Hydroxychloroquine (Plaquenil)

What Is Hydroxychloroquine and What Is It Used For?

Quick Answer: Hydroxychloroquine (Plaquenil) is a disease-modifying antirheumatic drug (DMARD) used to treat rheumatoid arthritis, systemic lupus erythematosus (SLE), juvenile idiopathic arthritis, discoid lupus, and certain photosensitive skin conditions. It works by modulating the immune system to reduce inflammation and disease activity.

Hydroxychloroquine belongs to a class of medications known as aminoquinolines. It was originally developed in the 1950s as a safer derivative of chloroquine, an antimalarial drug. While its exact mechanism of action in autoimmune diseases is not fully understood, research has revealed several important immunomodulatory effects. The drug accumulates in lysosomes within immune cells, raising the intracellular pH and thereby interfering with the processing and presentation of antigens by major histocompatibility complex (MHC) class II molecules. This disruption reduces the activation of T cells and dampens the overall immune response.

More recent research has demonstrated that hydroxychloroquine also inhibits toll-like receptor (TLR) signaling, particularly TLR7 and TLR9, which play critical roles in the pathogenesis of lupus. By blocking these receptors, hydroxychloroquine reduces the production of pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6). These anti-inflammatory properties make it a valuable tool in managing chronic autoimmune conditions where excessive immune activation drives tissue damage.

Hydroxychloroquine is listed on the WHO Model List of Essential Medicines, reflecting its importance in global healthcare. The European Alliance of Associations for Rheumatology (EULAR) and the American College of Rheumatology (ACR) both recommend it as a first-line treatment for systemic lupus erythematosus (SLE). In lupus management, hydroxychloroquine has been shown to reduce disease flares, protect against organ damage (particularly kidney involvement), improve survival rates, and reduce the risk of thrombosis.

Approved Indications

Hydroxychloroquine is approved and used for the following conditions:

• Rheumatoid arthritis (RA): Used as a first-line DMARD, often in combination with methotrexate and other DMARDs, to reduce joint inflammation, pain, and stiffness and slow the progression of joint damage.
• Systemic lupus erythematosus (SLE): Considered a cornerstone of lupus therapy. EULAR recommends it for all SLE patients without contraindications due to proven benefits in reducing flares, organ damage, and mortality.
• Discoid lupus erythematosus: Used to treat chronic skin manifestations of lupus, including the characteristic disc-shaped skin lesions.
• Juvenile idiopathic arthritis (JIA): Used in children and adolescents with inflammatory joint disease, though not recommended for children under 6 years or under 35 kg due to the risk of accidental overdose.
• Photosensitive skin conditions: Used for certain forms of light-induced skin rashes where immune modulation is beneficial.

Beyond its approved indications, hydroxychloroquine is sometimes used off-label for conditions such as Sjögren's syndrome, antiphospholipid syndrome, dermatomyositis, and sarcoidosis. In antiphospholipid syndrome, it may help reduce the risk of thrombotic events. However, off-label use should always be discussed with and supervised by a specialist physician.

What Should You Know Before Taking Hydroxychloroquine?

Quick Answer: Before starting hydroxychloroquine, inform your doctor about all medical conditions, especially eye problems, heart disease, liver or kidney disease, porphyria, psoriasis, myasthenia gravis, and epilepsy. A baseline eye examination is required before or within the first year of starting treatment.

Hydroxychloroquine is generally well tolerated compared to many other DMARDs, but certain medical conditions and circumstances require special caution. It is essential to have an open discussion with your prescribing physician about your complete medical history, all current medications (including over-the-counter drugs and supplements), and any planned surgeries or diagnostic procedures before beginning treatment.

Contraindications

You should not take hydroxychloroquine if:

• You are allergic to hydroxychloroquine or any of its inactive ingredients (including lactose monohydrate, povidone, maize starch, magnesium stearate, hypromellose, macrogol, and titanium dioxide).
• You have porphyria (a group of metabolic disorders involving increased excretion of certain blood pigments), as hydroxychloroquine can trigger acute porphyric attacks.
• You have psoriasis, as hydroxychloroquine may worsen the condition and patients with psoriasis appear more susceptible to severe skin reactions.
• You have pre-existing eye or hearing damage that could be exacerbated by the medication, particularly pre-existing maculopathy (damage to the macula of the eye).

Warnings and Precautions

Talk to your doctor before taking hydroxychloroquine if you have any of the following conditions or risk factors:

• Myasthenia gravis: If you have or have had myasthenia gravis (a disease causing general muscle weakness), hydroxychloroquine may worsen symptoms such as muscle weakness, difficulty swallowing, double vision, and drooping upper eyelids.
• Liver or kidney disease: Impaired liver or kidney function may affect how the drug is metabolized and eliminated from the body, potentially increasing the risk of adverse effects. Dose adjustments may be necessary.
• Cardiac conditions: If you have heart disease, a history of heart attack, congenital or acquired QT prolongation, or electrolyte imbalances (particularly low potassium or magnesium), the risk of cardiac side effects is increased.
• Epilepsy or seizure disorders: Hydroxychloroquine can lower the seizure threshold, particularly when taken with other medications that also lower the seizure threshold (such as mefloquine).
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency: Patients with G6PD deficiency may be at increased risk of hemolytic anemia.
• Diabetes: Hydroxychloroquine can lower blood sugar levels. If you take insulin or oral diabetes medications, blood sugar monitoring may need to be more frequent as your doctor may need to adjust your diabetes medication doses.
• Inactive chronic infections: If you have dormant hepatitis B virus, varicella zoster virus (chickenpox/shingles), or tuberculosis, hydroxychloroquine's immunomodulatory effects may theoretically allow reactivation.

Mental Health Considerations

Some patients taking hydroxychloroquine may experience changes in mental health, including irrational thoughts, anxiety, hallucinations, confusion, depression, and in rare cases, suicidal thoughts. These effects can occur even in individuals with no prior history of psychiatric conditions. If you or those around you notice any such changes, seek medical advice immediately. Your doctor will assess whether the medication should be continued or discontinued.

Pregnancy and Breastfeeding

If you are pregnant, planning to become pregnant, or breastfeeding, discuss the use of hydroxychloroquine with your doctor. While the drug does cross the placenta and has been associated with a small increased risk of birth defects, most rheumatology guidelines (including EULAR and ACR) actually recommend continuing hydroxychloroquine during pregnancy in women with SLE. This is because stopping the medication can trigger lupus flares that pose greater risks to both mother and baby, including preeclampsia, preterm birth, and fetal loss.

Hydroxychloroquine is excreted in small amounts in breast milk. The decision to breastfeed while taking this medication should be made in consultation with your doctor, weighing the benefits of breastfeeding and the benefits of continued treatment against any potential risks to the infant. Many experts consider it compatible with breastfeeding at standard therapeutic doses.

Use in Children

Small children are particularly sensitive to aminoquinoline drugs, and accidental overdose can be extremely dangerous and potentially fatal. Hydroxychloroquine should not be used in children under 6 years of age or those weighing less than 35 kg because the 200 mg tablet cannot be split (it has no score line) and accurate dosing for smaller children is not possible with this formulation. Always store the medication securely out of reach and sight of children.

Driving and Operating Machinery

Hydroxychloroquine can affect the eye's ability to focus at different distances (accommodation), which may cause blurred vision. If you experience visual disturbances, do not drive or operate machinery until your vision returns to normal. Discuss any visual changes with your doctor, as they may indicate a need to adjust or discontinue treatment.

How Does Hydroxychloroquine Interact with Other Drugs?

Quick Answer: Hydroxychloroquine interacts with many medications, particularly QT-prolonging drugs, digoxin, antacids, diabetes medications, cyclosporin, and tamoxifen. Always inform your doctor about all medications you are taking, including over-the-counter drugs and herbal supplements.

Drug interactions can alter how hydroxychloroquine works or increase the risk of serious side effects. It is critical to inform your healthcare provider about all medications you are currently taking, have recently taken, or plan to take. This includes prescription drugs, over-the-counter medications, vitamins, and herbal supplements. Below is a comprehensive overview of the most clinically significant interactions.

Major Interactions

Other Notable Interactions

Food and Drink Interactions

Grapefruit juice should be avoided while taking hydroxychloroquine, as it can inhibit the CYP3A4 enzyme responsible for metabolizing the drug, potentially increasing blood levels and the risk of side effects. Hydroxychloroquine can be taken with food or milk to reduce gastrointestinal side effects such as nausea and stomach upset.

What Is the Correct Dosage of Hydroxychloroquine?

Quick Answer: The dosage of hydroxychloroquine is individually determined by your doctor. The maximum recommended daily dose should not exceed 5 mg per kg of actual (real) body weight. For most adults, this translates to 200–400 mg daily. It may take 4 to 12 weeks before the full therapeutic effect is achieved.

Always take hydroxychloroquine exactly as prescribed by your doctor or pharmacist. The dosage is tailored to your specific condition, body weight, kidney function, and other individual factors. Modern guidelines emphasize using actual (real) body weight rather than ideal body weight when calculating the maximum safe dose, as this better predicts the risk of retinal toxicity during long-term treatment.

Adults

Children and Adolescents

Elderly Patients

No specific dosage adjustments are required for elderly patients based on age alone. However, elderly patients are more likely to have reduced kidney function, which may affect drug clearance. Your doctor may check kidney function and adjust the dose accordingly. Elderly patients should also be monitored more closely for side effects, particularly cardiac and ophthalmological effects.

Missed Dose

If you miss a dose, take it as soon as you remember. If it is nearly time for your next dose, skip the missed dose and continue with your regular schedule. Do not take a double dose to make up for a missed one. Because hydroxychloroquine has a very long half-life (approximately 40–50 days), missing a single dose occasionally is unlikely to significantly affect your treatment outcome. However, consistent daily use is important for optimal disease control.

Overdose

Symptoms of overdose may include severe headache, nausea, visual disturbances, drowsiness, seizures, cardiovascular collapse with dangerously low blood pressure, severe cardiac arrhythmias (irregular heartbeats), and cardiac arrest. Children are especially vulnerable because they are highly sensitive to the toxic effects of aminoquinoline drugs. Treatment of overdose requires immediate hospital care with cardiac monitoring, supportive therapy, and may require gastric decontamination if the patient presents early enough.

What Are the Side Effects of Hydroxychloroquine?

Quick Answer: The most common side effects of hydroxychloroquine are gastrointestinal symptoms (nausea, stomach cramps, abdominal pain) affecting more than 1 in 10 patients. Headache, dizziness, blurred vision, and skin rash are also common. Rare but serious side effects include retinal toxicity, cardiomyopathy, and severe skin reactions. Report any unusual symptoms to your doctor promptly.

Like all medications, hydroxychloroquine can cause side effects, although not everyone experiences them. Most side effects are mild and may improve as your body adjusts to the medication. However, some side effects can be serious and require immediate medical attention. The frequency categories below are based on standard pharmacological classification, with side effect data drawn from international regulatory sources including the EMA and FDA.

Long-Term Eye Effects

During continuous treatment, hydroxychloroquine may deposit in the cornea (the clear front surface of the eye), causing symptoms such as halos around lights, blurred vision, or light sensitivity. These corneal deposits are generally reversible if the medication is stopped or temporarily paused. Do not change your dose on your own – always consult your doctor.

The more serious concern is hydroxychloroquine retinopathy, which involves damage to the retina (the light-sensitive layer at the back of the eye). This condition is associated with long-term use, particularly after 5 years of continuous treatment and at cumulative doses above a certain threshold. Unlike corneal deposits, retinal damage can be irreversible if not detected early. This is why regular ophthalmological screening is essential. Modern screening methods using optical coherence tomography (OCT) and automated visual field testing can detect early retinal changes before significant vision loss occurs, allowing treatment to be stopped in time.

How Should You Store Hydroxychloroquine?

Quick Answer: Store hydroxychloroquine at room temperature in the original packaging, out of reach and sight of children. Do not use after the expiry date. Dispose of unused medication through a pharmacy – do not flush down the toilet or throw in household waste.

Proper storage of hydroxychloroquine is essential both for maintaining the medication's effectiveness and for preventing accidental exposure, particularly in households with young children. Aminoquinoline drugs are extremely toxic in children, and even a small accidental ingestion can be life-threatening.

• Temperature: Store at room temperature (below 25°C / 77°F). Do not freeze.
• Light and moisture: Keep in the original blister packaging to protect from moisture and light.
• Child safety: Store out of the sight and reach of children. Consider using a locked medication cabinet if young children are present in the household.
• Expiry date: Do not use after the expiry date printed on the packaging (EXP). The expiry date refers to the last day of the stated month.
• Disposal: Do not dispose of medications via wastewater or household waste. Return unused or expired tablets to your local pharmacy for safe disposal. This helps protect the environment.

What Does Hydroxychloroquine Contain?

Quick Answer: Each hydroxychloroquine film-coated tablet contains 200 mg of hydroxychloroquine sulfate as the active ingredient. Inactive ingredients include lactose monohydrate, povidone, maize starch, magnesium stearate, hypromellose, macrogol, and titanium dioxide (E171).

Active Ingredient

Each film-coated tablet contains 200 mg hydroxychloroquine sulfate, which is equivalent to approximately 155 mg of hydroxychloroquine base. Hydroxychloroquine sulfate is a 4-aminoquinoline compound that was first synthesized in 1946 as a less toxic alternative to chloroquine.

Inactive Ingredients (Excipients)

• Lactose monohydrate – a sugar used as a filler and binder. Patients with lactose intolerance should inform their doctor before taking this medication.
• Povidone – a binding agent that helps hold the tablet together.
• Maize starch – used as a disintegrant to help the tablet break down in the stomach.
• Magnesium stearate – a lubricant used in tablet manufacturing.
• Hypromellose – used in the film coating for protection and ease of swallowing.
• Macrogol – a plasticizer in the film coating.
• Titanium dioxide (E171) – a white pigment used in the film coating.

Tablet Appearance

Hydroxychloroquine 200 mg tablets are white, convex, film-coated, and marked with "HCQ" on one side and "200" on the other. They are supplied in PVC/aluminium blister packs, typically in packs of 100 tablets.

References

This article is based on the following peer-reviewed sources and international medical guidelines. All medical claims are supported by Level 1A evidence (systematic reviews and meta-analyses of randomized controlled trials) where available.

1. Fraenkel L, et al. 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care & Research. 2021;73(7):924–939. doi:10.1002/acr.24596
2. Fanouriakis A, et al. EULAR recommendations for the management of systemic lupus erythematosus: 2023 update. Annals of the Rheumatic Diseases. 2024;83(1):15–29. doi:10.1136/ard-2023-224141
3. Marmor MF, et al. Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision). Ophthalmology. 2016;123(6):1386–1394. doi:10.1016/j.ophtha.2016.01.058
4. World Health Organization. WHO Model List of Essential Medicines – 23rd List (2023). Geneva: WHO; 2023.
5. Ruiz-Irastorza G, et al. Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review. Annals of the Rheumatic Diseases. 2010;69(1):20–28.
6. Costedoat-Chalumeau N, et al. Hydroxychloroquine in systemic lupus erythematosus: results of a French multicentre controlled trial (PLUS Study). Annals of the Rheumatic Diseases. 2013;72(11):1786–1792.
7. National Institute for Health and Care Excellence (NICE). Rheumatoid arthritis in adults: management. NICE guideline [NG100]. Updated 2020.
8. European Medicines Agency (EMA). Hydroxychloroquine sulfate – Summary of Product Characteristics (SmPC).
9. U.S. Food and Drug Administration (FDA). Plaquenil (hydroxychloroquine sulfate) – Prescribing Information.
10. British National Formulary (BNF). Hydroxychloroquine sulfate – Drug monograph.

Editorial Team

This article was written and reviewed by the iMedic Medical Editorial Team, comprising licensed physicians with expertise in rheumatology, clinical pharmacology, and internal medicine. Our editorial process adheres to strict evidence-based methodology following the GRADE framework.