CHLOROQUINE PHOSPHATE
Clinical safety rating: caution
Comprehensive 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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CHLOROQUINE PHOSPHATE (CHLOROQUINE PHOSPHATE).
| Breastfeeding | Chloroquine is excreted into breast milk in small amounts (M/P ratio approximately 0.3-0.5). Infant dose is estimated <5% of maternal weight-adjusted dose. No adverse effects in breastfed infants reported. Considered compatible with breastfeeding. |
| 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. |
■ 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 any 4-aminoquinoline","Pre-existing retinopathy or visual field changes","Pregnancy (especially first trimester) due to potential fetal harm; use for malaria only if benefit outweighs risk","Lactation: caution, excreted in breast milk","G6PD deficiency (relative contraindication; 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."] |
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| 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. |