Fluracil25 mg/ml

Fluracil is a cytotoxic antimetabolite (fluoropyrimidine) chemotherapy agent used, always under the supervision of a physician experienced in cancer chemotherapy, for the following indications:

Systemic (Intravenous/Intra-arterial) Use — Established, Combination-Based

• Colorectal cancer (established): as part of combination chemotherapy regimens (e.g., with leucovorin/folinic acid, and commonly with oxaliplatin [FOLFOX] or irinotecan [FOLFIRI]) for adjuvant treatment and for metastatic/advanced disease.
• Gastric (stomach) cancer (established): as part of combination chemotherapy regimens for advanced or metastatic disease.
• Pancreatic cancer (established): as part of combination regimens for locally advanced or metastatic disease.
• Breast cancer (established, adjunct): as part of older combination regimens (e.g., with cyclophosphamide and methotrexate) in selected patients.
• Esophageal, anal, and certain head and neck cancers (guideline-supported, combination): typically combined with radiotherapy and/or other cytotoxic agents (e.g., with mitomycin and radiation for anal cancer; with cisplatin for esophageal/head-and-neck cancer) as part of established multimodal protocols.

Fluracil for systemic cancer treatment is used only in combination with leucovorin and/or other antineoplastic agents, or with radiotherapy, per the specific tumor protocol; it is not used as a stand-alone, self-directed treatment.

Topical Use — Established

• Actinic keratosis (established): topical cream/solution for multiple actinic (solar) keratoses of the face, ears, scalp, and other sun-exposed areas.
• Superficial basal cell carcinoma (established, when surgery is not appropriate): topical 5% cream/solution, used only when conventional surgical excision is medically or cosmetically inappropriate, and only under dermatologist supervision with follow-up.

Fluracil is not appropriate for self-directed use in any form; systemic use requires oncology supervision and topical use requires dermatologist supervision with appropriate follow-up to confirm treatment response.

5-Fluorouracil [5-FU] is available in two main formulations:

• Injection (systemic): a sterile aqueous solution of 5-Fluorouracil [5-FU] for intravenous (or, in some protocols, intra-arterial or ocular) use, commonly supplied at a concentration of 50 mg/mL in single-dose or multi-dose vials, ready for dilution per the treating oncologist's protocol.
• Topical cream/solution: 5-Fluorouracil [5-FU] formulated at strengths such as 0.5%, 1%, or 5% w/w for external application to the skin, in a cream or solution base with inactive excipients (e.g., emulsifying agents, preservatives) that vary by manufacturer.

No other active pharmaceutical ingredients are combined with 5-Fluorouracil [5-FU] in these formulations.

Fluracil is a fluorinated pyrimidine antimetabolite and one of the oldest and most widely used cytotoxic (cell-killing) chemotherapy agents, first introduced into clinical oncology in the early 1960s. It works by interfering with DNA and RNA synthesis in rapidly dividing cells, and remains a backbone component of combination chemotherapy for several common solid-organ cancers.

Given systemically (by intravenous or intra-arterial infusion/injection), Fluracil is used mainly for colorectal, gastric, pancreatic, breast, and certain other cancers, almost always combined with leucovorin (folinic acid) and/or other cytotoxic agents as part of a defined chemotherapy protocol. Given topically as a cream or solution, Fluracil is used to treat actinic keratosis and selected cases of superficial basal cell carcinoma of the skin. Because systemic Fluracil has a narrow margin between effective and toxic doses and carries a risk of severe, sometimes fatal toxicity — particularly in patients with reduced activity of the enzyme dihydropyrimidine dehydrogenase (DPD) — it must only be prescribed and administered under the direct supervision of a physician experienced in cancer chemotherapy, with appropriate laboratory monitoring.

Fluracil belongs to the antineoplastic (anticancer) agents class, specifically the antimetabolite / pyrimidine analog (fluoropyrimidine) subclass of chemotherapy drugs.

5-Fluorouracil [5-FU] is a fluorinated analog of the pyrimidine base uracil. It is itself inactive and must be converted intracellularly into active metabolites, principally:

• Fluorodeoxyuridine monophosphate (FdUMP): forms a stable complex with the enzyme thymidylate synthase and its cofactor, irreversibly inhibiting this enzyme and blocking conversion of deoxyuridine monophosphate to thymidine monophosphate — a step essential for DNA synthesis and repair. This is considered the primary mechanism of cytotoxicity.
• Fluorouridine triphosphate (FUTP): is incorporated into RNA in place of uridine triphosphate, disrupting RNA processing and normal RNA function.
• Fluorodeoxyuridine triphosphate (FdUTP): is incorporated into DNA, causing DNA strand breaks and impairing DNA synthesis and repair.

Through these combined effects, 5-Fluorouracil [5-FU] preferentially disrupts rapidly proliferating cells, including tumor cells, leading to cell-cycle arrest and cell death. 5-Fluorouracil [5-FU] is metabolized primarily by the enzyme dihydropyrimidine dehydrogenase (DPD), mainly in the liver; individuals with reduced or absent DPD activity are at markedly increased risk of severe, potentially fatal toxicity (see Precautions and Warnings). After intravenous administration, plasma elimination is rapid (elimination half-life of roughly 10–20 minutes), and metabolites are excreted mainly via the lungs (as carbon dioxide) and kidneys.

Fluracil must be administered only by trained healthcare personnel under oncology (systemic) or dermatology (topical) supervision:

• Systemic (IV) use: given as an intravenous bolus injection and/or continuous intravenous infusion (via a central line or infusion pump for multi-day continuous infusions), strictly according to the specific chemotherapy protocol; some protocols use intra-arterial infusion for regional therapy (e.g., hepatic artery infusion for liver metastases) or ocular subconjunctival/topical use after certain eye surgeries.
• Use appropriate cytotoxic drug handling and disposal precautions (gloves, eye protection, and safe-handling procedures) during preparation and administration; avoid skin/eye contact and inhalation of the solution.
• Do not administer if the solution is markedly discolored or contains visible particulate matter; if crystals have formed in the vial, follow the product labeling's instructions for warming/redissolving before use.
• Topical use: apply a thin layer to clean, dry affected skin using a gloved hand or applicator, avoiding contact with eyes, nostrils, mouth, and mucous membranes; wash hands thoroughly after application unless the hands are a treated area.

Only well-established, clinically significant interactions with Fluracil are listed below:

• Leucovorin (folinic acid): potentiates the cytotoxic (and therapeutic) effect of Fluracil by stabilizing its binding to thymidylate synthase; this combination is used intentionally in many regimens but also increases the risk and severity of Fluracil-related toxicity (especially diarrhea and mucositis), requiring close monitoring.
• Brivudine, sorivudine, and other potent DPD-inhibiting antivirals: irreversibly inhibit dihydropyrimidine dehydrogenase (DPD), the main enzyme that breaks down Fluracil; concomitant or recent use (within about 4 weeks) can cause severe, potentially fatal Fluracil toxicity and must be avoided (see Contraindications).
• Warfarin and other oral anticoagulants: Fluracil can increase anticoagulant effect and bleeding risk (increased INR/prothrombin time); more frequent coagulation monitoring is needed if used together.
• Phenytoin: Fluracil may increase phenytoin plasma levels, increasing the risk of phenytoin toxicity; monitor phenytoin levels and clinical status if co-administered.
• Metronidazole and cimetidine: may reduce the clearance of Fluracil, increasing plasma levels and toxicity risk; use with caution and closer monitoring.
• Live or live-attenuated vaccines: should generally be avoided during Fluracil treatment because of the risk of disseminated infection from chemotherapy-induced immunosuppression.
• Other myelosuppressive drugs or radiotherapy: combination increases the risk of additive bone marrow suppression and mucosal toxicity; dose and schedule are managed by the treating oncologist.

Always inform the treating physician of all medicines, supplements, and over-the-counter drugs being used before and during Fluracil therapy, including any recent antiviral treatment.

Side effects of Fluracil depend on the route (systemic vs. topical), dose, schedule (bolus vs. continuous infusion), and combination regimen used.

Systemic Use — Common

• Myelosuppression: leukopenia, neutropenia, thrombocytopenia, anemia (increasing risk of infection, bleeding, or need for transfusion)
• Nausea, vomiting, diarrhea (can be severe and dose-limiting)
• Stomatitis and mucositis (mouth/gut sores)
• Alopecia (hair thinning/loss)
• Hand-foot syndrome (palmar-plantar erythrodysesthesia), especially with continuous infusion schedules
• Photosensitivity and skin/nail hyperpigmentation
• Fatigue

Systemic Use — Serious / Less Common

• Severe myelosuppression with febrile neutropenia or serious infection
• Cardiotoxicity: chest pain, coronary vasospasm, arrhythmias, and rarely myocardial infarction or cardiac arrest, particularly in patients with pre-existing coronary artery disease
• Neurotoxicity: cerebellar ataxia, confusion, and rarely encephalopathy (more common with DPD deficiency or high doses)
• Severe gastrointestinal ulceration or bleeding
• Ocular effects with prolonged use (excessive tearing, lacrimal duct narrowing)

Topical Use

• Local skin reactions at the application site — redness, burning, itching, crusting, erosion, and peeling are common and expected as part of the treatment response; healing typically continues for some weeks after stopping treatment.
• Temporary hyper- or hypopigmentation of treated skin.

Patients (or caregivers) should promptly report fever, unusual bleeding or bruising, severe mouth sores, chest pain, or severe skin reactions to the treating physician.

Pregnancy: Systemic Fluracil is contraindicated in pregnancy; it has demonstrated embryotoxic and teratogenic effects in animal studies and can cause fetal harm. Pregnancy should be excluded before starting systemic Fluracil in patients of reproductive potential, and effective contraception should be used during treatment and for a period after the last dose, as advised by the treating physician. Topical Fluracil should be used in pregnancy only if clearly needed and only if the treating physician determines that the potential benefit justifies the potential risk to the fetus, given limited systemic absorption but incomplete safety data; consult a physician before any use in pregnancy.

Breastfeeding: Fluracil is excreted into breast milk, and breastfeeding is not recommended during systemic Fluracil treatment and for an appropriate period after the last dose, as advised by the treating physician, due to the potential for serious adverse effects in a nursing infant. For topical use, avoid application to the breast/nipple area and consult a physician regarding breastfeeding safety during treatment.

Fluracil must be administered (systemically) only under the supervision of a physician experienced in cancer chemotherapy, or (topically) under dermatologist supervision, with the following precautions observed:

• Dihydropyrimidine dehydrogenase (DPD) deficiency: patients with reduced or absent DPD activity are at markedly increased risk of severe, sometimes fatal toxicity (severe myelosuppression, mucositis, neurotoxicity) from systemic Fluracil. DPD testing before starting treatment is recommended where available; treatment should not be started in patients with known complete DPD deficiency (see Contraindications), and reduced starting doses with close monitoring are used in patients with known partial deficiency.
• Bone marrow suppression: complete blood counts must be monitored before and during each cycle; doses are withheld, reduced, or delayed for significant neutropenia, thrombocytopenia, or anemia.
• Cardiotoxicity: use with caution in patients with a history of coronary artery disease; discontinue promptly if chest pain, ECG changes, or other signs of cardiotoxicity occur during infusion.
• Gastrointestinal toxicity: severe diarrhea, mucositis, or stomatitis may require dose interruption, reduction, or discontinuation, and supportive care (hydration, antidiarrheal therapy as directed).
• Poor nutritional status or active serious infection: systemic Fluracil should be used with particular caution, and generally withheld, in patients who are poorly nourished or have a serious active infection, until the condition is corrected or controlled.
• Hepatic or renal impairment: use with caution and closer monitoring (see Use in Special Populations).
• Topical use: avoid excessive sun exposure to treated skin during and after treatment (photosensitivity/irritation); do not apply to open wounds, mucous membranes, or near the eyes; keep away from children and pets — accidental ingestion of topical Fluracil by pets can be fatal.
• Drug interactions: see Interaction section, particularly regarding DPD-inhibiting antivirals (brivudine/sorivudine), which must never be combined with Fluracil.

Fluracil must be handled and disposed of according to institutional cytotoxic drug procedures.

Overdose of Fluracil can cause severe, potentially fatal toxicity, primarily exaggerated myelosuppression, severe mucositis/gastrointestinal toxicity (including bleeding), and, less commonly, neurotoxicity or cardiotoxicity. If an overdose of Fluracil is suspected, seek immediate medical attention or contact emergency services/poison control right away. Management requires hospital-based supportive care with close monitoring of blood counts and organ function; a specific antidote (uridine triacetate) is available in some settings for early-recognized overdose or severe early-onset toxicity and should be given as directed by treating physicians, ideally within the recommended time window. Do not attempt home treatment for a suspected overdose of Fluracil.

Injection: Store Fluracil injection at room temperature (approximately 15–30°C), protected from light, and avoid exposure to temperatures below recommended range as some formulations may crystallize on cooling (if crystals appear, follow the product labeling's instructions for gentle warming/redissolving before use — do not use if the solution remains discolored or contains particulate matter). Topical cream/solution: store at room temperature (below 30°C), away from excessive heat and direct light. Keep all forms of Fluracil out of reach of children and pets — accidental ingestion, especially of topical product by pets, can be fatal.

Renal Impairment

Data on dosing of systemic Fluracil in significant renal impairment are limited; use with caution and closer monitoring for toxicity, as reduced clearance of active metabolites may increase toxicity risk.

Hepatic Impairment

Fluracil is partly metabolized by the liver; use with caution in hepatic impairment, with closer monitoring of liver function and toxicity, and dose reduction as directed by the treating oncologist for significant impairment.

Elderly Patients

Elderly patients may be at increased risk of toxicity (particularly myelosuppression, mucositis, and neurotoxicity); no fixed dose adjustment based on age alone is established, but closer clinical and laboratory monitoring is advised.

Pediatric Patients

Safety and efficacy of routine Fluracil dosing in pediatric patients have not been formally established for most indications; use in children occurs only within specialist pediatric oncology protocols under direct supervision of a pediatric oncologist (see Pediatric Uses).

DPD-Deficient Patients

See Precautions and Warnings and Contraindications regarding dihydropyrimidine dehydrogenase (DPD) deficiency, which significantly increases the risk of severe toxicity from systemic Fluracil.

The duration of Fluracil treatment is determined by the treating physician based on indication, regimen, response, and tolerability:

• For systemic combination chemotherapy (e.g., colorectal, gastric, or pancreatic cancer regimens), treatment is typically given in defined cycles (commonly repeated every 2–5 weeks depending on the regimen) for a planned number of cycles (often 6–12), or until disease progression or unacceptable toxicity occurs, per the specific protocol.
• For topical treatment of actinic keratosis, courses typically last about 2–4 weeks; for superficial basal cell carcinoma, courses typically last about 3–6 weeks, with the treating physician assessing skin response before deciding whether to extend, repeat, or stop treatment.

Do not stop, extend, or alter the treatment schedule of Fluracil without the treating physician's guidance, as premature discontinuation or missed monitoring can affect both safety and treatment outcomes.

Antineoplastic agents; Antimetabolites; Pyrimidine analogs (fluoropyrimidines).

5-Fluorouracil [5-FU] is a fluorinated pyrimidine that is converted intracellularly into active fluorinated nucleotide metabolites. The metabolite fluorodeoxyuridine monophosphate (FdUMP) forms a stable, essentially irreversible complex with the enzyme thymidylate synthase together with its folate cofactor, blocking the conversion of deoxyuridylate to thymidylate — a reaction required for DNA synthesis and repair. In addition, the metabolite fluorouridine triphosphate (FUTP) is misincorporated into RNA, disrupting RNA processing and function, and fluorodeoxyuridine triphosphate (FdUTP) is misincorporated into DNA, causing strand breaks. Together these effects disrupt DNA replication, RNA function, and cell division, producing selective cytotoxicity against rapidly dividing cells such as tumor cells.

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The safety and efficacy of Fluracil in routine pediatric use have not been formally established for most indications. Fluracil is used in children only as part of specialist pediatric oncology protocols (for select pediatric solid tumors) under the direct supervision of a pediatric oncologist, with dosing individualized per the specific protocol; it should not be used in children outside such supervised settings. Topical Fluracil for actinic keratosis or superficial basal cell carcinoma is not typically used in children, as these are predominantly adult conditions related to cumulative sun exposure.