The drug is particularly well suited for a subset of patients. How often have we seen an unfortunate young adult with active RA, who, prior to consultation, has tried every supplement and antiinflammatory diet, but then declines a trial of methotrexate or a biologic out of fear of side effects? Even after explaining that serious side effects with these more powerful drugs are uncommon and that the benefits far outweigh the risks, I’m often up against a wall of distrust and fear. Rather than have the patient leave the office empty-handed, I’m usually able to convince them to take a prescription for Plaquenil. It keeps them in the fold. It establishes trust. Over time, I can usually, if necessary, add a more effective drug.
Cautions & Dosing
Of course, no drug is absolutely safe. Plaquenil rashes are seen relatively frequently. Some patients simply don’t tolerate the drug. Diarrhea and headaches may be a reason for discontinuation, and rare cases of neuromyopathy have been reported. A 45-year-old patient of mine on Plaquenil for 12 years developed a cardiomyopathy. An endomyocardial biopsy was consistent with Plaquenil toxicity. The drug was stopped, but her ejection fraction never recovered.
We need to remain vigilant regarding retinal toxicity by dosing the drug based on lean body weight and remembering that most reported cases of retinal toxicity have been in patients prescribed greater than 5.5 mg/kg/day. (Or alternatively, as Ronald Melles, MD, and Michael Marmor, MD, recently suggested, dosage should be no greater than 5.0 mg/kg real weight).19 Because Plaquenil is primarily cleared by the kidneys, it’s prudent to decrease the dose in patients with renal insufficiency.
Our patients require Plaquenil eye check-ups, but these recommendations have evolved from earlier years in which a baseline assessment was followed indefinitely with check-ups every six months to the current recommendations by the American College of Ophthalmology that after a baseline evaluation, a second eye exam is not required for five years unless there are unusual risk factors.20
Improved Cancer Survival?
Lastly, who would have predicted that Plaquenil may play a role in the treatment of malignancy? Autophagy is the process of sequestration of stressed or damaged organelles and proteins into lysosomes where they are subsequently degraded. In established malignancy, an “autophagy switch” occurs, with increased autophagy activity and decreased apoptosis, both of which favor malignant cell survival. Plaquenil, through pH dependent inhibition of lysosomal activity, may partially block cancer upregulation of autophagy.21
