Hydroxychloroquine Eye Risk

Wrong Hydroxychloroquine Dose Is Common, Putting Eyes at Risk

Up to half of patients treated with the arthritis drug hydroxychloroquine (Plaquenil) are prescribed more than the recommended maximum amount, according to new research. In separate studies, Canadian and U.S. researchers found that 30 to 50 percent of patients didn’t receive the dose outlined in treatment guidelines; a smaller percentage didn’t get recommended eye exams.

Hydroxychloroquine is an antimalarial drug commonly used to treat rheumatoid arthritis (RA), lupus and other autoimmune diseases, either alone or as a part of combination therapy. Unlike some of the other traditional disease-modifying antirheumatic drugs (DMARDs) and biologics, it affects the immune response without suppressing the immune system or increasing the risk of infection. It’s generally safe at normal doses, but higher amounts can damage the retina, the light-sensitive tissue at the back of the eye, and result in partial or complete blindness. Hydroxychloroquine-related eye problems were once considered rare, but better detection methods now show that they occur in about 7 percent of patients. The risk increases with a higher dose and longer therapy.

Vision risks

Hydroxychloroquine is dosed according to body weight. The American Academy of Ophthalmology (AAO) currently defines an overdose of hydroxychloroquine as more than 5.0 milligrams (mg) per kilogram (kg) of body weight (1 kg equals 2.2 pounds) or more than 400 mg a day.

An eye exam is recommended at the start of treatment to detect any existing vision problems; follow-up tests are needed to catch retinal damage in the earliest stages, before symptoms appear. If found later, damage to the eye may be irreversible, even if the medication is stopped.

Yet Canadian researchers found in a study that approximately one-third of 90 arthritis patients at eight different rheumatology clinics weren’t prescribed appropriate weight-based doses of hydroxychloroquine, and 12 percent failed to have an eye exam in the first year of treatment.

This is “significantly below the standard of care,” says Sahil Koppikar, MD, a physician at Queens University in Ontario, Canada, who reported the findings at the annual meeting of the Canadian Rheumatology Association in February.

In a separate study, published in Ophthalmology in early 2017, Rebekah Braslow, MD, and colleagues at NorthShore University HealthSystem in Chicago retrospectively reviewed the records of more than 550 rheumatology patients seen by NorthShore ophthalmologists between 2009 and 2016. About half had been prescribed too much hydroxychloroquine, and dosing errors continued at the same rate even after the AAO issued revised treatment guidelines in 2016.

Why dosing goes wrong

Dr. Braslow says several things probably account for prescribing errors. Some of the blame falls on drug manufacturers, who offer only 200 mg pills, which are hard to calibrate to body weight. As Dr. Koppikar points out, it’s easier to prescribe a 400 mg pill than calculate an exact dose.

Changing and conflicting guidelines may also cause some confusion. The 2011 AAO guidelines recommended dosing hydroxychloroquine based on ideal body weight – what a patient should weigh for their height. This was supposed to ensure that people who were very short or overweight got the right amount of drug. The proposed daily dose was 6.5 mg per kg of ideal body weight. That recommendation was lowered in March 2016 to 5.0 mg per kg of actual body weight, up to a maximum of 400 mg a day.

The American College of Rheumatology (ACR) does not recommend a safe dosage, and although the ACR notes rheumatologists have received “a tremendous amount of information with regard to screening and preventing retinal toxicity,” it also acknowledges that some doctors still don’t dose according to patient weight.

“It behooves rheumatologists to adopt the recommendations of the American Academy of Ophthalmology because there is more toxicity [from hydroxychloroquine] than we previously appreciated,” says James Rosenbaum, MD, chief of ophthalmology at Devers Eye Institute and chief of arthritis and rheumatic diseases at Oregon Health & Science University, both in Portland, Oregon. “It is [also] far easier to determine actual body weight as opposed to calculating ideal body weight, so I prefer to rely on actual body weight.”

Both the AAO and ACR recommend that patients starting hydroxychloroquine have a baseline eye exam using newer imaging technologies. But while the AAO prefers optical coherence tomography (OCT), a noninvasive screening test for retinal disease, the ACR doesn’t specifically endorse it.

Dr. Rosenbaum says that the AAO’s guidelines are based on emerging data that show the value of OCT screening, and he points out that “since rheumatologists refer patients to ophthalmologists for screening, presumably the AAO guidelines will be the ones that tend to be actually followed.”

Make sure you get the right dose

It’s not clear what it will take to prevent incorrect dosing of hydroxychloroquine. Suggestions range from simple dosing charts and better monitoring of electronic medical records by doctors and pharmacists to more formulation options from drug makers and the use of compounding pharmacies. In the meantime, make sure you receive a baseline eye exam when starting hydroxychloroquine and talk to your doctor to make sure your dose isn’t too high.

Author: Linda Rath for the Arthritis Foundation

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