Chloroquine (Aralen) vs. Hydroxychloroquine (Plaquenil) for COVID-19?

Chloroquine (Aralen) vs. hydroxychloroquine (Plaquenil): What’s the difference?

What is Chloroquine? What is Hydroxychloroquine?

Chloroquine (Aralen) is an anti-malarial drug useful in treating several forms of malaria as well as amebiasis that has spread outside of the intestines. It suppresses malaria infection, stops acute attacks, and lengthens the time between treatment and relapse.

It is similar to hydroxychloroquine (Plaquenil), and both drugs are under investigation for treatment of the COVID-19 coronavirus disease.

Its mechanism of action is unknown; however, malarial parasites invade human red blood cells, and chloroquine may prevent malarial parasites from breaking down (metabolizing) hemoglobin in human red blood cells.  Chloroquine is effective against the malarial parasites Plasmodium vivax, P. malariae, P. ovale, and susceptible strains of P. falciparum.

Chloroquine is not effective for malaria prevention. Chloroquine is used off-label to treat porphyria cutanea tarda.

Hydroxychloroquine (Plaquenil) is an anti-malarial drug used to treat several forms of malaria as well as lupus erythematosus and rheumatoid arthritis. It is similar to chloroquine (Aralen). Its mechanism of action is unknown. Malarial parasites invade human red blood cells. Hydroxychloroquine may prevent malarial parasites from breaking down (metabolizing) hemoglobin in human red blood cells.

Hydroxychloroquine is effective against the malarial parasites Plasmodium vivax, P. malariae, P. ovale, and susceptible strains of P. falciparum.

What are the side effects of chloroquine and hydroxychloroquine?


Common side effects include

Other, rare side effects include:

Possible serious effects:

Other adverse reactions and side effects of Aralen

  • There have been rare reports of severe skin reactions such as erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and exfoliative dermatitis.
  • Chloroquine may precipitate a severe attack of psoriasis in patients with psoriasis and may worsen porphyria. Chloroquine should not be used in these conditions unless the benefit to the patient outweighs the potential risks.
  • People with retinal or visual field changes should not use chloroquine unless it is absolutely necessary.
  • Some strains of P. falciparum are resistant to chloroquine and hydroxychloroquine. Chloroquine resistance is widespread. Chloroquine should not be used for treatment of P. falciparum infections from areas of chloroquine resistance or malaria occurring in patients where chloroquine prophylaxis has failed. Patients infected with a resistant strains of plasmodia should be treated with another antimalarial drug.
  • Retinopathy, maculopathy, irreversible retinal damage, as well as macular degeneration have been reported. Retinopathy from chloroquine may be dose related. Initial and periodic eye examinations are recommended during prolonged treatment. Chloroquine should be discontinued immediately if there are changes in vision.
  • Chloroquine may cause acute extrapyramidal disorders (abnormal, uncontrollable body movements) that usually resolve after treatment is stopped.
  • Patients should be observed for evidence of muscular weakness. If weakness occurs treatment should be stopped.
  • Fatalities have occurred in children from accidental ingestion of small doses of chloroquine. Chloroquine should be kept out of the reach of children.


Side effects include

  • irritability,
  • headache,
  • weakness,
  • hair lightening or loss,
  • stomach upset,
  • nausea,
  • dizziness,
  • muscle pain,
  • rash and
  • itching.

Rarely, hydroxychloroquine can affect the bone marrow leading to reduced white blood cells (leukopenia) or platelets (thrombocytopenia) and abnormal red blood cells (anemia).

Rare but potentially serious eye toxicity can occur. This toxicity affects a part of the eye called the retina and can lead to color blindness and even loss of vision. An ophthalmologist (eye specialist) often can detect changes in the retina that suggest toxicity before serious damage occurs. Therefore, regular eye examinations, even when there are no symptoms, are mandatory.

Patients who are genetically deficient in a certain enzyme, called G6PD, can develop a severe anemia resulting from the rupture of red blood cells. This enzyme deficiency is more common in persons of African descent and can be evaluated by blood testing. Hydroxychloroquine may worsen psoriasis.

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What is the dosage for chloroquine vs. hydroxychloroquine?


  • For acute malaria attacks in adults the initial dose is 1 g followed by an additional 500 mg after 6 to 8 hours, then 500 mg 24 and 48 hours after the first dose.
  • The dose for treating children is 10 mg/kg for the first dose then 5 mg/kg daily for 2 days, starting 6 hours after the first dose.
  • The dose for treating intestinal amebiasis is 1 g daily for two days, followed by 500 mg daily for at least two to three weeks.
  • Chloroquine usually is combined with an effective intestinal amebicide.


  • The usual adult dose for treating malaria is 800 mg initially, followed by 400 mg 6-8 hours later and then 400 mg at 24 hours and 48 hours.
  • The dose for malaria prevention is 400 mg every week starting 1 or 2 weeks before exposure and for 4 weeks after leaving the high risk area.
  • The recommended adult dose for rheumatoid arthritis is 400-600 mg daily for 4-12 weeks followed by 200-400 mg daily.
  • Systemic lupus erythematosus is treated with 400 mg once or twice daily for several weeks then 200-400 mg daily.
  • Hydroxychloroquine should be taken with food or milk in order to reduce stomach upset.

What drugs interact with chloroquine and hydroxychloroquine?


  • Antacids and kaolin can reduce absorption of chloroquine.  Administration of this drug and these agents should be separated by at least 4 hours.
  • Cimetidine (Tagamet) can block the breakdown of chloroquine, increasing its blood levels. This combination should be avoided.
  • Chloroquine significantly reduces blood levels of ampicillin. Ingestion of ampicillin and chloroquine should be separated by at least two hours.
  • Chloroquine may increase cyclosporine blood levels. Cyclosporine blood levels should be monitored and, if necessary, chloroquine should be stopped.
  • Combining chloroquine and mefloquine may increase the risk of seizures.
  • Chloroquine can reduce the antibody response to primary immunization with intradermal human diploid-cell rabies vaccine.


  • Administration of hydroxychloroquine with penicillamine (Cuprimine, Depen) may increase penicillamine levels, increasing the risk of penicillamine side effects. The mechanism is unknown.
  • Combining telbivudine (Tyzeka) and hydroxychloroquine may increase the risk of unexplained muscle pain, tenderness, or weakness because both drugs cause such side effects.
  • Hydroxychloroquine suppresses the immune system and should not be combined with drugs that also suppress the immune system or live vaccines.

Are chloroquine and hydroxychloroquine safe to use while pregnant or breastfeeding?


There are no studies evaluating the safety and efficacy of chloroquine in during pregnancy. If you are pregnant this drug should be avoided unless it is necessary and the benefit outweighs the risk. Chloroquine is excreted in breast milk.


Hydroxychloroquine should only be used in pregnant women for malaria prophylaxis or treatment. Hydroxychloroquine may be secreted in breast milk and may cause side effects in the infant.

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