NON-FDA APPROVED USES
~Various generic manufacturers
*Prices represent cost per unit specified, are representative of "Average Wholesale Price" (AWP).
^Dosage is indicated in mg unless otherwise noted.
USUAL ADULT DOSING
500 mg of chloroquine phosphate is equivalent to 300 mg chloroquine base
- Treatment: 1 g (= 600 mg base) once, then 500 mg (= 300 mg base) at 6 h, 24 h and 48 h.
- Prophylaxis: (in chloroquine-sensitive regions): 500 mg (300mg base) PO starting one week prior to entry, continue once weekly and then four weeks after leaving the endemic region.
- 1 g (= 600 mg base) daily for 2 days, followed by 500 mg (=300 mg base) daily for 2-3 weeks.
ADULT RENAL DOSING
DOSING IN HEMODIALYSIS
DOSING IN PERITONEAL DIALYSIS
DOSING IN RENAL REPLACEMENT THERAPY
Other Adult Renal Dosing Information
No renal adjustment is recommended, however use caution in patients with renal impairment due to very long half-life. Close monitoring for adverse events is recommended.
USUAL PEDIATRIC DOSING
500 mg of chloroquine phosphate is equivalent to 300 mg chloroquine base.
- COVID-19: Chloroquine is currently under investigation for the prevention and treatment of COVID-19. Safety and efficacy have not been established in pediatric patients for this indication.
- Treatment: 16.6 mg/kg chloroquine phosphate (max initial dose of chloroquine phosphate = 1000 mg), followed by 8.3 mg/kg chloroquine phosphate (max subsequent dose of chloroquine phosphate= 500 mg) administered at 6, 24, and 48 hours after the initial dose (total of 4 doses).
- Prophylaxis (in chloroquine-sensitive regions): 8.3 mg/kg chloroquine phosphate (max dose of chloroquine phosphate = 500 mg) PO starting 1-2 weeks prior to entry, continue once weekly and then 4 weeks after leaving the endemic region.
- Extraintestinal amebiasis, liver abscess: 16.6 mg/kg chloroquine phosphate (max initial dose of chloroquine phosphate = 1000 mg) once daily for 21 days.
PEDIATRIC RENAL DOSING
No dosage adjustments are provided per the manufacturer, however renal dosing adjustments are recommended in adult patients. Monitor patients with renal dysfunction carefully for adverse effects.
ADVERSE DRUG REACTIONS
- Chloroquine is contraindicated for patients with preexisting retinopathy of the eye or known hypersensitivity to the 4-aminoquinoline compound. Short-term use (e.g., 5-10 days) is safe even in patients with preexisting retinal disease.
- Use of chloroquine in patients with psoriasis may precipitate a severe attack of psoriasis.
- Gastrointestinal complaints: diarrhea, anorexia, nausea, abdominal cramps, vomiting, loss of appetite
- Skin rash, pruritus
- Dizziness, headache, confusion
- Abnormal liver function tests
- Sensory-motor disorders
- Visual disturbances
- Chloroquine can prolong the PR, QRS and QTc intervals, especially in patients with underlying risk factors or use in combination with other QT-prolonging drugs.
- In one systemic review of cardiac toxicity (n=127) conduction disorders were the most common. The median duration of treatment of 7 years (min 3 days –max of 35 years).
- Cardiomyopathy has been rarely reported with high daily dosages of chloroquine.
- Severe hypoglycemia, especially in diabetics on antidiabetic medications
- Bone marrow suppression
- Fulminant hepatic failure
- Extrapyramidal reactions
- Suicidal behavior
- Retinal toxicity is generally dose-related and NOT reversible. Retinal damages usually occur with high daily doses >2.3 mg/kg base of actual body weight, impaired renal function, elderly patients, duration of treatment >5 years, and concurrent treatment with tamoxifen citrate.
- Pigmentary changes in skin and mucous membranes, bleaching of hair, and alopecia
- Hemolytic anemia in patients with G6PD deficiency- the manufacturer recommends using caution. However, one retrospective review no hemolysis was reported in patients who were G6PD deficient and were on hydroxychloroquine long term.
Effect of Interaction
Antacids may reduce the absorption of chloroquine
Separate co-administration by 4-hour interval
Antidiabetic drugs and insulin
Chloroquine may enhance the effects of a hypoglycemic treatment
Reduction in doses of antidiabetic agents may be needed
The activity of antiepileptic drugs might be impaired if co-administered with chloroquine
Monitor for seizures if coadministration can not be avoided
Cimetidine can inhibit the metabolism of chloroquine and increase serum concentrations
Avoid combination if possible or monitor for toxicity if the combination can not be avoided
An increased plasma cyclosporine level was reported with co-administration with hydroxychloroquine which would also be expected for chloroquine
Monitor cyclosporin serum levels in patients receiving
Chloroquine may increase digoxin serum levels
Monitor digoxin serum levels in patients receiving
Co-administration of chloroquine with other antimalarials that are known to lower the convulsion threshold (e.g. mefloquine) may increase the risk of convulsions
Avoid co-administration if possible or monitor for seizures if coadministration can not be avoided
Chloroquine has been reported to reduce the bioavailability of praziquantel
Chloroquine may decrease rabies-neutralizing antibody titer with co-administration
- P. ovale, P. malariae, and chloroquine-sensitive P. falciparum and P. vivax
- Tropheryma whipplei
- Coxiella burnetii
- E. histolytica
- It has modest activity in vitro against HIV alone and synergistic with select antivirals. It enhances HIV-1 infection in non-CD4 cells, not recommended for the treatment of HIV.
- In vitro studies demonstrated the activity of chloroquine against a range of other viruses: coronaviruses, influenza, hepatitis, human herpesviruses (HSV, VZV), flaviviruses (dengue, chikungunya), etc.
- Clinical trials failed to demonstrated efficacy against influenza, dengue, and chikungunya.
- Data on chloroquine in vitro activity against SARS-CoV-2 are conflicting. In a recent in vitro PBPK model, hydroxychloroquine was more potent than chloroquine in decreasing viral replication of SARS-CoV-2. Unfortunately in another study chloroquine did not show efficacy in inhibiting viral replication in a mouse SARS-CoV model.
- Chloroquine is not effective against chloroquine-resistant strains of P. falciparum and is not active against the exo-erythrocytic forms of P. vivax, P. ovale and P. malariae.
- Resistance to chloroquine first emerged in the late 1950s in Thailand and Colombia, then in the 1970s in New Guinea and eastern sub-Saharan Africa.
- Today, resistance P. falciparum occurs everywhere except in Central America west of Panama Canal, Haiti, Dominican Republic, and most of the Middle East.
- Resistance to chloroquine by P. vivax has also emerged in New Guinea, Indonesian archipelago and sporadic in the rest of Asia, and rare in South America.
- Latest information on chloroquine resistance in the world can be found www.wwarn.org
- Chloroquine belongs to a 4-aminoquinoline antibacterial class. It is a weak base and may exert its effect by concentrating the acid vesicles of the parasite and by inhibiting polymerization of heme, although the exact mechanism against Plasmodium is unknown.
- It accumulates in lymphocytes and macrophages resulting in anti-inflammatory properties, which is the main reason for its use in rheumatoid arthritis and lupus erythematosus diseases.
- Chloroquine increases endosomal pH required for virus/cell fusion, as well as interfering with the glycosylation of cellular receptors of SARS-CoV.
- Against COVID-19, chloroquine functioned at both entry and at post-entry stages of infection in Vero E6 cells.
- Chloroquine decreases the pH and confers antiviral effects against SARS-CoV-2.
- Furthermore, chloroquine has an immunomodulating effect, it reduces T-cell activation, differentiation and expression of co-stimulatory proteins and cytokines produced by T-cells and B- cells (e.g. IL-1, IL-6).
Metabolism and Excretion
Hepatic metabolism to desethyl metabolite. 41- 47% of unchanged drug and 7-12% of the metabolite are excreted unchanged in the urine (detected in urine up to 119 days after a single dose).
Cmax, Cmin, and AUC
26 mg of chloroquine base in four divided doses over 72 hours resulted in levels above 1mmol/L (note that mean toxic dose is 4.7 mg/dl).
- Very large Vd, up to 800 L/kg
- Widely distributed in body tissues such as eyes, brain, heart, kidney, liver and lungs. High levels attained in erythrocytes.
DOSING FOR DECREASED HEPATIC FUNCTION
Use with caution in patients with hepatic impairment. No dosing adjustment is recommended by the manufacturer, but close monitoring for adverse events is recommended.
- The use of chloroquine in pregnancy without an increase in the rate of birth defects has been reported in the literature. In a report of 169 infants exposed to in utero to 300 mg of chloroquine weekly throughout pregnancy did not result in increase teratogenicity. Chloroquine is the antimalarial prophylaxis considered probably safe in pregnancy and hydroxychloroquine is generally recommended for pregnant patients with an autoimmune disease.
- Embryonic deaths and ocular malformations in the offspring have been reported when pregnant rats received large doses of chloroquine.
BREAST FEEDING COMPATIBILITY
Chloroquine is excreted in breast milk (2.8%). The American Academy of Pediatrics considers chloroquine to be compatible with breastfeeding, but exposure inadequate for infant chemoprophylaxis. Separate chemoprophylaxis for the infant is required.
- Chloroquine is a 4-aminoquinoline derivative that has been used extensively for the treatment and prevention of malaria since 1946. Today its use for malaria is limited due to widespread resistance in P. falciparum and increasing resistance to P. vivax. Furthermore, chloroquine has fallen out of favor due to the availability of hydroxychloroquine (hydroxy analog of chloroquine) that is better tolerated.
- Chloroquine is currently in shortage in the U.S.
- Retinopathy is one of the most serious adverse events associated with chloroquine and it is NOT reversible but appears not to be an issue with short-term therapy.
- The American Academy of Ophthalmology recommends screening for chloroquine-related retinopathy: examination prior to therapy initiation to rule out preexisting maculopathy and annual screening after 5 years for patients on acceptable doses and without major risk factors.
- Chloroquine is recommended for the treatment of uncomplicated malaria caused by chloroquine-sensitive P. falciparum or P. vivax; and P. malariae, P. knowlesi, P. ovale from all regions. For the treatment of P. ovale and. P. vivax is used in combination with primaquine phosphate or tafenoquine. Primaquine and tafenoquine are needed to eradicate hypnozoites in the liver in order to prevent relapses.
- It is also one of the agents that can be used for malaria prophylaxis in select regions (Central America west of Panama Canal, Haiti, and the Dominican Republic). It must be started 1-2 weeks prior to travel, during travel (weekly) and for 4 weeks after leaving an endemic area.
- Chloroquine is used in combination with doxycycline for the treatment of C. burnetii and T. whipplei; it has been shown to restore doxycycline bactericidal activity against C. burnetii and T. whippleiin vitro (doxycycline, when used alone, is bacteriostatic against these pathogens). Hydroxychloroquine is preferred over chloroquine due to its long-term improved tolerance.
- Chloroquine has been used in a recent COVID-19 outbreak. Limited available data are largely based on in vitro studies, and a research letter and news reports from China.
- On March 28th, 2020, FDA issued Emergency Use Authorization for use of chloroquine phosphate or hydroxychloroquine sulfate supplied from the Strategic National Stockpile (SNS) for the treatment of COVID-19. According to FDA, “chloroquine phosphate may only be used to treat adult and adolescent patients who weigh 50 kg or more and are hospitalized with COVID-19, for whom a clinical trial is not available, or participation is not feasible”.
- In one in vitro study, activity against COVID-19 (SARS-CoV-2) was less potent for chloroquine compared to hydroxychloroquine.
- In a small, observational, non-randomized study (n=36) patients with SARS-CoV2 infection, administration of hydroxychloroquine 200 mg q8h for 10 days (n=20) resulted in higher clearance of virus (70%) on day 6 compared to controls (12.5%). Six patients also received azithromycin, and authors argued in a post-hoc analysis that the addition of azithromycin resulted in even higher, but statistically non-significant clearance. This study, however, has many limitations including small sample size, exclusions form analysis patients who were lost to follow-up (e.g. escalation of care, death), no clinical outcomes were reported or colation of viral clearance and clinical outcomes has been made.
- A pilot RCT of 30 patients comparing HCQ v. placebo, found that on day 7, COVID-19 nucleic acid of throat swabs was negative in 13 (86.7%) cases in the HCQ group and 14 (93.3%) cases in the control group (P >0.05). There no significant clinical difference between the groups. The study suggests that if HCQ has an effect it is at most modest, so larger studies need to be performed.
- Larger and properly designed studies are needed to determine the benefits of hydroxychloroquine in the treatment of COVID-19-positive patients and the role of combination therapy (e.g. with azithromycin).
Efficacy against other viruses
- Chloroquine have been found to have in vitro activity against many viruses other than SARS-CoV-2. However, clinical trials failed to demonstrate efficacy against influenza, dengue, ebola. More recently chloroquine has shown to delay clearance of the chikungunya virus.
- Rarely used today due to availability of other highly effective agents that are better tolerated (e.g. metronidazole)
Basis for recommendation
- CDC Guidelines for the treatment of malaria: https://www.cdc.gov/malaria/diagnosis_treatment/clinicians1.html (accessed 4/7/2020)
Comment: Chloroquine is recommended in combination with primaquine for the treatment of uncomplicated malaria caused by chloroquine-sensitive P. falciparum or P. vivax, and P. malariae, P. knowlesi, P. ovale from all regions.
- Zhou D, Dai SM, Tong Q. COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression. J Antimicrob Chemother. 2020. [PMID:32196083]
Comment: A brief review paper proving in great detail mechanism of action of chloroquine/hydroxychloroquine against SARS-CoV-2 virus and safety of both agents.
- Yao X, Ye F, Zhang M, et al. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020. [PMID:32150618]
Comment: In vitro study (PBPK model) suggesting that hydroxychloroquine is more potent than chloroquine in decreasing viral replication. EC50 values for chloroquine were >100 and 18.01 mcg at 24 and 48 hours, while EC50 values for hydroxychloroquine were 6.25 and 5.85 mcg at 24 and 48 hours. The inhibitory chloroquine was poor, the inhibition did not exceed 50%. The Efficacy was found to be concentration-dependent. Hydroxychloroquine was also found to have higher lung concentrations on days 1, 3, 5, and 10 compared to chloroquine.
- Cortegiani A, Ingoglia G, Ippolito M, et al. A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. J Crit Care. 2020. [PMID:32173110]
Comment: A systematic review of current data supporting the use of chloroquine and hydroxychloroquine for COVID-19: 6 articles (one narrative letter, one in-vitro study, one editorial, expert consensus paper, two national guideline documents) and numerous ongoing clinical trials, mostly in China. Data in this review is mostly pre-clinical and appropriately designed clinical trials on the effectiveness and safety of chloroquine and hydroxychloroquine for COVID-19 are desperately needed.
- Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020;14(1):72-73. [PMID:32074550]
Comment: In this letter from China, it was noted that “chloroquine was used in >100 patients and superior to the control treatment in inhibiting the exacerbation of pneumonia, improving lung imaging findings, promoting a virus-negative conversion, and shortening the disease course according to the news briefing”. The results were not published in a peer review journal and no information is available regarding patient characteristics, control treatment, etc.
- Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020. [PMID:32205204]
Comment: In this observational, non-randomized very small study (n=36) patients with SARS-CoV2 infection (6 patients were asymptomatic, 22 had URTI, 8 had LRTI) who received hydroxychloroquine 200 mg q8h for 10 days (n=20) were compared to controls (n=16, patients who did not receive hydroxychloroquine). On day 6, 70% of patients in hydroxychloroquine group clearance of virus compared to 12.5% in the control group (p=0.001). The study excluded from analysis patients who were lost to follow up (e.g. escalation of care, death, incomplete treatment). No clinical outcomes were reported. Six patients in this study also received azithromycin along with hydroxychloroquine. The authors concluded that combination therapy was more effective in clearing the virus, however, this was not statistically significant and groups were not well balanced at baseline (e.g. more patients in monotherapy had lower CT values).
- Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30(3):269-271. [PMID:32020029]
Comment: In this research letter, investigators note that chloroquine was highly effective in reducing viral replication at low molecular concentrations (EC50 = 1.13 mcg) using Vero E6 cells infected by SARS-CoV-2. Chloroquine does this by increasing the endosomal pH required for virus-cell fusion and interfering with the glycosylation of the cellular receptors of SARS-CoV.
- Chatre C, Roubille F, Vernhet H, et al. Cardiac Complications Attributed to Chloroquine and Hydroxychloroquine: A Systematic Review of the Literature. Drug Saf. 2018;41(10):919-931. [PMID:29858838]
Comment: A systematic review (n=127 patients) investigated cardiac complications attributed to chloroquine and hydroxychloroquine. 58.3% of patients received chloroquine and 39.4% received hydroxychloroquine with a median duration of treatment of 7 years (min 3 days –max of 35 years). Conduction disorders were the most common, followed by heart failure, ventricular hypertrophy, hypokinesia, heart failure, pulmonary arterial hypertension and valvular dysfunction. For 78 patients reported to have been withdrawn from treatment, 44.9% recovered normal heart function, 12.9% had irreversible damage and 30.8% death.
- Chu CS, Phyo AP, Lwin KM, et al. Comparison of the Cumulative Efficacy and Safety of Chloroquine, Artesunate, and Chloroquine-Primaquine in Plasmodium vivax Malaria. Clin Infect Dis. 2018;67(10):1543-1549. [PMID:29889239]
Comment: In this study of 644 patients with uncomplicated P. vivax malaria, artesunate cleared parasitemia significantly faster than chloroquine. Recurrence rates at day 28 were lowest with chloroquine-primaquine (0.5%; p < 0 .001), compared to chloroquine (8%) or artesunate (50%). Primaquine radical cure reduced the total recurrences by 92.4%.
- Roques P, Thiberville SD, Dupuis-Maguiraga L, et al. Paradoxical Effect of Chloroquine Treatment in Enhancing Chikungunya Virus Infection. Viruses. 2018;10(5). [PMID:29772762]
Comment: In this study efficacy of chloroquine was evaluated against the Chikungunya virus as a prophylactic agent in the non-human primate model and curative agent in a human cohort during an outbreak. In the animal model, there was a higher viremia and slower viral clearance (p < 0.003) with the administration of chloroquine, which correlated with type I IFN response and severe lymphopenia. Treatment also led to a delay in both Chikungunya virus-specific cellular and IgM responses. In humans, chloroquine treatment did not impact viremia or clinical parameters during the acute stage of the disease (day 1-14), but decreased levels of Eotaxine, IL-6, and MCP-1 over time levels (day 1-16).
- Mohammad S, Clowse MEB, Eudy AM, et al. Examination of Hydroxychloroquine Use and Hemolytic Anemia in G6PDH-Deficient Patients. Arthritis Care Res (Hoboken). 2018;70(3):481-485. [PMID:28556555]
Comment: A retrospective review of 275 patients who had G6PD levels measured and were on hydroxychloroquine, only 11 patients (4%) were G6PD deficient (all African American). Two patients developed hemolysis that occurred while they were not taking hydroxychloroquine. No hemolysis was reported in more than 700 months of hydroxychloroquine.
- Marmor MF, Kellner U, Lai TY, et al. Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision). Ophthalmology. 2016;123(6):1386-94. [PMID:26992838]
Comment: 2016 American Academy of Ophthalmology recommendations on screening for chloroquine and hydroxychloroquine-related retinopathy: examination prior to therapy initiation to rule out preexisting maculopathy and annual screening after 5 years for patients on acceptable doses and without major risk factors.
- Dowall SD, Bosworth A, Watson R, et al. Chloroquine inhibited Ebola virus replication in vitro but failed to protect against infection and disease in the in vivo guinea pig model. J Gen Virol. 2015;96(12):3484-3492. [PMID:26459826]
Comment: This study shows that chloroquine was not effective in protecting against Ebola virus infection and diseases in guinea pigs, despite in vitro inhibition of Ebola virus replication.
- Price RN, von Seidlein L, Valecha N, et al. Global extent of chloroquine-resistant Plasmodium vivax: a systematic review and meta-analysis. Lancet Infect Dis. 2014;14(10):982-91. [PMID:25213732]
Comment: Study methods and design confound in vitro determination; however, in available studies, 100% clearance document in humans receiving chloroquine.
- Paton NI, Lee L, Xu Y, et al. Chloroquine for influenza prevention: a randomised, double-blind, placebo controlled trial. Lancet Infect Dis. 2011;11(9):677-83. [PMID:21550310]
Comment: In this randomized, double-blind, placebo-controlled trial (N=1496), conducted in Singapore, chloroquine (500 mg daily for 1 week, then once per week for 12 weeks) was compared to placebo in the prevention of influenza. Chloroquine was not effective in preventing laboratory-confirmed influenza infection (4% vs. 5%, p=0.261). 45% of patients receiving chloroquine experienced adverse events, most commonly headache, dizziness, nausea, diarrhea and blurred vision.
- Tricou V, Minh NN, Van TP, et al. A randomized controlled trial of chloroquine for the treatment of dengue in Vietnamese adults. PLoS Negl Trop Dis. 2010;4(8):e785. [PMID:20706626]
Comment: In this randomized double-blind, placebo-controlled trial (n=307), a 3-day course of chloroquine was not effective in reducing the duration of Dengue virus viremia and NS1 antigenemia. There was a trend towards a lower incidence of dengue hemorrhagic fever in patients receiving chloroquine compared to placebo, however, use of chloroquine was associated with a higher rate of adverse events.
- Laufer MK, Thesing PC, Eddington ND, et al. Return of chloroquine antimalarial efficacy in Malawi. N Engl J Med. 2006;355(19):1959-66. [PMID:17093247]
Comment: Study documents return of efficacy of drug when not used after a hiatus of 12 years.
- Barnard DL, Day CW, Bailey K, et al. Evaluation of immunomodulators, interferons and known in vitro SARS-coV inhibitors for inhibition of SARS-coV replication in BALB/c mice. Antivir Chem Chemother. 2006;17(5):275-84. [PMID:17176632]
Comment: Chloroquine was inactive in mice against the SARS-CoV virus. It may be helpful if combined with another active agent due to its anti-inflammatory effects.
- Boulos A, Rolain JM, Raoult D. Antibiotic susceptibility of Tropheryma whipplei in MRC5 cells. Antimicrob Agents Chemother. 2004;48(3):747-52. [PMID:14982759]
Comment: We report here the first extensive study on the susceptibilities of three reference strains of Tropheryma whipplei to an antibiotic in cell culture by using a real-time PCR assay as previously described. A combination of doxycycline and hydroxychloroquine was bactericidal in vitro.
- Savarino A, Boelaert JR, Cassone A, et al. Effects of chloroquine on viral infections: an old drug against today's diseases? Lancet Infect Dis. 2003;3(11):722-7. [PMID:14592603]
The article discusses the mechanism and activity of chloroquine/hydroxychloroquine against viral infections such as HIV and SARS. Its immunomodulatory effects are also reviewed in detail: chloroquine/hydroxychloroquine suppresses the production/release of tumor necrosis factor and IL-6, which mediate the inflammatory complications of several viral diseases.
- Raoult D, Drancourt M, Vestris G. Bactericidal effect of doxycycline associated with lysosomotropic agents on Coxiella burnetii in P388D1 cells. Antimicrob Agents Chemother. 1990;34(8):1512-4. [PMID:2221859]
Comment: Doxycycline, when used as monotherapy, is bacteriostatic against C. burnetii in P388D1 cells due to acidic conditions of the phagolysosomes in which C. burnetii is located. However, when chloroquine was added, it leads to alkalization of C. burnetii-containing lysosomes which resulted in the sterilization of infection.
- Titus EO. Recent developments in the understanding of the pharmacokinetics and mechanism of action of chloroquine. Ther Drug Monit. 1989;11(4):369-79. [PMID:2662478]
Comment: Review paper summarizing studies related to the pharmacokinetics of chloroquine (published prior to 1989), dosing and mechanism of action in the treatment of malaria and rheumatoid arthritis.
- 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(5):280-4. [PMID:3510393]
Comment: This randomized trial demonstrates that co-administration of weekly chloroquine beginning 9 days before the first dose of rabies vaccine administration was negatively associated with log antibody titers.