Fluorouracil (Monograph)
Brand name: Adrucil
Drug class: Antineoplastic Agents
Introduction
Pyrimidine antagonist; antimetabolite; antineoplastic agent.205
Uses for Fluorouracil
Cancers
Treatment of adenocarcinoma of the colon, rectum, breast, stomach, and pancreas.205
Adjunct to surgery for the treatment of various solid tumors (e.g., adenocarcinoma of the colon,226 227 228 229 230 231 232 233 252 253 256 261 280 rectal carcinoma).230 234 235 236 237 238 239 240 242 243 280
Colorectal Cancer
Drug of choice (combined with leucovorin or levoleucovorin and other drugs [e.g., irinotecan, oxaliplatin]) for advanced colorectal cancer in the adjuvant or metastatic setting.289 386 387 388 397 410 411 412 413 414 415 446 447
Doublet regimens (i.e., fluorouracil, oxaliplatin, and leucovorin or levoleucovorin [FOLFOX]; fluorouracil, irinotecan, and leucovorin or levoleucovorin [FOLFIRI]; capecitabine and oxaliplatin [CapeOx; CapOx]) are the current standard of care for the adjuvant or palliative treatment of advanced colorectal cancer.411 412 415 416 417 419 420 446 10008
Fluorouracil combined with leucovorin or levoleucovorin is an acceptable treatment option in limited-resource settings or in patients unable to tolerate a doublet regimen.419
Weekly schedule of fluorouracil/leucovorin (high-dose leucovorin or Roswell Park regimen) has equal efficacy as monthly schedule (low-dose or Mayo Clinic schedule), but the weekly schedule is a preferred regimen for adjuvant therapy because of ease of use and less toxicity.386 388 (See Colorectal Cancer under Dosage and Administration.)
Bimonthly, continuous IV infusion schedule of fluorouracil/leucovorin (LV5FU2 or deGramont regimen) also evaluated as adjuvant therapy390 and shown to be safer than direct IV injection regimen of these drugs.388 390 Simplified version of this regimen also evaluated.391 (See Colorectal Cancer under Dosage and Administration.)
Role of regional adjuvant therapy (e.g., portal vein or hepatic artery infusion† [off-label]) for liver metastases requires further elucidation.230 253 256 257 258 259 260 264 275 280
Leucovorin and levoleucovorin enhance cytotoxicity,221 286 291 303 305 306 307 308 309 310 395 397 potentiate fluorouracil antineoplastic activity, and improve response for advanced colorectal carcinoma treatment.200 201 211 215 216 218 219 220 266 286 287 288 289 290 291 292 293 294 295 296 297 298 299 300 301 302 303 304 305 306 311 313 314 315 317 395
Leucovorin and levoleucovorin may potentiate risk of fluorouracil GI toxicity (e.g., diarrhea, nausea, stomatitis, vomiting) and myelosuppression.214 215 217 218 266 286 289 292 293 294 295 296 311 395
Breast Cancer
Combined with other drugs (e.g., cyclophosphamide, doxorubicin, methotrexate) as an adjunct to surgery and for metastatic breast cancer.244 249 251 279 319 320 322 323 324 325 326 328
Decision regarding use of adjuvant endocrine therapy with or without sequential combination chemotherapy may be guided by prognostic tools, such as recurrence score based on 21-gene assay results, to predict absolute benefit of combination chemotherapy in addition to adjuvant endocrine therapy.433
Adjunct to surgery, may improve outcome.244 245 246 247 248 249 250 251 254 270 271 272
Esophageal Cancer
Has been used alone330 334 336 and in combination therapy (e.g., with cisplatin)249 329 330 331 334 336 for the treatment of localized or advanced esophageal cancer† [off-label].
Head and Neck Cancer
Has been used in combination chemotherapy for metastatic or recurrent squamous cell carcinoma of the head and neck† [off-label].349
Has been used in combination chemotherapy with radiation therapy for palliative treatment of unresectable locally advanced head and neck cancer,337 and for larynx preservation in locally advanced laryngeal or hypopharyngeal cancer.354 355 356 357
Used in combination with docetaxel and cisplatin as induction therapy prior to radiotherapy or chemoradiotherapy in the treatment of locally advanced squamous cell carcinoma of the head and neck.393 394
Cervical Cancer
Has been used in combination with cisplatin concurrently with radiation therapy for invasive cervical cancer† [off-label].249 359 360 361 362 364
Metastatic or recurrent cervical cancer† [off-label].249 365 366 367 369 370 371
Renal Cell Carcinoma
Has been used alone374 or in combination regimens375 376 377 378 379 380 381 382 383 384 for the treatment of metastatic renal cell carcinoma†.
Carcinoid Tumors
Has been used for the treatment of carcinoid tumors†.249
Other Uses
Has been used as second-line therapy in the treatment of ovarian epithelial cancer†, including platinum-refractory disease.241 Also, cancers of the liver† (e.g., hepatoblastoma†).249
Related/similar drugs
Kisqali, Ibrance, Piqray, Opdivo, estradiol, tamoxifen, testosterone
Fluorouracil Dosage and Administration
Administration
Administer IV.205
Has been administered by regional infusion into the venous or arterial blood supply of a tumor† (e.g., portal vein or hepatic artery infusions for liver metastases).230 253 256 258 259 264 275 280
IV Administration
For solution and drug compatibility information, see Compatibility under Stability.
2.5- or 5-g pharmacy bulk package is intended for individual dose preparation, not for direct IV infusion.205
Use an established IV line to administer fluorouracil by direct IV injection.205
For IV infusion regimens, administer fluorouracil via a central venous catheter using a controlled infusion device (e.g., pump).205
Avoid extravasation.205
Dilution
No dilution necessary for usual injection formulation.205
Rate of Administration
Administer by direct IV injection or continuous IV infusion.205
Dosage
Base dosage on actual weight.205
May calculate dosage based on body surface area.215 218 220 266 275 286 289 292 293 294 295 296 298 300 304 305 317 320 321 322 323 328
Individualize dosage and dosage schedule based on tumor type, specific regimen, clinical response, and concomitant comorbidities.205
Consult published protocols for the dosage and method and sequence of administration of fluorouracil with other chemotherapeutic agents.
Adults
Colorectal Cancer
Various fluorouracil/leucovorin combination dosage regimens have been used.215 220 266 289 296 298 304 305 317
IV
Direct IV injection: 500 mg/m2 by direct IV injection in combination with leucovorin or levoleucovorin on days 1, 8, 15, 22, 29, and 36 in each 8-week cycle.205
IV infusion: 400 mg/m2 by direct IV injection on day 1 followed by 2400–3000 mg/m2 as a continuous IV infusion over 46 hours every 14 days in combination with leucovorin or levoleucovorin with or without oxaliplatin or irinotecan.205
Combination Regimen: Fluorouracil, Leucovorin, and Oxaliplatin (FOLFOX)
IVDay 1: Oxaliplatin 85 mg/m2 and leucovorin 200 mg/m2 concurrently (in separate containers using a Y-type administration set) by IV infusion over 2 hours, followed by fluorouracil 400 mg/m2 by direct IV injection, and then fluorouracil 600 mg/m2 by IV infusion over 22 hours.411 446
Day 2: Leucovorin 200 mg/m2 by IV infusion over 2 hours, followed by fluorouracil 400 mg/m2 by direct IV injection, and then fluorouracil 600 mg/m2 by IV infusion over 22 hours.411 446
Following schedule also used: Oxaliplatin 85–100 mg/m2 and leucovorin 400 mg/m2 by IV infusion over 2 hours, followed by fluorouracil 400 mg/m2 by direct IV injection, and then fluorouracil 2400–3000 mg/m2 by IV infusion over 46 hours.446
Repeat cycles every 2 weeks.411 446
Combination Regimen: Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI)
IVIrinotecan 180 mg/m2 and leucovorin 400 mg/m2 administered concurrently by IV infusion over 2 hours, followed by fluorouracil 400 mg/m2 by direct IV injection, and then fluorouracil 2400–3000 mg/m2 by IV infusion over 46 hours; repeat cycles every 2 weeks.418 446
Combination Regimen: Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan (FOLFOXIRI)
IVIrinotecan 165 mg/m2 by IV infusion over 1 hour, followed by leucovorin 200 mg/m2 and oxaliplatin 85 mg/m2 administered concurrently by IV infusion over 2 hours, and then fluorouracil 3200 mg/m2 by IV infusion over 48 hours; repeat cycles every 2 weeks.441 446
Monthly Schedule (Mayo Clinic Regimen)
Direct IV InjectionLeucovorin 20 mg/m2 IV or levoleucovorin 10 mg/m2 IV followed by fluorouracil 425 mg/m2 IV; administer fluorouracil and either leucovorin or levoleucovorin daily for 5 consecutive days and repeat regimen at 4-week intervals for 2 additional courses; thereafter, may repeat the regimen at intervals of 4–5 weeks provided toxicity from the previous course has resolved completely.286 289 386 388 395 Frequently administered for a total of 6 cycles in the adjuvant setting.386 388
Alternatively, leucovorin 200 mg/m2 IV or levoleucovorin 100 mg/m2 IV over ≥3 minutes followed by fluorouracil 370 mg/m2 IV; administer fluorouracil and either leucovorin or levoleucovorin daily for 5 consecutive days and repeat regimen at 4-week intervals for 2 additional courses; thereafter, may repeat the regimen at intervals of 4–5 weeks provided toxicity from the previous course has resolved completely.286 395 397
Adjust fluorouracil dosage in subsequent courses according to tolerance;286 395 reduce daily fluorouracil dosage by 20% for moderate hematologic or GI toxicity in prior course and by 30% for severe toxicity266 286 289 395 (leucovorin or levoleucovorin dosage is not adjusted286 395 ).
May increase fluorouracil dosage by 10% if no toxicity occurred in the prior course.286 395
Weekly Schedule (Roswell Park Regimen)
IV InfusionLeucovorin 500 mg/m2 as a 2-hour IV infusion followed by fluorouracil 500 mg/m2 as a slow IV injection administered 1 hour after the start of the leucovorin infusion.386 388 Administer both drugs weekly for 6 consecutive weeks followed by a 2-week rest; repeat cycles every 8 weeks for a total of 4 courses in the adjuvant setting.386 388
Adjust fluorouracil dosage in subsequent courses according to tolerance;286 reduce daily fluorouracil dosage by 20% for moderate hematologic or GI toxicity in prior course and by 30% for severe toxicity266 286 289 (leucovorin dosage is not adjusted286 ).
May increase fluorouracil dosage by 10% if no toxicity occurred in the prior course.286
Bimonthly Schedule (Modified deGramont Regimen)
IV InfusionLeucovorin 400 mg/m2 as a 2-hour IV infusion on day 1 followed by fluorouracil 400 mg/m2 as an IV injection on day 1; then fluorouracil 1500 mg/m2 as a continuous IV infusion over 23 hours on days 1 and 2 (i.e., total 3000 mg/m2 by continuous IV infusion over 46 hours);391 repeat cycles every 2 weeks.
Breast Cancer
Various combination regimens have been used; consult published protocols for dosages and method and sequence of administration.246 269 271 272 320 321 322 323 324 325 326 328
Avoid arbitrary dose reductions of adjuvant combination chemotherapy; dose intensity appears to be an important factor influencing clinical outcome in early node-positive breast cancer (increasing response with increasing intensity).244 322
IV
500 or 600 mg/m2 IV on days 1 and 8 of each 28-day cycle for a total of 6 cycles in combination with a cyclophosphamide-based regimen.205
Combination Regimen: Cyclophosphamide, Methotrexate, and Fluorouracil
IVRegimen containing IV fluorouracil in combination with oral cyclophosphamide and IV methotrexate is described in the table.320 321
|
Drug |
Dose |
Administration Days per Cycle |
|---|---|---|
|
Fluorouracil |
||
|
Cyclophosphamide |
||
|
Methotrexate |
Repeat monthly (i.e., allow a 2-week rest period between cycles).320 321
Total of 6–12 cycles (i.e., 6–12 months of therapy); clinical superiority between 6- versus 12-month regimens not demonstrated.244 319 320 321
Initial fluorouracil and methotrexate dosages have been reduced in patients >60 years of age.321 (See Geriatric Patients under Special Populations.)
Also, dosage was reduced if myelosuppression developed.320 321
Sequential Regimen: Cyclophosphamide, Methotrexate, and Fluorouracil Plus Doxorubicin
In early breast cancer and >3 positive axillary lymph nodes, doxorubicin addition may improve outcome, and sequential regimens (i.e., several courses of doxorubicin first) may be more effective than alternating regimens; no additional benefit when fewer positive nodes are present.323 326
IVInitially, doxorubicin hydrochloride 75 mg/m2 IV at 3-week intervals for 4 doses.323 328
Subsequently, fluorouracil 600 mg/m2 IV, methotrexate 40 mg/m2 IV, and cyclophosphamide 600 mg/m2 IV at 3-week intervals for 8 cycles.323 328
Total of about 9 months of therapy.323 328
Generally, myelosuppression has delayed cycle rather than reducing dosage.323 328
Gastric Cancer
IV
200–1000 mg/m2 as a continuous IV infusion over 24 hours in combination with a platinum-based regimen.205 Consult published protocols for frequency of dosing and duration of each cycle for the specific regimen.205
Pancreatic Cancer
IV
400 mg/m2 by direct IV injection on day 1 followed by 2400 mg/m2 as a continuous IV infusion over 46 hours every 14 days in combination with leucovorin or as part of a multi-drug regimen containing leucovorin.205
Dosage Modification for Toxicity
For grade 3 or 4 diarrhea or mucositis, grade 4 myelosuppression, or grade 2 or 3 palmar-plantar erythrodysesthesia (hand-foot syndrome), withhold therapy; resume therapy at a reduced dosage when the toxicity has resolved or improved to grade 1.205
Temporarily withhold therapy if cardiotoxicity (i.e., angina, myocardial infarction or ischemia, arrhythmia, heart failure) develops in patients with no history of coronary artery disease or cardiac dysfunction; also withhold therapy if hyperammonemic encephalopathy or neurologic effects (i.e., acute cerebellar syndrome, confusion, disorientation, ataxia, visual disturbance) occur.205 Manufacturer makes no dosage recommendations for resumption of fluorouracil therapy following development of cardiotoxicity, hyperammonemic encephalopathy, or neurologic effects.205
Special Populations
Geriatric Patients
Breast Cancer
In patients >60 years of age receiving oral cyclophosphamide, IV methotrexate, and IV fluorouracil combination therapy, reduce initial methotrexate dosage to 30 mg/m2 and fluorouracil dosage to 400 mg/m2.321
Cautions for Fluorouracil
Contraindications
-
Manufacturer states none known.205
Warnings/Precautions
Dipyrimidine Dehydrogenase (DPD) Activity Deficiency
Acute early-onset or unusually severe toxicity may indicate near-complete or total absence of DPD activity; withhold or permanently discontinue fluorouracil in such patients.205
Certain homozygous or compound heterozygous mutations in the DPD gene result in complete or near-complete absence of DPD activity.205 Patients with such mutations are at increased risk for acute early-onset and severe, life-threatening, or fatal toxicity (e.g., mucositis, diarrhea, neutropenia, neurotoxicity).205 Patients with partial DPD activity also may have increased risk of severe, life-threatening, or fatal toxicity.205
Safety not established in patients with complete absence of DPD activity.205
Data insufficient to support dosage recommendations for those with partial DPD activity.205
Cardiac Effects
Myocardial ischemia/infarction,205 207 208 heart failure,205 arrhythmias,205 and angina205 207 208 209 (including Prinzmetal variant angina)209 reported.
Administration of drug by continuous IV infusion and presence of coronary artery disease may increase risk of cardiotoxicity.205
Safety of resuming fluorouracil after resolution of cardiotoxicity not established.205
Nervous System Effects
Disorientation, confusion, ataxia, visual disturbances, and acute cerebellar syndrome reported.205 Insufficient data on risks of resuming fluorouracil after resolution of neurologic adverse effects.205
Hyperammonemic encephalopathy, in the absence of liver disease or other identifiable cause, reported.205 Altered mental status, confusion, disorientation, ataxia, or coma in presence of elevated serum ammonia concentrations, may occur ≤72 hours following initiation of fluorouracil infusion.205
If hyperammonemic encephalopathy or neurologic effects occur, temporarily interrupt therapy.205
GI Toxicity
Mucositis, stomatitis, and esophagopharyngitis and subsequent mucosal sloughing or ulceration reported more frequently following administration of the drug by direct IV injection compared with administration by continuous IV infusion.205 Diarrhea occurs frequently and may be severe.205
Temporarily withhold fluorouracil if grade 3 or 4 diarrhea or mucositis occurs; resume drug at a reduced dosage when the toxicity resolves or improves to grade 1.205 Potential for diarrhea to result in rapid clinical deterioration and death in patients receiving reduced folates (leucovorin, levoleucovorin) concomitantly; close monitoring is required.214 286 315 395
Initiate fluid and electrolyte replacement or antidiarrheal therapy as clinically necessary.205
Hand-foot Syndrome
Palmar-plantar erythrodysesthesia (hand-foot syndrome) reported.201 206
Erythematous, desquamative rash that involves the hands and feet,201 205 206 may be accompanied by tingling sensation, pain, swelling, and erythema with tenderness.205
If grade 2 or 3 hand-foot syndrome occurs, temporarily interrupt therapy until the toxicity resolves or improves to grade 1.205
May be treated with oral pyridoxine therapy or topical emollients (e.g., hand creams, udder balm).406 407
Hematologic Toxicity
Myelosuppression (e.g., neutropenia, thrombocytopenia, anemia), sometimes severe or fatal, reported.205 Nadir neutrophil count usually occurs 9–14 days following initiation of therapy.205
Obtain complete blood cell counts (CBCs) prior to each treatment cycle, weekly (if administered on a weekly or similar schedule), and as clinically indicated.205
If grade 4 myelosuppression occurs, temporarily interrupt therapy until the toxicity resolves or improves to grade 1.205
Fetal/Neonatal Morbidity and Mortality
May cause fetal harm.205
Advise women of childbearing potential and men with such female partners to use effective contraceptive methods during fluorouracil therapy and for up to 3 months after the last dose of the drug.205
If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.205
Impairment of Fertility
Results of animal studies suggest that fluorouracil may impair male and female fertility.205
Specific Populations
Pregnancy
Category D.205 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)
Lactation
Not known whether fluorouracil or its metabolites are distributed into human milk.205 Discontinue nursing or the drug.205
Pediatric Use
Safety and efficacy in children not established.205
Common Adverse Effects
Stomatitis, esophagopharyngitis, anorexia, nausea, vomiting, diarrhea, leukopenia (principally granulocytopenia), thrombocytopenia, anemia, alopecia, dermatitis (principally pruritic maculopapular rash).205
Drug Interactions
Drugs Metabolized by Hepatic Microsomal Enzymes
Substrates of CYP2C9: Fluorouracil or its metabolites may inhibit CYP isoenzyme 2C9.205
Specific Drugs
|
Drug |
Interaction |
Comments |
|---|---|---|
|
Coumarin anticoagulants (e.g., warfarin) |
Clinically significant elevations in coagulation parameters (e.g., increased prothrombin time [PT], increased INR)205 |
Closely monitor INR or PT; adjust anticoagulant dosage as necessary205 |
|
Leucovorin |
Leucovorin potentiates cytotoxicity of fluorouracil in certain GI cancers215 216 218 219 220 221 222 223 224 225 230 253 262 263 265 266 267 |
Used to therapeutic advantage in GI cancers200 201 202 203 204 212 215 216 218 219 220 230 253 Use concomitantly with extreme caution in geriatric or debilitated patients; more likely to develop serious toxicity214 286 |
|
Levoleucovorin |
Levoleucovorin enhances therapeutic effects of fluorouracil in colorectal cancer395 Levoleucovorin enhances fluorouracil toxicity395 |
Used to therapeutic advantage in colorectal cancer395 397 Use concomitantly with extreme caution in geriatric or debilitated patients; more likely to develop serious toxicity214 286 315 395 |
Fluorouracil Pharmacokinetics
Distribution
Extent
Distributed into intestinal mucosa, bone marrow, liver, CSF, and brain tissue.205
Usually higher concentration of fluorouracil or metabolites in tumor than in surrounding tissue or in corresponding normal tissue, and persists longer in some tumors than in the normal host tissues, perhaps due to impaired uracil catabolism; suggests some tumor specificity.a
Not known whether fluorouracil or its metabolites are distributed into human milk.205
Elimination
Metabolism
A small portion is anabolized in tissues to 5-fluoro-2′-deoxyuridine, then to active metabolite (5-fluoro-2′-deoxyuridine-5′-monophosphate).a
The major portion is degraded in the liver, to inactive metabolites (e.g., CO2, urea, α-fluoro-β-alanine, α-fluoro-β-guanidopropionic acid, and α-fluoro-β-ureidopropionic acid).a
Elimination Route
5–20% is excreted unchanged in urine within 6 hours.205
Metabolites (e.g., urea, α-fluoro-β-alanine) are excreted in urine over 3–4 hours.205
Half-life
8–20 minutes following direct IV injection; increases with dose.205
Stability
Storage
Parenteral
Injection
Discard unused portion of 2.5 or 5 g pharmacy bulk package 4 hours after the vial has been entered.205
20–25°C; do not freeze, protect from light.205
Fluorouracil precipitation occurs commonly, particularly following exposure to low temperatures.274
Ease of dissolution may depend on the crystal size and location (e.g., those lodged between the stopper and glass container).274 Attempts to dissolve precipitate with heat and agitation may be unsuccessful.274
Store in adequately heated areas during cold weather to minimize frequency of precipitation.274
Undiluted solutions stored in syringe: 25°C for up to 4 hours.205
Diluted solutions: 25°C for up to 4 hours.205
Compatibility
Parenteral
Solution Compatibilityb
|
Compatible |
|---|
|
Amino acids 4.25%, dextrose 25% |
|
Dextrose 5% in Ringer’s injection, lactated |
|
Dextrose 5% in water |
|
Sodium chloride 0.9% |
Drug Compatibility
|
Compatible |
|---|
|
Bleomycin sulfate |
|
Cyclophosphamide |
|
Cyclophosphamide with methotrexate sodium |
|
Etoposide |
|
Floxuridine |
|
Hydromorphone HCl |
|
Ifosfamide |
|
Methotrexate sodium |
|
Mitoxantrone HCl |
|
Vincristine sulfate |
|
Incompatible |
|
Carboplatin |
|
Ciprofloxacin |
|
Cisplatin |
|
Cytarabine |
|
Diazepam |
|
Doxorubicin HCl |
|
Epirubicin HCl |
|
Fentanyl citrate |
|
Leucovorin calcium |
|
Levoleucovorin calcium |
|
Metoclopramide HCl |
|
Morphine sulfate |
|
Compatible |
|---|
|
Allopurinol sodium |
|
Amifostine |
|
Anidulafungin |
|
Aztreonam |
|
Bleomycin sulfate |
|
Cisplatin |
|
Cyclophosphamide |
|
Doripenem |
|
Doxorubicin HCl |
|
Doxorubicin HCl liposome injection |
|
Etoposide phosphate |
|
Fludarabine phosphate |
|
Furosemide |
|
Gemcitabine HCl |
|
Granisetron HCl |
|
Heparin sodium |
|
Hydrocortisone sodium succinate |
|
Leucovorin calcium |
|
Linezolid |
|
Mannitol |
|
Melphalan HCl |
|
Methotrexate sodium |
|
Metoclopramide HCl |
|
Mitomycin |
|
Paclitaxel |
|
Palonosetron HCl |
|
Pemetrexed disodium |
|
Piperacillin sodium–tazobactam sodium |
|
Potassium chloride |
|
Propofol |
|
Sargramostim |
|
Teniposide |
|
Thiotepa |
|
Vinblastine sulfate |
|
Vincristine sulfate |
|
Incompatible |
|
Aldesleukin |
|
Droperidol |
|
Filgrastim |
|
Gallium nitrate |
|
Topotecan HCl |
|
Vinorelbine tartrate |
|
Variable |
|
Ondansetron HCl |
Actions
-
Precise mechanisms of action of fluorouracil have not been fully elucidated.a
-
May interfere with DNA synthesis, RNA processing, and protein synthesis.358
-
Main mechanism may be the binding of the deoxyribonucleotide of the drug (FdUMP) and the folate cofactor, N5–10-methylenetetrahydrofolate, to thymidylate synthase (TS) to form a covalently bound ternary complex, which inhibits the formation of thymidylate from uracil, interfering with DNA synthesis.358
-
In addition, FUTP can be incorporated into RNA in place of uridine triphosphate (UTP), producing a fraudulent RNA and interfering with RNA processing and protein synthesis.358
Advice to Patients
-
Importance of informing clinician of any known deficiency in DPD activity.205
-
Risk of cardiotoxicity.205 Importance of immediately informing clinician or seeking emergency care if new-onset chest pain, shortness of breath, dizziness, or lightheadedness occurs.205
-
Risk of CNS effects.205 Importance of immediately informing clinician or seeking emergency care if new-onset mental status changes (e.g., disorientation, confusion), visual disturbances, or difficulty with balance or coordination occurs.205
-
Importance of informing clinician if severe diarrhea or mucositis that prevents normal oral intake of food or fluids occurs.205
-
Importance of informing clinician if tingling, burning, redness, flaking, swelling, blisters, or sores on hands or feet occur.205
-
Risk of myelosuppression.205 Importance of monitoring CBCs during therapy.205 Importance of immediately contacting clinician if fever or other signs of infection occur.205
-
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription (e.g., warfarin) and OTC drugs as well as any concomitant illnesses.205
-
Risk of fetal harm.205 Necessity of advising women of childbearing potential and men who are partners of such women to avoid pregnancy and to use an effective method of contraception during and for up to 3 months after discontinuance of therapy.205 Importance of women informing their clinician if pregnancy occurs during therapy or up to 3 months after discontinuance of the drug.205
-
Importance of advising women to avoid breast-feeding during fluorouracil therapy.205
-
Risk of impaired female or male fertility.205
-
Importance of informing patients of other important precautionary information. 205 (See Cautions.)
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
|
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
|---|---|---|---|---|
|
Parenteral |
Injection, for IV use |
50 mg/mL* |
Fluorouracil Injection |
|
|
50 mg/mL (2.5 or 5 g) pharmacy bulk package* |
Adrucil |
Teva |
||
|
Fluorouracil Injection |
AHFS DI Essentials™. © Copyright 2024, Selected Revisions July 26, 2021. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.
References
Only references cited for selected revisions after 1984 are available electronically.
200. Machover D, Schwarzenberg L, Goldschmidt E et al. Treatment of advanced colorectal and gastric adenocarcinomas with 5-FU combined with high-dose folinic acid: a pilot study. Cancer Treat Rep. 1982; 66:1803-7. http://www.ncbi.nlm.nih.gov/pubmed/6982099?dopt=AbstractPlus
201. 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. http://www.ncbi.nlm.nih.gov/pubmed/3543246?dopt=AbstractPlus
202. Panasci L, Ford J, Margolese R. A phase II study of sequential methotrexate and fluorouracil in advanced colorectal cancer. Cancer Chemother Pharmacol. 1985; 15:164-6. http://www.ncbi.nlm.nih.gov/pubmed/4017165?dopt=AbstractPlus
203. Glimelius B, Ginman C, Graffman S et al. Sequential methotrexate-5-FU-leucovorin (MFL) in advanced colorectal cancer. Eur J Cancer Clin Oncol. 1986; 22:295-300. http://www.ncbi.nlm.nih.gov/pubmed/3486768?dopt=AbstractPlus
204. Hansen RM, Ritch PS, Anderson T. Sequential methotrexate, 5-fluorouracil, and calcium leucovorin in colorectal carcinoma. Am J Clin Oncol. 1986; 9:352-4. http://www.ncbi.nlm.nih.gov/pubmed/3489407?dopt=AbstractPlus
205. Teva Parenteral Medicines Inc. Adrucil (fluorouracil) injection prescribing information. North Wales, PA; 2017 Feb.
206. Feldman LD, Ajani JA. Fluorouracil-associated dermatitis of the hands and feet. JAMA. 1985; 254:3479. http://www.ncbi.nlm.nih.gov/pubmed/2933539?dopt=AbstractPlus
207. Monk MR, Sanchez JD, Phelps CD et al. Myocardial ischemia with fluorouracil and floxuridine therapy. Clin Pharm. 1987; 6:659-61. http://www.ncbi.nlm.nih.gov/pubmed/2961503?dopt=AbstractPlus
208. Burger AJ, Mannino S. 5-Fluorouracil-induced coronary vasospasm. Am Heart J. 1987; 114:433-6. http://www.ncbi.nlm.nih.gov/pubmed/3604903?dopt=AbstractPlus
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