CONTRAINDICATIONS:

Use of this drug is contraindicated in the presence of retinal or visual field changes attributable to any 4-aminoquinoline compound, in patients with known hypersensitivity to 4-aminoquinoline compounds, and for long-term therapy in children.

DESCRIPTION:

Hydroxychloroquine sulfate tablets contain 200 mg hydroxychloroquine sulfate, equivalent to 155 mg base, and are for oral administration.

MALARIA ACTIONS:

Like chloroquine phosphate, Hydroxychloroquine sulfate is highly active against the erythrocytic forms of P. vivax and malariae and most strains of P. falciparum (but not the gametocytes of P. falciparum). Hydroxychloroquine sulfate does not prevent relapses in patients with vivax or malariae malaria because it is not effective against exo-erythrocytic forms of the parasite, nor will it prevent vivax or malariae infection when administered as a prophylactic. It is highly effective as a suppressive agent in patients with vivax or malariae malaria, in terminating acute attacks, and significantly lengthening the interval between treatment and relapse. In patients with falciparum malaria, it abolishes the acute attack and effects complete cure of the infection, unless due to a resistant strain of P. falciparum.

WARNINGS:

General: Hydroxychloroquine sulfate is not effective against chloroquine-resistant strains of P. falciparum. Children are especially sensitive to the 4-aminoquinoline compounds.

Use of Hydroxychloroquine sulfate in patients with psoriasis may precipitate a severe attack of psoriasis. When used in patients with porphyria the condition may be exacerbated.

MALARIA:

Mild and transient headache, dizziness, and gastrointestinal complaints (diarrhea, anorexia, nausea, abdominal cramps and, on rare occasions, vomiting) may occur. Cardiomyopathy has been rarely reported with high daily dosages of hydroxychloroquine. In recent years, it has been found that certain strains of P. falciparum have become resistant to 4-aminoquinoline compounds (including hydroxychloroquine) as shown by the fact that normally adequate doses have failed to prevent or cure clinical malaria or parasitemia.

LUPUS ERYTHEMATOSUS AND RHEUMATOID ARTHRITIS:

Irreversible retinal damage has been observed in some patients who had received long-term or high-dosage 4-aminoquinoline therapy for discoid and systemic lupus erythematosus, or rheumatoid arthritis. Retinopathy has been reported to be dose related. When prolonged therapy with any antimalarial compound is contemplated, initial (base line) and periodic (every three months) ophthalmologic examinations should be performed. All patients on long-term therapy with this preparation should be questioned and examined periodically, including the testing of knee and ankle reflexes, to detect any evidence of muscular weakness. If weakness occurs, discontinue the drug. In the treatment of rheumatoid arthritis, if objective improvement (such as reduced joint swelling, increased mobility) does not occur within six months, the drug should be discontinued.

PRECAUTIONS:

General: antimalarial compounds should be used with caution in patients with hepatic disease or alcoholism or in conjunction with known hepatotoxic drugs. Periodic blood cell counts should be made if patients are given prolonged therapy. The drug should be administered with caution in patients having G-6-PD (glucose-6-phosphate dehydrogenase) deficiency.

Pregnancy: Usage of this drug during pregnancy should be avoided except in the suppression or treatment of malaria when in the judgment of the physician the benefit outweighs the possible hazard.

LUPUS ERYTHEMATOSUS AND RHEUMATOID ARTHRITIS:

Dermatologic reactions to Hydroxychloroquine sulfate may occur and, therefore, proper care should be exercised when it is administered to any patient receiving a drug with a significant tendency to produce dermatitis.

SIDE EFFECTS:

MALARIA:

Mild and transient headache, dizziness, and gastrointestinal complaints (diarrhea, anorexia, nausea, abdominal cramps and, on rare occasions, vomiting) may occur. Cardiomyopathy has been rarely reported with high daily dosages of hydroxychloroquine.

LUPUS ERYTHEMATOSUS AND RHEUMATOID ARTHRITIS:

CNS Reactions: Irritability, nervousness, emotional changes, nightmares, psychosis, headache, dizziness, vertigo, tinnitus, nystagmus, nerve deafness, convulsions, ataxia.

Neuromuscular Reactions: Skeletal muscle palsies or skeletal muscle myopathy or neuromyopathy leading to progressive weakness and atrophy of proximal muscle groups which may be associated with mild sensory changes, depression of tendon reflexes and abnormal nerve conduction.

Ocular Reactions:

The most common visual symptoms attributed to the retinopathy are: reading and seeing difficulties (words, letters, or parts of objects missing), photophobia, blurred distance vision, missing or blacked out areas in the central or peripheral visual field, light flashes and streaks. Retinopathy appears to be dose related and has occurred within several months (rarely) to several years of daily therapy; a small number of cases have been reported several years after antimalarial drug therapy was discontinued.

Dermatologic Reactions: Bleaching of hair, alopecia, pruritus, skin and mucosal pigmentation, photosensitivity, and skin eruptions (urticarial, morbilliform, lichenoid, maculopapular, purpuric, erythema annulare centrifugum, Stevens Johnsons syndrome, acute generalized exanthematous pustulosis, and exfoliative dermatitis).

Hematologic Reactions: Various blood dyscrasias such as aplastic anemia, agranulocytosis, leukopenia, thrombocytopenia (hemolysis in individuals with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency).

Gastrointestinal Reactions: Anorexia, nausea, vomiting, diarrhea, and abdominal cramps. Isolated cases of abnormal liver function and fulminant hepatic failure.

Miscellaneous Reactions: Weight loss, lassitude, exacerbation or precipitation of porphyria and nonlight-sensitive psoriasis. Cardiomyopathy has been rarely reported with high daily dosages of hydroxychloroquine.

OVERDOSAGE:

Toxic symptoms may occur within 30 minutes. These consist of headache, drowsiness, visual disturbances, cardiovascular collapse, and convulsions, followed by sudden and early respiratory and cardiac arrest. Treatment is symptomatic and must be prompt with immediate evacuation of the stomach by emesis or gastric lavage until the stomach is completely emptied. If finely powdered, activated charcoal is introduced by the stomach tube. Because of the importance of supporting respiration, tracheal intubation or tracheostomy, followed by gastric lavage, may also be necessary. Exchange transfusions have been 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 to help promote urinary excretion in cases of both overdosage and sensitivity.

DOSAGE AND ADMINISTRATION:

Malaria:

Suppression; In adults, 400 mg on exactly the same day of each week. In infants and children, the weekly suppressive dosage is 5 mg, calculated as base, per kg of body weight, but should not exceed the adult dose regardless of weight.

If circumstances permit, suppressive therapy should begin two weeks prior to exposure. However, failing this, in adults an initial double (loading) dose of 800 mg (= 620 mg base), or in children 10 mg base/kg may be taken in two divided doses, six hours apart. The suppressive therapy should be continued for eight weeks after leaving the endemic area.

Treatment of the acute attack; In adults, an initial dose of 800 mg (= 620 mg base) followed by 400 mg (= 310 mg base) in six to eight hours and 400 mg (= 310 mg base) on each of two consecutive days (total 2 g hydroxychloroquine sulfate or 1.55 g base). An alternative method, employing a single dose of 800 mg (= 620 mg base), has also proved effective.

For radical cure of vivax and malariae malaria concomitant therapy with an 8-aminoquinoline compound is necessary.

Lupus erythematosus; Initially, the average adult dose is 400 mg (=310 mg base) once or twice daily. This may be continued for several weeks or months, depending on the response of the patient. For prolonged maintenance therapy, a smaller dose, from 200 mg to 400 mg (= 155 mg to 310 mg base) daily will frequently suffice.

Rheumatoid arthritis; Several months of therapy may be required before maximum effects can be obtained. If objective improvement (such as reduced joint swelling, increased mobility) does not occur within six months, the drug should be discontinued.

Initial dosage; In adults, from 400 mg to 600 mg (=310 mg to 465 mg base) daily, each dose to be taken with a meal or a glass of milk.

Maintenance dosage; When a good response is obtained (usually in four to twelve weeks), the dosage is reduced by 50 percent and continued at a usual maintenance level of 200 mg to 400 mg (=155 mg to 310 mg base) daily, each dose to be taken with a meal or a glass of milk.

Corticosteroids and salicylates may be used in conjunction with this compound, and they can generally be decreased gradually in dosage or eliminated after the drug has been used for several weeks.

How Supplied: Each pack of Ruz-Hydroxychloroquine 200 mg tablets contains 100 film coated tablets in 10 blisters.

storage: Dispense in a tight, light-resistant container. Store at room temperature up to 30°C.

Reference: PDR 2000, page 2755-6

                  USPDI for Professional Health Care, 2004, Page 1567-70

                  Martindale 2005, Page 452-3