chloroquine

General

Genetic Implications: Genetic Implications

Pronunciation:
klor-oh-kwin


Trade Name(s)

  • Aralen

Ther. Class.

antimalarials

antirheumatics

(DMARDs)

Indications

  • Prophylaxis and treatment of acute attacks of malaria.
  • Treatment of extraintestinal amebiasis.

Unlabeled Use(s):

  • Treatment of severe rheumatoid arthritis.
  • Treatment of systemic lupus erythematosus.

Action

Inhibits protein synthesis in susceptible organisms by inhibiting DNA and RNA polymerase.

Therapeutic Effect(s):

  • Death of plasmodia responsible for causing malaria.
  • Death of amoeba responsible for causing amebiasis.
  • Improvement in inflammation in rheumatoid arthritis and systemic lupus erythematosus.

Pharmacokinetics

Absorption: Well absorbed following oral administration.

Distribution: Widely distributed; high tissue concentrations achieved. Crosses the placenta, enters breast milk.

Metabolism and Excretion: 30% metabolized by the liver. Metabolite also has antiplasmodial activity; 70% excreted unchanged by the kidneys.

Half-life: 3–5 days.

TIME/ACTION PROFILE (antimalarial activity)

ROUTEONSETPEAKDURATION
POrapid1–2 hrdays–wks

Contraindication/Precautions

Contraindicated in:

  • Hypersensitivity
  • Hypersensitivity to other 4-aminoquinolones (hydroxychloroquine)
  • Visual damage caused by chloroquine or other 4-aminoquinolones
  • Lactation: Lactation .

Use Cautiously in:

  • Liver disease
  • Alcoholism
  • Patients receiving hepatotoxic drugs
  • Porphyria (may exacerbate condition)
  • Psoriasis
  • Genetic implication G6PD deficiency (↑ risk of severe hemolysis)
  • Bone marrow depression
  • Hearing impairment
  • Epilepsy
  • OB:   Use only if potential maternal benefit justifies potential fetal risk
  • Pedi:  Extremely sensitive to chloroquine effects
  • Geri:  May be predisposed to adverse effects.

Adverse Reactions/Side Effects

CV: ECG changes (T-wave abnormalities, QRS prolongation), cardiomyopathy, hypotension

Derm: alopecia, dermatoses, photosensitivity, pigmentary changes, pruritus, skin eruptions, STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, urticaria

EENT: corneal opacities (reversible), hearing impairment, retinopathy, tinnitus, visual disturbances

GI: ↑ liver enzymes, abdominal cramps, anorexia, diarrhea, hepatitis, nausea, vomiting

Hemat: AGRANULOCYTOSIS, APLASTIC ANEMIA, LEUKOPENIA, thrombocytopenia

Neuro: agitation, anxiety, confusion, delirium, depression, extrapyramidal reactions, hallucinations, headache, insomnia, neuromyopathy, peripheral neuritis, personality changes, polyneuritis, psychosis, SEIZURES, weakness

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

  •  Antacids  may ↓ absorption (separate administration of these agents by at least 4 hr).
  • Blood levels may be ↑ by  cimetidine,  fluconazole,  ketoconazole,  clarithromycin,  erythromycin,  fluoxetine,  nefazodone,  paroxetine,  protease inhibitors,  quinidine,  ritonavir, and  verapamil  (concurrent use with  cimetidine, should be avoided).
  • May ↓ absorption of  ampicillin  (separate administration of these agents by at least 2 hr).
  • May ↑ levels of  cyclosporine,  fluoxetine,  lidocaine,  mirtazapine,  nefazodone,  paroxetine,  risperidone,  ritonavir,  thioridazine,  tricyclic antidepressants,  and  venlafaxine.
  •  Carbamazepine,  nevirapine,  phenobarbital,  phenytoin,  and  rifampin  may ↓ levels and efficacy.
  • May ↑ the risk of hepatotoxicity when administered with other  hepatotoxic agents.
  •  Urinary acidifiers  may ↑ renal excretion and ↓ effectiveness.
  • Concurrent use with  mefloquine  may ↑ risk of seizures.

Drug-Food:

Foods that acidify urine (see food sources for specific nutrients) may ↑ excretion and ↓ effectiveness.

Route/Dosage

Doses below expressed as chloroquine base: 1 mg of chloroquine base = 1.67 mg chloroquine phosphate or 1.25 mg chloroquine hydrochloride

Suppression/Prophylaxis of Malaria

PO (Adults): 300 mg once weekly, starting 2 wk prior to entering endemic areas and for 8 wk afterward. If suppressive therapy is not initiated prior to entering endemic area, initial dose should be 300 mg followed by another 300 mg dose 6 hr later, followed by the usual dose regimen.

PO (Children): 5 mg/kg once weekly, starting 2 wk prior to entering endemic areas and for 8 wk afterward (not to exceed 300 mg/day). If suppressive therapy is not initiated prior to entering endemic area, initial dose should be 5 mg/kg followed by another 5 mg/kg dose 6 hr later, followed by the usual dose regimen.

Treatment of Acute Attack of Malaria

PO (Adults): 600 mg initially, then 300 mg at 6–8 hr, 24 hr, and 48 hr after initial dose.

PO (Children): 10 mg/kg initially (not to exceed 600 mg), then 5 mg/kg at 6 hr, 24 hr, and 48 hr after initial dose (not to exceed 300 mg/day).

Extraintestinal Amebiasis

PO (Adults): 600 mg once daily for 2 days, then 300 mg once daily for at least 2–3 wk (in combination with other antiprotozoals).

PO (Children): 10 mg/kg (not to exceed 300 mg/day for 2–3 wk.

Rheumatoid Arthritis/Systemic Lupus Erythematosus

PO (Adults): 150 mg once daily; ↓ dosage following maximal response.

Availability (generic available)

Tablets: 250 mg (150-mg base), 500 mg (300-mg base)

Assessment

  • Determine baseline that includes current symptoms of disease, for future reference, prior to administration.

    • Assess deep tendon reflexes periodically to determine muscle weakness. If weakness occurs, discontinue therapy.
    • Assess hearing before starting and periodically during therapy. Discontinue therapy immediately if hearing impairment develops.
    • Perform ophthalmologic exam initially and periodically during therapy; discontinue therapy immediately if visual disturbances develop.
    • Observe for development of rash. Discontinue chloroquine at the first sign of skin reactions. Serious adverse reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis preclude further use.
  • Malaria: Assess patient for improvement in signs and symptoms of condition daily throughout therapy.
  • Rheumatoid Arthritis/Systemic Lupus Erythematosus: Assess degree of joint pain and limitation of motion monthly.

Lab Test Considerations:

Monitor CBC periodically throughout therapy. May cause ↓ WBC and platelet counts.

  • Monitor liver function tests periodically during therapy.

Implementation

  • For malaria suppression/prophylaxis, chloroquine therapy start 2 wk prior to potential exposures and continued for 8 wk after leaving the area.
  • PO Administer with meals to minimize GI distress.

Patient/Family Teaching

  • Instruct patient to take medication as directed and continue for full course of therapy, even if feeling better. Take missed doses as soon as remembered, except with regimens requiring doses more than once a day, for which missed doses should be taken within 1 hr or omitted. Do not double doses.
  • Review methods of minimizing exposure to mosquitoes with patients receiving chloroquine prophylactically (use insect repellent, wear long-sleeved shirt and long trousers, use screen or netting).
  • Advise patients to avoid use of alcohol while taking chloroquine.
  • Caution patient to keep chloroquine out of the reach of children; fatalities have occurred with ingestion of 3 or 4 tablets.
  • Explain need for periodic ophthalmic exams for patients on prolonged high-dose therapy. Advise patient that the risk of ocular damage may be decreased by the use of dark glasses in bright light. Protective clothing and sunscreen should also be used to reduce risk of dermatoses.
  • Advise patient to notify health care professional promptly if sore throat, fever, unusual bleeding or bruising, blurred vision, difficulty reading, visual changes, ringing in the ears, difficulty hearing, mental changes, or muscle weakness occurs or if diarrhea, anorexia, nausea, stomach pain, vomiting, or rash becomes pronounced or bothersome. Most adverse reactions are dose related.
  • Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected, or if breastfeeding.
  • Rheumatoid Arthritis/Systemic Lupus Erythematosus: Instruct patient to contact health care professional if no improvement is noticed within a few days. Treatment may require up to 6 mo for full benefit.

Evaluation/Desired Outcomes

  • Prevention of or improvement in signs and symptoms of malaria.
  • Regression of extraintestinal amebic disease.
  • Decrease in the symptoms and progression of rheumatoid arthritis and systemic lupus erythematosus.