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Posted By: Richard S. Pope, PA-C, MPAS
October 25, 2019
Hydroxychloroquine (Plaquenil) has been a staple for treatment of rheumatoid arthritis, systemic lupus erythematosis (SLE), and discoid lupus for many decades. It is also indicated for prevention and treatment of malaria caused by four types of protozoa of the genus Plasmodium.
Plaquenil was FDA-approved in 1955 and is now commonly ordered as hydroxychloroquine; it is produced by many companies worldwide. In rheumatic diseases, the dosage should be adjusted by weight to 5 mg/kg, as many patients need less than 400 mg daily.
The World Health Organization has listed hydroxychloroquine as one of its "Essential Medicines," that is, one of the safest and most effective drugs in a health system. In 2016 it was the 135th most prescribed medication in the United States, with more than 4 million prescriptions.
Hydroxychloroquine's mechanism of action is to increase intracellular lysosomal pH in antigen-presenting cells (APC). In inflammatory conditions, it blocks toll-like receptors (TLR) and activation of dendritic cells. TLRs recognize DNA-containing immune complexes, which leads to the production of interferon. This causes dendritic cells to mature and present antigens to T-cells, thereby reducing the anti-DNA auto-inflammatory process.
In April 2019, the European League Against Rheumatism (EULAR) released guidelines for the management of SLE, which were subsequently published in the Annals of Rheumatic Disease. The lead author, Antonis Fanouriakis, stated, "All patients with systemic lupus should take hydroxychloroquine."
With multiple beneficial effects, hydroxychloroquine is considered a disease-modifying antirheumatic drug, or DMARD. However, macular toxicity is a risk with long-term use of chloroquine and hydroxychloroquine, especially for patients receiving more than 5 mg/kg, in patients with chronic renal disease, or for those with preexisting retinal or macular disease. The risk begins to go up when a person takes the medication longer than 5 years or has a cumulative dose of more than 1000 grams. Macular changes are often not symptomatic, but patients should be counseled to report color vision changes or paracentral scotomas after beginning treatment. For those without retinal or macular disease, subsequent follow-up is recommended every 5 years, although some ophthalmologists recommend annual exams. If changes are seen on examination that are consistent with side effects, a decision regarding discontinuation is made between the patient and his or her providers.
Hydroxychloroquine is commonly used in rheumatic diseases and is generally safe and well tolerated. It is a drug that primary care clinicians should be familiar with.
- ClinCalc.com. Hydroxycholoroquine Sulfate Drug Usage Statistics, United States, 2006 - 2016. clincalc.com/DrugStats/Drugs/HydroxychloroquineSulfate. Accessed October 24, 2019.
- Fanouriakis A, Kostopoulou M, Alunno A, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Annals of the Rheumatic Diseases. 2019;78:736-745.
- Waller D, Renwick A, Hillier K, Renwick A. Medical Pharmacology and Therapeutics. 2nd ed. United States: Saunders Ltd; 2005.
- World Health Organization. WHO Model List of Essential Medicines 19th List. www.who.int/medicines/publications/essentialmedicines/EML_2015_FINAL_amended_NOV2015.pdf?ua=1. Accessed October 24, 2019.
Filed under: Rheumatology