gifting away Aralen Generic Name: Chloroquine Phosphate Class: Antimalarials VA Class: AP101 CAS Number: 50-63-5 Overview Side Effects Dosage Professional Interactions More Pregnancy Warnings Breastfeeding Warnings User Reviews Support Group Q & A Introduction Antimalarial; 4-aminoquinoline derivative. 136 Uses for Aralen 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 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 amebiasis 136 (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 Slideshow Flagyl Side Effects and What You Can Do About Them Aralen 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 Aralen 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 opacities 136 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 hallucinations 136 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 events 136 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 Aralen Specific Drugs Drug Interaction Comments Ampicillin Possible reduced ampicillin bioavailability 136 Administer chloroquine at least 2 hours before or after ampicillin 136 Antacids Possible reduced GI absorption of chloroquine 136 Administer chloroquine at least 4 hours before or after antacids 136 Cimetidine Possible inhibition of chloroquine metabolism resulting in increased concentrations of the antimalarial 136 Avoid concomitant use 136 Cyclosporine Possible increased cyclosporine concentrations 136 Closely monitor serum cyclosporine concentrations; if necessary, discontinue chloroquine 136 Mefloquine Serious ECG abnormalities, including QT c interval prolongation, may occur; increased risk for torsades de pointes or other serious ventricular arrhythmias 190 Increased risk of seizures 136 190 Do not administer mefloquine until 12 hours after last dose of chloroquine 190 Praziquantel Possible decreased praziquantel concentrations 184 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 US 182 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 adults 173 Aralen 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 hydroxychloroquine 109 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. 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 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 AHFS DI Essentials. Copyright 2017, Selected Revisions March 5, 2014. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, 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. [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. [PubMed 3893840] 107. Chow AW, Jewesson PJ. Pharmacokinetics and safety of antimicrobial agents during pregnancy. Rev Infect Dis . 1985; 7:287-313. [PubMed 3895351] 108. Public Health Laboratory Service Malaria Reference Laboratory. 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Antibody response to preexposure human diploid-cell rabies vaccine given concurrently with chloroquine. N Engl J Med . 1986; 314:280-4. [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. [PubMed 3796692] 120. Piette JC, Guillevin L, Chapelon C et al. Chloroquine cardiotoxicity. N Engl J Med . 1987; 317:710-1. [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. [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. [PubMed 3580253] 124. Ette EI, Essien EE, Ogonor JI et al. Chloroquine in human milk. J Clin Pharmacol . 1987; 27:499-502. [PubMed 3655001] 128. 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Chloroquine-resistant Plasmodium vivax . Lancet . 1989; 2:1395. [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. [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. [PubMed 2056216] 156. Schwartz IK, Lackritz EM, Patchen LC. Chloroquine-resistant Plasmodium vivax from Indonesia. N Engl J Med . 1991; 324:927. [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. [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. [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. [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. [PubMed 1039039 and ridicule
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