CARAC

Clinical safety rating: caution

Comprehensive clinical and safety monograph for CARAC (CARAC).

How it works

Carac (fluorouracil) is a fluorinated pyrimidine antimetabolite that inhibits thymidylate synthase, thereby interfering with DNA synthesis and repair. It also incorporates into RNA, disrupting RNA processing and function.

What the body does with it

Metabolism	Metabolized via the same catabolic pathway as uracil; primarily by dihydropyrimidine dehydrogenase (DPD) to dihydrofluorouracil, then further to α-fluoro-β-alanine (FBAL) and other metabolites. Less than 10% is excreted unchanged in urine.
Excretion	Primarily metabolized via dihydropyrimidine dehydrogenase (DPD) in the liver; ~10% excreted unchanged in urine; remaining metabolites eliminated renally (including CO2 and urea).
Half-life	Terminal elimination half-life is approximately 20 minutes for the parent drug, but the active metabolite 5-fluorouracil (5-FU) has a half-life of 8–20 minutes; due to rapid metabolism, prolonged exposure occurs with continuous infusion.
Protein binding	Approximately 10% bound to plasma proteins, primarily albumin.
Volume of Distribution	Apparent volume of distribution (Vd) for 5-FU is 0.5–0.8 L/kg; widely distributed into tissues including tumors.
Bioavailability	Topical bioavailability is low (<5% systemic absorption); oral bioavailability is highly variable (10–80%) due to first-pass metabolism; intravenous administration yields 100% bioavailability.
Onset of Action	Onset of action: within 1–2 hours after topical application for actinic keratosis; systemic absorption is minimal.
Duration of Action	Duration: Clinical effects (erythema, erosion) persist for 2–4 weeks after last application; systemic effects are transient due to rapid clearance.

Classification & Brands

Dosing & administration

Apply 0.5% cream twice daily for 2-4 weeks to affected area; maximum single dose 1g, not exceed 60g per course.

Dosage form	CREAM
Renal impairment	No adjustment required for topical administration; systemic absorption minimal.
Liver impairment	No adjustment required for topical administration; systemic absorption minimal.
Pediatric use	Not recommended for pediatric patients; safety and efficacy not established.
Geriatric use	No specific adjustment; use standard dosing; monitor for local reactions.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for CARAC (CARAC).

Breastfeeding	Contraindicated in breastfeeding. Excreted into breast milk (M/P ratio unknown). Potential for serious adverse reactions in nursing infants (immunosuppression, growth retardation).
Teratogenic Risk	FDA Pregnancy Category D. First trimester: Contraindicated due to embryocidal and teratogenic effects (malformations, fetal death). Second/Third trimester: Use only if clearly needed; risk of fetal hemorrhage, bone marrow depression, and meconium peritonitis.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

CARAC (fluorouracil) should not be used in patients with known hypersensitivity to any component of the formulation. Use caution in patients with dihydropyrimidine dehydrogenase (DPD) enzyme deficiency, as severe and fatal toxicities can occur.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to fluorouracil or any component; pregnancy (Risk Factor D); lactating women (do not breastfeed); patients with known DPD deficiency.

Clinical Precautions

Precautions	Avoid contact with eyes, mucous membranes, and open wounds. May cause intense local reactions (burning, crusting, erosion, pain, pruritus, scarring). Discontinue if severe systemic toxicity occurs. Avoid prolonged sun exposure. Use in females of reproductive potential requires adequate contraception. Not for use in patients with DPD deficiency without expert consultation.
Food/Dietary	No significant food interactions known. No dietary restrictions required.

Clinical Tips & Counseling

Drug interactions

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CARAC

Clinical safety rating: caution

Comprehensive clinical and safety monograph for CARAC (CARAC).

How it works

What the body does with it

Metabolism	Metabolized via the same catabolic pathway as uracil; primarily by dihydropyrimidine dehydrogenase (DPD) to dihydrofluorouracil, then further to α-fluoro-β-alanine (FBAL) and other metabolites. Less than 10% is excreted unchanged in urine.
Excretion	Primarily metabolized via dihydropyrimidine dehydrogenase (DPD) in the liver; ~10% excreted unchanged in urine; remaining metabolites eliminated renally (including CO2 and urea).
Half-life	Terminal elimination half-life is approximately 20 minutes for the parent drug, but the active metabolite 5-fluorouracil (5-FU) has a half-life of 8–20 minutes; due to rapid metabolism, prolonged exposure occurs with continuous infusion.
Protein binding	Approximately 10% bound to plasma proteins, primarily albumin.
Volume of Distribution	Apparent volume of distribution (Vd) for 5-FU is 0.5–0.8 L/kg; widely distributed into tissues including tumors.
Bioavailability	Topical bioavailability is low (<5% systemic absorption); oral bioavailability is highly variable (10–80%) due to first-pass metabolism; intravenous administration yields 100% bioavailability.
Onset of Action	Onset of action: within 1–2 hours after topical application for actinic keratosis; systemic absorption is minimal.
Duration of Action	Duration: Clinical effects (erythema, erosion) persist for 2–4 weeks after last application; systemic effects are transient due to rapid clearance.

Classification & Brands

Dosing & administration

Apply 0.5% cream twice daily for 2-4 weeks to affected area; maximum single dose 1g, not exceed 60g per course.

Dosage form	CREAM
Renal impairment	No adjustment required for topical administration; systemic absorption minimal.
Liver impairment	No adjustment required for topical administration; systemic absorption minimal.
Pediatric use	Not recommended for pediatric patients; safety and efficacy not established.
Geriatric use	No specific adjustment; use standard dosing; monitor for local reactions.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for CARAC (CARAC).

Breastfeeding	Contraindicated in breastfeeding. Excreted into breast milk (M/P ratio unknown). Potential for serious adverse reactions in nursing infants (immunosuppression, growth retardation).
Teratogenic Risk	FDA Pregnancy Category D. First trimester: Contraindicated due to embryocidal and teratogenic effects (malformations, fetal death). Second/Third trimester: Use only if clearly needed; risk of fetal hemorrhage, bone marrow depression, and meconium peritonitis.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to fluorouracil or any component; pregnancy (Risk Factor D); lactating women (do not breastfeed); patients with known DPD deficiency.

Clinical Precautions

Precautions	Avoid contact with eyes, mucous membranes, and open wounds. May cause intense local reactions (burning, crusting, erosion, pain, pruritus, scarring). Discontinue if severe systemic toxicity occurs. Avoid prolonged sun exposure. Use in females of reproductive potential requires adequate contraception. Not for use in patients with DPD deficiency without expert consultation.
Food/Dietary	No significant food interactions known. No dietary restrictions required.

Clinical Tips & Counseling

Drug interactions

Loading safety data…

Clinical Pearls	CARAC (fluorouracil cream 0.5%) is used for actinic keratoses. Apply twice daily for 2-4 weeks. Treatment site reactions (erythema, scaling) indicate efficacy; educate patients that these are expected. Avoid occlusive dressings. Monitor for photosensitivity; advise sun avoidance and sunscreen use.
Patient Advice	Apply a thin layer to affected areas twice daily for 2-4 weeks. · Do not cover the treated area with bandages or wraps. · Expect redness, scaling, and irritation; these indicate the medication is working. · Avoid sun exposure and use broad-spectrum sunscreen on treated areas. · Wash hands after application unless treating hands.