Adrucil

Name: Adrucil

Fluorouracil Side Effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • signs of infection such as fever, chills, sore throat, flu symptoms;
  • white patches or sores inside your mouth or throat, or on your lips;
  • pale skin, easy bruising or bleeding (nosebleeds, bleeding gums, or any bleeding that will not stop);
  • weakness or fainting;
  • bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds;
  • coughing up blood or vomit that looks like coffee grounds;
  • watery diarrhea, ongoing or severe vomiting;
  • pain, redness, numbness, and peeling skin on your hands or feet;
  • numbness or tingling anywhere in your body, loss of muscle control; or
  • sudden numbness or weakness (especially on one side of the body), sudden severe headache, slurred speech, problems with vision or balance.

Common side effects may include:

  • temporary hair loss;
  • mild to moderate nausea and vomiting, loss of appetite;
  • mild, itchy skin rash;
  • eye dryness, watering, or increased sensitivity to light; or
  • temporary loss of your fingernails or toenails.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Side Effects of Adrucil

Injectable:

Common side effects of fluorouracil injectable include

  • inflammation and ulceration of the mouth and throat
  • nausea
  • vomiting
  • loss of appetite
  • diarrhea
  • hair loss
  • skin inflammation

Topical:

Common side effects of fluorouracil cream and topical solution include

  • redness
  • dryness
  • burning
  • pain
  • erosion (loss of the upper layer of skin)
  • swelling
  • Irritation may continue for two or more weeks after treatment is over. The treated area may become unsightly during therapy.
  • Some patients get eye irritation. Eye irritation might consist of burning, sensitivity, itching, stinging, and watering. If you are concerned about side effects, talk to your doctor.
  • A few patients have reported side effects such as stomach pain, diarrhea, vomiting, fever, or chills, possibly due to the lack of a specific enzyme, DPD, in their body. If you experience any of these symptoms, discontinue therapy immediately, and contact your doctor.

This is not a complete list of this medication’s side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Adrucil Interactions

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

  • leucovorin (Fusilev)
  • chemotherapy medications such as bendamustine (Treanda), busulfan (Myerlan, Busulfex), carmustine (BiCNU, Gliadel Wafer), cyclophosphamide (Cytoxan), chlorambucil (Leukeran), ifosfamide (Ifex), lomustine (CeeNU), melphalan (Alkeran), procarbazine (Mutalane), or temozolomide (Temodar)
  • medications that suppress the immune system such as azathioprine (Imuran), cyclosporine (Neoral, Sandimmune), methotrexate (Rheumatrex), sirolimus (Rapamune), and tacrolimus (Prograf)

This is not a complete list of fluorouracil drug interactions. Ask your doctor or pharmacist for more information.

Adrucil Overdose

If you take too much this medication, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

If this medication is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

Cautions for Adrucil

Contraindications

  • Poor nutritional state.205

  • Depressed bone marrow function.205

  • Potentially serious infections.205

  • Known hypersensitivity to fluorouracil.205

Warnings/Precautions

Warnings

Maximum Dosage.

Do not exceed 800 mg daily.205

Poor Risk Patients

Use extreme caution in patients with history of high-dose pelvic irradiation, previous use of alkylating agents, widespread bone marrow metastases, impaired hepatic or renal function.205

Dipyrimidine Dehydrogenase Activity Deficiency

Deficiency of dipyrimidine dehydrogenase activity may cause prolonged fluorouracil clearance and toxicity.205

Severe, unexpected toxic reactions (including stomatitis, diarrhea, neutropenia, and neurotoxicity) have been reported.205

Rechallenge with fluorouracil (at a reduced dosage) has caused recurrent, progressive toxicity and increased morbidity.205

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm.205

Advise women to avoid becoming pregnant.205

Inform women who become pregnant while taking fluorouracil that there is a potential hazard to the fetus.205

Use during pregnancy only if the potential benefit justifies the risk to the fetus.205

Combination Therapy

Any therapy that adds stress, interferes with nutrition, or depresses bone marrow function will increase fluorouracil toxicity.205

Leucovorin and Levoleucovorin

Extreme caution when combined with leucovorin or levoleucovorin in geriatric or debilitated patients, since they are more likely to develop serious fluorouracil toxicity.214 286 395 (See Interactions and also see GI Toxicity under Cautions.)

Sensitivity Reactions

Hand-foot Syndrome

Palmar-plantar erythrodysesthesia (hand-foot syndrome); in some cases, with prolonged infusions of high dosages.201 206

Erythematous, desquamative rash that involves the hands and feet,201 206 may be accompanied by tingling or painful hands and feet, swollen palms and soles, and phalangeal tenderness.205

Effects may gradually disappear over 5–7 days after fluorouracil discontinuance.205

May be treated with oral pyridoxine therapy, but safety and efficacy of pyridoxine for this condition have not been fully established.205

General Precautions

Toxicity

Highly toxic, very low therapeutic index; therapeutic response is unlikely without some evidence of toxicity.a 205 (See Boxed Warning.)

May produce severe hematologic toxicity, GI hemorrhage, and even death.205 a

Severe toxicity most likely in poor risk patients, but fatality may occur even in those in relatively good condition.205

GI Toxicity

Discontinue promptly at first visible sign of stomatitis or esophagopharyngitis.205

Discontinue promptly for intractable vomiting.205

Discontinue promptly for diarrhea, frequent bowel movements, watery stools.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

Discontinue promptly for GI ulceration and bleeding.205

Hematologic Toxicity

Discontinue promptly for leukopenia (WBC < 3500/mm3) or rapidly falling WBC;205 a place in protective isolation and take appropriate measures for prevention of infection if the leukocyte count drops to < 2000/mm3.a

Discontinue promptly for thrombocytopenia (platelets < 100,000/mm3).205

Discontinue promptly for hemorrhage from any site.205

Specific Populations

Pregnancy

Category D.205 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Not known whether fluorouracil is distributed into milk.205 Discontinue nursing while receiving the drug; fluorouracil inhibits DNA, RNA, and protein synthesis.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 a

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

Before Using Adrucil

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Although there is no specific information comparing use of fluorouracil in children with use in other age groups, it is not expected to cause different side effects or problems in children than it does in adults.

Geriatric

Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults. Although there is no specific information comparing use of fluorouracil in the elderly with use in other age groups, it is not expected to cause different side effects or problems in older people than it does in younger adults.

Pregnancy

Pregnancy Category Explanation
All Trimesters X Studies in animals or pregnant women have demonstrated positive evidence of fetal abnormalities. This drug should not be used in women who are or may become pregnant because the risk clearly outweighs any possible benefit.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

  • Brivudine
  • Measles Virus Vaccine, Live
  • Mumps Virus Vaccine, Live
  • Rotavirus Vaccine, Live
  • Rubella Virus Vaccine, Live
  • Tegafur
  • Varicella Virus Vaccine

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Acenocoumarol
  • Adenovirus Vaccine
  • Allopurinol
  • Azanidazole
  • Bacillus of Calmette and Guerin Vaccine, Live
  • Benznidazole
  • Cholera Vaccine, Live
  • Cimetidine
  • Influenza Virus Vaccine, Live
  • Isoconazole
  • Methotrexate
  • Metronidazole
  • Nimorazole
  • Ornidazole
  • Oxypurinol
  • Phenprocoumon
  • Poliovirus Vaccine, Live
  • Secnidazole
  • Smallpox Vaccine
  • Tamoxifen
  • Tinidazole
  • Typhoid Vaccine
  • Warfarin
  • Yellow Fever Vaccine

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Fosphenytoin
  • Leucovorin
  • Levamisole
  • Levoleucovorin
  • Phenytoin
  • Thiamine

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

  • Chickenpox (including recent exposure) or
  • Herpes zoster (shingles)—Risk of severe disease affecting other parts of the body
  • Infection—Fluorouracil can decrease your body's ability to fight infection
  • Kidney disease or
  • Liver disease—Effects of fluorouracil may be increased because of slower removal from the body

Adrucil Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common
  • Diarrhea
  • heartburn
  • sores in mouth and on lips
Less common
  • Black, tarry stools
  • cough or hoarseness, accompanied by fever or chills
  • fever or chills
  • lower back or side pain, accompanied by fever or chills
  • nausea and vomiting (severe)
  • painful or difficult urination, accompanied by fever or chills
  • stomach cramps
Rare
  • Blood in urine or stools
  • pinpoint red spots on skin
  • unusual bleeding or bruising

Check with your doctor as soon as possible if any of the following side effects occur:

Rare
  • Chest pain
  • cough
  • shortness of breath
  • tingling of hands and feet, followed by pain, redness, and swelling
  • trouble with balance

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common
  • Loss of appetite
  • nausea and vomiting
  • skin rash and itching
  • weakness
Less common
  • Dry or cracked skin

This medicine often causes a temporary loss of hair. After treatment with fluorouracil has ended, normal hair growth should return.

After you stop using this medicine, it may still produce some side effects that need attention. During this period of time, check with your doctor immediately if you notice the following side effects:

  • Black, tarry stools
  • blood in urine or stools
  • cough or hoarseness, accompanied by fever or chills
  • fever or chills
  • lower back or side pain, accompanied by fever or chills
  • painful or difficult urination, accompanied by fever or chills
  • pinpoint red spots on skin
  • unusual bleeding or bruising

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Uses of Adrucil

  • It is used to treat colorectal cancer.
  • It is used to treat breast cancer.
  • It is used to treat stomach cancer.
  • It is used to treat pancreatic cancer.
  • It may be given to you for other reasons. Talk with the doctor.

Adrucil Description

Adrucil® (fluorouracil injection USP), a nucleoside metabolic inhibitor, is a sterile, nonpyrogenic injectable solution for intravenous administration. Each 10 mL contains 500 mg fluorouracil, USP; pH is adjusted to 8.6 to 9.4 with sodium hydroxide.

Chemically, fluorouracil, USP, a fluorinated pyrimidine, is 5-fluoro-2,4 (1H,3H)-pyrimidinedione. It is a white to practically white crystalline powder which is sparingly soluble in water. The structural formula is:

C4H3FN2O2 M.W. 130.08

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