Hydroxychloroquine is an aminoquinoline like chloroquine. It is a commonly prescribed medication in the treatment of uncomplicated malaria ( caused by P. falciparum, P. malariae, P. ovale, or P. vivax ), rheumatoid arthritis, chronic discoid lupus erythematosus, and systemic lupus erythematosus.
Hydroxychloroquine is also used for the prophylaxis of malaria in regions where chloroquine resistance is unlikely. It was developed during World War II as a derivative of quinacrine with less severe side effects. Chloroquine and hydroxychloroquine are both being investigated for the treatment of SARS-CoV-2.
Hydroxychloroquine was granted FDA approval on 18 April 1955. A recent study reported a fatality in the group being treated with hydroxychloroquine for COVID-19.
Hydroxychloroquine affects the function of lysozomes in humans as well as plasmodia. Altering the pH of the lysozomes reduces low affinity self antigen presentation in autoimmue diseases and interferes with the ability of plasmodia to proteolyse hemoglobin for their energy requirements.
Hydroxychloroquine has a long duration of action as it may be taken on a weekly basis for some indications. Hydroxychloroquine may lead to severe hypoglycemia and so diabetic patients are advised to monitor their blood glucose levels.
Hydroxychloroquine is not effective against malaria in areas where chloroquine resistance has been reported.
The exact mechanisms of hydroxychloroquine are unknown. It has been shown that hydroxychloroquine accumulates in the lysosomes of the malaria parasite, raising the pH of the vacuole. This activity interferes with the parasite's ability to proteolyse hemoglobin, preventing the normal growth and replication of the parasite. Hydroxychloroquine can also interfere with the action of parasitic heme polymerase, allowing for the accumulation of the toxic product beta-hematin.
Hydroxychloroquine accumulation in human organelles also raise their pH, which inhibits antigen processing, prevents the alpha and beta chains of the major histocompatibility complex (MHC) class II from dimerizing, inhibits antigen presentation of the cell, and reduces the inflammatory response. Elevated pH in the vesicles may alter the recycling of MHC complexes so that only the high affinity complexes are presented on the cell surface.
The raised pH in endosomes, prevent virus particles (such as SARS-CoV and SARS-CoV-2) from utilizing their activity for fusion and entry into the cell.
Hydroxychloroquine is N-dealkylated by CYP3A4 to the active metabolite desethylhydroxychloroquine, as well as the inactive metabolites desethylchloroquine and bidesethylchloroquine. Desethylhydroxychloroquine is the major metabolite.
Absorption: Hydroxychloroquine is 67-74% bioavailable. Bioavailability of the R and S enantiomers were not significantly different. Following a 200mg oral dose, hydroxychloroquine reached a Cmax of 129.6ng/mL with a Tmax of 3.26h in the blood and a Cmax of 50.3ng/mL with a Tmax of 3.74h in the plasma. Following 155mg and 310mg intravenous doses, Cmax in the blood ranged from 1161-2436ng/mL with an average of 1918ng/mL.
Route of elimination: 40-50% of hydroxychloroquine is excreted renally, while only 16-21% of a dose is excreted in the urine as unchanged drug. 5% of a dose is sloughed off in skin and 24-25% is eliminated through the feces.
Half life: Oral hydroxychloroquine has an absorption half life of 3-4 hours. A 200mg oral dose of hydroxychloroquine has a half life of 537 hours or 22.4 days in blood, and 2963 hours or 123.5 days in plasma. A 155mg intravenous dose has a half life of 40 days.
All medicines may cause side effects, but many people have no, or minor, side effects. Some medical conditions may interact with Hydroxychloroquine.
Tell your doctor or pharmacist if you have any medical conditions.
Patients experiencing an overdose may present with headache, drowsiness, visual disturbances, cardiovascular collapse, convulsions, hypokalemia, rhythm and conduction disorders including QT prolongation, torsades de pointes, ventricular tachycardia, and ventricular fibrillation. This may progress to sudden respiratory and cardiac arrest.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider.
