Chloroquine

Pharmacologic Category

Aminoquinoline (Antimalarial); Antimalarial Agent

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 to 2 weeks prior to exposure; continue while in endemic area and for 4 weeks after leaving endemic area (CDC 2018)

Malaria treatment, uncomplicated: 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) is necessary (CDC 2013).

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]).

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling; the following guidelines have been used by some clinicians (Aronoff 2007):

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

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

Hemodialysis, peritoneal dialysis: Administer 50% of dose.

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

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.

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)

Dosing: Renal Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer’s labeling; in adult patients, dosage adjustment suggested.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.

Calculations

• Creatinine Clearance by Cockcroft-Gault
• Creatinine Clearance by Cockcroft-Gault (SI units)
• Creatinine Clearance by Cockcroft-Gault with IBW
• Creatinine Clearance by Cockcroft-Gault with IBW (SI units)
• Creatinine Clearance by Jelliffe
• Creatinine Clearance by Sanaka
• Glomerular Filtration Rate by Abbreviated MDRD
• Glomerular Filtration Rate by Abbreviated MDRD (SI units)
• Glomerular Filtration Rate by MDRD
• Glomerular Filtration Rate by MDRD (IDMS-Traceable SCr)
• Glomerular Filtration Rate by MDRD (SI units)
• Glomerular Filtration Rate by Schwartz
• Glomerular Filtration Rate Estimate in African Americans by AASK Equation

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).

Limitations of use: Chloroquine does not prevent relapses in patients with vivax or 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.

* See Uses in AHFS Essentials for additional information.

Use: Off-Label: Adult

Discoid lupus erythematosusLevel of Evidence [B]

Data from a prospective, randomized, controlled, double-blind clinical trial supports the use of chloroquine in the treatment of discoid lupus erythematosus ^Ref. 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 ^Ref. Additional data may be necessary to further define the role of chloroquine in the treatment of this condition.

Level of Evidence Definitions

Level of Evidence Scale

Clinical Practice Guidelines

Malaria:

CDC, “Guidelines for Treatment of Malaria in the United States,” Table - July 2013

CDC, “Health Information for International Travel, 2018” (The Yellow Book)

CDC, “Treatment of Malaria (Guidelines for Clinicians),” July 2013

WHO, “Guidelines for the Treatment of Malaria,” 2010

Opportunistic Infections:

DHHS, Guidelines for the Prevention and Treatment of Opportunistic Infections Among HIV-Exposed and HIV-Infected Children, November 2013

DHHS, Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents

Administration: Pediatric

Oral: Administer with meals to decrease GI upset; chloroquine phosphate tablets have also been mixed with chocolate syrup or enclosed in gelatin capsules to mask the bitter taste

Storage/Stability

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

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.[PubMed 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.[PubMed 9784772]

Medication Patient Education with HCAHPS Considerations

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.

Frequently reported side effects of this drug

• Abdominal pain

• Abdominal cramps

• Lack of appetite

• Nausea

• Vomiting

• Headache

• Diarrhea

• Skin discoloration

• Hair discoloration

• Hair loss

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

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

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

• Blurred vision

• Vision changes

• Vision loss

• Eye pain

• Severe eye irritation

• Abnormal movements

• Agitation

• Seizures

• Trouble sleeping

• Confusion

• Behavioral changes

• Mood changes

• Sensing things that seem real but are not

• Trouble 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 a significant reaction like 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. 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 brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Medication Safety Issues

International issues:

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)

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; Glader 2017; Luzzatto 2016; Youngster 2010). Safety in Class I G6PD deficiency (ie, severe form of the deficiency associated with chronic hemolytic anemia) is generally unknown (Glader 2017). 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.

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 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.

* See Cautions in AHFS Essentials for additional information.

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. However, malaria infection increases the risk of prematurity, spontaneous abortion, and stillbirth (CDC 2018).

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. If travel cannot be avoided, chloroquine may be used as prophylaxis. Chloroquine is recommended for the treatment of pregnant women with uncomplicated malaria in chloroquine-sensitive regions; when caused by chloroquine-sensitive P. vivax or P. ovale, infected pregnant women should be maintained on chloroquine prophylaxis for the duration of their pregnancy (refer to current guidelines). Chloroquine may be used in all trimesters of pregnancy (CDC 2013; CDC 2018; Lalloo 2016). Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of chloroquine may be altered (Chukwuani 2004; Fakeye 2002; Karunajeewa 2010; Lee 2008; Massele 1997; Salman 2017; Wilby 2011).

Breast-Feeding Considerations

Chloroquine and its desethylchloroquine (DECQ) metabolite are present in breast milk.

Per product labeling, 11 lactating women with malaria were given a single oral dose of chloroquine 600 mg. The maximum daily dose to the breastfeeding infant was calculated to be 0.7% of the maternal dose. Additional information has been published and results are variable, likely due to various maternal doses and dosing regimens, routes of administration, and assay methods (Akintonwa 1988; Boelaert 2001; Deturmeny 1984; Edstein 1986; Ette 1987; Law 2008; Ogunbona 1987). Using data from available studies, the relative infant dose (RID) of chloroquine and its metabolite was calculated to be 0.9% to 9.5% (chloroquine) and 0.19% to 2.5% (DECQ). These RID calculations used a modified formula, based on average milk concentrations (not C_max) and total days of maternal therapy (not a single daily dose) to take into consideration the intermittent dosing and long half-life of chloroquine (Law 2008). In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000).

Available guidelines consider the amount of chloroquine exposure to the nursing infant to be acceptable when normal maternal doses for malaria (prophylaxis or treatment) are used (CDC 2018; Lalloo 2016; WHO 2002). Chloroquine is also considered compatible with breastfeeding when used for rheumatic disorders. Infants exposed to chloroquine via breast milk should be monitored for hemolysis and jaundice, particularly premature infants or infants <1 month of age; avoid breastfeeding infants who are G-6-PD deficient (WHO 2002). Due to the potential for serious adverse reactions in the breastfeeding infant, the manufacturer recommends a decision be made to discontinue breastfeeding or to discontinue the drug, taking into account the importance of treatment to the mother. The amount of chloroquine obtained by a breastfeeding infant from breast milk would not provide adequate protection if therapy for malaria in the infant is needed (CDC 2018). Breastfed infants should be treated with chloroquine when otherwise indicated.

Briggs' Drugs in Pregnancy & Lactation

• Chloroquine

Adverse Reactions

Frequency not defined.

Cardiovascular: Atrioventricular block, bundle branch block, cardiac arrhythmia, cardiomyopathy, ECG changes (including prolonged QRS and QTc intervals, T-wave inversion, or depression), hypotension, torsades de pointes, ventricular fibrillation, ventricular tachycardia

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

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

Endocrine & metabolic: 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: 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), transient scotomata, visual field defects

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

* See Cautions in AHFS Essentials for additional information.

Allergy and Idiosyncratic Reactions

• QuiNIDine/QuiNINE Derivative Allergy

Metabolism/Transport Effects

Substrate of CYP2D6 (major), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions Open Interactions

Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). 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. Risk D: Consider therapy modification

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

Agalsidase Beta: Chloroquine may diminish the therapeutic effect of Agalsidase Beta. Risk X: 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. Risk D: Consider therapy modification

Androgens: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Exceptions: Danazol. Risk C: 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. Risk D: Consider therapy modification

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

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

Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: 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. Risk X: Avoid combination

Asunaprevir: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk D: Consider therapy modification

Bacampicillin: Chloroquine may decrease the serum concentration of Bacampicillin. 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. Bacampicillin is a prodrug of ampicillin. Risk D: Consider therapy modification

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

Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Cardiac Glycosides: Aminoquinolines (Antimalarial) may increase the serum concentration of Cardiac Glycosides. Risk C: 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. Risk D: Consider therapy modification

Cimetidine: May increase the serum concentration of Chloroquine. Risk C: Monitor therapy

CloBAZam: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). Risk D: Consider therapy modification

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

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

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Risk D: Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). 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). Risk D: Consider therapy modification

Dacomitinib: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of dacomitinib with CYP2D6 subtrates that have a narrow therapeutic index. Risk D: 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. Risk D: 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. Risk D: Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

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. Risk D: Consider therapy modification

Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). 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. Risk D: Consider therapy modification

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

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

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: 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. Risk C: Monitor therapy

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

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

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Imatinib: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: 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. Risk D: Consider therapy modification

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

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

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

Maitake: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: 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. Risk X: Avoid combination

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Risk D: Consider therapy modification

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

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

Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: 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. Risk C: 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. Risk C: Monitor therapy

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Panobinostat: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

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

Perhexiline: CYP2D6 Substrates (High risk with Inhibitors) may increase the serum concentration of Perhexiline. Perhexiline may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

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

Praziquantel: Chloroquine may decrease the serum concentration of Praziquantel. Risk C: 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. Risk C: Monitor therapy

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

Prothionamide: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: 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. Risk D: 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. Risk C: 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. Exceptions: Pimozide. Risk C: 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. Risk C: 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. Risk C: 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. Exceptions: Domperidone. Risk C: 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. Risk C: 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. Risk C: 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). Risk X: 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. Risk C: Monitor therapy

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

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

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

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

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: 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. Risk C: Monitor therapy

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). 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. Risk D: Consider therapy modification

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

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Gene Testing May Be Considered

• G6PD - Chloroquine

Genes of Interest

• Cytochrome P450 2D6
• Cytochrome P450 3A4

Monitoring Parameters

Evaluate neuromuscular function periodically during prolonged therapy. Periodic CBC in patients receiving prolonged therapy

Ophthalmologic exam at baseline (fundus examination within the first year plus visual fields and spectral-domain optical coherence tomography [SD OCT] 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]).

Advanced Practitioners Physical Assessment/Monitoring

Assess results of CBC and monitor for retinopathy, hearing loss, or myopathy regularly. Teach patient to report anemia, muscle weakness, or visual or auditory changes.

Nursing Physical Assessment/Monitoring

Assess results of CBC and monitor for retinopathy, hearing loss, or myopathy regularly. Teach patient to report anemia, muscle weakness, or visual or auditory changes.

Dosage Forms: US

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]

Dosage Forms: Canada

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]

Anatomic Therapeutic Chemical (ATC) Classification

• P01BA01

Generic Available (US)

Yes

Pricing: US

Tablets (Chloroquine Phosphate Oral)

250 mg (per each): $9.19

500 mg (per each): $5.40 - $23.85

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

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

Pharmacodynamics/Kinetics

Absorption: Rapid and almost complete

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

Protein binding: ~55%

Metabolism: Partially hepatic to main metabolite, desethylchloroquine

Half-life: 3 to 5 days

Time to peak serum concentration: Oral: Within 1-2 hours

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

Local Anesthetic/Vasoconstrictor Precautions

Chloroquine is one of the drugs confirmed to prolong the QT interval and is accepted as having a risk of causing torsade de pointes. The risk of drug-induced torsade de pointes is extremely low when a single QT interval prolonging drug is prescribed. In terms of epinephrine, it is not known what effect vasoconstrictors in the local anesthetic regimen will have in patients with a known history of congenital prolonged QT interval or in patients taking any medication that prolongs the QT interval. Until more information is obtained, it is suggested that the clinician consult with the physician prior to the use of a vasoconstrictor in suspected patients, and that the vasoconstrictor (epinephrine, mepivacaine and levonordefrin [Carbocaine® 2% with Neo-Cobefrin®]) be used with caution.

Dental Health Professional Considerations

See Local Anesthetic/Vasoconstrictor Precautions

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Stomatitis.

Effects on Bleeding

Thrombocytopenia has been reported.

Related Information

• Drug-Induced Prolongation of the QT Interval and Torsades de Pointes

Index Terms

Chloroquine Phosphate

FDA Approval Date

October 31, 1949

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Brand Names: International

A-CO (NL); Alexoquine (EG); Antimal (AE); Aralen (MX); Aralen Phosphate (AE, BF, BH, BJ, CI, CY, EC, EG, ET, GH, GM, GN, IL, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, PE, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM); Arechin (PL); Arquin (IN); Avloclor (BF, BJ, CI, ET, GB, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM); Avloquin (BD); Bidimalaquin (VN); Cadiquin (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM); Chemochin (HR); Chlorochin (CH, HR); Chlorofoz (PH); Chloromax (PH); Chlorquin (NZ); Clit (BD); Clo-Kit Junior (IN); Clorochina Bayer (IT); Clorochina Bifosfato (IT); Crocan (KR); Delagil (BB, BD, BM, BS, BZ, GY, HU, JM, PR, RU, SR, TT, UA); Demoquine (GR); Dichinalex (IT); Diroquine (TH); Emquin (IN); Heliopar (FI); Heroquine (JO); Klarquine (PK); Klorokinfosfat (SE); Lagaquin (BB, BF, BJ, BM, BS, BZ, CI, ET, GH, GM, GN, GY, JM, KE, LR, MA, ML, MR, MU, MW, NE, NG, PR, SC, SD, SL, SN, SR, TN, TT, TZ, UG, ZA, ZM); Malachlo (KR); Malaquin (AE, BH, CY, IL, IQ, IR, JO, KW, LB, LY, OM, SA, SY, YE, ZW); Malarex (AE, BH, CY, ID, IL, IQ, IR, JO, KW, LB, LY, MY, OM, PH, SA, SY, YE); Malarivon (BB, BM, BS, BZ, GB, GY, JM, PR, SR, TT); Malarquine (EG); Malaviron (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM); Malquin (BD); Maquine (AE, BH, CY, IL, IQ, IR, JO, KW, LB, LY, OM, SA, SY, YE); Nivaquine (AR, CH, FR, LB, LU); Pluschlo (ZW); Quinacris (BR); Resochin (AE, AT, BF, BG, BH, BJ, CI, CY, DE, ES, ET, GH, GM, GN, HR, ID, IL, IN, IQ, IR, IT, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZA, ZM); Resochina (PT)

Last Updated 3/13/20