Carac cream, 0.5%

Name: Carac cream, 0.5%

Carac cream, 0.5% 33 mg
Carac cream, 0.5% drug
Carac cream, 0.5% side effects
Carac cream, 0.5% serious side effects
Carac cream, 0.5% effects of

Description

Carac (fluorouracil cream) Cream, 0.5%, contains fluorouracil for topical dermatologic use. Chemically, fluorouracil is 5-fluoro-2,4(1H, 3H)-pyrimidinedione. The molecular formula is C 4 H 3 FN 2 O 2 . Fluorouracil has a molecular weight of 130.08.

Carac Cream contains 0.5% fluorouracil, with 0.35% being incorporated into a patented porous microsphere (Microsponge) * composed of methyl methacrylate / glycol dimethacrylate crosspolymer and dimethicone. The cream formulation contains the following other inactive ingredients: carbomer 940, dimethicone, glycerin, methyl gluceth-20, methyl methacrylate / glycol dimethacrylate crosspolymer, methylparaben, octyl hydroxy stearate, polyethylene glycol 400, polysorbate 80, propylene glycol, propylparaben, purified water, sorbitan monooleate, stearic acid, and trolamine.

Contraindications

Fluorouracil may cause fetal harm when administered to a pregnant woman. Fluorouracil is contraindicated in women who are or may become pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.

No adequate and well-controlled studies have been conducted in pregnant women with either topical or parenteral forms of fluorouracil. One birth defect (ventricular septal defect) and cases of miscarriage have been reported when fluorouracil was applied to mucous membrane areas. Multiple birth defects have been reported in the fetus of a patient treated with intravenous fluorouracil.

Animal reproduction studies have not been conducted with Carac. Fluorouracil, the active ingredient, has been shown to be teratogenic in mice, rats, and hamsters when administered parenterally at doses greater than or equal to 10, 15, and 33 mg/kg/day, respectively, [4X, 11X, and 20X, respectively, the Maximum Recommended Human Dose (MRHD) based on body surface area (BSA)]. Fluorouracil was administered during the period of organogenesis for each species. Embryolethal effects occurred in monkeys at parenteral doses greater than 40 mg/kg/day (65X the MRHD based on BSA) administered during the period of organogenesis.

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

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

Adverse Reactions

The following were adverse events considered to be drug-related and occurring with a frequency of >/=1% with Carac: application site reaction (94.6%) and eye irritation (5.4%). The signs and symptoms of facial irritation (application site reaction) are presented below.

Summary of Facial Irritation Signs and Symptoms--Pooled Phase 3 Studies

Clinical Sign or Symptom	Active One Week N=85	Active Two Week N=87	Active Four Week N=85	ALL Active Treatments N=257	Vehicle Treatments N=127
	n (%)	n (%)	n (%)	n (%)	n (%)
Erythema	76 (89.4)	82 (94.3)	82 (96.5)	240 (93.4)	76 (59.8)
Dryness	59 (69.4)	76 (87.4)	79 (92.9)	214 (83.3)	60 (47.2)
Burning	51 (60.0)	70 (80.5)	71 (83.5)	192 (74.7)	28 (22.0)
Erosion	21 (24.7)	38 (43.7)	54 (63.5)	113 (44.0)	17 (13.4)
Pain	26 (30.6)	34 (39.1)	52 (61.2)	112 (43.6)	7 (5.5)
Edema	12 (14.1)	28 (32.2)	51 (60.0)	91 (35.4)	6 (4.7)

During clinical trials, irritation generally began on day 4 and persisted for the remainder of treatment. Severity of facial irritation at the last treatment visit was slightly below baseline for the vehicle group, mild to moderate for the 1 week active treatment group, and moderate for the 2 and 4 week active treatment groups. Mean severity declined rapidly for each active group after completion of treatment and was below baseline for each group at the week 2 post-treatment follow-up visit.

Thirty-one patients (12% of those treated with Carac in the Phase 3 clinical studies) discontinued study treatment early due to facial irritation. Except for three patients, discontinuation of treatment occurred on or after day 11 of treatment.

Eye irritation adverse events, described as mild to moderate in intensity, were characterized as burning, watering, sensitivity, stinging and itching. These adverse events occurred across all treatment arms in one of the two Phase 3 studies.

Summary of All Adverse Events Reported in >/=1% of Patients in the Combined Active Treatment and Vehicle Groups--Pooled Phase 3 Studies
9721 and 9722 Combined

Adverse Event	Active One Week N=85	Active Two Week N=87	Active Four Week N=85	ALL Active Treatments N=257	Vehicle Treatments N=127
	n (%)	n (%)	n (%)	n (%)	n (%)
Body as a whole	7 (8.2)	6 (6.9)	12 (14.1)	25 (9.7)	15 (11.8)
Headache	3 (3.5)	2 (2.3)	3 (3.5)	8 (3.1)	3 (2.4)
Common Cold	4 (4.7)	0	2 (2.4)	6 (2.3)	3 (2.4)
Allergy	0	2 (2.3)	1 (1.2)	3 (1.2)	2 (1.6)
Infection Upper Respiratory	0	0	0	0	2 (1.6)
Musculoskeletal	1 (1.2)	1 (1.1)	1 (1.2)	3 (1.2)	5 (3.9)
Muscle Soreness	0	0	0	0	2 (1.6)
Respiratory	5 (5.9)	0	1 (1.2)	6 (2.3)	6 (4.7)
Sinusitis	4 (4.7)	0	0	4 (1.6)	2 (1.6)
Skin & Appendages	78 (91.8)	83 (95.4)	82 (96.5)	243 (94.6)	85 (66.9)
Application Site Reaction	78 (91.8)	83 (95.4)	82 (96.5)	243 (94.6)	83 (65.4)
Irritation Skin	1 (1.2)	0	2 (2.4)	3 (1.2)	0
Special Senses	6 (7.1)	4 (4.6)	6 (7.1)	16 (6.2)	6 (4.7)
Eye Irritation	5 (5.9)	3 (3.4)	6 (7.1)	14 (5.4)	3 (2.4)

Adverse Experiences Reported by Body System:

In the Phase 3 studies, no serious adverse event was considered related to study drug. A total of five patients, three in the active treatment groups and two in the vehicle group, experienced at least one serious adverse event. Three patients died as a result of adverse event(s) considered unrelated to study drug (stomach cancer, myocardial infarction, and cardiac failure).

Post-treatment clinical laboratory tests other than pregnancy tests were not performed during the Phase 3 clinical studies. Clinical laboratory tests were performed during conduct of a Phase 2 study of 104 patients and 21 patients in a Phase 1 study. No abnormal serum chemistry, hematology, or urinalysis results in these studies were considered clinically significant.

How Supplied

Cream--30 gram tube NDC 0066-7150-30

Store at Controlled Room Temperature 20 to 25°C (68 to 77°F) [see USP].

Prescribing Information as of December 2003(a)

Keep out of the reach of children.

Rx only

Manufactured for:

Dermik Laboratories

A division of Aventis Pharmaceuticals Inc

Berwyn, PA 19312 USA

Manufactured by:

Pharmaceutical Manufacturing Research Services, Inc

Horsham, PA 19044 USA

*Microsponge is a registered trademark of Cardinal Health, Inc. or one of its subsidiaries.
# Efudex is a registered trademark of ICN Pharmaceuticals, Inc.

PATIENT INFORMATION

Carac Cream, 0.5%

(fluorouracil cream)

Read this leaflet carefully before you start to use your medicine. Read the information you get every time you get more medicine. There may be new information about the drug. This leaflet does not take the place of talks with your doctor. If you have any questions or are not sure about something, ask your doctor or pharmacist.

What is Carac?

Carac (Care ack) is a cream used by adults to treat skin conditions on the face and front part of the scalp called solar keratosis or actinic keratosis.

Who should not use Carac?

Do not use Carac

if you are pregnant or might become pregnant. Carac may harm your unborn child.
if you are nursing a baby. We do not know if Carac can pass to the baby through the milk.
if you have dihydropyrimidine dehydrogenase (DPD) enzyme deficiency. The active ingredient in Carac, fluorouracil, can cause serious side effects in patients who are DPD enzyme deficient. If you have DPD enzyme deficiency and use medications containing fluorouracil, you may develop serious side effects such as stomach pain, bloody diarrhea, vomiting, fever, or chills.
if you are allergic to the ingredients in Carac. Ask your doctor or pharmacist about the inactive ingredients.
if under 18 years of age. Carac should not be used in children.

Tell your doctor if you are able to become pregnant. Your doctor may advise you about birth control to avoid pregnancy.

How should I use Carac?

Use Carac once a day as instructed by your doctor. Use it only on your skin. You should use Carac for up to 4 weeks.

Clean the area where you will apply Carac. Rinse well and dry the area with a towel and wait 10 minutes before applying Carac.
Put Carac on your face as directed by your physician, using your fingertips. Use enough to cover the affected skin.
Avoid contact with your eyes, nostrils, and mouth.
Wash your hands as soon as you finish putting the Carac on your skin.
A moisturizer/sunscreen may be applied 2 hours after Carac has been applied. Do not use any other skin products including creams, lotions, medications or cosmetics-unless instructed by your doctor.

What should I avoid while using Carac?

Avoid sunlight or other ultraviolet light (such as tanning booths) as much as possible while using Carac. 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 Carac. If you do become pregnant, stop using Carac and tell your doctor right away.

What are the possible side effects of Carac?

Most patients using Carac get skin reactions where the medicine is used. These reactions include redness, dryness, burning, pain, erosion (loss of the upper layer of skin), and 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.

Storage information

Keep this medicine at room temperature (68-77°F/20-25°C). Throw away unused medicine. Keep this medicine out of the reach of children.

General advice about prescription medicines

Medicines are sometimes prescribed for conditions that are not described in patient information leaflets. Do not use it for a condition for which it was not prescribed. This medicine is for your use only. Never give it to other people. It may harm them even if their skin problem appears to be the same as yours. Do not use Carac after the expiration date on the tube.

Prescribing Information as of December 2003(a).