Chloroquine - Warnings and Precautions

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-Erythrocytic 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 including Cardiomyopathy and QT prolongation Fatal and life-threatening cardiotoxicity, including cardiomyopathy and arrhythmias, have been reported with the use of chloroquine (see ADVERSE REACTIONS and OVERDOSAGE ).

In multiple cases, endomyocardial biopsy showed association of the cardiomyopathy with phospholipidosis in the absence of inflammation, infiltration, or necrosis.

Patients may present with ventricular hypertrophy and conduction disorders.

ECG findings include atrioventricular, right or left bundle branch block.

Chronic toxicity should be considered when conduction disorders (bundle branch block / atrio-ventricular heart block) are diagnosed.

QT interval prolongation, torsades de pointes, and ventricular arrhythmias have been reported with the use of chloroquine.

The risk is greater if chloroquine is administered at high doses.

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 ).

Monitor for signs and symptoms of cardiotoxicity during chloroquine therapy.

Discontinue chloroquine if cardiotoxicity is suspected or demonstrated by tissue biopsy.

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.

Retinopathy 1 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 SD-OCT.