CHLOROQUINE PHOSPHATE
Clinical safety rating
cautionComprehensive clinical and safety monograph for CHLOROQUINE PHOSPHATE (CHLOROQUINE PHOSPHATE).
Chloroquine is a 4-aminoquinoline that acts as a blood schizonticide. It inhibits heme polymerase in malaria parasites, preventing the conversion of toxic heme to hemozoin, leading to accumulation of toxic heme and parasite death. It also has anti-inflammatory and immunomodulatory effects via inhibition of toll-like receptors and cytokine production.
| Metabolism | Hepatic metabolism via CYP2C8 and CYP3A4 to major metabolite desethylchloroquine; other minor metabolites. Renal excretion of parent drug and metabolites. |
| Excretion | Renal: 50-70% as unchanged drug; hepatic/biliary: 20-30% as metabolites; fecal: up to 20%. |
| Half-life | Terminal elimination half-life: 30-60 days (range 20-100 days); prolonged due to extensive tissue distribution and slow release from lysosomes. |
| Protein binding | 50-60% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Vd: 100-150 L/kg (range 50-200 L/kg); extremely large indicating extensive tissue penetration and accumulation. |
| Bioavailability | Oral: 80-90% (rapidly absorbed from GI tract); bioavailability is nearly complete with food enhancing absorption. |
| Onset of Action | Oral: 2-3 hours (antiparasitic effect); IV: 15-30 minutes (for acute malaria). |
| Duration of Action | Oral: 24-48 hours for antimalarial effect; chronic dosing for rheumatoid arthritis requires 6-12 weeks for full effect. |
| Molecular Weight | 515.86 |
600 mg base (1 g phosphate) orally once daily for 2 days, then 300 mg base (500 mg phosphate) orally once daily for 3 days for malaria. For extraintestinal amebiasis: 600 mg base (1 g phosphate) orally once daily for 2 days, then 300 mg base (500 mg phosphate) orally once daily for 2-3 weeks.
| Dosage form | TABLET |
| Renal impairment | For CrCl <10 mL/min: use 50% of normal dose. For CrCl 10-50 mL/min: no adjustment required. For intermittent hemodialysis: no supplemental dose needed. |
| Liver impairment | Severe impairment (Child-Pugh C): maximum 300 mg base (500 mg phosphate) every 12 hours; monitor for toxicity. Mild to moderate impairment: no adjustment needed. |
| Pediatric use | For malaria: 10 mg base/kg (16.7 mg phosphate/kg) orally once daily for 2 days, then 5 mg base/kg (8.3 mg phosphate/kg) orally once daily for 3 days. Maximum single dose: 600 mg base (1 g phosphate). For extraintestinal amebiasis: 10 mg base/kg (16.7 mg phosphate/kg) orally once daily for 2-3 weeks (max 300 mg base/day). |
| Geriatric use | No specific dose adjustment; use with caution due to increased risk of QT prolongation and accumulation with renal impairment. Consider lower initial dose and monitor renal function. |
| 1st trimester | Use only if clearly needed; potential teratogenicity. Human data limited; animal studies show embryotoxicity. Generally avoided unless treating acute malaria. |
| 2nd trimester | Use only if clearly needed; theoretical risk of retinopathy and ototoxicity. Monitor fetal growth if used long-term. |
| 3rd trimester | Use only if clearly needed; may cause fetal harm (retinopathy, ototoxicity, cardiac effects). Avoid near term if possible. |
Clinical note
Comprehensive clinical and safety monograph for CHLOROQUINE PHOSPHATE (CHLOROQUINE PHOSPHATE).
| Placental transfer | Chloroquine crosses the placenta readily; achieves fetal serum concentrations similar to maternal. |
| Breastfeeding | Small amounts excreted into breast milk; considered compatible with breastfeeding by the American Academy of Pediatrics (AAP). However, monitor infant for potential effects (e.g., irritability, pruritus). |
| Lactation Rating | L2 (Probably Compatible) |
| Teratogenic Risk | Chloroquine phosphate crosses the placenta. First trimester: limited data suggest no major increase in congenital malformations, but risk cannot be excluded. Second and third trimesters: no specific fetal risks documented at standard doses; however, high doses (e.g., for malaria treatment) may cause retinal toxicity or ototoxicity. Overall, considered low teratogenic risk, but benefit-risk assessment required. |
| Fetal Monitoring | Baseline and periodic complete blood count, liver function tests, and ophthalmologic examination (retinal toxicity risk with prolonged use). Monitor for QT prolongation via ECG if concomitant QT-prolonging drugs. In pregnancy, monitor for signs of hemolysis in G6PD-deficient patients. |
| Fertility Effects | No evidence of adverse effects on fertility in humans. Animal studies show no impairment. |
■ FDA Black Box Warning
None explicitly required in current FDA labeling for chloroquine; however, serious adverse effects such as irreversible retinal damage, cardiac toxicity, and hypoglycemia are well-documented. Not receiving a black box warning in standard product labeling.
| Serious Effects |
Hypersensitivity to chloroquine or related compounds (e.g., amodiaquine)Pre-existing retinopathyGlucose-6-phosphate dehydrogenase (G6PD) deficiency (relative; may cause hemolysis)
| Precautions | Retinopathy: irreversible retinal damage with prolonged use; baseline and periodic ophthalmologic exams recommended for chronic therapy., Cardiac toxicity: QTc prolongation, ventricular arrhythmias, cardiomyopathy; avoid in patients with pre-existing cardiac conditions or concurrent QTc-prolonging drugs., Hypoglycemia: can cause severe hypoglycemia, especially in diabetics., Neuropsychiatric effects: seizures, psychosis, suicidal ideation., Hematologic toxicity: agranulocytosis, aplastic anemia (rare)., Hepatotoxicity: elevated liver enzymes, hepatic failure., Ototoxicity: irreversible hearing loss., G6PD deficiency: hemolytic anemia risk with acute hemolysis. |
| Food/Dietary | No specific food restrictions. Absorption enhanced by food; take with meals to reduce GI upset. Avoid grapefruit juice if QT prolongation concern. |
| Clinical Pearls | Chloroquine has a narrow therapeutic index; toxicity can cause retinopathy, especially with cumulative doses >460g base. Baseline and annual eye exams are mandatory. For acute malaria, may need loading dose. Contraindicated in G6PD deficiency due to hemolysis risk. QT prolongation possible; avoid with other QT-prolonging drugs. |
| Patient Advice | Take exactly as prescribed; do not miss doses or double up. · Can cause blurred vision; avoid driving until vision clears. · Report vision changes, hearing loss, or unusual bleeding immediately. · May cause GI upset; take with food or milk. · Finishing full course is critical even if symptoms improve. · Use sunscreen; may increase sensitivity to sunlight. |
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