ARALEN
Clinical safety rating
cautionComprehensive clinical and safety monograph for ARALEN (ARALEN).
Chloroquine, a 4-aminoquinoline, accumulates in acidic organelles such as food vacuoles of malaria parasites, inhibiting heme polymerase and preventing the conversion of toxic heme to hemozoin. It also interferes with DNA synthesis and repair by intercalating into DNA. Additionally, it has immunomodulatory effects via inhibition of Toll-like receptors and cytokine production.
| Metabolism | Chloroquine is extensively metabolized in the liver via cytochrome P450 enzymes, primarily CYP2C8 and CYP3A4, to active metabolites such as desethylchloroquine. It has a long elimination half-life of approximately 1-2 months. |
| Excretion | Primarily renal (approximately 70% as unchanged drug); minor biliary/fecal (about 10-20%). |
| Half-life | Terminal elimination half-life ranges from 30 to 60 days (mean ~45 days) due to extensive tissue binding; clinical context: prolonged half-life allows weekly dosing for malaria prophylaxis. |
| Protein binding | Approximately 50-60% bound; primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Very large, 100-200 L/kg; extensive tissue distribution (liver, spleen, kidney, lungs, melanin-containing tissues). |
| Bioavailability | Oral: 80-90%. |
| Onset of Action | Oral: antimalarial effect begins within 1-2 hours; parenteral (intramuscular): onset within 15-30 minutes; intravenous: immediate. |
| Duration of Action | Single dose provides antimalarial effect for 1-2 weeks; chronic therapy for autoimmune diseases requires 4-6 weeks for full effect. |
| Molecular Weight | 319.87 |
Adults: 500 mg (300 mg base) orally once weekly on the same day each week for prophylaxis of malaria; 1 g (600 mg base) orally initially, followed by 500 mg (300 mg base) at 6, 24, and 48 hours for treatment of acute malaria.
| Dosage form | TABLET |
| Renal impairment | For malaria prophylaxis: No adjustment necessary. For treatment: If CrCl < 10 mL/min, reduce dose by 50%. |
| Liver impairment | No formal guidelines; use caution in severe hepatic impairment due to potential accumulation. Consider dose reduction in Child-Pugh class C. |
| Pediatric use | Prophylaxis: 5 mg/kg base (8.3 mg/kg salt) orally once weekly, max 300 mg base. Treatment: 10 mg/kg base (16.7 mg/kg salt) orally initially, followed by 5 mg/kg base at 6, 24, and 48 hours, max 600 mg base on day 1. |
| Geriatric use | No specific adjustments; consider age-related renal impairment and potential increased risk of QT prolongation. Monitor for cardiac effects. |
| 1st trimester | Avoid due to potential teratogenicity (ototoxicity, skeletal defects) from animal studies. Use only if benefit outweighs risk. |
| 2nd trimester | Caution; may accumulate in fetal tissues. Use only if clearly needed. |
| 3rd trimester | Caution near term; risk of neonatal hemolytic anemia, jaundice, and ocular toxicity. |
Clinical note
Comprehensive clinical and safety monograph for ARALEN (ARALEN).
| Placental transfer | Readily crosses placenta; fetal drug levels similar to maternal levels. |
| Breastfeeding | Excreted into breast milk in low amounts; caution due to potential for infant toxicity (e.g., ocular, allergic reactions). Consider risk-benefit. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Pregnancy category C. First trimester: No conclusive evidence of major malformations in human studies, but animal studies show embryotoxicity and fetotoxicity. Second and third trimesters: Risk of sensorineural hearing loss, vestibular damage, and retinal toxicity in the fetus if used for prolonged periods or at high doses; accumulation in fetal ocular tissues reported. |
| Fetal Monitoring | Maternal: baseline and periodic ophthalmologic exams (especially for retinal toxicity); complete blood count; hepatic and renal function tests. Fetal: ultrasound for growth and anatomy; assessment for hearing and vision in neonates with prolonged in utero exposure. |
| Fertility Effects | No conclusive evidence of adverse effects on fertility in humans. Animal studies have shown reversible effects on spermatogenesis and ovarian function at high doses; clinical significance unknown. |
■ FDA Black Box Warning
Retinopathy: Irreversible retinal damage including retinopathy and visual disturbances; risk increases with cumulative dose and duration of use; contraindicated in patients with pre-existing retinopathy; baseline and periodic ophthalmologic exams required.
| Serious Effects |
Hypersensitivity to chloroquine or 4-aminoquinolinesRetinal or visual field changesPorphyriaG6PD deficiency (risk of hemolysis)
| Precautions | Retinopathy risk with prolonged use; cardiac effects including conduction disorders (e.g., QT prolongation) and cardiomyopathy; exacerbation of psoriasis and porphyria; neuropsychiatric effects (e.g., psychosis, seizures); hematologic toxicity (eg, agranulocytosis, aplastic anemia); hypoglycemia; myopathy; ototoxicity. Use with caution in hepatic or renal impairment, G6PD deficiency, and pregnancy (benefit vs risk). |
| Food/Dietary | Avoid grapefruit juice as it may increase chloroquine levels. No other significant food interactions. |
| Clinical Pearls | Chloroquine (Aralen) can cause retinal toxicity; cumulative dose should not exceed 200g. Use with caution in G6PD deficiency. Can prolong QTc interval; avoid with other QTc-prolonging drugs. |
| Patient Advice | Take with food to reduce gastrointestinal upset. · Do not exceed prescribed dose; overdose can be fatal. · Report any vision changes immediately; regular eye exams are required. · Avoid alcohol as it may increase risk of liver toxicity. · Inform your doctor if you have a history of heart rhythm problems. |
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