brand name | preparation | manufacturer | route | form | dosage^ | cost* |
Aralen phosphate | Chloroquine phosphate | ~Various generic manufacturers | PO | tab | 250 mg | $2.82 |
PO | tab | 500 mg | $7.32-14.75 |
*Prices represent the specified cost per unit and the "Average Wholesale Price" (AWP).
^Dosage is indicated in mg unless otherwise noted.
500 mg of chloroquine phosphate is equivalent to 300 mg chloroquine base. 250 mg of chloroquine phosphate is equivalent to 150 mg chloroquine base.
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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.
Drug | Effect of Interaction | Recommendations/Comments |
Antacids | 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 |
Antiepileptic drugs | The activity of antiepileptic drugs might be impaired if co-administered with chloroquine. | Monitor for seizures if coadministration can not be avoided |
Cimetidine | 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. |
Cyclosporin | 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 |
Digoxin | Chloroquine may increase digoxin serum levels | Monitor digoxin serum levels in patients receiving |
Co-administration of chloroquine with other antimalarials 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. | Avoid coadministration | |
Chloroquine may decrease rabies-neutralizing antibody titer with co-administration[22] | Avoid coadministration |
89%
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).
50-65%
26 mg of chloroquine base in four divided doses over 72 hours resulted in levels above 1mmol/L (note that the mean toxic dose is 4.7 mg/dl).
Days-2 months[21]
Use with caution in patients with hepatic impairment. The manufacturer recommends no dosing adjustment, 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: CQ utilizes CYP2C8, CYP3A4/5 and CYP2D6; with the drug substrate, effects are reviewed with available information. Authors point out that a considerable proportion of the world population predicted to be ultra-rapid or poor metabolizers are identified as having high-risk phenotypes for either therapeutic failure or adverse drug reactions
Comment: The HERO-HCQ was a multicenter, double-blind, randomized, placebo-controlled study that included adult healthcare workers with potential exposure to patients with COVID-19. Subjects were randomized to receive placebo or hydroxychloroquine at a dose of 600 mg twice daily on day 1, followed by 400 mg daily for 29 days. The primary outcome was a composite of confirmed or suspected clinical infection with COVID-19 through 30 days, which the authors did not find a significant difference between the placebo and hydroxychloroquine groups (7.8% vs. 6.0%, respectively; 95% Cl –4.60-0.87; p=0.20). There was no significant difference in PCR-confirmed, symptomatic COVID-19 between the placebo and hydroxychloroquine groups (0.4% vs. 0.9%, respectively; 95% Cl –1.54-0.50; p=0.34). Furthermore, no significant difference in the incidence of serious adverse events to day 60 was noted between the two groups.
Comment: The HYCOVID trial was a double-blind, placebo-controlled, randomized study that included adult patients with PCR-confirmed COVID-19 infections 2 days before randomization. Patients were randomized to receive either placebo or hydroxychloroquine at the dose of 400 mg PO twice daily on day 1, followed by 200 mg PO twice daily for 8 days. The primary endpoint was the rate of the composite endpoint of mortality and initiation of invasive mechanical ventilation within 14 days following randomization, which the authors did not find a significant difference between the placebo and hydroxychloroquine groups (6.5% vs. 7.3%, respectively; relative risk 1.12; 95% Cl 0.45-2.80, p=0.82).
Comment: This randomized, double-blind, placebo-controlled clinical trial included adult healthcare workers with ongoing exposure to persons with COVID-19. Subjects were randomized to receive either placebo or hydroxychloroquine at a dose of 400 mg twice, separated by 6-8 hours, followed by 400 mg once weekly or 400 mg twice weekly for 12 weeks. The primary endpoint was a rate of PCR-confirmed COVID-19, which the authors did not find a significant difference between placebo and once weekly hydroxychloroquine (1.2% vs 0.8%, respectively; hazard ratio 0.65; 95% Cl 0.18-2.32), or twice weekly hydroxychloroquine (1.2% vs. 1.4%, respectively; hazard ratio 1.18; 95% Cl 0.40-3.51).
Comment: A study of available trial information found that the OR all-cause mortality for hydroxychloroquine was 1.11 (95% CI: 1.02, 1.20; I² = 0%; 26 trials; 10,012 patients) and for chloroquine was 1.77 (95% CI: 0.15, 21.13, I² = 0%; 4 trials; 307 patients). Enhanced mortality was seen with HCQ, not so with chloroquine, but the drug had no benefit.
Comment: The BCN-PEP-CoV2 trial was an open-label, randomized trial that included asymptomatic adults who had a recent history of close-contact exposure to a PCR-confirmed case patient with COVID-19 and had no COVID-19-like symptoms during the 2 weeks before enrollment. Subjects are randomized to either the standard-of-care or hydroxychloroquine group at a dose of 800 mg on day 1 followed by 400 mg daily for 6 days. The primary endpoint was the rate for PCR-confirmed, symptomatic COVID-19 episodes, in which the authors did not find a significant difference between the standard-of-care hydroxychloroquine groups (5.7% vs 6.2%, respectively; risk ratio 0.86; 95% Cl 0.52-1.42).
Comment: The WHO Solidarity Trial was a multicenter, open-label, randomized trial that included adult patients who were hospitalized with a diagnosis of COVID-19. Patients were randomized to five study groups: standard-of-care, remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a. For hydroxychloroquine, the regimen used was 800 mg at hour 0 and 6, followed by 400 mg twice daily starting at hour 12 for 10 days. The primary endpoint was the rate of in-hospital mortality, which the authors did not find a significant difference between the standard-of-care and hydroxychloroquine groups (9.27% vs. 10.98%, respectively; rate ratio 1.19; 95% Cl 0.89-1.59, p=0.23). Furthermore, hydroxychloroquine was not found to reduce the initiation of ventilation.
Comment: The RECOVERY trial was a multicenter, open-label, randomized trial that included adult patients hospitalized with COVID-19. Patients were randomized to either standard-of-care or hydroxychloroquine at a dose of 800 mg at hours 0 and 6, followed by 400 mg twice daily starting at hour 12 for 9 days or until discharge, whichever occurred earlier. The primary endpoint was all-cause mortality within 28 days after randomization, which the authors did not find a significant difference between the standard-of-care and hydroxychloroquine groups (25.0% vs. 27.0%, respectively; rate ratio 1.09; 95% Cl 0.97-1.23, p=0.15). However, the hydroxychloroquine group had a longer duration of hospitalization and a lower probability of being discharged within 28 days compared to the standard-of-care group.
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%.
Rating: Important
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. Of 78 patients reported to have been withdrawn from treatment, 44.9% recovered normal heart function, 12.9% had irreversible damage, and 30.8% died.
Rating: Important
Comment: In this study, the 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 (days 1-14) but decreased Eotaxine, IL-6, and MCP-1 overtime levels (days 1-16).
Rating: Important
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 recommends screening for chloroquine and hydroxychloroquine-related retinopathy: examination before therapy initiation to rule out preexisting maculopathy and annual screening after 5 years for patients on acceptable doses and without significant 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 documents 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 preventing influenza. Chloroquine was ineffective 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.
Rating: Important
Comment: In this randomized, double-blind, placebo-controlled trial (n=307), a 3-day chloroquine course was ineffective 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: The study documents the return of efficacy of the drug when not used after a hiatus of 12 years.
Comment: We report here the first extensive study on the susceptibilities of three reference strains of Tropheryma whipplei to an antibiotic in cell culture using a real-time PCR assay as previously described. A combination of doxycycline and hydroxychloroquine was bactericidal in vitro.
Comment: When used as monotherapy, doxycycline is bacteriostatic against C. burnetii in P388D1 cells due to the acidic conditions of the phagolysosomes in which C. burnetii is located. However, when chloroquine is added, it leads to the alkalization of C. burnetii-containing lysosomes, which sterilizes the 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.
Comment: CDC guidelines recommend using chloroquine to treat uncomplicated malaria due to chloroquine susceptible strains of P. vivax, P. ovale, P. malariae, or P. kwnowlesi.
Comment:
Since generic the package insert is rarely updated.