formulation","Known retinopathy of any etiology","Pre-existing visual field defects","Concurrent use of tamoxifen (increased risk of retinopathy)","Porphyria (may exacerbate attacks)","G6PD deficiency (rare but caution)"]
| Precautions | ["Retinopathy: irreversible, dose and duration dependent. Monitor with fundoscopy, visual fields, spectral-domain optical coherence tomography (SD-OCT).","Cardiotoxicity: cardiomyopathy, conduction disorders (e.g., QT prolongation, torsades de pointes). Avoid with other QT-prolonging drugs.","Hypoglycemia: can cause severe hypoglycemia, especially in diabetic patients.","Neuropsychiatric effects: agitation, psychosis, suicidal ideation.","Hematologic toxicity: agranulocytosis, aplastic anemia (rare).","Neuromuscular toxicity: vacuolar myopathy, neuropathy.","Drug interactions: CYP2D6 inhibitors (e.g., fluoxetine) may increase levels. Caution with antidiabetic agents.","Pregnancy: Use only if clearly needed; crosses placenta.","Hepatic/renal impairment: dose adjustment may be required."] |
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| Teratogenic Risk |
| Hydroxychloroquine is considered low risk for teratogenicity. Studies have not shown an increased risk of major congenital malformations, spontaneous abortion, or fetal death when used at therapeutic doses during pregnancy. There is no evidence of fetal harm from first trimester exposure. Continued use throughout pregnancy is recommended for maternal autoimmune disease management, as disease flares pose greater risk. No specific trimester risks identified. |
| Fetal Monitoring | No specific fetal monitoring is required for hydroxychloroquine use alone. However, baseline and periodic ophthalmologic examinations are recommended for long-term use due to risk of retinal toxicity. For pregnant patients, routine prenatal monitoring is appropriate. In cases of maternal autoimmune disease, additional monitoring for disease activity and fetal well-being (e.g., ultrasound, nonstress tests) may be indicated based on maternal condition. |
| Fertility Effects | Hydroxychloroquine does not appear to adversely affect fertility in women or men. Studies in patients with autoimmune diseases suggest no negative impact on ovarian reserve or sperm parameters. In fact, by controlling autoimmune disease activity, hydroxychloroquine may improve fertility outcomes in affected individuals. |