Chloroquine Phosphate 500 mg Tablet, Coated, 25-count — NDC 62135-717-26 (Billing 62135-0717-26)

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 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.

Skeletal Muscle Myopathy and Neuropathy Skeletal muscle myopathy or neuropathy leading to progressive weakness and atrophy of proximal muscle groups, and abnormal nerve conduction, have been reported. Muscle and nerve biopsies have shown associated phospholipidosis. Assess muscle strength and deep tendon reflexes periodically in patients on long-term therapy with chloroquine.

Discontinue chloroquine if muscle or nerve toxicity 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 gl… [Excerpted — this section continues on DailyMed.]

ADVERSE REACTIONS The following adverse reactions have been identified during post-approval use of chloroquine or other 4-aminoqunoline compounds. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Ocular disorders: Maculopathy and macular degeneration have been reported and may be irreversible.

Irreversible retinopathy with retinal pigmentation changes (bull’s eye appearance) and visual field defects (paracentral scotomas) in patients receiving long-term or high-dosage 4-aminoquinoline therapy have been reported (see WARNINGS ). Visual disturbances (blurring of vision and difficulty of focusing or accommodation); nyctalopia; scotomatous vision with field defects of paracentral, pericentral ring types, and typically temporal scotomas (e.g., difficulty in reading with words tending to disappear, seeing half an object, misty vision, and fog before the eyes) have been reported.

Reversible corneal opacities have also been reported. Immune system disorders: Urticaria, anaphylactic reaction including angioedema. Ear and labyrinth disorders: Nerve type deafness; tinnitus, reduced hearing in patients with preexisting auditory damage.

Musculoskeletal and connective tissue-disorders: Sensorimotor disorders, skeletal muscle myopathy or neuromyopathy leading to progressive weakness and atrophy of proximal muscle groups, depression of tendon reflexes and abnormal nerve conduction. Gastrointestinal disorders: Hepatitis, increased liver enzymes, anorexia, nausea, vomiting, diarrhea, abdominal cramps. Skin and subcutaneous tissue disorders: Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis.

Pleomorphic skin eruptions, skin and mucosal pigmentary changes; lichen planus-like eruptions, pruritus,; drug rash with eosinophilia and systemic symptoms (DRESS syndrome); photosensitivity and hair loss and bleaching of hair pigment. Blood and lymphatic system disorders: Pancytopenia, aplastic anemia, reversible agranulocytosis, thrombocytopenia and neutropenia. Hemolytic anemia in G6PD deficient patients (see PRECAUTIONS ).

Nervous system disorders: Convulsions, mild and transient headache, polyneuropathy, acute extrapyramidal disorders (such as dystonia, dyskinesia, tongue protrusion, torticollis) (see WARNINGS and OVERDOSAGE ). Neuropsychiatric disorders: Neuropsychiatric changes including psychosis, delirium, anxiety, agitation, insomnia, confusion, hallucinations, personality changes, depression, suicidal behavior, suicidal ideation, affect/emotional lability, irritability, nervousness, nightmares/sleep terrors, depression, delusions, paranoia, and mania.

Cardiac disorders: Hypotension, electrocardiographic changes (particularly, inversion or depression of the T-wave with widening of the QRS complex), and cardiomyopathy (which may result in cardiac failure and in some cases a fatal outcome). Cardiac arrhythmias, conduction disorders such as bundle branch block / atrio-ventricular block, QT interval prolongation, torsade de pointes, ventricular tachycardia and ventricular fibrillation have been reported with therapeutic doses of chloroquine as well as with overdose. The risk is greater if chloroquine is administered at high doses.

Fatal cases have been reported (see WARNINGS, Cardiac Effects and OVERDOSAGE ). Metabolic and Nutritional disorders: Hypoglycemia (see WARNINGS ). To report SUSPECTED ADVERSE REACTIONS, contact Chartwell RX, LLC. at 1-845-262-1683, or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

PRECAUTIONS Hematological Effects/Laboratory Tests Complete blood cell counts should be checked periodically if patients are given prolonged therapy (see ADVERSE REACTIONS ). Chloroquine may cause hemolysis in glucose-6 phosphate dehydrogenase (G-6-PD) deficiency. Blood monitoring may be needed as hemolytic anemia may occur, in particular in association with other drugs that cause hemolysis (see ADVERSE REACTIONS ).

Auditory Effects In patients with preexisting auditory damage, chloroquine should be administered with caution. In case of any defects in hearing, chloroquine should be immediately discontinued, and the patient closely observed (see ADVERSE REACTIONS ). Use in Patients with Hepatic Impairment Since Chloroquine phosphate tablets are known to concentrate in the liver, it should be used with caution in patients with hepatic disease or alcoholism or in conjunction with known hepatotoxic drugs.

Central Nervous System Effects Chloroquine may increase the risk of convulsions in patients with a history of epilepsy. Drug Interactions Antacids and kaolin: Antacids and kaolin can reduce absorption of chloroquine; an interval of at least 4 hours between intake of these agents and chloroquine should be observed. Cimetidine: Cimetidine can inhibit the metabolism of chloroquine, increasing its plasma level.

Concomitant use of cimetidine should be avoided. Insulin and other antidiabetic drugs: As chloroquine may enhance the effects of a hypoglycemic treatment, a decrease in doses of insulin or other antidiabetic drugs may be required. Arrhythmogenic drugs: There may be an increased risk of inducing ventricular arrhythmias if chloroquine is used concomitantly with other arrhythmogenic drugs, such as amiodarone or moxifloxacin.

Ampicillin: In a study of healthy volunteers, chloroquine significantly reduced the bioavailability of ampicillin. An interval of at least two hours between intake of ampicillin and chloroquine should be observed. Cyclosporine: After introduction of chloroquine (oral form), a sudden increase in serum cyclosporine level has been reported.

Therefore, close monitoring of serum cyclosporine level is recommended and, if necessary, chloroquine should be discontinued. Mefloquine: Co-administration of chloroquine and mefloquine may increase the risk of convulsions. The blood concentrations of chloroquine and desethylchloroquine (the major metabolite of chloroquine, which also has antimalarial properties) were negatively associated with log antibody titers.

Chloroquine taken in the dose recommended for malaria prophylaxis can reduce the antibody response to primary immunization with intradermal human diploid-cell rabies vaccine. Praziquantel: In a single-dose interaction study, chloroquine has been reported to reduce the bioavailability of praziquantel. Tamoxifen: Concomitant use of chloroquine with drugs known to induce retinal toxicity such as tamoxifen is not recommended (see WARNINGS ).

Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis There is insufficient evidence regarding the carcinogenicity of chloroquine in experimental animals. Mutagenesis Chloroquine is reported in the literature to be a weak genotoxic agent which may elicit both gene mutations and chromosomal/DNA breaks. Mechanisms may involve DNA intercalation or induction of oxidative stress.

The publications reported both positive and negative results in the in vitro reverse gene mutation assays using bacteria (Ames test) and in the in vivo studies using rodents (mouse bone marrow cell sister chromatid exchange, mouse bone marrow cell chromosome abnormality, and rat DNA strand breaks in multiple organs when animals were dosed by intraperitoneal route). Those chromosomal effects were not observed when Chloroquine was administered in animals orally (i.e. the therapeutic route of administration). Altogether those cellular and rodent data show evidence of genotoxic potential but discrepancies have been noted between published data.

Fertil… [Excerpted — this section continues on DailyMed.]