fluorouracil

Trade Name:

Efudex® Cream

IV generic brands available

Synonym:

5-fluorouracil

5-FU

Appearance:

Colourless to faint yellow solution

; may be mixed into larger volumes of fluids

Monograph Name:

fluorouracil

Monograph Body:

Drug Monograph

A - Drug Name

fluorouracil

SYNONYM(S): 5-fluorouracil; 5-FU

COMMON TRADE NAME(S): Efudex® Cream; IV generic brands available

B - Mechanism of Action and Pharmacokinetics

Fluorouracil was developed based on the observation that some tumour cells utilized the base pair uracil for DNA synthesis more efficiently than did normal cells. It is a fluorinated pyrimidine antimetabolite that is metabolized intracellularly to its active form, fluorouridine monophosphate (FdUMP), which then inhibits DNA synthesis by inhibiting thymidylate synthetase and the normal production of thymidine. Effects on RNA (incorporation into RNA and RNA inhibition) also occur. Fluorouracil is cell cycle phase-specific (S-phase).

Absorption

Bioavailability

Topical: Insignificant (<5-10%)

Distribution

Into all body water by passive diffusion, crosses placenta, high and persistent levels in malignant effusions.

Cross blood brain barrier?

yes

PPB

10 %

Metabolism

Activated in target cells, 80% of dose degraded in liver by dihydropyrimidine dehydrogenase (DPD).

Active metabolites

FdUMP, FdUTP, FUTP

Inactive metabolites

yes

Elimination

60-80% excreted as respiratory CO₂, 2-3% by biliary system. Higher clearance occurs in IV infusions than IV injections, due to saturation of metabolic or transport processes at higher drug concentrations.

Urine

15-20% as intact drug within 6 hours.

Half-life

6-20 minutes; dose-dependent.

C - Indications and Status

Health Canada Approvals:

Breast cancer (adjuvant/palliative)
Gastrointestinal cancer (adjuvant/palliative colorectal, gastric, pancreatic - palliative)
Genitourinary cancer (bladder, prostate - palliative)
Head and neck cancer (palliative)
Gynecological (ovarian; palliative)
Premalignant keratoses (topical)
Superficial basal cell carcinoma (topical)

Other Uses:

Gastrointestinal cancer (hepatobiliary, neuroendocrine tumours, small bowel and appendix, esophageal, anal)
Genitourinary cancer (penile, renal cell)
Gynecological cancer (vulvar)
Primary unknown
Skin (squamous cell)
Lung (neuroendocrine)

D - Adverse Effects

Emetogenic Potential:

Low (Bolus)
Minimal (CIV)

Extravasation Potential: Irritant

The following table lists side effect incidences reported from the fluorouracil arm (IV infusion on days 1 and 2) in a phase III study in advanced colorectal cancer patients. Incidences marked with "^" were reported from other sources, including severe adverse effects from other studies or post-marketing

ORGAN SITE	SIDE EFFECT* (%)	ONSET**
Cardiovascular	Arrhythmia (<10%) ^	I
	Arterial/venous thromboembolism (6%)	E
	Cardiotoxicity (<10%) ^	D
	ECG changes (69%) (asymptomatic; severe in rare cases)^	I
Dermatological	Alopecia (17%) (mild)	E
	Erythema (including necrosis, with topical application)	I E
	Hand-foot syndrome (13%)	E
	Nail disorder (occasional)	E
	Photosensitivity (occasional)	E
	Radiation recall reaction (rare)	I E
	Rash (20%) (extremities, sometimes on trunk) / dry skin (may be severe)	E
Gastrointestinal	Anorexia (19%)	E
	Diarrhea (45%) (6% severe)	E
	GI ulcer or bleeding (rare)	E
	Mucositis (29%) (3% severe)	E
	Nausea, vomiting (55%) (4% severe)	I
Hematological	Anemia (91%) (2% severe)	E
	Hemolysis (rare)	E
	Myelosuppression ± infection, bleeding (48%) (13% severe)	E
Hepatobiliary	↑ Bilirubin (36%) (11% severe)	D
	Hepatic necrosis (rare; may be fatal)	D
Hypersensitivity	Hypersensitivity (rare; including anaphylaxis)	I
Injection site	Vein discolouration (occasional)	I
Nervous System	Ataxia / acute cerebellar syndrome (rare, reversible, but may persist following discontinuation of treatment)	E D
	Confusion	E D
	Extrapyramidal disorder or cortical dysfunction (rare; usually reversible)	E D
	Leukoencephalopathy (rare)	E D
	Optic neuritis , oculomotor disturbance (rare)	E D
Ophthalmic	Conjunctivitis (25%) and/or tearing^	I E
	Other - tear duct fibrosis (rare, reversible)	E D

* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare" may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal reports.

** I = immediate (onset in hours to days) E = early (days to weeks)
D = delayed (weeks to months) L = late (months to years)

The most common side effects for fluorouracil include ECG changes, nausea/vomiting, myelosuppression ± infection (including anemia), bleeding, diarrhea, ↑ bilirubin, mucositis, conjunctivitis, rash and anorexia.

Following longer IV infusions, mucositis, hand-foot syndrome and diarrhea occur most commonly. Diarrhea may be profuse and life-threatening following administration of leucovorin with fluorouracil. Leukopenia is the usual dose-limiting toxicity after IV bolus administration

Patients with dihydropyrimidine dehydrogenase deficiency (DPD) are at risk of severe life-threatening toxicity with fluorouracil. While severe deficiency is rare, 3-4% of the population has some degree of DPD deficiency. No dose has been proven safe for patients with complete absence of DPD activity.

Excessive lacrimation can occur. Transient blurring of vision, eye irritation and excessive nasal discharge have also been reported. The onset of eye symptoms may occur at any time during treatment. Fluorouracil has been demonstrated in tear fluid causing acute and chronic conjunctivitis that can lead to tear duct fibrosis.

Acute cerebellar syndrome is manifested as ataxia of the trunk or extremities, disturbance of gait and speech, coarse nystagmus and dizziness. The ataxia syndrome is related to peak plasma levels of the drug rather than to cumulative dose, and is therefore more common with bolus doses than with infusions. It usually resolves after treatment is discontinued, but may persist in some cases. Leukoencephalopathy has been reported with symptoms such as decreased alertness, agitation, and disorientation memory deficit. This usually resolves within a few days of discontinuing fluorouracil.

Palmar-plantar erythrodysesthesia or hand-foot syndrome has been noted with protracted and high dose continuous infusion. The syndrome begins with dysesthesias of the palms and soles that progress to pain and tenderness. There is associated symmetrical swelling and erythema of the hand and foot. The syndrome resolves gradually over 5 to 7 days with cessation of drug infusion.

Cardiotoxicity has been reported and may be caused by coronary vasospasm, endothelial cell damage or increased thrombogenicity. It occurs in less than 10% of patients, of which up to 8% may be fatal. Cardiac effects include ECG changes, angina, arrhythmias, myocardial infarction, heart failure and are usually reported within 72 h of the first cycle of fluorouracil. Cardiotoxicity is independent of dose or underlying cardiac risk factors, but may be more common with infusions. Patients should be rechallenged only when there are no other treatment options.

Fluorouracil has the potential to enhance radiation injury to tissues. While often called radiation recall reactions, the timing of the radiation may be before, concurrent with or even after the administration of the fluorouracil. Recurrent injury to a previously radiated site may occur weeks to months following radiation.

Hemolytic-uremic syndrome has been reported when used in combination with mitomycin C.

Topical use:

When applied to a lesion, the following occurs: Erythema, usually followed by vesiculation, erosion, ulceration, necrosis and epithelization. The lower frequency and intensity of activity in adjacent normal skin indicates a selective cytotoxic property. An occlusive dressing is not essential, and may increase the incidence of inflammatory reactions in adjacent normal skin. Therapy is usually continued to reach the erosion, necrosis and ulceration stage (2-4 weeks), after which healing occurs over 4-8 weeks. The most frequent local reactions are pain, pruritus, hyperpigmentation and burning at the application site. Avoid prolonged exposure to sunlight or ultraviolet light during treatment and 1-2 months after ending treatment as the intensity of the reaction may be increased.

E - Dosing

Refer to protocol by which patient is being treated.

Patients should be tested for DPD deficiency before starting treatment with fluorouracil. Refer to the DPD Deficiency Guidance for Clinicians for more information.

In patients with unrecognized DPD deficiency, acute, life-threatening toxicity may occur; if acute grade 2-4 toxicity develops, treatment should be stopped immediately and permanent discontinuation considered based on clinical assessment of the toxicities.

Consider a reduced starting dose for patients who are heavily pretreated, malnourished or have poor performance status, or in patients with large third space collections or edema.

Adults:

IV bolus:

q4w: 425 mg/m² day x 5 days
q4w: 500-600 mg/m² days 1 & 8

IV infusion:

q3w: 200 mg/m²/day on days 1-21 as continuous infusion
q3-4w: 750-1000 mg/m²/day x 4-5 days as continuous infusion
q2w: 600 mg/m²/day x 22 hours on days 1 and 2
q2w: 2400 mg/m² over 46 hours starting on day 1

Topical:

Twice daily: x 1-4 weeks. Stop when erosion evident, usually 2-4 weeks. Allow 1-2 months for healing. Total area treated at one time should not exceed 500 cm² (23x23 cm). Larger areas should be treated one section at a time.

Dosage with Toxicity:

Modify according to protocol by which patient is being treated.

Toxicity or Counts (x 10⁹/L)	During Cycle	For Next cycle
Platelets < 80 or ANC < 1.5	Hold*	May consider ↓
Bleeding, febrile neutropenia	Hold*	↓ by 25%
≥ grade 3 GI	Hold*	↓ by 25%
≥ grade 3 Hand-Foot Syndrome	Hold*	↓ by 25%
CNS	Hold*	↓ by 25%
Cardiac	Hold*	Consider discontinuing
* Do not retreat until ANC ≥ 1.5 x 10⁹/L , platelets ≥ 100 x 10⁹/L and organ toxicity ≤ grade 2. With severe toxicity, consider testing for DPD deficiency prior to rechallenge.

Dosage with Hepatic Impairment:

Consider dose reduction with moderate to severe hepatic impairment.

Suggested:

Bilirubin		AST/ALT	Fluorouracil (% previous dose)
< 2 x ULN	and	3-5 x ULN	75 %
2-4 x ULN	or	5-10 x ULN	50-75%
> 4 x ULN	or	> 10 x ULN	Discontinue

Dosage with Renal Impairment:

No adjustment required, although reduction may be considered with severe renal insufficiency.

Dosage in the elderly:

Elderly patients are at a higher risk of developing toxicities, likely due to lower bone marrow reserve.

F - Administration Guidelines

IV Push or Intermittent Infusion:

Slow push through sidearm of free-flowing IV (5% Dextrose, Normal Saline)
May be mixed in 50mL minibag (NS or D5W); infuse over 15 min.
Store unopened vials at 15ºC to 25ºC. Protect from light.

IV Continuous Infusion:

Refer to local guidelines on preparation of fluorouracil IV infusion for central or peripheral lines. A lower concentration is usually used for peripheral IV infusions to prevent vein irritation.
Continuous infusion using CADD infusion pump, or similar device
Infusion volume, duration and administration via central or peripheral line depend on the regimen used.
If given peripherally, inspect peripheral infusion sites daily and replace if evidence of irritation or extravasation.
Incompatible with doxorubicin, epirubicin, diazepam, methotrexate and cytarabine; line must be flushed between administrations of fluorouracil and these agents.
Store at room temperature (15 to 25ºC). Protect from light.

Topical:

Glove or non-metal applicator preferred. If fingertips used, wash hands immediately afterward.
Exercise care when applying the cream near the eyes, nostrils and mouth.

Antidote for Fluorouracil Overdose:

Uridine triacetate is a prodrug of uridine and is a specific antidote for treating fluorouracil overdose or severe early onset toxicities. If available, consider administering as soon as possible (i.e. within 96 hours) for suspected overdose. If not available, treatment is symptomatic and supportive.

For usage approval and supply, contact Health Canada’s Special Access Program (SAP) (Phone: 613-941-2108. On-call service is available for emergencies). Uridine triacetate (Vistogard®) is supplied by its manufacturer in the United States.

The recommended dosing and administration for uridine triacetate in patients ≥18 years is:

10 grams (1 packet of coated granules) orally every 6 hours for 20 doses in total, without regards to meals.
Granules should not be chewed. They should be mixed with 3 to 4 ounces of soft foods such as applesauce, pudding or yogurt.
The dose should be ingested within 30 minutes of preparation, followed by at least 4 ounces of water.
Refer to the prescribing information on dose preparation for NG-tube or G-tube use.

Additional resources on the management of fluorouracil infusion overdose:

Management of Fluorouracil Infusion Overdose Guideline (Alberta Health Services)
Management of Fluorouracil Infusion Overdose at the BCCA - Interim Guidance (BC Cancer Agency)

G - Special Precautions

Contraindications:

patients with poor nutritional state
patients with depressed bone marrow function (prior pelvic irradiation / marrow infiltration)
patients with potentially serious infections
patients with known hypersensitivity to the drug or any of its excipients
patients with known complete absence of dihydropyrimidine dehydrogenase (DPD) activity. Refer to the DPD Deficiency Guidance for Clinicians for more information.
Fluorouracil should not be used within 4 weeks of treatment with brivudine, sorivudine or their chemically related analogues.

Other Warnings/Precautions:

Use with extreme caution in patients who:
- have undergone recent major surgery,
- have renal or hepatic impairment,
- have widespread bone marrow involvement,
- have previous use of other myelosuppressive chemotherapeutic agents,
- have a history of high dose irradiation to bone marrow-bearing areas,
- have a history of heart disease,
- or are suspected to have DPD deficiency. Refer to the DPD Deficiency Guidance for Clinicians for more information.
Avoid the use of live vaccines.

Other Drug Properties:

Carcinogenicity: Probable

Pregnancy and Lactation:

Mutagenicity: Yes
Embryotoxicity: Yes
Teratogenicity: Yes
Crosses placental barrier: Yes

Fluorouracil is contraindicated in pregnancy. Appropriate contraception should be used by both sexes during treatment, and for at least 6 months after the last dose (generic recommendation).
Breastfeeding: Contraindicated
Fertility effects: Probable

H - Interactions

Laboratory tests for bilirubin (icteric index) and urinary 5-HIAA may increase or have false positive results. Increases in T3 and T4 levels have been reported in euthyroid, advanced breast cancer patients treated with single agent fluorouracil, and these changes were reversible within 4 weeks after the end of treatment.

AGENT	EFFECT	MECHANISM	MANAGEMENT
Brivudine, sorivudine and chemically related analogues	Significant ↑ in 5-FU exposure and toxicities	Irreversible DPD inhibition	CONTRAINDICATED Use alternative antiviral therapy or allow at least 4 weeks washout period between brivudine/ sorivudine/ analogues and starting 5-FU treatment. Immediate hospitalization with measures to reduce 5-FU toxicity is recommended, in case of accidental use of nucleoside analogues that inhibit DPD in 5-FU treated patients .
mitomycin	↑ incidence of hemolytic-uremic syndrome with long-term usage	Unknown	Caution
cimetidine	↑ serum concentrations of fluorouracil; fatal cases have been reported	appears to interfere with fluorouracil metabolism (e.g. by inhibiting hepatic enzymes and reducing hepatic blood flow)	Caution; observe for increased toxicity of fluorouracil
leucovorin	↑ cytotoxic and toxic effects of fluorouracil	Leucovorin stabilizes the bond to thymidylate synthetase	Some protocols are designed to take advantage of this effect; monitor toxicity closely
metronidazole	↑ serum concentration and/or toxicity of fluorouracil; fatal cases have been reported	↓ clearance of fluorouracil	Avoid if possible
phenytoin	↑ phenytoin levels and toxicity	Possible inhibition or decreased synthesis of CYP2C9 by fluorouracil	Monitor phenytoin levels and patient
Thiazide diuretics	↑ myelosuppression	↓ renal excretion of fluorouracil	Consider an alternative antihypertensive
warfarin	↑ effects of warfarin; fatal cases have been reported	↓ CYP2C9 enzymes for metabolism; reduced warfarin clearance	Monitor INR closely; adjust warfarin doses accordingly

I - Recommended Clinical Monitoring

Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.

Recommended Clinical Monitoring

Monitor Type	Monitor Frequency
CBC	Baseline and before each cycle
Liver function tests	Baseline and before each cycle
Renal function tests	Baseline and before each cycle
Clinical assessment and grading of stomatitis, diarrhea, bleeding, infection, local site toxicity, skin effects (rash or hand-foot-syndrome), cardiovascular, ophthalmic effects, and neurotoxicity	At each visit

Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version

Suggested Clinical Monitoring

Monitor Type	Monitor Frequency
INR in patients taking warfarin	Baseline and as clinically indicated

K - References

Budd GT, Fleming TR, Bukowski RM et al. 5-fluorouracil and folinic Acid in the treatment of metastatic colorectal cancer: a randomized comparison. A Southwest oncology group study. J Clin Oncol 1987;5:272-7.

Fluorouracil: ASHP's Interactive Handbook on Injectable Drugs.

Fluorouracil drug monograph Cancer Drug Manual. British Columbia Cancer Agency (BCCA). Accessed November 21, 2018.

Gradishar WJ, Vokes EE, et al. 5-Fluorouracil cardiotoxicity: A critical review. Annals of Oncology 1990;1: 409-14.

Griffin JD, Garnick MB. Eye toxicity of cancer chemotherapy: a review of the literature. Cancer 1981;48(7):1539-49.

Health Canada's Special Access Programs, Health Canada. Accessed May 26, 2021.

Management of Fluorouracil Infusion Overdose Guideline. Alberta Health Services, Feb 2016.

Management of Fluorouracil Infusion Overdose at the BCCA - Interim Guidance. BC Cancer Agency, May 2015.

McEvoy GK, editor. AHFS Drug Information 2009. Bethesda: American Society of Health-System Pharmacists, p. 1074-8.

Prescribing Information: Uridine triacetate (Vistogard®). Wellstat Therapeutics (US), Feb 2017.

Product Monograph: Fluorouracil. Sandoz Canada, April 3, 2012.

Product Monograph: Fluorouracil. Biolyse Pharma Corp., March 7, 2018.

Product Monograph: Irinotecan. Pfizer Canada Inc., Feb 11, 2015.

Product Monograph: Efudex® (fluorouracil topical). Valeant Canada Limited. December 15, 2004.

Saif MW, Shah MM, Shah AR. Fluoropyrimidine-associated cardiotoxicity: revisited. Expert Opin Drug Saf 2009; 8(2): 191-202

Sara JD, Kaur J, Kodhadadi R, et al. 5-fluorouracil and cardiotoxicity: a review. Ther Adv Med Oncol 2018;10:1-18.

Sorrentino MF, Kim J, Foderaro AE, et al. Fluorouracil induced cardiotoxicity: review of the literature. Cardiol J 2012;19(5):453-8.

Summary of Product Characteristics: Efudix®. Meda Pharmaceuticals (UK), March 2014.

April 2024 Removed previous manufacturer name from antidote information

L - Disclaimer

Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.

The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.

The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.

Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.

While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.

CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.

Info Sheet Name:

fluorouracil(Injection) (patient)

Info Sheet Introduction:

For treating breast, colorectal or other digestive system cancers, and many other types of cancer

Info Sheet Date: Monday, April 24, 2023 Info Sheet body:

Medication Information Sheet

fluorouracil (flue-row-YOUR-a-sill)

This document provides general information about your medication. It does not replace the advice of your health care professional. Always discuss your therapy with your health care professional and refer to the package insert for more details.

Other Name: 5-FU, 5-fluorouracil

Appearance:

Colourless to faint yellow solution

; may be mixed into larger volumes of fluids

What is this medication for?

For treating breast, colorectal or other digestive system cancers, and many other types of cancer

What should I do before I have this medication?

Tell your health care team if you have or had significant medical condition(s), especially if you have or had:
- recent major surgery
- liver or kidney problems
- heart problems, including irregular heartbeat, or
- any allergies
Tell your health care team if you have had fluorouracil before, especially if you had severe side effects from it

Remember to:

Tell your health care team about all of the other medications you are taking.
Keep taking other medications that have been prescribed for you, unless you have been told not to by your health care team.

Your health care team may ask you to have a blood test to check for DPD deficiency before starting treatment. DPD deficiency is when you have low or no activity of an enzyme called DPD (dihydropyrimidine dehydrogenase). A deficiency can cause you to have severe side effects from fluorouracil. See the Testing for people taking capecitabine or 5-fluorouracil (5-FU) pamphlet for more information.

How will this medication affect sex, pregnancy and breastfeeding?

Talk to your health care team about:
- How this treatment may affect your sexual health.
- How this treatment may affect your ability to have a baby, if this applies to you.
This treatment may harm an unborn baby. Tell your health care team if you or your partner are pregnant, become pregnant during treatment, or are breastfeeding.
- If there is any chance of pregnancy happening, you and your partner together must use 2 effective forms of birth control at the same time until 6 months after your last treatment dose. Talk to your health care team about which birth control options are best for you.
- Do not use hormonal birth control (such as birth control pills), unless your health care team told you that they are safe. Talk to your health care team about the safest birth control for you.
Do not breastfeed while on this treatment.

How is this medication given?

This drug is given by injection into a vein.

Talk to your health care team about your treatment schedule.
If you missed your treatment appointment, talk to your health care team to find out what to do.

To help prevent Hand-foot syndrome:

Hand-foot syndrome is a side-effect of fluorouracil. It affects the skin on your hands and the bottom of your feet and usually starts with tingling or swelling of your skin. It can become painful, red and numb. In worse cases, your skin may start to peel and you can get blisters or sores.

Do not do activities that cause rubbing or pressure on your skin, like heavy-duty washing, gripping tools, typing, playing musical instruments, and driving.
Moisturize your hands and feet often, especially in the skin folds.
Wear loose, comfortable footwear and clothes.
Rest and try to keep off your feet.
Do not let your hands and feet get too hot.

What else do I need to know while on this medication?

This medication can interact with other medications and can result in the treatment not working as well or cause severe side effects.

Make sure your health care team knows about all your medications (prescription, over-the-counter, herbals and supplements), especially if you take medication to treat epilepsy, infections, stomach acid or blood clots. Check with your health care team before starting or stopping any of them.
For mild aches and pain or fever:
- If you feel unwell, take your temperature before taking any medications for pain or fever. They may hide a fever.
- You may take acetaminophen (Tylenol®) tablets. Ask your health care team about the right dose for you.
- Ibuprofen (Advil®, Motrin®), naproxen (Aleve®) or aspirin (acetylsalicylic acid, ASA), including low dose aspirin for heart conditions, may increase your chance of bleeding. Talk to your health care team before you start or stop these medications.
- Talk to your health care team or go to the closest emergency room right away if you have a fever. See the Fever pamphlet for more information.
DO protect your skin from the sun. Wear a long sleeved shirt, long pants and a hat. Apply sunscreen with UVA and UVB protection and an SPF of at least 30. Your skin may be more sensitive to the sun and you could develop a bad sunburn or rash more easily.
DO talk to your health care team about your risk of getting other cancers after this treatment.
DO NOT smoke or drink alcohol while on treatment without talking to your health care team first. Smoking and drinking can make side effects worse and make your treatment not work as well.

What are the side effects of this medication?

The following table lists side effects that you may have when getting fluorouracil. The table is set up to list the most common side effects first and the least common last. It is unlikely that you will have all of the side effects listed and you may have some that are not listed.

Read over the side effect table so that you know what to look for and when to get help. Refer to this table if you experience any side effects while on fluorouracil.

Side effects and what to do	When to contact health care team?
Very Common Side Effects (in 50 or more out of 100 people)

Low neutrophils (white blood cells) in the blood (neutropenia)

(More likely with fast injections; May be severe)

When neutrophils are low, you are at risk of getting an infection more easily. Ask your health care team for the Neutropenia (Low white blood cell count) pamphlet for more information.

What to look for?

If you feel hot or unwell (for example if you have chills or a new cough), you must check your temperature to see if you have a fever.
Do not take medications that treat a fever before you take your temperature (for example, Tylenol®, acetaminophen, Advil® or ibuprofen).
Do not eat or drink anything hot or cold right before taking your temperature.

You have a fever if your temperature taken in your mouth (oral temperature) is:

38.3°C (100.9°F) or higher at any time
OR
38.0°C (100.4°F) or higher for at least one hour.

What to do?

If your health care team has told you that you have low neutrophils:

Wash your hands often to prevent infection.
Check with your health care team before getting any vaccines, surgeries, medical procedures or visiting your dentist.
Keep a digital thermometer at home so you can easily check for a fever.

If you have a fever:

If you have a fever, try to contact your health care team. If you are unable to talk to the team for advice, you must get emergency medical help right away.

If you have a fever, try to contact your health care team. If you are unable to talk to the team for advice, you MUST get emergency medical help right away.

Low platelets in the blood

(More likely with fast injections; May be severe)

When your platelets are low, you are at risk for bleeding and bruising. Ask your health care team for the Low Platelet Count pamphlet for more information.

What to look for?

Watch for signs of bleeding:
- bleeding from your gums
- unusual or heavy nosebleeds
- bruising easily or more than normal
- black coloured stools (poo) or blood in your stools (poo)
- coughing up red or brown coloured mucus
- dizziness, constant headache or changes in your vision
- heavy vaginal bleeding
- red or pink coloured urine (pee)

What to do?

If your health care team has told you that you have low platelets:

Tell your pharmacist that your platelet count may be low before taking any prescriptions or over-the-counter medication.
Check with your healthcare team before you go to the dentist.
Take care of your mouth and use a soft toothbrush.
Try to prevent cuts and bruises.
Ask your health care team what activities are safe for you.
Your treatment may have to be delayed if you have low platelets. Your health care team may recommend a blood transfusion.

If you have signs of bleeding:

If you have a small bleed, clean the area with soap and water or a saline (saltwater) rinse. Apply pressure for at least 10 minutes.

If you have bleeding that does not stop or is severe (very heavy), you must get emergency medical help right away.

Talk to your health care team if you have any signs of bleeding. If you have bleeding that doesn’t stop or is severe (very heavy), you MUST get emergency help right away.

Changes in heart rhythm

What to look for?

These are usually mild and have no symptoms.
Your health care team may monitor this for you.
You may have an irregular heartbeat, shortness of breath, chest pain or fainting spells.

What to do?

Get emergency medical help right away if you have any symptoms of changes in your heart rhythm.

Get emergency medical help right away

Nausea and vomiting (generally mild)

What to look for?

Nausea is feeling like you need to throw up. You may also feel light-headed.
You may feel nausea within hours to days after your treatment.

What to do?

To help prevent nausea:

It is easier to prevent nausea than to treat it once it happens.
Drink clear liquids and have small meals. Get fresh air and rest.
Do not eat spicy, fried foods or foods with a strong smell.
Limit caffeine (like coffee, tea) and avoid alcohol.

If you have nausea or vomiting:

Take your anti-nausea medication(s) as prescribed.
Ask your health care team for the Nausea & Vomiting pamphlet for more information.
Talk to your health care team if:
- nausea lasts more than 48 hours
- vomiting lasts more than 24 hours or if it is severe

Talk to your healthcare team if nausea lasts more than 48 hours or vomiting lasts more than 24 hours or if it is severe

Side effects and what to do	When to contact health care team?
Common Side Effects (in 25 to 49 out of 100 people)

Diarrhea (may be severe)

What to look for?

Loose, watery, unformed stool (poo) that may happen days to weeks after you get your treatment.

What to do?

If you have diarrhea:

Take anti-diarrhea medication if your health care team prescribed it or told you to take it.
Do not eat foods or drinks with artificial sweetener (like chewing gum or ‘diet’ drinks), coffee and alcohol.
Eat many small meals and snacks instead of 2 or 3 large meals.
Drink at least 6 to 8 cups of liquids each day, unless your health care team has told you to drink more or less.
Talk to your health care team if you can’t drink 6 to 8 cups of liquids each day when you have diarrhea. You may need to drink special liquids with salt and sugar, called Oral Rehydration Therapy.
Talk to your health care team if your diarrhea does not improve after 24 hours of taking diarrhea medication or if you have diarrhea more than 7 times in one day.

Ask your health care team for the Diarrhea pamphlet for more information.

Talk to your health care team if no improvement after 24 hours of taking diarrhea medication or if severe (more than 7 times in one day)

Liver problems (may be severe)

Your health care team may check your liver function with a blood test. The liver changes do not usually cause any symptoms.

What to look for?

Rarely, you may develop yellowish skin or eyes, unusually dark pee or pain on the right side of your belly. This may be severe.

What to do?

If you have any symptoms of liver problems, get emergency medical help right away.

Get emergency medical help right away

Mouth sores (may be severe)

What to look for?

Round, painful, white or gray sores inside your mouth that can occur on the tongue, lips, gums, or inside your cheeks.
In more severe cases they may make it hard to swallow, eat or brush your teeth.
They may last for 3 days or longer.

What to do?

To help prevent mouth sores:

Take care of your mouth by gently brushing and flossing regularly.
Rinse your mouth often with a homemade mouthwash.
To make a homemade mouthwash, mix 1 teaspoonful of baking soda and 1 teaspoonful of salt in 4 cups (1L) of water.
Do not use store-bought mouthwashes, especially those with alcohol, because they may irritate your mouth.

If you have mouth sores:

Avoid hot, spicy, acidic, hard or crunchy foods.
Your doctor may prescribe a special mouthwash to relieve mouth sores and prevent infection.
Talk to your health care team as soon as you notice mouth or lip sores or if it hurts to eat, drink or swallow.

Ask your health care team for the Oral Care (Mouth Care) pamphlet for more information.

Talk to your health care team as soon as you notice mouth or lip sores or if it hurts to eat, drink or swallow

Eye problems

What to look for?

Your eyes may feel dry, irritated, or painful.
They may look red and have a lot of tears.
They may feel sensitive to light and your vision may be blurry.

What to do?

Avoid wearing contact lenses.
Wear sunglasses with UV protection.
Use protective eyewear (goggles or helmet with face mask) when playing sports, mowing the lawn or doing anything that may get particles or fumes in your eyes.
You may try artificial tears (eye drops) or ointment.

Contact your health care team as soon as possible

Side effects and what to do	When to contact health care team?
Less Common Side Effects (in 10 to 24 out of 100 people)

Rash; dry, itchy skin, Skin sensitivity to sunlight

What to look for?

You may have cracked, rough, flaking or peeling areas of the skin.
Your skin may look red and feel warm, like a sunburn.
Your skin may itch, burn, sting or feel very tender when touched.
The rash may be seen in areas where you have had radiation before.
When your skin is exposed to the sun, you may get an itchy, red rash that looks like a sunburn or other skin reactions.

What to do?

Use fragrance-free skin moisturizer every day.
Protect your skin from the sun and the cold. When you are in the sun, wear long sleeved shirts, long pants and a hat.
Use sunscreen with UVA and UVB protection and an SPF of at least 30.
Use a lip balm with sunscreen on your lips.
Avoid perfumed products and lotions that contain alcohol.
Drink 6 to 8 cups of non-alcoholic, non-caffeinated liquids each day, unless your health care team has told you to drink more or less.

Rash may be severe in some rare cases and cause your skin to blister or peel. If this happens, get emergency medical help right away.

Talk to your health care team if it does not improve or if it is severe

Low appetite

What to look for?

Loss of interest in food or not feeling hungry.
Weight loss.

What to do?

Try to eat your favourite foods.
Eat small meals throughout the day.
You may need to take meal supplements to help keep your weight up.
Talk to your health care team if you have no appetite.

Ask your health care team for the Loss of Appetite pamphlet for more information.

Talk to your health care team if it does not improve or if it is severe

Hair thinning or loss (generally mild)

What to look for?

Your hair may begin to become thin or fall out during or after treatment.
In most cases, your hair will grow back after treatment, but the texture or colour may change.
In very rare cases, hair loss may be permanent.

What to do?

Use a gentle soft brush.
Do not use hair sprays, bleaches, dyes and perms.

Talk to your health care team if this bothers you

Rash on your hands and feet (hand-foot syndrome)

(More likely with long infusions)

What to look for?

Tingling or swelling of the skin on the palms of your hands and the bottoms of your feet. This can become painful, red and numb.
In worse cases your skin may start to peel and you can get blisters or sores.
This may happen days or weeks after you start treatment.

What to do?

To help prevent Hand-foot syndrome:

Do not do activities that cause rubbing or pressure on your skin, like heavy-duty washing, gripping tools, typing, playing musical instruments, and driving.
Moisturize your hands and feet often, especially in the skin folds.
Wear loose, comfortable footwear and clothes.
Rest and try to keep off your feet.
Do not let your hands and feet get too hot.

Ask your health care team for the Hand-foot syndrome pamphlet for more information.

Talk to your health care team if it does not improve or if it is severe

Other rare, but serious side effects are possible.
If you experience ANY of the following, speak to your cancer health care provider or get emergency medical help right away:

shortness of breath, pain in the chest that may spread to the arm or belly, coughing up blood
swelling in your legs, ankles and belly
pain, swelling and hardening of the vein in an arm or leg
have trouble seeing, speaking, or using your arms and legs
confusion, severe weakness, problems with your balance or have falls
unusual muscle spasms, tremors, irregular or jerky movements
redness or rash in areas where you had radiation before
itchiness, rash, swollen lips, face or tongue, chest and throat tightness, during or shortly after the medication is given
have red-brown coloured pee

Who do I contact if I have questions or need help?

My cancer health care provider is: ______________________________________________

During the day I should contact:________________________________________________

Evenings, weekends and holidays:______________________________________________

Other Notes:

____________________________________________________________________________

April 2023 Updated information sheet

For more links on how to manage your symptoms go to www.cancercareontario.ca/symptoms.

The information set out in the medication information sheets, regimen information sheets, and symptom management information (for patients) contained in the Drug Formulary (the "Formulary") is intended to be used by health professionals and patients for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or side effects of a certain drug, nor should it be used to indicate that use of a particular drug is safe, appropriate or effective for a given condition.

A patient should always consult a healthcare provider if he/she has any questions regarding the information set out in the Formulary. The information in the Formulary is not intended to act as or replace medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.

Info Sheet (English):

fluorouracilInjection patient.pdf Info Sheet (French):

fluorouracilInjection pour le patient.pdf Monograph:

fluorouracil.pdf Phonetic Spelling:

flue-row-YOUR-a-sill

Cancer Type: Breast Gastrointestinal Anus Colorectal Esophagus Gastric / Stomach Hepatobiliary / Liver / Bile Duct Neuroendocrine (GI) Pancreas Small bowel and appendix Genitourinary Bladder / Urothelial Penile Prostate Renal cell / Kidney Gynecologic Ovary Vulva Head and Neck Squamous Cell Lung Neuroendocrine (Lung) Skin Squamous Cell Unknown Primary Type of Content: Drug Monograph Status: Null Info Sheet Status: Null Global Date: Thursday, April 4, 2024 Universal Date: 2024-04-04 00:00:00 AddThis: Title URL: fluorouracil Drug Display Status: Active Revision Summary:
Drug Monograph: Removed previous manufacturer name from antidote information