ADRUCIL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ADRUCIL (ADRUCIL).
Fluorouracil (5-FU) is a pyrimidine analog that inhibits thymidylate synthase, interfering with DNA synthesis. It is metabolized to its active metabolites, which incorporate into RNA and DNA, causing cytotoxicity primarily in S-phase cells.
| Metabolism | Hepatic metabolism via dihydropyrimidine dehydrogenase (DPD) to dihydrofluorouracil (DHFU). Further catabolism via beta-alanine pathway. Approximately 80% of the drug is cleared via metabolic breakdown. |
| Excretion | Primarily hepatic metabolism; renal excretion of metabolites accounts for ~60-80% of the dose. Unchanged fluorouracil excreted renally is <10%. Fecal excretion is minimal (<5%). |
| Half-life | Biphasic elimination: initial t1/2α ~10-20 minutes, terminal t1/2β ~20-24 hours. Accumulation occurs with continuous infusion. |
| Protein binding | 10-15% bound to albumin; minimal binding to other plasma proteins. |
| Volume of Distribution | 0.5-1.0 L/kg; distributes into extracellular fluid, crosses blood-brain barrier (CSF levels 0.1-0.3 of plasma). |
| Bioavailability | Oral: <10% (inconsistent, not used); Topical: ~5% systemic absorption (minimal); Intravenous: 100%. |
| Onset of Action | Intravenous: 1-3 minutes; Topical: 2-3 weeks for actinic keratosis; Intraarterial: immediate local effect. |
| Duration of Action | Intravenous: Plasma levels negligible after 3 hours, but effect on RNA/DNA lasts 24-48 hours. Topical: 2-6 weeks for lesion resolution. |
12 mg/kg IV bolus daily for 4 days, then if no toxicity, 6 mg/kg IV on days 6, 8, 10, and 12; or 15 mg/kg IV weekly; or 500-600 mg/m2 IV every 3-4 weeks.
| Dosage form | INJECTABLE |
| Renal impairment | GFR 30-50 mL/min: reduce dose by 20%; GFR 10-29 mL/min: reduce dose by 50%; GFR <10 mL/min: administer 50% of dose every 48 hours or consider alternative. |
| Liver impairment | Child-Pugh A: no adjustment necessary; Child-Pugh B: reduce dose by 50%; Child-Pugh C: reduce dose by 75% or avoid use. |
| Pediatric use | 12 mg/kg IV daily for 4 days, then 6 mg/kg IV on days 6, 8, 10, and 12, maximum 600 mg/day; or 500 mg/m2 IV weekly. |
| Geriatric use | Reduce initial dose by 20% in patients >70 years old; monitor for myelosuppression and mucositis; consider weekly dosing regimen. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ADRUCIL (ADRUCIL).
| Breastfeeding | Contraindicated. Fluorouracil is present in breast milk; M/P ratio unknown. Risk of severe neonatal toxicity (myelosuppression, gastrointestinal toxicity). |
| Teratogenic Risk | FDA Pregnancy Category D. First trimester: high risk of fetal malformations (neural tube defects, cleft palate, skeletal abnormalities). Second and third trimesters: risk of growth restriction, neurodevelopmental deficits, and fetal death. |
| Fetal Monitoring |
■ FDA Black Box Warning
WARNING: The drug should be administered only under the supervision of a qualified physician experienced in cancer chemotherapy. Severe toxic reactions, including myelosuppression, mucositis, and neurotoxicity, may occur. Patients should be hospitalized for initial therapy. Dose-limiting toxicities include stomatitis and diarrhea. Not for use in poor-risk patients or those with dihydropyrimidine dehydrogenase (DPD) deficiency.
| Serious Effects |
["Hypersensitivity to fluorouracil or any component","Dihydropyrimidine dehydrogenase (DPD) deficiency","Severe infection or bone marrow depression","Poor nutritional status","Major surgery within the past 30 days","Pregnancy"]
| Precautions | ["Myelosuppression: monitor CBCs; withhold for grade 4 toxicity","Gastrointestinal toxicity: stomatitis, diarrhea, mucositis; dose adjust for severe symptoms","Cardiotoxicity: risk of myocardial ischemia, angina, arrhythmias","Hand-foot syndrome (palmar-plantar erythrodysesthesia): interrupt therapy if severe","Hepatotoxicity: monitor liver function","Neurotoxicity: cerebellar ataxia, confusion","Rash, photosensitivity, hyperpigmentation","Pregnancy: can cause fetal harm"] |
| Food/Dietary |
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| Maternal: complete blood count with differential, liver and renal function tests, electrolytes. Fetal: ultrasound for growth and anatomy, fetal heart rate monitoring. |
| Fertility Effects | Gonadal suppression: oligospermia or azoospermia in males; amenorrhea and ovarian failure in females. Irreversible in some cases. |
| Avoid grapefruit and grapefruit juice (CYP3A4 interaction). Caution with alcohol (hepatotoxicity risk). Folate supplementation may increase toxicity; use only if prescribed. |
| Clinical Pearls | ADRUcil (fluorouracil) is an antimetabolite used in colorectal, breast, head/neck cancers. Monitor for cardiotoxicity (angina, MI) especially with continuous infusion. DPD deficiency screening (blood test) required before treatment due to risk of severe toxicity. Administer via central line to reduce phlebitis. Palmar-plantar erythrodysesthesia (hand-foot syndrome) common; manage with dose delay/reduction and pyridoxine. |
| Patient Advice | Avoid sun exposure and use SPF 50+ sunscreen during treatment and for months after. · Report chest pain, shortness of breath, or palpitations immediately. · Use cold packs on hands/feet to reduce hand-foot syndrome symptoms. · Do not take aspirin or NSAIDs without doctor approval due to bleeding risk. · Maintain good oral hygiene; report mouth sores promptly. · Use effective contraception during and for 6 months after treatment. · Do not receive live vaccines during therapy. |