Skip to Content

Chloroquine

Pronunciation

Pronunciation

(KLOR oh kwin)

Index Terms

  • Chloroquine Phosphate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral, as phosphate:

Aralen: 500 mg [equivalent to chloroquine base 300 mg]

Generic: 250 mg [equivalent to chloroquine base 150 mg], 500 mg [equivalent to chloroquine base 300 mg]

Brand Names: U.S.

  • Aralen

Pharmacologic Category

  • Aminoquinoline (Antimalarial)
  • Antimalarial Agent

Pharmacology

Binds to and inhibits DNA and RNA polymerase; interferes with metabolism and hemoglobin utilization by parasites; inhibits prostaglandin effects; chloroquine concentrates within parasite acid vesicles and raises internal pH resulting in inhibition of parasite growth; may involve aggregates of ferriprotoporphyrin IX acting as chloroquine receptors causing membrane damage; may also interfere with nucleoprotein synthesis

Absorption

Rapid and almost complete

Distribution

Widely in body tissues including eyes, heart, kidneys, liver, leukocytes, and lungs where retention is prolonged

Metabolism

Partially hepatic to main metabolite, desethylchloroquine

Excretion

Urine (~70%; ~35% as unchanged drug); acidification of urine increases elimination; small amounts of drug may be present in urine months following discontinuation of therapy

Time to Peak

Serum: Oral: Within 1-2 hours

Half-Life Elimination

3-5 days

Protein Binding

50% to 65%

Use: Labeled Indications

Malaria: Suppressive treatment and acute attacks of malaria due to Plasmodium vivax, P. malariae, P. ovale, and susceptible strains of P. falciparum.

Extraintestinal amebiasis: Treatment of extraintestinal amebiasis.

Use: Unlabeled

Rheumatoid arthritis; discoid lupus erythematosus

Contraindications

Hypersensitivity to 4-aminoquinoline compounds or any component of the formulation; the presence of retinal or visual field changes either attributable to 4-aminoquinoline compounds or to any other etiology

Dosing: Adult

Note: Each 250 mg of chloroquine phosphate is equivalent to 150 mg of chloroquine base

Malaria chemoprophylaxis: Oral: 500 mg (300 mg base) weekly on the same day each week; begin 1-2 weeks prior to exposure; continue while in endemic area and for 4 weeks after leaving endemic area (CDC, 2014)

Malaria treatment: Oral: 1 g (600 mg base) on day 1, followed by 500 mg (300 mg base) 6-, 24-, and 48 hours after first dose (CDC, 2009)

Extraintestinal amebiasis: Oral: 1 g (600 mg base) daily for 2 days followed by 500 mg daily (300 mg base) for at least 2-3 weeks; may be combined with an intestinal amebicide.

Lupus erythematosus (off-label use): 250 mg (150 mg base) once daily for ≥3 months. Note: Not considered first-line agent (Bezerra, 2005; Lesiak, 2008)

Rheumatoid arthritis (off-label use): 250 mg (150 mg base) once daily for ≥1 year. Note: Not considered first-line agent (Fowler, 1984; Freedman, 1960)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Each 250 mg of chloroquine phosphate is equivalent to 150 mg of chloroquine base

Malaria chemoprophylaxis: Oral: 8.3 mg/kg/week (5 mg/kg base) on the same day each week (not to exceed 500 mg/dose [300 mg base/dose]); begin 1-2 weeks prior to exposure; continue while in endemic area and for 4 weeks after leaving endemic area (CDC, 2014)

Malaria treatment: Oral: 16.6 mg/kg (10 mg/kg base) on day 1 (maximum: 1000 mg [600 mg base]), followed by 8.3 mg/kg (5 mg/kg base) (maximum: 500 mg [300 mg base]) 6-, 24-, and 48 hours after first dose (CDC, 2009)

Dosing: Renal Impairment

The FDA-approved labeling does not contain renal dosing adjustment guidelines; the following guidelines have been used by some clinicians (Aronoff, 2007):

CrCl ≥10 mL/minute: No dosage adjustment necessary.

CrCl <10 mL/minute: Administer 50% of dose.

Hemodialysis effects: Minimally removed by hemodialysis.

Hemodialysis, peritoneal dialysis: Administer 50% of dose.

Continuous renal replacement therapy (CRRT): No dosage adjustment necessary.

Dosing: Hepatic Impairment

No dosage adjustment provided in manufacturer’s labeling; use with caution.

Extemporaneously Prepared

A 15 mg chloroquine phosphate/mL oral suspension (equivalent to 9 mg chloroquine base/mL) may be made from tablets and a 1:1 mixture of Ora-Sweet® and Ora-Plus®. Crush three 500 mg chloroquine phosphate tablets (equivalent to 300 mg base/tablet) in a mortar and reduce to a fine powder. Add 15 mL of the vehicle and mix to a uniform paste; mix while adding the vehicle in incremental proportions to almost 100 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 100 mL. Label “shake well before using” and “protect from light”. Stable for up to 60 days when stored in the dark at room temperature or refrigerated (preferred).

Allen LV Jr and Erickson MA 3rd, "Stability of Alprazolam, Chloroquine Phosphate, Cisapride, Enalapril Maleate, and Hydralazine Hydrochloride in Extemporaneously Compounded Oral Liquids," Am J Health Syst Pharm, 1998, 55(18):1915-20. 9784772

Storage

Store at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F); protect from light.

Drug Interactions

Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Consider therapy modification

Agalsidase Alfa: Chloroquine may diminish the therapeutic effect of Agalsidase Alfa. Avoid combination

Agalsidase Beta: Chloroquine may diminish the therapeutic effect of Agalsidase Beta. Avoid combination

Ampicillin: Chloroquine may decrease the serum concentration of Ampicillin. Management: Chloroquine prescribing information recommends separating administration of ampicillin and chloroquine by at least 2 hours to minimize any potential negative impact of chloroquine on ampicillin bioavailability. Consider therapy modification

Antacids: May decrease the serum concentration of Chloroquine. Management: Separate administration of antacids and chloroquine by at least 4 hours to minimize any potential negative impact of antacids on chloroquine bioavailability. Consider therapy modification

Anthelmintics: Aminoquinolines (Antimalarial) may decrease the serum concentration of Anthelmintics. Monitor therapy

Antipsychotic Agents (Phenothiazines): Antimalarial Agents may increase the serum concentration of Antipsychotic Agents (Phenothiazines). Monitor therapy

Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Artemether: May enhance the adverse/toxic effect of Antimalarial Agents. Management: Artemether/Lumefantrine (combination product) should not be used with other antimalarials unless there is no other treatment option. Avoid combination

Asunaprevir: May increase the serum concentration of CYP2D6 Substrates. Consider therapy modification

Beta-Blockers: Aminoquinolines (Antimalarial) may decrease the metabolism of Beta-Blockers. Exceptions: Atenolol; Carteolol (Ophthalmic); Levobunolol; Metipranolol; Nadolol; Sotalol. Monitor therapy

Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Cardiac Glycosides: Aminoquinolines (Antimalarial) may increase the serum concentration of Cardiac Glycosides. Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Monitor therapy

CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates. Consider therapy modification

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Monitor therapy

CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Dapsone (Systemic): Antimalarial Agents may enhance the adverse/toxic effect of Dapsone (Systemic). Specifically, concomitant use of antimalarial agents with dapsone may increase the risk of hemolytic reactions. Dapsone (Systemic) may enhance the adverse/toxic effect of Antimalarial Agents. Specifically, concomitant use of dapsone with antimalarial agents may increase the risk for hemolytic reactions. Management: Closely monitor patients for signs/symptoms of hemolytic reactions with concomitant use of dapsone and antimalarial agents, particularly in patients deficient in glucose-6-phosphate dehydrogenase (G6PD), methemoglobin reductase, or with hemoglobin M. Consider therapy modification

Dapsone (Topical): Antimalarial Agents may enhance the adverse/toxic effect of Dapsone (Topical). Specifically, the risk of hemolytic reactions may be increased. Management: Closely monitor for signs/symptoms of hemolytic reactions with concomitant use of topical dapsone and antimalarial agents. Patients with glucose-6-phosphate dehydrogenase deficiency may be at particularly high risk for adverse hematologic effects. Consider therapy modification

Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates. Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Highest Risk QTc-Prolonging Agents: Moderate Risk QTc-Prolonging Agents may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination

Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Ivabradine: May enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Avoid combination

Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Kaolin: May decrease the serum concentration of Chloroquine. Management: Separate administration of kaolin and chloroquine by at least 4 hours to minimize any potential negative impact of kaolin on chloroquine bioavailability. Consider therapy modification

Lanthanum: May decrease the serum concentration of Chloroquine. Management: Administer chloroquine at least two hours before or after lanthanum. Consider therapy modification

Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Lumefantrine: Antimalarial Agents may enhance the adverse/toxic effect of Lumefantrine. Management: Artemether/Lumefantrine (combination product) should not be used with other antimalarials unless there is no other treatment option. Avoid combination

Mefloquine: Aminoquinolines (Antimalarial) may enhance the adverse/toxic effect of Mefloquine. Specifically, the risk for QTc-prolongation and the risk for convulsions may be increased. Mefloquine may increase the serum concentration of Aminoquinolines (Antimalarial). Management: Avoid concurrent use, and delay administration of mefloquine until at least 12 hours after the last dose of an aminoquinoline antimalarial when possible. Avoid combination

MiFEPRIStone: May enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Avoid combination

Mitotane: May decrease the serum concentration of CYP3A4 Substrates. Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Moderate Risk QTc-Prolonging Agents: May enhance the QTc-prolonging effect of other Moderate Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Nitric Oxide: May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when nitric oxide is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine. Monitor therapy

Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Panobinostat: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of sensitive CYP2D6 substrates when possible, particularly those substrates with a narrow therapeutic index. Consider therapy modification

Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates. Monitor therapy

Perhexiline: CYP2D6 Substrates may increase the serum concentration of Perhexiline. Perhexiline may increase the serum concentration of CYP2D6 Substrates. Monitor therapy

Prilocaine: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine in infants receiving such agents. Monitor therapy

QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying): May enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Monitor therapy

Rabies Vaccine: Chloroquine may diminish the therapeutic effect of Rabies Vaccine. Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Sodium Nitrite: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Sodium Nitrite. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Monitor therapy

St John's Wort: May decrease the serum concentration of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Tetracaine (Topical): May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Monitor therapy

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Adverse Reactions

Frequency not defined.

Cardiovascular: Cardiomyopathy, ECG changes (rare; including prolonged QRS and QTc intervals, T wave inversion or depression), hypotension (rare), torsades de pointes (rare)

Central nervous system: Agitation, anxiety, confusion, decreased deep tendon reflex, delirium, depression, extrapyramidal reaction (dystonia, dyskinesia, protrusion of the tongue, torticollis), hallucination, headache, insomnia, personality changes, polyneuropathy, psychosis, seizure

Dermatologic: Alopecia, bleaching of hair, blue gray skin pigmentation, erythema multiforme (rare), exacerbation of psoriasis, exfoliative dermatitis (rare), lichen planus, pleomorphic rash, pruritus, skin photosensitivity, Stevens-Johnson syndrome (rare), toxic epidermal necrolysis (rare), urticaria

Gastrointestinal: Abdominal cramps, anorexia, diarrhea, nausea, vomiting

Hematologic & oncologic: Agranulocytosis (rare; reversible), aplastic anemia, neutropenia, pancytopenia, thrombocytopenia

Hepatic: Hepatitis, increased liver enzymes

Hypersensitivity: Anaphylactoid reaction, anaphylaxis, angioedema

Immunologic: DRESS syndrome

Neuromuscular & skeletal: Myopathy, neuromuscular disease, proximal myopathy

Ophthalmic: Accommodation disturbances, blurred vision, corneal opacity (reversible), macular degeneration (may be irreversible), maculopathy (may be irreversible), nocturnal amblyopia, retinopathy (including irreversible changes in some patients long-term or high-dose therapy), visual field defects

Otic: Deafness (nerve), hearing loss (risk increased in patients with pre-existing auditory damage), tinnitus

Warnings/Precautions

Concerns related to adverse effects:

• Cardiovascular effects: Has been associated with ECG changes, AV block, and cardiomyopathy (rare). Generally these are dose and/or duration dependent. May cause QT prolongation and subsequent torsade de pointes; avoid use in patients with diagnosed or suspected congenital long QT syndrome.

• Extrapyramidal effects: Acute extrapyramidal disorders may occur, usually resolving after discontinuation of therapy and/or symptomatic treatment.

• Hematologic effects: Rare hematologic reactions including reversible agranulocytosis, aplastic anemia, neutropenia, pancytopenia, and thrombocytopenia have been reported; monitor CBC during prolonged therapy. Consider discontinuation if severe blood disorders occur that are unrelated to disease.

• Neuromuscular effects: Skeletal muscle myopathy or neuromyopathy, leading to progressive weakness and atrophy of proximal muscle groups have been reported; muscle strength (especially proximal muscles) should be assessed periodically during prolonged therapy; discontinue therapy if weakness occurs.

• Ophthalmic effects: Retinopathy, maculopathy, and macular degeneration have occurred; irreversible retinal damage has occurred with prolonged or high dose 4-aminoquinoline therapy; risk factors include age, duration of therapy, and/or high doses. Monitoring is required, especially with prolonged therapy. Discontinue immediately if signs/symptoms occur; visual changes may progress even after therapy is discontinued.

Disease-related concerns:

• Auditory damage: Use with caution in patients with preexisting auditory damage; discontinue immediately if hearing defects are noted.

• G6PD deficiency: Use with caution in patients with known G6PD; use of 4-aminoquinolines such as chloroquine has been associated with hemolysis and renal impairment in this population.

• Hepatic impairment: Use with caution in patients with hepatic impairment, alcoholism, or concurrent therapy with hepatotoxic agents.

• Porphyria: Use with caution in patients with porphyria; may exacerbate disease symptoms.

• Psoriasis: Use with caution in patients with psoriasis; may exacerbate disease symptoms.

• Seizure disorder: Use with caution in patients with a history of seizure disorder; may cause seizures.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Appropriate use: Chloroquine does not prevent relapses in patients with vivax or malariae malaria; will not prevent vivax or malariae infection when administered as a prophylactic. Also consult current CDC guidelines for treatment recommendations.

• Chloroquine resistance: Certain strains of P. falciparum are resistant to 4-aminoquinoline compounds. Prior to initiation of therapy, it should be determined if chloroquine is appropriate for use in the region to be visited; do not use for the treatment of P. falciparum acquired in areas of chloroquine resistance or where chloroquine prophylaxis has failed. Patients should be treated with another antimalarial if patient is infected with a resistant strain of plasmodia.

Monitoring Parameters

Ophthalmic exams at baseline and periodically thereafter during prolonged therapy; visual acuity, expert slit-lamp, fundoscopic and visual field tests are recommended. Evaluate neuromuscular function periodically during prolonged therapy. Periodic CBC in patients receiving prolonged therapy

Pregnancy Considerations

In animal reproduction studies, drug accumulated in fetal ocular tissues and remained for several months following drug elimination from the rest of the body. Chloroquine and its metabolites cross the placenta and can be detected in the cord blood and urine of the newborn infant (Akintonwa, 1988; Essien, 1982; Law, 2008). In one study, chloroquine and its metabolites were measurable in the cord blood 89 days (mean) after the last maternal dose (Law, 2008).

Malaria infection in pregnant women may be more severe than in nonpregnant women and has a high risk of maternal and perinatal morbidity and mortality. Therefore, pregnant women and women who are likely to become pregnant are advised to avoid travel to malaria-risk areas. Chloroquine is recommended for the treatment of pregnant women for uncomplicated malaria in chloroquine-sensitive regions; when caused by chloroquine-sensitive P. vivax or P. ovale, pregnant women should be maintained on chloroquine prophylaxis for the duration of their pregnancy (refer to current guidelines) (CDC, 2011; CDC, 2012).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience abdominal pain, nausea, vomiting, headache, diarrhea, skin discoloration, hair discoloration, or hair loss. Have patient report immediately to prescriber signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), arrhythmia, vision changes, eye pain, severe eye irritation, weight loss, bruising, bleeding, mood changes, hearing impairment, tinnitus, muscle weakness, or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Hide