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

☞ 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.

☞ 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

☞ 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

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

☞ 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.

☞ 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.