Solving the Hydroxychloroquine Dosing Dilemma With a Smartphone App | Mobile Health and Telemedicine | JAMA Ophthalmology | JAMA Network
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Figure.  Mathematical Relationship Between the Actual Body Weight and Ideal Body Weight Methods
Mathematical Relationship Between the Actual Body Weight and Ideal Body Weight Methods

Equation of the equality line: height (cm) = weight (kg) + 79.71.

1.
Braslow  RA, Shiloach  M, Macsai  MS.  Adherence to hydroxychloroquine dosing guidelines by rheumatologists: an electronic medical record–based study in an integrated health care system.  Ophthalmology. 2017;124(5):604-608.PubMedGoogle ScholarCrossref
2.
Browning  DJ.  The prevalence of hydroxychloroquine retinopathy and toxic dosing, and the role of the ophthalmologist in reducing both.  Am J Ophthalmol. 2016;166(6):ix-xi.PubMedGoogle ScholarCrossref
3.
Melles  RB, Marmor  MF.  The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy.  JAMA Ophthalmol. 2014;132(12):1453-1460.PubMedGoogle ScholarCrossref
4.
Browning  DJ, Lee  C, Rotberg  D.  The impact of different algorithms for ideal body weight on screening for hydroxychloroquine retinopathy in women.  Clin Ophthalmol. 2014;8:1401-1407.PubMedGoogle ScholarCrossref
5.
Marmor  MF, Kellner  U, Lai  TY, Melles  RB, Mieler  WF; American Academy of Ophthalmology.  Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision).  Ophthalmology. 2016;123(6):1386-1394.PubMedGoogle ScholarCrossref
Research Letter
February 2018

Solving the Hydroxychloroquine Dosing Dilemma With a Smartphone App

Author Affiliations
  • 1Rhode Island Eye Institute, Providence
  • 2Section of Ophthalmology, Providence Veterans Affairs Medical Center, Providence, Rhode Island
  • 3Charlotte, Eye, Ear, Nose, and Throat Associates, Charlotte, North Carolina
  • 4Department of Medicine, Newton-Wellesley Hospital, Newton, Massachusetts
  • 5Retina Service, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts
JAMA Ophthalmol. 2018;136(2):218-219. doi:10.1001/jamaophthalmol.2017.6076

Hydroxychloroquine retinopathy (HCR) is a potentially blinding disease. Once HCR is detected, there is no treatment and the disease often continues to progress, even when the medication is stopped. Hence, primary prevention by appropriate dosing of hydroxychloroquine offers the best chance of minimizing the risk of HCR.

This strategy remains challenging in practice as up to 56% of patients receive hydroxychloroquine at doses that place them at higher risk for HCR.1 A key reason is disagreement in how to calculate dosages of hydroxychloroquine.2,3 There are 2 methods: one uses ideal body weight (IBW); the other uses actual body weight (ABW). The IBW method assumes that hydroxychloroquine is stored mostly in lean tissue.2 The daily dose must be normalized by lean body mass. This makes the calculation more complicated than the ABW method, which assumes that the drug is distributed evenly in muscle, skin, and fat.3 We describe a free smartphone app—DoseChecker—that can rapidly calculate the optimal weekly dose of hydroxychloroquine using elements of both methods.

Methods

The code for the DoseChecker app was written by one of us (E.M.P.) using the smartBASIC app. SmartBASIC provides an XCode shell for a Basic interpreter and the interpreter is then used to generate an app compatible with the iOS operating system. Massachusetts Eye and Ear became the Apple Developer for the app on May 4, 2017. The app became available in the App Store on September 10, 2017.

ABW Method

Maximum Daily Dose = 5 (mg/kg/d) × ABW (kg)

IBW Method

The National Lung and Blood Institute formula is expressed in pounds: IBW (lb) = 4.28 × Height (in) − 134.32. It is then converted to kilograms.

Maximum Daily Dose = 6.5 (mg/kg/d) × IBW (kg).

The calculation uses the National Lung and Blood Institute IBW formula for women.4 The app does not distinguish between men and women since 95% of HCR occurs in women; because the IBW calculation yields a lower value for women than for men of the same height, it results in a more conservative dosage for men. By equating the maximum daily dose formulas for each method and solving algebraically, the equation for the line of equality is derived (Figure).

Results

The DoseChecker app uses 2 new approaches to hydroxychloroquine dosing:

  1. Instead of selecting the IBW or ABW method, the app uses both methods. It determines the maximum dose to avoid toxic effects using both calculation methods and preferentially selects the method that recommends the lower dose. The premise here is that to avoid toxic effects the lowest dose is the safest dose. The Figure shows the mathematical relationship between the 2 methods.

  2. The app uses an adjustable weekly dosing schedule. Since the drug is only available as a 200-mg tablet, the app suggests a total weekly hydroxychloroquine dose using a combination of 400-mg and 200-mg daily doses.

This regimen will yield the highest therapeutic dose attainable without exceeding the toxic limit, defined as the lower dose of the 2 methods.

Discussion

The DoseChecker app is available in the app store for phones with iOS operating systems. The prescribing physician enters the patient’s height and weight, touches the calculate button, and the recommended weekly dosing appears immediately. The dosing recommendations always fall within the approved drug labeling and are for use only by a clinician, which eliminates the need for US Food and Drug Administration regulation as a class I mobile medical device. Prescribing physicians still need to consider other factors that may affect the risk for HCR, including systemic disease, concomitant retinal disease, and the cumulative dose.5 Ophthalmologists should also adhere to the American Academy of Ophthalmology recommendations for screening and follow-up.5 Further studies are needed to evaluate the influence of DoseChecker on physician prescribing patterns for hydroxychloroquine.

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Article Information

Accepted for Publication: November 8, 2017.

Corresponding Author: Paul B. Greenberg, MD, MPH, Section of Ophthalmology, Providence Veterans Affairs Medical Center, 830 Chalkstone Ave, Providence, RI 02908 (paul_greenberg@brown.edu).

Published Online: January 4, 2018. doi:10.1001/jamaophthalmol.2017.6076

Author Contributions: Drs Perlman and Greenberg had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Perlman, Greenberg, Browning, Miller.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Perlman, Greenberg, Browning, Miller.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Perlman, Browning.

Administrative, technical, or material support: All authors.

Study supervision: Perlman, Greenberg, Browning, Miller.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Browning reports receiving grants from DRCR network, Regeneron Pharmaceuticals, Genentech Inc, Ohr Pharmaceutical Inc, Hawk Pharmaceuticals, and Alcon Co outside the submitted work; and a patent with Springer Inc with royalties paid and stock in Zeiss. Dr Miller reports receiving personal fees from Amgen Inc, KalVista Pharmaceuticals, Biogen Idec Inc, and Alcon Research Council; grants from Lowy Medical Research Institute Ltd outside the submitted work; and nonfinancial support from Maculogix Inc. Dr Miller has a patent through the Massachusetts Eye and Ear Institute/Valeant Pharmaceuticals with royalties paid to Valeant Pharmaceuticals, and a patent with ONL Therapeutics LLC, with royalties paid to ONL Therapeutics LLC. No other conflicts were reported.

Disclaimer: The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government.

Additional Contributions: Leo A. Kim, MD, PhD, John B. Miller, MD, and George N. Papaliodis, MD (Massachusetts Eye and Ear) pilot tested the app and provided feedback. They received no compensation for their contributions.

References
1.
Braslow  RA, Shiloach  M, Macsai  MS.  Adherence to hydroxychloroquine dosing guidelines by rheumatologists: an electronic medical record–based study in an integrated health care system.  Ophthalmology. 2017;124(5):604-608.PubMedGoogle ScholarCrossref
2.
Browning  DJ.  The prevalence of hydroxychloroquine retinopathy and toxic dosing, and the role of the ophthalmologist in reducing both.  Am J Ophthalmol. 2016;166(6):ix-xi.PubMedGoogle ScholarCrossref
3.
Melles  RB, Marmor  MF.  The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy.  JAMA Ophthalmol. 2014;132(12):1453-1460.PubMedGoogle ScholarCrossref
4.
Browning  DJ, Lee  C, Rotberg  D.  The impact of different algorithms for ideal body weight on screening for hydroxychloroquine retinopathy in women.  Clin Ophthalmol. 2014;8:1401-1407.PubMedGoogle ScholarCrossref
5.
Marmor  MF, Kellner  U, Lai  TY, Melles  RB, Mieler  WF; American Academy of Ophthalmology.  Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision).  Ophthalmology. 2016;123(6):1386-1394.PubMedGoogle ScholarCrossref
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