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Fluorouracil (systemic): Drug information

Fluorouracil (systemic): Drug information
(For additional information see "Fluorouracil (systemic): Patient drug information" and see "Fluorouracil (systemic): Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Adrucil [DSC]
Pharmacologic Category
  • Antineoplastic Agent, Antimetabolite;
  • Antineoplastic Agent, Antimetabolite (Pyrimidine Analog)
Dosing: Adult

Anal carcinoma (off-label use): IV: 1,000 mg/m2/day continuous infusion days 1 to 4 and days 29 to 32 (in combination with mitomycin and radiation therapy) (Ajani 2008; Flam 1996).

Bladder cancer, muscle invasive (off-label use): IV: 500 mg/m2/day continuous infusion during radiation therapy fractions 1 to 5 and 16 to 20 (in combination with mitomycin and radiation therapy) (James 2012).

Breast cancer:

CEF or FEC regimen: IV: 500 mg/m2 on days 1 and 8 every 28 days (in combination with cyclophosphamide and epirubicin) for 6 cycles (Levine 1998).

CMF regimen: IV: 600 mg/m2 on days 1 and 8 every 28 days (in combination with cyclophosphamide and methotrexate) for 6 cycles (Goldhirsch 1998; Levine 1998).

CAF or FAC regimen (off-label dosing): IV: 500 mg/m2 on days 1 and 8 every 21 to 28 days (in combination with cyclophosphamide and doxorubicin) for 6 cycles (Assikis 2003).

Cervical cancer (off-label use): IV: 1,000 mg/m2/day continuous infusion days 1 to 4 (in combination with cisplatin and radiation therapy) every 3 weeks for 3 cycles (Eifel 2004; Morris 1999).

Colorectal cancer: IV: 400 mg/m2 bolus on day 1, followed by 2,400 to 3,000 mg/m2 over 46 hours (as a continuous infusion) every 2 weeks (in combination with leucovorin ± either oxaliplatin or irinotecan) or

Roswell Park regimen: IV: 500 mg/m2 (bolus) on days 1, 8, 15, 22, 29, and 36 (1 hour after the start of leucovorin) every 8 weeks (in combination with leucovorin) for 4 cycles (Haller 2005).

FOLFOX6 and mFOLFOX6 regimen: IV: 400 mg/m2 bolus on day 1, followed by 2,400 mg/m2 over 46 hours (as a continuous infusion) every 2 weeks (in combination with leucovorin and oxaliplatin) until disease progression or unacceptable toxicity occurs (Cheeseman 2002).

FOLFIRI regimen: IV: 400 mg/m2 bolus on day 1, followed by 2,400 mg/m2 over 46 hours (as a continuous infusion) every 2 weeks (in combination with leucovorin and irinotecan) until disease progression or unacceptable toxicity occurs; after 2 cycles, may increase continuous infusion fluorouracil dose to 3,000 mg/m2 over 46 hours (Andre 1999).

FOLFOXIRI regimen: IV: 3,200 mg/m2 over 48 hours (as a continuous infusion) every 14 days (in combination with leucovorin, oxaliplatin, and irinotecan) until disease progression or unacceptable toxicity up to a maximum of 12 cycles (Falcone 2007).

FLOX regimen (off-label dosing) : IV: 500 mg/m2 bolus on days 1, 8, 15, 22, 29, and 36 (1 hour after the start of leucovorin) every 8 weeks (in combination with leucovorin and oxaliplatin) for 3 cycles (Kuebler 2007).

Adjuvant therapy duration; completely resected stage 3 colon cancer (off label):

Low risk (T1, T2, or T3 and N1): A duration of therapy of 3 or 6 months of fluoropyrimidine/oxaliplatin-based adjuvant chemotherapy may be offered (ASCO [Lieu 2019]).

High risk (T4 and/or N2): A duration of therapy of 6 months of fluoropyrimidine/oxaliplatin-based adjuvant chemotherapy should be offered (ASCO [Lieu 2019]). In a pooled analysis of 6 phase 3 studies, superior disease-free survival has been demonstrated with 6 months (compared to 3 months) of adjuvant FOLFOX therapy in the subgroup of patients with T4 and/or N2 stage 3 colon cancer (Grothey 2018).

Esophageal cancer (off-label use):

CF regimen (esophageal or gastroesophageal junction cancer): IV: 1,000 mg/m2/day continuous infusion days 1 to 4 (total dose is 4,000 mg/m2) and days 29 to 32 (total dose is 4,000 mg/m2) of a 35-day treatment cycle (preoperative chemoradiation; in combination with cisplatin) (Tepper 2008) or 1,000 mg/m2/day continuous infusion days 1 to 4 (total dose/cycle is 4,000 mg/m2) every 3 weeks for 2 cycles (neoadjuvant chemotherapy prior to surgery; in combination with cisplatin) (Alderson 2017).

FLOT regimen (locally advanced, resectable gastroesophageal junction adenocarcinoma): IV: 2,600 mg/m2 continuous infusion over 24 hours on day 1 every 2 weeks (in combination with leucovorin, oxaliplatin, and docetaxel) for 4 preoperative cycles and 4 postoperative cycles (Al-Batran 2019).

FOLFOX/nivolumab: IV: 400 mg/m2 bolus on day 1, followed by 1,200 mg/m2/day on days 1 and 2 (as a continuous infusion) every 2 weeks (in combination with leucovorin, oxaliplatin, and nivolumab) until disease progression or unacceptable toxicity (Janjigian 2021).

MCF regimen: IV: 300 mg/m2/day continuous infusion for up to 6 months (in combination with mitomycin and cisplatin) (Ross 2002).

Pembrolizumab/Cisplatin/Fluorouracil (esophageal or gastroesophageal junction cancer): IV: 800 mg/m2/day as a continuous infusion on days 1 to 5 every 3 weeks (total dose/cycle is 4,000 mg/m2); continue pembrolizumab and fluorouracil until disease progression, unacceptable toxicity, or (in patients without disease progression) for up to 24 months (Sun 2021). Refer to protocol for further details.

TCF or DCF regimen: IV: 750 mg/m2/day continuous infusion days 1 to 5 every 3 weeks (in combination with docetaxel and cisplatin) until disease progression or unacceptable toxicity occurs (Ajani 2007; Van Cutsem 2006).

Gastric cancer: IV: 200 to 1,000 mg/m2/day as a continuous infusion over 24 hours (as part of a platinum-containing regimen); the duration and frequency of each cycle varies based on the dose and regimen.

CF regimen: IV: 1,000 mg/m2/day continuous infusion days 1 to 4 and days 29 to 32 of a 35-day treatment cycle (preoperative chemoradiation; in combination with cisplatin) (Tepper 2008).

FLOT regimen: IV: 2,600 mg/m2 continuous infusion over 24 hours on day 1 every 2 weeks (in combination with leucovorin, oxaliplatin, and docetaxel) for 4 preoperative cycles and 4 postoperative cycles (Al-Batran 2019).

FOLFOX/nivolumab: IV: 400 mg/m2 bolus on day 1, followed by 1,200 mg/m2/day on days 1 and 2 (as a continuous infusion) every 2 weeks (in combination with leucovorin, oxaliplatin, and nivolumab) until disease progression or unacceptable toxicity (Janjigian 2021).

TCF or DCF regimen: IV: 750 mg/m2/day continuous infusion days 1 to 5 every 3 weeks (in combination with docetaxel and cisplatin) until disease progression or unacceptable toxicity occurs (Ajani 2007; Van Cutsem 2006).

ToGA regimen (HER2-positive): IV: 800 mg/m2/day continuous infusion days 1 to 5 every 3 weeks (in combination with cisplatin and trastuzumab) until disease progression or unacceptable toxicity occurs (Bang 2010).

Glaucoma surgery, adjunctive therapy (off-label use):

Intraoperative topical application: Ophthalmic: Apply sponge soaked in fluorouracil 50 mg/mL for 5 minutes (Cabourne 2015; Palanca-Capistrano 2009; WuDunn 2002). Additional data may be necessary to further define the role of fluorouracil in glaucoma surgery.

Postoperative subconjunctival injection: Ophthalmic: 5 mg once daily for 10 days or 5 mg once daily for 1 week, then every other day the next week for a total of 10 doses (Cabourne 2015). Additional data may be necessary to further define the role of fluorouracil in glaucoma surgery.

Head and neck cancer, squamous cell (off-label use):

Platinum-Fluorouracil (CF) regimen: IV: 1,000 mg/m2/day continuous infusion days 1 to 4 every 3 weeks (in combination with cisplatin) for at least 6 cycles (Gibson 2005) or 1,000 mg/m2/day continuous infusion days 1 to 4 every 4 weeks (in combination with carboplatin) (Forastiere 1992) or 600 mg/m2/day continuous infusion days 1 to 4, 22 to 25, and 43 to 46 (in combination with carboplatin and radiation) (Bourhis 2012; Denis 2004).

TPF regimen: IV: 1,000 mg/m2/day continuous infusion days 1 to 4 every 3 weeks (in combination with docetaxel and cisplatin) for 3 cycles, and followed by chemoradiotherapy (Posner 2007) or 750 mg/m2/day continuous infusion days 1 to 5 every 3 weeks (in combination with docetaxel and cisplatin) for up to 4 cycles, followed by radiation in patients without progressive disease (Vermorken 2007).

Platinum, 5-FU, and cetuximab regimen: IV: 1,000 mg/m2/day continuous infusion days 1 to 4 every 3 weeks (in combination with cetuximab and either cisplatin or carboplatin) for a total of up to 6 cycles (Vermorken 2008).

Hepatobiliary cancer (off-label use): IV: 600 mg/m2 (bolus) on days 1, 8, and 15 every 4 weeks (in combination with gemcitabine and leucovorin) (Alberts 2005). Additional data may be needed to further define the role of fluorouracil in this condition.

Neuroendocrine tumors, pancreatic (off-label use): IV: 400 mg/m2/day (bolus) days 1 to 5 every 28 days (in combination with doxorubicin and streptozocin) for at least 4 cycles and until disease progression or unacceptable toxicity occurs (Kouvaraki 2004). Additional data may be necessary to further define the role of fluorouracil in the management of this condition.

Pancreatic cancer:

Potentially curable disease, adjuvant therapy: Note: American Society of Clinical Oncology (ASCO) guidelines recommend 6 months of adjuvant therapy; if preoperative chemotherapy therapy was received, a total of 6 months of adjuvant therapy (including the preoperative regimen) is recommended (ASCO [Khorana 2019]).

mFOLFIRINOX regimen: IV: 2,400 mg/m2 as a continuous infusion over 46 hours every 14 days (in combination with leucovorin, irinotecan, and oxaliplatin) for 24 weeks (Conroy 2018). According to ASCO guidelines, mFOLFIRINOX is the preferred first-line adjuvant regimen for potentially curable disease (ASCO [Khorana 2019]).

Fluorouracil with leucovorin (off-label dosing): IV: 425 mg/m2/day (bolus) days 1 to 5 every 28 days (in combination with leucovorin) for 6 cycles (Neoptolemos 2004; Neoptolemos 2010). According to ASCO guidelines for potentially curable pancreatic cancer, fluorouracil with leucovorin may be considered as an alternative therapy if toxicity/tolerance is a concern (ASCO [Khorana 2019]).

Chemoradiation therapy (off-label dosing): IV: 250 mg/m2/day continuous infusion for 3 weeks prior to and then throughout radiation therapy; an additional 12 weeks of fluorouracil (as a continuous infusion, 4 weeks on and 2 weeks off for 2 cycles) was administered beginning 3 to 5 weeks after completion of chemoradiation (Regine 2008). Note: According to ASCO guidelines for potentially curable pancreatic cancer, adjuvant chemoradiation therapy may be considered for patients not receiving preoperative therapy and who present with positive margins (microscopically) following surgery and/or node-positive disease after completion of 4 to 6 months of systemic adjuvant chemotherapy (ASCO [Khorana 2019]).

Advanced or metastatic disease:

FOLFIRINOX regimen: IV: 400 mg/m2 bolus on day 1, followed by 2,400 mg/m2 (as a continuous infusion) over 46 hours every 14 days (in combination with leucovorin, irinotecan, and oxaliplatin) until disease progression or unacceptable toxicity occurs for a recommended 12 cycles (Conroy 2011).

OFF regimen (second-line therapy): IV: 2,000 mg/m2/day continuous infusion over 24 hours on days 1, 8, 15, and 22 every 6 weeks (in combination with oxaliplatin and leucovorin) until disease progression or unacceptable toxicity (Oettle 2014; Pelzer 2011).

Penile cancer, advanced, squamous cell (off-label use): IV: 800 to 1,000 mg/m2/day continuous infusion for 4 days every 21 days (in combination with cisplatin) (Di Lorenzo 2012). Additional data may be needed to further define the role of fluorouracil in this condition.

Unknown primary cancer, squamous cell (off-label use): IV: 750 mg/m2/day continuous infusion for 5 days every 21 days (in combination with docetaxel and cisplatin) for 3 cycles (Pointreau 2009) or 500 mg/m2/day continuous infusion for 5 days every 21 days (in combination with paclitaxel and cisplatin) for 3 cycles (Hitt 2005) or 400 mg/m2 bolus on day 1 followed by 1,200 mg/m2/day continuous infusion for 2 days (over 46 hours) every 2 weeks (in combination with leucovorin and oxaliplatin) (Cheeseman 2002) or 700 mg/m2/day continuous infusion for 5 days (in combination with cisplatin) every 28 days until disease progression or unacceptable toxicity occurs (Kusaba 2007). Additional data may be needed to further define the role of fluorouracil in this condition.

Vulvar cancer, advanced (off-label use): IV: 750 mg/m2/day continuous infusion days 1 to 5 every 14 days for 2 cycles (in combination with concomitant radiation and mitomycin) (Landoni 1996). Additional data may be needed to further define the role of fluorouracil in this condition.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling; use with caution. The following adjustments have been suggested:

CrCl <50 mL/minute and continuous renal replacement therapy (CRRT): No dosage adjustment necessary (Aronoff 2007).

Hemodialysis:

Administer standard dose following hemodialysis on dialysis days (Janus 2010).

Administer 50% of standard dose following hemodialysis (Aronoff 2007).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling; use with caution. The following adjustments have been suggested:

Bilirubin >5 mg/dL: Avoid use (Floyd 2006).

Hepatic impairment (degree not specified): Administer <50% of dose, then increase if toxicity does not occur (Koren 1992).

Dosing: Pediatric

(For additional information see "Fluorouracil (systemic): Pediatric drug information")

Note: Dose, frequency, number of doses, and/or start date may vary by protocol and treatment phase. Refer to individual protocols.

Hepatoblastoma: Limited data available: Infants, Children, and Adolescents: IV: 600 mg/m2/dose every 3 weeks on day 2 or 3 (in combination with cisplatin, vincristine ± doxorubicin) (Douglass 1993; Ortega 2000; Watanabe 2013)

Nasopharyngeal carcinoma: Limited data available: Children ≥8 years and Adolescents: Continuous IV infusion: 1,000 mg/m2/day for 3 to 5 days every 3 to 4 weeks for 3 to 4 cycles (in combination with other chemotherapy agents) (Buehrlen 2012; Casanova 2012; Mertens 2005; Rodriguez-Galindo 2005)

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

There are no pediatric specific dosage adjustments available; refer to protocols. Based on experience in adult patients, extreme caution should be used in patients with renal impairment and dosing adjustment is suggested.

Dosing: Hepatic Impairment: Pediatric

There are no pediatric specific dosage adjustments available; refer to protocols. Based on experience in adult patients, extreme caution should be used in patients with hepatic impairment and dosing adjustment is suggested.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Obesity: Adult

ASCO Guidelines for appropriate chemotherapy dosing in adults with cancer with a BMI ≥30 kg/m2: Utilize patient's actual body weight (full weight) for calculation of body surface area- or weight-based dosing, particularly when the intent of therapy is curative; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full weight-based dosing with subsequent cycles, if cause of toxicity (eg, hepatic or renal impairment) is clearly established and fully resolved (ASCO [Griggs 2021]).

Dosing: Adjustment for Toxicity: Adult

Withhold treatment for the following (may resume at a reduced dose following resolution or improvement to grade 1):

Dermatologic toxicity: Grade 2 or 3 palmar-plantar erythrodysesthesia (hand-foot syndrome [HFS]); initiate supportive care for symptomatic relief of HFS.

GI toxicity: Grade 3 or 4 diarrhea (administer fluids, electrolyte replacement, and/or antidiarrheal treatments as necessary); grade 3 or 4 mucositis.

Hematologic toxicity: Grade 4 myelosuppression.

Withhold treatment for the following (there is no recommended dose for resumption):

Cardiovascular toxicity: Angina, MI/ischemia, arrhythmia, or heart failure (in patients with no history of coronary artery disease or myocardial dysfunction)

CNS toxicity: Acute cerebellar syndrome, confusion, disorientation, ataxia, or visual disturbances

Hyperammonemic encephalopathy (initiate ammonia-lowering therapy).

Evidence of acute early-onset or unusually severe toxicity indicative of dihydropyrimidine dehydrogenase deficiency: Withhold or permanently discontinue fluorouracil depending on the onset, duration, and severity of toxicity.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous:

Generic: 500 mg/10 mL (10 mL); 1 g/20 mL (20 mL); 5 g/100 mL (100 mL)

Solution, Intravenous [preservative free]:

Adrucil: 500 mg/10 mL (10 mL [DSC]); 2.5 g/50 mL (50 mL [DSC]); 5 g/100 mL (100 mL [DSC])

Generic: 500 mg/10 mL (10 mL); 1 g/20 mL (20 mL); 2.5 g/50 mL (50 mL); 5 g/100 mL (100 mL)

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Generic: 50 mg/mL (10 mL, 100 mL); 500 mg/10 mL (10 mL); 5 g/100 mL (100 mL)

Administration: Adult

IV: IV administration rate varies by protocol; refer to specific reference for protocol. May be administered by IV push, IV bolus, or as a continuous infusion. Fluorouracil may be an irritant (Pérez Fidalgo 2012); avoid extravasation.

The pharmacy bulk vial is NOT for direct infusion.

When administering bolus fluorouracil, 30 minutes of cryotherapy is recommended to prevent oral mucositis (MASCC/ISOO [Elad 2020]).

Ophthalmic (off-label route):

Intraoperative topical application: Aseptically apply fluorouracil-saturated sponges to surgical site of glaucoma filtration surgery for 5 minutes (Cabourne 2015; WuDunn 2002).

Postoperative subconjunctival injections were administered 90 to 180 degrees away from the surgical site (Cabourne 2015).

Administration: Pediatric

IV: Administration rate varies by protocol; refer to specific reference for protocol. May be administered undiluted by IV push, or further diluted in appropriate fluids and administered by IV bolus, or as a continuous infusion. Avoid extravasation (may be an irritant).

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 1]).

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).

Use: Labeled Indications

Breast cancer: Management of breast cancer

Colon and rectal cancer: Management of colon and rectal cancer

Gastric cancer: Management of stomach (gastric) cancer

Pancreatic cancer: Management of pancreatic cancer

Guideline recommendations: American Society of Clinical Oncology:

Potentially curable pancreatic cancer: American Society of Clinical Oncology (ASCO) guidelines (ASCO [Khorana 2019]) recommend fluorouracil as part of the modified FOLFIRINOX regimen (fluorouracil, leucovorin, oxaliplatin, and irinotecan), as the preferred adjuvant therapy in patients without concerns for toxicity or tolerance, and in the absence of medical or surgical contraindications. Alternatively, if there are concerns of toxicity or tolerance, fluorouracil (plus leucovorin calcium) is an option that may be offered.

Locally advanced, unresectable pancreatic cancer: According to the ASCO guidelines for locally advanced, unresectable pancreatic cancer (ASCO [Balaban 2016]), induction with ≥6 months of initial systemic therapy (with a combination regimen) is recommended in patients with an Eastern Cancer Cooperative Group (ECOG) performance status of 0 or 1, a favorable comorbidity profile, a preference for aggressive therapy, and a suitable support system; there is no clear evidence to encourage one regimen over another. If disease progression occurs, treatment according to guidelines for metastatic pancreatic cancer should be offered.

Metastatic pancreatic cancer: ASCO guidelines (ASCO [Sohal 2020]) recommend the FOLFIRINOX regimen (fluorouracil, leucovorin, oxaliplatin, and irinotecan) as first-line therapy in patients with an ECOG performance status of 0 or 1, a favorable comorbidity profile, a preference for aggressive therapy, a suitable support system, and access to a chemotherapy port/infusion pump management service. For patients who received an alternative first-line (gemcitabine-based) therapy and meet the above criteria, preferred second-line therapy includes fluorouracil in combination with irinotecan (liposomal) or conventional irinotecan (if liposomal irinotecan is unavailable), or fluorouracil in combination with oxaliplatin may also be considered. For patients with a performance status of 2 or with comorbidities, fluorouracil (with leucovorin; may add irinotecan [liposomal]) may be considered as an option for second-line therapy (with proactive dose/schedule adjustments to minimize toxicities).

Use: Off-Label: Adult

Anal carcinoma; Bladder cancer (muscle invasive); Cervical cancer; Esophageal cancer; Glaucoma surgery (adjunctive therapy); Head and neck cancer; Hepatobiliary cancers (advanced); Neuroendocrine tumors (pancreatic); Penile cancer (advanced) (squamous cell); Unknown primary cancer (squamous cell); Vulvar cancer, advanced

Medication Safety Issues
Sound-alike/look-alike issues:

Fluorouracil may be confused with floxuridine, flucytosine

High alert medication:

This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

Administration issues:

Continuous infusion: Serious errors have occurred when doses administered by continuous ambulatory infusion pumps have inadvertently been given over 1 to 4 hours instead of the intended extended continuous infusion duration. Depending on protocol, infusion duration may range from 46 hours to 7 days for fluorouracil continuous infusions. Ambulatory pumps utilized for continuous infusions should have safeguards to allow for detection of programming errors. If using an elastomeric device for ambulatory continuous infusion, carefully select the device and double check the flow rate. Appropriate prescribing (in single daily doses [not course doses] with instructions to infuse over a specific time period), appropriate training/certification/education of staff involved with dispensing and administration processes, and independent double checks should be utilized throughout dispensing and administration procedures.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency not defined. Toxicity depends on duration of treatment and/or rate of administration.

Cardiovascular: Angina pectoris, cardiac arrhythmia, cardiac failure, cerebrovascular accident, ischemic heart disease, local thrombophlebitis, myocardial infarction, vasospasm, ventricular ectopy

Central nervous system: Cerebellar syndrome (acute), confusion, disorientation, euphoria, headache

Dermatologic: Alopecia, changes in nails (including nail loss), dermatitis, hyperpigmentation (supravenous), maculopapular rash (pruritic), palmar-plantar erythrodysesthesia, skin fissure, skin photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis, xeroderma

Gastrointestinal: Anorexia, diarrhea, esophagopharyngitis, gastrointestinal hemorrhage, gastrointestinal ulcer, mesenteric ischemia (acute), nausea, stomatitis, tissue sloughing (gastrointestinal), vomiting

Hematologic & oncologic: Agranulocytosis, anemia, leukopenia (nadir: days 9 to 14; recovery by day 30), pancytopenia, thrombocytopenia

Hypersensitivity: Anaphylaxis, hypersensitivity reaction (generalized)

Ophthalmic: Lacrimal stenosis, lacrimation, nystagmus, photophobia, visual disturbance

Respiratory: Epistaxis

<1%, postmarketing, and/or case reports: Dysgeusia (Syed 2016)

Contraindications

There are no contraindications listed in the manufacturer’s US labeling.

Canadian labeling: Known hypersensitivity to fluorouracil or any component of the formulation; debilitated patients; poor nutritional state; depressed bone marrow function following radiotherapy or therapy with other antineoplastic agents; potentially serious infections.

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: Fluorouracil can cause severe and fatal hematologic toxicity (neutropenia, thrombocytopenia, and anemia). The neutrophil nadir usually occurs between 9 to 14 days after administration.

• Cardiotoxicity: Based on postmarketing reports, fluorouracil may cause cardiotoxicity (angina, MI/ischemia, arrhythmia, and heart failure). Risk factors for cardiotoxicity include continuous infusion administration (versus IV bolus) and coronary artery disease. The risks of resuming fluorouracil in patients with resolved cardiotoxicity have not been established. In a scientific statement from the AHA, fluorouracil has been determined to be an agent that may either cause reversible direct myocardial toxicity or exacerbate underlying myocardial dysfunction (magnitude: moderate/major) (AHA [Page 2016]).

• GI toxicity: Fluorouracil is associated with severe diarrhea. Mucositis, stomatitis, or esophagopharyngitis (which may lead to mucosal sloughing or ulceration) may occur with fluorouracil. The incidence of mucositis is reported to be higher with IV bolus fluorouracil administration (vs continuous infusion).

• Hand-foot syndrome: Fluorouracil is associated with palmar-plantar erythrodysesthesia (hand-foot syndrome; HFS). Symptoms of HFS include a tingling sensation, pain, swelling, erythema with tenderness, and desquamation. HFS occurs more commonly when fluorouracil is administered as a continuous infusion (compared to IV bolus) and has been reported to occur more frequently in patients with prior chemotherapy exposure. The onset of HFS is usually after 8 to 9 weeks of fluorouracil, although may occur earlier.

• Hyperammonemic encephalopathy: Fluorouracil may result in hyperammonemic encephalopathy in the absence of liver disease or other identifiable cause (postmarketing reports). The onset of hyperammonemic encephalopathy signs/symptoms (altered mental status, confusion, disorientation, coma, or ataxia, in the presence of concomitant elevated serum ammonia level) was within 72 hours after fluorouracil infusion initiation. The risks of resuming fluorouracil in patients with resolved hyperammonemic encephalopathy have not been established.

• Neurotoxicity: Fluorouracil may cause neurologic toxicity, including acute cerebellar syndrome and other neurologic events (postmarketing reports). Neurologic symptoms included confusion, disorientation, ataxia, or visual disturbances. There are insufficient data on the risks of resuming fluorouracil in patients with resolved neurologic toxicity.

Disease-related concerns:

• Dihydropyrimidine dehydrogenase deficiency: Patients with select homozygous or compound heterozygous dihydropyrimidine dehydrogenase (DPD) gene mutations that result in complete or near complete absence of DPD activity are at increased risk for acute early-onset of toxicity and severe, life-threatening, or fatal adverse reactions (eg, mucositis, diarrhea, neutropenia, neurotoxicity) due to fluorouracil. Patients with partial DPD activity may also have increased risk of severe, life-threatening, or fatal adverse reactions when administered fluorouracil. Based on clinical assessment of toxicity onset, duration, and severity, withhold or permanently discontinue fluorouracil in patients with evidence of acute early-onset or unusually severe toxicity, which may indicate near complete or total absence of DPD activity. There is no fluorouracil dose that has been proven safe in patients with complete absence of DPD activity and data are insufficient to recommend a specific dose in patients with partial DPD activity as measured by any specific test.

Concurrent drug therapy issues:

• Warfarin: Clinically significant coagulation parameter elevations have been reported with concomitant use of warfarin and fluorouracil. Closely monitor INR and prothrombin time in patients receiving concomitant coumarin-derivative anticoagulants such as warfarin and adjust the anticoagulant dose accordingly.

Other warnings/precautions:

• Administration safety issues: Serious errors have occurred when doses administered by continuous ambulatory infusion pumps have inadvertently been given over 1 to 4 hours instead of the intended extended continuous infusion duration. Depending on protocol, infusion duration may range from 46 hours to 7 days for fluorouracil continuous infusions. Ambulatory pumps utilized for continuous infusions should have safeguards to allow for detection of programming errors. If using an elastomeric device for ambulatory continuous infusion, carefully select the device and double check the flow rate. Appropriate prescribing (in single daily doses [not course doses] with instructions to infuse over a specific time period), appropriate training/certification/education of staff involved with dispensing and administration processes, and independent double checks should be utilized throughout dispensing and administration procedures (ISMP [Smetzer 2015]).

• Antidote: Uridine triacetate (formerly called vistonuridine), has been studied in cases of fluorouracil overdose. In a clinical study of 98 patients who received uridine triacetate for fluorouracil toxicity (due to overdose, accidental capecitabine ingestion, or possible DPD deficiency), 96 patients recovered fully (Bamat 2013). Of 17 patients receiving uridine triacetate beginning within 8 to 96 hours after fluorouracil overdose, all patients fully recovered (von Borstel 2009). Refer to Uridine Triacetate monograph.

Metabolism/Transport Effects

Inhibits CYP2C9 (weak)

Drug Interactions

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination

Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy

Brivudine [INT]: May enhance the adverse/toxic effect of Fluorouracil Products. Risk X: Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy

Cimetidine: May increase the serum concentration of Fluorouracil Products. Risk C: Monitor therapy

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination

Cladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine. Risk X: Avoid combination

Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification

COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Risk C: Monitor therapy

COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy

COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Consider administration of a 3rd dose of COVID-19 vaccine, at least 28 days after completion of the primary 2-dose series, in patients 5 years of age and older taking immunosuppressive therapies. Risk D: Consider therapy modification

COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification

Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination

Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination

Echinacea: May diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider avoiding echinacea in patients receiving therapeutic immunosuppressants, such cytotoxic chemotherapy. If combined, monitor for reduced efficacy of cytotoxic chemotherapy. Risk D: Consider therapy modification

Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination

Folic Acid: May enhance the adverse/toxic effect of Fluorouracil Products. Risk C: Monitor therapy

Fosphenytoin-Phenytoin: CYP2C9 Inhibitors (Weak) may increase the serum concentration of Fosphenytoin-Phenytoin. Risk C: Monitor therapy

Gemcitabine: May increase the serum concentration of Fluorouracil (Systemic). Risk C: Monitor therapy

Gimeracil: May increase the serum concentration of Fluorouracil Products. Risk X: Avoid combination

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy

Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy

Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification

Interferons (Alfa): May increase the serum concentration of Fluorouracil Products. Risk C: Monitor therapy

Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider therapy modification

Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification

Leucovorin Calcium-Levoleucovorin: May enhance the adverse/toxic effect of Fluorouracil Products. Risk C: Monitor therapy

Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification

MetroNIDAZOLE (Systemic): May increase the serum concentration of Fluorouracil Products. Risk C: Monitor therapy

Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination

Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy

Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy

Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider therapy modification

Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy

Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy

Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination

Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If post-exposure rabies vaccination is required during immunosuppressant therapy, administer a 5th dose of vaccine and check for rabies antibodies. Risk D: Consider therapy modification

Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification

Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination

Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination

Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification

Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor therapy

Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination

Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination

Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination

Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination

TOLBUTamide: CYP2C9 Inhibitors (Weak) may increase the serum concentration of TOLBUTamide. Risk C: Monitor therapy

Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination

Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination

Vaccines (Inactivated): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Vaccines (Inactivated). Management: Give inactivated vaccines at least 2 weeks prior to initiation of chemotherapy when possible. Patients vaccinated less than 14 days before initiating or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider therapy modification

Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Vitamin K Antagonists (eg, warfarin): Fluorouracil Products may increase the serum concentration of Vitamin K Antagonists. Management: Monitor INR and for signs/symptoms of bleeding closely when a fluorouracil product is combined with a vitamin K antagonist (eg, warfarin). Anticoagulant dose adjustment will likely be necessary. Risk D: Consider therapy modification

Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination

Reproductive Considerations

Patients who can become pregnant and patients with partners who can become pregnant should use effective contraception during treatment and for 3 months following cessation of fluorouracil therapy.

Pregnancy Considerations

Based on the mechanism of action and available human data, fluorouracil may cause fetal harm if administered during pregnancy (NTP 2013). Use in the first trimester is not recommended (Silverstein 2020).

The European Society for Medical Oncology has published guidelines for diagnosis, treatment, and follow-up of cancer during pregnancy. The guidelines recommend referral to a facility with expertise in cancer during pregnancy and encourage a multidisciplinary team (obstetrician, neonatologist, oncology team). In general, if chemotherapy is indicated, it should be avoided during in the first trimester, there should be a 3-week time period between the last chemotherapy dose and anticipated delivery, and chemotherapy should not be administered beyond week 33 of gestation (ESMO [Peccatori 2013]).

A long-term observational research study is collecting information about the diagnosis and treatment of cancer during pregnancy. For additional information about the pregnancy and cancer registry or to become a participant, contact Cooper Health (1-877-635-4499).

Breastfeeding Considerations

It is not known if fluorouracil is present in breast milk.

Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends a decision be made to discontinue breastfeeding or to discontinue fluorouracil, taking into account the importance of treatment to the breastfeeding patient. Other guidance suggests waiting at least 24 hours after the last dose of fluorouracil and feeding with breast milk; however, actual recommendations should be individualized. Patients may maintain milk supply by expressing during treatment; however, milk supply is expected to be decreased by systemic chemotherapy (ABM [Johnson 2020]).

Dietary Considerations

Increase dietary intake of thiamine.

Monitoring Parameters

CBC with differential and platelet count (prior to each treatment cycle, weekly if administered on a weekly or similar schedule, and as clinically indicated), renal function tests, LFTs, INR, and prothrombin time (monitor closely in patients receiving concomitant coumarin-derivative anticoagulants). Monitor for signs/symptoms of palmar-plantar erythrodysesthesia syndrome, cardiotoxicity, CNS toxicity, stomatitis, diarrhea, and hyperammonemic encephalopathy. Promptly evaluate any symptoms suggestive of cardiotoxicity. Consider monitoring ECG in patients on concomitant QT prolonging medications.

The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

Mechanism of Action

Fluorouracil is a pyrimidine analog antimetabolite that interferes with DNA and RNA synthesis; after activation, F-UMP (an active metabolite) is incorporated into RNA to replace uracil and inhibit cell growth; the active metabolite F-dUMP, inhibits thymidylate synthetase, depleting thymidine triphosphate (a necessary component of DNA synthesis).

Pharmacokinetics

Distribution: Fluorouracil distributes throughout the body, including brain tissue, CSF, bone marrow, intestinal mucosa, and liver.

Metabolism: Hepatic; via a dehydrogenase enzyme; FU must be metabolized to form active metabolites, 5-fluoroxyuridine monophosphate (F-UMP) and 5-5-fluoro-2’-deoxyuridine-5’-O-monophosphate (F-dUMP)

Half-life elimination: Following bolus infusion: 8 to 20 minutes

Excretion: Urine (5% to 20% as unchanged drug within 6 hours; metabolites over 3 to 4 hours)

Pricing: US

Solution (Fluorouracil Intravenous)

1 g/20 mL (per mL): $0.33 - $1.43

2.5 gm/50 mL (per mL): $0.29 - $0.69

5 g/100 mL (per mL): $0.29 - $0.69

500 mg/10 mL (per mL): $0.30 - $1.59

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • 5-Fluril (BD);
  • 5-FU (DE, JP, KR);
  • Agicil (MT);
  • Fivoflu (IN, JO, PH, VE, ZW);
  • Flonida (IN);
  • Fluonco (PH);
  • Flurablastin (DK, FI, NO, SE);
  • Fluracedyl (BE, MY, NL, PH);
  • Fluroblastin (VE);
  • Fluroblastine (BE);
  • Fluroxan (BD, LK);
  • Fu Ke (CN);
  • La-Fu (CZ);
  • Pharmauracil (PK);
  • Raciwel (LK);
  • Ribofluor (DE);
  • Sinofuan Implant (CN);
  • Triosules (AR);
  • Utoral (PH)


For country abbreviations used in Lexicomp (show table)

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