Nursing care
Antimetabolite chemotherapy: mucositis, hand-foot syndrome and rescue safety
Written and reviewed by Sophia Chen, MSN, RN, OCN · 4 min read · Updated October 2026
Short answer
Antimetabolites such as fluorouracil, capecitabine, cytarabine and methotrexate mimic the building blocks cells need to make DNA, so dividing cells stall and die. Nursing priorities are monitoring blood counts, catching mucositis, diarrhoea and hand-foot syndrome early, checking warfarin interactions, confirming DPD testing for fluoropyrimidines, and supporting leucovorin rescue with high-dose methotrexate.
How antimetabolites work
Antimetabolites are look-alikes of normal molecules. Fluorouracil interferes with DNA synthesis, partly by blocking the enzyme thymidylate synthase, and capecitabine is an oral drug converted to fluorouracil in the body. Methotrexate is a folate analog that blocks the folate pathway cells need to build DNA. Cytarabine is a related agent used mainly in blood cancers.
Because they act while cells are copying DNA, the tissues hit hardest are the fast-dividing ones: bone marrow, the mouth and gut lining, and skin. That explains the shared pattern of low blood counts, mouth sores and diarrhoea, which is the frame to use when an exam question lists several of these drugs together.
Shared adverse effects to assess every visit
Myelosuppression brings infection and bleeding risk, so review counts before each cycle as ordered and teach fever reporting. Mucositis can be severe with fluorouracil; inspect the mouth, encourage gentle oral care and report sores that stop the patient eating or drinking. Diarrhoea can lead quickly to dehydration and electrolyte loss.
Hand-foot syndrome, called palmar-plantar erythrodysesthesia, is listed for both fluorouracil and capecitabine. It starts as redness, tingling or tenderness of palms and soles and can progress to blistering. The labels direct the team to withhold the drug when these effects become severe, so early reporting changes treatment rather than just comfort care.
Boxed warnings, rescue and key interactions
Fluorouracil and capecitabine carry a boxed warning for serious harm or death in people with complete DPD deficiency, an inherited problem breaking the drug down. The labels advise testing for DPYD variants before starting unless treatment is urgent. Capecitabine also carries a boxed warning for bleeding with warfarin, and fluorouracil can raise the INR, so anticoagulated patients need closer INR checks.
High-dose methotrexate needs leucovorin rescue, intravenous hydration, urine alkalinisation and methotrexate levels, all timed by protocol. A missed or late leucovorin dose is a reportable safety event. The methotrexate label lists interacting drugs, including NSAIDs and proton pump inhibitors, so review the medication list before each course. Fluorouracil overdose has a specific antidote, uridine triacetate.
Worked example: capecitabine at home
Consider a hypothetical patient taking capecitabine at home who calls to say they have had several loose stools today and their palms are red and sore. Options include taking the next dose and an over-the-counter antidiarrhoeal, holding the next dose and contacting the oncology team, doubling tomorrow's dose to stay on schedule, or simply applying moisturiser.
Holding the dose and contacting the oncology team is safest, because the label advises withholding capecitabine for significant diarrhoea or hand-foot syndrome and then resuming at the same or a reduced dose. Continuing risks dehydration and worsening skin damage, doubling up is not a safe way to catch up on chemotherapy, and moisturiser alone does not address the toxicity.
Patient teaching across the class
Teach patients to report fever, mouth sores, diarrhoea, nausea that prevents drinking, unusual bleeding and skin changes on hands or feet, and to keep a diary of symptoms between visits. Patients on oral agents should know exactly when to stop and call, because they are managing chemotherapy without a nurse present.
These drugs can harm a fetus, so contraception counselling is part of every plan. Patients on warfarin should not adjust it themselves and should expect more frequent INR checks. For methotrexate, make sure the patient understands the purpose and timing of leucovorin and that skipping it is not safe.
Sources and further reading
DailyMed: Fluorouracil injection prescribing information. Mechanism, DPD deficiency boxed warning, mucositis, hand-foot syndrome, INR rise with warfarin and uridine triacetate for overdose.
DailyMed: Capecitabine tablets prescribing information. Conversion to fluorouracil, boxed warnings for DPD deficiency and vitamin K antagonist bleeding, withholding for diarrhoea and hand-foot syndrome.
DailyMed: Methotrexate injection prescribing information. Folate analog mechanism, leucovorin rescue, hydration, urine alkalinisation, level monitoring and interacting drugs.
The next step on this is the same as on everything else here: answer questions and read the rationales. Our pharmacology practice questions are the closest set to what this page covers.
One question from the pharmacology set
A client with heart failure is started on furosemide 40 mg PO daily. Which findings should the nurse report to the provider before administering the next dose? Select all that apply.
Rationale
Furosemide is a loop diuretic, so the two things you are watching are potassium and kidney function. A potassium of 2.9 mEq/L is below the 3.5–5.0 reference range and puts the client at risk for dysrhythmia — hold and report. Muscle cramps with palpitations are the clinical face of that same hypokalemia, so they are reported together, not separately. A creatinine that doubles signals the diuresis has outrun renal perfusion. A blood pressure of 132/78 and a 1 kg loss are the expected response to the drug working, not reasons to hold it.
Answer: A, D, E
Common questions
What is leucovorin rescue?
Leucovorin is a folate form given on a set schedule after high-dose methotrexate to protect normal cells. It is paired with hydration, urine alkalinisation and methotrexate level checks, and doses must not be missed or delayed.
Why is DPD testing done before fluorouracil or capecitabine?
People with complete DPD deficiency cannot break these drugs down normally and can suffer serious or fatal toxicity. The labels advise testing for DPYD variants first unless treatment is urgent.
What does hand-foot syndrome look like?
Redness, swelling, tingling or pain on the palms and soles, which can progress to blistering and peeling. Severe cases lead the team to withhold the drug, so early reporting matters.
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