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Chloroquine

Medically reviewed by Drugs.com. Last updated on Nov 5, 2020.

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:

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

Pharmacologic Category

  • Aminoquinoline (Antimalarial)
  • Antimalarial Agent

Pharmacology

Antimalarial: 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.

Antiviral (coronavirus disease 2019 [COVID-19]): Not fully understood; however, it may change the pH at the cell membrane surface and inhibit viral fusion. It may also inhibit glycosylation of viral proteins (Wang 2020).

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

Healthy subjects: 74.7 ± 30.1 hours (Salako 1984).

Chronic renal insufficiency: 191.4 ± 69.1 hours (range: 103.5 to 309.9 hours) (Salako 1984).

Protein Binding

~55%

Special Populations: Renal Function Impairment

Half-life is prolonged with chronic kidney impairment and there is reduced conversion to desethylchloroquine (Krishna 1996; Salako 1984).

Use: Labeled Indications

Malaria: Treatment of uncomplicated malaria due to susceptible strains of Plasmodium vivax, Plasmodium malariae, Plasmodium ovale, and Plasmodium falciparum; prophylaxis of malaria (in geographic areas where chloroquine resistance is not present). Note: The CDC guidelines also recommend chloroquine for chloroquine-sensitive Plasmodium knowlesi malaria (CDC 2020).

Limitations of use: Chloroquine alone does not prevent relapses in patients with P. vivax or P. ovale malaria (not effective against exoerythrocytic forms). Do not use for the treatment of complicated malaria (high-grade parasitemia and/or complications [eg, cerebral malaria, acute renal failure]) or for malaria prophylaxis in areas where chloroquine resistance occurs (resistance to chloroquine is widespread in P. falciparum and reported in P. vivax).

Extraintestinal amebiasis: Treatment of extraintestinal amebiasis.

Off Label Uses

Discoid lupus erythematosus

Data from a prospective, randomized, controlled, double-blind clinical trial support the use of chloroquine in the treatment of discoid lupus erythematosus [Bezerra 2005]. Chloroquine also demonstrated a reduction in epidermal vascular endothelial growth factor (VEGF) expression resulting in a significant reduction in the median number of CD34+ dermal blood vessels [Lesiak 2009]. Additional data may be necessary to further define the role of chloroquine in the treatment of this condition.

Contraindications

Hypersensitivity to chloroquine, 4-aminoquinoline compounds, or any component of the formulation; the presence of retinal or visual field changes of any etiology (when used for indications other than acute malaria)

Dosing: Adult

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

Malaria, prophylaxis: Oral: 500 mg (300 mg base) weekly on the same day each week; begin 1 to 2 weeks prior to exposure; continue while in endemic area and for 4 weeks after leaving endemic area. Note: For use only in areas with chloroquine-sensitive malaria (CDC Yellow Book 2020).

Malaria, uncomplicated, 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. Note: For treatment of chloroquine-sensitive P. vivax and P. ovale, concomitant therapy with an 8-aminoquinoline (eg, primaquine, tafenoquine) is necessary (CDC 2020).

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

Lupus erythematosus (off-label use): Not considered first-line agent (Bezerra 2005; Lesiak 2008). Due to the risk of retinal toxicity, do not exceed a daily dose of 2.3 mg/kg/day of chloroquine phosphate using actual body weight; intermediate doses may be obtained by splitting tablets or eliminating a tablet on certain days of the week (AAO [Marmor 2016]).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Dosage expressed as chloroquine phosphate. Chloroquine phosphate 16.6 mg is equivalent to 10 mg chloroquine base.

Malaria:

Chemoprophylaxis: Infants, Children, and Adolescents: Oral: 8.3 mg/kg chloroquine phosphate once weekly on the same day each week; maximum dose: 500 mg chloroquine phosphate/dose. Begin 1 to 2 weeks prior to exposure; continue while in endemic area and continue for at least 4 weeks after leaving endemic area (CDC 2014); if suppressive therapy is delayed, double the initial loading dose (16.6 mg/kg, up to 1,000 mg chloroquine phosphate) and administer in 2 divided doses 6 hours apart; continue for 8 weeks after leaving endemic area

Treatment, acute attack, uncomplicated: Infants, Children, and Adolescents: Oral: Initial 16.6 mg/kg chloroquine phosphate (maximum initial dose: 1,000 mg chloroquine phosphate); followed by 8.3 mg/kg chloroquine phosphate (maximum dose: 500 mg chloroquine phosphate/dose) administered at 6, 24, and 48 hours after initial dose for a total of 4 doses (CDC 2013)

Extraintestinal amebiasis, liver abscess: Children and Adolescents: Limited data available: Oral: 16.6 mg/kg chloroquine phosphate/dose once daily in combination with metronidazole or tinidazole for 21 days followed by paromomycin or iodoquinol; maximum dose: 1,000 mg chloroquine phosphate/dose (Bradley 2015; Seidel 1984; Tony 1992)

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Extemporaneously Prepared

16.67 mg chloroquine PHOSPHATE/mL (equivalent to 10 mg chloroquine BASE/mL) Oral Suspension (ASHP Standard Concentration) (ASHP 2017)

A 16.67 mg chloroquine PHOSPHATE/mL oral suspension (equivalent to 10 mg chloroquine BASE/mL) may be made from tablets. Crush two 500 mg chloroquine PHOSPHATE tablets (equivalent to 300 mg BASE/tablet) in a mortar and reduce to a fine powder. Add a small amount of sterile water for irrigation, USP and mix to a uniform paste; mix while adding cherry syrup in incremental proportions to almost 60 mL; transfer to a calibrated amber glass bottle, rinse mortar with cherry syrup, and add sufficient quantity of cherry syrup to make 60 mL. Label "shake well". Stable for 4 weeks when stored at room temperature or refrigerated (Mirochnick 1994).

Mirochnick M, Barnett E, Clark DF, McNamara E, Cabral H. Stability of chloroquine in an extemporaneously prepared suspension stored at three temperatures. Pediatr Infect Dis J. 1994;13(9):827-828.7808855

15 mg chloroquine PHOSPHATE/mL (equivalent to 9 mg chloroquine BASE/mL) Oral Suspension

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, 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):1915-1920.9784772

A 15 mg chloroquine PHOSPHATE/mL oral suspension (equivalent to 9 mg chloroquine BASE/mL) may be made using chloroquine phosphate pharmaceutical grade powder and SyrSpend SF PH4. Weigh 1,500 mg of chloroquine phosphate powder, add to mortar and triturate to a fine powder. Add a small amount of vehicle and mix to a uniform base, mix while adding the vehicle in incremental proportions to almost 100 mL; transfer to calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 100 mL. Label "shake well". Stable for up to 90 days when stored at room temperature or refrigerated.

Ferreira AO, Polonini HC, Silva SL, Patrício FB, Brandão MAF, Raposo NRB. Feasibility of amlodipine besylate, chloroquine phosphate, dapsone, phenytoin, pyridoxine hydrochloride, sulfadiazine, sulfasalazine, tetracycline hydrochloride, trimethoprim and zonisamide in SyrSpend(®) SF PH4 oral suspensions. J Pharm Biomed Anal. 2016;118:105-112.26540625

Administration

Oral: Administer with food to decrease GI adverse effects (Medical Letter October 2019).

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

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

Agalsidase Beta: Chloroquine may diminish the therapeutic effect of Agalsidase Beta. Management: Avoid concomitant use of chloroquine with agalsidase beta when possible as chloroquine could antagonize intracellular alpha-galactosidase activity. Consider therapy modification

Amisulpride (Oral): May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Monitor therapy

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

Androgens: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy

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

Antidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

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

Bacampicillin: Chloroquine may decrease the serum concentration of Bacampicillin. Management: Separate the administration of ampicillin and chloroquine by at least 2 hours to minimize any potential negative impact of chloroquine on ampicillin bioavailability. Bacampicillin is a prodrug of ampicillin. Consider therapy modification

Beta-Blockers: Aminoquinolines (Antimalarial) may decrease the metabolism of Beta-Blockers. Monitor therapy

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

Cholera Vaccine: Chloroquine may diminish the therapeutic effect of Cholera Vaccine. Management: Administer cholera vaccine at least 10 days prior to initiation of chloroquine. Consider therapy modification

Cimetidine: May increase the serum concentration of Chloroquine. Avoid combination

Ciprofloxacin (Systemic): Chloroquine may enhance the hyperglycemic effect of Ciprofloxacin (Systemic). Chloroquine may enhance the hypoglycemic effect of Ciprofloxacin (Systemic). Chloroquine may enhance the QTc-prolonging effect of Ciprofloxacin (Systemic). Monitor therapy

CycloSPORINE (Systemic): Chloroquine may increase the serum concentration of CycloSPORINE (Systemic). Monitor therapy

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

Domperidone: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Domperidone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification

Fexinidazole [INT]: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Avoid combination

Haloperidol: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Haloperidol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

Herbs (Hypoglycemic Properties): May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Hypoglycemia-Associated Agents: May enhance the hypoglycemic effect of other Hypoglycemia-Associated Agents. Monitor therapy

Kaolin: May decrease the serum concentration of Chloroquine. Management: Separate the 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

Local Anesthetics: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. 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

Maitake: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy

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

Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. 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. Monitor therapy

Ondansetron: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Ondansetron. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

Pegvisomant: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy

Pentamidine (Systemic): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Pentamidine (Systemic). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

Pimozide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Avoid combination

Praziquantel: Chloroquine may decrease the serum concentration of Praziquantel. 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

Primaquine: Chloroquine may increase the serum concentration of Primaquine. Monitor therapy

Prothionamide: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy

QT-prolonging Agents (Highest Risk): May enhance the QTc-prolonging effect of Chloroquine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification

QT-prolonging Antidepressants (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

QT-prolonging Antipsychotics (Moderate Risk): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

QT-prolonging Class IC Antiarrhythmics (Moderate Risk): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Class IC Antiarrhythmics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

QT-prolonging Kinase Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

QT-prolonging Miscellaneous Agents (Moderate Risk): May enhance the QTc-prolonging effect of Chloroquine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

QT-prolonging Quinolone Antibiotics (Moderate Risk): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Quinolone Antibiotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Miscellaneous Agents (Moderate Risk). Avoid combination

Quinolones: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Quinolones may diminish the therapeutic effect of Agents with Blood Glucose Lowering Effects. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy

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

Remdesivir: Chloroquine may diminish the therapeutic effect of Remdesivir. Avoid combination

Salicylates: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. 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

Tamoxifen: May enhance the adverse/toxic effect of Chloroquine. Specifically, concomitant use of tamoxifen and chloroquine may increase the risk of retinal toxicity. Monitor therapy

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

Frequency not defined:

Cardiovascular: Atrioventricular block, bundle branch block, cardiac arrhythmia, cardiac failure, cardiomyopathy, ECG changes (including flattened T wave on ECG, inversion T wave on ECG, prolonged QT interval on ECG, widened QRS complex on ECG), hypotension, torsades de pointes, ventricular fibrillation, ventricular tachycardia

Dermatologic: Alopecia, bleaching of hair, blue-gray skin pigmentation (oral mucosa and hard palate, nails, and skin [Gallo 2009; Horta-Bass 2018; Manger 2017]), erythema multiforme, exacerbation of psoriasis, exfoliative dermatitis, lichen planus, pleomorphic rash, pruritus, skin photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria

Endocrine & metabolic: Exacerbation of porphyria, severe hypoglycemia

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

Hematologic & oncologic: Agranulocytosis (reversible), aplastic anemia, hemolytic anemia (in G6PD-deficient patients), neutropenia, pancytopenia, thrombocytopenia

Hepatic: Hepatitis, increased liver enzymes

Hypersensitivity: Anaphylaxis, angioedema

Immunologic: Drug reaction with eosinophilia and systemic symptoms

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, sensorimotor neuropathy, sensorineural hearing loss, suicidal tendencies

Neuromuscular & skeletal: Asthenia, myopathy, neuromuscular disease, proximal myopathy

Ophthalmic: Accommodation disturbances, blurred vision, corneal opacity (reversible), macular degeneration (may be irreversible), maculopathy (may be irreversible), night blindness, retinal pigment changes (bull’s eye appearance), retinopathy (including irreversible changes in long-term or high-dose therapy), transient scotomata, visual field defect (paracentral scotomas)

Otic: Hearing loss (risk increased in patients with preexisting auditory damage), tinnitus

Postmarketing:

Hepatic: Hepatic impairment (FDA Safety Alert, April 1, 2020)

Renal: Renal insufficiency (FDA Safety Alert, April 1, 2020)

Warnings/Precautions

Concerns related to adverse effects:

• Cardiovascular effects: Cases of cardiomyopathy resulting in cardiac failure (sometimes fatal) have been reported during long term therapy at high doses. Monitor for signs and symptoms of cardiomyopathy; discontinue if cardiomyopathy develops. Consider chronic toxicity and discontinue chloroquine if conduction disorders (bundle branch block/AV block) are diagnosed. QT prolongation, torsade de pointes, and ventricular arrhythmias (some fatal) have been reported; risk is increased with high doses. Use with caution in patients with cardiac disease, history of ventricular arrhythmias, uncorrected hypokalemia and/or hypomagnesemia, or bradycardia, and during concomitant administration with QT interval prolonging agents due to potential for QT prolongation. In a scientific statement from the American Heart Association, chloroquine has been determined to be an agent that may either cause direct myocardial toxicity or exacerbate underlying myocardial dysfunction (magnitude: major) (AHA [Page 2016]).

• 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.

• Hypoglycemia: Severe hypoglycemia, including loss of consciousness, has been reported in patients treated with or without antidiabetic agents. Counsel patients about risk of hypoglycemia and associated signs and symptoms.

• 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.

• Retinal toxicity: Retinal toxicity, potentially causing irreversible retinopathy, is predominantly associated with high daily doses and a duration of >5 years of use of chloroquine or hydroxychloroquine in the treatment of rheumatic diseases. Other major risk factors include concurrent tamoxifen use, renal impairment, lower body weight, and potentially the presence of macular disease. Risk is most accurately assessed on the basis of duration of use relative to daily dose/body weight (Marmor [AAO 2016]; Melles 2014). Based on these risks, the American Academy of Ophthalmology (AAO) recommends not exceeding a daily chloroquine phosphate dosage of 2.3 mg/kg using actual body weight. Previous recommendations to use ideal body weight are no longer advised; very thin patients in particular were at increased risk for retinal toxicity using this practice. Current AAO guidelines do not specifically address dosing in obese patients. AAO also recommends baseline screening for retinal toxicity and annual screening beginning after 5 years of use (or sooner if major risk factors are present) (Marmor [AAO 2016]).

Disease-related concerns:

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

• G6PD deficiency: Although the manufacturer’s labeling recommends chloroquine be used with caution in patients with G6PD deficiency due to a potential for hemolytic anemia, there is limited data to support this risk. Many experts consider chloroquine, when given in usual therapeutic doses to WHO Class II and III G6PD deficient patients, to probably be safe (Cappellini 2008; Luzzatto 2016; Youngster 2010). In a trial conducted in West Africa involving 74 G6PD deficient patients (predominantly Class III deficiency), there were no cases of hemolysis reported following exposure to usual doses of chloroquine (Mandi 2005). In addition, the ACR Rheumatology guidelines do not mention the need to evaluate G6PD levels prior to initiation of therapy (Singh 2015).

• 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.

Other warnings/precautions:

• Appropriate use: Chloroquine does not prevent relapses in patients with vivax or ovale malaria (not effective against exoerythrocytic forms); additional treatment with an antimalarial effective against these forms (eg, an 8-aminoquinoline) is required for the treatment of infections with P. vivax and P. ovale. Do not use for the treatment of complicated malaria (high-grade parasitemia and/or complications [eg, cerebral malaria, acute renal failure]).

• Chloroquine resistance: Chloroquine is not effective against chloroquine- or hydroxychloroquine-resistant strains of Plasmodium species. Chloroquine resistance is widespread in P. falciparum and is reported in P. vivax. Prior to initiation of chloroquine for prophylaxis, it should be determined if chloroquine is appropriate for use in the region to be visited; do not use for malaria prophylaxis in areas where chloroquine resistance occurs. Patients should be treated with another antimalarial if patient is infected with a resistant strain of plasmodia.

Monitoring Parameters

ECG, signs and symptoms of cardiomyopathy, blood glucose (if symptoms of hypoglycemia occur), CBC (with differential) at baseline and periodically. Evaluate neuromuscular function periodically during prolonged therapy; in patients at risk of torsades de pointes, monitor ECG at baseline and periodically during therapy to assess for QTc prolongation.

Ophthalmologic exam at baseline (fundus examination within the first year plus visual fields and spectral-domain optical coherence tomography if maculopathy is present) to screen for retinal toxicity, followed by annual screening beginning after 5 years of use (or sooner if major risk factors are present) (Marmor [AAO 2016]).

Pregnancy Considerations

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).

Chloroquine has not been found to increase the risk of adverse fetal events when used in recommended doses for malaria prophylaxis (CDC Yellow Book 2020). Retinal toxicity is a known risk following long-term use or high doses of chloroquine. Although animal reproduction studies have shown accumulation of chloroquine in fetal ocular tissues, an association between chloroquine and fetal ocular toxicity has not been confirmed in available human studies (Gaffar 2019; Osadchy 2011).

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. Malaria infection during pregnancy can lead to miscarriage, premature delivery, low birth weight, congenital infection, and/or perinatal death. Therefore, pregnant women and women who are likely to become pregnant are advised to avoid travel to malaria-risk areas. When travel is unavoidable, pregnant women should take precautions to avoid mosquito bites and use effective prophylactic medications.

Indications and dosing for chloroquine treatment and prophylaxis of uncomplicated malaria are the same in pregnant and nonpregnant adults. Chloroquine may be used in all trimesters of pregnancy (CDC 2020; CDC Yellow Book 2020).

Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of chloroquine may be altered (Chukwuani 2004; Fakeye 2002; Karunajeewa 2010; Lee 2008; Massele 1997; Olafuyi 2019; Salman 2017; Wilby 2011). Available studies suggest dose adjustments could be needed, but data are not sufficient to determine what an appropriate dosing change is when chloroquine is used for the treatment or prophylaxis of malaria during pregnancy (Karunajeewa 2010; Salman 2017). Pregnant patients should be closely monitored for response to treatment, especially when chloroquine is used during the second and third trimesters (WHO 2015).

Chloroquine has been under evaluation for the management of coronavirus disease 2019 (COVID-19). An emergency use authorization (EUA) was issued by the FDA in April 2020 authorizing use of chloroquine for hospitalized patients. It was revoked in June 2020 amid concerns for safety and lack of efficacy. Chloroquine should only be given as part of a clinical trial (FDA 2020; NIH 2020).

Data collection to monitor maternal and infant outcomes following exposure to COVID-19 during pregnancy is ongoing. Health care providers are encouraged to enroll females exposed to COVID-19 during pregnancy in the Organization of Teratology Information Specialists (OTIS) pregnancy registry (877-311-8972; https://mothertobaby.org/join-study/) or the PRIORITY (Pregnancy CoRonavIrus Outcomes RegIsTrY) (415-754-3729, https://priority.ucsf.edu/).

Patient Education

What is this drug used for?

• It is used to treat or prevent malaria.

• It is used to treat a type of bowel infection.

• It may be given to you for other reasons. Talk with the doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Abdominal pain

• Abdominal cramps

• Lack of appetite

• Nausea

• Vomiting

• Headache

• Diarrhea

• Skin discoloration

• Hair discoloration

• Hair loss

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes

• Low blood sugar like dizziness, headache, fatigue, feeling weak, shaking, fast heartbeat, confusion, increased hunger, or sweating

• Blurred vision

• Vision changes

• Vision loss

• Abnormal movements

• Restlessness

• Seizures

• Trouble sleeping

• Confusion

• Behavioral changes

• Mood changes

• Sensing things that seem real but are not

• Change in hearing

• Noise or ringing in the ears

• Muscle pain

• Muscle weakness

• Burning or numbness feeling

• Chills

• Sore throat

• Bruising

• Bleeding

• Heart problems like cough or shortness of breath that is new or worse, swelling of the ankles or legs, abnormal heartbeat, weight gain of more than five pounds in 24 hours, dizziness, or passing out

• Severe loss of strength and energy

• Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Chloroquine phosphate fact sheets – Health care provider; Patient

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Frequently Asked Questions