Idiosyncratic hypersensitivity reactions have occurred.For prolonged treatment of lupus or rheumatoid arthritis, adverse effects include the acute symptoms, plus altered eye pigmentation, acne, anemia, bleaching of hair, blisters in mouth and eyes, blood disorders, cardiomyopathy, convulsions, vision difficulties, diminished reflexes, emotional changes, excessive coloring of the skin, hearing loss, hives, itching, liver problems or liver failure, loss of hair, muscle paralysis, weakness or atrophy, nightmares, psoriasis, reading difficulties, tinnitus, skin inflammation and scaling, skin rash, vertigo, weight loss, and occasionally urinary incontinence. Hydroxychloroquine can worsen existing cases of both psoriasis and porphyria.Children may be especially vulnerable to developing adverse effects from hydroxychloroquine overdoses. Eyes
One of the most serious side effects is retinopathy (generally with chronic use). People taking 400 mg of hydroxychloroquine or less per day generally have a negligible risk of macular toxicity, whereas the risk begins to increase when a person takes the medication over five years or has a cumulative dose of more than 1000 grams. The daily safe maximum dose for eye toxicity can be estimated from a persons height and weight. Macular toxicity is related to the total cumulative dose rather than the daily dose. Regular eye screening, even in the absence of visual symptoms, is recommended to begin when either of these risk factors occurs.Toxicity from hydroxychloroquine may be seen in two distinct areas of the eye: the cornea and the macula. The cornea may become affected (relatively commonly) by an innocuous cornea verticillata or vortex keratopathy and is characterized by whorl-like corneal epithelial deposits.
Both neostigmine and pyridostigmine antagonize the action of hydroxychloroquine.While there may be a link between hydroxychloroquine and hemolytic anemia in those with glucose-6-phosphate dehydrogenase deficiency, this risk may be low in those of African descent.Specifically, the US Food and Drug Administrations (FDA) drug label for hydroxychloroquine lists the following drug interactions:
Digoxin (wherein it may result in increased serum digoxin levels)
Insulin or anti-diabetic medication (wherein it may enhance the effects of a hypoglycemic treatment)
Drugs that prolong QT interval and other arrhythmogenic drugs (as Hydroxychloroquine prolongs the QT interval and may increase the risk of inducing serious abnormal heart rhythms (ventricular arrhythmias) if used concurrently)
Mefloquine and other drugs known to lower the seizure threshold (co-administration with other antimalarials known to lower the convulsion threshold may increase risk of convulsions)
Antiepileptics (concurrent use may impair the antiepileptic activity)
Methotrexate (combined use is unstudied and may increase the frequency of side effects)
Cyclosporin (wherein an increased plasma cyclosporin level was reported when used together). Pharmacology
Pharmacokinetics
Hydroxychloroquine has similar pharmacokinetics to chloroquine, with rapid gastrointestinal absorption, large distribution volume, and elimination by the kidneys. Cytochrome P450 enzymes (CYP2D6, 2C8, 3A4 and 3A5) metabolize hydroxychloroquine to N-desethylhydroxychloroquine. Both agents also inhibit CYP2D6 activity and may interact with other medications that depend on this enzyme. Pharmacodynamics
Antimalarials are lipophilic weak bases and easily pass plasma membranes. The free base form accumulates in lysosomes (acidic cytoplasmic vesicles) and is then protonated, resulting in concentrations within lysosomes up to 1000 times higher than in culture media. This increases the pH of the lysosome from four to six.