Hydroxychloroquine Sulfate

Frequency Not Defined

Nausea, vomiting

Headache

Dizziness

Irritability

Muscle weakness

Aplastic anemia

Leukopenia

Thrombocytopenia

Corneal changes or deposits (visual disturbances, blurred vision, photophobia; reversible on discontinuance)

Retinal damage with long-term use

Bleaching of hair

Alopecia

Pruritus

Skin and musculoskeletal pigmentation changes

Weight loss, anorexia

Cardiomyopathy (rare)

Hemolysis (individuals with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency)

Prolongs QT interval

Ventricular arrhythmias and torsade de pointes

Vertigo

Tinnitus

Nystagmus

Nerve deafness

Deafness

Irreversible retinopathy with retinal pigmentation changes (bull’s eye appearance)

Visual field defects (paracentral scotomas)

Visual disturbances (visual acuity)

Maculopathies (macular degeneration)

Decreased dark adaptation

Color vision abnormalities

Corneal changes (edema and opacities)

Abdominal pain

Fatigue

Liver function tests abnormal

Hepatic failure acute

Urticaria

Angioedema

Bronchospasm

Decreased appetite

Hypoglycemia

Porphyria

Weight decreased

Sensorimotor disorder

Skeletal muscle myopathy or neuromyopathy

Headache

Dizziness

Seizure

Ataxia

Extrapyramidal disorders such as dystonia

Dyskinesia

Tremor

Rash

Pruritus

Pigmentation disorders in skin and mucous membranes

Hair color changes

Alopecia

Dermatitis bullous eruptions including erythema multiforme

Stevens-Johnson syndrome

Toxic epidermal necrolysis

Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome)

Photosensitivity

Dermatitis exfoliative

Acute generalized exanthematous pustulosis (AGEP); AGEP has to be distinguished from psoriasis; hydroxychloroquine may precipitate attacks of psoriasis

Pyrexia

Hyperleukocytosis

Pregnancy category: C

Lactation: Drug is concentrated in breast milk (American Academy of Pediatrics committee states that it is compatible with nursing)

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Contraindications

• Hypersensitivity to 4-aminoquinoline derivatives.109

• Retinal or visual field changes attributable to 4-aminoquinoline derivatives or to any other etiology.109

• Long-term use in children.109

Warnings/Precautions

Warnings

Chloroquine-resistant P. falciparum confirmed in all areas with P. falciparum malaria, except the Caribbean, Central America west of the Panama Canal, and some countries in the Middle East.115

High prevalence of chloroquine-resistant P. vivax confirmed in Papua New Guinea and Indonesia;115 143 also reported in Burma (Myanmar), India, and Central and South America.143

Do not use for prevention of malaria in individuals traveling to malarious areas where chloroquine-resistant P. falciparum or chloroquine-resistant P. vivax malaria reported.115 134

Do not use for treatment of uncomplicated P. falciparum malaria or uncomplicated malaria caused by unidentified plasmodial species if the infection was acquired in areas with chloroquine resistance.143 144

Dose-related retinopathy reported, which may progress even after the drug is discontinued.109 Irreversible retinal damage has occurred in some patients who received long-term or high-dosage 4-aminoquinoline therapy for treatment of discoid and systemic lupus erythematosus or rheumatoid arthritis.109

Whenever long-term therapy contemplated, perform initial (base line) and periodic (every 3 months) ophthalmologic examinations, including visual acuity, slit-lamp, funduscopic, and visual field tests.109

Immediately discontinue hydroxychloroquine and closely observe patient for possible progression if there is any indication of abnormalities in visual acuity or visual field, abnormalities in the retinal macular area (such as pigmentary changes or loss of foveal reflex), or if any other visual symptoms (e.g., light flashes and streaks) occur which are not fully explainable by difficulties of accommodation or corneal opacities.109

Skeletal muscle palsies or skeletal muscle myopathy or neuromyopathy reported.109 May lead to progressive weakness and atrophy of proximal muscle groups and may be associated with mild sensory changes, depression of tendon reflexes, and abnormal nerve conduction.109

Patients receiving prolonged therapy should be questioned and examined periodically for evidence of muscular weakness; test knee and ankle reflexes.109

Discontinue hydroxychloroquine if muscular weakness occurs.109

May exacerbate psoriasis and precipitate a severe attack in patients with the disease.109 Use in psoriasis patients only if potential benefits outweigh risks.109

May exacerbate porphyria.109 Use in patients with porphyria only if potential benefits outweigh risks.109

Sensitivity Reactions

Erythema multiforme,109 Stevens-Johnson syndrome,109 toxic epidermal necrolysis,109 exfoliative dermatitis,109 and photosensitivity109 reported rarely.

General Precautions

Dermatologic reactions may occur; use with caution in patients with tendency for dermatitis.109

Aplastic anemia, agranulocytosis, leukopenia, thrombocytopenia (hemolysis in patients with G-6-PD deficiency) reported rarely.109

Periodically monitor CBCs in patients receiving prolonged treatment.109 Consider discontinuing hydroxychloroquine if any severe blood disorder occurs and is not attributable to the disease being treated.109

Use with caution in patients with G-6-PD deficiency.109

Specific Populations

Category C.b

Chloroquine has been used for prevention and treatment of malaria in pregnant women without evidence of adverse effects on the fetus.115 134

Manufacturer states avoid during pregnancy, except for prevention or treatment of malaria when clinician determines that possible benefits of the drug outweigh potential risks to fetus.109

CDC states pregnancy not a contraindication when hydroxychloroquine indicated for prevention or treatment of malaria.115 143

Distributed into milk.102 Amount of drug present in human milk does not appear to be harmful to nursing infants, but is insufficient to provide adequate protection against malaria in these infants.115 When prevention of malaria indicated, such infants should receive recommended dosages of appropriate antimalarial agent(s).115

Pediatric patients are especially sensitive to 4-aminoquinoline derivatives.109 Fatalities reported following accidental ingestion of relatively small doses.109

Prolonged therapy with hydroxychloroquine contraindicated in children; safe use of the drug for treatment of juvenile arthritis not established.109

May concentrate in the liver;a use with caution in patients with hepatic disease or alcoholism and in those receiving other hepatotoxic drugs.109

Possible increased risk of toxicity in patients with impaired renal function;109 use with caution in individuals with impaired renal function and/or metabolic acidosis.109

Common Adverse Effects

Ocular effects; skeletal muscle myopathy or neuromyopathy; GI effects (anorexia, diarrhea, nausea, abdominal cramps, vomiting); CNS effects (headache, dizziness); dermatologic effects.109

Distribution

Extent

Distributed into milk.102

Elimination

Metabolism

Partially metabolized; major metabolites are desethylhydroxychloroquine and desethylchloroquine.100 Bisdesethylchloroquine, a carboxylic acid derivative, also formed in small amounts.100

Elimination Route

Hydroxychloroquine and its metabolites slowly excreted by the kidneys.100

Storage

Oral

Room temperature ≤30°C in tight, light-resistant container.109

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name