Chloroquine Phosphate

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

Contraindications

• Hypersensitivity to chloroquine or other 4-aminoquinoline derivatives.136

• Retinal or visual field changes attributable to 4-aminoquinoline derivatives or to any other etiology.136 After weighing possible benefits and risks to the patient, some clinicians may elect to use chloroquine in these patients for treatment of acute attacks of malaria caused by susceptible Plasmodium.136

Warnings/Precautions

Warnings

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

High prevalence of chloroquine-resistant P. vivax confirmed in Papua New Guinea and Indonesia;115 143 also reported in Burma (Myanmar), India, and Central and South America.143

Do not use for prevention of malaria in individuals traveling to malarious areas where chloroquine-resistant P. falciparum or chloroquine-resistant P. vivax malaria reported.115 134 136

Do not use for treatment of uncomplicated P. falciparum malaria or uncomplicated malaria caused by unidentified plasmodial species if the infection was acquired in areas with chloroquine resistance.136 143 144

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

Retinopathy and maculopathy (as well as macular degeneration) reported, especially in patients receiving long-term treatment or high chloroquine dosage.136 May be irreversible in some patients.136

Visual disturbances reported in patients receiving chloroquine include blurred vision and difficulty in focusing or accommodation.136 Nyctalopia,136 scotomatous vision with field defects of paracentral, pericentral ring types, and typically temporal scotomas (e.g., difficulty reading with words tending to disappear, seeing half an object, misty vision, fog before the eyes), 136 and reversible corneal opacities136 also reported.

Dose-related retinopathy reported, which may progress even after the drug is discontinued.136 Retinal changes may be reversible if detected early, but usually are permanent and may rarely result in blindness.a

Risk factors for development of retinopathy during chloroquine treatment include age, duration of treatment, and high daily and/or cumulated dosage.136

Whenever long-term treatment contemplated, perform initial (base line) and periodic ophthalmologic examinations, including visual acuity, slit-lamp, funduscopic, and visual field tests.136

Immediately discontinue chloroquine and closely observe patient for possible progression if there is any indication of abnormalities in visual acuity or visual field, abnormalities in the retinal macular area (such as pigmentary changes or loss of foveal reflex), or if any other visual symptoms (e.g., light flashes and streaks) occur which are not fully explainable by difficulties of accommodation or corneal opacities.136

Mild and transient headache,136 polyneuritis,136 fatigue,a nervousness,a anxiety,136 apathy,a irritability,a agitation,136 aggressiveness,a confusion,136 insomnia,136 delirium,136 and hallucinations136 have occurred.

Personality changes,136 depression,136 and psychosis,136 reported rarely.

Acute extrapyramidal disorders (e.g., dystonia, dyskinesia, tongue protrusion, torticollis) may occur;136 usually resolve after drug discontinued and/or patient receives symptomatic treatment.136

Seizures reported; advise patients with a history of epilepsy about the risk.136

Skeletal muscle myopathy or neuromyopathy occur rarely; neuromyopathy is manifested as slowly progressing weakness which first affects proximal muscles of lower extremities.136

Patients receiving prolonged therapy should be questioned and examined periodically for evidence of muscular weakness; test knee and ankle reflexes.136

Discontinue chloroquine if muscular weakness occurs.136

May exacerbate psoriasis and precipitate a severe attack in patients with the disease.136 Use in psoriasis patients only if potential benefits outweigh risks.136

May exacerbate porphyria.136 Use in patients with porphyria only if potential benefits outweigh risks.136

Sensitivity Reactions

Erythema multiforme,136 Stevens-Johnson syndrome,136 toxic epidermal necrolysis,136 exfoliative dermatitis,136 and similar desquamation-type adverse events136 reported rarely.

Urticaria,136 anaphylactic/anaphylactoid reaction including angioedema,136 and drug rash with eosinophilia and systemic symptoms (DRESS syndrome)136 also reported.

General Precautions

Aplastic anemia, pancytopenia, reversible agranulocytosis, thrombocytopenia, and neutropenia reported rarely.136

Periodically monitor CBCs in patients receiving prolonged treatment.136 Consider discontinuing chloroquine if any severe blood disorder occurs and is not attributable to the disease being treated.136

Use with caution in patients with G-6-PD deficiency.136

Nerve-type deafness, usually irreversible, reported after prolonged therapy with high dosage.136 a Tinnitus and reduced hearing reported in patients with pre-existing auditory damage.136

Use with caution in patients with preexisting auditory damage.136 Discontinue chloroquine immediately and closely observe patient if any hearing defects occur.136

Hepatitis and increased liver enzymes reported.136

Specific Populations

Category C.c

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

Manufacturer states avoid during pregnancy, except for prevention or treatment of malaria when clinician determines that possible benefits of the drug outweigh potential risks to fetus.136

CDC states pregnancy not a contraindication when chloroquine indicated for prevention or treatment of malaria.115 143

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

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

Distributed into milk.122 123 124 136 Discontinue nursing or the drug.136

Amount of drug present in milk does not appear to be harmful to nursing infants, but is insufficient to provide adequate protection against malaria in these infants.115 When prevention of malaria indicated, such infants should receive recommended dosages of appropriate antimalarial agent(s).115

Pediatric patients are especially sensitive to 4-aminoquinoline derivatives.136 Fatalities reported following accidental ingestion of relatively small doses.136

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.136

Substantially eliminated by kidneys; possible increased risk of toxicity in patients with impaired renal function.136 Select dosage with caution and assess renal function periodically since geriatric patients are more likely to have renal impairment.136

Concentrates in the liver; use with caution in patients with hepatic disease or alcoholism and in those receiving known hepatotoxic drugs.136

Substantially eliminated by kidneys; possible increased risk of toxicity in patients with impaired renal function.

Common Adverse Effects

Ocular effects; skeletal muscle myopathy or neuromyopathy; GI effects (anorexia, nausea, vomiting, diarrhea, abdominal cramps); dermatologic effects (pleomorphic skin eruptions, skin and mucosal pigmentary changes).136

Specific Drugs