~Various generic manufacturers
*Prices represent cost per unit specified, are representative of "Average Wholesale Price" (AWP).
^Dosage is indicated in mg unless otherwise noted.
500 mg of chloroquine phosphate is equivalent to 300 mg chloroquine base
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.
500 mg of chloroquine phosphate is equivalent to 300 mg chloroquine base.
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.
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
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).
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).
Use with caution in patients with hepatic impairment. No dosing adjustment is recommended by the manufacturer, but close monitoring for adverse events is recommended.
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.
Efficacy against other viruses
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.
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.
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.
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.
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.
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).
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.
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.
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%.
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).
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.
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.
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.
Comment: Study methods and design confound in vitro determination; however, in available studies, 100% clearance document in humans receiving chloroquine.
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.
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.
Comment: Study documents return of efficacy of drug when not used after a hiatus of 12 years.
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.
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.
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.
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.
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.
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.
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