hydroxychloroquine

General

Genetic Implications:

Pronunciation:
hye-drox-ee-klor-oh-kwin

Trade Name(s)

• Plaquenil

Ther. Class.
antimalarials
antirheumatics (DMARDs)

Indications

• Treatment of uncomplicated malaria in geographic areas where chloroquine resistance is not reported.
• Prophylaxis of malaria in geographic areas where chloroquine resistance is not reported.
• Acute and chronic rheumatoid arthritis.
• Chronic discoid lupus erythematosus and systemic lupus erythematosus.

Action

Inhibits protein synthesis in susceptible organisms by inhibiting DNA and RNA polymerase.

Therapeutic Effect(s):

• Death of plasmodia responsible for causing malaria.
• Also has anti-inflammatory properties.

Active against chloroquine-sensitive strains of: Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale, and Plasmodium vivax.

Pharmacokinetics

Absorption: Highly variable (31–100%) following oral administration.

Distribution: Widely distributed; high concentrations in RBCs; crosses the placenta; excreted into breast milk.

Metabolism and Excretion: Partially metabolized by the liver to active metabolites; partially excreted unchanged by the kidneys.

Half-life: 40 days.

TIME/ACTION PROFILE (blood levels)

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity to hydroxychloroquine or chloroquine;
• Previous visual damage from hydroxychloroquine or chloroquine.

Use Cautiously in:

• Concurrent use of hepatotoxic drugs;
• Hepatic impairment or alcoholism;
• Use of high doses (>5 mg/kg base), duration of use >5 yr, renal impairment, concurrent use of tamoxifen or macular disease (↑ risk of retinopathy);
•  G6PD deficiency;
• Psoriasis;
• Porphyria;
• Bone marrow depression;
• Obesity (determine dose by ideal body weight);
• Pedi:  Safety and effectiveness for treatment of rheumatoid arthritis, chronic discoid lupus erythematosus, or systemic lupus erythematosus not established in children
• Geri:  ↓ renal function may ↑ risk of adverse reactions in older adults.

Adverse Reactions/Side Effects

CV: HF, TORSADES DE POINTES, heart block, QT interval prolongation

Derm: DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), ERYTHEMA MULTIFORME, STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, acute generalized exanthematous pustulosis, alopecia, hair color changes, hyperpigmentation, photosensitivity, pruritus, rash, urticaria

EENT: corneal deposits, nystagmus, retinopathy, tinnitus, vertigo, visual disturbances

Endo: hypoglycemia

GI: HEPATOTOXICITY, abdominal pain, anorexia, diarrhea, ↑ liver enzymes, nausea, vomiting

Hemat: AGRANULOCYTOSIS, APLASTIC ANEMIA, leukopenia, thrombocytopenia

Metabolic: ↓ weight

Neuro: SEIZURES, SUICIDAL THOUGHTS/BEHAVIORS, aggressiveness, anxiety, ataxia, dizziness, dyskinesia, dystonia, fatigue, headache, irritability, neuromyopathy, nightmares, peripheral neuritis, personality changes, psychoses, tremor

Resp: PULMONARY HYPERTENSION, bronchospasm

Misc: ANGIOEDEMA

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

• Concurrent use of other  QT interval-prolonging drugs  may ↑ risk of torsade de pointes.
• May ↑ the risk of hepatotoxicity when administered with  hepatotoxic drugs.
• May ↑ risk of hypoglycemia when used with  antidiabetic agents.
• Use with  mefloquine  may ↑ risk of seizures.
•  Antacids  may bind to and ↓ the absorption of hydroxychloroquine; separate administration by ≥4 hr.
•  Cimetidine  may ↑ levels; avoid concurrent use.
•  Urinary acidifiers  may ↑ renal excretion.
• May ↑ levels of  digoxin  or  cyclosporine.

Route/Dosage

200 mg hydroxychloroquine sulfate = 155 mg of hydroxychloroquine base

Malaria

PO (Adults): Prophylaxis– 400 mg sulfate (310 mg base) once weekly; start 2 wk prior to entering malarious area; continue for 4 wk after leaving area.  Treatment– 800 mg sulfate (620 mg base), then 400 mg sulfate (310 mg base) at 6 hr, 24 hr, and 48 hr after initial dose.

PO (Children ≥31 kg):   Prophylaxis– 6.5 mg/kg sulfate (5 mg/kg base) (not to exceed 400 mg sulfate [310 mg base]) once weekly; start 2 wk prior to entering malarious area; continue for 4 wk after leaving area.  Treatment– 13 mg/kg sulfate (10 mg/kg base) (not to exceed 800 mg sulfate [620 mg base]) initially, then 6.5 mg/kg sulfate (5 mg/kg base) (not to exceed 400 mg sulfate [310 mg base]) at 6 hr, 24 hr, and 48 hr after initial dose.

Rheumatoid Arthritis

PO (Adults): 400–600 mg sulfate (310–465 mg base) per day in 1–2 divided doses; once adequate response obtained, may ↓ dose to maintenance dose of 200–400 mg sulfate (155–310 mg base) per day in 1–2 divided doses.

Lupus Erythematosus

PO (Adults): 200–400 mg sulfate (155–310 mg base) per day in 1–2 divided doses.

Availability (generic available)

Tablets: 200 mg sulfate (155 mg base)

Cost:

Generic: $14.88/100

Assessment

• Assess deep tendon reflexes periodically to determine muscle weakness. Therapy may be discontinued should this occur.

  • Obtain baseline ocular exam within first yr of therapy. Patients on prolonged high-dose therapy should have eye exams prior to and every 3–6 mo during therapy to detect retinal damage. Monitor patients without risk factors every 5 yrs. Retinal changes may progress even after therapy is completed.
• Monitor ECG for cardiomyopathy and QT prolongation periodically during therapy.
• Monitor for signs and symptoms of DRESS (fever, rash, lymphadenopathy, and/or facial swelling, associated with involvement of other organ systems (hepatitis, nephritis, hematologic abnormalities, myocarditis, myositis) during therapy. May resemble an acute viral infection. Eosinophilia is often present. Discontinue therapy if signs occur.
• Assess for rash periodically during therapy. May cause Stevens-Johnson syndrome. Discontinue therapy if severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis and/or eosinophilia.
• Assess for suicidal tendencies, depression, or changes in behavior periodically during therapy.
• Malaria or Lupus Erythematosus: Assess patient for improvement in signs and symptoms of condition daily throughout course of therapy.
• Rheumatoid Arthritis: Assess patient monthly for pain, swelling, and range of motion.

Lab Test Considerations:

Monitor CBC and platelet count periodically throughout therapy. May cause decreased RBC, WBC, and platelet counts. If severe decreases occur that are not related to the disease process, hydroxychloroquine should be discontinued.

• Monitor liver function tests periodically during therapy.
• May cause hypoglycemia.

Implementation

• Do not confuse hydroxychloroquine with hydroxyurea.
• PO 

  Administer with milk or meals to minimize GI distress.

  • Tablets may be crushed and placed inside empty capsules for patients with difficulty swallowing. Contents of capsules may also be mixed with a teaspoonful of jam, jelly, or Jell-O prior to administration.
• Malaria Prophylaxis: Hydroxychloroquine therapy should be started 2 wk prior to potential exposure and continued for 4–6 wk after leaving the malarious area.

Patient/Family Teaching

• Instruct patient to take medication exactly as directed and continue full course of therapy even if feeling better. Missed doses should be taken as soon as remembered unless it is almost time for next dose. Do not double doses.
• Advise patients to avoid use of alcohol while taking hydroxychloroquine.
• Caution patient to keep hydroxychloroquine out of reach of children; fatalities have occurred with ingestion of 3 or 4 tablets.
• Explain need for periodic ophthalmic exams for patients on prolonged high-dose therapy. Advise patient that the risk of ocular damage may be decreased by the use of dark glasses in bright light. Protective clothing and sunscreen should also be used to reduce risk of dermatoses.
• Advise patient to notify health care professional promptly if sore throat, fever, unusual bleeding or bruising, blurred vision, visual changes, ringing in the ears, difficulty hearing, or muscle weakness occurs.
• Rep:  Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected, or if breast feeding. Inform patient of pregnancy exposure registry that monitors pregnancy outcomes in women exposed to hydroxychloroquine during pregnancy. Encourage patients to register by contacting 1-877-311-8972.
• Malaria Prophylaxis:

  Review methods of minimizing exposure to mosquitoes with patients receiving hydroxychloroquine prophylactically (use repellent, wear long-sleeved shirt and long trousers, use screen or netting).

  • Advise patient to notify health care professional if fever develops while traveling or within 2 mo of leaving an endemic area.
• Rheumatoid Arthritis: Instruct patient to contact health care professional if no improvement is noticed within a few days. Treatment for rheumatoid arthritis may require up to 6 mo for full benefit.

Evaluation/Desired Outcomes

• Prevention or resolution of malaria.
• Improvement in signs and symptoms of rheumatoid arthritis.
• Improvement in symptoms of lupus erythematosus.