chloroquine

Chloroquine

Chloroquine also known as chloroquine phosphate or Aralen phosphate, is an aminoquinoline with antimalarial, anti-inflammatory, and potential chemosensitization and radiosensitization activities 1). Chloroquine is an antimalarial drug that was developed in 1934 and it is in the sulfonamides class of drugs. Chloroquine is related in structure to quinine but more potent against Plasmodium falciparum, ovale, malariae and vivax, and better tolerated than quinine. Chloroquine is FDA-approved for the treatment and prevention of uncomplicated malaria in countries where chloroquine-sensitive malaria (certain strains of Plasmodium falciparum, Plasmodium ovale, Plasmodium vivax, and Plasmodium malariae) is present 2). These countries include Mexico, areas of Central America to the west of the Panama Canal, the Caribbean, East Asia, as well as some Middle Eastern countries 3). Chloroquine is also effective in extraintestinal amebiasis and as an antiinflammatory agent for therapy of rheumatoid arthritis and systemic lupus erythematosus (SLE) and discoid lupus erythematosus (DLE) 4). Chloroquine has been replaced by hydroxychloroquine as an antiinflammatory agent in rheumatic diseases and these are unapproved, off-label uses. Chloroquine is currently administered orally when used as a prophylaxis for malaria, as well as for the treatment of chronic autoimmune diseases 5). Also, current research suggests that chloroquine may be helpful as an antitumor medication for the treatment of cancer in association with chemotherapy and radiation 6). Chloroquine’s potential chemosensitizing and radiosensitizing activities in cancer may be related to its inhibition of autophagy, a cellular mechanism involving lysosomal degradation that minimizes the production of reactive oxygen species (ROS) related to tumor reoxygenation and tumor exposure to chemotherapeutic agents and radiation. Chloroquine is available only with your doctor’s prescription.

Chloroquine is available in tablets of 250 and 500 mg in generic forms and under the brand name Aralen. The recommended dosage for prevention of malaria in adults is 500 mg once weekly (on exactly the same day of the week) starting 1 to 2 weeks before and continuing for at least 8 weeks after travel to an area where malaria is common. Your doctor will tell you how many tablets to take for each dose. If you are unable to start taking chloroquine for 2 weeks before traveling, your doctor may tell you to take double the dose right away (for the first dose). For treatment of sudden, severe attacks of malaria in adults, one dose is usually taken right away, followed by half the dose 6 to 8 hours later and then half the dose once a day for the next 2 days. Under severe or emergency cases of malaria, chloroquine can be administered parenterally 7). Some research has shown that parenteral chloroquine administration is potentially toxic; therefore, subcutaneous administration has been shown to be a more effective method in circumstances of severe malaria 8).

For prevention and treatment of malaria in infants and children, the amount of chloroquine phosphate is based on the child’s weight. Your doctor will calculate this amount and tell you how much chloroquine phosphate your child should receive.

When used as a treatment for extraintestinal amebiasis, chloroquine dosing 21 mg/kg for three weeks 9). It is usually taken in combination with other amebicides.

Chloroquine phosphate may cause an upset stomach. Take chloroquine phosphate with food. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Use chloroquine phosphate exactly as directed. Do not use more or less of it or use it more often than prescribed by your doctor.

Common side effects of chloroquine include headache, blurred vision, anorexia, nausea, diarrhea, skin rash and itching.

Keep all appointments with your doctor and the laboratory. Your doctor may order certain lab tests and electrocardiograms (ECG, a test to monitor your heart rate and rhythm) to check your response to chloroquine phosphate. Your doctor will also test your reflexes to see if you have muscle weakness that may be caused by the drug.

If you are taking chloroquine phosphate for a long period of time, your doctor will recommend frequent eye exams. It is very important that you keep these appointments. Chloroquine phosphate can cause serious vision problems. If you experience any changes in vision, stop taking chloroquine phosphate and call your doctor immediately.

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

Figure 1. Chemical structure of chloroquine

chloroquine chemical structure
Chloroquine Warnings

Chloroquine can cause dangerous effects on your heart, especially if you also use certain other medicines. Seek emergency medical attention if you have fast or pounding heartbeats and sudden dizziness (like you might pass out).

Taking chloroquine long-term or at high doses may cause irreversible damage to the retina of your eye that could progress to permanent vision problems. You may not be able to use chloroquine if you have a history of vision changes or damage to your retina.

Stop taking chloroquine and call your doctor at once if you have blurred vision, trouble focusing, distorted vision, blind spots, trouble reading, hazy or cloudy vision, increased sensitivity to light.

Notice

Chloroquine has been studied for the treatment and prevention of coronavirus disease 2019 (COVID-19).

On March 28, 2020, the Food and Drug Administration (FDA) granted an Emergency Use Authorization (EUA) for use of oral formulations of chloroquine to treat adults and adolescents who weigh at least 110 pounds (50 kg) and who are hospitalized with COVID-19, but who are unable to participate in a clinical study 10). However, FDA canceled this on June 15, 2020 because clinical studies showed that chloroquine is unlikely to be effective for treatment of COVID-19 in these patients and some serious side effects, such as irregular heartbeat, were reported 11).

The COVID-19 Treatment Guidelines Panel (the Panel) recommends against the use of chloroquine or hydroxychloroquine and/or azithromycin for the treatment of COVID-19 in hospitalized patients and in nonhospitalized patients 12). The FDA and the National Institutes of Health state that chloroquine should ONLY be taken for the treatment of COVID-19 under the direction of a doctor in a clinical study. Do not buy this medication online without a prescription. If you experience irregular heartbeats, dizziness, or fainting while taking chloroquine, call your local emergency services number for emergency medical treatment. If you have other side effects, be sure to tell your doctor.

Do not take chloroquine that is strictly intended for veterinary use – such as to treat fish in aquariums or for use in other animals – to treat or prevent COVID-19. The FDA reports that serious injury and death have been reported in people misusing these preparations 13).

Is chloroquine effective for COVID-19?

Coronavirus disease 2019 (COVID-19) is caused by the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus type 2), the cause of the global pandemic of respiratory illness. In laboratory tests and cell culture systems, both hydroxychloroquine and chloroquine have been shown to have a spectrum of antiviral activity that is believed to be due to interference with viral binding to glycoprotein cell receptors or inhibition of endosomal pH regulation, which inhibits fusion between SARS-CoV-2 and the host cell membrane 14). Hydroxychloroquine can prevent the SARS-CoV and SARS-CoV-2 viruses from attaching to and entering cells. Chloroquine inhibits glycosylation of the cellular angiotensin-converting enzyme 2 (ACE 2) receptor, which may interfere with the binding of SARS-CoV to the cell receptor 15). In vitro studies (test tube studies) have suggested that both chloroquine and hydroxychloroquine may block the transport of SARS-CoV-2 from early endosomes to endolysosomes, possibly preventing the release of the viral genome 16). Both chloroquine and hydroxychloroquine also have immunomodulatory effects, which have been hypothesized to be another potential mechanism of action for the treatment of COVID-19.

Azithromycin has antiviral and anti-inflammatory properties. When used in combination with hydroxychloroquine, it has been shown to have a synergistic effect on SARS-CoV-2 in vitro and in molecular modeling studies 17), 18). However, despite demonstrating antiviral activity in some in vitro systems, neither hydroxychloroquine plus azithromycin nor hydroxychloroquine alone reduced upper or lower respiratory tract viral loads or demonstrated clinical efficacy in a rhesus macaque model 19).

In face of the growing burden of severe illness posed by COVID-19, chloroquine and hydroxychloroquine were proposed as possibly effective in preventing or ameliorating the course and prevent mortality 20), 21), 22). However, multiple human clinical studies have provided data that hydroxychloroquine (Plaquenil) does not provide a medical benefit for hospitalized patients with COVID-19 23), 24), 25).

Use of hydroxychloroquine is controversial, and has been politicized in the U.S. by various groups. Mixed studies have reported both a positive and negative effect, and data may not be robust or reliable: it can include data from study reviews, nonrandomized groups, retrospective research, observational data or from a statistically small sample size of patients. Research for COVID-19 is often quick to be published in non-peer reviewed, preprint online services due to the urgency of the pandemic. However, in general, preprint data should not be used to guide clinical practice. In addition, some hydroxychloroquine studies have been retracted due to lack of confidence in the data, including a Lancet study 26) and one from the New England Journal of Medicine 27).

Hydroxychloroquine, chloroquine, and azithromycin are not approved by the Food and Drug Administration (FDA) for the treatment of COVID-19 28). Furthermore, in June 15, 2020, the FDA revoked the emergency use authorization (EUA) of oral hydroxychloroquine and chloroquine phosphate for the treatment of COVID-19 29). An emergency use authorization (EUA) can allow quicker access to critical medical products when there are no approved alternative options.

  • Based on an evaluation of the scientific data to date, the FDA concluded that chloroquine and hydroxychloroquine are not likely to be effective in the treatment of COVID-19 for the authorized uses in the EUA.
  • In addition, the risk for serious side effects with hydroxychloroquine and chloroquine phosphate are a concern. This includes the possibility of adverse cardiovascular (heart) events such as an abnormal heart rhythm which could be fatal.
  • Additional worldwide studies are still ongoing to assess the use of these agents for the treatment or prevention or COVID-19, including early-stage outpatient and use with supplements such as zinc or vitamin D or with azithromycin. However, the FDA states hydroxychloroquine should not be used outside of clinical trials in the U.S.

The World Health Organization (WHO) and the U.S. National Institutes of Health (NIH) have also stopped studies evaluating hydroxychloroquine for the treatment of COVID-19 due to a lack of benefit. Current NIH and US treatment guidelines do not recommend use of hydroxychloroquine and chloroquine phosphate for COVID-19 treatment outside of clinical studies.

Although earlier studies suggested that hydroxychloroquine could inhibit the SARs-CoV-2 virus and was more potent than chloroquine, recent studies do not support the use of hydroxychloroquine or chloroquine phosphate. The FDA stated on June 15, 2020 that the suggested dosing regimens for chloroquine and hydroxychloroquine are unlikely to kill or inhibit the virus that causes COVID-19 30).

Do studies show chloroquine is not effective for COVID-19?

Yes, multiple studies provide data that chloroquine is ineffective in the treatment of SARS-CoV-2, the virus that causes COVID-19 disease.

Hospitalized patients

In a large, randomized, controlled, open-label study evaluating a number of potential treatments for patients hospitalized with COVID-19 in the United Kingdom, the RECOVERY Trial from the University of Oxford 31). The RECOVERY study is being conducted by researchers at the University of Oxford in the UK (the hydroxychloroquine arm is now halted) 32). Hydroxychloroquine did not decrease 28-day mortality when compared to the usual standard of care 33). Patients who were randomized to receive hydroxychloroquine had a longer median hospital stay than those who received the standard of care. In addition, among patients who were not on invasive mechanical ventilation at the time of randomization, those who received hydroxychloroquine were more likely to subsequently require intubation or die during hospitalization than those who received the standard of care 34).

  • In the RECOVERY Trial, investigators reported that there was no beneficial effect or reduction of death in hospitalized patients with COVID-19 receiving hydroxychloroquine 35).
  • In this study, 1561 patients received hydroxychloroquine and were compared to 3155 patients receiving standard care only. No difference was found in the primary endpoint, which was the incidence of death at 28 days (26.8% hydroxychloroquine vs. 25% usual care).
  • In addition, hydroxychloroquine treatment was associated with an increased length of stay in the hospital and increased need for invasive mechanical ventilation.
  • Based on this data, investigators stopped enrollment in the RECOVERY hydroxychloroquine arm on June 5th, 2020 36).

The results from several additional large randomized controlled trials have been published; these trials have failed to show a benefit for hydroxychloroquine with or without azithromycin or azithromycin alone in hospitalized adults with COVID-19. In the Solidarity trial 37), an international randomized controlled platform trial that enrolled hospitalized patients with COVID-19, the hydroxychloroquine arm was halted for futility. There was no difference in in-hospital mortality between patients in the hydroxychloroquine arm and those in the control arm 38). Similarly, PETAL 39), a randomized, placebo-controlled, blinded study, was stopped early for futility. In this study, there was no difference in the median scores on the COVID Outcomes Scale between patients who received hydroxychloroquine and those who received placebo 40). Data from two additional randomized studies of hospitalized patients with COVID-19 did not support using hydroxychloroquine plus azithromycin over hydroxychloroquine alone 41), 42). In RECOVERY, azithromycin alone (without hydroxychloroquine) did not improve survival or other clinical outcomes when compared to the usual standard of care 43).

In addition to these randomized trials, data from large retrospective observational studies do not consistently show evidence of a benefit for hydroxychloroquine with or without azithromycin in hospitalized patients with COVID-19 44), 45), 46).

In a multicenter, randomized, open-label, controlled trial published in July 2020 by Cavalcanti and colleagues in the New England Journal of Medicine 47), hydroxychloroquine use was studied in patients who were hospitalized with mild-to-moderate COVID-19.

  • Patients received hydroxychloroquine (400 mg twice daily for 7 days), hydroxychloroquine with azithromycin (hydroxychloroquine 400 mg twice daily + azithromycin 500 mg once daily for 7 days), or standard care only.
  • The clinical status of these patients at day 15 was not improved as compared with the patients receiving only standard care.
  • In addition, researchers noted that prolonged QT intervals (which may lead to abnormal heart rates and death) and elevated liver enzymes were higher in patients receiving hydroxychloroquine, either with or without azithromycin.

A retrospective, observational study conducted from March to early May of 2020 48) did report a positive effect with hydroxychloroquine on hospitalized patient mortality, used alone and with azithromycin when compared to no treatment. The study authors note a limitation to their analysis was the retrospective, non-randomized, non-blinded study design 49).

  • Researchers looked at 2,541 patients, with a median total hospitalization time of 6 days.
  • Mortality, by treatment, was 20.1% for hydroxychloroquine + azithromycin, 13.5% for hydroxychloroquine alone, 22.4% for azithromycin alone, and 26.4% for neither drug. The primary cause of death was respiratory failure in 88% of patients.
  • Adjunct therapy with corticosteroids (methylprednisolone and/or prednisone) and anti-IL-6 tocilizumab was provided in 68% and 4.5% of patients, respectively.
  • Factors such as greater glucocorticoid use in the hydroxychloroquine groups and the nonrandomized study design suggested this data may be flawed and that prospective, randomized controlled studies were needed to validate these results.

Given the lack of a benefit seen in the randomized clinical trials, the COVID-19 Treatment Guidelines Panel (the Panel) recommends against using hydroxychloroquine or chloroquine and/or azithromycin to treat COVID-19 in hospitalized patients 50).

Nonhospitalized patients

Several randomized trials have not shown a clinical benefit for hydroxychloroquine in nonhospitalized patients with early, asymptomatic, or mild COVID-19 51), 52). In an open-label trial, Mitja et al. 53) randomized 307 nonhospitalized people who were recently confirmed to have COVID-19 to receive hydroxychloroquine or no antiviral treatment. Patients in the hydroxychloroquine arm received hydroxychloroquine 800 mg on Day 1 followed by 400 mg daily for an additional 6 days. The authors reported no difference in the mean reduction in SARS-CoV-2 RNA at Day 3 or the time to clinical improvement between the two arms 54). In another trial 55), treating patients who had asymptomatic or mild COVID-19 with hydroxychloroquine with or without azithromycin did not result in greater rates of virologic clearance (as measured by a negative polymerase chain reaction [PCR] result on Day 6).

A randomized, double-blind, placebo-controlled trial from Skipper and colleagues published in the Annals of Internal Medicine in July 2020 56) was conducted in 423 outpatients (not in the hospital) with early COVID-19.

  • Patients received oral hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 more days) or a placebo (inactive treatment).
  • Researchers found that over a 14 day period a change in symptom severity and the percent of patients with ongoing symptoms did not differ significantly between groups, signaling no effect from the hydroxychloroquine treatment.
  • However, side effects were significantly greater in the group receiving hydroxychloroquine compared to placebo (43% hydroxychloroquine versus 22% placebo). Rates of hospitalizations and deaths did not differ significantly.

An open-label, prospective, randomized trial compared oral azithromycin 500 mg once daily for 3 days plus standard of care to standard of care alone in nonhospitalized, high-risk, older adults who had laboratory-confirmed or suspected COVID-19 57). No differences were observed between the arms in the primary endpoints of time to first self-reported recovery and hospitalization or death due to COVID-19 58). These findings remained consistent in an analysis that was restricted to participants with positive SARS-CoV-2 PCR results. The study was ultimately halted due to futility 59). Similarly, in a preliminary report from ATOMIC-2, adding oral azithromycin 500 mg once daily to standard of care for 14 days did not reduce the risk of hospitalization or death among 292 participants with mild to moderate COVID-19 60).

While ongoing clinical trials are still evaluating the use of chloroquine, hydroxychloroquine, and azithromycin in outpatients, the existing data suggest that it is unlikely that clinical benefits will be identified for these agents. The COVID-19 Treatment Guidelines Panel (the Panel) recommends against the use of chloroquine or hydroxychloroquine and/or azithromycin for the treatment of COVID-19 in nonhospitalized patients 61).

Chloroquine study for prevention after exposure to COVID-19

A randomized, double-blind, placebo-controlled study published online in the New England Journal of Medicine in June 2020 62) looked at prevention of COVID-19 after exposure to the virus (post-exposure prophylaxis or PEP).

  • Researchers evaluated over 800 people in the U.S. and Canada who had been exposed to COVID-19. The primary outcome was the incidence of either laboratory-confirmed COVID-19 or illness compatible with the virus within 14 days.
  • Hydroxychloroquine was given as 800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 additional days. Patients started treatment within 4 days after exposure, defined as being in close contact with a COVID-19 patient for more than 10 minutes without protection.
  • Results showed that hydroxychloroquine did not prevent COVID-19 when compared to a placebo (used as post-exposure prophylaxis). The incidence of COVID-19 did not differ significantly between those who took hydroxychloroquine (11.8%) and those who took placebo (14.3%).
  • Side effects were more common in the hydroxychloroquine group (40.1% compared to 16.8% with placebo), but were not reported as serious. Common adverse events included nausea, loose stools, and stomach pain.
  • Limitations in this study 63) were many, and included inability to confirm self-reported COVID-19 exposure, adherence to study drug, starting drug up to 4 days after reported exposure to the virus, lack of survey completion, and enrollment of a lower-risk population.

Chloroquine special precautions before taking chloroquine

You should NOT use chloroquine if you are allergic to chloroquine phosphate, chloroquine hydrochloride, hydroxychloroquine (Plaquenil), primaquine, quinine, or any other drugs.

High doses or long-term use of chloroquine may cause irreversible damage to your retina (the membrane layer inside your eye that helps produce vision). This could progress to permanent vision problems. The risk of retinal damage is higher in people with pre-existing eye problems, kidney disease, or people who also take tamoxifen.

To make sure chloroquine is safe for you, tell your doctor if you have ever had:

  • vision changes or damage to your retina caused by an anti-malaria medication
  • heart disease, heart rhythm disorder (such as long QT syndrome)
  • diabetes
  • a stomach disorder
  • an allergy to quinine
  • liver or kidney disease
  • psoriasis
  • alcoholism
  • porphyria (a genetic enzyme disorder that causes symptoms affecting the skin or nervous system)
  • a genetic enzyme deficiency called glucose-6-phosphate dehydrogenase (G6PD) deficiency.

Using chloroquine alone or with other medicines (eg, azithromycin) may increase your risk of heart rhythm problems (eg, QT prolongation, ventricular fibrillation, ventricular tachycardia).

Tell your doctor if you have or have ever had liver disease, heart disease, a prolonged QT interval (a rare heart problem that may cause irregular heartbeat, fainting, or sudden death), an irregular heartbeat, a low level of magnesium or potassium in your blood, psoriasis, porphyria or other blood disorders, G6PD deficiency (an inherited blood disease), dermatitis (skin inflammations), seizures, vision problems, diabetes, kidney problems, or if you drink large amounts of alcohol.

Tell your doctor if you are pregnant or plan to become pregnant. Malaria is more likely to cause serious illness or death in a pregnant woman. Having malaria during pregnancy may also increase the risk of miscarriage, stillbirth, premature delivery, and low birth weight.

It is not known whether chloroquine will harm an unborn baby. If you are pregnant, ask your doctor about the risks of traveling to areas where malaria is common such as Africa, South America, and Southern Asia.

It may not be safe to breastfeed while using this medicine. Ask your doctor about any risk.

Chloroquine is not approved for treating lupus or rheumatoid arthritis in anyone younger than 18 years old.

Tell your doctor and pharmacist what prescription and nonprescription drugs, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention acetaminophen (Tylenol, others); azithromycin (Zithromax); cimetidine (Tagamet); cyclosporine (Gengraf, Neoral, Sandimmune); digoxin (Lanoxin), insulin and oral medication for diabetes; medications for seizures such as carbamazepine (Carbatrol, Epitol, Equetro, Tegretol, Teril), phenytoin (Dilantin, Phenytek), or valproic acid (Depakene); certain medications for irregular heartbeat such as amiodarone (Pacerone); methotrexate (Trexall, Xatmep); moxifloxacin (Avelox); praziquantel (Biltricide); and tamoxifen (Nolvadex). Your doctor may need to change the doses of your medications or monitor you carefully for side effects. Many other medications may also interact with hydroxychloroquine, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.

If you are taking antacids, take them 4 hours before or 4 hours after chloroquine. If you are taking ampicillin, take it at least 2 hours before or 2 hours after chloroquine.

Tell your doctor if you have ever had vision changes while taking chloroquine (Aralen), hydroxychloroquine or primaquine.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of chloroquine to prevent and treat malaria in children. However, children are more sensitive to the effects of this medicine than adults. Safety and efficacy of chloroquine to treat extraintestinal amebiasis have not been established in children.

Geriatric

Although appropriate studies on the relationship of age to the effects of chloroquine have not been performed in the geriatric population, geriatric-specific problems are not expected to limit the usefulness of chloroquine in the elderly. However, elderly patients are more likely to have age-related kidney problems, which may require caution and an adjustment in the dose for patients receiving chloroquine.

Chloroquine drug interactions

Chloroquine can cause a serious heart problem. Your risk may be higher if you also use certain other medicines for infections, asthma, heart problems, high blood pressure, depression, mental illness, cancer, malaria, or HIV.

If you take an antibiotic called ampicillin, take it 2 hours before or 2 hours after you take your chloroquine dose.

The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using chloroquine with any of the following medicines is not recommended. Your doctor may decide not to treat you with chloroquine or change some of the other medicines you take:

  • Aurothioglucose
  • Bepridil
  • Cisapride
  • Dronedarone
  • Mesoridazine
  • Pimozide
  • Piperaquine
  • Saquinavir
  • Sparfloxacin
  • Terfenadine
  • Thioridazine
  • Ziprasidone

Using chloroquine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Acarbose
  • Albiglutide
  • Alfuzosin
  • Alogliptin
  • Amiodarone
  • Amisulpride
  • Amitriptyline
  • Anagrelide
  • Apomorphine
  • Aripiprazole
  • Aripiprazole Lauroxil
  • Arsenic Trioxide
  • Asenapine
  • Astemizole
  • Atazanavir
  • Auranofin
  • Azithromycin
  • Bedaquiline
  • Buprenorphine
  • Buserelin
  • Canagliflozin
  • Carbamazepine
  • Ceritinib
  • Chlorpromazine
  • Chlorpropamide
  • Cimetidine
  • Ciprofloxacin
  • Citalopram
  • Clarithromycin
  • Clofazimine
  • Clomipramine
  • Clozapine
  • Crizotinib
  • Cyclobenzaprine
  • Cyclosporine
  • Dabrafenib
  • Dapagliflozin
  • Dasatinib
  • Degarelix
  • Delamanid
  • Desipramine
  • Deslorelin
  • Deutetrabenazine
  • Disopyramide
  • Dofetilide
  • Dolasetron
  • Domperidone
  • Donepezil
  • Doxepin
  • Droperidol
  • Dulaglutide
  • Ebastine
  • Efavirenz
  • Empagliflozin
  • Encorafenib
  • Entrectinib
  • Eribulin
  • Erythromycin
  • Escitalopram
  • Exenatide
  • Famotidine
  • Felbamate
  • Fingolimod
  • Flecainide
  • Fluconazole
  • Fluoxetine
  • Formoterol
  • Foscarnet
  • Fosphenytoin
  • Fostemsavir
  • Galantamine
  • Gatifloxacin
  • Gemifloxacin
  • Glasdegib
  • Glimepiride
  • Glipizide
  • Glyburide
  • Gonadorelin
  • Goserelin
  • Granisetron
  • Halofantrine
  • Haloperidol
  • Histrelin
  • Hydroquinidine
  • Hydroxychloroquine
  • Hydroxyzine
  • Ibutilide
  • Iloperidone
  • Imipramine
  • Inotuzumab Ozogamicin
  • Insulin
  • Insulin Aspart, Recombinant
  • Insulin Bovine
  • Insulin Degludec
  • Insulin Detemir
  • Insulin Glulisine
  • Insulin Lispro, Recombinant
  • Itraconazole
  • Ivabradine
  • Ivosidenib
  • Ketoconazole
  • Lapatinib
  • Lefamulin
  • Lenvatinib
  • Leuprolide
  • Levofloxacin
  • Linagliptin
  • Liraglutide
  • Lixisenatide
  • Lofexidine
  • Lumefantrine
  • Macimorelin
  • Mefloquine
  • Metformin
  • Methadone
  • Methotrimeprazine
  • Metronidazole
  • Mifepristone
  • Miglitol
  • Mirtazapine
  • Mizolastine
  • Moricizine
  • Moxifloxacin
  • Nafarelin
  • Nateglinide
  • Nelfinavir
  • Nilotinib
  • Norfloxacin
  • Octreotide
  • Ofloxacin
  • Olanzapine
  • Ondansetron
  • Osilodrostat
  • Osimertinib
  • Ozanimod
  • Paliperidone
  • Panobinostat
  • Papaverine
  • Paroxetine
  • Pasireotide
  • Pazopanib
  • Pentamidine
  • Perphenazine
  • Pimavanserin
  • Pioglitazone
  • Pipamperone
  • Pitolisant
  • Ponesimod
  • Posaconazole
  • Pramlintide
  • Probucol
  • Procainamide
  • Prochlorperazine
  • Promethazine
  • Propafenone
  • Protriptyline
  • Quetiapine
  • Quinidine
  • Quinine
  • Ranolazine
  • Remdesivir
  • Repaglinide
  • Ribociclib
  • Rilpivirine
  • Risperidone
  • Ritonavir
  • Rosiglitazone
  • Saxagliptin
  • Selpercatinib
  • Semaglutide
  • Sertindole
  • Sertraline
  • Sevoflurane
  • Siponimod
  • Sitagliptin
  • Sodium Phosphate
  • Sodium Phosphate, Dibasic
  • Sodium Phosphate, Monobasic
  • Solifenacin
  • Sorafenib
  • Sotalol
  • Sulpiride
  • Sultopride
  • Sunitinib
  • Tacrolimus
  • Tamoxifen
  • Telaprevir
  • Telavancin
  • Telithromycin
  • Tetrabenazine
  • Tolazamide
  • Tolbutamide
  • Tolterodine
  • Toremifene
  • Trazodone
  • Triclabendazole
  • Trimipramine
  • Triptorelin
  • Vandetanib
  • Vardenafil
  • Vemurafenib
  • Venlafaxine
  • Vilanterol
  • Vildagliptin
  • Vinflunine
  • Voclosporin
  • Voriconazole
  • Vorinostat
  • Zotepine
  • Zuclopenthixol

Using chloroquine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Aluminum Carbonate, Basic
  • Aluminum Hydroxide
  • Aluminum Phosphate
  • Ampicillin
  • Calcium Carbonate
  • Ciprofloxacin
  • Cyclosporine
  • Digoxin
  • Dihydroxyaluminum Aminoacetate
  • Dihydroxyaluminum Sodium Carbonate
  • Kaolin
  • Magaldrate
  • Magnesium Carbonate
  • Magnesium Hydroxide
  • Magnesium Oxide
  • Magnesium Trisilicate
  • Praziquantel
  • Sodium Bicarbonate

This list is not complete. other drugs may interact with chloroquine, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible drug interactions are listed here.

Other interactions

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of chloroquine. Make sure you tell your doctor if you have any other medical problems, especially:

  • Allergy to 4-aminoquinoline compounds (eg, hydroxychloroquine).
  • Blood or bone marrow problems
  • Eye or vision problems (eg, retinal or visual field changes) caused by 4-aminoquinoline compounds—Should not be used in patients with these conditions.
  • Eye or vision problems (eg, macular degeneration, retinopathy).
  • Hearing problems
  • Muscle weakness
  • Porphyria (blood disorder)
  • Psoriasis (skin disease)
  • Stomach or bowel problems. Use with caution. May make these conditions worse.
  • Bradycardia (slow heartbeat)
  • Heart disease
  • Heart rhythm problems, or history of heart rhythm problems
  • Hypokalemia (low potassium in the blood) or uncorrected low potassium
  • Hypomagnesemia (low magnesium in the blood) or uncorrected low magnesium. Use with caution. May prolong the QT interval.
  • Epilepsy or history of epilepsy. May increase risk for seizures.
  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency. May cause hemolytic anemia in patients with this condition.
  • Kidney disease
  • Liver disease. Use with caution. The effects may be increased because of the slower removal of chloroquine from the body.

Chloroquine uses

Chloroquine remains the first choice of antimalarial prophylaxis (prevention) as well as treatment. For malaria prophylaxis, 500 mg is typically administered orally two weeks before, during, and up to 8 weeks after exposure to an endemic area, taken as a weekly dose. The FDA also recommends chloroquine for the treatment of extraintestinal amebiasis. Chloroquine phosphate is used occasionally to decrease the symptoms of rheumatoid arthritis and to treat systemic lupus erythematosus (SLE) and discoid lupus erythematosus (DLE), sarcoidosis, and porphyria cutanea tarda. Talk to your doctor about the possible risks of using this drug for your condition.

Chloroquine dosage

The dose of chloroquine will be different for different patients. Follow your doctor’s orders or the directions on the label. The following information includes only the average doses of chloroquine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

  • NOTE: Chloroquine phosphate (chloroquine salt) 16.6 mg is equivalent to 10 mg chloroquine base. Each 500 mg tablet of chloroquine phosphate (chloroquine salt) is equivalent to 300 mg chloroquine base.

Adult dose for malaria prevention

For the prophylaxis of malaria in geographic areas where chloroquine resistance is not reported.

For oral dosage form (tablets): 500 milligrams (mg) once a week on the same day of each week starting 2 weeks before traveling to an area where malaria occurs, and continued for up to 8 weeks after leaving the area.

Comments:

  • Prophylaxis should start 1 to 2 weeks prior to exposure or travel to malarious areas and should continue for up to 8 weeks after leaving the endemic area.
  • If possible, suppressive therapy should start 2 weeks prior to exposure; if unable to start 2 weeks before exposure, an initial loading dose of 1 g chloroquine salt (600 mg chloroquine base) may be taken orally in 2 divided doses, 6 hours apart. Each 500 mg tablet of chloroquine phosphate (chloroquine salt) is equivalent to 300 mg chloroquine base.
  • Chloroquine should be administered on the same day of each week.
  • If malaria develops while using this drug for chemoprophylaxis, it should not be used as part of the treatment regimen.

Children dose for malaria prevention

For the prophylaxis of malaria in geographic areas where chloroquine resistance is not reported (i.e., for prophylaxis against chloroquine-sensitive Plasmodium species).

For oral dosage form (tablets):

  • Dose is based on body weight and must be determined by your doctor. The dose is usually 5 milligram (mg) per kilogram (kg) of body weight once per week on the same day each week starting 2 weeks before traveling to an area where malaria occurs, and continued for up to 8 weeks after leaving the area.

Comments:

  • Prophylaxis should start 1 to 2 weeks prior to exposure or travel to malarious areas and should continue for up to 8 weeks after leaving the endemic area.
  • Pediatric dose should not exceed the adult dose regardless of weight.
  • If possible, suppressive therapy should start 2 weeks prior to exposure; if unable to start 2 weeks before exposure, an initial loading dose of 10 mg/kg base (16.7 mg/kg salt [chloroquine phosphate]) may be taken orally in 2 divided doses, 6 hours apart.
  • Chloroquine should be administered on the same day of each week.
  • If malaria develops while using this drug for chemoprophylaxis, it should not be used as part of the treatment regimen.

Adult dose for treatment of malaria

For the treatment of uncomplicated malaria due to Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale, and Plasmodium vivax.

For treatment of malaria (adults with body weight at least 60 kg): At first, 1000 milligrams (mg) once a day. Then, 500 mg 6 to 8 hours after the first dose, and 500 mg on the second and third days of treatment.

Adults with low body weight (less than 60 kg): Dose is based on body weight and must be determined by your doctor. At first, 10 milligram (mg) per kilogram (kg) of body weight. Then, 5 mg per kg of body weight taken 6 hours, 24 hours, and 36 hours after the first dose. 

Comments:

  • Recommended for uncomplicated malaria (Plasmodium falciparum or species not identified) in regions with chloroquine sensitivity
  • Recommended for uncomplicated malaria (Plasmodium malariae, Plasmodium knowlesi, Plasmodium vivax [unless chloroquine-resistant Plasmodium vivax suspected], or Plasmodium ovale) in all regions; if treating Plasmodium vivax or Plasmodium ovale infections, concomitant treatment with primaquine or tafenoquine (after quantitative testing to rule out glucose-6-phosphate dehydrogenase [G6PD] deficiency) is recommended.
  • Recommended for uncomplicated malaria treatment for pregnant women in regions with chloroquine sensitivity
  • Pregnant patients with Plasmodium vivax and Plasmodium ovale infections should receive chloroquine prophylaxis (300 mg base orally once a week) during pregnancy; after delivery, patients with normal G6PD activity should be treated with primaquine or tafenoquine or continue chloroquine prophylaxis for 1 year (total).
  • Concomitant therapy with an 8-aminoquinoline compound is necessary for radical cure of Plasmodium vivax and Plasmodium ovale infections.

Children dose for treatment of malaria

For the treatment of uncomplicated malaria due to Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale, and Plasmodium vivax.

For treatment of malaria: 

  • Dose is based on body weight and must be determined by your doctor. At first, 10 milligram (mg) per kilogram (kg) of body weight. Then, 5 mg per kg of body weight taken 6 hours, 24 hours, and 36 hours after the first dose.

Comments:

  • Children dose should never exceed adult dose.
  • Recommended for uncomplicated malaria (Plasmodium falciparum or species not identified) in regions with chloroquine sensitivity
  • Recommended for uncomplicated malaria (Plasmodium malariae, Plasmodium knowlesi, Plasmodium vivax [unless chloroquine-resistant Plasmodium vivax suspected], or Plasmodium ovale) in all regions; if treating Plasmodium vivax or Plasmodium ovale infections, concomitant treatment with primaquine or, in children 16 years or older, tafenoquine (after quantitative testing to rule out glucose-6-phosphate dehydrogenase [G6PD] deficiency) is recommended.
  • Concomitant therapy with an 8-aminoquinoline compound is necessary for radical cure of Plasmodium vivax and Plasmodium ovale infections.
  • Current guidelines should be consulted for additional information.

Adult dose for liver infection caused by protozoa (amebiasis)

For the treatment of extraintestinal amebiasis.

  • 1000 milligrams (mg) once a day, taken for 2 days. This is followed by 500 mg once a day for at least 2 to 3 weeks.

Comments:

  • Treatment is usually combined with an effective intestinal amebicide.

Adult dose for sarcoidosis

For the treatment of sarcoidosis.

  • Intrathoracic and cutaneous sarcoidosis: 250 mg twice a day for 4 to 17 months; a treatment course should be limited to 6 months to minimize risk of ocular damage
  • Pulmonary sarcoidosis: 750 mg per day for 6 months, then tapered every 2 months to 250 mg per day
  • Nervous system sarcoidosis (neurosarcoidosis): 250 mg twice a day for 6 to 18 months

What should I do if I forget a dose?

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Chloroquine side effects

The most severe adverse effects associated with high doses of chloroquine include retinal toxicity, long and subtle symptoms of reduced visual acuity, diplopia, and bilateral loss of vision 64). High doses have also been shown to cause severe psychiatric issues, such as paranoia, hallucinations, and suicidal ideations 65).

  • Dermatological reactions include pruritus and photosensitivity.
  • Retinopathy will typically present with the inability to focus between near and far objects.
  • Neuropathy can include seizures, paranoia, and hallucinations.

When administered intramuscularly, chloroquine has been shown to cause potentially lethal hypotension 66).

Side effects from chloroquine phosphate can occur. Tell your doctor if any of these symptoms are severe or do not go away:

  • headache
  • nausea
  • loss of appetite
  • diarrhea
  • upset stomach
  • stomach pain
  • rash
  • itching
  • hair loss

If you experience any of the following symptoms, call your doctor immediately:

  • seeing light flashes and streaks
  • blurred vision
  • reading or seeing difficulties (words disappear, seeing half an object, misty or foggy vision)
  • difficulty hearing
  • ringing in ears
  • muscle weakness
  • drowsiness
  • vomiting
  • irregular heartbeats
  • convulsions
  • difficulty breathing
  • mood or mental changes
  • decreased consciousness or loss of consciousness
  • thinking about harming or killing yourself

Chloroquine overdose

In case of chloroquine overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can’t be awakened, immediately call your local emergency services number.

Symptoms of chloroquine overdose may include: 

  • nausea
  • vomiting
  • headache
  • drowsiness
  • visual disturbances
  • convulsions
  • irregular heartbeat
  • cold, clammy skin
  • decreased urine
  • dry mouth
  • fast, weak pulse
  • increased thirst
  • lightheadedness, dizziness, or fainting
  • loss of appetite
  • muscle pain or cramps
  • numbness or tingling in the hands, feet, or lips.

Chloroquine toxicity

Chloroquine toxicity is rare but has been known to occur when unusually high doses of chloroquine are ingested or after chronic IV administration. Accidental ingestion has also occurred in children 67). When toxicity is present, the most common symptom is retinal toxicity. Treatment of chloroquine toxicity includes mechanical ventilation and administration of diazepam and epinephrine, although these methods have not been a proven method of treatment in all cases 68).

Chloroquine contraindications

There are reports of cases with death in relating to chloroquine administered to patients with porphyria cutaneous tarda 69). Chloroquine should not be used in patients with retinal or vision changes unless it is to treat acute malaria. Chloroquine is also contraindicated in patients who suffer from a known hydroxychloroquine-sensitivity.

References   [ + ]