Meningitis: What It Is and How to Avoid It Watch Video

Chloroquine Phosphate

Pronunciation

Class: Antimalarials
VA Class: AP101
CAS Number: 50-63-5
Brands: Aralen

Introduction

Antimalarial; 4-aminoquinoline derivative.136

Uses for Chloroquine Phosphate

Prevention of Malaria

Prevention (prophylaxis) of malaria caused by Plasmodium malariae, P. ovale, chloroquine-susceptible P. vivax, and chloroquine-susceptible P. falciparum.115 121 134 136

Can be used for prevention of malaria in individuals traveling to malarious areas where chloroquine-resistant P. falciparum malaria has not been reported.115 121 134 (See Chloroquine-resistant Plasmodium under Cautions.)

Risk of acquiring malaria varies substantially from traveler to traveler and from region to region (even within a single country) because of differences in intensity of malaria transmission within the various regions and season, itinerary, duration, and type of travel.115 121 Malaria transmission occurs in large areas of Africa, Central and South America, parts of the Caribbean, Asia (including South Asia, Southeast Asia, and the Middle East), Eastern Europe, and the South Pacific.115 Mosquito avoidance measures must be used in conjunction with prophylaxis since no drug is 100% effective in preventing malaria.115 121

Choice of antimalarial for prophylaxis depends on traveler’s risk of acquiring malaria in area(s) visited, risk of exposure to drug-resistant P. falciparum, other medical conditions (e.g., pregnancy), cost, and potential adverse effects.115 121 134

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;115 134 136 terminal prophylaxis with a 14-day regimen of primaquine may be indicated in addition to chloroquine prophylaxis if travelers were exposed in areas where P. ovale or P. vivax is endemic.115 134 136

Slideshow: It’s Buggin’ Me! How to Safely Use an Insect Repellent

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 are available from CDC at and .115

Treatment of Uncomplicated Malaria

Treatment of uncomplicated malaria caused by P. malariae, P. ovale, chloroquine-susceptible P. vivax, or chloroquine-susceptible P. falciparum.134 136 143 144

For treatment of uncomplicated malaria caused by chloroquine-susceptible P. falciparum, P. malariae, or P. knowlesi or treatment of uncomplicated malaria when plasmodial species not identified and infection was acquired in areas where chloroquine resistance not reported, CDC recommends chloroquine (or hydroxychloroquine).143 144 Alternatively, CDC states that any of the regimens recommended for treatment of uncomplicated chloroquine-resistant P. falciparum malaria (fixed combination of atovaquone and proguanil [atovaquone/proguanil], fixed combination of artemether and lumefantrine [artemether/lumefantrine], regimen of quinine in conjunction with doxycycline, tetracycline, or clindamycin) may be used if preferred, more readily available, or more convenient.143 144

Pediatric patients with uncomplicated malaria generally can receive same treatment regimens recommended for adults using age- and weight-appropriate drugs and dosages.143 144

Because chloroquine active only against asexual erythrocytic forms of Plasmodium (not exoerythrocytic stages), 14-day regimen of primaquine indicated to eradicate hypnozoites and prevent delayed primary attacks or relapse and provide a radical cure whenever chloroquine used for treatment of P. ovale or P. vivax malaria.134 143

Assistance with diagnosis or treatment of malaria available from 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

Extraintestinal Amebiasis

Has been used for treatment of extraintestinal amebiasis136 (including liver abscess) caused by Entamoeba histolytica.

Ineffective for treatment of intestinal amebiasis.a

A nitroimidazole derivative (metronidazole, tinidazole) followed by a luminal amebicide (iodoquinol, paromomycin, diloxanide furoate) is regimen of choice for mild to moderate or severe intestinal amebiasis and for amebic hepatic abscess.134

Rheumatoid Arthritis

Has been used for treatment of rheumatoid arthritis.a

When a disease-modifying antirheumatic drug (DMARD) indicated, other DMARDs (hydroxychloroquine, leflunomide, methotrexate, minocycline, sulfasalazine) recommended.103 104

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

Lupus Erythematosus

Has been used as an adjunct to topical corticosteroid therapy in treatment of discoid lupus erythematosus and as an adjunct to systemic corticosteroid and/or salicylate therapy in treatment of systemic lupus erythematosus.a

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

Porphyria Cutanea Tarda and Polymorphous Light Eruptions

Has been used with some success in treatment of porphyria cutanea tarda.185 186 187 (See Patients with Psoriasis or Porphyria under Cautions.)

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

Sarcoidosis

Has been used with some success in the treatment of sarcoidosis.188 189

Chloroquine Phosphate Dosage and Administration

Administration

Administer orally.136

Oral Administration

Administration with a meal may minimize adverse GI effects.121 134

For prevention of malaria, give once weekly on same day each week.136

Dosage

Available as chloroquine phosphate;136 dosage usually expressed in terms of chloroquine.136

Each 500-mg tablet of chloroquine phosphate contains 300 mg of chloroquine.136

Dosage in children is based on body weight.136

Pediatric Patients

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

5 mg/kg (8.3 mg/kg of chloroquine phosphate) once weekly on same day each week.115 134 136

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

If exposure occurred in areas where P. ovale or P. vivax is endemic, terminal prophylaxis with a 14-day regimen of primaquine may be indicated;115 136 give during final 2 weeks of chloroquine prophylaxis or, if not feasible, give after chloroquine prophylaxis discontinued.115

Treatment of Uncomplicated Chloroquine-susceptible Malaria
Oral

Initial dose of 10 mg/kg of chloroquine (16.7 mg/kg of chloroquine phosphate) followed by 5 mg/kg (8.3 mg/kg of chloroquine phosphate) given at 6, 24, and 48 hours after initial dose.134 144

Adults

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

300 mg (500 mg of chloroquine phosphate) once weekly on same day each week.134 115 136

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

If exposure occurred in areas where P. ovale or P. vivax is endemic, terminal prophylaxis with a 14-day regimen of primaquine may be indicated;115 136 give during final 2 weeks of chloroquine prophylaxis or, if not feasible, give after chloroquine prophylaxis discontinued.115

Treatment of Uncomplicated Chloroquine-susceptible Malaria
Oral

Initial dose of 600 mg of chloroquine (1 g of chloroquine phosphate) followed by 300 mg (500 mg of chloroquine phosphate) given at 6, 24, and 48 hours after initial dose.134 144

Prophylaxis of P. ovale or P. vivax When Primaquine Deferred during Pregnancy
Oral

300 mg (500 mg of chloroquine phosphate) once weekly for duration of the pregnancy.143 144 Give after usual treatment regimen and continue until a 14-day regimen of primaquine can be given after delivery to provide a radical cure.143 144

Extraintestinal Amebiasis
Oral

600 mg of chloroquine (1 g of chloroquine phosphate) once daily for 2 days, followed by 300 mg (500 mg of chloroquine phosphate) once daily for at least 2–3 weeks; usually used in conjunction with an intestinal amebicide.136

Rheumatoid Arthritis
Oral

150 mg (250 mg of chloroquine phosphate) daily.a Reduce dosage after remission or maximum improvement occurs.a

Response may not occur until after >4–6 weeks of therapy.a Some clinicians recommend the drug be continued for 4 months before being considered ineffective for treatment of rheumatoid arthritis.a

Lupus Erythematosus
Oral

150 mg (250 mg of chloroquine phosphate) daily.a

When used in conjunction with topical corticosteroids in treatment of discoid lupus erythematosus, skin lesions may regress within 3–4 weeks and new lesions may not appear.a When systemic and cutaneous manifestations of lupus erythematosus subside, reduce chloroquine dosage gradually over several months, and discontinue as soon as possible.a

Prescribing Limits

Pediatric Patients

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

Maximum dose 300 mg (500 mg of chloroquine phosphate).115 134 136

Treatment of Uncomplicated Chloroquine-susceptible Malaria
Oral

Maximum dose 600 mg (1 g of chloroquine phosphate).134

Adults

Malaria
Treatment of Uncomplicated Chloroquine-susceptible Malaria
Oral

Maximum initial dose 600 mg (1 g of chloroquine phosphate); maximum subsequent doses 300 mg (500 mg of chloroquine phosphate).136

Special Populations

Hepatic Impairment

No specific recommendations available regarding need for dosage adjustment in individuals with hepatic impairment;136 use with caution.136 (See Hepatic Impairment under Cautions.)

Renal Impairment

No specific recommendations available regarding need for dosage adjustment in individuals with renal impairment;136 substantially eliminated by the kidneys.136 (See Renal Impairment under Cautions.)

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.136

Cautions for Chloroquine Phosphate

Contraindications

  • Hypersensitivity to chloroquine or other 4-aminoquinoline derivatives.136

  • Retinal or visual field changes attributable to 4-aminoquinoline derivatives or to any other etiology.136 After weighing possible benefits and risks to the patient, some clinicians may elect to use chloroquine in these patients for treatment of acute attacks of malaria caused by susceptible Plasmodium.136

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.115 134 136

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.136 143 144

Malaria patients who do not respond to chloroquine treatment should be switched to a regimen recommended for chloroquine-resistant P. falciparum (e.g., atovaquone/proguanil, artemether/lumefantrine, regimen of quinine in conjunction with doxycycline, tetracycline, or clindamycin) or chloroquine-resistant P. vivax (e.g., quinine and doxycycline [or tetracycline] in conjunction with primaquine, atovaquone/proguanil in conjunction with primaquine, mefloquine in conjunction with primaquine).143

Ocular Effects

Retinopathy and maculopathy (as well as macular degeneration) reported, especially in patients receiving long-term treatment or high chloroquine dosage.136 May be irreversible in some patients.136

Visual disturbances reported in patients receiving chloroquine include blurred vision and difficulty in focusing or accommodation.136 Nyctalopia,136 scotomatous vision with field defects of paracentral, pericentral ring types, and typically temporal scotomas (e.g., difficulty reading with words tending to disappear, seeing half an object, misty vision, fog before the eyes), 136 and reversible corneal opacities136 also reported.

Dose-related retinopathy reported, which may progress even after the drug is discontinued.136 Retinal changes may be reversible if detected early, but usually are permanent and may rarely result in blindness.a

Risk factors for development of retinopathy during chloroquine treatment include age, duration of treatment, and high daily and/or cumulated dosage.136

Whenever long-term treatment contemplated, perform initial (base line) and periodic ophthalmologic examinations, including visual acuity, slit-lamp, funduscopic, and visual field tests.136

Immediately discontinue chloroquine 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.136

Nervous System Effects

Mild and transient headache,136 polyneuritis,136 fatigue,a nervousness,a anxiety,136 apathy,a irritability,a agitation,136 aggressiveness,a confusion,136 insomnia,136 delirium,136 and hallucinations136 have occurred.

Personality changes,136 depression,136 and psychosis,136 reported rarely.

Acute extrapyramidal disorders (e.g., dystonia, dyskinesia, tongue protrusion, torticollis) may occur;136 usually resolve after drug discontinued and/or patient receives symptomatic treatment.136

Seizures reported; advise patients with a history of epilepsy about the risk.136

Neuromuscular Effects

Skeletal muscle myopathy or neuromyopathy occur rarely; neuromyopathy is manifested as slowly progressing weakness which first affects proximal muscles of lower extremities.136

Patients receiving prolonged therapy should be questioned and examined periodically for evidence of muscular weakness; test knee and ankle reflexes.136

Discontinue chloroquine if muscular weakness occurs.136

Patients with Psoriasis or Porphyria

May exacerbate psoriasis and precipitate a severe attack in patients with the disease.136 Use in psoriasis patients only if potential benefits outweigh risks.136

May exacerbate porphyria.136 Use in patients with porphyria only if potential benefits outweigh risks.136

Sensitivity Reactions

Hypersensitivity Reactions

Erythema multiforme,136 Stevens-Johnson syndrome,136 toxic epidermal necrolysis,136 exfoliative dermatitis,136 and similar desquamation-type adverse events136 reported rarely.

Urticaria,136 anaphylactic/anaphylactoid reaction including angioedema,136 and drug rash with eosinophilia and systemic symptoms (DRESS syndrome)136 also reported.

General Precautions

Hematologic Effects

Aplastic anemia, pancytopenia, reversible agranulocytosis, thrombocytopenia, and neutropenia reported rarely.136

Periodically monitor CBCs in patients receiving prolonged treatment.136 Consider discontinuing chloroquine if any severe blood disorder occurs and is not attributable to the disease being treated.136

Use with caution in patients with G-6-PD deficiency.136

Otic Effects

Nerve-type deafness, usually irreversible, reported after prolonged therapy with high dosage.136 a Tinnitus and reduced hearing reported in patients with pre-existing auditory damage.136

Use with caution in patients with preexisting auditory damage.136 Discontinue chloroquine immediately and closely observe patient if any hearing defects occur.136

Hepatic Effects

Hepatitis and increased liver enzymes reported.136

Specific Populations

Pregnancy

Category C.c

Has been used for prophylaxis and treatment of malaria in pregnant women without evidence of adverse effects on the fetus.107 108 109 115 121

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.136

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

Because malaria infection in pregnant women is associated with high risks of maternal and perinatal morbidity and mortality (e.g., miscarriage, premature delivery, low birth weight, congenital infection and/or perinatal death), CDC recommends prompt chloroquine treatment in pregnant women with uncomplicated malaria caused by P. malariae, P. ovale, chloroquine-susceptible P. falciparum, or chloroquine-susceptible P. vivax.143

Because use of primaquine should be deferred during pregnancy, CDC recommends that pregnant women being treated for P. ovale or P. vivax malaria receive chloroquine prophylaxis for the duration of the pregnancy (after the initial chloroquine treatment regimen) until primaquine can be given after delivery to provide a radical cure.143 144

Lactation

Distributed into milk.122 123 124 136 Discontinue nursing or the drug.136

Amount of drug present in 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.136 Fatalities reported following accidental ingestion of relatively small doses.136

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.136

Substantially eliminated by kidneys; possible increased risk of toxicity in patients with impaired renal function.136 Select dosage with caution and assess renal function periodically since geriatric patients are more likely to have renal impairment.136

Hepatic Impairment

Concentrates in the liver; use with caution in patients with hepatic disease or alcoholism and in those receiving known hepatotoxic drugs.136

Renal Impairment

Substantially eliminated by kidneys; possible increased risk of toxicity in patients with impaired renal function.

Common Adverse Effects

Ocular effects; skeletal muscle myopathy or neuromyopathy; GI effects (anorexia, nausea, vomiting, diarrhea, abdominal cramps); dermatologic effects (pleomorphic skin eruptions, skin and mucosal pigmentary changes).136

Interactions for Chloroquine Phosphate

Specific Drugs

Drug

Interaction

Comments

Ampicillin

Possible reduced ampicillin bioavailability136

Administer chloroquine at least 2 hours before or after ampicillin136

Antacids

Possible reduced GI absorption of chloroquine136

Administer chloroquine at least 4 hours before or after antacids136

Cimetidine

Possible inhibition of chloroquine metabolism resulting in increased concentrations of the antimalarial136

Avoid concomitant use136

Cyclosporine

Possible increased cyclosporine concentrations136

Closely monitor serum cyclosporine concentrations; if necessary, discontinue chloroquine136

Mefloquine

Serious ECG abnormalities, including QTc interval prolongation, may occur; increased risk for torsades de pointes or other serious ventricular arrhythmias190

Increased risk of seizures136 190

Do not administer mefloquine until ≥12 hours after last dose of chloroquine190

Praziquantel

Possible decreased praziquantel concentrations184

Rabies vaccine

Possible interference with immune response to intradermally administered human diploid-cell rabies vaccine (HDCV) (no longer commercially available in US)116 117 136 182

Although intradermal HDCV no longer commercially available in US, consider that individuals traveling outside of US who are exposed to rabies may receive postexposure prophylaxis regimens that include rabies vaccines not commercially available in US182

Typhoid vaccine

Oral live typhoid vaccine (Vivotif): Potential interference with immune response to the vaccine;173 no evidence of altered anti-S. typhi immune response in healthy adults173

Chloroquine Phosphate Pharmacokinetics

Absorption

Bioavailability

Rapidly and almost completely absorbed from GI tract following oral administration;a 136 peak plasma concentrations generally attained within 1–2 hours.a

Food

Bioavailability of chloroquine is greater when administered with food;a rate of absorption is unaffected but peak plasma concentrations and AUCs are higher.a

Distribution

Extent

Widely distributed into body tissues.a

Chloroquine binds to melanin-containing cells in the eyes and skin; skin concentrations of the drug are considerably higher than plasma concentrations.a Also concentrates in erythrocytes and binds to platelets and granulocytes.a

Crosses placenta in mice.136 Distributed into milk.122 123 124 136

Plasma Protein Binding

50–65%.106

Elimination

Metabolism

Partially metabolized; major metabolite is desethylchloroquine.122 123 124 136 147 Desethylchloroquine also has antiplasmodial activity, but is slightly less active than chloroquine.114

Elimination Route

Chloroquine and its metabolites slowly excreted by the kidneys; unabsorbed drug is excreted in feces.a

Up to 70% of a dose is excreted unchanged in urine and up to 25% of dose may be excreted in urine as desethylchloroquine.a Small amounts of chloroquine may be present in urine for weeks, months, and occasionally years after the drug is discontinued.a

Half-life

Usually 72–120 hours.a

Serum concentrations decline in a biphasic manner and terminal half-life increases with increasing doses.a Terminal half-life is 3.1 hours after a single 250-mg oral dose, 42.9 hours after a single 500-mg oral dose, and 312 hours after a single 1-g oral dose.a

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C) in tight container.136

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 Gametocytocidal 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.115 143 145 154 156 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

  • Active in vitro against the trophozoite form of Entamoeba histolytica.a Acts as a tissue amebicide.a

  • 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 chloroquine out of reach of children since they are especially sensitive to 4-aminoquinoline derivatives.136

  • For prevention of malaria, necessity of starting chloroquine prophylaxis 1–2 weeks before arriving in an area with malaria and continuing during stay 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

  • Advise patients with a history of epilepsy about the risk of seizures.136

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.136

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.136

  • Importance of informing patients of other important precautionary information.136 (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

Chloroquine Phosphate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

150 mg (of chloroquine)*

Chloroquine Phosphate Tablets

300 mg (of chloroquine)*

Aralen Phosphate

Sanofi-Aventis

Chloroquine Phosphate Tablets

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.

Aralen 500MG Tablets (SANOFI-AVENTIS U.S.): 25/$190.00 or 75/$545.96

Chloroquine Phosphate 250MG Tablets (GLOBAL PHARMACEUTICAL CORP): 30/$72.99 or 90/$205.97

Chloroquine Phosphate 500MG Tablets (WEST-WARD): 7/$36.99 or 21/$108.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions March 5, 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.

101. Trigg PI, Wensdorfer WH, Sheth UK et al. Intramuscular chloroquine in children. Lancet. 1984; 2:288. [IDIS 188799] [PubMed 6146836]

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]

106. White NJ. Clinical pharmacokinetics of antimalarial drugs. Clin Pharmacokinet. 1985; 10:187-215. [IDIS 202191] [PubMed 3893840]

107. Chow AW, Jewesson PJ. Pharmacokinetics and safety of antimicrobial agents during pregnancy. Rev Infect Dis. 1985; 7:287-313. [IDIS 200121] [PubMed 3895351]

108. Public Health Laboratory Service Malaria Reference Laboratory. Prevention of malaria in pregnancy and early childhood. BMJ. 1984; 289:1296-7. [IDIS 192762] [PubMed 6437523]

109. Wolfe MS, Cordero JF. Safety of chloroquine in chemosuppression of malaria during pregnancy. BMJ. 1985; 290:1466-7. [IDIS 201367] [PubMed 3922534]

110. Akintonwa A, Odutola TA, Edeki T et al. Hemodialysis clearance of chloroquine in uremic patients. Ther Drug Monit. 1986; 8:285-7. [IDIS 220380] [PubMed 3750371]

114. Verdier F, LeBras J, Clavier F et al. Blood levels and in vitro activity of desethylchloroquine against Plasmodium falciparum. Lancet. 1984; 1:1186-7. [IDIS 185836] [PubMed 6144914]

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. Taylor DN, Wasi C, Bernard K. Chloroquine prophylaxis associated with a poor antibody response to human diploid cell rabies vaccine. Lancet. 1984; 1:1405. [IDIS 186824] [PubMed 6145850]

117. Pappaioanou M, Fishbein DB, Dreesen DW et al. Antibody response to preexposure human diploid-cell rabies vaccine given concurrently with chloroquine. N Engl J Med. 1986; 314:280-4. [IDIS 209991] [PubMed 3510393]

119. Ratliff NB, Estes ML, Myles JL et al. Diagnosis of chloroquine cardiomyopathy by endomyocardial biopsy. N Engl J Med. 1987; 316:191-3. [IDIS 224846] [PubMed 3796692]

120. Piette JC, Guillevin L, Chapelon C et al. Chloroquine cardiotoxicity. N Engl J Med. 1987; 317:710-1. [IDIS 233346] [PubMed 3627179]

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

122. Edstein MD, Veenendaal JR, Newman K et al. Excretion of chloroquine, dapsone and pyrimethamine in human milk. Br J Clin Pharmacol. 1986; 22:733-5. [IDIS 224280] [PubMed 3567020]

123. Ogunbona FA, Onyeji CO, Bolaji OO et al. Excretion of chloroquine and desethylchloroquine in human milk. Br J Clin Pharmacol. 1987; 23:473-6. [IDIS 228665] [PubMed 3580253]

124. Ette EI, Essien EE, Ogonor JI et al. Chloroquine in human milk. J Clin Pharmacol. 1987; 27:499-502. [IDIS 233119] [PubMed 3655001]

128. White NJ, Miller KD, Churchill FC et al. Chloroquine treatment of severe malaria in children: pharmacokinetics, toxicity, and new dosage recommendations. N Engl J Med. 1988; 319:1493-500. [IDIS 248321] [PubMed 3054558]

133. Krogstad DJ, Herwaldt BL. Chemoprophylaxis and treatment of malaria. N Engl J Med. 1988; 319:1538-40. [IDIS 248326] [PubMed 3185677]

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

136. Sanofi-Aventis. Aralen (chloroquine phosphate) tablets prescribing information. Bridgewater, NJ; 2013 Mar.

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.

145. Whitby M, Wood G, Veenendaal JR et al. Chloroquine-resistant Plasmodium vivax. Lancet. 1989; 2:1395. [IDIS 261420] [PubMed 2574333]

147. Panisko DM, Keystone JS. Treatment of malaria: 1990. Drugs. 1990; 39:160-89. [PubMed 2183998]

148. White NJ. Drug treatment and prevention of malaria. Eur J Clin Pharmacol. 1988; 34:1-14. [IDIS 242316] [PubMed 3282892]

149. White NJ. Antiparasitic drugs in children. Clin Pharmacokinet. 1989; 17(Suppl 1):138-55. [PubMed 2692937]

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]

154. Collignon P. Chloroquine resistance in Plasmodium vivax. J Infect Dis. 1991; 164:222-3. [IDIS 284165] [PubMed 2056216]

156. Schwartz IK, Lackritz EM, Patchen LC. Chloroquine-resistant Plasmodium vivax from Indonesia. N Engl J Med. 1991; 324:927. [IDIS 279271] [PubMed 2000121]

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.

171. Mirochnick M, Barnett E, Clarke DF et al. Stability of chloroquine in an extemporaneously prepared suspension stored at three temperatures. Ped Infect Dis J. 1994; 13:827-8.

173. Berna Products. Vivotif (typhoid vaccine live oral Ty21a) prescribing information. Coral Gables, FL; 2006 Aug.

180. Baguet JP, Tremel F, Fabre M. Chloroquine cardiomyopathy with conduction disorders. Heart. 1999; 81:221-3. [IDIS 423686] [PubMed 9922366]

181. Reuss-Borst M, Berner B, Wulf G et al. Complete heart block as a rare complication of treatment with chloroquine. J Rheumatol. 1999; 26:1394-5. [IDIS 429747] [PubMed 10381062]

182. Centers for Disease Control and Prevention. Human rabies prevention—United States, 1999: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 1999; 48(No. RR-1):1-21.

184. Bayer Healthcare Pharmaceuticals Inc. Biltricide (praziquantel) film-coated tablets prescribing information. Wayne, NJ; 2011 Apr.

185. Sarkany RP. The management of porphyria cutanea tarda. Clin Exp Dermatol. 2001; 26:225-32. [PubMed 11422163]

186. 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.

187. Badminton MN, Elder GH. Management of acute and cutaneous porphyrias. Int J Clin Pract. 2002; 56:272-8. [IDIS 482137] [PubMed 12074210]

188. Baltzan M, Mehta S, Kirkham TH et al. Randomized trial of prolonged chloroquine therapy in advanced pulmonary sarcoidosis. Am J Respir Crit Care Med. 1999; 160:192-7. [IDIS 432954] [PubMed 10390399]

189. Fazzi P. Pharmacotherapeutic management of pulmonary sarcoidosis. Am J Respir Med. 2003; 2:311-20. [PubMed 14719997]

190. Teva Pharmaceuticals. Mefloquine hydrochloride tablets prescribing information. Sellersville, Pa; 2013 Jun.

a. AHFS Drug Information 2004. McEvoy GK, ed. Chlorquine Hydrochloride and Chloroquine Phosphate. Bethesda, MD: American Society of Health-System Pharmacists; 2004:822-7.

c. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 6th ed. Philadelphia; PA: Lippincott Wiliams & Wilkins; 2002:239-41.

Hide
(web5)