chloroquine (Rx)

Frequency Not Defined

Ocular disorders: Maculopathy, macular degeneration, visual disturbances, nyctalopia, scotomatous vision with field defects of paracentral, pericentral ring types, typically temporal scotomas (eg, difficulty in reading with words tending to disappear, seeing half an object, misty vision, and fog before the eyes), reversible corneal opacities

Immune system disorders: Urticaria, anaphylactic reaction (eg, angioedema)

Ear and labyrinth disorders: Nerve type deafness, tinnitus, reduced hearing in patients with preexisting auditory damage

Musculoskeletal and connective tissue-disorders: Sensorimotor disorders, skeletal muscle myopathy or neuromyopathy, depression of tendon reflexes, abnormal nerve conduction

Gastrointestinal disorders: Hepatitis, increased liver enzymes, anorexia, nausea, vomiting, diarrhea, abdominal cramps

Skin and subcutaneous tissue disorders: Erythema multiforme, Stevens Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, pleomorphic skin eruptions, skin and mucosal pigment changes, lichen planus-like eruptions, pruritus, drug rash with eosinophilia and systemic symptoms (DRESS syndrome), photosensitivity, hair loss

Blood and lymphatic system disorders: Pancytopenia, aplastic anemia, reversible agranulocytosis, thrombocytopenia, neutropenia, hemolytic anemia in G6PD deficient patients

Nervous system disorders: Convulsions, mild and transient headache, polyneuropathy, acute extrapyramidal disorders (eg, dystonia, dyskinesia, tongue protrusion, torticollis)

Neuropsychiatric disorders: Psychosis, delirium, anxiety, agitation, insomnia, confusion, hallucinations, personality changes, depression, suicidal behavior

Cardiac disorders: Hypotension, ECG changes (particularly, inversion or depression of the T-wave with widening of the QRS complex), cardiomyopathy, cardiac arrhythmias, conduction disorders (eg, bundle branch block / atrioventricular [AV] block, QT interval prolongation, torsade de pointes, ventricular tachycardia, ventricular fibrillation)

Metabolic and nutritional disorders: Hypoglycemia

Contraindications

Hypersensitivity to chloroquine, 4-aminoquinolones

Psoriasis, porphyria, retinal or visual field changes

Cautions

Acute extrapyramidal disorders may occur; reactions usually resolve after treatment discontinuation and/or symptomatic treatment

Not effective in most areas; CDC recommends mefloquine or atovaquone/proguanil - check CDC traveler information for specific recommendations for region

May cause hemolysis in glucose-6 phosphate dehydrogenase (G-6-PD) deficiency; blood monitoring may be needed as hemolytic anemia may occur, in particular in association with other drugs that cause hemolysis

Experimental data showed a potential risk of inducing gene mutations; there are insufficient data in humans to rule out an increased risk of cancer in patients receiving long-term treatment

Cases of cardiomyopathy resulting in cardiac failure, in some cases with fatal outcome, have been reported in patients treated during long term therapy at high doses with chloroquine; monitor for signs and symptoms of cardiomyopathy and discontinue chloroquine if cardiomyopathy develops

May cause conduction disorders (eg, bundle branch block / AV heart block) are diagnosed; if cardiotoxicity is suspected, prompt discontinuation of chloroquine may prevent life-threatening complications

Monitor knee and ankle reflexes in patients on long-term therapy to detect any evidence of muscular weakness; if weakness occurs, discontinue therapy

A number of fatalities have been reported following the accidental ingestion of chloroquine; advise to keep medication out of the reach of children because they are especially sensitive to the 4-aminoquinoline compounds

Use in patients with psoriasis may precipitate a severe attack of psoriasis; may be exacerbated condition when used in patients with porphyria; do not use in these conditions unless the benefit to the patient outweighs the potential risks

Shown to cause severe hypoglycemia including loss of consciousness that could be life-threatening in patients treated with or without antidiabetic medications; patients should be warned about risk of hypoglycemia and associated clinical signs and symptoms; patients presenting with clinical symptoms suggestive of hypoglycemia during treatment with chloroquine should have blood glucose level checked and treatment reviewed as necessary

Caution with history of auditory damage

Caution with hepatic disease, alcoholism, and coadministration with other hepatotoxic drugs

May provoke seizures in patients with history of epilepsy

QT prolongation

• QT interval prolongation, torsade de pointes, and ventricular arrhythmias have been reported
• The risk increases with higher doses chloroquine; fatal cases have been reported
• Use with caution in patients with cardiac disease, a history of ventricular arrhythmias, uncorrected hypokalemia and/or hypomagnesemia, or bradycardia (<50 bpm)

Retinopathy

• Irreversible retinal damage observed
• Significant risk factors for retinal damage include daily doses of chloroquine phosphate >2.3 mg/kg of actual body weight, durations of use >5 years, subnormal glomerular filtration, and concurrent macular disease
• Perform baseline ophthalmological examination within the first year of starting chloroquine phosphate tablets
• Baseline exam should include: best corrected distance visual acuity (BCVA), an automated threshold visual field (VF) of the central 10 degrees (with retesting if an abnormality is noted), and spectral domain optical coherence tomography (SD-OCT)
• Exams (including BCVA, VF and SD-OCT) should be monitored annually in individuals with significant risk factors and may be deferred up to 5 years for individuals without risk factors
• In patients of Asian descent, it is recommended that visual field testing be performed in the central 24 degrees instead of the central 10 degrees
• Discontinue if ocular toxicity is suspected and closely monitor; retinal changes (and visual disturbances) may progress even after cessation of therapy

Drug interaction overview

• Plasma concentrations of chloroquine and desethylchloroquine (major metabolite of chloroquine) were negatively associated with log antibody titers; the recommended dose of chloroquine for malaria prophylaxis can reduce the antibody response to primary immunization with intradermal human diploid-cell rabies vaccine
• Concomitant use of chloroquine with drugs known to induce retinal toxicity such as tamoxifen is not recommended

• Effects of other drugs on chloroquine

  • Antacids and kaolin can reduce absorption of chloroquine; observe for at least 4 hr between intake of these agents and chloroquine
  • Cimetidine can inhibit the metabolism of chloroquine, increasing its plasma level; avoid use

• Chloroquine effects on other drugs

  • As chloroquine may enhance the effects of a hypoglycemic treatment, a decrease in doses of insulin or other antidiabetic drugs may be required.
  • Chloroquine significantly reduced the bioavailability of ampicillin; monitor at least 2 hr between intake of ampicillin and chloroquine
  • After introduction of chloroquine (oral form), a sudden increase in serum cyclosporine level has been reported; closely monitor of serum cyclosporine level and if necessary, discontinue chloroquine
  • May increase risk of inducing ventricular arrhythmias if chloroquine is used concomitantly with other arrhythmogenic drugs (eg, amiodarone, moxifloxacin)
  • In a single-dose interaction study, chloroquine has been reported to reduce the bioavailability of praziquantel
  • Coadministration of chloroquine and mefloquine may increase the risk of convulsions

Pregnancy

In humans, at recommended doses for prophylaxis and treatment of malaria, observational studies as well as a meta-analysis, including a small number of prospective studies with chloroquine exposure during pregnancy, have shown no increase in the rate of birth defects or spontaneous abortions

Avoid use during pregnancy except in prophylaxis or treatment of malaria when benefit outweighs potential risk to fetus

Animal data

• In animal studies, embryofetal developmental toxicity was shown at doses ranging from 250-1500 mg/kg body weight; approximately 3-16x the maximum recommended therapeutic dose based on a body surface area comparison
• Preclinical data showed a potential risk of genotoxicity in some test systems

Lactation

Owing to the potential for serious adverse reactions in nursing infants from chloroquine, a decision should be made whether to discontinue nursing or chloroquine, taking into account the potential clinical benefit of the drug to the mother

Excretion of chloroquine and the major metabolite, desethylchloroquine, in breast milk was investigated in eleven lactating mothers following a single oral dose of chloroquine (600-mg base); maximum daily dose of the drug that the infant can receive from breastfeeding was about 0.7% of the maternal start dose of the drug in malaria

Separate prophylaxis for the infant is required

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Active against erythrocytic forms of Plasmodium vivax & P. malariae and most strains of Plasmodium falciparum

Precise mechanism not known

Absorption

Bioavailability: ~89%

Peak plasma time: 1-2 hr

Distribution

Distributed widely in body tissues (eg, eyes, heart, kidneys, liver, lungs) where retention prolonged; crosses placenta; enters breast milk

Metabolism

Partially in liver

Elimination

Half-life: 3-5 days

Excretion: urine (~70% as unchanged drug); acidification of urine increases elimination

Small amounts may be present in urine months following discontinuation of therapy