PLAQUENIL
Clinical safety rating
cautionComprehensive 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. |
| Molecular Weight | 335.87 Da |
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 | Hydroxychloroquine crosses the placenta. Data from large studies do not show an increased risk of major birth defects or miscarriage. Use is acceptable in autoimmune diseases when benefits outweigh risks. |
| 2nd trimester | No evidence of fetal harm; continued use is generally considered safe for maternal autoimmune disease management. |
| 3rd trimester | The drug can accumulate in fetal tissues. No specific adverse effects noted; however, monitoring for neonatal effects such as hypoglycemia or QT prolongation is theoretical. Use if clearly needed. |
Clinical note
Comprehensive clinical and safety monograph for PLAQUENIL (PLAQUENIL).
| Placental transfer | Hydroxychloroquine crosses the placenta with cord blood levels similar to maternal blood levels. Extensive transfer occurs. |
| Breastfeeding | Hydroxychloroquine is excreted into breast milk in small amounts. The relative infant dose is estimated at <2% of maternal weight-adjusted dose. No adverse effects in infants have been reported. Compatible with breastfeeding in most cases. |
| Lactation Rating | L2 (Safer) |
| 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. |
| 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. |
■ FDA Black Box Warning
No FDA boxed warning.
| Serious Effects |
Known hypersensitivity to hydroxychloroquine or any component of the formulationRetinopathy (pre-existing, particularly if retinal changes present)Porphyria (may exacerbate)
| 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 |
| Food/Dietary | No significant food interactions. Taking with food or milk may reduce gastrointestinal upset. |
| Clinical Pearls | Plaquenil (hydroxychloroquine) can cause irreversible retinopathy; cumulative dose > 5 g/kg increases risk. Obtain baseline and annual eye exams. Do not co-administer with QT-prolonging drugs. Check G6PD level before starting (can cause hemolysis in deficiency). Use with caution in renal or hepatic impairment, myasthenia gravis, and psoriasis. |
| Patient Advice | Take exactly as prescribed; do not increase dose or stop without consulting doctor. · Report vision changes, such as blurred vision or difficulty reading, immediately. · May take with food or milk to reduce upset stomach. · Avoid alcohol while taking this medication. · Tell all healthcare providers you are taking hydroxychloroquine. · Do not take with antacids or kaolin; separate by at least 4 hours. |
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