Drug class: Antimalarials

Medically reviewed by Drugs.com on Jun 10, 2024. Written by ASHP.

Introduction

Antimalarial; 4-aminoquinoline derivative.¹⁰⁰

Uses for Chloroquine Phosphate

Prevention of Malaria

Prevention (prophylaxis) of malaria caused by Plasmodium malariae, P. ovale, chloroquine-susceptible P. vivax, and chloroquine-susceptible P. falciparum.^{100 115 121 134}

Do not use for prevention of malaria in areas where chloroquine resistance has been reported.^{115 121 134} (See Chloroquine-resistant Plasmodium under Cautions.)

Active only against asexual erythrocytic forms of Plasmodium (not exoerythrocytic stages) and cannot prevent delayed primary attacks or relapse of P. ovale or P. vivax malaria or provide a radical cure.^{100 115 134} Therefore, an 8-aminoquinoline antimalarial (14-day regimen of primaquine or single dose of tafenoquine) is indicated in addition to chloroquine prophylaxis if travelers were exposed in areas with P. ovale or P. vivax malaria.^{100 115 134}

Information on risk of malaria in specific countries and mosquito avoidance measures and recommendations regarding whether prevention of malaria indicated and choice of antimalarials for prevention are available from CDC at [Web] and [Web].¹¹⁵

Treatment of Uncomplicated Malaria

Treatment of uncomplicated malaria caused by P. malariae, P. knowlesi, P. ovale, chloroquine-susceptible P. vivax, or chloroquine-susceptible P. falciparum.^{100 134 143 144}

Do not use for treatment of malaria in areas where chloroquine resistance has been reported.^{115 143} (See Chloroquine-resistant Plasmodium under Cautions.)

Because chloroquine is active only against asexual erythrocytic forms of Plasmodium (not exoerythrocytic stages), an 8-aminoquinoline (14-day regimen of primaquine or single dose of tafenoquine) is indicated in conjunction with chloroquine to eradicate hypnozoites and prevent relapse in patients being treated for P. ovale or P. vivax malaria.^{100 134 143}

Information on recommended regimens for treatment of malaria is available from CDC at [Web].^{143 144} Assistance with diagnosis or treatment of malaria available from CDC Malaria Hotline at 770-488-7788 or 855-856-4713 from 9:00 a.m. to 5:00 p.m. Eastern Standard Time or CDC Emergency Operation Center at 770-488-7100 after hours and on weekends and holidays.^{143 144}

Extraintestinal Amebiasis

Has been used for treatment of extraintestinal amebiasis caused by Entamoeba histolytica.¹⁰⁰

A nitroimidazole derivative (metronidazole, tinidazole) followed by a luminal amebicide (iodoquinol, paromomycin) is regimen of choice for treatment of extraintestinal amebiasis.¹³⁴

Lupus Erythematosus

Has been used in treatment of discoid lupus erythematosus^{† [off-label]} and systemic lupus erythematosus^{† [off-label]}.²¹³ Hydroxychloroquine preferred if a 4-aminoquinoline derivative used in the treatment of autoimmune diseases.²¹³

Rheumatoid Arthritis

Has been used for treatment of rheumatoid arthritis^{† [off-label]}.²¹³

When a conventional disease-modifying antirheumatic drug (DMARD) indicated, other conventional DMARDs (hydroxychloroquine, leflunomide, methotrexate, sulfasalazine) recommended.¹⁰³

Porphyria Cutanea Tarda

Has been used for treatment of porphyria cutanea tarda^{† [off-label]}.^{185 186 187}

Sarcoidosis

Has been used for treatment of sarcoidosis^{† [off-label]}.^{188 189}

Coronavirus Disease 2019 (COVID-19)

Was targeted for investigation as a potential option for treatment and prevention of coronavirus disease 2019 (COVID-19)^† caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during early stages of the COVID-19 pandemic based on some evidence of in vitro activity against SARS-CoV-2,^{198 212 231} possibility that immunomodulatory activity of 4-aminoquinoline derivatives (chloroquine and hydroxychloroquine) might contribute to anti-inflammatory responses in patients with viral infections,^{193 198 213 215 216 231} and initial anecdotal reports and preliminary information from small trials.^{197 218} However, safety and efficacy for treatment or prevention of COVID-19 not established,²³⁰ and NIH²³¹ and IDSA²³² recommend against use of chloroquine or hydroxychloroquine (alone or in conjunction with other antivirals or other drugs) in the treatment or prevention of COVID-19.

Chloroquine Phosphate Dosage and Administration

Administration

Administer orally.^{100 136}

Administration with a meal may minimize adverse GI effects.^{121 134}

Extemporaneously Compounded Oral Suspension

Standardize 4 Safety

Standardized concentrations for an extemporaneously compounded oral suspension of chloroquine have been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care²⁵² . Because recommendations from the S4S panels may differ from the manufacturer’s prescribing information, caution is advised when using concentrations that differ from labeling, particularly when using rate information from the label.²⁵² For additional information on S4S (including updates that may be available), see [Web].²⁵²

Chloriquine label should state the 10 mg/mL concentration reflects base chloroquine and not the chloroquine salt.

Dosage

Available as chloroquine phosphate;^{100 136} dosage expressed as chloroquine phosphate or as the base (chloroquine).^{100 136}

Each 500-mg tablet of chloroquine phosphate contains 300 mg of chloroquine.^{100 136}

Pediatric Patients

Malaria

Prevention of Malaria in Areas without Chloroquine-resistant Plasmodium

Oral

8.3 mg/kg of chloroquine phosphate (5 mg/kg of chloroquine) once weekly on same day each week.^{100 115 134}

Initiate prophylaxis 1–2 weeks prior to entering malarious area and continue during stay and for 4 weeks after leaving the area.^{100 115 121}

If exposure occurred in areas where P. ovale or P. vivax is endemic, terminal prophylaxis with an 8-aminoquinoline antimalarial (14-day regimen of primaquine or single dose of tafenoquine) also indicated.^{100 115}

Treatment of Uncomplicated Chloroquine-susceptible Malaria

Oral

Initial dose of 16.7 mg/kg of chloroquine phosphate (10 mg/kg of chloroquine) followed by 8.3 mg/kg of chloroquine phosphate (5 mg/kg of chloroquine) given at 6, 24, and 48 hours after initial dose.^{100 134 144}

If chloroquine used for treatment of malaria caused by P. ovale or P. vivax, treatment with an 8-aminoquinoline antimalarial (14-day regimen of primaquine or single dose of tafenoquine) also indicated to provide a radical cure.^{143 144}

Adults

Malaria

Prevention of Malaria in Areas without Chloroquine-resistant Plasmodium

Oral

500 mg of chloroquine phosphate (300 mg of chloroquine) once weekly on same day each week.^{100 134 115}

Initiate prophylaxis 1–2 weeks prior to entering malarious area and continue during and for 4 weeks after leaving the area.^{100 115}

If exposure occurred in areas where P. ovale or P. vivax is endemic, terminal prophylaxis with an 8-aminoquinoline antimalarial (14-day regimen of primaquine or single dose of tafenoquine) also indicated.^{100 115}

Treatment of Uncomplicated Chloroquine-susceptible Malaria

Oral

Initial dose of 1 g of chloroquine phosphate (600 mg of chloroquine) followed by 500 mg of chloroquine phosphate (300 mg of chloroquine) given at 6, 24, and 48 hours after initial dose.^{100 134 144}

If chloroquine used for treatment of malaria caused by P. ovale or P. vivax, treatment with an 8-aminoquinoline antimalarial (14-day regimen of primaquine or single dose of tafenoquine) also indicated to provide a radical cure.^{143 144}

Extraintestinal Amebiasis

Oral

1 g of chloroquine phosphate (600 mg of chloroquine) once daily for 2 days, followed by 500 mg of chloroquine phosphate (300 mg of chloroquine) once daily for at least 2–3 weeks; usually used in conjunction with an intestinal amebicide.¹⁰⁰

Prescribing Limits

Pediatric Patients

Malaria

Prevention of Malaria in Areas Without Chloroquine-resistant Plasmodium

Oral

Maximum dose 500 mg of chloroquine phosphate (300 mg of chloroquine).^{100 115 134}

Treatment of Uncomplicated Chloroquine-susceptible Malaria

Oral

Maximum dose 1 g of chloroquine phosphate (600 mg of chloroquine).¹³⁴

Special Populations

Hepatic Impairment

No specific recommendations available regarding need for dosage adjustment in individuals with hepatic impairment;¹³⁶ use with caution.¹³⁶

Renal Impairment

No specific recommendations available regarding need for dosage adjustment in individuals with renal impairment;¹³⁶ substantially eliminated by the kidneys.¹³⁶

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.¹³⁶

Cautions for Chloroquine Phosphate

Contraindications

• Hypersensitivity to 4-aminoquinoline derivatives.¹⁰⁰

• Retinal or visual field changes attributable to any etiology.¹⁰⁰

Warnings/Precautions

Warnings

Cardiac Effects

Cardiomyopathy resulting in cardiac failure, fatal in some cases, reported in patients receiving chloroquine.¹⁰⁰ Cardiac arrhythmias, conduction disorders such as bundle branch block/AV block, QT interval prolongation, torsades de pointes, ventricular tachycardia, and ventricular fibrillation reported with therapeutic dosages and overdosages of chloroquine.¹⁰⁰ Hypotension and ECG changes (particularly inversion or depression of T wave and widening of QRS complex) reported.¹⁰⁰

Use with caution in patients with cardiac disease, history of ventricular arrhythmias, uncorrected hypokalemia and/or hypomagnesemia, or bradycardia (<50 bpm), and in those receiving concomitant therapy with other drugs with potential to prolong QT interval.¹⁰⁰

Consider chronic toxicity when conduction disorders (bundle branch block/AV heart block) or biventricular hypertrophy are diagnosed.¹⁰⁰

Monitor for signs and symptoms of cardiomyopathy; discontinue the drug if cardiomyopathy develops.¹⁰⁰

If cardiotoxicity suspected, prompt discontinuance of chloroquine may prevent life-threatening complications.¹⁰⁰

Hypoglycemia

Severe hypoglycemia, including loss of consciousness that could be life-threatening, reported in patients receiving chloroquine who were or were not receiving treatment with antidiabetic agents.¹⁰⁰

Advise patients about risk of hypoglycemia and associated clinical signs and symptoms.¹⁰⁰ If clinical symptoms suggestive of hypoglycemia occur during chloroquine treatment, assess blood glucose and review treatment as clinically indicated.¹⁰⁰ In patients already receiving insulin or other antidiabetic agents, consider that decreased dosage of these drugs may be required.¹⁰⁰

Ocular Effects

Retinopathy and maculopathy (as well as macular degeneration) reported, especially in patients receiving long-term treatment or high chloroquine dosage.¹³⁶ May be irreversible in some patients.¹³⁶

Visual disturbances reported in patients receiving chloroquine include blurred vision and difficulty in focusing or accommodation.¹³⁶ Nyctalopia,¹³⁶ scotomatous vision with field defects of paracentral, pericentral ring types, and typically temporal scotomas (e.g., difficulty reading with words tending to disappear, seeing half an object, misty vision, fog before the eyes), ¹³⁶ and reversible corneal opacities¹³⁶ also reported.

Dose-related retinopathy reported, which may progress even after the drug is discontinued.¹³⁶

Risk factors for development of retinopathy during chloroquine treatment include age, duration of treatment, and high daily and/or cumulated dosage.¹³⁶

Whenever long-term treatment contemplated, perform initial (base line) and periodic ophthalmologic examinations, including visual acuity, slit-lamp, funduscopic, and visual field tests.¹³⁶

Immediately discontinue chloroquine and closely observe patient for possible progression if there is any indication of abnormalities in visual acuity or visual field, abnormalities in the retinal macular area (such as pigmentary changes or loss of foveal reflex), or if any other visual symptoms (e.g., light flashes and streaks) occur which are not fully explainable by difficulties of accommodation or corneal opacities.¹³⁶

Neuropsychiatric and Nervous System Effects

Mild and transient headache,¹³⁶ polyneuritis,¹³⁶ anxiety,¹³⁶ agitation,¹³⁶ confusion,¹³⁶ insomnia,¹³⁶ delirium,¹³⁶ and hallucinations¹³⁶ have occurred.

Acute extrapyramidal disorders (e.g., dystonia, dyskinesia, tongue protrusion, torticollis) may occur;¹³⁶ usually resolve after drug discontinued and/or patient receives symptomatic treatment.¹³⁶

Seizures reported; advise patients with a history of epilepsy about the risk.¹³⁶

Neuropsychiatric events, including psychosis, delirium, anxiety, agitation, insomnia, confusion, hallucinations, personality changes, depression, and suicidal behavior, reported in patients receiving chloroquine.¹⁰⁰

Neuromuscular Effects

Skeletal muscle myopathy or neuromyopathy occur rarely; neuromyopathy is manifested as slowly progressing weakness which first affects proximal muscles of lower extremities.¹³⁶

Patients receiving prolonged therapy should be questioned and examined periodically for evidence of muscular weakness; test knee and ankle reflexes.¹³⁶

Discontinue chloroquine if muscular weakness occurs.¹³⁶

Patients with Psoriasis or Porphyria

May exacerbate psoriasis and precipitate a severe attack in patients with the disease.¹³⁶ Use in psoriasis patients only if potential benefits outweigh risks.¹³⁶

May exacerbate porphyria.¹³⁶ Use in patients with porphyria only if potential benefits outweigh risks.¹³⁶

Inappropriate Use

CDC issued a health advisory concerning inappropriate use of chloroquine and hydroxychloroquine.²²² Advise patients and the public to not ingest aquarium products or any other chemical products that contain chloroquine since these products are not intended for human consumption and can lead to serious health consequences, including death.²²²

Advise patients and the public that chloroquine and hydroxychloroquine should be used only under supervision of a healthcare provider.²²² Inappropriate uses of chloroquine and hydroxychloroquine include taking any commercially available non-pharmaceutical preparations of the drugs, taking the drugs without a prescription or without supervision by a healthcare provider, and taking additional doses of the drugs not recommended by a healthcare provider.²²²

Chloroquine-resistant Plasmodium

Chloroquine-resistant P. falciparum confirmed in all areas with P. falciparum malaria, except the Caribbean and Central America west of the Panama Canal.¹¹⁵

Chloroquine-resistant P. vivax confirmed in Papua New Guinea and Indonesia;^{115 143} rare cases also reported in Burma (Myanmar), India, and Central and South America.¹⁴³

Do not use for prevention of malaria in individuals traveling to malarious areas where chloroquine-resistant P. falciparum or chloroquine-resistant P. vivax malaria reported.^{115 134 136}

Do not use for treatment of uncomplicated P. falciparum malaria or uncomplicated malaria caused by unidentified plasmodial species if the infection was acquired in areas with chloroquine resistance.^{136 143 144}

Sensitivity Reactions

Hypersensitivity Reactions

Erythema multiforme,¹³⁶ Stevens-Johnson syndrome,¹³⁶ toxic epidermal necrolysis,¹³⁶ exfoliative dermatitis,¹³⁶ and similar desquamation-type adverse events¹³⁶ reported rarely.

Urticaria,¹³⁶ anaphylactic/anaphylactoid reaction including angioedema,¹³⁶ and drug rash with eosinophilia and systemic symptoms (DRESS syndrome)¹³⁶ also reported.

General Precautions

Hematologic Effects

Aplastic anemia, pancytopenia, reversible agranulocytosis, thrombocytopenia, and neutropenia reported rarely.¹³⁶

Periodically monitor CBCs in patients receiving prolonged treatment.¹³⁶ Consider discontinuing chloroquine if any severe blood disorder occurs and is not attributable to the disease being treated.¹³⁶

Use with caution in patients with G-6-PD deficiency.¹³⁶

Otic Effects

Nerve-type deafness, usually irreversible, reported after prolonged therapy with high dosage.¹³⁶ Tinnitus and reduced hearing reported in patients with pre-existing auditory damage.¹³⁶

Use with caution in patients with preexisting auditory damage.¹³⁶ Discontinue chloroquine immediately and closely observe patient if any hearing defects occur.¹³⁶

Hepatic Effects

Hepatitis and increased liver enzymes reported.¹³⁶

Specific Populations

Pregnancy

Has been used for prophylaxis and treatment of malaria in pregnant women without evidence of adverse effects on the fetus.^{107 112 115 121}

Manufacturer states avoid during pregnancy, except for prevention or treatment of malaria when clinician determines that possible benefits of the drug outweigh potential risks to fetus.¹³⁶

CDC states pregnancy not a contraindication when chloroquine indicated for prevention or treatment of malaria.^{115 143}

Lactation

Distributed into milk.^{122 123 124 136} Discontinue nursing or the drug.¹³⁶

Amount of drug present in milk does not appear to be harmful to nursing infants, but is insufficient to provide adequate protection against malaria in these infants.¹¹⁵ When prevention of malaria indicated, such infants should receive recommended dosages of appropriate antimalarial agent(s).¹¹⁵

Pediatric Use

Pediatric patients are especially sensitive to 4-aminoquinoline derivatives.¹³⁶ Fatalities reported following accidental ingestion of relatively small doses.¹³⁶

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.¹³⁶

Substantially eliminated by kidneys; possible increased risk of toxicity in patients with impaired renal function.¹³⁶ Select dosage with caution and assess renal function periodically since geriatric patients are more likely to have renal impairment.¹³⁶

Hepatic Impairment

Concentrates in the liver; use with caution in patients with hepatic disease or alcoholism and in those receiving known hepatotoxic drugs.¹³⁶

Renal Impairment

Substantially eliminated by kidneys; possible increased risk of toxicity in patients with impaired renal function.

Common Adverse Effects

Ocular effects; skeletal muscle myopathy or neuromyopathy; GI effects (anorexia, nausea, vomiting, diarrhea, abdominal cramps); dermatologic effects (pleomorphic skin eruptions, skin and mucosal pigmentary changes).¹³⁶

Drug Interactions

Drugs that Prolong QT Interval

Concomitant use with drugs known to prolong QT interval may increase risk of QT interval prolongation and ventricular arrhythmias;¹⁰⁰ if concomitant use necessary, use caution.¹⁰⁰

Specific Drugs

Chloroquine Phosphate Pharmacokinetics

Absorption

Bioavailability

Rapidly and almost completely absorbed from GI tract following oral administration;¹⁰⁰ peak plasma concentrations generally attained within 1–2 hours.^a

Food

Bioavailability of chloroquine is greater when administered with food;^a rate of absorption is unaffected but peak plasma concentrations and AUCs are higher.^a

Distribution

Extent

Widely distributed into body tissues.^a

Chloroquine binds to melanin-containing cells in the eyes and skin; skin concentrations of the drug are considerably higher than plasma concentrations.^a Also concentrates in erythrocytes and binds to platelets and granulocytes.^a

Crosses placenta in mice.¹³⁶ Distributed into milk.^{122 123 124 136}

Plasma Protein Binding

50–65%.¹⁰⁶

Elimination

Metabolism

Partially metabolized; major metabolite is desethylchloroquine.^{122 123 124 136 147} Desethylchloroquine also has antiplasmodial activity, but is slightly less active than chloroquine.¹¹⁴

Elimination Route

Chloroquine and its metabolites slowly excreted by the kidneys; unabsorbed drug is excreted in feces.^a

Up to 70% of a dose is excreted unchanged in urine and up to 25% of dose may be excreted in urine as desethylchloroquine.^a Small amounts of chloroquine may be present in urine for weeks, months, and occasionally years after the drug is discontinued.^a

Half-life

Usually 72–120 hours.^a

Serum concentrations decline in a biphasic manner and terminal half-life increases with increasing doses.^a Terminal half-life is 3.1 hours after a single 250-mg oral dose, 42.9 hours after a single 500-mg oral dose, and 312 hours after a single 1-g oral dose.^a

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C) in tight container.¹³⁶

Actions and Spectrum

• A blood schizonticidal agent active against asexual erythrocytic forms of susceptible P. malariae, P. ovale, P. vivax, and P. falciparum.¹⁰⁰ Not active against gametocytes and exoerythrocytic forms of plasmodia, including hypnozoite liver stage forms of P. ovale and P. vivax.¹⁰⁰

• Chloroquine-resistant P. falciparum confirmed in all areas where P. falciparum malaria occurs, except the Caribbean and Central America west of the Panama Canal.¹¹⁵

• Chloroquine-resistant P. vivax confirmed in Papua New Guinea and Indonesia.^{115 143 154 156} Rare cases of chloroquine-resistant P. vivax also documented in Burma (Myanmar), India, and Central and South America.¹⁴³

• To date, no widespread evidence of chloroquine resistance in P. malariae, P. ovale, or P. knowlesi.¹⁴³

• Chloroquine-resistant Plasmodium also are resistant to hydroxychloroquine.¹⁰⁰

• Active in vitro against the trophozoite form of Entamoeba histolytica.^a Acts as a tissue amebicide.^a

• Has anti-inflammatory activity.^a Mechanism(s) of action in the treatment of rheumatoid arthritis and lupus erythematosus not determined.^a

Advice to Patients

• Importance of keeping chloroquine out of reach of children since they are especially sensitive to 4-aminoquinoline derivatives.¹³⁶

• For prevention of malaria, necessity of starting chloroquine prophylaxis 1–2 weeks before arriving in an area with malaria and continuing during stay and for 4 weeks after leaving the area.¹¹⁵ Necessity of taking protective measures to reduce contact with mosquitoes (protective clothing, insect repellents, mosquito nets, remaining in air-conditioned or well-screened areas).^{115 121 134}

• Possibility of contracting malaria during travel, regardless of prophylactic regimen used.^{115 121} Importance of seeking medical attention as soon as possible if febrile illness develops during or after return from a malaria-endemic area and of informing clinician of possible malaria exposure.^{115 121 134}

• Advise patients with a history of epilepsy about the risk of seizures.¹³⁶

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.¹³⁶

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹³⁶

• Importance of informing patients of other important precautionary information.¹³⁶ (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Frequently asked questions

• An Update: Is hydroxychloroquine effective for COVID-19?

Medical Disclaimer