Fluorouracil 50mg/ml Inj, 50ml

Fluorouracil (5-FU) is a pyrimidine analog antimetabolite. It acts by interfering with DNA and RNA synthesis. 5-FU is converted intracellularly to several active metabolites: 1. Fluorodeoxyuridine monophosphate (FdUMP), which inhibits thymidylate synthase (TS), thereby blocking the synthesis of thymidylate, a precursor of DNA. This leads to 'thymineless death' of rapidly dividing cells. 2. Fluorouridine triphosphate (FUTP), which is incorporated into RNA, leading to abnormal RNA synthesis and function. 3. Fluorodeoxyuridine triphosphate (FdUTP), which is incorporated into DNA, leading to DNA damage and fragmentation. The net effect is the disruption of nucleic acid synthesis and function, leading to cell death, particularly in rapidly proliferating cancer cells.

Urgent Side Effects: Seek Medical Help Right Away

Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:

Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin (with or without fever)
+ Wheezing
+ Tightness in the chest or throat
+ Difficulty breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of nervous system problems, including:
+ Changes in mood or behavior
+ Confusion
+ Fever
+ Numbness or tingling in the hands or feet
+ Stiff neck
+ Sensitivity to bright lights
+ Severe muscle weakness
Signs of infection, such as:
+ Fever
+ Chills
+ Severe sore throat
+ Ear or sinus pain
+ Cough
+ Increased or discolored sputum
+ Painful urination
+ Mouth sores
+ Wounds that won't heal
Signs of bleeding, including:
+ Vomiting or coughing up blood
+ Vomit that resembles coffee grounds
+ Blood in the urine
+ Black, red, or tarry stools
+ Bleeding gums
+ Abnormal vaginal bleeding
+ Unexplained bruises or bruises that enlarge
+ Uncontrollable bleeding
Feeling extremely tired or weak
Chest pain or pressure
Shortness of breath, significant weight gain, or swelling in the arms or legs
Abnormal heartbeat
Dizziness or fainting
Changes in vision
Redness or irritation on the palms of the hands or soles of the feet
Balance problems
Excessive sleepiness
Uncontrolled eye movements
Headache

Administration Site Reactions

This medication may cause irritation at the injection site. If the medication leaks from the vein, it can also cause irritation around the affected area. Inform your nurse if you experience any redness, burning, pain, swelling, or fluid leakage at the injection site.

Other Possible Side Effects

Like all medications, this drug can cause side effects. However, many people may not experience any side effects or only minor ones. If you're concerned about any of the following side effects or if they persist, contact your doctor:

Diarrhea
Upset stomach or vomiting
Decreased appetite
Mouth irritation or mouth sores
Hair loss
Dry skin
Changes in nail condition

This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.

Before Taking This Medication: Important Information to Share with Your Doctor

It is essential to inform your doctor about the following:

Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced.
Certain health conditions, including:
+ Poor nutrition
+ Infections
+ Bone marrow problems, such as:
- Low white blood cell count
- Low platelet count
- Low red blood cell count
If you have dihydropyrimidine dehydrogenase (DPD) deficiency
If you are breast-feeding. Note: You should not breast-feed while taking this medication.

This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. They will help determine if it is safe to take this medication with your other medications and health conditions. Never start, stop, or change the dose of any medication without first consulting your doctor.

It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Regular blood work and laboratory tests, as directed by your doctor, are crucial to monitor your condition.

This medication can cause low blood cell counts, which may lead to bleeding problems, infections, or anemia. In severe cases, these conditions can be life-threatening. If you have any questions or concerns, discuss them with your doctor. You may be more susceptible to infections, so it is vital to practice good hygiene by washing your hands frequently and avoiding close contact with people who have infections, colds, or flu.

Be cautious, as this medication can increase your risk of bleeding easily. To minimize this risk, use a soft toothbrush and an electric razor, and avoid injuries. If you experience stomach upset, vomiting, diarrhea, or loss of appetite, consult your doctor, as they may be able to suggest ways to alleviate these side effects. If you have diarrhea or vomiting, it is crucial to prevent dehydration and electrolyte imbalances; your doctor will provide guidance on how to manage these conditions.

Patients who lack the enzyme dihydropyrimidine dehydrogenase (DPD) are at a higher risk of severe and potentially life-threatening side effects, including mouth irritation or sores, diarrhea, low white blood cell counts, and nerve problems.

This medication may also increase the risk of heart problems, such as heart attack, heart failure, and abnormal heartbeat, particularly in individuals with a history of heart disease. Discuss your cardiovascular health with your doctor. Before receiving any vaccinations, consult your doctor, as some vaccines may not be effective or may increase the risk of infection when taken with this medication.

Additionally, this medication can increase your sensitivity to the sun, making you more prone to sunburn. Take necessary precautions when exposed to the sun, and inform your doctor if you experience excessive sunburn.

This medication may affect fertility, potentially leading to difficulties in becoming pregnant or fathering a child. If you plan to conceive, discuss your options with your doctor before starting treatment. Women who are pregnant or may become pregnant should not take this medication, as it can harm the unborn baby. If you or your partner may become pregnant, it is essential to use birth control during treatment and for a specified period after the last dose, as directed by your doctor. If you or your partner becomes pregnant, notify your doctor immediately.

• Brivudine, Sorivudine, and related antivirals (e.g., netivudine): Potent DPD inhibitors, leading to massive increase in 5-FU exposure and severe, potentially fatal toxicity (e.g., myelosuppression, mucositis, neurotoxicity). Concomitant use is absolutely contraindicated.
• Live vaccines: Increased risk of severe or fatal infection due to immunosuppression.

• Leucovorin: Enhances the cytotoxic effects of 5-FU by stabilizing the binding of FdUMP to thymidylate synthase, leading to increased efficacy but also increased toxicity (e.g., myelosuppression, diarrhea, mucositis). Dose adjustments of 5-FU may be needed.
• Allopurinol: May decrease the cytotoxic effects of 5-FU by inhibiting its metabolism, potentially reducing efficacy. Not routinely recommended for concurrent use.
• Cimetidine, Metronidazole, Interferon alfa: May increase 5-FU plasma concentrations and toxicity.
• Thiazide diuretics: May increase myelosuppression.
• Warfarin: May enhance the anticoagulant effect of warfarin, increasing bleeding risk. Monitor INR closely.
• Phenytoin: May decrease phenytoin levels.
• Other myelosuppressive agents (e.g., other chemotherapies, radiation therapy): Additive myelosuppression.

• Folic acid supplements: May theoretically interfere with 5-FU action, but clinical significance is generally low unless very high doses are used.

• Diarrhea (frequency, severity, presence of blood)
• Mucositis/Stomatitis (oral pain, redness, ulcers)
• Nausea and vomiting
• Hand-foot syndrome (palmar-plantar erythrodysesthesia - redness, swelling, pain, blistering of palms/soles)
• Fatigue
• Signs of infection (fever, chills, sore throat)
• Bleeding/bruising (petechiae, epistaxis)
• Neurological symptoms (ataxia, confusion, lethargy, headache)
• Cardiac symptoms (chest pain, shortness of breath, palpitations)

Fluorouracil is classified as Pregnancy Category D. It can cause fetal harm when administered to a pregnant woman. It is a known teratogen and embryotoxic in animals. Avoid use during pregnancy. If used during pregnancy, the patient should be apprised of the potential hazard to the fetus.

Lactation Risk Category L5 (Contraindicated). It is unknown if fluorouracil is excreted in human milk. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is contraindicated during fluorouracil therapy and for a period after the last dose (e.g., at least 1 week, or as advised by a healthcare professional).

Safety and efficacy have not been established in pediatric patients. However, fluorouracil is used off-label in various pediatric malignancies (e.g., solid tumors, brain tumors) based on adult data and clinical experience. Dosing is typically based on body surface area, and close monitoring for toxicity is essential. Pediatric patients may be more susceptible to certain toxicities.

No overall differences in safety or effectiveness have been observed between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Elderly patients may have reduced renal or hepatic function, or more comorbidities, requiring careful monitoring and potential dose adjustments. Increased risk of myelosuppression and other toxicities may be observed in the elderly.

• DPD deficiency: Patients with partial or complete DPD deficiency are at significantly increased risk of severe, life-threatening, or fatal toxicity. Consider DPD testing prior to initiation, especially if severe toxicity is anticipated or occurs early.
• Leucovorin interaction: Leucovorin enhances 5-FU's activity and toxicity. Ensure correct dosing and administration sequence (leucovorin typically given before or concurrently with 5-FU).
• Hand-foot syndrome (PPE): Common side effect. Advise patients on preventative measures (e.g., avoiding friction/heat, moisturizing) and early reporting. Pyridoxine (Vitamin B6) or topical emollients may help.
• Cardiotoxicity: Although rare, 5-FU can cause cardiotoxicity (angina, MI, arrhythmias, cardiomyopathy), especially in patients with pre-existing cardiac disease. Monitor for cardiac symptoms.
• Neurotoxicity: Rare but can occur (e.g., cerebellar ataxia, confusion, lethargy). More common with high-dose bolus regimens or DPD deficiency.
• Diarrhea and Mucositis: These are dose-limiting toxicities. Aggressive management with antidiarrheals (e.g., loperamide) and oral hygiene/pain control is crucial. Severe cases may require hospitalization and IV fluids.
• Extravasation: Fluorouracil is an irritant. Administer via a free-flowing IV line. If extravasation occurs, apply cold compresses and elevate the limb. Hyaluronidase may be considered.

• Other antimetabolites (e.g., Gemcitabine, Pemetrexed, Methotrexate)
• Other cytotoxic agents (e.g., Oxaliplatin, Irinotecan, Paclitaxel)
• Targeted therapies (e.g., Bevacizumab, Cetuximab, Panitumumab)
• Immunotherapy (e.g., Pembrolizumab, Nivolumab)

If your symptoms or health problems persist or worsen, it is essential to contact your doctor for further guidance. To ensure safe use, never share your medication with others, and do not take medication prescribed for someone else. Store all medications in a secure location, out of reach of children and pets, to prevent accidental ingestion. Dispose of unused or expired medications properly. Unless instructed to do so by a healthcare professional, avoid flushing medications down the toilet or pouring them down the drain. If you are unsure about the proper disposal method, consult your pharmacist, who can also inform you about potential drug take-back programs in your area. Some medications may come with an additional patient information leaflet, which your pharmacist can provide. If you have any questions or concerns about your medication, discuss them with your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately contact your local poison control center or seek emergency medical attention. Be prepared to provide information about the medication taken, the amount, and the time it was taken to ensure prompt and effective treatment.