Efudex

Skin irritation, burning, redness, dryness, pain, swelling, tenderness, or changes in skin color may occur at the site of application. Eye irritation (e.g., stinging, watering), trouble sleeping, irritability, temporary hair loss, or abnormal taste in the mouth may also occur.If any of these effects persist or worsen, contact your doctor or pharmacist promptly.Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor immediately if any of these rare but very serious side effects occur: stomach/abdominal pain, bloody diarrhea, vomiting, signs of infection (e.g., fever, chills, persistent sore throat), easy bruising/bleeding, mouth sores.A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any of the following symptoms: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Injectable:

This medication is available in an injectable form to be given directly into a vein (IV) by a healthcare professional.

Topical:

• Cream
  • Use fluorouracil once a day as instructed by your doctor. Use it only on your skin.
    • Clean the area where you will apply fluorouracil. Rinse well and dry the area with a towel and wait 10 minutes before applying fluorouracil.
    • Use enough to cover the affected area of skin.
    • Avoid contact with your eyes, nostrils, and mouth.
    • Wash your hands as soon as you finish putting the fluorouracil on your skin.
    • Do not use any other skin products including creams, lotions, medications or cosmetics unless instructed by your doctor.
• Topical solution
  • Apply solution preferably with a nonmetal applicator or suitable glove. If applied with the fingers, the hands should be washed immediately afterward.
• What you should avoid while using fluorouracil cream or topical solution:
  • Avoid sunlight or other ultraviolet light (such as tanning booths) as much as possible while using fluorouracil. Sunlight may increase your side effects. When exposed to sunlight, wear a hat and use sunscreen.
  • Do not cover the treated skin with a dressing.
  • Do not breast feed or become pregnant while using fluorouracil. If you do become pregnant, stop using fluorouracil and tell your doctor right away.

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.

Fluorouracil interferes with the growth of skin cells. Fluorouracil works by causing the death of cells which are growing fastest, such as abnormal skin cells.

Fluorouracil topical is used to treat scaly overgrowths of skin (actinic or solar keratoses). Fluorouracil topical may also be used in the treatment of superficial basal cell carcinoma.

Fluorouracil topical may also be used for purposes other than those listed in this medication guide.

Do not use other prescription or over-the-counter skin products without first talking to your doctor during treatment with fluorouracil topical. They may interfere with the treatment or increase irritation of the skin.

Avoid exposure to sunlight or artificial UV rays (e.g., sun lamps) during and immediately following treatment with fluorouracil topical. Use a sunscreen with a minimum sun protection factor (SPF) 15 and wear protective clothing when sun exposure is unavoidable. Individuals with fair skin may require a sunscreen with a higher SPF rating.

Fluorouracil interferes with the growth of skin cells. Fluorouracil works by causing the death of cells which are growing fastest, such as abnormal skin cells.

Fluorouracil topical (for the skin) is used to treat scaly overgrowths of skin (actinic or solar keratoses). Fluorouracil topical may also be used in the treatment of superficial basal cell carcinoma.

Fluorouracil topical may also be used for purposes not listed in this medication guide.

This medication can harm an unborn baby or cause birth defects. Do not use fluorouracil topical if you are pregnant.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

• If you have an allergy to fluorouracil or any other part of Efudex (fluorouracil (topical)).
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have dihydropyrimidine dehydrogenase deficiency.
• If you are pregnant or may be pregnant. Do not take this medicine if you are pregnant.
• If you are breast-feeding. Do not breast-feed while you take Efudex.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Efudex with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Efudex is recommended for the topical treatment of multiple actinic or solar keratoses. In the 5% strength, it is also useful in the treatment of superficial basal cell carcinomas when conventional methods are impractical, such as with multiple lesions or difficult treatment sites. Safety and efficacy in other indications have not been established.

The diagnosis should be established prior to treatment, since this method has not been proven effective in other types of basal cell carcinomas. With isolated, easily accessible basal cell carcinomas, surgery is preferred since success with such lesions is almost 100%. The success rate with Efudex Cream and Solution is approximately 93%, based on 113 lesions in 54 patients. Twenty-five lesions treated with the solution produced 1 failure and 88 lesions treated with the cream produced 7 failures.

Efudex may cause fetal harm when administered to a pregnant woman.

There are no adequate and well-controlled studies in pregnant women with either the topical or the parenteral forms of fluorouracil. One birth defect (cleft lip and palate) has been reported in the newborn of a patient using Efudex as recommended. One birth defect (ventricular septal defect) and cases of miscarriage have been reported when Efudex was applied to mucous membrane areas. Multiple birth defects have been reported in a fetus of a patient treated with intravenous fluorouracil.

Animal reproduction studies have not been conducted with Efudex. Fluorouracil administered parenterally has been shown to be teratogenic in mice, rats, and hamsters when given at doses equivalent to the usual human intravenous dose; however, the amount of fluorouracil absorbed systemically after topical administration to actinic keratoses is minimal (see CLINICAL PHARMACOLOGY). Fluorouracil exhibited maximum teratogenicity when given to mice as single intraperitoneal injections of 10 to 40 mg/kg on Day 10 or 12 of gestation. Similarly, intraperitoneal doses of 12 to 37 mg/kg given to rats between Days 9 and 12 of gestation and intramuscular doses of 3 to 9 mg/kg given to hamsters between Days 8 and 11 of gestation were teratogenic and/or embryotoxic (i.e., resulted in increased resorptions or embryolethality). In monkeys, divided doses of 40 mg/kg given between Days 20 and 24 of gestation were not teratogenic. Doses higher than 40 mg/kg resulted in abortion.

Efudex should not be used in patients with dihydropyrimidine dehydrogenase (DPD) enzyme deficiency. A large percentage of fluorouracil is catabolized by the DPD enzyme. DPD enzyme deficiency can result in shunting of fluorouracil to the anabolic pathway, leading to cytotoxic activity and potential toxicities.

Efudex is contraindicated in women who are or may become pregnant during therapy. If this drug is used during pregnancy, or if the patient becomes pregnant while using this drug, the patient should be apprised of the potential hazard to the fetus.

Efudex is also contraindicated in patients with known hypersensitivity to any of its components.

The most frequent adverse reactions to Efudex occur locally and are often related to an extension of the pharmacological activity of the drug. These include burning, crusting, allergic contact dermatitis, pruritus, scarring, rash, soreness, and ulceration. Ulcerations, other local reactions, cases of miscarriage, and a birth defect (ventricular septal defect) have been reported when Efudex was applied to mucous membrane areas. Leukocytosis is the most frequent hematological side effect.

Although a causal relationship is remote, other adverse reactions which have been reported infrequently are:

Central Nervous System: Emotional upset, insomnia, irritability.

Gastrointestinal: Medicinal taste, stomatitis.

Hematological: Eosinophilia, thrombocytopenia, toxic granulation.

Integumentary: Alopecia, blistering, bullous pemphigoid, discomfort, ichthyosis, scaling, suppuration, swelling, telangiectasia, tenderness, urticaria, skin rash.

Special Senses: Conjunctival reaction, corneal reaction, lacrimation, nasal irritation.

Miscellaneous: Herpes simplex.

To report SUSPECTED ADVERSE REACTIONS, contact Valeant Pharmaceuticals North America LLC at 1-800-321-4576 and/or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

NDC 0187-3204-47

Rx only

Efudex® (fluorouracil) Topical Cream, 5%

FOR TOPICAL USE ONLY

NOT FOR OPHTHALMIC, ORAL, OR INTRAVAGINAL USE

VALEANT

Net Wt. 40 g

Efudex  fluorouracil solution

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0187-3202 Route of Administration TOPICAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Fluorouracil (Fluorouracil) Fluorouracil 0.5 g  in 10 mL

Inactive Ingredients Ingredient Name Strength propylene glycol   Tromethamine   methylparaben   propylparaben   edetate disodium   HYDROXYPROPYL CELLULOSE (1200000 MW)

Packaging # Item Code Package Description 1 NDC:0187-3202-10 1 BOTTLE in 1 CARTON 1 10 mL in 1 BOTTLE 2 NDC:0187-3202-02 1 BOTTLE in 1 CARTON 2 25 mL in 1 BOTTLE

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA016831 07/29/1970 02/28/2008

Efudex  fluorouracil solution

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0187-3203 Route of Administration TOPICAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Fluorouracil (Fluorouracil) Fluorouracil 1.25 g  in 10 mL

Inactive Ingredients Ingredient Name Strength propylene glycol   Tromethamine   methylparaben   propylparaben   edetate disodium   HYDROXYPROPYL CELLULOSE (1200000 MW)

Packaging # Item Code Package Description 1 NDC:0187-3203-10 1 BOTTLE in 1 CARTON 1 10 mL in 1 BOTTLE 2 NDC:0187-3203-02 1 BOTTLE in 1 CARTON 2 25 mL in 1 BOTTLE

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA016831 07/29/1970 01/31/2010

Efudex  fluorouracil cream

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0187-3204 Route of Administration TOPICAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Fluorouracil (Fluorouracil) Fluorouracil 2 g  in 40 g

Inactive Ingredients Ingredient Name Strength methylparaben   polysorbate 60   propylene glycol   propylparaben   WATER   stearyl alcohol   petrolatum

Packaging # Item Code Package Description 1 NDC:0187-3204-47 1 TUBE in 1 CARTON 1 40 g in 1 TUBE

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA016831 07/29/1970

Labeler - Valeant Pharmaceuticals North America LLC (042230623)

Establishment
Name	Address	ID/FEI	Operations
Valeant Pharmaceuticals International, Inc		245141858	MANUFACTURE(0187-3202, 0187-3203, 0187-3204)

Establishment
Name	Address	ID/FEI	Operations
Mylan Institutional Inc.		965542777	MANUFACTURE(0187-3202, 0187-3203, 0187-3204)

Revised: 05/2017   Valeant Pharmaceuticals North America LLC

Applies to fluorouracil topical: topical cream, topical solution

Along with its needed effects, fluorouracil topical (the active ingredient contained in Efudex) 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 while taking fluorouracil topical:

• Redness and swelling of normal skin

Some side effects of fluorouracil topical 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

• Burning feeling where medicine is applied
• increased sensitivity of skin to sunlight
• itching
• oozing
• skin rash
• soreness or tenderness of skin

Less common or rare

• Darkening of skin
• scaling
• watery eyes