Methotrexate vs Plaquenil

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For patients with rheumatoid arthritis (RA) or other types of autoimmune diseases, certain drugs that modify the immune system's response can help control symptoms and slow disease progression. Methotrexate and Plaquenil are two such drugs prescribed for these conditions. They each work differently to reduce inflammation in the body but both have efficacy in managing RA symptoms. Methotrexate is a disease-modifying antirheumatic drug (DMARD), affecting cell growth by inhibiting folic acid activity, which reduces inflammation associated with RA. Plaquenil, on the other hand, is classified as an antimalarial DMARD and works primarily by suppressing the immune system's overactive response that causes ongoing inflammation in patients with autoimmune diseases.

What is Methotrexate?

Methotrexate (MTX) was first synthesized in the 1940s and is a cornerstone drug for treating several conditions such as rheumatoid arthritis, psoriasis, and certain types of cancer. It works by inhibiting an enzyme involved in the rapid growth of cells and reducing inflammation. The medication can be taken orally or administered via injection. MTX acts quickly but might lead to adverse effects like nausea, mouth ulcers, hair thinning or liver toxicity which necessitates regular blood monitoring.

On the other hand, Hydroxychloroquine (generic name for Plaquenil), developed in the mid-20th century as an antimalarial agent but also found effective against auto-immune diseases including lupus and rheumatoid arthritis. Unlike methotrexate that targets rapidly dividing cells, hydroxychloroquine prevents immune activation by decreasing antigen presentation to T-cells thus dampening inflammatory response. This mechanism translates into fewer side-effects compared to MTX but it usually takes longer time period to show full therapeutic benefits. These two drugs are often used complementarily depending upon individual condition severity and patient's tolerance towards potential side effects.

What conditions is Methotrexate approved to treat?

Methotrexate is approved for the treatment of several conditions:

  • Rheumatoid arthritis, including juvenile idiopathic arthritis

  • Severe and disabling psoriasis that hasn't responded to other treatments

  • Certain types of cancer, like acute lymphoblastic leukemia, breast cancer, and lung cancer Plaquenil (Hydroxychloroquine), on the other hand:

  • Is commonly used for treating and preventing malaria

  • Can also be prescribed for rheumatoid arthritis and lupus.

How does Methotrexate help with these illnesses?

Methotrexate helps to manage autoimmune diseases by interfering with the rapid growth of cells in the body, particularly those involved in inflammation. It does this by inhibiting an enzyme called dihydrofolate reductase, which is necessary for DNA synthesis and thus cell reproduction. By slowing down cell reproduction, Methotrexate can reduce the severity of inflammation typically associated with conditions such as rheumatoid arthritis or psoriasis. Inflammation plays a significant role in these conditions' symptoms like joint pain and skin lesions. Therefore, by managing inflammation at a cellular level, Methotrexate can limit the negative impact of these diseases and help patients control their symptoms better.

On the other hand, Plaquenil (Hydroxychloroquine) also manages autoimmune diseases but it operates differently from Methotrexate. While its precise mechanisms are not fully understood yet, it's believed that Plaquenil interferes with communication between cells in the immune system. By disrupting this communication process, Plaquenil can prevent an overactive immune response which often leads to unnecessary inflammation and damage within these autoimmune conditions.

What is Plaquenil?

Plaquenil, with the generic name hydroxychloroquine, is an antimalarial medication that is also widely used to treat autoimmune conditions such as rheumatoid arthritis and lupus. It works by reducing inflammation within the body, though its exact mechanism of action is not completely understood. Plaquenil was first approved by the FDA in 1955 and has proven effective for many patients suffering from chronic inflammatory conditions. Unlike methotrexate which can cause significant liver toxicity and requires regular blood testing for safety monitoring, Plaquenil generally carries less risk of severe side effects. However, it's important to note that long-term use may lead to retinal damage so periodic eye exams are recommended while using this medication. Its mild side-effect profile makes it a preferred choice for many clinicians and patients grappling with these chronic conditions.

What conditions is Plaquenil approved to treat?

Plaquenil, also known as hydroxychloroquine, is approved for the treatment of:

  • Rheumatoid arthritis
  • Systemic lupus erythematosus (commonly referred to as "lupus")
  • Acute and chronic malaria (although it's not typically the first choice for this use)

How does Plaquenil help with these illnesses?

Plaquenil, also known as hydroxychloroquine, is an antimalarial drug that has been repurposed to treat autoimmune conditions such as rheumatoid arthritis and lupus. It works by reducing the immune system's response, thereby decreasing inflammation in the body and preventing damage to vital organs caused by these diseases. This function is similar to methotrexate; however, Plaquenil operates on a different pathway within cells and can be considered less potent yet safer than methotrexate overall. Because of its gentler action on the body systems while still providing symptom relief for patients with autoimmune disorders, Plaquenil may be prescribed when a patient does not respond well or cannot tolerate stronger drugs like methotrexate due to side effects.

How effective are both Methotrexate and Plaquenil?

Methotrexate and hydroxychloroquine (Plaquenil) are both commonly used in the treatment of rheumatic diseases, particularly Rheumatoid Arthritis. They were initially approved by the FDA decades apart; methotrexate in 1953 and Plaquenil in 1955. Their mechanisms of action differ significantly - methotrexate is a folic acid antagonist that primarily inhibits cell growth while hydroxychloroquine is an antimalarial drug with anti-inflammatory properties.

Both medications have been directly compared for their effectiveness in treating rheumatoid arthritis. A study conducted in 1990, demonstrated similar efficacy between methotrexate and Plaquenil when it came to controlling signs and symptoms of the disease over a six-month period. However, it was noted that patients treated with methotrexate showed slightly higher improvement rate than those on Plaquenil.

A review published in The Cochrane Library documented that methotrexate appears to be highly effective at reducing inflammation associated with RA starting from first few weeks of treatment, demonstrating favorable outcomes among many other DMARDs (Disease-Modifying Antirheumatic Drugs). This has led to its widespread use globally as a first-line therapy for RA. Additionally, evidence suggests that low-dose weekly regimens (7.5–25 mg/week) can mitigate side effects such as hepatotoxicity or bone marrow suppression.

Hydroxychloroquine demonstrates its therapeutic benefits slower than other DMARDs but offers fewer side effects making it suitable for long-term treatment especially for mild cases of RA or as part of combination therapies due to its good safety profile. Yet studies suggest Hydroxychloroquine should not be considered as potent or effective as Methothexrate alone but may provide significant additive benefits when used together which would allow lower doses of each medication thereby minimizing potential toxicities.

abstract image of a researcher studying a bottle of drug.

At what dose is Methotrexate typically prescribed?

Oral dosages of Methotrexate range from 7.5-20 mg/week, but research has suggested that a starting dose of 7.5 mg/week could be enough for managing rheumatoid arthritis in many patients. Children and adolescents' dosage should be determined by their doctor based on the child's weight and overall health condition. In either population, dosage can be increased after a few weeks if there is no response or as tolerated by the patient's body without causing serious side effects. The maximum weekly dosage that should not exceed under any circumstances is 20 mg/week.

On the other hand, Plaquenil (Hydroxychloroquine) is typically prescribed at a daily dose of 200–400 mg for adults suffering from conditions like lupus or rheumatoid arthritis. For children and adolescents, their treating physician will determine an appropriate dosage based on their body weight; generally it shouldn't surpass 6.5mg/kg (of ideal body weight). It's important to note that exceeding the recommended maximum daily dose increases risk for potential vision problems.

At what dose is Plaquenil typically prescribed?

Plaquenil treatment typically commences with a dose of 200–400 mg/day, depending on the individual's weight and disease severity. This dosing can be split into two doses, taken approximately 12 hours apart. In some cases, if the response to therapy is not sufficient after several weeks or months at this level, your doctor might increase the daily dose up to a maximum of 600 mg/day divided into two doses for a short period of time. It's essential that patients adhere strictly to these guidelines due to potential side effects related to overdose such as vision impairment.

What are the most common side effects for Methotrexate?

Typical side effects of methotrexate include:

  • Nausea and vomiting
  • Stomach pain or upset stomach
  • Dizziness, tiredness or drowsiness
  • Headache
  • Hair loss, skin rash or itchiness
  • Inflammation in the mouth (mouth sores)
  • Decreased appetite (anorexia)

Whereas, common side effects of Plaquenil are:

  • Diarrhea and stomach cramps
  • Mild nausea or stomach pain
  • Loss of appetite
  • Tired feeling, sleep problems (insomnia)
  • Skin rashes or changes in skin color
  • Hair loss or changes in hair texture

It's crucial to remember that any medication can have potential side effects and these may vary from person to person. Always consult with a healthcare professional before starting a new medication.

abstract image of a patient experiencing side effect

Are there any potential serious side effects for Methotrexate?

Methotrexate, in rare instances, may cause serious side effects that require immediate medical attention. These include:

  • Unusual bleeding or bruising
  • Signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat
  • Blurred vision or sudden loss of vision
  • Irregular heartbeat, chest pain or discomfort
  • Severe dizziness and fainting
  • Low white blood cell count - fever, mouth sores, skin sores, sore throat
  • Liver problems – including nausea and vomiting (may be severe), loss of appetite right upper abdominal discomfort , yellowing eyes/skin (jaundice), dark urine.

On the other hand Plaquenil has its own potential side effects which include:

  • Vision changes such as light flashes/streaks/halos/blurred vision/difficulty reading at night.
  • Symptoms related to heart complications like chest pain/discomfort/shortness of breath/swelling legs/irregular heartbeats.
  • Muscle weakness/twitches/uncontrolled movement/balance issues/trouble speaking/swallowing/thinking etc indicating nervous system disorders.

If you experience any such symptoms while on Methotrexate or Plaquenil therapy contact health care professional without delay.

What are the most common side effects for Plaquenil?

Plaquenil, a medication frequently used to treat conditions such as lupus and rheumatoid arthritis, has its own unique set of potential side effects. These may include:

  • Nausea or stomach cramps
  • Diarrhea
  • Dizziness or headache
  • Occasional ringing in the ears or loss of balance (vestibular symptoms)
  • Rarely, blurred vision or other changes in vision due to an effect on the retina
  • Less common: rash, changes in skin pigmentation,
  • Very rarely: muscle weakness Please note that while some patients might experience these side effects they tend to be less severe than those associated with Methotrexate. It's important for patients taking Plaquenil to have regular eye exams and report any visual symptoms immediately.

Are there any potential serious side effects for Plaquenil?

Plaquenil, while generally well-tolerated, can occasionally cause serious side effects. If you experience any of the following symptoms after taking Plaquenil, seek medical attention immediately:

  • Signs of an allergic reaction such as hives, itching or skin rash
  • Difficulties in breathing or swallowing due to throat swelling
  • Symptoms suggesting heart problems including chest discomfort and irregular heartbeat
  • Changes in mood or behavior that are unusual for you
  • Vision disturbances like blurred vision; seeing halos around lights; sensitivity to light; temporary loss of vision
  • Muscle weakness leading to unsteadiness when walking
  • Severe abdominal pain accompanied by persistent vomiting.

These adverse reactions may not be exhaustive and it's advisable to consult your healthcare provider if you feel uncomfortable after taking Plaquenil.

Contraindications for Methotrexate and Plaquenil?

Both Methotrexate and Plaquenil, like many other drugs used for the treatment of autoimmune diseases, may cause side effects that could potentially worsen your health condition. If you notice an increase in symptoms or new symptoms emerging, such as persistent sore throat, fever, fatigue or gastrointestinal issues after starting these medications, please seek medical attention immediately.

Neither Methotrexate nor Plaquenil should be taken if you are using certain antibiotics (like penicillin) or have been taking biologic agents (such as adalimumab). Always give a detailed history of your medication to your physician; some drugs require a washout period to clear from the system to prevent dangerous interactions with Methotrexate and Plaquenil. In addition, both these drugs can potentially harm an unborn child; hence they must not be administered during pregnancy without consulting with a doctor.

How much do Methotrexate and Plaquenil cost?

For the brand name versions of these drugs:

  • The price for 60 tablets of Rheumatrex, a brand-name version of methotrexate (2.5 mg), averages around $100 which works out to approximately $1.66/day depending on your dose.
  • The price for 30 tablets of Plaquenil (200 mg) averages around $180, working out to approximately $6/day.

Thus, if you are in the higher dosage range for Rheumatrex like taking up to three doses per week, then branded Plaquenil may be more expensive on a per-day treatment basis. However, cost should not be the primary consideration when determining which one is right for you; efficacy and side effects play significant roles too.

For the generic versions of methotrexate and hydroxychloroquine (Plaquenil):

  • Methotrexate (2.5 mg tablets) can be obtained in packs starting from 12 capsules with approximate costs ranging from $0.50 to $3/day depending on whether you take it once or thrice weekly.
  • Hydroxychloroquine is available in packs starting from 30 capsules at an average cost between $4 and$5 per day.

It's important to note that prices may vary widely based on location, pharmacy choice, and insurance coverage. Generic medications typically offer substantial savings over their brand-name counterparts without sacrificing effectiveness or safety.

Popularity of Methotrexate and Plaquenil

Methotrexate, a disease-modifying antirheumatic drug (DMARD), is commonly prescribed for the treatment of rheumatoid arthritis and several types of cancer. In 2020, it was estimated to have been prescribed to about 2 million people in the US. Methotrexate accounted for just over 18% of DMARD prescriptions in the US. The prevalence of methotrexate has been relatively steady since its approval by FDA in the 1980s.

Hydroxychloroquine, also known as Plaquenil, is another DMARD that's often used for treating autoimmune conditions such as lupus and rheumatoid arthritis. In addition to this, it's an established antimalarial medication. Hydroxychloroquine was prescribed to approximately 3 million people in the USA during 2020 due to its temporary use for COVID-19 at that time which boosted its prescription rate temporarily; otherwise it accounts closer around under one million prescriptions annually normally in US.


Both Methotrexate and Plaquenil (hydroxychloroquine) have a long-standing record of usage in patients with autoimmune diseases such as rheumatoid arthritis, lupus, and psoriasis. They are backed by numerous clinical studies indicating their efficacy over placebo treatments. In some cases, the drugs may be combined for a synergistic effect or when one drug alone is not sufficient to manage symptoms.

Methotrexate acts primarily by inhibiting the metabolism of folic acid which is crucial for rapidly dividing cells like those found in inflammatory conditions. On the other hand, Plaquenil works mainly by reducing inflammation process though its exact mechanism is still not completely understood.

Methotrexate is often considered a first-line treatment option for certain autoimmune diseases due to its potent anti-inflammatory effects. However, because of potential side effects including liver damage and bone marrow suppression amongst others it requires careful monitoring.

Plaquenil on the other hand has milder side effects but can affect vision requiring regular eye check-ups while using this medication.

Both drugs are available in generic form, representing significant cost savings especially for patients who must pay out-of-pocket. Both Methotrexate and Plaquenil may require an adjustment period meaning that full therapeutic effects might take weeks to months to be noticeable.

In terms of adverse reactions both drugs are generally well-tolerated but with different profiles: methotrexate being more likely associated with gastrointestinal disturbance and potential liver toxicity; plaquenil less commonly affecting stomach but potentially causing retinal damage over time.

For both drugs patients need close medical supervision particularly during initiation phase or dose adjustments; they should seek immediate help if experiencing unusual symptoms that may suggest severe drug reaction or worsening condition.