What is the risk associated with Plaquenil (Hydroxychloroquine)?

From the Guidelines

Plaquenil (Hydroxychloroquine) carries a significant risk of retinal toxicity, which can be minimized by maintaining a daily dosage of ≤5 mg/kg/day actual body weight, with the risk being <2% for usage up to 10 years 1. The most significant concern with Plaquenil is retinal toxicity, which can lead to permanent vision loss if not detected early.

Key Points to Consider

• Patients taking Plaquenil should have a baseline eye examination before starting treatment and regular screenings thereafter, typically annually for those on long-term therapy.
• The risk of retinal toxicity increases with higher daily dosing (>5 mg/kg real body weight) and longer duration of use (>5 years) 1.
• Other potential side effects include cardiac complications (QT prolongation, cardiomyopathy), skin reactions, hypoglycemia, and blood disorders.
• Patients should report any visual changes, muscle weakness, or irregular heartbeat immediately.
• The medication should be taken with food to reduce gastrointestinal side effects, and patients should inform all healthcare providers about this medication.
• Regular blood work to monitor complete blood counts and liver/kidney function is recommended.

Recommendations for Safe Use

• Widespread adoption of more sensitive testing techniques, such as optical coherence tomography and automated visual fields, by eye care providers will allow the detection of early toxicity and thus preserve the patient’s visual function 1.
• Providers should be sensitive to the medical value of HCQ, and not stop the drug for uncertain indications.
• Effective communication among prescribing physicians, patients, and eye care providers will optimize the utility and safety of HCQ.

From the FDA Drug Label

Therefore, hydroxychloroquine sulfate is not recommended in patients taking other drugs that have the potential to prolong the QT interval or are arrhythmogenic [see Warnings and Precautions (5.1)]. 7. 2 Insulin or Other Antidiabetic Drugs Hydroxychloroquine sulfate may enhance the effects of insulin and antidiabetic drugs, and consequently increase the hypoglycemic risk. 7. 3 Drugs that Lower the Seizure Threshold Hydroxychloroquine sulfate can lower the seizure threshold. 7.4 Antiepileptics The activity of antiepileptic drugs might be impaired if co-administered with hydroxychloroquine sulfate. 7. 5 Methotrexate Concomitant use of hydroxychloroquine sulfate and methotrexate may increase the incidence of adverse reactions. 7.6 Cyclosporine An increased plasma cyclosporin level was reported when cyclosporin and hydroxychloroquine sulfate were co-administered. 7. 7 Digoxin Concomitant hydroxychloroquine sulfate and digoxin therapy may result in increased serum digoxin levels. 7. 8 Cimetidine Concomitant use of cimetidine resulted in a 2-fold increase of exposure of chloroquine, which is structurally related to hydroxychloroquine. 7. 9 Rifampicin Lack of efficacy of hydroxychloroquine was reported when rifampicin was concomitantly administered. 7.10 Praziquantel Chloroquine has been reported to reduce the bioavailability of praziquantel. 7. 11 Antacids and kaolin Antacids and kaolin can reduce absorption of chloroquine; an interval of at least 4 hours between intake of these agents and chloroquine should be observed. 7. 12 Ampicillin In a study of healthy volunteers, chloroquine significantly reduced the bioavailability of ampicillin.

The risk associated with Plaquenil (Hydroxychloroquine) includes:

• Cardiac risks: Prolongation of the QT interval or arrhythmogenic effects
• Hypoglycemic risk: Enhanced effects of insulin and antidiabetic drugs
• Seizure risk: Lowering of the seizure threshold
• Adverse reactions: Increased incidence of adverse reactions with concomitant use of methotrexate
• Drug interactions: Increased plasma cyclosporin level, increased serum digoxin levels, and reduced bioavailability of praziquantel and ampicillin These risks are based on the information provided in the drug labels 2, 2, and 2.

From the Research

Risk of Retinal Toxicity

The risk of retinal toxicity associated with Plaquenil (Hydroxychloroquine) is a significant concern, as it can lead to irreversible maculopathy and vision loss.

• The incidence of hydroxychloroquine-related retinopathy in patients treated with recommended dosages of the drug for a mean of 8.7 years was reduced to 0.5% 3.
• However, the risk of retinal toxicity rises to nearly 1% with a total cumulative dose of 1,000 g, which is approximately 5 to 7 years of normal use 4.
• A baseline ophthalmic examination should be performed on all patients before initiating Plaquenil, and annual screenings are recommended, especially for high-risk patients or those taking the drug for more than 6 years 3, 5, 4.

Factors Contributing to Retinal Toxicity

Several factors can contribute to the risk of retinal toxicity associated with Plaquenil, including:

• High doses of the drug, above the recommended 6.5 mg/kg/day 3, 6.
• Long-term use of the drug, exceeding 6 years 3, 5, 4.
• Preexisting kidney or liver dysfunction, which can affect the clearance of the drug 4.
• Concurrent use of other medications, such as nonsteroidal anti-inflammatory drugs (NSAIDs) 4.

Screening and Monitoring

Regular screening and monitoring are essential to minimize the risk of retinal toxicity associated with Plaquenil.

• Annual ophthalmologic screenings are recommended for patients taking hydroxychloroquine, especially those with risk factors or taking high doses of the drug 5, 4.
• A baseline ophthalmic examination should be performed before initiating Plaquenil therapy to confirm the absence of preexisting fundus pathology 3, 5.
• Patients should be educated on the potential risks of retinal toxicity and the importance of regular eye exams to monitor for any changes in their vision or retinal health 7.