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Fluorouracil topical

Pronunciation

Class: Skin and Mucous Membrane Agents, Miscellaneous
ATC Class: L01BC02
VA Class: DE600
Molecular Formula: C4H3FN2O2
CAS Number: 51-21-8
Brands: Carac, Efudex, Fluoroplex

Introduction

Pyrimidine antagonist; antimetabolite; antineoplastic agent.a b c g

Uses for Fluorouracil

Actinic Keratoses

Used topically for the treatment of multiple actinic (solar) keratoses.b c e g

Curettage or cryotherapy are preferred treatment options for isolated lesions.a

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Basal Cell Carcinoma

Used topically for the treatment of superficial basal cell carcinoma when conventional methods are impractical (e.g., in patients with multiple lesions or difficult treatment sites).a b g Efficacy not established for treatment of other basal cell carcinomas; establish diagnosis before initiating treatment.a b g

When lesions are isolated and easily accessible, conventional techniques (e.g., surgery, curettage and dessication, cryotherapy) are preferred because they have a higher response rate.a b g

Fluorouracil Dosage and Administration

General

  • Following topical application, response is manifested by erythema, followed by scaling, tenderness, vesiculation, erosion, ulceration, necrosis, and reepithelialization.a b c g

  • Complete healing of actinic keratoses lesions may not occur until 1–2 months after cessation of therapy.a b g

  • Evaluate patients treated for superficial basal cell carcinoma for a reasonable period of time to determine if a cure has been obtained.a b g

Administration

Topical Administration

Apply cream or solution topically with a nonmetallic applicator, clean fingertips, or gloved fingers in an amount sufficient to cover lesions.a b e g If the fingers are used to apply the drug, wash hands immediately afterward.a b e g

For external use only; notfor ophthalmic, oral, or intravaginal use.e g Avoid contact with eyes, nose, mouth, or other mucous membranes.a b c e f g (See Local Inflammatory Reactions under Cautions.)

Actinic Keratoses

Apply topically to lesions as a 0.5, 1, or 5% cream or as a 2 or 5% solution.b c e g Apply 0.5% cream to lesions on the face and anterior scalp.a e

Apply a sufficient amount of 1–5% cream or 2–5% solution to cover lesions twice daily.a b c g

Apply a thin film of 0.5% cream to lesions on face and anterior scalp once daily.a e f

Wash skin and wait 10 minutes before applying 0.5% cream to affected area(s) of face and anterior scalp.e f

Basal Cell Carcinoma

Apply topically as a 5% cream or solution;a b apply a sufficient amount to cover lesions twice daily.a b

Dosage

At equivalent concentrations, solutions are considered more effective than creams.a

Adults

Actinic Keratoses

For multiple actinic (solar) keratoses, increased frequency of application, longer duration of treatment, or temporary, initial combination therapy with topical tretinoin may be necessary on areas other than the head and neck (e.g., hands, arms).a c

Topical

Apply 1–5% cream or 2–5% solution twice daily.a b c g Continue therapy until erosion, necrosis, and ulceration stage is reached, usually 2–4 weeks (for 5% cream or 2–5% solution)b g or 2–6 weeks (for 1% cream)c after initiation of treatment, then discontinue the drug.a b c g

Apply 0.5% cream once daily to face and anterior scalp for up to 4 weeks as tolerated.a e f Generally, local irritation resolves within 2 weeks of cessation of drug.e

Basal Cell Carcinoma
Confirmed Superficial Basal Cell Carcinoma
Topical

Apply 5% cream or solution twice daily for at least 3–6 weeks; may require up to 10–12 weeks before the lesions are obliterated.a b g

Prescribing Limits

Adults

Actinic Keratoses
Topical

0.5% cream: Maximum 4 weeks of therapy recommended.e f

Special Populations

No special population dosage recommendations at this time.g

Cautions for Fluorouracil

Contraindications

  • Known hypersensitivity to fluorouracil or any ingredient in the formulation.a c e g

  • Dihydropyrimidine dehydrogenase activity deficiency.b e (See Dihydropyrimidine Dehydrogenase Activity Deficiency under Cautions.)

  • Known or suspected pregnancy.b c e g (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm.b c e g Birth defects (i.e., cleft lip and palate, ventricular septal defect) and miscarriages reported.b e g

Advise women to avoid becoming pregnant during therapy.b f g If used during pregnancy, or if patient becomes pregnant, apprise of potential fetal hazard.b e g

Dihydropyrimidine Dehydrogenase Activity Deficiency

Deficiency of dihydropyrimidine dehydrogenase activity may cause prolonged fluorouracil clearance and toxicity.b e

Risk of severe, unexpected toxic reactions including stomatitis, diarrhea, neutropenia, and neurotoxicity; life-threatening symptoms including severe abdominal pain, bloody diarrhea, vomiting, fever, and chills reported following topical application of 5% fluorouracil.b e Discontinue therapy if symptoms of toxicity occur.b e

Local Inflammatory Reactions

Local inflammatory reactions (e.g., swelling, scaling, pain, pruritus, burning, soreness, tenderness, suppuration, scarring, hyperpigmentation) occur in most patients.a

Avoid application to mucous membranes due to the possibility of local inflammation and ulceration.e

Occlusive Dressings

Occlusive dressings may increase percutaneous penetration of drug.b g

Increased incidence and severity of inflammatory reactions in adjacent normal skin with use of occlusive dressings.b c g If required, apply a porous gauze dressing.b g

Sensitivity Reactions

Photosensitivity Reactions

Exposure to ultraviolet (UV) light increases the intensity of the inflammatory reaction.a b c g (See Local Inflammatory Reactions under Cautions.) Minimize exposure to UV rays during and immediately following treatment.a g

Hypersensitivity Reactions

Hypersensitivity reactions, including allergic contact dermatitis, reported.c

Potential delayed hypersensitivity reaction; however, patch testing may be inconclusive.c e

General Precautions

Precautions Related to Treatment of Actinic Keratosis

Treatment responses in areas that appear clinically normal may indicate sites of subclinical actinic keratoses.a c

Topical Administration Precautions

Possible increased absorption through ulcerated or inflamed skin.b c e g Possible systemic toxicity when applied to large ulcerated area(s).a

Response in treated areas may be unsightly during therapy and, in some cases, for several weeks after therapy is discontinued.a b c g

Laboratory Monitoring

If an affected area does not respond to treatment or keratotic lesion recurs following therapy, perform a biopsy to confirm the diagnosis of solar keratoses or as indicated in the management of superficial basal cell carcinoma.a b c e g

Specific Populations

Pregnancy

Category X.b c e g (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Not known whether topical fluorouracil is distributed into milk.b c e g Discontinue nursing or the drug.b c e g

Pediatric Use

Safety and efficacy not established.b c e g

Geriatric Use

No substantial differences in safety and efficacy measures were demonstrated in patients 65 years of age compared with younger adults.e

Common Adverse Effects

Local effects (e.g., burning,b c e g dryness,e allergic contact dermatitis,b c g erosions,b e g erythema,b e g hyperpigmentation,b c g irritation,b c g pain,b c e g photosensitivity,b g pruritus,b c g scarring,b c g rash,b g soreness,b g ulceration,b g edema,e telangiectasia),a c eye irritatione .

Fluorouracil Pharmacokinetics

Absorption

Bioavailability

Following application of fluorouracil 5% cream, approximately 6% of the topical dose is absorbed systemically, with peak plasma concentrations attained in 1 hour.a b e g

Absorption of the drug into cells may be selectively greater in diseased skin than in normal skin.a

Distribution

Extent

Not known whether fluorouracil is distributed into human milk.b c e g

Elimination

Metabolism

Anabolized to active metabolites (e.g., 5-fluoro-2′-deoxyuridine-5′-monophosphate); catabolized to inactive metabolites (e.g., CO2, urea, α-fluoro-β-alanine).b d g

Stability

Storage

Topical

Creams and Solutions

Cream 0.5%: 20–25°C.e

Cream 1%: Tight containers at 15–30°C; avoid freezing.a c

Cream and solutions 2 and 5%: 25°C (may be exposed to 15–30°C);b g avoid freezing.a

Actions

  • Interferes with DNA synthesis and, to a lesser extent, the formation of RNA by inhibiting the methylation of deoxyuridylic acid to thymidylic acid, a DNA precursor.a b e g

  • Since DNA and RNA are essential for cell division and growth, may create a thymine deficiency, which provokes unbalanced growth and death of the cell.b e g

  • Effects of DNA and RNA deprivation are most marked on cells that grow more rapidly.e g

Advice to Patients

  • Importance of clinicians instructing patients about proper use of the drug, including associated precautions.f Importance of reading manufacturer’s patient information.f

  • Keep out of reach of children.e f

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed; necessity for clinicians to advise women to avoid becoming pregnant during therapy, and advise pregnant women of risk to the fetus.b e f

  • Importance of not using the drug for any disorder other than that for which it was prescribed.e f

  • Risk of photosensitivity reaction;a b c e f g importance of using sunscreen products and wearing protective clothing over treated areas.f

  • Importance of washing hands immediately after application, if the drug is applied with fingers.b c e f g

  • Advise patients not to apply on the eyelids or directly into the eyes, nose, or mouth.b c e f g

  • Advise patients being treated for superficial basal cell carcinoma to contact their clinician if any suspicious lesion arises in the treatment area.b g

  • Warn patients that the reaction in the treated areas may be unsightly during therapy and, in some cases, for several weeks after therapy is discontinued.a b c e f g

  • Advise patients to continue therapy until erosion, necrosis, and ulceration stage is reached, usually 2–6 weeks after initiation of treatment, then discontinue the drug.a b c f

  • Advise patients not to apply other topical medications, moisturizing creams, or cosmetics on the affected area, unless specifically directed otherwise by their clinician.f

  • Inform patients that if abdominal pain, bloody diarrhea, vomiting, fever, or chills occur during therapy to discontinue the drug and contact their clinician.e f

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.e f

  • Importance of informing patients of other important precautionary information.e f (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Fluorouracil

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Topical

Cream

0.5%

Carac

Dermik

1%

Fluroplex

Allergan

5%

Efudex

Valeant

Solution

2%*

Efudex

Valeant

Fluorouracil Topical Solution

Taro

5%*

Efudex

Valeant

Fluorouracil Topical Solution

Taro

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Carac 0.5% Cream (DERMIK): 30/$322.00 or 90/$903.00

Efudex 5% Cream (VALEANT): 40/$345.99 or 120/$903.35

Efudex 5% Solution (VALEANT): 10/$126.00 or 30/$359.95

Fluoroplex 1% Cream (ALLERGAN DERMATOLOGICS): 30/$330.00 or 90/$969.93

Fluorouracil 2% Solution (TARO): 10/$65.99 or 30/$179.97

Fluorouracil 5% Cream (TARO): 40/$249.98 or 120/$709.87

Fluorouracil 5% Solution (TARO): 10/$101.99 or 30/$283.89

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions April 1, 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

a. AHFS drug information 2008. McEvoy GK, ed. Fluorouracil. Bethesda, MD: American Society of Health-System Pharmacists; 2008: 3611.

b. Valeant Pharma. Efudex (fluorouracil 2 or 5%) cream and solution prescribing information. Costa Mesa, CA; 2005 Sept.

c. Allergan. Fluoroplex (fluorouracil 1%) topical cream prescribing information. Irvine, CA; 2003 Jan.

d. AHFS drug information 2008. McEvoy GK, ed. Fluorouracil. Bethesda, MD: American Society of Health-System Pharmacists; 2008: 1068–72.

e. Dermik. Carac (fluorouracil 0.5%) topical cream prescribing information. Bridgewater, NJ; 2006 Nov.

f. Dermik. Carac (fluorouracil 0.5%) topical cream patient information. Bridgewater, NJ; 2003 Dec.

g. Taro Pharmaceutical. Fluorouracil 2% and 5% topical solution prescribing information. Hawthorne, NY; 2003 Nov.

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