|
This information has been developed and provided by an independent third-party source. Merck & Co., Inc. does not endorse and is not responsible for the accuracy of the content, or for practices or
standards of non-Merck sources.
ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(hye droks ee KLOR oh kwin)
Generic Available (U.S.)
Yes
Index Terms
U.S. Brand Names
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Suppression and treatment of acute attacks of malaria; treatment of systemic lupus erythematosus (SLE) and rheumatoid arthritis
Use: Unlabeled/Investigational
Porphyria cutanea tarda, polymorphous light eruptions
Pregnancy Considerations
Malaria infection in pregnant women may be more severe than in nonpregnant women. Therefore, pregnant women and women who are likely to become pregnant are advised to avoid travel to malaria-risk areas. Hydroxychloroquine is recommended as an alternative treatment of pregnant women for uncomplicated malaria in chloroquine-sensitive regions. Women exposed to hydroxychloroquine for the treatment of rheumatoid arthritis or systemic lupus erythematosus during pregnancy may be enrolled in the Organization of Teratology Information Specialists (OTIS) Autoimmune Diseases Study pregnancy registry (877-311-8972).
Lactation
Enters breast milk (AAP considers “compatible”; AAP 2001 update pending)
Contraindications
Hypersensitivity to hydroxychloroquine, 4-aminoquinoline derivatives, or any component of the formulation; retinal or visual field changes attributable to 4-aminoquinolines; long-term use in children
Warnings/Precautions
Boxed warnings:
• Experienced physician: See “Other warnings/precautions” below.
Concerns related to adverse effects:
• Cardiovascular: Rare cardiomyopathy has been associated with long-term use of hydroxychloroquine.
• Hematologic: Aminoquinolines have been associated with rare hematologic reactions, including agranulocytosis, aplastic anemia, and thrombocytopenia; monitoring (CBC) is recommended in prolonged therapy.
• Neuromuscular: Myopathy, neuromyopathy, and progressive weakness have been associated with aminoquinoline derivatives; muscle strength (especially proximal muscles) should be assessed periodically during prolonged therapy.
• Ophthalmic effects: Hydroxychloroquine has been associated with important adverse effects on vision, including loss of visual acuity, macular pigmentary changes, and loss of foveal reflex. Risk factors include daily doses >6.5 mg/kg lean body weight. Baseline assessment of renal and hepatic function is recommended (Jones, 1999). Monitoring is recommended in long-term therapy.
Disease-related concerns:
• G6PD deficiency: Use with caution in patients with known G6PD; use of 4-aminoquinolines such as chloroquine has been associated with hemolysis and renal impairment in this population.
• Hepatic impairment: Use with caution in patients with hepatic impairment, alcoholism, or concurrent therapy with hepatotoxic agents.
• Porphyria: Use with caution in patients with porphyria; may exacerbate disease.
• Psoriasis: Use with caution in patients with psoriasis; may exacerbate disease.
Special populations:
• Pediatrics: Use caution due to increased sensitivity to aminoquinolones; long-term use in children is contraindicated.
Other warnings/precautions:
• Appropriate use: Malaria: Hydroxychloroquine is not effective against chloroquine-resistant strains of P. falciparum.
• Experienced physician: [U.S. Boxed Warning]: Should be prescribed by physicians familiar with its use.
Adverse Reactions
Frequency not defined.
Cardiovascular: Cardiomyopathy (rare, relationship to hydroxychloroquine unclear)
Central nervous system: Ataxia, dizziness, emotional changes, headache, irritability, lassitude, nervousness, nightmares, psychosis, seizure, vertigo
Dermatologic: Alopecia, angioedema, bleaching of hair, pigmentation changes (skin and mucosal; black-blue color), rash (acute generalized exanthematous pustulosis, erythema annulare centrifugum, exfoliative dermatitis, lichenoid, maculopapular, morbilliform, purpuric, Stevens-Johnson syndrome, urticarial), urticaria
Gastrointestinal: Abdominal cramping, anorexia, diarrhea, nausea, vomiting, weight loss
Hematologic: Agranulocytosis, aplastic anemia, hemolysis (in patients with glucose-6-phosphate deficiency), leukopenia, thrombocytopenia
Hepatic: Abnormal liver function/hepatic failure (isolated cases)
Neuromuscular & skeletal: Myopathy, palsy, or neuromyopathy leading to progressive weakness and atrophy of proximal muscle groups (may be associated with mild sensory changes, loss of deep tendon reflexes, and abnormal nerve conduction)
Ocular: Abnormal color vision, abnormal retinal pigmentation, atrophy, attenuation of retinal arterioles, corneal changes/deposits (visual disturbances, blurred vision, photophobia [reversible on discontinuation]), decreased visual acuity, disturbance in accommodation, keratopathy, macular edema, nystagmus, optic disc pallor/atrophy, pigmentary retinopathy, retinopathy (early changes reversible [may progress despite discontinuation if advanced]), scotoma
Otic: Deafness, tinnitus
Miscellaneous: Exacerbation of porphyria and nonlight sensitive psoriasis
Respiratory: Bronchospasm, respiratory failure (myopathy-related)
Drug Interactions
Anthelmintics: Aminoquinolines (Antimalarial) may decrease the serum concentration of Anthelmintics. Risk C: Monitor therapy
Antipsychotic Agents (Phenothiazines): Antimalarial Agents may increase the serum concentration of Antipsychotic Agents (Phenothiazines). Risk C: Monitor therapy
Artemether: May enhance the adverse/toxic effect of Antimalarial Agents. Management: Artemether/Lumefantrine (combination product) should not be used with other antimalarials unless there is no other treatment option. Risk X: Avoid combination
BCG: Immunosuppressants may diminish the therapeutic effect of BCG. Risk X: Avoid combination
Beta-Blockers: Aminoquinolines (Antimalarial) may decrease the metabolism of Beta-Blockers. Exceptions: Atenolol; Carteolol; Carteolol (Ophthalmic); Levobunolol; Metipranolol; Nadolol. Risk C: Monitor therapy
Cardiac Glycosides: Aminoquinolines (Antimalarial) may increase the serum concentration of Cardiac Glycosides. Risk D: Consider therapy modification
Dapsone: May enhance the adverse/toxic effect of Antimalarial Agents. More specifically, dapsone may increase the risk for hemolytic reactions. Antimalarial Agents may enhance the adverse/toxic effect of Dapsone. More specifically, antimalarial agents may increase the risk for hemolytic reactions. Management: Closely monitor patients for signs/symptoms of hemolytic reactions with concomitant use of dapsone and antimalarial agents, particularly in patients deficient in glucose-6-phosphate dehydrogenase (G6PD), methemoglobin reductase, or with hemoglobin M. Risk D: Consider therapy modification
Dapsone (Systemic): Antimalarial Agents may enhance the adverse/toxic effect of Dapsone (Systemic). Specifically, concomitant use of antimalarial agents with dapsone may increase the risk of hemolytic reactions. Dapsone (Systemic) may enhance the adverse/toxic effect of Antimalarial Agents. Specifically, concomitant use of dapsone with antimalarial agents may increase the risk for hemolytic reactions. Management: Closely monitor patients for signs/symptoms of hemolytic reactions with concomitant use of dapsone and antimalarial agents, particularly in patients deficient in glucose-6-phosphate dehydrogenase (G6PD), methemoglobin reductase, or with hemoglobin M. Risk D: Consider therapy modification
Dapsone (Topical): Antimalarial Agents may enhance the adverse/toxic effect of Dapsone (Topical). Specifically, the risk of hemolytic reactions may be increased. Management: Closely monitor for signs/symptoms of hemolytic reactions with concomitant use of topical dapsone and antimalarial agents. Patients with glucose-6-phosphate dehydrogenase deficiency may be at particularly high risk for adverse hematologic effects. Risk D: Consider therapy modification
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Risk C: Monitor therapy
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification
Lumefantrine: Antimalarial Agents may enhance the adverse/toxic effect of Lumefantrine. Management: Artemether/Lumefantrine (combination product) should not be used with other antimalarials unless there is no other treatment option. Risk X: Avoid combination
Mefloquine: Aminoquinolines (Antimalarial) may enhance the adverse/toxic effect of Mefloquine. Specifically, the risk for QTc-prolongation and the risk for convulsions may be increased. Mefloquine may increase the serum concentration of Aminoquinolines (Antimalarial). Management: Avoid concurrent use, and delay administration of mefloquine until at least 12 hours after the last dose of an aminoquinoline antimalarial when possible. Risk X: Avoid combination
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Risk C: Monitor therapy
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy
Vaccines (Live): Hydroxychloroquine may enhance the adverse/toxic effect of Vaccines (Live). Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (due to GI irritation).
Mechanism of Action
Interferes with digestive vacuole function within sensitive malarial parasites by increasing the pH and interfering with lysosomal degradation of hemoglobin; inhibits locomotion of neutrophils and chemotaxis of eosinophils; impairs complement-dependent antigen-antibody reactions
Pharmacodynamics/Kinetics
Onset of action: Rheumatic disease: May require 4-6 weeks to respond
Absorption: Rapid and complete
Protein binding: 55%
Metabolism: Hepatic; metabolites include desethylhydroxychloroquine and desethylchloroquine
Half-life elimination: 32-50 days
Time to peak: Rheumatic disease: Several months
Excretion: Urine (as metabolites and unchanged drug [up to 60%]); may be enhanced by urinary acidification
Dosage
Note: Hydroxychloroquine sulfate 200 mg is equivalent to 155 mg hydroxychloroquine base and 250 mg chloroquine phosphate. All doses below expressed as hydroxychloroquine sulfate. Second-line alternative treatment for malaria (chloroquine is preferred).
Oral:
Children:
Malaria, chemoprophylaxis: 6.5 mg/kg once weekly (not to exceed 400 mg/dose); begin 2 weeks before exposure; continue for 4 weeks (per CDC guidelines) after leaving endemic area; if suppressive therapy is not begun prior to the exposure, double the initial dose and give in 2 doses, 6 hours apart and continue treatment for 8 weeks
Malaria, acute attack: 13 mg/kg initially (not to exceed 800 mg/dose), followed by 6.5 mg/kg (not to exceed 400 mg/dose) at 6, 24, and 48 hours
Adults:
Malaria, chemoprophylaxis: 400 mg weekly on same day each week; begin 2 weeks before exposure; continue for 4 weeks (per CDC guidelines) after leaving endemic area; if suppressive therapy is not begun prior to the exposure, double the initial dose and give in 2 doses, 6 hours apart and continue treatment for 8 weeks
Malaria, acute attack: 800 mg initially, followed by 400 mg at 6, 24, and 48 hours
Rheumatoid arthritis: Initial: 400-600 mg/day taken with food or milk; increase dose gradually until optimum response level is reached; usually after 4-12 weeks dose should be reduced by 1/2 to a maintenance dose of 200-400 mg/day
Lupus erythematosus: 400 mg every day or twice daily for several weeks-months depending on response; 200-400 mg/day for prolonged maintenance therapy
Dosage adjustment in renal impairment: Use with caution; dosage adjustment may be necessary in severe dysfunction (Bernstein, 1992); specific guidelines not available.
Administration: Oral
Administer with food or milk.
Monitoring Parameters
Ophthalmologic exam at baseline and every 3 months during prolonged therapy (including visual acuity, slit-lamp, fundoscopic, and visual field exam); CBC at baseline and periodically; muscle strength (especially proximal, as a symptom of neuromyopathy) during long-term therapy
Dietary Considerations
May be taken with food or milk.
Patient Education
It is important to complete full course of therapy. May be taken with meals to decrease GI upset and bitter aftertaste. Avoid excessive alcohol. You should have regular ophthalmic exams (every 3 months) if using this medication over extended periods. You may experience skin discoloration (blue/black), hair bleaching, or skin rash. If you have psoriasis, you may experience exacerbation. You may experience dizziness, headache, nervousness, abnormal color vision, lightheadedness, nausea, vomiting, loss of appetite, or increased sensitivity to sunlight. Report any changes in hearing acuity or ringing in ears, any changes in vision (visual disturbances, blurred vision), weakness, numbness, tingling, tremors in muscles, skin rash or itching, persistent GI disturbances, chest pain or palpitation, CNS changes, unusual fatigue, or easy bruising or bleeding.
Geriatric Considerations
No specific recommendations for dosing.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Infectious Diseases Comment
CDC periodically updates a list of geographic areas with common chloroquine resistance. Information may be viewed at: http://www.cdc.gov/malaria/diagnosis_treatment/tx_clinicians.htm and http://www.cdc.gov/malaria/pdf/treatmenttable.pdf.
Mental Health: Effects on Mental Status
May cause dizziness or nervousness
Mental Health: Effects on Psychiatric Treatment
May rarely cause agranulocytosis; use caution with clozapine and carbamazepine
Nursing: Physical Assessment/Monitoring
Evaluate results of CBC, liver function tests, and ophthalmic exam prior to treatment and periodically throughout. Monitor for dermatologic, neuromuscular, or ocular changes.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, oral, as sulfate: 200 mg [equivalent to 155 mg base]
Plaquenil®: 200 mg [equivalent to 155 mg base]
Pricing: U.S. (www.drugstore.com)
Tablets (Hydroxychloroquine Sulfate)
200 mg (60): $35.99
Tablets (Plaquenil)
200 mg (60): $204.33
Extemporaneously Prepared
A 25 mg/mL hydroxychloroquine sulfate oral suspension may be made with tablets. With a towel moistened with alcohol, remove the coating from fifteen 200 mg hydroxychloroquine sulfate tablets. Crush tablets in a mortar and reduce to a fine powder. Add 15 mL of Ora-Plus® and mix to a uniform paste; add an additional 45 mL of vehicle and mix until uniform. Mix while adding sterile water for irrigation in incremental proportions to almost 120 mL; transfer to a calibrated bottle, rinse mortar with sterile water, and add sufficient quantity of sterile water to make 120 mL. Label "shake well". A 30-day expiration date is recommended, although stability testing has not been performed.
Pesko LJ, "Compounding: Hydroxychloroquine," Am Druggist, 1993, 207(4):57.
References
American Academy of Pediatrics Committee on Drugs, “Transfer of Drugs and Other Chemicals Into Human Breast Milk,” Pediatrics, 2001, 108:776-89.
Bernstein HN, “Ocular Safety of Hydroxychloroquine (Plaquenil),” South Med J, 1992, 85(3):274-9.
Buchanan NM, Toubi E, Khamashta MA, et al, “The Safety of Hydroxychloroquine in Lupus Pregnancy: Experience in 27 Pregnancies,” Br J Rheumatol, 1995, 34(Suppl 1):14.
Centers for Disease Control and Prevention, “Guidelines for the Treatment of Malaria in the United States.” Available at http://www.cdc.gov/malaria/diagnosis_treatment/index.html and http://www.cdc.gov/malaria/pdf/treatmenttable.pdf
“Drugs for Parasitic Infections,” Med Lett Drugs Ther, 1993, 35(911):111-22.
Emery H, “Clinical Aspects of Systemic Lupus Erythematosus in Childhood,” Pediatr Clin North Am, 1986, 33(5):1177-90.
Furst DE, “Rational Use of Disease-Modifying Antirheumatic Drugs,” Drugs, 1990, 39(1):19-37.
Giannini EH and Cawkwell GD, “Drug Treatment in Children With Juvenile Rheumatoid Arthritis. Past, Present, and Future,” Pediatr Clin North Am, 1995, 42(5):1099-125.
“Guidelines for the Management of Rheumatoid Arthritis. American College of Rheumatology Ad Hoc Committee on Clinical Guidelines,” Arthritis Rheum, 1996, 39(5):713-22.
Hart LE and Tugwell P, “The Use of Disease-Modifying Antirheumatic Drugs in the Management of Rheumatoid Arthritis,” Postgrad Med J, 1989, 65(770):905-12.
Jones SK, “Ocular Toxicity and Hydroxychloroquine: Guidelines for Screening,” Br J Derm, 1999, 140(1):3-7.
Kutz DC and Bridges AJ, “Bullous Rash and Brown Urine in a Systemic Lupus Erythematosus Patient Treated With Hydroxychloroquine,” Arthritis Rheum, 1995, 38(3):440-3.
Levy M, Buskila D, Gladman DD, et al, “Pregnancy Outcome Following First Trimester Exposure to Chloroquine,” Am J Perinatol, 1991, 8(3):174-8.
Ostensen M, Brown ND, Chiang PK, et al, "Hydroxychloroquine in Human Breast Milk," Eur J Clin Pharmacol, 1985, 28(3):357.
Panisko DM and Keystone JS, “Treatment of Malaria - 1990,” Drugs, 1990, 39(2):160-89.
Seguin P, Camus C, Leroy JP, et al, “Respiratory Failure Associated With Hydroxychloroquine Neuromyopathy,” Eur Neurol, 1995, 35(4):236-7.
Tett SE, Cutler DJ, Day RO, et al, “Bioavailability of Hydroxychloroquine Tablets in Healthy Volunteers,” Br J Clin Pharmacol, 1989, 27(6):771-9.
Wang R, “Hydroxychloroquine Cardiotoxicity,” Clin Toxicol, 1995, 33(5):548.
White NJ, “The Treatment of Malaria,” N Engl J Med, 1996, 335(11):800-6.
International Brand Names
Lexi-Comp.com
Last full review/revision May 2011
|
