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Hydroxychloroquine Sulfate

Pronunciation

Class: Antimalarials
VA Class: AP101
CAS Number: 747-36-4
Brands: Plaquenil

Introduction

Antimalarial; 4-aminoquinoline derivative.109

Uses for Hydroxychloroquine Sulfate

Malaria

Prevention (prophylaxis) of malaria caused by Plasmodium malariae, P. ovale, chloroquine-susceptible P. vivax, and chloroquine-susceptible P. falciparum.109 115 Alternative when chloroquine is unavailable.115 121 134

Treatment of uncomplicated malaria caused by P. malariae, P. ovale, chloroquine-susceptible P. vivax, or chloroquine-susceptible P. falciparum.109 134 143 144 Alternative when chloroquine is unavailable.134 143 144

Do not use for prevention or treatment of malaria in areas where chloroquine resistance has been reported.115 134 143 144 (See Chloroquine-resistant Plasmodium under Cautions.)

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Active only against asexual erythrocytic forms of Plasmodium (not exoerythrocytic stages) and cannot prevent delayed primary attacks or relapse of P. ovale or P. vivax malaria or provide a radical cure; 14-day regimen of primaquine usually also indicated to eradicate hypnozoites and prevent relapse in patients exposed to or being treated for P. ovale or P. vivax malaria.109 115 143 144

Information on risk of malaria in specific countries and mosquito avoidance measures and recommendations regarding whether prevention of malaria indicated and choice of antimalarials for prevention available from CDC at and .115

Assistance with diagnosis or treatment of malaria available by contacting CDC Malaria Hotline at 770-488-7788 or 855-856-4713 from 9:00 a.m. to 5:00 p.m. Eastern Standard Time or CDC Emergency Operation Center at 770-488-7100 after hours and on weekends and holidays.143 144

Rheumatoid Arthritis

Treatment of rheumatoid arthritis.103 104 109

One of several disease-modifying antirheumatic drugs (DMARDs) that can be used when DMARD therapy is appropriate.103 104

Consider risk of severe and sometimes irreversible toxicity if used for prolonged periods in treatment of rheumatoid arthritis.109 (See Cautions.)

Lupus Erythematosus

Treatment of discoid lupus erythematosus and systemic lupus erythematosus.109 Used as an adjunct to corticosteroids and/or other appropriate therapy.a

Consider risk of severe and sometimes irreversible toxicity if used for prolonged periods in treatment of lupus erythematosus.109 (See Cautions.)

Q Fever

Treatment of Q fever endocarditis caused by Coxiella burnetii; used in conjunction with doxycycline.111 112 113

CDC recommends a 2- to 3-week regimen of doxycycline for treatment of acute Q fever, a 1-year regimen of doxycycline and hydroxychloroquine for treatment of acute Q fever in patients with preexisting valvular heart disease (to prevent progression of acute disease to endocarditis), and a 1.5- to 3-year regimen of doxycycline and hydroxychloroquine for treatment of chronic Q fever.113

Porphyria Cutanea Tarda and Polymorphous Light Eruptions

Has been used in treatment of porphyria cutanea tarda.114 116 117 (See Patients with Psoriasis or Porphyria under Cautions.)

Has been effective in some cases when used in the treatment of polymorphous light eruptions.

Hydroxychloroquine Sulfate Dosage and Administration

Administration

Oral Administration

Administer orally.109

When used in treatment of rheumatoid arthritis, administer with a meal or glass of milk.109

Dosage

Available as hydroxychloroquine sulfate; dosage usually expressed as hydroxychloroquine.109

Each 200-mg tablet of hydroxychloroquine sulfate contains 155 mg of hydroxychloroquine.109

Pediatric Patients

Malaria
Prevention of Malaria in Areas Without Chloroquine-resistant Plasmodium
Oral

5 mg/kg (6.5 mg/kg of hydroxychloroquine sulfate) once weekly on same day each week.109 115

Initiate prophylaxis 1–2 weeks prior to entering malarious area and continue during stay and for 4 weeks after leaving the area.115

If not initiated prior to entering malarious area, manufacturer recommends a loading dose of 10 mg/kg (13 mg/kg of hydroxychloroquine sulfate) given in 2 equally divided doses 6 hours apart followed by usual dosage.109

If exposure occurred in areas where P. ovale or P. vivax is endemic, terminal prophylaxis with 14-day regimen of primaquine may be indicated;115 give during final 2 weeks of hydroxychloroquine prophylaxis or, if not feasible, give after hydroxychloroquine prophylaxis discontinued.115

Treatment of Uncomplicated Chloroquine-susceptible Malaria
Oral

Initial dose of 10 mg/kg (13 mg/kg of hydroxychloroquine sulfate) followed by 5 mg/kg (6.5 mg/kg of hydroxychloroquine sulfate) given at 6, 24, and 48 hours after initial dose.109 144

Adults

Malaria
Prevention of Malaria in Areas Without Chloroquine-resistant Plasmodium
Oral

310 mg (400 mg of hydroxychloroquine sulfate) once weekly on same day each week.109 115

Initiate prophylaxis 1–2 weeks prior to entering malarious area and continue during stay and for 4 weeks after leaving the area.115

If not initiated prior to entering malarious area, manufacturer recommends a loading dose of 620 mg (800 mg of hydroxychloroquine sulfate) followed by usual dosage.109

If exposure occurred in areas where P. ovale or P. vivax is endemic, terminal prophylaxis with 14-day regimen of primaquine may be indicated;115 give during final 2 weeks of hydroxychloroquine prophylaxis or, if not feasible, give after hydroxychloroquine prophylaxis discontinued.115

Treatment of Uncomplicated Chloroquine-susceptible Malaria
Oral

Initial dose of 620 mg (800 mg of hydroxychloroquine sulfate) followed by 310 mg (400 mg of hydroxychloroquine sulfate) given at 6–8 hours, 24, and 48 hours after initial dose.109 144 Alternatively, manufacturer states that a single 620-mg dose (800 mg of hydroxychloroquine sulfate) may be effective.109

Rheumatoid Arthritis
Oral

Initiate treatment with 310–465 mg (400–600 mg of hydroxychloroquine sulfate) daily.109 If adverse effects occur, dosage may be temporarily reduced; after 5–10 days, increase dosage gradually until an optimum response occurs without recurrence of adverse effects.109

A response may not occur until after 4–12 weeks and several months of therapy may be required to attain optimum response.109 When a good response is obtained, decrease dosage by 50% and continue treatment with a maintenance dosage of 155–310 mg (200–400 mg of hydroxychloroquine sulfate) daily.109

If relapse occurs after hydroxychloroquine is discontinued, the drug can be reinitiated or continued on an intermittent schedule if there is no evidence of adverse ocular effects.109

If objective improvement of rheumatoid arthritis (e.g., reduced joint swelling, increased mobility) does not occur within 6 months, hydroxychloroquine should be discontinued.109

Lupus Erythematosus
Oral

310 mg (400 mg of hydroxychloroquine sulfate) once or twice daily for several weeks or months depending on response of the patient.109 For prolonged maintenance therapy, 155–310 mg (200–400 mg of hydroxychloroquine sulfate) daily may be adequate.109

Q Fever
Acute Q Fever in Patients with Preexisting Valvular Heart Disease
Oral

CDC recommends 465 mg (600 mg of hydroxychloroquine sulfate) daily in conjunction with oral doxycycline (200 mg daily) for 1 year.113 Adjust hydroxychloroquine dosage to maintain plasma hydroxychloroquine concentrations at 1 ± 0.2 mcg/mL.113

Chronic Q Fever
Oral

CDC recommends 465 mg (600 mg of hydroxychloroquine sulfate) daily in conjunction with oral doxycycline (200 mg daily) for 1.5–3 years.113

Prescribing Limits

Pediatric Patients

Malaria
Prevention of Malaria in Areas Without Chloroquine-resistant Plasmodium
Oral

Maximum 310 mg (400 mg of hydroxychloroquine sulfate) daily, regardless of weight.115

Special Populations

Hepatic Impairment

No specific recommendations available regarding need for dosage adjustment in individuals with hepatic impairment;109 use with caution.109 (See Hepatic Impairment under Cautions.)

Renal Impairment

No specific recommendations available regarding need for dosage adjustment in individuals with renal impairment;109 use with caution.109 (See Renal Impairment under Cautions.)

Cautions for Hydroxychloroquine Sulfate

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 Plasmodium

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

Ocular Effects

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

Neuromuscular Effects

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

Patients with Psoriasis or Porphyria

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

Hypersensitivity Reactions

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

General Precautions

Dermatologic Effects

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

Hematologic Effects

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

Pregnancy

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

Lactation

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 Use

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

Hepatic Impairment

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

Renal Impairment

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

Hydroxychloroquine Sulfate Pharmacokinetics

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

Stability

Storage

Oral

Tablets

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

Actions and Spectrum

  • A blood schizonticidal agent active against asexual erythrocytic forms of most strains of Plasmodium malariae, P. ovale, P. vivax, and susceptible P. falciparum.a Not active against preerythrocytic or exoerythrocytic forms of plasmodia.a Gametocidal for P. malariae and P. vivax, but has no direct activity against gametocytes of P. falciparum.a

  • Chloroquine-resistant P. falciparum confirmed in all areas where P. falciparum malaria occurs, 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 Chloroquine-resistant P. vivax also documented in Burma (Myanmar), India, and Central and South America.143

  • To date, no widespread evidence of chloroquine resistance in P. malariae, P. ovale, or P. knowlesi.143 161

  • Chloroquine-resistant P. falciparum also are resistant to hydroxychloroquine109 and may be cross-resistant to pyrimethamine or quinine.a Cross-resistance between chloroquine and mefloquine reported in P. falciparum and P. vivax in vitro.152 153

  • Has anti-inflammatory activity; mechanism(s) of action in the treatment of rheumatoid arthritis and lupus erythematosus not determined.a

Advice to Patients

  • Importance of keeping hydroxychloroquine out of reach of children since they are especially sensitive to 4-aminoquinoline derivatives.109

  • For prevention of malaria, necessity of starting hydroxychloroquine prophylaxis 1–2 weeks before arriving in an area with malaria and continuing during and for 4 weeks after leaving the area.115

  • Necessity of taking protective measures to reduce contact with mosquitoes (protective clothing, insect repellents, mosquito nets, remaining in air-conditioned or well-screened areas).115 121 134

  • Possibility of contracting malaria during travel, regardless of prophylactic regimen used.115 121 134

  • Importance of seeking medical attention as soon as possible if febrile illness develops during or after return from a malaria-endemic area and of informing clinician of possible malaria exposure.115 121 134

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.109

  • Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.109

  • Importance of advising patients of other important precautionary information.109 (See Cautions.)

Preparations

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

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

Hydroxychloroquine Sulfate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

155 mg (of hydroxychloroquine)*

Hydroxychloroquine Sulfate Tablets

Plaquenil

Sanofi-Aventis

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Hydroxychloroquine Sulfate 200MG Tablets (WATSON LABS): 60/$35.99 or 180/$88.99

Plaquenil 200MG Tablets (SANOFI-AVENTIS U.S.): 60/$182.99 or 180/$529.96

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions March 4, 2014. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

100. McChesney EW. Animal toxicity and pharmacokinetics of hydroxychloroquine sulfate. Am J Med. 1983; 75(Suppl. 1A):11-8. [IDIS 174380] [PubMed 6408923]

101. Janssen NM, Genta MS. The effects of immunosuppressive and anti-inflammatory medications on fertility, pregnancy, and lactation. Arch Inter Med. 2000; 160:610-9.

102. American Academy of Pediatrics Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics. 1989; 84:924-36. [IDIS 260411] [PubMed 2677964]

103. Singh JA, Furst DE, Bharat A et al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2012; 64:625-39. [PubMed 22473917]

104. . Drugs for rheumatoid arthritis. Treat Guidel Med Lett. 2012; 10:37-44; quiz 2 p following 44. [PubMed 22538522]

105. Clark P, Casas E, Tugwell P et al. Hydroxychloroquine compared with placebo in rheumatoid arthritis: a randomized controlled trial. Ann Intern Med. 1993; 119:1067-71. [IDIS 322560] [PubMed 8239224]

107. Harris ED Jr. Hydroxychloroquine is safe and probably useful in rheumatoid arthritis. Ann Intern Med. 1993; 119:1146-7. [IDIS 322565] [PubMed 8239236]

108. Makin AJ, Wendon J, Fitt S. Fulminant hepatic failure secondary to hydroxychloroquine. Gut. 1994; 35:569-70. [IDIS 330037] [PubMed 8175002]

109. Sanofi-Aventis US. Plaquenil (hydroxychloroquine sulfate) tablets prescribing information. Bridgewater, NJ; 2012 Apr.

111. Raoult D, Houpikian P, Dupont HT et al. Treatment of Q fever endocarditis: comparison of 2 regimens containing doxycycline and ofloxacin or hydrochloroquine. Arch Intern Med. 1999; 159:167-73. [IDIS 418047] [PubMed 9927100]

112. Lupoglazoff JM, Brouqui P, Magnier S et al. Q fever tricuspid valve endocarditis. Arch Dis Child. 1997; 77:448-9. [IDIS 398559] [PubMed 9487972]

113. Centers for Disease Control and Prevention. Q fever—California, Georgia, Pennsylvania, and Tennessee, 2000-2001. MMWR Morb Mortal Wkly Rep. 2002; 51:924-5. [PubMed 12403408]

114. Bruce AJ, Ahmed I. Childhood-onset porphyria cutanea tarda: successful therapy with low-dose hydroxychloroquine (Plaquenil). J Am Acad Dermatol. 1998; 38(5 pt 2):810-3. [IDIS 406218] [PubMed 9591792]

115. Centers for Disease Control and Prevention. CDC health information for international travel, 2014. Atlanta, GA: US Department of Health and Human Services. Updates may be available at CDC website.

116. Wallace DJ. The use of chloroquine and hydroxychloroquine for non-infectious conditions other than rheumatoid arthritis or lupus: a critical review. Lupus. 1996; 5(Suppl 1):S59-64.

117. Petersen CS, Thomsen K. High-dose hydroxychloroquine treatment of porphyria cutanea tarda. J Am Acad Dermatol. 1992; 26:614-9. [PubMed 1597548]

121. . Advice for travelers. Treat Guidel Med Lett. 2012; 10:45-56. [PubMed 22777212]

134. Anon. Drugs for parasitic infections. Treat Guidel Med Lett. 2010; 8:e1-16.

143. Centers for Disease Control and Prevention. CDC treatment guidelines: Treatment of malaria (guidelines for clinicians). 2013 Jul. From the CDC website. Accessed 2013 Sep 27.

144. Centers for Disease Control and Prevention. Guidelines for treatment of malaria in the United States (based on drugs currently available for use in the United States–updated July 1, 2013). From the CDC website. Accessed 2013 Sep 27.

152. Chehuan YF, Costa MR, Costa JS et al. In vitro chloroquine resistance for Plasmodium vivax isolates from the Western Brazilian Amazon. Malar J. 2013; 12:226. [PubMed 23819884]

153. Zatra R, Lekana-douki JB, Lekoulou F et al. In vitro antimalarial susceptibility and molecular markers of drug resistance in Franceville, Gabon. BMC Infect Dis. 2012; 12:307. [PubMed 23153201]

161. World Health Organization (WHO). Guidelines for the treatment of malaria. 2nd edition. Geneva, Switzerland: World Health Organization; 2010. Updates may be available at WHO website.

a. AHFS Drug Information 2004. McEvoy GK, ed. hydroxychloroquine Sulfate. Bethesda, MD: American Society of Health-System Pharmacists; 2004:827-8.

b. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 6th ed. Philadelphia; PA: Lippincott Wiliams & Wilkins; 2002:671-4.

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