Care During Chemotherapy and Beyond
Trade names: Rheumatrex®, TrexallTM
Other names: Amethopterin, Methotrexate Sodium, MTX
Drug type: Methotrexate is an anti-cancer ("antineoplastic"
or "cytotoxic") chemotherapy drug. This medication is classified as an "antimetabolite."
(For more detail, see "How this drug works" section below).
What this drug is used for:
- Used in the treatment of breast, head and neck, lung, stomach, and esophagus cancers.
Acute lymphoblastic leukemia (ALL), sarcomas, non-Hodgkin's lymphoma (NHL), gestational
trophoblastic cancer, and mycosis fungoides (cutaneous T-cell lymphoma).
Note: If a drug has been approved for one use, physicians
may elect to use this same drug for other problems if they believe it may be helpful.
How this drug is given:
- As an infusion into the vein (intravenous, IV).
- As an injection into the muscle (intramuscular, IM).
- Another method it is given is by intraventricular or intrathecal infusion.
This method is used when drugs need to reach the cerebrospinal fluid (CSF) the fluid
that is surrounding the brain and spinal cord, the drug is infused directly into
the spinal fluid.
- There is also a pill form of methotrexate.
- The amount of methotrexate and how it is given depends on many factors, including
your height and weight, your general health or other health problems, and the type
of cancer or condition being treated. Your doctor will determine your dose,
schedule and how it is given.
Important things to remember about the side effects of methotrexate:
- Most people do not experience all of the side effects listed.
- Side effects are often predictable in terms of their onset and duration.
- Side effects are almost always reversible and will go away after treatment is complete.
- There are many options to help minimize or prevent side effects.
- There is no relationship between the presence or severity of side effects and the
effectiveness of the medication.
- The side effects of methotrexate and their severity depend on how much of the drug
is given. In other words, high doses may produce more severe side effects.
- In some cases leucovorin infusion (see leucovorin) may be given 24 hours after methotrexate
to lessen the side effects of methotrexate.
The following side effects are common (occurring in greater than 30%) for
patients taking methotrexate:
- Low blood counts. Your white and red blood cells and platelets may temporarily
decrease. This can put you at increased risk for infection, anemia and/or
Nadir: Meaning low point, nadir is the point in time between chemotherapy
cycles in which you experience low blood counts.
These side effects are less common side effects (occurring in about 10-29%)
of patients receiving methotrexate:
- Kidney toxicity (see kidney problems) particularly with high-doses. In severe cases
can lead to kidney failure. Care is taken to make sure patient is well hydrated
with IV fluids before infusion of high-dose methotrexate.
- Skin rash, reddening of the skin (with high doses).
- Hair loss
- Eye irritation (conjunctivitis) (see eye problems).
- Increases in blood tests measuring liver function, often seen with high dose treatment.
These return to normal within about 10 days. (see liver problems).
- Darkening of the skin where previous radiation treatment has been given. (radiation
recall - see skin reactions).
- Loss of fertility. Meaning, your ability to conceive or father a child may
be affected by methotrexate. Discuss this issue with your health care provider.
Side effects specific to intrathecal administration of methotrexate (the
drug is infused directly into the cerebrospinal fluid (CSF) the fluid that is surrounding
the brain and spinal cord):
- Acute chemical arachnoiditis: a syndrome that can be seen immediately after the
infusion of methotrexate intrathecally. It is an inflammation of the membrane
surrounding the brain and spinal column. Symptoms are: severe headache, stiff
neck, seizures, vomiting, and fever.
- Central neurotoxicity: Less-common, seen with intrathecal or very high IV dose methotrexate.
Symptoms are; difficulty with speech, paralysis of the arms and legs, seizures,
or coma. This may develop within 6 days of treatment and resolves within 48-72
Not all side effects are listed above. Some that are rare (occurring in less than
10% of patients) are not listed here. However, you should always inform your
health care provider if you experience any unusual symptoms.
When to contact your doctor or health care provider:
Contact your health care provider immediately, day or night, if you
should experience any of the following symptoms:
- Fever of 100.4° F (38° C) or higher, chills (possible signs of infection).
The following symptoms require medical attention, but are not an emergency.
Contact your health care provider within 24 hours of noticing any of the
- Unusual bleeding or bruising
- Black or tarry stools, or blood in your stools or urine
- Extreme fatigue (unable to carry on self-care activities)
- Mouth sores (painful redness, swelling or ulcers)
- Nausea (interferes with ability to eat and unrelieved with prescribed medication)
- Vomiting (vomiting more than 4-5 times in a 24 hour period)
- Diarrhea (4-6 episodes in a 24-hour period)
- No urine output in a 12 hour period
- Yellowing of the skin or eyes
- Swelling of the feet or ankles. Sudden weight gain.
- Signs of infection such as redness or swelling, pain on swallowing, coughing up
mucous, or painful urination.
- Unable to eat or drink for 24 hours or have signs of dehydration: tiredness, thirst,
dry mouth, dark and decrease amount of urine, or dizziness.
Always inform your health care provider if you experience any unusual symptoms.
- Before starting methotrexate treatment, make sure you tell your doctor about any
other medications you are taking (including prescription, over-the-counter, vitamins,
herbal remedies, etc.). Do not take aspirin, or products containing
aspirin unless your doctor specifically permits this.
- Do not take non-steroidal anti-inflammatory drugs (NSAIDS) such as ibuprophen or
naproxen unless your doctor specifically permits this. Bone marrow suppression,
intestinal irritation and severe anemia have occurred with combined usage of non-steroidal
anti-inflammatory drugs (NSAIDS) and methotrexate.
- Folic acid supplements should be avoided while on methotrexate. Folic acid
may counteract the anti-cancer effects of methotrexate.
- If you are on warfarin (Coumadin®) as a blood-thinner,
adjustments may need to be made to your dose based on blood work.
- Do not receive any kind of immunization or vaccination without your doctor's approval
while taking methotrexate.
- Inform your health care professional if you are pregnant or may be pregnant prior
to starting this treatment. Pregnancy category D (methotrexate may be hazardous
to the fetus. Women who are pregnant or become pregnant must be advised of
the potential hazard to the fetus).
- For both men and women: Do not conceive a child (get pregnant) while taking methotrexate.
Barrier methods of contraception, such as condoms, are recommended. Discuss with
your doctor when you may safely become pregnant or conceive a child after therapy.
- Do not breast feed while taking this medication.
- Drink at least two to three quarts of fluid every 24 hours, unless you are instructed
- You may be at risk of infection so try to avoid crowds or people with colds and
those not feeling well, and report fever or any other signs of infection immediately
to your health care provider.
- Wash your hands often.
- To help treat/prevent mouth sores, use a soft toothbrush, and rinse three times
a day with 1/2 to 1 teaspoon of baking soda and/or 1/2 to 1 teaspoon of salt mixed
with 8 ounces of water.
- Use an electric razor and a soft toothbrush to minimize bleeding.
- Avoid contact sports or activities that could cause injury.
- To reduce nausea, take anti-nausea medications as prescribed by your doctor, and
eat small, frequent meals.
- Avoid sun exposure. Wear SPF 15 (or higher) sunblock and protective clothing.
- In general, drinking alcoholic beverages should be kept to a minimum or avoided
completely. You should discuss this with your doctor.
- Get plenty of rest.
- Maintain good nutrition.
- If you experience symptoms or side effects, be sure to discuss them with your health
care team. They can prescribe medications and/or offer other suggestions that
are effective in managing such problems.
Monitoring and testing:
You will be checked regularly by your health care professional while you are taking
methotrexate, to monitor side effects and check your response to therapy.
Periodic blood work to monitor your complete blood count (CBC) as well as the function
of other organs (such as your kidneys and liver) will also be ordered by your doctor.
Blood levels of this drug may be monitored in patients receiving high-dose methotrexate.
How this drug works:
Cancerous tumors are characterized by cell division, which is no longer
controlled as it is in normal tissue. "Normal" cells stop dividing when they
come into contact with like cells, a mechanism known as contact inhibition.
Cancerous cells lose this ability. Cancer cells no longer have the normal
checks and balances in place that control and limit cell division. The process
of cell division, whether normal or cancerous cells, is through the cell cycle.
The cell cycle goes from the resting phase, through active growing phases, and then
to mitosis (division).
The ability of chemotherapy to kill cancer cells depends on its ability to halt
cell division. Usually, the drugs work by damaging the RNA or DNA that tells
the cell how to copy itself in division. If the cells are unable to divide,
they die. The faster the cells are dividing, the more likely it is that chemotherapy
will kill the cells, causing the tumor to shrink. They also induce cell suicide
(self-death or apoptosis).
Chemotherapy drugs that affect cells only when they are dividing are called cell-cycle
specific. Chemotherapy drugs that affect cells when they are at rest are called
cell-cycle non-specific. The scheduling of chemotherapy is set based on the
type of cells, rate at which they divide, and the time at which a given drug is
likely to be effective. This is why chemotherapy is typically given in cycles.
Chemotherapy is most effective at killing cells that are rapidly dividing.
Unfortunately, chemotherapy does not know the difference between the cancerous cells
and the normal cells. The "normal" cells will grow back and be healthy but in the
meantime, side effects occur. The "normal" cells most commonly affected by
chemotherapy are the blood cells, the cells in the mouth, stomach and bowel, and
the hair follicles; resulting in low blood counts, mouth sores, nausea, diarrhea,
and/or hair loss. Different drugs may affect different parts of the body.
Methotrexate belongs to the class of chemotherapy drugs called antimetabolites.
Antimetabolites are very similar to normal substances within the cell. When
the cells incorporate these substances into the cellular metabolism, they are unable
to divide. Antimetabolites are cell-cycle specific. They attack cells
at very specific phases in the cycle. Antimetabolites are classified according
to the substances with which they interfere.
- Folic acid antagonist: Methotrexate.
- Pyrimidine antagonist: 5-Fluorouracil, Foxuridine, Cytarabine,
Capecitabine, and Gemcitabine.
- Purine antagonist: 6-Mercaptopurine and 6-Thioguanine.
- Adenosine deaminase inhibitor: Cladribine, Fludarabine and
Methotrexate exerts its chemotherapeutic effect by being able to counteract and
compete with folic acid in cancer cells resulting in folic acid deficiency in the
cells and causing their death. This action also effects normal cells which
can cause significant side effects in the body, such as: low white, red and platelet
blood cell counts, hair loss, mouth sores, difficulty swallowing, diarrhea, liver,
lung, nerve and kidney damage. These complications and side effects
of high-dose methotrexate can be either prevented or decreased by using leucovorin,
which provides a source of folic acid for the body's cells. Leucovorin is
normally started 24 hours after high-dose methotrexate is given. This delay
gives the methotrexate a chance to exert its anti cancer effects.
Note: We strongly encourage you to talk with your health
care professional about your specific medical condition and treatments. The information
contained in this website is meant to be helpful and educational, but is not a substitute
for medical advice.
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