Hydroxychloroquine (Plaquenil): Indications, Mechanism of Action, Drug Interactions

Hydroxychloroquine is a popular drug that has been used since the 1950s to treat a wide range of conditions such as malaria, rheumatoid arthritis, juvenile rheumatoid arthritis, lupus erythematosus, and photodermatitis. In 2018, it was the 129th most commonly prescribed medication in the United States, with more than 5 million prescriptions. Although there are more modern analogs, for certain conditions, hydroxychloroquine continues to be the first-line drug due to its high efficacy and safety. It has been successfully used to prevent and treat malaria, except in severe or complicated cases. It also can decrease the pain and swelling of arthritis, prevent joint damage, and reduce the risk of long-term disability. This drug is sold under the names Plaquenil, Hydroxychloroquine sulfate, Quineprox, etc.

Hydroxychloroquine for Covid-19

In the early months of the Covid-19 pandemic, scientists were actively studying hydroxychloroquine as a possible drug to treat the disease. At the start of the epidemic in China, a small study was published on the effects of chloroquine (a closely related drug) on coronavirus. Although the drug itself was not considered antiviral, in the past it was found to be able to prevent viruses from entering cells. However, this effect was shown only in laboratory settings but not in humans. The conclusions of the Chinese were picked up by the famous French infectious disease specialist Didier Raoult. According to him, he has long used hydroxychloroquine to treat infections. His study of the combination of hydroxychloroquine and the antibiotic azithromycin, he claimed, led to a significant reduction in mortality in the elderly. Although only 24 people participated in the study, Raoult’s statements began to circulate on social networks. However, later and larger studies have not confirmed the earlier findings. As a result, the world’s leading medical regulators do not recommend the use of these drugs against coronavirus due to their ineffectiveness and possible side effects. However, hydroxychloroquine as a treatment for Covid-19 continues to be at the center of controversy in the scientific community.

Price comparison

There are brand-name and generic versions of hydroxychloroquine. Prices for sale per tablet can vary significantly depending on the manufacturer. On the wave of speculations about hydroxychloroquine being effective against Covid-19, demand has skyrocketed and prices rose substantially. Brand-name Plaquenil by Sanofi (60 tablets) can be bought for $500–$700 in retail outlets. Subsequently, the use of generics became relevant as never before. Generic Plaquenil can cost as low as $20 per 60 tablets, although its average price reaches $50. The most affordable hydroxychloroquine is produced in India and can be purchased both at your local pharmacy and online.

Indications for use

Hydroxychloroquine is indicated for:

  • malaria;
  • rheumatoid arthritis;
  • juvenile chronic arthritis;
  • discoid and systemic lupus erythematosus;
  • pathologies of the skin, which were caused or complicated by sunlight (photodermatitis).

Hydroxychloroquine is occasionally prescribed for children over 6 years of age unless treatment involves long-term use of the drug (as the risk of toxic effects is increased). The daily dose is 6.5 mg/kg.

Dosage and administration of Hydroxychloroquine

The method of administration depends on the drug form and other factors. The physician determines the dosage regimen and the duration of therapy individually, depending on the indications, the clinical situation, and the age of the patient.

To prevent malaria, hydroxychloroquine is usually taken once a week, starting 7–14 days before arrival in a malarial area and a few weeks after leaving the danger zone. For rheumatoid arthritis, the medicine is taken once or twice daily. During treatment, the doctor may increase or decrease the dose.

The medicine is taken orally. To reduce the risk of side effects, only the lowest effective dose should be used. The daily dose should not exceed 6.5 mg per kilogram of body weight; usually, it can be 200 or 400 mg per day. To avoid indigestion, hydroxychloroquine can be taken with food or milk.

Mechanism of action

Hydroxychloroquine is a derivative of 4-aminoquinoline, an antimalarial drug that is similar to chloroquine in terms of the mechanism of action on the body. How hydroxychloroquine works remains unclear to this day. According to one version, it inhibits the synthesis of a substance that would neutralize hemozoin, the waste products of plasmodium after feeding on blood components. Because of this, plasmodium accumulates heme (the iron-containing part of hemoglobin that carries oxygen in our blood) and dies from its toxicity. Later, Plaquenil began to be used against rheumatoid arthritis and lupus, falling into the list of the safest and most effective drugs of the World Health Organization.

The mechanism of action against viruses is different, although it is also unclear. In a recent study, scientists suggested that it acts on sigma receptors in the cell membrane, which prevents viruses from getting inside.

Side effects of Hydroxychloroquine

Hydroxychloroquine can cause the following side effects:

  • retinopathy
  • the formation of pigment deposits in the cornea, which is accompanied by a reversible fear of light and blurred vision
  • feeling of flickering in the eyes
  • digestive disorders (nausea, vomiting, stomach cramps, diarrhea, anorexia);
  • anemia, thrombocytopenia, neutropenia
  • dermatitis, depigmentation of the skin
  • muscle weakness
  • vestibular disorders (tinnitus, dizziness, hearing loss)
  • emotional disorders
  • headache, nervousness
  • agranulocytosis
  • toxic psychosis
  • hair loss
  • myelosuppression

Diarrhea, stomach cramps, and nausea are among the side effects of the digestive system. Patients may become irritable and experience mania, psychosis, hallucinations, suicidal thoughts, and other disturbances.

As the dosage increases, there is a growing risk of retinopathy, which is damage to the retina that can lead to blindness. To calculate the risk of retinopathy, doctors came up with a special calculator, according to which doses of more than 5 mg per kilogram of body weight should be taken with caution. In rare cases, severe, and sometimes deadly, skin lesions (Stevens-Johnson syndrome, toxic epidermal necrosis), as well as hematopoietic disorders, are possible. Also, potentially lethal consequences of using the drug can be the prolongation of the QT interval of the heart (ventricular arrhythmia) and cardiomyopathy.

An overdose of hydroxychloroquine is manifested by headache, visual disturbance, and vascular collapse. Diazepam is administered to exclude a negative effect on the heart. In severe situations, dopamine is administered, after which the patient must be medically monitored.


Before buying hydroxychloroquine, check that there are no contraindications:

  • individual hypersensitivity to hydroxychloroquine and 4-aminocholine derivatives;
  • retinopathy;
  • maculopathy;
  • pregnancy;
  • the need for long-term treatment of children.

With caution, the drug is prescribed for visual impairment, blood diseases, neurological pathologies, psoriasis, renal and hepatic dysfunction, and impaired cardiac conduction.

If it becomes necessary to use hydroxychloroquine during lactation, the physician must carefully weigh the potential risks and benefits of using the drug, taking the duration of therapy into account.

Drug Interactions

Hydroxychloroquine may interact with certain drugs for diarrhea (kaolin) and antacids (such as magnesium/aluminum hydroxide), impairing the absorption of the drug. If you are taking these drugs, take hydroxychloroquine at least 4 hours before or after these products.

Hydroxychloroquine, widely known as Plaquenil, is the first-line therapy for lupus erythematous and numerous autoimmune/inflammatory diseases. Although its use for Covid-19 is controversial, the pandemic led to a significant rise in demand and cost. While brand-name Plaquenil is sold at highly inflated prices, generic hydroxychloroquine is affordable and widely available. There is a potential risk of dangerous side effects when taking Plaquenil. Use the drug with caution and report any alarming signs to your physician.

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