INDICATIONS

FDA

  • Malaria prophylaxis and treatment (caused by P. vivax, P. malariae, P. ovale, and chloroquine-susceptible strains of P. falciparum)
  • Amebic liver abscess

FORMS

brand name

preparation

manufacturer

route

form

dosage^

cost*

Aralen phosphate

Chloroquine phosphate

~Various generic manufacturers

PO

tab

250mg

$2.47

PO

tab

500mg

$5.64

*Prices represent cost per unit specified, are representative of "Average Wholesale Price" (AWP).
^Dosage is indicated in mg unless otherwise noted.

USUAL ADULT DOSING

  • Treatment of P. vivax, P. ovale, P. malariae, & chloroquine-sensitive P. falciparum: chloroquine phosphate 1gm salt (600mg base) once, then 500mg salt (300mg base) 6hr later, then 500mg at 24 h and 48h.
    • Chloroquine HCL 160-200 mg (base) IM or IV q6h (IV n/a in US).
  • Prevention (in chloroquine sensitive regions): 500mg salt (300mg base) PO starting one week prior to entry, continue once weekly and then four weeks after leaving endemic region.

ADULT RENAL DOSING

DOSING FOR GLOMERULAR FILTRATION OF 50-80

Usual dose

DOSING FOR GLOMERULAR FILTRATION OF 10-50

Usual dose

DOSING FOR GLOMERULAR FILTRATION OF <10 ML/MIN

150-300mg PO once daily

DOSING IN HEMODIALYSIS

No data

DOSING IN PERITONEAL DIALYSIS

No data

DOSING IN HEMOFILTRATION

No data

PEDIATRIC DOSING

USUAL PEDIATRIC DOSING

  • 500 mg tablets of chloroquine phosphate = chloroquine base 300 mg
  • Malaria treatment: 10 mg base/kg (max: 600mg base) PO loading dose then 5 mg base/kg (max 300 mg base) PO at 6, 24, and 48 hours after loading dose.
    • Give in combination with primaquine x14 days for P. vivax or P. ovale
  • Malaria prophylaxis: 5 mg base/kg per dose (max dose: 300 mg base) PO once weekly beginning 1 to 2 weeks prior to travel to endemic area; continue weekly dosing while in area and for 4 weeks after leaving area.

PEDIATRIC RENAL DOSING

Reduce dose by 50% if CrCl < 10 mL/min

Pediatric Dosing Author: George K Siberry, MD, MPH

ADVERSE DRUG REACTIONS

OCCASIONAL

  • Visual disturbances
  • Hemolysis with G6PD deficiency
  • GI intolerance
  • Pruritus
  • Weight loss
  • Alopecia

RARE

  • CNS: headache, confusion, dizziness, and psychosis
  • Peripheral neuropathy
  • Extraocular muscle palsies
  • QTc prolongation
  • Corneal opacities and retinopathy
  • Pancytopenia
  • Erythema multiforme, Steven-Johnson syndrome, and toxic epidermal necrolysis

DRUG INTERACTIONS

  • Any drugs that can prolong QTc (macrolides, antipsychotics, tricyclic antidepressants, amiodarone, fluoroquinolones, methadone...): may result in additive QTc prolongation with chloroquine co-administration. Avoid co-administration.
  • Aluminum and magnesium salts: decrease absorption of chloroquine. Administer chloroquine 2-4 hours before antacid.
  • Cimetidine: may increase chloroquine serum concentrations. Monitor for toxicity.
  • Mefloquine: co-administration may increase risk of seizure.
  • Rabies vaccine (intradermal human diploid-cell rabies vaccine): may decrease rabies-neutralizing antibody titer with chloroquine co-administration[7].

SPECTRUM

P. ovale, P. malariae, and chloroquine-sensitive P. falciparum and P. vivax.

PHARMACOLOGY

MECHANISM

The exact mechanism of action of chloroquine is not fully understood but may be related to ability of chloroquine to bind to DNA and alter its properties or to interfere with the parasite’s ability to metabolize and utilize erythrocyte hemoglobin.

PHARMACOKINETIC PARAMETERS

Absorption

89%

Metabolism and Excretion

Hepatic metabolism to desethyl metabolite. 47% of unchanged drug and 7-12% of metabolite are excreted unchanged in the urine.

Protein Binding

50-65%

Cmax, Cmin, and AUC

26 mg of chloroquine base in four divided dose over 72 hours resulted in levels above 1mmol/L (note that mean toxic dose is 4.7 mg/dl).

T1/2

4 days to 1 month.

Distribution

Widely distributed in body tissues such as eyes, heart, kidney, liver and lungs. High levels attained in erythrocytes.

DOSING FOR DECREASED HEPATIC FUNCTION

30-50% decrease in dose is recommended.

PREGNANCY RISK

C-Embryotoxic and teratogenic in animals studies. In a report of 169 infants exposed to in utero to 300 mg of chloroquine weekly throughout pregnancy did not result in increase teratogenicity. Chloroquine is the antimalarial prophylaxis considered probably safe in pregnancy. There is no other antimalarial prophylaxis with enough data in pregnancy; therefore, pregnant women should be strongly discouraged to travel in a chloroquine-resistant malarial region. From Drugs in Pregnancy and Lactation(2011): "Although some studies have suggested a low risk of congenital malformations, the lack of a pattern in the defects suggests that a causative association is unlikely. In any event, the maternal and fetal benefit of preventing and treating malaria far outweighs the risk, if any, to the embryo-fetus."

BREAST FEEDING COMPATIBILITY

2.8% of dose is excreted in breast milk. The American Academy of Pediatrics considers chloroquine to be compatible with breast feeding, but exposure inadequate for infant chemoprophylaxis. Separate chemoprophylaxis for the infant is required.

COMMENTS

  • Oral antimalarial agent, effective as malaria prophylaxis in Mexico and Central America above the Panama Canal.
    • Some chloroquine resistance in the Middle East.
    • Substantial resistance in continental South America.
  • Mefloquine or Malarone recommended for travel to areas with chloroquine-resistant P. falciparum.
  • Use with caution in pts with history of seizures and visual field changes.
  • If chloroquine is unavailable, hydroxychloroquine is an acceptable alternative.

References

  1. Yao X, Ye F, Zhang M, et al. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020.  [PMID:32150618]
  2. Price RN, von Seidlein L, Valecha N, et al. Global extent of chloroquine-resistant Plasmodium vivax: a systematic review and meta-analysis. Lancet Infect Dis. 2014;14(10):982-91.  [PMID:25213732]

    Comment: Study methods and design confound in vitro determination; however, in available studies, 100% clearnace document in humans receiving chloroquine.

  3. Laufer MK, Thesing PC, Eddington ND, et al. Return of chloroquine antimalarial efficacy in Malawi. N Engl J Med. 2006;355(19):1959-66.  [PMID:17093247]

    Comment: Study documents return of efficacy of drug when not used after a hiatus of 12 years.

  4. Baird JK. Effectiveness of antimalarial drugs. N Engl J Med. 2005;352(15):1565-77.  [PMID:15829537]

    Comment: Reviews anti-malarial drugs and proper use in different settings.

  5. Savarino A, Boelaert JR, Cassone A, et al. Effects of chloroquine on viral infections: an old drug against today's diseases? Lancet Infect Dis. 2003;3(11):722-7.  [PMID:14592603]
  6. Titus EO. Recent developments in the understanding of the pharmacokinetics and mechanism of action of chloroquine. Ther Drug Monit. 1989;11(4):369-79.  [PMID:2662478]
  7. Pappaioanou M, Fishbein DB, Dreesen DW, et al. Antibody response to preexposure human diploid-cell rabies vaccine given concurrently with chloroquine. N Engl J Med. 1986;314(5):280-4.  [PMID:3510393]
  8. White NJ. Clinical pharmacokinetics of antimalarial drugs. Clin Pharmacokinet. 1985;10(3):187-215.  [PMID:3893840]

Chloroquine is a sample topic from the Johns Hopkins ABX Guide.

To view other topics, please or .

Pediatrics Central™ is an all-in-one application that puts valuable medical information, via your mobile device or the web, in the hands of clinicians treating infants, children, and adolescents. .

Last updated: March 22, 2020