No universally accepted standards exist regarding methods of screening, follow-up frequency, or judging risks for patients taking antimalarial drugs. Follow-up should be determined by the patient's RISK for developing toxicity. In 2002 the American Academy of Ophthalmology published guidelines for monitoring patients taking antimalarial drugs and identified six risk factors for developing toxicity.

Risk Assessment (American Academy of Ophthalmology Guidelines1)
	Low risk	Higher risk
Dosage	<6.5 mg/kg hydroxychloroquine <3 mg/kg chloroquine	>6.5 mg/kg hydroxychloroquine >3 mg/kg chloroquine
Duration of use	<5 years	>5 years
Habitus (physique)	Lean or average weight	High fat level (unless dosage is appropriately low)
Age	<60 years	>60 years
Renal/liver disease	None	Present
Concomitant retinal disease	None	Present
Marmor M, Carr R, Easterbrook M, et al. Recommendations of Screening for Chloroquine and Hydroxychloroquine Retinopathy. Ophthalmology 2002; 109:1377-1382.

Dosage and Risk: Daily dosage levels are important.

Dosage levels that can cause toxicity are

• >6.5 mg/kg hydroxychloroquine (Plaquenil)
• >3 mg/kg chloroquine (Arlen)

The patient's weight is a critical factor in dosing the medication. With Plaquenil, the typical dosage is either 200 or 400 mg per day. 200 mg daily puts anyone under 68 pounds at risk.¹ 400 mg of Plaquenil daily puts anyone under 135 pounds at a higher risk for toxicity. Therefore, 200mg of Plaquenil daily is a safe dosage for almost all adults; they will have virtually no risk of retinal complications at that level of dosing.¹³

Determination of Weight For hydroxychloroquine toxicity-- 1 kg = 2.2 pounds; 6.5mg/2.2 pounds = 2.95mg/pound. So, for 400 mg/2.95 = 135 pounds. 1 kg = 2.2 pounds; 6.5mg/2.2 pounds = 2.95mg/pound. So, for 200 mg/2.95 = 68 pounds. For chloroquine toxicity-- Typically prescribed at 250 mg/day 1 kg = 2.2 pounds; 3/2.2 pounds = 1.36mg/pound. So, for 250 mg/1.36 = 183 pounds.

Physique and Risk:

Obesity is another risk factor that may cause an overestimation of the safe dose because these drugs don't accumulate in fat and bone,^{1, 13} Often toxic effects develop in those who are small and/or obese.¹⁴

How do you define whether someone is obese? According to the experts, determine the patient's BMI (Body Mass Index). The patient is at higher risk for toxicity if the number is 25 or higher.15   OR, use the following formula14 Men--50 kg plus 2.3 kg per inch over 5 feet Women--45.5 kg plus 2.3 kg per inch over 5 feet

Case Report Patient and Dosing: The patient upon whom this course revolves was 5 feet 1 inch in height and weighed 155 pounds. Her BMI number was 29.5 for her height and weight. A BMI of 30 is considered clinically obese. In her case, she was probably overdosed given her body weight. Dosage should be based on "ideal body weight" and not actual weight.¹⁴

Other Risk Factors for Toxicity

It is rare, but even if the patient is dosed properly for weight, toxicity can occur. To date, there are less than 25 published reports of toxicity occurring at daily doses less than 6.5 mg/kg of Plaquenil and at durations less than 10 years.^{1, 14, 15, 16} Some experts believe those susceptible to antimalarial toxicity have an ABCA4 gene abnormality, similar to patients with Stargardt's disease.¹⁷

• Duration
  The longer the patient is on an antimalarial drug, the more likely he/she is to develop toxicity; however, there is an extremely low chance of toxicity within the first FIVE years of usage of the drug.
• Advanced age
  The AAO believes anyone over the age of 60 is at risk.
• Renal/liver disease
  Antimalarial drugs are cleared both through the kidney and liver.
• Concomitant retinal disease
  For example, age related macular degeneration

Follow-Up Frequency

• Low Risk Patients:
  
  Some experts feel an annual exam is not necessary under the age of 60 with no other risk factors. For example, the AAO recommends that individuals between the ages of 40 and 64 with no risk factors only need an ophthalmologic examination every two to four years.¹ Many rheumatologists prefer their patients be monitored every six months.
  
  Personal Recommendation: Exam annually (unless patient has high risk factors, then biannual exam). Perform same tests for low risk patients as for high risk patients.
• High Risk Patients:
  
  American Academy of Ophthalmology Guidelines¹
  • Evaluate at least once a year
  • BVA
  • Dilated fundus exam
  • 10-2 visual fields -OR- Amsler grid
  
  American Optometric Association Guidelines (AOA does not divide patients into low and high risk)³
  • Evaluate every six months
  • BVA
  • Dilated fundus exam
  • Central threshold visual field
  • Amsler grid
  • Color vision testing
  • Periodic fundus photography

Visual Abnormalities Detected

If questionable early toxicity is noted

• Follow the patient closely every 3 months.
• Consider performing specialized testing such as fluorescein angiography or multifocal ERG.

• Discontinue the drug immediately.
• Re-evaluate in 3 months after discontinuation of the drug (visual function can continue to deteriorate after the drug is discontinued because it can take anywhere from months to years for these meds to clear the blood¹).

	URL: http://www.opt.indiana.edu/ce/plaq/risks.htm Revised: May 7, 2007
	IU Optometry home page: http://www.opt.indiana.edu/ Comments (content): Dr. Julie Torbit at jtorbit@indiana.edu Comments: Web Administrator Page design and coding: Terri Greene Copyright © 2007, The Trustees of Indiana University