Plaquenil side effects and how to avoid them

Diarrhea, weight loss, and eye problems are some Plaquenil side effects. Here's how to avoid them.

By Georgia C. Yalanis, MD | May 7, 2021 Medically reviewed by Josephine Bawab, Pharm.D.

Plaquenil is the brand name for hydroxychloroquine sulfate. It’s an antimalarial drug that was also approved by the U.S. Food and Drug Administration (FDA) for the treatment of acute and chronic rheumatoid arthritis, systemic lupus erythematosus, discoid lupus erythematosus, and other inflammatory autoimmune diseases.

Plaquenil is a disease-modifying antirheumatic drug (DMARD), which helps regulate or normalize an overactive immune system. This decreases painful inflammation in the body of rheumatology patients.

Plaquenil is a prescription medication that is not available over-the-counter. It usually takes one to three months to start working and often is taken over a long period of time. While Plaquenil is considered safe for long-term use, patients should be aware of the side effects, warnings, and interactions of Plaquenil with other drugs.

Common side effects of Plaquenil

Plaquenil is an older drug and generally well-tolerated. With all of the activity around hydroxychloroquine during the coronavirus pandemic, much of the historical literature has been edited or removed. Even the FDA and CDC websites do not contain the information they once did. The drug has been redefined in the context of COVID-19.

Most side effects from taking Plaquenil are mild and do not require medical attention. These include:

Dizziness or feelings of lightheadedness or fainting
Ataxia or a lack of muscle control or muscle weakness
Headache
Abdominal pain
Nausea
Vomiting
Diarrhea
Pruritis or itchy skin
Weight loss from loss of appetite
Hair bleaching
Photosensitivity
Tinnitus or hearing ringing or noises in the ears
Vision changes
Tiredness

Sometimes, diarrhea and weight loss from taking Plaquenil can be severe and may require medical attention.

Diarrhea

Severe diarrhea requiring medical attention would include:

Diarrhea that has lasted more than two days
More than six episodes of diarrhea within 24 hours
Diarrhea that is black, tarry, or contains pus
Bloody diarrhea
Diarrhea accompanied by persistent vomiting
Severe pain in the abdomen or rectum
Diarrhea accompanied by a fever of 102°F or higher
Signs of severe dehydration include feelings of dizziness or lightheadedness, extreme thirst, dry mucous membranes (mouth, lips, eyes, nose), or infrequent urination with dark yellow or strong-smelling urine

Weight changes

Plaquenil suppresses appetite. Therefore, most people who experience body weight changes from taking Plaquenil experience weight loss. Some people taking Plaquenil may experience weight gain from fluid retention, but weight gain is generally not a common side effect of Plaquenil.

Severe weight changes requiring medical attention would include evidence of rapid weight loss or gain, which is the loss or gain of 10 or more pounds in one month.

Photosensitivity

Plaquenil can cause increased sensitivity to the sun, referred to as photosensitivity. This sensitivity may be exacerbated in individuals with systemic lupus erythematosus and porphyria cutanea tarda who are already photosensitive. Individuals with these conditions may experience a sunburn, painful blistering, and changes to skin color while taking Plaquenil.

Serious side effects of Plaquenil

Some people taking Plaquenil may experience serious side effects. These include:

Blood and blood cell disorders including agranulocytosis, thrombocytopenia, aplastic anemia, and leukopenia
Seizures
Angioedema or swelling of the mucosa and under the skin
Bronchospasm or difficulty breathing, shortness of breath, and wheezing from spasm of the airways
Serious skin conditions like exfoliative dermatitis, toxic epidermal necrolysis, or a psoriasis exacerbation
Stevens-Johnson syndrome or flu-like symptoms accompanied by a painful, blistering rash
Porphyria exacerbation
Drug reactions with eosinophilia and systemic symptoms
Serious eye problems from high-dose or long-term use including retinal damage, retinopathy, or macular degeneration
Myopathy
Fulminant hepatic failure
Serious heart problems including cardiomyopathy, ventricular arrhythmia, QT prolongation, and torsades de pointes
Suicidality
Hypoglycemia or low blood sugar

Eye problems

People who are taking high doses of Plaquenil or who have been taking Plaquenil for a long time are more likely to experience serious damage to the eyes in the form of retinal damage, retinopathy, and macular degeneration. Retinopathy occurs in almost 20% of patients taking Plaquenil for 20 years or more, according to a review on hydroxychloroquine published in the journal Eye.

Retinal damage and retinopathy

Plaquenil is toxic to the retina, which is responsible for creating the images we visually perceive. When these cells are damaged or diseased, various forms of vision problems can occur, including loss of color, central, and peripheral vision.

In clinical studies, retinal toxicity has occurred 2.8 times more frequently in patients with cumulative Plaquenil doses of 1,250 grams or more. Significant risk also occurs in individuals taking daily doses greater than 6.5 mg/kg of body weight per day. Damage to the retina is serious and irreversible. Discontinue Plaquenil if retinal toxicity is suspected. Healthcare providers may recommend an eye exam to establish a baseline before patients start Plaquenil.

Macular degeneration

Macular degeneration causes loss of central vision, commonly associated with blurry vision. Patients should notify their healthcare provider if they notice any type of vision loss or blurry vision.

Rash

Some people taking Plaquenil may experience a very rare, but severe skin rash called Stevens-Johnson syndrome. It is a disorder of the skin and mucous membranes that starts with flu-like symptoms and quickly progresses to a painful, blistering rash that rapidly spreads throughout the body. The skin will then peel, forming painful erosions. Stevens-Johnson syndrome has only been recorded in the literature in fewer than 26 people and is more likely to occur in individuals with systemic lupus erythematosus. Patients should notify their healthcare provider right away if they experience flu-like symptoms accompanied by a rash or a severe skin rash alone.

QT prolongation

Plaquenil may affect the heart rhythm causing a condition called QT prolongation. People taking certain medications that prolong the QT interval on an ECG should have their ECG routinely monitored to prevent arrhythmias or any type of irregular heartbeat.

Plaquenil and hair loss

Hair loss is not a documented side effect of Plaquenil. If it does occur, it is so extremely rare that it is not documented in the literature. In fact, hydroxychloroquine is actually used to prevent hair loss from other medications. However, hair hypopigmentation, or hair color lightening, can occur from damage to pigment cells.

How long do Plaquenil side effects last?

Common and temporary side effects like nausea, vomiting, and headache usually resolve after several weeks and often go away on their own. More serious side effects may be permanent (retinal damage) or may resolve within a few weeks to several months once the medication has been discontinued (certain blood cell disorders).

Plaquenil contraindications and warnings

Withdrawal

There is no associated withdrawal with discontinuing the use of Plaquenil. However, symptom recurrence is common with discontinued use.

Toxicity

Plaquenil is considered a safe drug for long-term use, with many people taking it indefinitely. The maximum dose varies according to the condition it is being used to treat. For malaria treatment, 1,600 mg may be given within the first 24 hours. For lupus and rheumatoid arthritis, a starting dose of 600 mg is common. The maximum maintenance dose is 400 mg per day. Do not take doses of 400 mg or more per day as they are associated with increased side effects.

Overdosing on Plaquenil can have potentially serious effects. Plaquenil can be toxic to the cells in the eye or blood cells at very high doses or with long-term use. Overdosing may also cause toxic symptoms related to the heart, such as headache, drowsiness, visual disturbance, or cardiovascular collapse within 30 minutes of overdose. Patients should notify their healthcare provider if they think they have taken too much medication.

Restrictions

Plaquenil is contraindicated in patients with known hypersensitivity to 4-aminoquinoline compounds such as amodiaquine and chloroquine.

Individuals with known eye pathology, heart pathology, or an abnormal heart rhythm, kidney or liver disease, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and certain skin conditions should use caution when taking Plaquenil. Use caution when using Plaquenil in pediatric patients.

Clinical trials involving Plaquenil are generally not performed due to the increased incidence of arrhythmias in certain individuals.

Plaquenil and pregnancy

Plaquenil is considered safe for use during pregnancy. Use caution when taking Plaquenil while breastfeeding as it can be found in human milk and infants are more sensitive to its toxic effects.

Plaquenil interactions

Individuals taking the following medications could experience a harmful drug interaction and should not take Plaquenil:

Cisapride
Dronedarone
Eliglustat
Pimozide
Thioridazine

People taking other drugs that modify the immune system like cyclosporine should have blood cell counts monitored while taking Plaquenil. Additionally, Plaquenil may increase the serum concentration of cyclosporine when administered together. Patients taking both cyclosporine and Plaquenil should have their serum cyclosporine levels closely monitored.

How to avoid Plaquenil side effects

It is important to follow medical advice while taking this medication. Take all of the doses exactly how and when they are prescribed by a healthcare professional. Do not take more or less medication than prescribed. Patients should continue this medication even if they feel better after the first few doses.
Store the medication correctly. Plaquenil should be stored at room temperature (68 to 77°F).
Swallow the tablet whole. Do not crush, break, or chew it. Take it with food or right after a meal. Antacids and kaolin can reduce the absorption of Plaquenil. Do not take antacids for four hours before or after taking Plaquenil.
Patients should disclose a full medication list, health history, and allergies before taking Plaquenil. This includes all medications and supplements, any medical conditions the patient has, or any allergic reactions they have had to medications in the past.
Avoid unnecessary sun exposure, sunbathing, or use of tanning beds. Patients should use sunscreen when they are outside and wear sun-protective clothing like hats and long-sleeves.
Plaquenil is safe for daily and lifetime use. Patients should notify their healthcare provider immediately if they have any concerns or experience any type of allergic reaction to this or other medications.