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

Medically reviewed by Drugs.com. Last updated on June 15, 2020.

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Introduction

Antimalarial; 4-aminoquinoline derivative.¹³⁶

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.^{115 121 134 136}

Can be used for prevention of malaria in individuals traveling to malarious areas where chloroquine-resistant P. falciparum malaria has not been reported.^{115 121 134} (See Chloroquine-resistant Plasmodium under Cautions.)

Risk of acquiring malaria varies substantially from traveler to traveler and from region to region (even within a single country) because of differences in intensity of malaria transmission within the various regions and season, itinerary, duration, and type of travel.^{115 121} Malaria transmission occurs in large areas of Africa, Central and South America, parts of the Caribbean, Asia (including South Asia, Southeast Asia, and the Middle East), Eastern Europe, and the South Pacific.¹¹⁵ Mosquito avoidance measures must be used in conjunction with prophylaxis since no drug is 100% effective in preventing malaria.^{115 121}

Choice of antimalarial for prophylaxis depends on traveler’s risk of acquiring malaria in area(s) visited, risk of exposure to drug-resistant P. falciparum, other medical conditions (e.g., pregnancy), cost, and potential adverse effects.^{115 121 134}

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;^{115 134 136} terminal prophylaxis with a 14-day regimen of primaquine may be indicated in addition to chloroquine prophylaxis if travelers were exposed in areas where P. ovale or P. vivax is endemic.^{115 134 136}

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. ovale, chloroquine-susceptible P. vivax, or chloroquine-susceptible P. falciparum.^{134 136 143 144}

For treatment of uncomplicated malaria caused by chloroquine-susceptible P. falciparum, P. malariae, or P. knowlesi or treatment of uncomplicated malaria when plasmodial species not identified and infection was acquired in areas where chloroquine resistance not reported, CDC recommends chloroquine (or hydroxychloroquine).^{143 144} Alternatively, CDC states that any of the regimens recommended for treatment of uncomplicated chloroquine-resistant P. falciparum malaria (fixed combination of atovaquone and proguanil [atovaquone/proguanil], fixed combination of artemether and lumefantrine [artemether/lumefantrine], regimen of quinine in conjunction with doxycycline, tetracycline, or clindamycin) may be used if preferred, more readily available, or more convenient.^{143 144}

Pediatric patients with uncomplicated malaria generally can receive same treatment regimens recommended for adults using age- and weight-appropriate drugs and dosages.^{143 144}

Because chloroquine active only against asexual erythrocytic forms of Plasmodium (not exoerythrocytic stages), 14-day regimen of primaquine indicated to eradicate hypnozoites and prevent delayed primary attacks or relapse and provide a radical cure whenever chloroquine used for treatment of P. ovale or P. vivax malaria.^{134 143}

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}

Coronavirus Disease 2019 (COVID-19)

Being investigated for and has been used in the management of coronavirus disease 2019 (COVID-19)† caused by the SARS-CoV-2 virus.^{194 195 196 200 211 215 220 221}

Targeted for investigation based on evidence of in vitro activity against SARS-CoV-2 (see Actions and Spectrum)^{191 212} and on initial anecdotal reports and preliminary information from small trials.^{194 195 196 220} In addition, 4-aminoquinoline derivatives (chloroquine, hydroxychloroquine) have immunomodulatory activity that theoretically could contribute to anti-inflammatory responses in patients with viral infections.^{193 196 213 215}

Although efficacy and safety not clearly established,^{220 224} chloroquine has been included in some guidelines as an option for treatment of COVID-19.^{211 220}

Various clinical trials evaluating use of chloroquine (alone or in conjunction with other antivirals or other drugs) have been initiated in the US and other countries.^{194 200 221} Information on the status of some clinical trials evaluating chloroquine for treatment or prevention of COVID-19 is available at [Web].²⁰⁰

On March 28, 2020, FDA issued an emergency use authorization (EUA) that permits chloroquine and hydroxychloroquine to be distributed from the Strategic National Stockpile (SNS) to public health authorities to facilitate availability of the drugs during the COVID-19 pandemic for use only in hospitalized adults and adolescents weighing ≥50 kg for whom a clinical trial is not available or participation not feasible.²²⁴ FDA concluded that emergency use of chloroquine and hydroxychloroquine for treatment of COVID-19 met criteria for issuance of an EUA because SARS-CoV-2 can cause a serious or life-threatening disease or condition, including severe respiratory illness; based on the totality of scientific evidence available to FDA, it is reasonable to believe that the drugs may be effective in treating COVID-19 and, when used under EUA conditions, known and potential benefits outweigh known and potential risks; and there are no adequate, approved, and available alternatives to emergency use of chloroquine and hydroxychloroquine for treatment of COVID-19.²²⁴ To request chloroquine and/or hydroxychloroquine under the EUA, healthcare providers should contact their local or state health departments;^{225 226} distribution to states will be managed by the Office of the Assistant Secretary for Preparedness and Response (ASPR) and Federal Emergency Management Agency (FEMA).²²⁹ To mitigate risks of this unapproved use, the EUA includes certain mandatory requirements (including adverse event reporting to the FDA MedWatch program).^{224 225 226} For additional information, consult the EUA,²²⁴ EUA fact sheets for healthcare providers,^{225 226} and EUA fact sheets for patients and parent/caregivers^{227 228} available at the FDA website.

Extraintestinal Amebiasis

Has been used for treatment of extraintestinal amebiasis¹³⁶ (including liver abscess) caused by Entamoeba histolytica.

Ineffective for treatment of intestinal amebiasis.^a

A nitroimidazole derivative (metronidazole, tinidazole) followed by a luminal amebicide (iodoquinol, paromomycin, diloxanide furoate) is regimen of choice for mild to moderate or severe intestinal amebiasis and for amebic hepatic abscess.¹³⁴

Lupus Erythematosus

Has been used as an adjunct to topical corticosteroid therapy in treatment of discoid lupus erythematosus† and as an adjunct to systemic corticosteroid and/or salicylate therapy in treatment of systemic lupus erythematosus†.^a

Consider risk of severe and sometimes irreversible toxicity if used for prolonged periods in treatment of lupus erythematosus.^a (See Cautions.)

Rheumatoid Arthritis

Has been used for treatment of rheumatoid arthritis†.^a

When a disease-modifying antirheumatic drug (DMARD) indicated, other DMARDs (hydroxychloroquine, leflunomide, methotrexate, minocycline, sulfasalazine) recommended.^{103 104}

Consider risk of severe and sometimes irreversible toxicity if used for prolonged periods in treatment of rheumatoid arthritis.^a (See Cautions.)

Porphyria Cutanea Tarda and Polymorphous Light Eruptions

Has been used with some success in treatment of porphyria cutanea tarda†.^{185 186 187} (See Patients with Psoriasis or Porphyria under Cautions.)

Has been effective in some cases when used in treatment of polymorphous light eruptions†.^a

Sarcoidosis

Has been used with some success in the treatment of sarcoidosis†.^{188 189}

Chloroquine Dosage and Administration

Administration

Administer orally.^{102 136}

Oral Administration

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

For prevention of malaria, give once weekly on same day each week.¹³⁶

Dosage

Available as chloroquine phosphate;^{102 136} dosage expressed as chloroquine phosphate or as the base (chloroquine).^{102 136}

Each 500-mg tablet of chloroquine phosphate contains 300 mg of chloroquine.^{102 136}

Dosage in children is based on body weight.^{102 136}

Pediatric Patients

Malaria

Prevention of Malaria in Areas without Chloroquine-resistant Plasmodium

Oral

5 mg/kg (8.3 mg/kg of chloroquine phosphate) once weekly on same day each week.^{115 134 136}

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

If exposure occurred in areas where P. ovale or P. vivax is endemic, terminal prophylaxis with a 14-day regimen of primaquine may be indicated;^{115 136} give during final 2 weeks of chloroquine prophylaxis or, if not feasible, give after chloroquine prophylaxis discontinued.¹¹⁵

Treatment of Uncomplicated Chloroquine-susceptible Malaria

Oral

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

Adults

Malaria

Prevention of Malaria in Areas without Chloroquine-resistant Plasmodium

Oral

300 mg (500 mg of chloroquine phosphate) once weekly on same day each week.^{134 115 136}

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

If exposure occurred in areas where P. ovale or P. vivax is endemic, terminal prophylaxis with a 14-day regimen of primaquine may be indicated;^{115 136} give during final 2 weeks of chloroquine prophylaxis or, if not feasible, give after chloroquine prophylaxis discontinued.¹¹⁵

Treatment of Uncomplicated Chloroquine-susceptible Malaria

Oral

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

Prophylaxis of P. ovale or P. vivax When Primaquine Deferred during Pregnancy

Oral

300 mg (500 mg of chloroquine phosphate) once weekly for duration of the pregnancy.^{143 144} Give after usual treatment regimen and continue until a 14-day regimen of primaquine can be given after delivery to provide a radical cure.^{143 144}

Coronavirus Disease 2019 (COVID-19)†

Treatment of COVID-19†

Oral

Efficacy and safety not established;²²⁴ optimal dosage and duration of treatment not known.^{220 224}

The EUA for hospitalized adults and adolescents weighing ≥50 kg (see Coronavirus Disease 2019 [COVID-19] under Uses) suggests 1 g on day 1, then 500 mg daily for 4–7 days of total treatment based on clinical evaluation.²²⁵

Various other dosage regimens recommended in other countries or being investigated are presented below:^{194 200 211}

500 mg of chloroquine phosphate twice daily for 10 days.¹⁹⁴

500 mg of chloroquine phosphate twice daily for 7 days in adults 18–65 years of age weighing more than 50 kg or 500 mg of chloroquine phosphate twice daily on days 1 and 2, then 500 mg once daily on days 3–7 in adults weighing less than 50 kg.²¹¹

Initial dose of 600 mg (of chloroquine) followed by 300 mg (of chloroquine) 12 hours later on day 1, then 300 mg (of chloroquine) twice daily on days 2–5.¹⁹⁴

Extraintestinal Amebiasis

Oral

600 mg of chloroquine (1 g of chloroquine phosphate) once daily for 2 days, followed by 300 mg (500 mg of chloroquine phosphate) once daily for at least 2–3 weeks; usually used in conjunction with an intestinal amebicide.¹³⁶

Lupus Erythematosus†

Oral

150 mg (250 mg of chloroquine phosphate) daily.^a

When used in conjunction with topical corticosteroids in treatment of discoid lupus erythematosus, skin lesions may regress within 3–4 weeks and new lesions may not appear.^a When systemic and cutaneous manifestations of lupus erythematosus subside, reduce chloroquine dosage gradually over several months, and discontinue as soon as possible.^a

Rheumatoid Arthritis†

Oral

150 mg (250 mg of chloroquine phosphate) daily.^a Reduce dosage after remission or maximum improvement occurs.^a

Response may not occur until after >4–6 weeks of therapy.^a Some clinicians recommend the drug be continued for 4 months before being considered ineffective for treatment of rheumatoid arthritis.^a

Prescribing Limits

Pediatric Patients

Malaria

Prevention of Malaria in Areas Without Chloroquine-resistant Plasmodium

Oral

Maximum dose 300 mg (500 mg of chloroquine phosphate).^{115 134 136}

Treatment of Uncomplicated Chloroquine-susceptible Malaria

Oral

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

Adults

Malaria

Treatment of Uncomplicated Chloroquine-susceptible Malaria

Oral

Maximum initial dose 600 mg (1 g of chloroquine phosphate); maximum subsequent doses 300 mg (500 mg of chloroquine phosphate).¹³⁶

Special Populations

Hepatic Impairment

No specific recommendations available regarding need for dosage adjustment in individuals with hepatic impairment;¹³⁶ use with caution.¹³⁶ (See Hepatic Impairment under Cautions.)

Renal Impairment

No specific recommendations available regarding need for dosage adjustment in individuals with renal impairment;¹³⁶ substantially eliminated by the kidneys.¹³⁶ (See Renal Impairment under Cautions.)

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

Contraindications

• Hypersensitivity to 4-aminoquinoline derivatives.¹⁰²

• Retinal or visual field changes attributable to any etiology.¹⁰²

Warnings/Precautions

Warnings

Inappropriate Use

CDC issued a health advisory concerning inappropriate use of chloroquine and hydroxychloroquine.²²² At least 1 death reported in individuals who ingested non-pharmaceutical chloroquine (marketed for aquarium use) in an attempt to prevent or treat COVID-19.²²² 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, Central America west of the Panama Canal, and some countries in the Middle East.¹¹⁵

High prevalence of chloroquine-resistant P. vivax confirmed in Papua New Guinea and Indonesia;^{115 143} 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}

Malaria patients who do not respond to chloroquine treatment should be switched to a regimen recommended for chloroquine-resistant P. falciparum (e.g., atovaquone/proguanil, artemether/lumefantrine, regimen of quinine in conjunction with doxycycline, tetracycline, or clindamycin) or chloroquine-resistant P. vivax (e.g., quinine and doxycycline [or tetracycline] in conjunction with primaquine, atovaquone/proguanil in conjunction with primaquine, mefloquine in conjunction with primaquine).¹⁴³

Cardiac Effects

Cardiomyopathy resulting in cardiac failure, fatal in some cases, reported in patients receiving chloroquine.¹⁰² 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.¹⁰² Hypotension and ECG changes (particularly inversion or depression of T wave and widening of QRS complex) reported.¹⁰²

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.¹⁰²

Consider chronic toxicity when conduction disorders (bundle branch block/AV heart block) or biventricular hypertrophy are diagnosed.¹⁰²

Monitor for signs and symptoms of cardiomyopathy; discontinue the drug if cardiomyopathy develops.¹⁰²

If cardiotoxicity suspected, prompt discontinuance of chloroquine may prevent life-threatening complications.¹⁰²

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.¹⁰²

Advise patients about risk of hypoglycemia and associated clinical signs and symptoms.¹⁰² If clinical symptoms suggestive of hypoglycemia occur during chloroquine treatment, assess blood glucose and review treatment as clinically indicated.¹⁰² In patients already receiving insulin or other antidiabetic agents, consider that decreased dosage of these drugs may be required.¹⁰²

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 Retinal changes may be reversible if detected early, but usually are permanent and may rarely result in blindness.^a

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 fatigue,^a nervousness,^a anxiety,¹³⁶ apathy,^a irritability,^a agitation,¹³⁶ aggressiveness,^a 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.¹⁰²

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

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 a} 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

Category C.^c

Has been used for prophylaxis and treatment of malaria in pregnant women without evidence of adverse effects on the fetus.^{107 108 109 115 121}

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}

Because malaria infection in pregnant women is associated with high risks of maternal and perinatal morbidity and mortality (e.g., miscarriage, premature delivery, low birth weight, congenital infection and/or perinatal death), CDC recommends prompt chloroquine treatment in pregnant women with uncomplicated malaria caused by P. malariae, P. ovale, chloroquine-susceptible P. falciparum, or chloroquine-susceptible P. vivax.¹⁴³

Because use of primaquine should be deferred during pregnancy, CDC recommends that pregnant women being treated for P. ovale or P. vivax malaria receive chloroquine prophylaxis for the duration of the pregnancy (after the initial chloroquine treatment regimen) until primaquine can be given after delivery to provide a radical cure.^{143 144}

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

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;¹⁰² if concomitant use necessary, use caution.¹⁰²

Specific Drugs

Chloroquine Pharmacokinetics

Absorption

Bioavailability

Rapidly and almost completely absorbed from GI tract following oral administration;^{a 136} 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 most strains of Plasmodium malariae, P. ovale, P. vivax, and susceptible P. falciparum.^a Not active against preerythrocytic or exoerythrocytic forms of plasmodia.^a Gametocytocidal for P. malariae and P. vivax, but has no direct activity against gametocytes of P. falciparum.^a

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

• High prevalence of chloroquine-resistant P. vivax confirmed in Papua New Guinea and Indonesia.^{115 143 145 154 156} 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.^{143 161}

• Chloroquine-resistant P. falciparum also are resistant to hydroxychloroquine¹⁰⁹ and may be cross-resistant to pyrimethamine or quinine.^a Cross-resistance between chloroquine and mefloquine reported in P. falciparum and P. vivax in vitro.^{152 153}

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

• Has in vitro activity against various viruses, including coronaviruses.^{191 192 193 213 214}

• Evidence of in vitro activity against SARS-CoV-1 (causative agent of severe acute respiratory syndrome [SARS]),^{192 199} MERS-CoV (causative agent of Middle East respiratory syndrome [MERS]),¹⁹⁵ and SARS-CoV-2 (causative agent of COVID-19).^{191 194} In addition to in vitro activity in Vero E6 cells infected with SARS-CoV-2, there is some evidence the drug may block infection when uninfected cells are exposed to SARS-CoV-2.^{191 194 212}

• 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.^{115 121 134}

• 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.)

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?

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