Hydroxychloroquine Sulfate

HYDROXYCHLOROQUINE SULFATE- hydroxychloroquine sulfate tablet
Accord Healthcare, Inc.,

1 INDICATIONS AND USAGE

1.1 Malaria

Hydroxychloroquine sulfate is indicated in adult and pediatric patients for the:

• Treatment of uncomplicated malaria due to Plasmodium falciparum, Plasmodium malariae, Plasmodium vivax, and Plasmodium ovale.
• Prophylaxis of malaria in geographic areas where chloroquine resistance is not reported.

Limitations of Use:

Hydroxychloroquine sulfate is not recommended for:

• Treatment of complicated malaria.
• Treatment of malaria by chloroquine or hydroxychloroquine-resistant strains of Plasmodium species [see Microbiology (12.4)] .
• Treatment of malaria acquired in geographic areas where chloroquine resistance occurs or when the Plasmodium species has not been identified.
• Prophylaxis of malaria in geographic areas where chloroquine resistance occurs.
• Prevention of relapses of P. vivax or P. ovale because it is not active against the hypnozoite liver stage forms of these parasites. For radical cure of P. vivax and P. ovale infections, concomitant therapy with an 8-aminoquinoline drug is necessary [see Microbiology (12.4)] .

For the most current information about drug resistance, refer to the latest recommendations from the Center for Disease Control and Prevention ¹.

1.2 Rheumatoid Arthritis

Hydroxychloroquine sulfate is indicated for the treatment of acute and chronic rheumatoid arthritis in adults.

1.3 Systemic Lupus Erythematosus

Hydroxychloroquine sulfate is indicated for the treatment of systemic lupus erythematosus in adults.

1.4 Chronic Discoid Lupus Erythematosus

Hydroxychloroquine sulfate is indicated for the treatment of chronic discoid lupus erythematosus in adults.

2 DOSAGE AND ADMINISTRATION

2.1 Important Administration Instructions

Administer Hydroxychloroquine sulfate orally with food or milk. Do not crush or divide the tablets.

2.2 Dosage for Malaria in Adult and Pediatric Patients

Hydroxychloroquine sulfate is not recommended in pediatric patients less than 31 kg because the lowest available strength (200 mg) exceeds the recommended dose for these patients and it cannot be divided.

Prophylaxis

Treatment must start 2 weeks before travel to an endemic area. Advise the patient to take the prophylaxis dosage once a week, staring 2 weeks prior to travel to the endemic area, on the same day every week, continuing the same weekly dose while in the endemic area, and for 4 weeks after leaving the endemic area. The recommended prophylaxis dosage is:

• Adult patients: 400 mg once a week
• Pediatric patients ≥ 31kg: 6.5 mg/kg actual body weight (up to 400 mg) once a week

Treatment of Uncomplicated Malaria

The dosages for the treatment of uncomplicated malaria are:

• Adult patients: Administer 800 mg initially; subsequently administer 400 mg at 6 hours, 24 hours, and 48 hours after the initial dose (total dosage = 2000 mg).
• Pediatric patients ≥ 31 kg: Administer 13 mg/kg (up to 800 mg) initially; subsequently administer 6.5 mg/kg (up to 400 mg) at 6 hours, 24 hours, and 48 hours after the initial dose (total dosage = 31 mg/kg — up to 2000 mg).

For radical cure of P. vivax and P. ovale infections, concomitant therapy with an 8-aminoquinoline drug is necessary [see Microbiology (12.4)] .

2.3 Dosage for Rheumatoid Arthritis in Adults

The recommended dosage is:

• Initial dosage: 400 mg to 600 mg daily as a single daily dose or two divided doses. The action of hydroxychloroquine is cumulative and may require weeks to months for maximum therapeutic effect. Daily doses exceeding 5 mg/kg (actual weight) of hydroxychloroquine sulfate increase the incidence of retinopathy [see Warnings and Precautions (5.2)] .
• Chronic dosage: 200 mg once daily to 400 mg daily, as a single dose or two divided doses.

Corticosteroids, salicylates, and other antirheumatic agents may be used concomitantly with hydroxychloroquine sulfate.

2.4 Dosage for Systemic Lupus Erythematosus in Adults

The recommended dosage is 200 mg given once daily, or 400 mg given once daily or in two divided doses.

2.5 Dosage for Chronic Discoid Lupus Erythematosus in Adults

The recommended dosage is 200 mg given once daily, or 400 mg given once daily or in two divided doses.

3 DOSAGE FORMS AND STRENGTHS

Tablets:

Hydroxychloroquine sulfate tablets, USP 100 mg are white to off white, peanut shaped, biconvex, film coated tablets, debossed with “H2” on one side and plain on the other side.

Hydroxychloroquine sulfate tablets, USP 200 mg are white to off white, peanut shaped, biconvex, film coated tablet debossed with”H11″ on one side and plain on the other side.

Hydroxychloroquine sulfate tablets, USP 300 mg are white to off white, peanut shaped, biconvex, film coated tablets, debossed with “H3” on one side and plain on the other side.

Hydroxychloroquine sulfate tablets, USP 400 mg are white to off white, peanut shaped, biconvex, film coated tablets, debossed with “H” and “4” on either side of break-line on one side and break-line on the other side.

4 CONTRAINDICATIONS

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

5 WARNINGS AND PRECAUTIONS

5.1 Cardiomyopathy and Ventricular Arrhythmias

Fatal and life-threatening cases of cardiotoxicity, including cardiomyopathy, have been reported in patients treated with hydroxychloroquine sulfate. Signs and symptoms of cardiac compromise have occurred during acute and chronic hydroxychloroquine sulfate treatment. In multiple cases, endomyocardial biopsy showed association of the cardiomyopathy with phospholipidosis in the absence of inflammation, infiltration, or necrosis. Drug-induced phospholipidosis may occur in other organ systems [ See Warnings and Precautions (5.7), (5.10) ] .

Patients may present with ventricular hypertrophy, pulmonary hypertension and conduction disorders including sick sinus syndrome. ECG findings include atrioventricular, right or left bundle branch block.

Hydroxychloroquine sulfate has a potential to prolong the QT interval. Ventricular arrhythmias (including torsades de pointes) have been reported in hydroxychloroquine sulfate -treated patients. The magnitude of QT prolongation may increase with increasing concentrations of the drug. Therefore, the recommended dose should not be exceeded [see Adverse Reactions (6), Overdosage (10)] . Avoid hydroxychloroquine sulfate administration in patients with congenital or documented acquired QT prolongation and/or known risk factors for prolongation of the QT interval such as:

• Cardiac disease, e.g., heart failure, myocardial infarction.
• Proarrhythmic conditions, e.g., bradycardia (< 50 bpm).
• History of ventricular dysrhythmias.
• Uncorrected hypokalemia and/or hypomagnesemia.
• Concomitant administration with QT interval prolonging agents as this may lead to an increased risk for ventricular arrhythmias [see Drug Interactions (7.1)]

Therefore, hydroxychloroquine sulfate is not recommended in patients taking other drugs that have the potential to prolong the QT interval. Correct electrolyte imbalances prior to use. Monitor cardiac function as clinically indicated during hydroxychloroquine sulfate therapy. Discontinue hydroxychloroquine sulfate if cardiotoxicity is suspected or demonstrated by tissue biopsy.