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Methotrexate (Folitrax): What to Expect From Treatment

Medically reviewed by Dr. Naresh Gundu, Medical Oncologist, MBBS (Chalmeda Anand Rao Institute of Medical Sciences, Karimnagar) · DNB Internal Medicine (Sir Gangaram Hospital, New Delhi) · DM Medical Oncology (AIIMS) · Last reviewed September 2026

Methotrexate is familiar to many families as a low-dose arthritis tablet. At cancer doses, it is a very different treatment — given by drip in hospital, with close monitoring and a protective follow-on medicine called leucovorin built into the schedule from the start.

Prescription-only medicine.

Methotrexate is a prescription-only medicine given under the supervision of a specialist oncologist. It cannot be started, adjusted or stopped on the basis of anything read online or in any source outside a direct clinical consultation with your treating team. It is not suitable for everyone — see who this is not for below.

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In short

Methotrexate (Folitrax) blocks cell division by interrupting the way cells use folate. At cancer doses — far higher than those used for arthritis — it can cause mouth sores, nausea, low blood counts, and strain on the kidneys and liver. A follow-on medicine called leucovorin is given after each infusion to protect healthy cells. Side effects are monitored closely throughout.

In detail

Why does the methotrexate dose for cancer look so different from arthritis?

Methotrexate is prescribed for cancer at doses that can be many times higher than those used for arthritis or psoriasis. That gap is why the side effects are so different. If someone in your family takes methotrexate as a weekly tablet for arthritis, their experience is unlikely to be a guide to yours.

At cancer doses, methotrexate floods the system with a molecule that blocks an enzyme cancer cells need to copy their DNA. Because rapidly dividing cells — healthy and cancerous alike — depend on this pathway, the treatment affects more than just the tumour. That is where side effects come from.

At these doses, methotrexate is given by drip in hospital, not as a tablet at home. The length of your stay depends on the dose your oncologist has prescribed and how quickly your body clears the drug.

At a glance

What is leucovorin rescue, and what other terms will you hear?

AntifolateA medicine that blocks the body's use of folate, a B-vitamin cells need to copy their DNA. Methotrexate is the most widely used antifolate in cancer treatment.

High-dose methotrexateA cancer regimen using methotrexate in large amounts given by IV drip. It requires hospital admission, urinary alkalinisation, leucovorin rescue, and close monitoring of blood levels throughout.

Leucovorin rescueA planned course of folinic acid — a form of folate that bypasses the block methotrexate creates — given after the infusion to protect healthy cells. It does not cancel the effect on cancer cells.

MTX levelA blood test measuring how much methotrexate remains in your bloodstream. Your team checks this at set intervals after the infusion to confirm the drug is clearing safely before you are discharged.

Urinary alkalinisationMaking the urine less acidic during high-dose treatment, usually by adding sodium bicarbonate to your drip. This helps the kidneys clear methotrexate more safely and reduces the risk of kidney damage.

Eligibility

Who should not take methotrexate?

Methotrexate is not suitable for everyone, and eligibility for this treatment is decided by an oncologist based on your individual clinical situation.

Have significantly reduced kidney functionMethotrexate is cleared almost entirely through the kidneys, and impaired clearance allows the drug to accumulate to dangerous levels
Have active liver disease, cirrhosis, or significant alcohol-related liver damage
Are pregnant or trying to conceiveMethotrexate is known to cause serious harm to a developing pregnancy
Are breastfeeding
Have an active, uncontrolled infection
Have large collections of fluid in the chest or abdomen, which can act as a reservoir for the drug and slow its clearance

Certain medicines — including some anti-inflammatory drugs, antibiotics, and supplements — can raise methotrexate to dangerous levels. Tell your oncologist about every medicine and supplement you take before treatment begins.

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Checklist

Which side effects should you report to your team?

Mouth sores or ulcers that make eating or swallowing difficult
Nausea or vomiting not controlled by the anti-sickness medicines you have been given
Fever, chills, or unusual tiredness that could suggest infection
Passing less urine than usual, or urine that looks very dark or frothy
Yellowing of the skin or whites of the eyes
Any new skin rash or unusual redness, especially after sun exposure
Headache, confusion, or any sudden change in how you feel mentally

In detail

Why do you need leucovorin after the methotrexate infusion?

After a high-dose methotrexate infusion, your team will give you leucovorin — also called folinic acid. This is not a correction of a problem. It was scheduled before your first dose was given, and it is a standard part of the protocol.

Leucovorin provides a form of folate that healthy cells can use even while methotrexate is still present in your bloodstream. Cancer cells cannot use it in the same way — which is why leucovorin protects healthy tissue without reversing what the treatment is doing to the tumour.

The timing and number of leucovorin doses depends on how quickly methotrexate is leaving your body. Your team will check your MTX level at set intervals and adjust the leucovorin schedule based on those results.

You will remain in hospital until your MTX level falls to the threshold your oncologist has set. Ask your team what that threshold is and what the result needs to show before discharge — it helps to understand what you are waiting for.

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Common questions

Frequently asked questions

My neighbour takes methotrexate as a tablet for arthritis. Why is my dose so different?

The gap between arthritis and cancer doses is very large — sometimes by a factor of many hundreds. In arthritis, methotrexate works through a different mechanism at low doses and is taken weekly as a tablet. In cancer, it is given at doses high enough to overwhelm certain cellular defences and requires IV administration, hospital admission, leucovorin rescue, and close monitoring of blood levels. What your neighbour experiences as a low-dose arthritis medicine is not a guide to your treatment.

Does leucovorin cancel out the chemotherapy?

No. Leucovorin provides a form of folate that bypasses the exact block methotrexate creates. Healthy cells can use it; cancer cells, because of how they handle folate differently, cannot use it as effectively. This is the biology that makes leucovorin rescue possible — it protects normal tissue without reversing the effect on the tumour. Your oncologist would not include it in the schedule if it cancelled the benefit.

What should I do about mouth sores?

Tell your team as soon as you notice mouth sores developing — do not wait for your next scheduled appointment. They are a common side effect of methotrexate and are more manageable when caught early. Your team may recommend specific mouth rinses and will advise on eating while your mouth is sore. Avoid over-the-counter products that contain alcohol, which can worsen irritation, without checking with your team first.

Will I lose my hair on methotrexate?

Hair thinning can happen, but the complete hair loss associated with some other chemotherapy agents is less common with methotrexate alone. How much hair change you experience depends on the dose and the specific regimen you are on. Ask your oncologist what to expect in your treatment, because what applies to one protocol does not necessarily apply to another.

Can I take folic acid supplements during methotrexate treatment for cancer?

Ask your oncologist before taking any folic acid or folate supplement during cancer treatment — the guidance is different from what applies to arthritis patients. In arthritis, low-dose folic acid is often given alongside methotrexate to reduce side effects. In cancer treatment, taking extra folate could potentially reduce the drug's effectiveness. Do not start, change, or stop any supplement, vitamin, or herbal preparation without your team's specific guidance.

How long will I be in hospital for each methotrexate treatment?

You will usually stay for several days, but the exact length depends on how quickly your body clears the drug, which varies between people. You will not be discharged until your MTX blood level falls to the threshold your oncologist has set as safe. Clearance can take longer than expected in some people, which extends the stay. Your team will give you the most accurate estimate for your specific regimen and will keep you informed as results come in.

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The medical oncologists on the CION panel

Chemotherapy is prescribed, dosed and supervised by a medical oncologist. These are the six on the CION panel.

Dr. Naresh Gundu

Medical Oncologist

MBBS · DNB Internal Medicine (Sir Gangaram, New Delhi) · DM Medical Oncology (AIIMS)

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Dr. C. Raghavendra Reddy

Medical Oncologist

MBBS (Gold Medal) · DNB · DM (Medical Oncology, Gold Medal) · Kukatpally

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Dr. Bharati Devi Gorantla

Medical Oncologist

MBBS · MD · DM (Adyar, Chennai) · ECMO · MRCP SCE (UK)

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Dr. Owais Mohammed

Medical Oncologist

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Dr. T. Raghavender Reddy

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MBBS · DM (Medical Oncology) · MD (Radiation Oncology) · L.B. Nagar

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Dr. N. Kiranmayee

Medical Oncologist

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