Difference Between Methotrexate And Methotrexate Sodium

Methotrexate and Methotrexate Sodium, while closely related in name and medical use, hold distinct characteristics that differentiate them in the fields of pharmacology and patient treatment. Originally developed for their potent effectiveness in treating cancer, these compounds are now widely used across various medical conditions, including autoimmune diseases. This distinction, however, often leads to confusion regarding their specific applications and implications in treatment.

Methotrexate is a chemotherapy agent and immune system suppressant. Methotrexate Sodium, its derivative, is the sodium salt form that dissolves more readily in water and is primarily used in specific injectable formulations. The key difference lies in their physical form and solubility, which influences their use in medical practice, particularly in how they are administered to patients.

Focusing on their pharmacological profiles, Methotrexate works by inhibiting the metabolism of folic acid, which is crucial for cell growth and replication. This mechanism is crucial in the treatment of cancer and autoimmune diseases. Methotrexate Sodium, while similar, is used in cases where a quicker and more soluble formulation is required, making it preferable for certain therapeutic conditions.

Chemical Composition

Methotrexate Basics

Methotrexate (MTX) is classified chemically as an antimetabolite. As a derivative of folic acid, it plays a crucial role in hindering the body’s ability to process and use folic acid, which is vital for the synthesis of nucleic acid. This interruption is particularly significant as it affects the replication of rapidly dividing cells, such as those seen in cancerous tumors and certain immune cells involved in autoimmune diseases.

The molecular formula of Methotrexate is C20H22N8O5, showcasing a complex structure that includes carbon, hydrogen, nitrogen, and oxygen elements. This composition allows it to easily integrate into the metabolic pathways that manage folic acid.

Methotrexate Sodium Basics

Methotrexate Sodium, the sodium salt form of Methotrexate, maintains the same fundamental chemical properties as its parent compound but differs in its physical form. Its solubility in water is a defining feature, allowing for its use in liquid formulations suitable for injection. This form is beneficial in clinical settings where rapid absorption and immediate drug action are required.

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Chemically, Methotrexate Sodium can be denoted as C20H21N8NaO5, indicating the addition of a sodium atom. This change enhances its dissolution rate in bodily fluids, facilitating faster and more efficient drug delivery into the bloodstream.


Absorption and Metabolism

The absorption of Methotrexate varies based on the form administered. Oral Methotrexate is absorbed through the gastrointestinal tract but can be inconsistent, with bioavailability ranging from 60% to 90%. Factors such as dose size and the presence of food can affect absorption rates.

Once absorbed, Methotrexate enters the liver where it undergoes metabolism. The drug is partially metabolized by enzymes to form polyglutamated derivatives, which can remain active within cells for weeks. This transformation allows Methotrexate to inhibit enzymes involved in purine metabolism, extending its therapeutic effects over time.

Methotrexate Sodium, when administered via injection, bypasses the gastrointestinal system, leading to nearly complete bioavailability. This method ensures direct entry into systemic circulation, providing quicker onset of action, which is crucial in managing severe symptoms that require immediate attention.

Excretion Patterns

Methotrexate is primarily excreted through the kidneys. It is crucial for patients to have adequate renal function to effectively eliminate the drug, as impaired renal function can lead to increased toxicity. Approximately 90% of the administered dose is excreted unchanged in the urine within 24 hours.

Monitoring kidney function is essential, especially in patients receiving higher doses or long-term therapy. Ensuring hydration and occasionally adjusting the dosage based on renal performance are standard practices to mitigate risk and enhance patient safety.

Medical Uses

Uses of Methotrexate

Methotrexate serves multiple roles in medical treatment, primarily in:

  • Cancer Treatment: It is used to treat types of cancer such as leukemia, breast cancer, and lung cancer, where cell proliferation is rapid.
  • Autoimmune Disorders: Conditions like rheumatoid arthritis, psoriasis, and Crohn’s disease benefit from its ability to suppress the immune system and reduce inflammation.

The flexibility of Methotrexate in dosing schedules allows it to be tailored to individual patient needs, ranging from weekly doses in arthritis to high doses in cancer chemotherapy protocols.

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Uses of Methotrexate Sodium

Methotrexate Sodium is particularly used in clinical settings where:

  • Injectable Treatments are preferred. Its solubility makes it ideal for intravenous, intramuscular, or subcutaneous injections, providing options for rapid and targeted therapy.
  • High-dose Methotrexate Therapy is required. Its efficient absorption and rapid onset of action are beneficial in treating severe episodes of autoimmune disorders or aggressively proliferating tumors.

Side Effects

Common Side Effects

Both forms of Methotrexate can cause side effects, such as:

  • Nausea and Vomiting
  • Diarrhea
  • Fatigue
  • Mouth Sores

These side effects are generally manageable with supportive care and dose adjustments.

Long-term Risks

Long-term use of Methotrexate, especially in higher doses, can lead to more serious side effects such as:

  • Liver Damage: Regular liver function tests are necessary to monitor health.
  • Bone Marrow Suppression: This can lead to decreased blood cell counts, increasing the risk of infections and anemia.
  • Pulmonary Toxicity: Monitoring lung function is crucial as some patients may develop lung complications.

Dosage Forms

Tablet and Injection Forms

Methotrexate is available in several dosage forms, each designed to suit various treatment requirements and patient preferences. Tablets are commonly used for chronic conditions such as rheumatoid arthritis, where patients may take the medication regularly at home. The typical tablet dosages range from 2.5 mg to 10 mg, often taken once a week rather than daily to reduce side effects.

Injection forms of Methotrexate provide a more direct and sometimes immediate intervention, particularly useful in severe cases of autoimmune disorders or aggressive cancers. Methotrexate Sodium especially is favored in injectable form due to its enhanced solubility, making it ideal for intramuscular, intravenous, or subcutaneous administration. This form is critical in hospital settings or during acute care when swift therapeutic action is needed.

Comparative Analysis

Comparing tablets and injections:

  • Tablets offer convenience and are less invasive, suitable for long-term management of conditions.
  • Injections provide better absorption and faster response, crucial in critical care situations.


Treatment Efficacy

Methotrexate’s effectiveness in treating inflammatory and neoplastic diseases is well-documented. Its ability to interfere with DNA synthesis, repair, and cellular replication helps manage symptoms and progression in various medical conditions.

  • Cancer: Methotrexate reduces the proliferation of cancer cells, often leading to remission in cases like leukemia.
  • Autoimmune diseases: For diseases like rheumatoid arthritis, it decreases the immune system’s abnormal response, leading to significant improvements in symptoms and quality of life.
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Comparative Studies

Studies comparing Methotrexate with other treatments often highlight its efficacy. For instance, in rheumatoid arthritis, Methotrexate is considered more effective than some first-line treatments, with many patients achieving sustained remission or minimal disease activity.

Patient Considerations

Who Should Use Methotrexate

Methotrexate is suitable for patients requiring management of severe or chronic conditions, such as:

  • Cancer patients, particularly those with leukemia, breast cancer, or lung cancer.
  • Individuals with severe rheumatoid arthritis or psoriasis, where other medications have failed.

Who Should Use Methotrexate Sodium

Methotrexate Sodium is often chosen for patients who:

  • Need rapid action of the medication, such as in acute lymphoblastic leukemia.
  • Cannot tolerate oral medications or have issues with gastrointestinal absorption.

Physician Insights

Doctor Recommendations

Physicians typically recommend Methotrexate based on a patient’s medical history, severity of the disease, and their overall health profile. Regular monitoring through blood tests, liver function tests, and renal function assessments are critical to ensure the safety and effectiveness of the treatment.

Choosing Between the Two

The choice between Methotrexate and Methotrexate Sodium often depends on:

  • The urgency of treatment: Immediate conditions may necessitate the use of injectable Methotrexate Sodium.
  • Patient compliance and convenience: Oral tablets may be preferred by patients managing chronic conditions at home.

Frequently Asked Questions

What is Methotrexate?

Methotrexate is a medication used primarily to treat cancer and autoimmune diseases by inhibiting cell growth. It interferes with the growth of certain cells of the body, especially cells that reproduce quickly.

What is Methotrexate Sodium?

Methotrexate Sodium is the sodium salt version of Methotrexate, which is more soluble in water. It is often used in liquid form for injectable delivery, especially in hospital settings or other clinical environments.

How do Methotrexate and Methotrexate Sodium differ?

The primary difference between Methotrexate and Methotrexate Sodium is their chemical form. Methotrexate Sodium is more water-soluble, which can influence its absorption rate and the way it is administered.

When is Methotrexate Sodium preferred over Methotrexate?

Methotrexate Sodium is often preferred in situations where rapid absorption is needed or where injection is the preferred method of delivery, due to its higher solubility.


In conclusion, understanding the distinctions between Methotrexate and Methotrexate Sodium is crucial for healthcare professionals and patients alike. These differences, primarily related to chemical form and solubility, impact their pharmacological use and patient management strategies.

In summary, while both medications serve critical roles in the treatment of cancer and autoimmune diseases, the choice between Methotrexate and Methotrexate Sodium should be guided by specific clinical needs, patient health profiles, and treatment goals. This ensures that each patient receives the most effective and appropriate treatment for their individual condition.

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