HYDROXYCHLOROQUINE SULFATE- hydroxychloroquine sulfate_tablet

CLINICAL PHARMACOLOGY
Pharmacokinetics: Following chronic oral administration of hydroxychloroquine, significant levels of three metabolites, desethylhydroxychloroquine (DHCQ), desethylchloroquine (DCQ), and bidesethylhydroxychloroquine (BDCQ) have been found in plasma and blood, with DHCQ being the major metabolite. The absorption half-life was approximately 3 to 4 hours and the terminal half-life ranged from 40 to 50 days. The long half-life can be attributed to extensive tissue uptake rather than through decreased excretion. Peak plasma levels of hydroxychloroquine were seen in about 3 to 4 hours. Renal clearance in rheumatoid arthritis (RA) patients taking Hydroxychloroquine sulfate tablets for at least six months seemed to be similar to that of the single dose studies in volunteers, suggesting that no change occurs with chronic dosing. Range for renal clearance of unchanged drug was approximately 16 to 30% and did not correlate with creatinine clearance; therefore, a dosage adjustment is not required for patients with renal impairment. In RA patients, there was large variability as to the fraction of the dose absorbed (i. 30 to 100%), and mean hydroxychloroquine levels were significantly higher in patients with less disease activity. Cellular levels of patients on daily hydroxychloroquine have been shown to be higher in mononuclear cells than polymorphonuclear leucocytes. Mechanism of action: Plasmodium Activity in vitro and in Clinical Infections: Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale, Plasmodium vivax P. ovale Plasmodium Drug Resistance: P. falciparum Resistance of Plasmodium INDICATIONS AND USAGE en dash Malaria 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 INDICATIONS AND USAGE en dash Malaria WARNINGS Mechanism of action:.
Microbiology - Malaria
Mechanism of action: Plasmodium Activity in vitro and in Clinical Infections: Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale, Plasmodium vivax P. ovale Plasmodium Drug Resistance: P. falciparum Resistance of Plasmodium INDICATIONS AND USAGE en dash Malaria 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 INDICATIONS AND USAGE en dash Malaria WARNINGS.

Rheumatoid Arthritis and Systemic Lupus Erythematosus
Mechanism of action:
INDICATIONS AND USAGE
Malaria Hydroxychloroquine sulfate tablets are indicated for the treatment of uncomplicated malaria due to P. falciparum, P. malariae, P. ovale, P. vivax Hydroxychloroquine sulfate tablets are indicated for the prophylaxis of malaria in geographic areas where chloroquine resistance is not reported. Limitations of Use in Malaria Hydroxychloroquine sulfate tablets are not recommended for the treatment of complicated malaria. Hydroxychloroquine sulfate tablets are not effective against chloroquine or hydroxychloroquine-resistant strains of Plasmodium CLINICAL PHARMACOLOGY en dash Microbiology Plasmodium Hydroxychloroquine sulfate tablets are not recommended for malaria prophylaxis in geographic areas where chloroquine resistance occurs. Hydroxychloroquine sulfate tablets do not prevent relapses of P. vivax P.ovale P. vivax P. ovale CLINICAL PHARMACOLOGY en dash Microbiology Prior to prescribing Hydroxychloroquine sulfate tablets for the treatment or prophylaxis of malaria, consult the Centers for Disease Control and Prevention (CDC) Malaria website (http://www.cdc.gov/malaria). Lupus Erythematosus Hydroxychloroquine sulfate tablets are indicated for the treatment of chronic discoid lupus erythematosus and systemic lupus erythematosus in adults. Rheumatoid Arthritis Hydroxychloroquine sulfate tablets are indicated for the treatment of acute and chronic rheumatoid arthritis in adults.

One Hydroxychloroquine sulfate tablet contains 200 mg of hydroxychloroquine sulfate, which is equivalent to 155 mg base. Take Hydroxychloroquine sulfate tablets with a meal or a glass of milk. Malaria Prophylaxis Weight-based dosing in adults and pediatric patients: Treatment of Uncomplicated Malaria Weight based dosage in adults and pediatric patients: For radical cure of P. vivax P. malariae Lupus Erythematosus The recommended adult dosage is 200 to 400 mg (155 to 310 mg base) daily, administered as a single daily dose or in two divided doses. Doses above 400 mg a day are not recommended. The incidence of retinopathy has been reported to be higher when this maintenance dose is exceeded. Rheumatoid Arthritis The action of hydroxychloroquine is cumulative and may require weeks to months to achieve the maximum therapeutic effect (see CLINICAL PHARMACOLOGY Initial adult dosage: Maintenance adult dosage: Do not exceed 600 mg or 6.5 mg/kg (5 mg/kg base) per day, whichever is lower, as the incidence of retinopathy has been reported to be higher when this maintenance dose is exceeded. Corticosteroids and salicylates may be used in conjunction with Hydroxychloroquine sulfate tablets, and they can generally be decreased gradually in dosage or eliminated after a maintenance dose of Hydroxychloroquine sulfate tablets has been achieved.

The following adverse reactions have been identified during post-approval use of Hydroxychloroquine sulfate tablets 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. Blood and lymphatic system disorders: Cardiac disorders: WARNINGS OVERDOSAGE OVERDOSAGE DRUG INTERACTIONS Ear and labyrinth disorders: Eye disorders: Gastrointestinal disorders: General disorders and administration site conditions: Hepatobiliary disorders: Immune system disorders: Metabolism and nutrition disorders: Musculoskeletal and connective tissue disorders: Nervous system disorders: Psychiatric disorders: Skin and subcutaneous tissue disorders: To report SUSPECTED ADVERSE REACTIONS, contact Prasco Laboratories at 1-866-525-0688 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

Use of Hydroxychloroquine sulfate tablets is contraindicated in patients with known hypersensitivity to 4-aminoquinoline compounds.

Teratogenic Effects:

Digoxin Insulin or antidiabetic drugs Drugs that prolong QT interval and other arrhythmogenic drugs Mefloquine and other drugs known to lower the convulsive threshold Antiepileptics Methotrexate Cyclosporin The following interactions have been observed on treatment with the structurally related substance chloroquine phosphate, and therefore cannot be ruled out for hydroxychloroquine. Praziquantel Antacids and kaolin Cimetidine Ampicillin

WARNINGS
Resistant strains of malaria: P. falciparum CLINICAL PHARMACOLOGY en dash Microbiology Ocular: A baseline ocular examination is recommended within the first year of starting Hydroxychloroquine sulfate 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 ocular coherence tomography (SD-OCT). For individuals with significant risk factors (daily dose of hydroxychloroquine sulfate greater than 5.0 mg/kg base 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. For individuals without significant risk factors, annual exams 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 hydroxychloroquine 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. Cardiac Effects, including Cardiomyopathy and QT prolongation: Hydroxychloroquine sulfate tablets prolong the QT interval. Ventricular arrhythmias and torsades de pointes have been reported in patients taking Hydroxychloroquine sulfate tablets (see OVERDOSAGE DRUG INTERACTIONS Worsening of psoriasis and porphyria: Proximal Myopathy and Neuropathy: Neuropsychiatric events, including suicidality: Hypoglycemia: DRUG INTERACTIONS ADVERSE REACTIONS
OVERDOSAGE
The 4-aminoquinoline compounds are very rapidly and completely absorbed after ingestion, and in accidental overdosage, or rarely with lower doses in hypersensitive patients, toxic symptoms may occur within 30 minutes. The symptoms of overdosage may include headache, drowsiness, visual disturbances, cardiovascular collapse, convulsions, hypokalemia, rhythm and conduction disorders including QT prolongation, torsades de pointes, ventricular tachycardia and ventricular fibrillation, followed by sudden potentially fatal respiratory and cardiac arrest. Treatment is symptomatic and must be prompt. Immediate gastric lavage until the stomach is completely emptied is indicated. After lavage, activated charcoal is introduced by the stomach tube within 30 minutes of ingestion of the drug may inhibit further intestinal absorption. To be effective, the dose of activated charcoal should be at least five times the estimated dose of hydroxychloroquine ingested. Consideration should be given to administering diazepam parenterally since studies suggest that it may be beneficial in reversing chloroquine and hydroxychloroquine cardiotoxicity. Respiratory support and shock management should be instituted as necessary. Exchange transfusions are used to reduce the level of 4-aminoquinoline drug in the blood. A patient who survives the acute phase and is asymptomatic should be closely observed for at least six hours. Fluids may be forced and sufficient ammonium chloride (8 g daily in divided doses for adults) may be administered for a few days to acidify the urine. This will promote urinary excretion in cases of both overdosage and sensitivity. However, caution must be exercised in patients with impaired renal function and/or metabolic acidosis.

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HYDROXYCHLOROQUINE SULFATE- hydroxychloroquine sulfate_tablet Product manual source documgent