Efudex (Page 2 of 2)

Carcinogenesis, Mutagenesis, Impairment of Fertility:

Adequate long-term studies in animals to evaluate carcinogenic potential have not been conducted with fluorouracil. Studies with the active ingredient of EFUDEX, 5-fluorouracil, have shown positive effects in in vitro tests for mutagenicity and on impairment of fertility.

5-Fluorouracil was positive in three in vitro cell neoplastic transformation assays. In the C3H/10T½ clone 8 mouse embryo cell system, the resulting morphologically transformed cells formed tumors when inoculated into immunosuppressed syngeneic mice.

While no evidence for mutagenic activity was observed in the Ames test (three studies), fluorouracil has been shown to be mutagenic in the survival count rec-assay with Bacillus subtilis and in the Drosophila wing-hair spot test. Fluorouracil produced petite mutations in Saccharomyces cerevisiae and was positive in the micronucleus test (bone marrow cells of male mice).

Fluorouracil was clastogenic in vitro (i.e., chromatid gaps, breaks, and exchanges) in Chinese hamster fibroblasts at concentrations of 1.0 and 2.0 mcg/mL and has been shown to increase sister chromatid exchange in vitro in human lymphocytes. In addition, 5-fluorouracil has been reported to produce an increase in numerical and structural chromosome aberrations in peripheral lymphocytes of patients treated with this product.

Doses of 125 to 250 mg/kg, administered intraperitoneally, have been shown to induce chromosomal aberrations and changes in chromosome organization of spermatogonia in rats. Spermatogonial differentiation was also inhibited by fluorouracil, resulting in transient infertility. However, in studies with a strain of mouse which is sensitive to the induction of sperm head abnormalities after exposure to a range of chemical mutagens and carcinogens, fluorouracil was inactive at oral doses of 5 to 80 mg/kg/day. In female rats, fluorouracil administered intraperitoneally at doses of 25 and 50 mg/kg during the preovulatory phase of oogenesis significantly reduced the incidence of fertile matings, delayed the development of preimplantation and postimplantation embryos, increased the incidence of preimplantation lethality and induced chromosomal anomalies in these embryos. Single-dose intravenous and intraperitoneal injections of 5-fluorouracil have been reported to kill differentiated spermatogonia and spermatocytes (at 500 mg/kg) and to produce abnormalities in spermatids (at 50 mg/kg) in mice.

Pregnancy:

See CONTRAINDICATIONS.

Nursing Mothers:

It is not known whether EFUDEX is excreted in human milk. Because there is some systemic absorption of fluorouracil after topical administration (see CLINICAL PHARMACOLOGY), because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue use of the drug, taking into account the importance of the drug to the mother.

Pediatric Use:

Safety and effectiveness in children have not been established.

ADVERSE REACTIONS:

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 Bausch Health US, LLC at 1-800-321-4576 and/or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

OVERDOSAGE:

There have been no reports of overdosage with EFUDEX.

The oral LD50 for the 5% topical cream was 234 mg/kg in rats and 39 mg/kg in dogs. These doses represented 11.7 and 1.95 mg/kg of fluorouracil, respectively. Studies with a 5% topical solution yielded an oral LD50 of 214 mg/kg in rats and 28.5 mg/kg in dogs, corresponding to 10.7 and 1.43 mg/kg of fluorouracil, respectively. The topical application of the 5% cream to rats yielded an LD50 of greater than 500 mg/kg.

DOSAGE AND ADMINISTRATION:

When EFUDEX is applied to a lesion, a response occurs with the following sequence: erythema, usually followed by vesiculation, desquamation, erosion, and re-epithelialization.

EFUDEX should be applied preferably with a nonmetal applicator or suitable glove. If EFUDEX is applied with the fingers, the hands should be washed immediately afterward.

Actinic or Solar Keratosis:

Apply cream or solution twice daily in an amount sufficient to cover the lesions. Medication should be continued until the inflammatory response reaches the erosion stage, at which time use of the drug should be terminated. The usual duration of therapy is from 2 to 4 weeks. Complete healing of the lesions may not be evident for 1 to 2 months following cessation of EFUDEX therapy.

Superficial Basal Cell Carcinomas:

Only the 5% strength is recommended. Apply cream or solution twice daily in an amount sufficient to cover the lesions. Treatment should be continued for at least 3 to 6 weeks. Therapy may be required for as long as 10 to 12 weeks before the lesions are obliterated. As in any neoplastic condition, the patient should be followed for a reasonable period of time to determine if a cure has been obtained.

HOW SUPPLIED:

EFUDEX Solution is available in 10 mL drop dispensers containing either 2% (NDC 0187-3202-10) or 5% (NDC 0187-3203-10) fluorouracil and 25 mL drop dispensers containing either 2% (NDC 0187-3202-02) or 5% (NDC 0187-3203-02) fluorouracil on a weight/weight basis compounded with disodium edetate, hydroxypropyl cellulose, methylparaben, propylene glycol, propylparaben, and tris (hydroxymethyl) aminomethane.

EFUDEX Cream is available in 40 g tubes containing 5% fluorouracil (NDC 0187-3204-47) in a vanishing cream base consisting of methylparaben, polysorbate 60, propylene glycol, propylparaben, purified water, stearyl alcohol, and white petrolatum.

Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F).

Distributed by:
Bausch Health US, LLC
Bridgewater, NJ 08807 USA

Manufactured by:
Mylan Institutional Inc.
Sugar Land, TX 77478 USA

EFUDEX is a trademark of Bausch Health Companies Inc. or its affiliates.

© 2020 Bausch Health Companies Inc. or its affiliates

Rev. 04/2020

9734600

115797

PRINCIPAL DISPLAY PANEL — 40 g Cream Carton

NDC 0187-3204-47

Rx only

Efudex® (fluorouracil) Topical Cream, 5%

FOR TOPICAL USE ONLY

NOT FOR OPHTHALMIC, ORAL, OR INTRAVAGINAL USE

Net Wt. 40 g

5%

Ortho Dermatologics

carton
(click image for full-size original)

PRINCIPAL DISPLAY PANEL — Solution Carton

imagenotavail1

PRODUCT DELISTED –

IMAGE NOT AVAILABLE

PRINCIPAL DISPLAY PANEL — Solution Carton

imagenotavail2

PRODUCT DELISTED –

IMAGE NOT AVAILABLE

EFUDEX
fluorouracil solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG 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
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:0187-3202-10 1 BOTTLE in 1 CARTON contains a BOTTLE
1 10 mL in 1 BOTTLE This package is contained within the CARTON (0187-3202-10)
2 NDC:0187-3202-02 1 BOTTLE in 1 CARTON contains a BOTTLE
2 25 mL in 1 BOTTLE This package is contained within the CARTON (0187-3202-02)
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 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
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:0187-3203-10 1 BOTTLE in 1 CARTON contains a BOTTLE
1 10 mL in 1 BOTTLE This package is contained within the CARTON (0187-3203-10)
2 NDC:0187-3203-02 1 BOTTLE in 1 CARTON contains a BOTTLE
2 25 mL in 1 BOTTLE This package is contained within the CARTON (0187-3203-02)
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 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 Multilevel Packaging
1 NDC:0187-3204-47 1 TUBE in 1 CARTON contains a TUBE
1 40 g in 1 TUBE This package is contained within the CARTON (0187-3204-47)
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA016831 07/29/1970
Labeler — Bausch Health US LLC (831922468)
Establishment
Name Address ID/FEI Operations
Bausch Health Companies Inc. 245141858 MANUFACTURE (0187-3202), MANUFACTURE (0187-3203), MANUFACTURE (0187-3204)
Establishment
Name Address ID/FEI Operations
Mylan Institutional Inc. 965542777 MANUFACTURE (0187-3202), MANUFACTURE (0187-3203), MANUFACTURE (0187-3204)

Revised: 04/2020 Bausch Health US LLC

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