The Complications Of Arriving at a Hydroxychloroquine Dosage
Complication #1: Wide Variance of Response
Hydroxychloroquine is an effective drug, and however, it can provide very different side effects in other people. In reviewing those who have taken Hydroxychloroquine, the most significant thing stopping people from taking it is the side effects, which greatly depend upon the individual. What this means is that different individuals have different tolerance for Hydroxychloroquine. Even with these known variances in tolerance — MDs continue to recommend 400 MG per day virtually universally. This is illogical and is why our dosage recommendation is based on a lower initial dosage with incremental increases. This issue is explained in the following quotation from Arthritis.org.
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% of patients didn’t receive the dose outlined in treatment guidelines; a smaller percentage didn’t get recommended eye exams.
Hydroxychloroquine is generally safe at normal doses, but higher amounts can damage the retina, the light-sensitive tissue at the back of the eye, and could result in partial or complete blindness. Hydroxychloroquine-related eye problems were once considered rare, but better detection methods now show they occur in a greater proportion of patients — more than the 7% originally thought. More recent data show retinal toxicity occurs in more than 10% of patients who have taken hydroxychloroquine for more than 10 years, and in anywhere from 20% to 50% of those who have taken the drug more than 20 years. The risk increases not only with a higher dose and more years taking it but also in African Americans and people who are slender.
Yet Canadian researchers found in a study that approximately one-third of 90 arthritis patients at eight different rheumatology clinics were not prescribed appropriate weight-based doses of hydroxychloroquine, and 12% 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 rheumatologist at Women’s College Hospital in Toronto, Canada.
In a separate study, published in Ophthalmology in early 2017, Rebekah Braslow, MD, and colleagues at NorthShore University HealthSystem in Chicago 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.
Complication #2: The Complication of Generic Effectiveness Combined With HCQ’s Long Lead Time or Half-Life
As with many generic drugs, some generic hydroxychloroquine versions, particularly those manufactured in India, are ineffective or low in effectiveness; however, the problem with this is taking a while for Hydroxychloroquine to show its effect. This is explained in the following quotation. Here is a review from Drug.com from a person who took Hydroxychloroquine for rheumatoid arthritis.
This medication hydroxychloroquine has been an absolute lifesaver for me! I was diagnosed with Undifferentiated Connective Tissue Disease 10 years ago. I’ve been taking Plaquenil for 8 years. I take 400 mg 5 days per week. It took about 4 months to build up enough in my system to start working.
HCQ has a half-life of 40 days. So if you take a dose of 400 MG daily, in 40 days, that 200 MG will still be circulating in your body.
The presentation by the medical establishment that all generics are identical to the brand name version of the drug is false, as bioequivalence is commonly falsified and easy to falsify.
The dosage varies depending on whether Hydroxychloroquine is taken short or long-term, and this is because the drug has a delayed effect.
This is why many MDs begin with a higher initial dosage than the longer-term one, as the Medical News Today article explains.
For rheumatoid arthritis (RA), you’ll begin Plaquenil treatment by taking a starting dosage of the drug. (The starting dosage is higher than the dosage you’ll take on a long-term basis.) Once Plaquenil begins reducing your RA symptoms, your doctor will decrease your dosage.
The typical starting dosage of Plaquenil for RA is 400 mg to 600 mg daily. This total daily dosage may be taken as a single dose once daily or as divided doses twice daily.
So if you’re taking 400 mg of Plaquenil daily, you may take 400 mg as either a single dose once daily or 200 mg twice daily. If you develop side effects, your doctor may reduce your starting dosage of Plaquenil to help decrease the side effects.
After Plaquenil begins reducing your RA symptoms, your doctor may lower your dosage. Usually, the maintenance (long-term) dosage of Plaquenil for RA is 200 mg to 400 mg daily. And this total daily dosage may be taken as a single dose once daily or as divided doses twice daily.
Plaquenil dosages for RA shouldn’t be more than 600 mg daily. In addition, you shouldn’t take a daily dosage of Plaquenil that’s higher than 5 mg of drug per kilogram (kg) of your body weight.
However, here is the issue with starting with a higher initial dosage. Here is a review from Drug.com from a person who took Hydroxychloroquine for rheumatoid arthritis.
I started this Rx just over 3 wks. ago and upon further research of good vs. bad, decided to half my Dr’s daily dose to 200mg/day rather than 400mg. This proved to be wise decision as I broke out in a severe case of hives, going on 3 days now.
Complication #3: The Issue of Macular Degeneration
A longer-term side effect is macular degeneration, so periodic eye exams are essential when taking Hydroxychloroquine.
Due to these and even more factors, Hydroxychloroquine is one of the more challenging drugs to dose correctly. The dosage for HCQ is widely known, but it is too high, and medicine has done a poor job of adjusting the dosage.
Retinopathy’s irreversibility—the threat of permanent vision loss—and its substantial prevalence in patients with a large drug exposure history, have marked retinopathy as the most concerning potential toxicity. The risk of ocular toxicity increases with the cumulative hydroxychloroquine dose. The prevalence of retinopathy in those using the drug less than 10 years is less than 2%; in contrast, the prevalence in patients with more than 20 years of exposure is reported to be as high as 20%.26
Currently, initial screening followed by yearly screening beginning 5 years thereafter is recommended for patients at low risk of toxicity. Patients determined by an ophthalmologist to be at higher risk of retinopathy should be screened yearly. As identified by the American Academy of Ophthalmology, major risk factors for retinopathy include duration of use, concomitant tamoxifen exposure, significant renal disease, and preexisting retinal and macular disease.
And this quote from Arthritis.ca is similar — and explains when retinal damage tends to occur.
The most common vision-related issue are corneal deposits. This is usually due to high daily doses or HCQ and rarely occurs at doses of 400 mg per day or less. The deposits do not affect vision but can cause sensitivity to light and the appearance of halos or rings around lights. Very rarely HCQ can cause deposits at the back of the eye (retinal deposits). If this occurs, you might notice blurred vision, decreased night and peripheral vision, difficulties focusing your eyes, reading or seeing words and letters, and parts of objects may also appear to be missing. Damage to the retina is extremely rare in cases where a person has been taking HCQ for less than two years. However, once damage occurs, it may be permanent, therefore, appropriate monitoring of your eyes is essential.
Complication #4: The Pill Size Versus the Dosage
This issue is a confusion between the purchasing unit and the dosage.
The appropriate dose of Hydroxychloroquine depends on the patient’s body weight. The American Academy of Ophthalmology (AAO) currently defines an overdose of Hydroxychloroquine as more than 5 milligrams (mg) per kilogram (2.2 pounds) of body weight or more than 400 mg a day. Dr. Braslow says several things probably account for prescribing errors. Some 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 and faster to prescribe a 400 mg pill than calculate an exact dose, but that puts patients at risk.
This means that even though the problems with side effects from HCQ are well known, the packaging unit (pill dosage) controls the dosage! And this same problem has been going on for many years now.
Complication #5: The Body Weight Versus the Metabolically Active Body Weight
Changing and conflicting guidelines may also confuse. The 2011 AAO guidelines recommended dosing Hydroxychloroquine based on ideal body weight — what a patient should weigh for their height rather than their actual weight. This was supposed to ensure that people who were very short or overweight got the right amount of drugs. The proposed daily dose was 6.5 mg per kilogram (kg) of ideal body weight, and that recommendation was lowered in March 2016 to 5 mg per kg of actual body weight, up to a maximum of 400 mg daily.
This is an issue that is larger than just HCQ because most of the population in the US and many other countries is overweight. However, fat is not metabolically active — and does not process much of any drug. This means accounting for how overweight a person is and then using the ideal body weight or the body weight without the excess body fat to arrive at a proper dosage.
A study of about 200 patients with a history of hydroxychloroquine retinopathy, including 36 Asian patients, found that the pericentral pattern occurred in half the Asian patients but only 2% of the white patients.
Therefore, the American Academy of Ophthalmology now recommends reducing the dose limit from 6.5 mg/kg of ideal body weight to no more than 5.0 mg/kg of real body weight.
Improvements from Entirely Basic Changes in One Canadian Hospital
One Canadian hospital instituted three simple interventions: dosing charts and scales in all clinic offices and requiring patients receiving hydroxychloroquine to have their weight entered in their electronic medical records. Ten months after these changes were introduced, the percentage of patients receiving the right dose of hydroxychloroquine increased from 30% to 89% and the percentage undergoing eye screening tests increased from 51% to 91%.
These are fundamental changes — and the fact that these changes nearly eliminated the problems also shows how little mental effort went into dosage adjustments previously.
Dosage Recommendation #1: The Dosage Recommendation For Hydroxychloroquine Manufactured Outside of India
The dosage from non-Indian manufactured HCQ is the standard level.
Keep reading and see the calculator below.
Dosage Recommendation #2: The Dosage Recommendation For Hydroxychloroquine Manufactured in India
The problem is knowing how much less active ingredient there is. This is a current area of testing we are engaging in, so I don’t have the answer presently. When I do, this article will be updated with that information.
Until that research is complete, the recommended dosage for taking Indian-manufactured Hydroxychloroquine is 20% higher. Remember — as we cover in the articles on generic drugs, generic drugs made in India or China have the following issues.
These countries do not have functioning drug regulatory bodies.
The FDA and EMA (Europe’s FDA) spend minimal effort regulating the manufacturing facilities they approve to export to the US and Europe.
Pharmaceutical manufacturers face cutthroat price competition; therefore, reducing the active ingredient in the drugs they sell is one way to compete.
Therefore, given the expected reduced active ingredient, this would be between .24 MG per pound of body weight.
Important Information About Taking Hydroxychloroquine
Hydroxychloroquine doesn’t work immediately. It may be 12 weeks or longer before you notice any benefit. Because it’s a long-term treatment it’s important to keep taking hydroxychloroquine unless you have severe side effects:
Before starting on hydroxychloroquine your doctor may take a blood test to check that your liver and kidneys are working normally, but you won’t need any regular blood tests during the treatment.
Your doctor will ask you about any problems with your eyesight and may suggest you have a vision test. Hydroxychloroquine won’t usually be prescribed if you have maculopathy, problems with the central part of the retina in the eye.
The Autoimmune Dosage Calculator
This dosage is for autoimmune disorders and is daily; cancer dosages are higher.
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