PLAQUENIL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PLAQUENIL (PLAQUENIL).
Antimalarial and immunosuppressant; inhibits heme polymerase in Plasmodium, preventing conversion of toxic heme to hemozoin; also inhibits lysosomal function, antigen presentation, and cytokine production (e.g., IL-1, TNF-alpha) in autoimmune diseases.
| Metabolism | Hepatic metabolism primarily via CYP2D6, CYP3A4, and CYP2C8; partially excreted unchanged in urine. |
| Excretion | Renal (50-70% unchanged), fecal (20-30% as metabolites), minor biliary. |
| Half-life | Terminal elimination half-life: 32-50 days (range 22-124 days) due to extensive tissue distribution and slow release from melanin-rich tissues; requires long-term dosing to achieve steady state (3-6 months). |
| Protein binding | ~50% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | Extensive: 500-800 L/kg (total Vd), indicating deep tissue sequestration (e.g., eyes, skin, liver, kidneys). |
| Bioavailability | Oral: ~75% (range 67-90%) with interindividual variability; food may increase absorption. |
| Onset of Action | Oral: 4-12 weeks for autoimmune diseases (e.g., SLE, rheumatoid arthritis); 2-4 weeks for antimalarial prophylaxis. |
| Duration of Action | Clinical effects persist for weeks to months after discontinuation due to slow elimination from tissues; anti-inflammatory effects typically last 2-4 weeks after last dose. |
400 mg (310 mg base) orally daily, or 400 mg/day in divided doses; maintenance: 200-400 mg/day
| Dosage form | TABLET |
| Renal impairment | No specific guidelines; caution with severe impairment (CrCl <30 mL/min) – reduce dose by 50% or extend interval |
| Liver impairment | No specific guidelines; caution with severe hepatic impairment (Child-Pugh C) – consider dose reduction by 50% |
| Pediatric use | 6.5 mg/kg (base) orally daily, maximum 400 mg/day; malaria: 13 mg/kg base initially, then 6.5 mg/kg at 6, 24, and 48 hours |
| Geriatric use | Start at lower end of dosing range; monitor for retinal toxicity (cumulative dose >1000 g or >5 years use) |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PLAQUENIL (PLAQUENIL).
| Breastfeeding | Hydroxychloroquine is excreted into breast milk in small amounts. Milk-to-plasma ratio approximately 0.45. Amount ingested by infant relative to maternal dose is less than 2%. No adverse effects in nursing infants reported. Considered compatible with breastfeeding. |
| Teratogenic Risk | Plaquenil (hydroxychloroquine) is not associated with major teratogenic effects. First trimester exposure: no increased risk of major malformations above baseline. Second and third trimesters: possible low risk of fetal hearing loss and retinal toxicity with maternal long-term use. No documented fetal cardiotoxicity. |
■ FDA Black Box Warning
No FDA boxed warning.
| Serious Effects |
["Hypersensitivity to hydroxychloroquine or 4-aminoquinoline derivatives","Pre-existing retinopathy of any etiology","Long-term therapy in children (not a contraindication for short-term malaria treatment)"]
| Precautions | ["Retinal toxicity: Dose-related, cumulative risk; baseline and annual ophthalmologic exams recommended","Cardiomyopathy: Rare but potentially fatal; discontinue if signs of conduction abnormalities or heart failure develop","Hypoglycemia: Can occur, particularly in patients with diabetes or on antidiabetic agents","QT prolongation: Risk increased with concurrent use of other QT-prolonging drugs or electrolyte disturbances","Myopathy/neuropathy: Reversible upon discontinuation","Blood dyscrasias: Monitor for unexplained infection, bruising, or bleeding"] |
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| Fetal Monitoring | Monitor for maternal retinal toxicity (baseline and annual ophthalmologic exam). Monitor maternal complete blood count and liver function tests periodically. Fetal monitoring: consider fetal auditory screening if high cumulative dose exposure. No specific fetal echocardiography required. |
| Fertility Effects | No significant effects on fertility. Hydroxychloroquine does not impair ovulation, spermatogenesis, or implantation. Can be used in patients attempting conception. |