Chloroquine Phosphate

CHLOROQUINE PHOSPHATE — chloroquine phosphate tablet
A-S Medication Solutions

DESCRIPTION

Chloroquine phosphate tablets 250 mg, chloroquine phosphate, USP, is a 4-aminoquinoline compound for oral administration. It is a white, odorless, bitter tasting, crystalline substance, freely soluble in water.

Chloroquine phosphate is an antimalarial and amebicidal drug.

Chemically, it is 7-chloro-4-[[4- (diethylamino)-1-methylbutyl]amino] quinoline phosphate (1:2) and has the following structural formula:

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Each tablet contains 250 mg of chloroquine phosphate USP, equivalent to 150 mg chloroquine base.

Inactive Ingredients: Colloidal silicon dioxide, dibasic calcium phosphate, magnesium stearate, microcrystalline cellulose, pregelatinized starch and sodium starch glycolate.

CLINICAL PHARMACOLOGY

Chloroquine is rapidly and almost completely absorbed from the gastrointestinal tract, and only asmall proportion of the administered dose is found in the stools. Approximately 55% of the drug inthe plasma is bound to nondiffusible plasma constituents. Excretion of chloroquine is quite slow,but is increased by acidification of the urine. Chloroquine is deposited in the tissues in considerableamounts. In animals, from 200 to 700 times the plasma concentration may be found in the liver,spleen, kidney, and lung; leukocytes also concentrate the drug. The brain and spinal cord, incontrast, contain only 10 to 30 times the amount present in plasma.

Chloroquine undergoes appreciable degradation in the body. The main metabolite isdesethylchloroquine, which accounts for one fourth of the total material appearing in the urine;bisdesethylchloroquine, a carboxylic acid derivative, and other metabolic products as yetuncharacterized are found in small amounts. Slightly more than half of the urinary drug productscan be accounted for as unchanged chloroquine.

Microbiology

Mechanism of Action: Chloroquine, a 4-aminoquinoline, is an anti-protozoal agent. The precise mechanism by which chloroquine exhibits activity is not known. Chloroquine, may exert its effect against Plasmodium species by concentrating in the acid vesicles of the parasite and by inhibiting polymerization of heme. It can also inhibit certain enzymes by its interaction with DNA.

Activity in Vitro and in Clinical Infections: Chloroquine is active against the erythrocytic forms of susceptible strains of Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale, and Plasmodium vivax. Chloroquine is not active against the gametocytes and the exoerythrocytic forms including the hypnozoite stage (P. vivax and P. ovale) of the Plasmodium parasites.
In vitro studies with Chloroquine demonstrated that it is active against the trophozoites of Entamoeba histolytica.

Drug Resistance:

Resistance of Plasmodium parasites to chloroquine is widespread (see INDICATIONS AND USAGE, Limitations of Use in Malaria and WARNINGS).
Plasmodium parasites exhibiting reduced susceptibility to hydroxychloroquine also show reduced susceptibility to chloroquine.
Patients in whom chloroquine or hydroxychloroquine have failed to prevent or cure clinical malaria or parasitemia, or patients who acquired malaria in a geographic area where chloroquine resistance is known to occur should be treated with another form of antimalarial therapy (see WARNINGS and INDICATIONS AND USAGE, Limitations of Use).

INDICATIONS AND USAGE

Chloroquine phosphate is indicated for the:

  • Treatment of uncomplicated malaria due to susceptible strains of P. falciparum, P.malariae, P. ovale, and P.vivax.
  • Prophylaxis of malaria in geographic areas where resistance to chloroquine is not present.
  • Treatment of extraintestinal amebiasis.

Chloroquine phosphate tablets do not prevent relapses in patients with vivax or ovale malaria because it is not effective against exoerythrocytic forms of the parasites.
Limitations of Use in Malaria:

  • Do not use chloroquine phosphate tablets for the treatment of complicated malaria (high-grade parasitemia and/or complications e.g., cerebral malaria or acute renal failure).
  • Do not use chloroquine phosphate tablets for malaria prophylaxis in areas where chloroquine resistance occurs, Resistance to chloroquine phosphate tablets is widespread in P. falciparum , and is reported in P.vivax (see WARNINGS).
  • Concomitant therapy with an 8-aminoquinoline drug is necessary for treatment of the hypnozoite liver stage forms of P.vivax and P.ovale (see DOSAGE AND ADMINISTRATION).

CONTRAINDICATIONS

Use of chloroquine phosphate tablets for indications other than acute malaria is contraindicated in the presence of retinal or visual field changes of any etiology.
Use of chloroquine phosphate tablets is contraindicated in patients with known hypersensitivity to 4-aminoquinoline compounds.

WARNINGS

Chloroquine-Resistant Malaria
Chloroquine phosphate tablets are not effective against chloroquine-or hydroxychloroquine resistant strains of Plasmodium species (see CLINICAL PHARMACOLOGY, Microbiology). Chloroquine resistance is widespread in P. falciparum and is reported in P. vivax. Before using chloroquine for prophylaxis, it should be ascertained whether chloroquine is appropriate for use in the region to be visited by the traveler. Information regarding the geographic areas where resistance to chloroquine occurs, is available at the Centers for Disease Control and Prevention (www.cdc.gov\malaria).
Patients infected with a resistant strain of plasmodia as shown by the fact that normally adequate doses have failed to prevent or cure clinical malaria or parasitemia should be treated with another form of antimalarial therapy.
Treatment of Exo-Erythocytic Forms of Malaria
Chloroquine does not treat the hypnozoite liver stage forms of Plasmodium and will therefore not prevent relapses of malaria due to P. vivax or P. ovale. Additional treatment with an anti-malarial agent active against these forms, such as an 8-aminoquinoline, is required for the treatment of infections with P. vivax and P. ovale.
Cardiac Effects
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 (see
ADVERSE REACTIONS and OVERDOSAGE). Monitor for signs and symptoms of cardiomyopathy and discontinue chloroquine if cardiomyopathy develops. Chronic toxicity should be considered when conduction disorders (bundle branch block / atrio-ventricular heart block) are diagnosed. If cardiotoxicity is suspected, prompt discontinuation of chloroquine may prevent life-threatening complications. QT interval prolongation, torsades de pointes, and ventricular arrhythmias have been reported. The risk is greater if chloroquine is administered at high doses. Fatal cases have been reported. Chloroquine should be used with caution in patients with cardiac disease, a history of ventricular arrhythmias, uncorrected hypokalemia and/or hypomagnesemia, or bradycardia (<50 bpm), and during concomitant administration with QT interval prolonging agents due to potential for QT interval prolongation (see WARNINGS, PRECAUTIONS, Drug Interactions, ADVERSE REACTIONS and OVERDOSAGE)
Hypoglycemia
Chloroquine has been shown to cause severe hypoglycemia including loss of consciousness
that could be life-threatening in patients treated with or without antidiabetic medications (see
PRECAUTIONS, Drug Interactions). Patients treated with chloroquine phosphate tablets should be warned about the risk of hypoglycemia and the associated clinical signs and symptoms. Patients presenting with clinical symptoms suggestive of hypoglycemia during treatment with chloroquine should have their blood glucose level checked and treatment reviewed as necessary.
Retinopathy1
Irreversible retinal damage has been observed in some patients who had received chloroquine. Significant risk factors for retinal damage include daily doses of chloroquine phosphate greater than 2.3 mg/kg of actual body weight, durations of use greater than five years, subnormal glomerular filtration, use of some concomitant drug products such as tamoxifen citrate (see PRECAUTIONS), and concurrent macular disease.
A baseline ophthalmological examination should be performed within the first year of starting
chloroquine phosphate tablets. The 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). For individuals with significant risk factors (daily dose of chloroquine phosphate greater than 2.3 mg/kg of actual body weight, subnormal glomerular filtration, use of tamoxifen citrate or concurrent macular disease) monitoring should include annual examinations which include BCVA, VF and SDOCT.
For individuals without significant risk factors, annual exams (including BCVA, VF and SD-OCT) can usually be deferred until five years of treatment.
In individuals of Asian descent, retinal toxicity may first be noticed outside the macula. 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.
It is recommended that chloroquine be discontinued if ocular toxicity is suspected and the patient should be closely observed given that retinal changes (and visual disturbances) may progress even after cessation of therapy.
Central Nervous System Effects
Acute extrapyramidal disorders may occur with chloroquine (see PRECAUTIONS, ADVERSE
REACTIONS and OVERDOSAGE). These adverse reactions usually resolve after treatment
discontinuation and/or symptomatic treatment.
Muscular Weakness
All patients on long-term therapy with chloroquine should be questioned and examined periodically, including testing knee and ankle reflexes, to detect any evidence of muscular weakness. If weakness occurs, discontinue the drug.
Pediatric Accidental Ingestion
A number of fatalities have been reported following the accidental ingestion of chloroquine,
sometimes in relatively small doses (0.75 g or 1 g chloroquine phosphate in one 3-year-old child). Patients should be strongly warned to keep chloroquine phosphate tablets out of the reach of children because they are especially sensitive to the 4-aminoquinoline compounds (see OVERDOSAGE and ADVERSE REACTIONS).
Worsening of Psoriasis and Porphyria
Use of chloroquine phosphate tablets in patients with psoriasis may precipitate a severe attack of psoriasis. When used in patients with porphyria the condition may be exacerbated. Chloroquine phosphate tablets should not be used in these conditions unless the benefit to the patient outweighs the potential risks.

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