Class: Antimalarials
VA Class: AP101
CAS Number: 50-63-5

Medically reviewed by Drugs.com on Nov 29, 2021. Written by ASHP.

Introduction

Antimalarial; 4-aminoquinoline derivative.

Uses for Chloroquine

Prevention of Malaria

Prevention (prophylaxis) of malaria caused by Plasmodium malariae, P. ovale, chloroquine-susceptible P. vivax, and chloroquine-susceptible P. falciparum.

Do not use for prevention of malaria in areas where chloroquine resistance has been reported. (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. 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.

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].

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.

Do not use for treatment of malaria in areas where chloroquine resistance has been reported. (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.

Information on recommended regimens for treatment of malaria is available from CDC at [Web]. 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.

Extraintestinal Amebiasis

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

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

Lupus Erythematosus

Has been used in treatment of discoid lupus erythematosus† and systemic lupus erythematosus†. Hydroxychloroquine preferred if a 4-aminoquinoline derivative used in the treatment of autoimmune diseases.

Rheumatoid Arthritis

Has been used for treatment of rheumatoid arthritis†.

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

Porphyria Cutanea Tarda

Has been used for treatment of porphyria cutanea tarda†.

Sarcoidosis

Has been used for treatment of sarcoidosis†.

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, possibility that immunomodulatory activity of 4-aminoquinoline derivatives (chloroquine and hydroxychloroquine) might contribute to anti-inflammatory responses in patients with viral infections, and initial anecdotal reports and preliminary information from small trials. However, safety and efficacy for treatment or prevention of COVID-19 not established, and NIH and IDSA 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 Dosage and Administration

Administration

Administer orally.

Administration with a meal may minimize adverse GI effects.

Dosage

Available as chloroquine phosphate; dosage expressed as chloroquine phosphate or as the base (chloroquine).

Each 500-mg tablet of chloroquine phosphate contains 300 mg of chloroquine.

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.

Initiate prophylaxis 1–2 weeks prior to entering malarious area and continue during stay and for 4 weeks after leaving the area.

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.

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.

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.

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.

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

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.

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.

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.

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.

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).

Treatment of Uncomplicated Chloroquine-susceptible Malaria

Oral

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

Special Populations

Hepatic Impairment

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

Renal Impairment

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

Geriatric Patients

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

Cautions for Chloroquine

Contraindications

• Hypersensitivity to 4-aminoquinoline derivatives.

• Retinal or visual field changes attributable to any etiology.

Warnings/Precautions

Warnings

Cardiac Effects

Cardiomyopathy resulting in cardiac failure, fatal in some cases, reported in patients receiving chloroquine. 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. Hypotension and ECG changes (particularly inversion or depression of T wave and widening of QRS complex) reported.

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.

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

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

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

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.

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

Ocular Effects

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

Visual disturbances reported in patients receiving chloroquine include blurred vision and difficulty in focusing or accommodation. Nyctalopia, 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), and reversible corneal opacities also reported.

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

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

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

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.

Neuropsychiatric and Nervous System Effects

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

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

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

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

Neuromuscular Effects

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

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

Discontinue chloroquine if muscular weakness occurs.

Patients with Psoriasis or Porphyria

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

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

Inappropriate Use

CDC issued a health advisory concerning inappropriate use of chloroquine and hydroxychloroquine. 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.

Advise patients and the public that chloroquine and hydroxychloroquine should be used only under supervision of a healthcare provider. 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.

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.

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

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.

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.

Sensitivity Reactions

Hypersensitivity Reactions

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

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

General Precautions

Hematologic Effects

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

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

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

Otic Effects

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

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

Hepatic Effects

Hepatitis and increased liver enzymes reported.

Specific Populations

Pregnancy

Has been used for prophylaxis and treatment of malaria in pregnant women without evidence of adverse effects on the fetus.

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.

CDC states pregnancy not a contraindication when chloroquine indicated for prevention or treatment of malaria.

Lactation

Distributed into milk. Discontinue nursing or the drug.

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. When prevention of malaria indicated, such infants should receive recommended dosages of appropriate antimalarial agent(s).

Pediatric Use

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

Geriatric Use

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

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

Hepatic Impairment

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

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).

Interactions for Chloroquine

Drugs that Prolong QT Interval

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

Specific Drugs

Chloroquine Pharmacokinetics

Absorption

Bioavailability

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

Food

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

Distribution

Extent

Widely distributed into body tissues.

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

Crosses placenta in mice. Distributed into milk.

Plasma Protein Binding

50–65%.

Elimination

Metabolism

Partially metabolized; major metabolite is desethylchloroquine. Desethylchloroquine also has antiplasmodial activity, but is slightly less active than chloroquine.

Elimination Route

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

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

Half-life

Usually 72–120 hours.

Serum concentrations decline in a biphasic manner and terminal half-life increases with increasing doses. 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.

Stability

Storage

Oral

Tablets

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

Actions and Spectrum

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

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

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

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

• Chloroquine-resistant Plasmodium also are resistant to hydroxychloroquine.

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

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

Advice to Patients

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

• 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. Necessity of taking protective measures to reduce contact with mosquitoes (protective clothing, insect repellents, mosquito nets, remaining in air-conditioned or well-screened areas).

• Possibility of contracting malaria during travel, regardless of prophylactic regimen used. 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.

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

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

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

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

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

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Frequently asked questions

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

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