Hydroxychloroquine, brand name Plaquenil, is an oral prescription drug used to treat or prevent malaria, as well as to treat lupus and rheumatoid arthritis. It’s also called HCQS or hydroxychloroquine sulfate. Hydroxychloroquine and a related drug, chloroquine, belong to the antimalarial quinoline drugs class.
Researchers have traced hydroxychloroquine use as far back as the 1600s when Peruvians made a powder from tree bark for medicinal purposes.
During World War II, millions of soldiers used an earlier form of HCQS, chloroquine, to protect against malaria. Researchers discovered that the drug improved soldiers’ skin rashes and arthritis. This led researchers to discover the drug’s effectiveness against lupus and other inflammatory diseases.
In 1955, drugmakers introduced hydroxychloroquine, a new form of chloroquine that maintained its efficacy while reducing toxicity.
Today, Concordia Pharmaceuticals Inc. markets the drug under the brand name Plaquenil, and several other drug companies manufacture its generic form.
The drug’s most common side effects are stomach pain, headache, vomiting and nausea, according to the Centers for Disease Control and Prevention.
In late March 2020, the U.S. Food and Drug Administration granted an Emergency Use Authorization for chloroquine and hydroxychloroquine after small, limited studies showed the drug’s potential to treat COVID-19.
In a 2022 clinical research trial of 8,152 patients, researchers found that, when used for COVID-19 treatment, hydroxychloroquine increases the risk of diarrhea, nausea or vomiting and may increase the risk of cardiac toxicity and cognitive dysfunction or delirium.
How It Works
Researchers don’t know exactly how hydroxychloroquine works to treat malaria. But researchers think the drug alters the way the immune system works to treat symptoms of lupus and arthritis. Specifically, it works by disrupting cell processes at the molecular level to lessen the immune system’s response.
Because the body’s natural immune response can cause inflammation, reducing the immune response helps treat rheumatoid arthritis.
People with lupus have overactive immune systems that attack the body instead of protecting it. Because hydroxychloroquine calms the immune system, it helps control symptoms of lupus.
How to Take Plaquenil
Each Plaquenil hydroxychloroquine tablet contains 200 mg of hydroxychloroquine sulfate. Depending on the condition being treated, the dosage varies. Patients should take the recommended dose with food or milk.
Dosage for Malaria Prevention and Treatment
People trying to prevent malaria should start taking HCQS two weeks prior to traveling to a country or area where malaria is present. Continue taking the drug for four weeks after leaving the area of exposure. The recommended dose is 400 mg once a week on the same day of each week.
In children, the dose is 6.5 mg per kilogram of body weight. The total dose should not exceed 400 mg.
Adults taking HCQS for uncomplicated malaria start with 800 mg. Then they take 400 mg at 6, 24 and 48 hours after the first dose. This is a total of 2,000 mg.
In children with malaria, the dose is 13 mg per kilogram of body weight, not to exceed 800 mg. Then they take 6.5 mg per kilogram, not to exceed 400 mg, at 6, 24 and 48 hours after the initial dose.
Dosage for Lupus
Adults with lupus take 200 to 400 mg as a single daily dose, or divided into two doses. The drug’s medication insert doesn’t recommend doses above 400 mg a day.
Dosage for Rheumatoid Arthritis
The starting dose in adults is 400 to 600 mg in a single daily dose or divided into two doses. If a patient suffers side effects, a medical provider may lower the initial dose temporarily.
After patients respond well to the medication, medical providers will reduce the dose to 200 to 400 mg once daily or divided into two doses. This is a maintenance dose.
The dose shouldn’t exceed 600 mg or 6.5 mg per kilogram of body weight, whichever is lower. At doses higher than this, the risk of retinopathy side effects may increase.
According to the Plaquenil prescribing information, hydroxychloroquine interacts with several medications. The drug label also warns about drug interactions with chloroquine because the two drugs are similar.
There are no known interactions between hydroxychloroquine and alcohol, but heavy drinkers may have damaged livers and medical providers may have to lower the medication dosage.
Tell your medical provider if you have gastrointestinal problems, neurological disorders, blood disorders or sensitivity to quinine before taking this drug.
This isn’t a complete list of drug interactions. Make sure you tell your medical provider about all medications, vitamins and supplements you are taking. Report any signs of toxicity, such as visual changes or rash, to your medical provider immediately.
- Using hydroxychloroquine and digoxin together may increase digoxin levels.
- Diabetes medications or insulin
- Hydroxychloroquine may increase the effectiveness of diabetic drugs or insulin, and medical providers may need to adjust medication dosages.
- Drugs that prolong QT interval and other arrhythmogenic drugs
- Because hydroxychloroquine prolongs the QT interval, it should not be used with other drugs that have the potential to induce cardiac arrhythmias.
- Mefloquine and other drugs that may lower the convulsive threshold
- Using hydroxychloroquine with other antimalarials that lower the convulsion threshold may increase the risk of convulsions.
- Antiepileptic drugs may be less effective if used with hydroxychloroquine.
- Using methotrexate with hydroxychloroquine may increase the incidence of adverse effects.
- Using cyclosporin and hydroxychloroquine together may increase levels of cyclosporin in the blood.
- Antacids and kaolin
- Using antacids and/or kaolin with chloroquine lower the drug’s absorption. Take these substances at least four hours apart.
- Chloroquine significantly reduced ampicillin’s bioavailability in studies.
- Cimetidine interferes with the metabolism of chloroquine, increasing chloroquine levels in the blood. Patients shouldn’t take these drugs together.
- Bioavailability of praziquantel is reduced by chloroquine.
Hydroxychloroquine and COVID-19
Because of hydroxychloroquine and chloroquine’s antiviral and antibacterial properties, researchers have been investigating the drugs as potential treatments for COVID-19. This has caused concern among some medical providers and patients with lupus and arthritis who worry about drug shortages.
“A prolonged shortage of [hydroxychloroquine] might deprive people with SLE [lupus] of a low-cost, safe, effective and well-tolerated drug. Patients are terrified that they might lose access to the drug that prevents their disease from damaging other vital organs,” according to an article by Drs. Deepak Jakhar and Ishmeet Kaur in Nature Medicine.
“A prolonged shortage of [hydroxychloroquine] might deprive people with SLE [lupus] of a low-cost, safe, effective and well-tolerated drug. Patients are terrified that they might lose access to the drug that prevents their disease from damaging other vital organs.”
The FDA granted Emergency Use Authorizations for medical providers to use HCQS on hospitalized COVID-19 patients. This drug has not yet proven effective for coronavirus in clinical trials, but some small studies have shown promise.
For example, a small Chinese study showed that chloroquine inhibited SARS-CoV-2 — the virus responsible for COVID-19 — in petri dishes, Jakhar and Kaur wrote. Based on this information, Chinese experts recommended medical providers treat coronavirus cases with 500 mg chloroquine twice daily for 10 days. Then, another Chinese study showed hydroxychloroquine had similar, more potent effects on the virus than chloroquine.
French tests showed about 50 percent of patients who tested positive for COVID-19 and took hydroxychloroquine tested negative after three days of treatment, Forbes reported.
But there have also been some serious cardiac side effects reported, and some overseas hospitals have halted hydroxychloroquine and chloroquine treatment for some patients. In France, one patient on hydroxychloroquine developed potentially fatal heart rhythms, and the hospital stopped his HCQS treatment, Newsweek reported.
In Brazil, a small study with 81 COVID-19 patients stopped early after patients taking a higher dose of chloroquine developed irregular heartbeats, the New York Times reported.
When hydroxychloroquine is combined with azithromycin — or Zithromax — the risk of dangerous heart problems increase.
For some patients, “the remedy is more harmful than the disease itself,” Professor Émile Ferrari, the head of the cardiology department at the Pasteur hospital in Nice, France, told Newsweek.
On April 24, 2020, the FDA warned that use of hydroxychloroquine or chloroquine to treat COVID-19 should be limited to only patients hospitalized with the illness. The agency also stressed that people should not take the drug to prevent getting the disease.
Hydroxychloroquine and chloroquine “should be used for COVID-19 only when patients can be appropriately monitored in the hospital as required by the EUA or are enrolled in a clinical trial with appropriate screening and monitoring,” the agency said. “FDA is reviewing the safety of their use when used outside of the setting of hospitalized patients for whom use was authorized.”
Serious side effects of these medicines include QT interval prolongation, ventricular tachycardia and ventricular fibrillation. Some of these can be fatal. Taking these drugs together with azithromycin (Zithromax, Z-Pak) — or other drugs that prolong the QT interval — may increase the risk of these side effects.
Seek emergency medical attention if you experience irregular heartbeats, dizziness or fainting while taking these drugs to treat COVID-19.
As of April 17, 2020, there were ongoing COVID-19 clinical trials for hydroxychloroquine, and people can read about them on ClinicalTrials.gov.
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