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 2011, the American Academy of Ophthalmology updated guidelines for monitoring patients taking antimalarial drugs.

Risk Assessment (American Academy of Ophthalmology Guidelines1)
	Higher risk
Duration of use	>5 years
Daily dose Hydroxychloroquine (HCQ)	>400 mg/day (>6.5 mg/kg ideal body weight for short individuals)
Chloroquine (CQ)	>250 mg/day (>3.0 mg/kg ideal body weight for short individuals)
Cumulative dose	>1000 g (total) HCQ >460 g (total) CQ
Age	Elderly
Systemic disease	Kidney or liver dysfunction
Ocular disease	Retinal disease or maculopathy
Marmor M, Carr R, Easterbrook M, et al. Recommendations of Screening for Chloroquine and Hydroxychloroquine Retinopathy. Ophthalmology 2002; 109:1377-1382.

Dosage and Risk

Cumulative dose:

Cumulative dose is now considered a more critical factor in developing toxicity than daily dose/kilogram (which older literature focused upon).¹⁹ New data has shown that the risk of toxicity begins to increase sharply towards 1% after approximately 5 to 7 years of use.¹⁹ A cumulative dose that exceeds 1000g (total) Hydroxychloroquine (HCQ) and 460 g (total) Chloroquine (CQ) increases the risk of retinal toxicity. Patients prescribed the standard dose of 400mg daily of HCQ will reach the cumulative dose of 1000g in 7 years. A cumulative dose of 460g CQ is reached in 5 years with the typical daily dose of 250mg.¹⁹

Daily dosage:

Daily dosage levels are still important. The typical dosage of Plaquenil is either 200 or 400 mg per day. Doses greater than > 6.5 mg/kg of Plaquenil (or >300mg/kg of Arlen) have been associated with increased risk for retinal toxicity.  New recommendations suggest that daily doses be limited to 400 mg Hydroxychlorquine (HCQ) or 250mg Chloroquine (CQ), unless the patient is short in stature. Lower doses should be calculated for short individuals based upon their ideal body weight.¹⁹

In regards to daily dosing, 200 mg daily puts anyone under 68 pounds at risk (see below).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

For hydroxychloroquine toxicity--
1 kg = 2.2 pounds; 6.5mg/2.2 pounds = 2.95mg/pound. So, for 400 mg HCQ/2.95 = 135 pounds.
1 kg = 2.2 pounds; 6.5mg/2.2 pounds = 2.95mg/pound. So, for 200 mg HCQ/2.95 = 68 pounds

For chloroquine toxicity--
Typically prescribed at 250 CQ mg/day
1 kg = 2.2 pounds; 3/2.2 pounds = 1.36mg/pound. So, for 250 mg CQ/1.36 = 183 pounds.

Physique and Risk

If a person is short in stature or obese, the typical dose of antimalarial drugs may be too high. An overestimation of the safe dose can occur in those who are small and/or obese since these drugs don’t accumulate in fat and bone.^1,13,14 Dosing should be based on "ideal body weight" and not actual weight.¹  Obese individuals should be dosed on the basis of height, by finding an estimation of their “ideal” body weight.¹⁹

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

Other Risk Factors for Toxicity

It is rare, but even if the patient is dosed properly for height and weight, toxicity can still occur.^{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 that the elderly are more at risk to develop toxicity

• 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

• The American Academy of Ophthalmology updated 2011 guidelines recommend:¹⁹

  Ø  Baseline examination within first year of usage of HCQ or CQ

  Ø  Annual screening after 5 years of use

•   The American Optometric Association guidelines are much older and recommend:

  Ø  Baseline examination when starting the HCQ or CQ

  Ø  Evaluate the patient every 6 months

Visual Abnormalities Detected

If questionable early toxicity is noted

• Begin following the patient every 3-6 months for changes
• Obtain specialized testing (if not already performed) such as multifocal ERG, autofluorescence, or spectral domain OCT

If definite changes are noted at the fundus or there are repeatable defects on the VF or other testing:

• 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: Feb 7, 2011
	IU Optometry home page: http://www.opt.indiana.edu/ Comments (content): Dr. Julie Torbit at jtorbit@indiana.edu Comments: Online CE Coordinator Page design and coding: Terri Greene Copyright © 2007, The Trustees of Indiana University