ARALEN HYDROCHLORIDE
Clinical safety rating
cautionComprehensive clinical and safety monograph for ARALEN HYDROCHLORIDE (ARALEN HYDROCHLORIDE).
Chloroquine, a 4-aminoquinoline, accumulates in acidic organelles such as lysosomes and food vacuoles of malaria parasites, raising pH and inhibiting hemozoin polymerization, which leads to toxic heme accumulation and parasite death. It also has anti-inflammatory and immunomodulatory effects by inhibiting TLR signaling and cytokine production.
| Metabolism | Hepatic metabolism via CYP2C8, CYP3A4, and CYP2D6 to desethylchloroquine and other metabolites. |
| Excretion | Renal (~70% unchanged), with 10-20% in feces; biliary elimination is minor. |
| Half-life | 48-72 hours (terminal elimination half-life); prolonged to weeks with chronic dosing due to extensive tissue accumulation, especially in the liver, spleen, and melanin-containing tissues. |
| Protein binding | 50-60%, primarily to albumin and α1-acid glycoprotein. |
| Volume of Distribution | 50-100 L/kg; extensive tissue sequestration including erythrocytes, liver, spleen, and melanin-containing tissues like skin and retina. |
| Bioavailability | Oral: ~70-80% (variable due to first-pass metabolism); intravenous: 100%. |
| Onset of Action | Oral: 1-2 hours for antimalarial effect; intravenous: minutes. |
| Duration of Action | Single dose: antimalarial effect lasts 3-4 weeks; chronic therapy for autoimmune conditions requires weeks for full effect, and therapeutic effects persist for weeks after discontinuation. |
| Molecular Weight | 319.87 |
Chloroquine phosphate 500 mg (300 mg base) orally once weekly for prophylaxis; 600 mg base (1 g phosphate) orally initially, followed by 300 mg base (500 mg phosphate) at 6, 24, and 48 hours for treatment of malaria.
| Dosage form | INJECTABLE |
| Renal impairment | Severe renal impairment (GFR <10 mL/min): reduce dose by 50% or increase dosing interval. |
| Liver impairment | Use with caution in patients with hepatic impairment; no specific dose adjustment guidelines available; contraindicated in severe hepatic disease or porphyria. |
| Pediatric use | Prophylaxis: 5 mg base/kg orally once weekly (max 300 mg base). Treatment: 10 mg base/kg orally initially, then 5 mg base/kg at 6, 24, and 48 hours (max 600 mg base total). |
| Geriatric use | Start at lower end of dosing range due to increased risk of adverse effects (e.g., QT prolongation, retinal toxicity); monitor renal function. |
| 1st trimester | Avoid: Potential teratogenic effects, including ototoxicity and skeletal deformities, particularly at high doses. Use only if benefit outweighs risk. |
| 2nd trimester | Use with caution: Risk of maternal and fetal toxicity, including ototoxicity and retinal damage. Monitor closely. |
| 3rd trimester | Use with caution: Accumulation in fetal tissues (especially melanin-containing tissues). Risk of neonatal hemolytic anemia if G6PD deficiency present. |
Clinical note
Comprehensive clinical and safety monograph for ARALEN HYDROCHLORIDE (ARALEN HYDROCHLORIDE).
| Placental transfer | Extensive: Chloroquine readily crosses the placenta, achieving fetal plasma concentrations similar to maternal levels. |
| Breastfeeding | Excreted into breast milk in small amounts; theoretical risk of toxicity in nursing infants, especially with prolonged use. Monitor infant for rash, visual changes, and hearing impairment. |
| Lactation Rating | L3 (Moderately Safe) - limited data, potential for adverse effects. |
| Teratogenic Risk | Chloroquine hydrochloride crosses the placenta. First trimester: associated with increased risk of spontaneous abortion and congenital abnormalities (cochleovestibular and ocular) at high doses. Second and third trimesters: possible ototoxicity and retinal toxicity; use only for malaria prophylaxis or treatment when benefit outweighs risk. |
| Fetal Monitoring | Baseline and periodic ophthalmic examinations (including fundoscopy and visual field testing) due to risk of retinopathy; complete blood count and liver function tests. Fetal monitoring: ultrasound for growth and anatomy if used in first trimester; consider auditory screening for newborns if exposed in utero. |
| Fertility Effects | Chloroquine has not been associated with significant adverse effects on fertility in humans. Animal studies have not shown impaired fertility. No specific effects on spermatogenesis or oogenesis reported. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Hypersensitivity to chloroquine or 4-aminoquinoline derivativesPre-existing retinopathy or visual field defectsKnown G6PD deficiency (relative contraindication, caution required)Porphyria (may exacerbate)
| Precautions | Retinopathy and irreversible retinal damage with prolonged use or high doses; requires baseline and periodic ophthalmologic exams, QT prolongation and ventricular arrhythmias, especially with concomitant QT-prolonging drugs or electrolyte abnormalities, Severe hypoglycemia including loss of consciousness, Neuropsychiatric effects including psychosis and suicidal ideation, Hemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficiency |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may increase drug levels and toxicity. Limit alcohol intake to reduce risk of liver toxicity. Administer with food to decrease gastrointestinal irritation. Avoid antacids containing aluminum or magnesium; separate by at least 4 hours. |
| Clinical Pearls | ARALEN HYDROCHLORIDE (chloroquine hydrochloride) is used for malaria prophylaxis and treatment, and for amebiasis. Monitor for retinal toxicity with long-term use; baseline and periodic ophthalmologic exams recommended. Caution in patients with hepatic disease, G6PD deficiency, or porphyria. May exacerbate psoriasis and myasthenia gravis. QT prolongation possible; avoid with other QT-prolonging drugs. Administer with food to reduce GI upset. For acute malaria, dose may be divided to improve tolerance. In severe malaria, use parenteral form with cardiac monitoring. |
| Patient Advice | Take this medication exactly as prescribed; do not skip doses for malaria prophylaxis. · If vomiting occurs within 1 hour of a dose, contact your healthcare provider for instructions. · Report any vision changes, such as blurred vision or difficulty focusing, immediately. · Avoid alcohol and limit caffeine intake as they may increase gastrointestinal side effects. · Use effective contraception during treatment if you are of childbearing potential. · Do not take antacids or kaolin within 4 hours of this medication. · Seek medical attention if you experience signs of allergic reaction: rash, hives, swelling, or difficulty breathing. |
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