Adrucil

Action

Inhibits DNA and RNA synthesis, leading to death of rapid-growing neoplastic cells. Cell-cycle-S-phase specific.

Availability

Cream: 1%, 5%

Injection: 50 mg/ml in 10-ml ampules and 10-, 20-, and 100-ml vials

Solution: 1%, 2%, 5%

Indications and dosages

➣ Advanced colorectal cancer

Adults: 370 mg/m² I.V. for 5 days, preceded by leucovorin 200 mg/m² daily for 5 days; may be repeated q 4 to 5 weeks. No single daily dose should exceed 800 mg.

➣ Colon, rectal, breast, gastric, and pancreatic cancer

Adults: Initially, 12 mg/kg/day I.V. for 4 days; then 6 mg/kg I.V. on days 6, 8, 10, and 12. Maximum dosage is 800 mg/day. For maintenance, start 30 days after last dose. If no toxicity, use dosage from first course. If toxicity occurs, give 10 to 15 mg/kg/week as single dose after toxicity subsides. Don't exceed 1 g/week.

➣ Actinic (solar) keratoses

Adults: 1% solution or cream applied once or twice daily to lesions on head, neck, or chest; 2% to 5% solution or cream may be needed for other areas.

➣ Superficial basal cell carcinoma

Adults: 5% solution or cream applied b.i.d. for 3 to 6 weeks (up to 12 weeks)

Contraindications

• Hypersensitivity to drug or its components

• Bone marrow depression

• Dihydropyrimidine dehydrogenase enzyme deficiency (with topical route)

• Poor nutritional status

• Serious infection

• Pregnancy or breastfeeding

Precautions

Use cautiously in:

• renal or hepatic impairment, infections, edema, ascites

• obese patients.

Administration

See Consult facility's cancer protocols to ensure correct dosage, administration technique, and cycle length.

• Give antiemetic before fluorouracil, as ordered, to reduce GI upset.

• Know that drug may be given without dilution by direct I.V. injection over 1 to 3 minutes.

• For I.V. infusion, dilute with dextrose 5% in water, sterile water, or normal saline solution in plastic bag (not glass bottle). Infusion may be given over a period of 24 hours or more.

See Be aware of the importance of leucovorin rescue with fluorouracil therapy, if prescribed.

• Check infusion site frequently to detect extravasation.

• Use nonmetal applicator or appropriate gloves to apply topical form.

• Avoid applying topical form to mucous membranes or irritated skin.

• Don't use occlusive dressings over topical form.

• Know that pyridoxine may be given with fluorouracil to reduce risk of palmar-plantar erythrodysesthesia (hand-foot syndrome).

Adverse reactions

CNS: confusion, disorientation, euphoria, ataxia, headache, weakness, malaise, acute cerebellar syndrome or dysfunction

CV: angina, myocardial ischemia, thrombophlebitis

EENT: vision changes, photophobia, lacrimation, lacrimal duct stenosis, nystagmus, epistaxis

GI: nausea, vomiting, diarrhea, stomatitis, anorexia, GI ulcer, GI bleeding

Hematologic: anemia, leukopenia, thrombocytopenia

Skin: alopecia, maculopapular rash, melanosis of nails, nail loss, palmar-plantar erythrodysesthesia, photosensitivity, local inflammation reaction (with cream), dermatitis

Other: fever, anaphylaxis

Interactions

Drug-drug. Bone marrow depressants (including other antineoplastics): additive bone marrow depression

Irinotecan: dehydration, neutropenia, sepsis

Leucovorin calcium: increased risk of fluorouracil toxicity

Live-virus vaccines: decreased antibody response to vaccine, increased risk of adverse reactions

Drug-diagnostic tests. Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, bilirubin, lactate dehydrogenase, urinary 5-hydroxyindoleacetic acid: increased levels

Albumin, granulocytes, platelets, red blood cells, white blood cells (WBCs): decreased levels

Drug-behaviors. Sun exposure: increased risk of phototoxicity

Patient monitoring

See Watch for signs and symptoms of toxicity, especially stomatitis and diarrhea. If these occur, stop drug and notify prescriber. Note that toxicity may take 1 to 3 weeks to develop.

• Monitor CBC, WBC and platelet counts, and kidney and liver function test results.

• Assess fluid intake and output.

• With long-term use, watch for serious rash on hands and feet. If it occurs, consult prescriber regarding need for pyridoxine.

• Assess for bleeding tendency.

• Monitor blood glucose level in patients at risk for hyperglycemia.

Patient teaching

See Emphasize importance of taking leucovorin as prescribed with high-dose therapy.

See Instruct patient to report signs and symptoms of toxicity, particularly stomatitis and diarrhea. Tell him that these may not occur for 1 to 3 weeks.

• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.

• Tell patient to avoid activities that can cause injury. Instruct him to use soft toothbrush and electric razor to avoid gum and skin injury.

• Advise patient to minimize GI upset by eating frequent, small servings of food and drinking adequate fluids.

• Tell patient that drug may cause reversible hair loss.

• Inform patient that he'll undergo regular blood testing during therapy.

See Advise female to inform prescriber immediately if she is pregnant. Caution her not to breastfeed.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and behaviors mentioned above.