chloroquine

General

Genetic Implications: Genetic Implications

Pronunciation:
klor-oh-kwin


Trade Name(s)

  • Aralen

Ther. Class.

antimalarials

Indications

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

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.

Pharmacokinetics

Absorption: Well absorbed following oral administration.

Distribution: Widely distributed to tissues.

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–weeks

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
  • Porphyria (may exacerbate condition)
  • Psoriasis
  • Genetic implication Glucose–6–phosphate dehydrogenase (G6PD) deficiency (↑ risk of severe hemolysis);
  • Bone marrow depression
  • Hearing impairment
  • Seizure disorders
  • OB:  Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
  • Pedi:  Children extremely sensitive to effects;
  • Geri:  Older adults 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 (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN), 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 ≥4 hr.
  •   Cimetidine, fluconazole,  ketoconazole,  clarithromycin   erythromycin,  fluoxetine,  nefazodone,  paroxetine,  protease inhibitors,  quinidine,  ritonavir, and  verapamil  may ↑ levels and risk of toxicity; avoid concurrent use with cimetidine.
  • May ↓ absorption of  ampicillin ; separate administration of these agents by ≥2 hr.
  • May ↑ levels and risk of toxicity of  cyclosporine,   fluoxetine,  lidocaine,   mirtazapine,  nefazodone,  paroxetine, risperidone,  ritonavir,  thioridazine,  tricyclic antidepressants, and  venlafaxine.
  •   Carbamazepine, nevirapine,  phenobarbital,  phenytoin, and  rifampin  may ↓ levels and effectiveness.
  • May ↑ risk of hepatotoxicity when administered with other  hepatotoxic agents.
  •   Urinary acidifiers  may ↑ renal excretion and ↓ effectiveness.
  •   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.

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 ≥2–3 wk (in combination with other antiprotozoals).

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

Availability (generic available)

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

Assessment

  • Assess deep tendon reflexes periodically to determine muscle weakness.  If weakness occurs, discontinue chloroquine.

    • Assess hearing before starting and periodically during therapy.  If hearing impairment occurs, discontinue chloroquine.
    • Perform ophthalmologic exam initially and periodically during therapy.  If visual disturbances occur,  discontinue chloroquine.
    • Observe for development of rash.  If rash occurs,  discontinue chloroquine. Serious adverse reactions such as SJS or TEN preclude further use.
  • Malaria: Assess patient for improvement in signs/symptoms of condition daily throughout therapy.

Lab Test Considerations:

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

  • Monitor liver function tests periodically during therapy.

Implementation

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

Patient/Family Teaching

  • Explain purpose and side effects of medication to patient. Advise patient to read  Patient Information  before starting therapy.
  • Advise 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.
  • Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications.
  • 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 patient 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 ↓ by the use of dark glasses in bright light. Protective clothing and sunscreen should also be used to ↓ risk of skin reactions.
  • Advise patient to notify health care provider 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.
  • Rep:  Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes

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