Pronunciation: high-drox-ee-KLOR-oh-kwin SULL-fate
Class: 4–aminoquinoline compound, Antirheumatic

Trade Names

Plaquenil Sulfate
- Tablets 200 mg (equivalent to 155 mg base)

Apo-Hydroxyquine (Canada)
Gen-Hydroxychloroquine (Canada)

Pharmacology

May interfere with parasitic nucleoprotein (DNA/RNA) synthesis and parasite growth or cause lysis of parasite or infected erythrocytes. In rheumatoid arthritis, may suppress formation of antigens responsible for symptom-producing hypersensitivity reactions.

Slideshow: Drug Treatment for Rheumatoid Arthritis - What Are Your Options?

Pharmacokinetics

Absorption

Hydroxychloroquine is readily absorbed from the GI tract. T _max is 1 to 3 h.

Distribution

Hydroxychloroquine concentrates in the liver, spleen, kidney, heart, lungs, and brain.

Metabolism

It is partially hepatic to active de-ethylated metabolites.

Elimination

Approximately 50% of the unchanged drug is excreted in urine. Elimination in urine is very slow and may persist for months or years after discontinuation. Renal excretion is increased by acidification and decreased by alkalinization of the urine. The plasma t _½ is approximately 32 days.

Special Populations

Renal Function Impairment

Use with caution.

Hepatic Function Impairment

Use with caution.

Children

Use with caution. A number of fatalities have been reported following ingestion of chloroquines.

Indications and Usage

Prophylaxis and treatment of acute attacks of malaria caused by Plasmodium vivax , Plasmodium malariae , Plasmodium ovale , and susceptible strains of Plasmodium falciparum . Treatment of chronic discoid and systemic lupus erythematosus (SLE) and acute or chronic rheumatoid arthritis in patients not responding to other therapies.

Contraindications

Retinal or visual field changes caused by any 4-aminoquinoline compound; hypersensitivity to 4-aminoquinoline compounds; long-term therapy in children.

Dosage and Administration

Acute Attack of Malaria
Adults

PO 800 mg (620 mg of base) followed by 400 mg in 6 to 8 h and 400 mg on each of 2 consecutive days. Alternatively, a single 800 mg dose (620 mg of base) has proved effective.

Children

PO 10 mg/kg (base), up to adult dose; followed by 5 mg/kg (base), not exceeding 310 mg of base, 6 h after first dose; followed in 18 h after the second dose by 5 mg/kg (base). A fourth dose of 5 mg/kg (base) is given 24 h after third dose.

Lupus Erythematosus
Adults

PO Initially 400 mg/day or twice daily. For prolonged therapy, reduce to 200 to 400 mg/day (155 to 310 mg of base).

Rheumatoid Arthritis
Adults Initial dose

PO 400 to 600 mg/day (310 to 465 mg of base) with food or milk.

Maintenance

PO After good response (usually 4 to 12 wk), reduce dosage 50% and continue at 200 to 400 mg/day (155 to 310 mg of base).

Suppression of Malaria

Begin 2 wk prior to exposure; continue for 8 wk after leaving area.

Adults

PO 400 mg (310 mg of base) weekly on same day each week.

Children

PO 5 mg/kg of base weekly on same day each week, up to max 400 mg (310 mg of base).

General Advice

• Administer prescribed dose with food or milk to minimize GI side effects.
• Disease-modifying antirheumatic drugs, glucocorticoids, salicylates, NSAIDs, and analgesics may be continued during treatment of rheumatoid arthritis with hydroxychloroquine.

Storage/Stability

Store tablets at controlled room temperature (up to 86°F).

Drug Interactions

Beta-blockers (eg, metoprolol)

Plasma levels and CV effects of certain beta-blockers may be increased.

Cimetidine

Pharmacologic effect of hydroxychloroquine may be increased.

Cyclosporine

Serum levels may be increased by hydroxychloroquine, increasing the risk of nephrotoxicity.

Digoxin

May increase serum digoxin levels.

Hepatotoxic drugs

May increase potential for hepatotoxicity.

Magnesium sulfate

Absorption of hydroxychloroquine may be reduced, decreasing the pharmacologic effect; antacid activity of magnesium sulfate may be decreased.

Mefloquine

Coadministration may increase risk of seizures.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypotension; ECG changes; cardiomyopathy (rare).

CNS

Headache; irritability; nervousness; emotional changes; nightmares; psychosis; dizziness; vertigo; nystagmus; nerve deafness; convulsions; ataxia.

Dermatologic

Bleaching of hair; alopecia; pruritus; skin and mucosal pigmentation; skin eruptions; exacerbation of psoriasis.

EENT

Disturbance of accommodation with blurred vision; transient corneal edema; corneal opacities; decreased corneal sensitivity; retinal edema; retinal atrophy; abnormal retinal pigmentation; loss of retinal reflexes; optic disc pallor and atrophy; scotoma; retinopathy; tinnitus.

GI

Anorexia; nausea; vomiting; diarrhea; abdominal cramps.

Hematologic

Aplastic anemia; agranulocytosis; leukopenia; thrombocytopenia; hemolysis in G-6-PD deficiency; exacerbation of porphyria.

Metabolic

Weight loss.

Miscellaneous

Immunoblastic lymphadenopathy; extraocular muscle palsies; skeletal muscle weakness; absent or hypoactive deep tendon reflexes.

Precautions

Monitor Baseline disease activity Document baseline disease state activity in patient being treated for rheumatoid arthritis or lupus erythematosus. Reassess periodically to document response to therapy. CBC Ensure CBC with differential and platelet count is evaluated before starting therapy and periodically thereafter during prolonged therapy. Muscular weakness Ensure patient on long term therapy is periodically evaluated for development of muscular weakness.

Pregnancy

Category C . Avoid use in pregnancy, except in suppression of malaria when benefit outweighs the possible hazard.

Lactation

Excreted in breast milk.

Children

Deaths have occurred following accidental ingestion of relatively small doses. Do not exceed recommended doses for children with malaria. Not indicated for juvenile rheumatoid arthritis.

Renal Function

Use with caution.

Hepatic Function

Use with caution. May increase risk of hepatotoxicity.

Special Risk Patients

May exacerbate psoriasis, porphyria, or other dermatitis; may cause hemolysis in patients with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.

Alcoholism

May increase risk of hepatotoxicity.

Muscular weakness

If weakness occurs, discontinue.

Ophthalmic effects

Irreversible retinal damage with long-term hydroxychloroquine therapy has been observed. Retinal changes and visual disturbances may progress after cessation of therapy. Ensure that ophthalmologic exam is obtained before starting therapy and periodically (eg, every 3 mo) thereafter during prolonged therapy.

Overdosage

Symptoms

Headache, drowsiness, visual disturbances, CV collapse, convulsions, respiratory and cardiac arrest, bradycardia, ventricular fibrillation.

Patient Information

• Advise patient to take each dose with milk or food to minimize stomach upset.
• Advise patient to continue other medications for arthritis or lupus as recommended by health care provider.
• Advise patient with arthritis that it may take several months of treatment before max benefit is seen. Advise patient to notify health care provider if symptoms have not improved after 6 mo of treatment or if symptoms appear to be getting worse.
• Instruct patient to take medication once weekly for malaria prophylaxis, beginning 2 wk prior to arrival in malaria-infected area, while in the malaria-infected area, and for 8 wk after leaving the malaria-infected area.
• Advise patient that protective clothing, insect repellants, and bednets are important components of malaria prophylaxis.
• Advise patient to immediately report any of the following to health care provider: any visual changes; muscle weakness; ringing in the ears or hearing loss; fever; sore throat; unusual bleeding or bruising; unusual pigmentation (eg, blue-black) of the skin; bleaching or loss of hair; mood or mental changes.
• Advise patient to notify health care provider if persistent or bothersome nausea, vomiting, diarrhea, stomach pain, or other symptoms develop.
• Advise patient that drug may cause dizziness and to use caution while driving or performing other tasks requiring mental alertness, coordination, or physical dexterity until tolerance is determined.
• Advise patient medication may cause photosensitivity (sensitivity to sunlight) and to avoid unnecessary exposure to sunlight or tanning lamps, and to use sunscreens and wear protective clothing to avoid photosensitivity reactions.

Copyright © 2009 Wolters Kluwer Health.