capecitabine, Xeloda

 Indications

Metastatic colorectal cancer. Adjuvant treatment for

Dukes’ C colon cancer following primary resection.

Metastatic breast cancer that has worsened despite

prior therapy with anthracycline (daunorubicin, doxorubicin,

idarubicin) (to be used in combination with

docetaxel). Metastatic breast cancer that is resistant to

both paclitaxel and an anthracycline (daunorubicin,

doxorubicin, idarubicin) or is resistant to paclitaxel

and further anthracycline therapy is contraindicated.

Action

Converted in tissue to 5-fluorouracil (5-FU), which

inhibits DNA and RNA synthesis by preventing thymidine

production. The enzyme responsible for the final step

in the conversion to 5-FU may be found in higher concentrations

in some tumors. Therapeutic Effects:

Death of rapidly replicating cells, particularly malignant

ones.

Pharmacokinetics

Absorption: Well absorbed after oral administration.

Distribution: Unknown.

Metabolism and Excretion: Metabolized

mostly in tissue and by the liver to 5-FU; 5-FU is metabolized

by dihydropyrimidine dehydrogenase to a less toxic compound; inactive metabolites are excreted primarily

in urine.

Half-life: 45 min.

TIME/ACTION PROFILE (blood levels)

ROUTE ONSET PEAK DURATION

PO unknown† 1.5 hr (2 hr

for 5-FU)‡

unknown

†Onset of antineoplastic effect is 6 wk.

‡Peak 5-FU levels occur at 2 hr.

Contraindications/Precautions

Contraindicated in: Hypersensitivity to capecitabine

or 5-FU; Severe renal impairment (CCr 30 mL/

min); OB: May cause fetal harm; Lactation: Potential for

serious adverse effects in nursing infants.

Use Cautiously in: Dihydropyrimidine dehydrogenase

deficiency (patients atqrisk of 5-FU toxicity);

Mild-moderate renal impairment (pstarting dose to

75% in patients with CCr 30–50 mL/min); Hepatic dysfunction;

Coronary artery disease; Rep: Women of reproductive

potential and men with female partners of

reproductive potential (use effective contraception);

Pedi: Safety not established; Geri:qrisk of severe diarrhea

in patients 80 yr.

Adverse Reactions/Side Effects

CNS: fatigue, headache, dizziness, insomnia. EENT:

eye irritation, epistaxis, rhinorrhea. CV: edema, chest

pain. GI: DIARRHEA, NECROTIZING ENTEROCOLITIS, abdominal

pain, anorexia, constipation, dysgeusia, hyperbilirubinemia,

nausea, stomatitis, vomiting, dyspepsia,

xerostomia. Derm: STEVENS-JOHNSON SYNDROME, TOXIC

EPIDERMAL NECROLYSIS, dermatitis, hand-and-foot syndrome,

nail disorder, alopecia, erythema, rashes. F

and E: dehydration. GU: acute renal failure,pfertility.

Hemat: anemia, leukopenia, thrombocytopenia.

MS: arthralgia, myalgia. Neuro: peripheral neuropathy.

Resp: cough, dyspnea. Misc: fever.

Interactions

Drug-Drug: Mayqrisk of bleeding with warfarin

(frequent monitoring of PT/INR recommended). Toxicityqby

concurrent leucovorin. Antacids mayqabsorption.

Mayqblood levels and risk of toxicity from

phenytoin (may need topphenytoin dose).qincidence

of acute renal failure with other nephrotoxic

drugs.

Drug-Food: Foodqabsorption, although capecitabine

should be given within 30 min after a meal.

Route/Dosage

PO (Adults): 1250 mg/m2 twice daily for 14 days, followed

by 7-day rest period; given in 3-wk cycles.

Renal Impairment

PO (Adults): CCr 30–50 mL/min—pinitial dose to

75% of usual.

Availability (generic available)

Tablets: 150 mg, 500 mg.