Capiibine Special Precautions

Coagulopathy: Capecitabine may increase the anticoagulant effects of warfarin; the bleeding events including death, have occurred with concomitant use clinically significant increases in PT and INR have occurred within several days to months after capecitabine initiation (in patients previously stabilized on anticoagulants), and may continue up to 1 month after capecitabine discontinuation. May occur in patients with or without liver metastases. Monitor PT and INR frequently and adjust anticoagulation dosing accordingly. An increased risk of coagulopathy is correlated with cancer diagnosis and age older than 60 years.
GI toxicity: May cause diarrhea (may be severe); median time to first occurrence of grade 2 to 4 diarrhea was 34 days and median duration of grades 3 or 4 diarrhea was 5 days. Withhold treatment for grade 2 to 4 diarrhea subsequent doses should be reduced after grade 3 or 4 diarrhea on occurrence of grade 2 diarrhea. Antidiarrheal therapy (eg, loperamide) is recommended. Dehydration may occur rapidly in patients with diarrhea, nausea, vomiting, anorexia, and/or weakness; adequately hydrate prior to treatment initiation. Elderly patients may be at higher risk for dehydration interrupt treatment for grade 2 or higher dehydration; correct precipitating factors and ensure rehydration prior to resuming therapy; may require dose modification (based on precipitating factor). Necrotizing enterocolitis has been reported.
Cardiotoxicity: Cardiotoxicity has been observed with capecitabine including myocardial infarction, ischemia, angina, dysrhythmias, cardiogenic arrest, cardiac failure, sudden death, electrocardiogram changes, and cardiomyopathy. These adverse reactions may be more common in patients with a history of coronary artery disease.
Dihydropyrimidine dehydrogenase deficiency: Patients with certain homozygous or heterozygous mutations of the Dihydropyrimidine dehydrogenase (DPD) enzymes are at increased risk for acute early - onset (potentially severe, life threatening, or fatal) toxicity due to total or near total absence of DPD activity. Toxicity may include mucositis/stomatitis, diarrhea, neutropenia and neurotoxicity. Patients with partial DPD activity are also at risk for severe, life threatening or fatal toxicity. May require therapy interruption or permanent discontinuation, depending on the onset duration and severity of toxicity observed. No capecitabine dose has been shown to be safe in patients with complete DPD deficiency, data are insufficient to recommend a dose in patients with partial DPD deficiency.
Dermatologic toxicity: Stevens - Johnson syndrome and toxic epidermal necrolysis (TEN) have been reported (some fatal); permanently discontinue capecitabine if a severe dermatologic or mucocutaneous reaction occurs.
Hand-foot syndrome: May cause hand-and-foot syndrome (Palmar-plantar erythrodysesthesia or chemotherapy-induced acral erythema); characterized by numbness, dysesthesia/paresthesia, tingling, painless or painful swelling, erythema, desquamation, blistering and severe pain. The median onset is 79 days (range: 11 to 360 days). If grade 2 or 3 hand-and-foot syndrome occurs, interrupt administration of capecitabine until the event resolves or decreases in intensity to grade 1. Following grade 3 hand-and-foot syndrome, decrease subsequent doses of therapy.
Hepatotoxicity: Grade 3 and 4 hyperbilirubinemia have been observed in patients with and without hepatic metastases at baseline (median onset; 64 days). Transaminase and alkaline phosphatase elevation have also been reported. If capecitabine-related grade 3 or 4 hyperbilirubinemia occurs, interrupt treatment until bilirubin 3 or less times the ULN. Bilirubin elevations may require dose reductions.
Bone marrow suppression: Bone marrow suppression may occur, hematologic toxicity is more common when used in combination therapy; use with caution; dosage adjustments may be required. The product labeling recommends that patients with baseline platelets <100,000/mm³ and/or neutrophils < 1,500/mm³ not receive capecitabine therapy and also to withhold therapy for grade 3 or 4 hematologic toxicity during treatment.
Fluorouracil/leucovorin (FU/LV): In patients with colorectal cancer, treatment with capecitabine immediately following 6 weeks of FU/LV therapy has been associated with an increased incidence of grade ≥3 toxicity, when compared to patients receiving the reverse sequence, capecitabine (two 3-week courses) followed by Fluorouracil/leucovorin.
Fluoropyrimidine overdose: Uridine triacetate (formerly called vistonuridine), has been studied in cases of fluoropyrimidine overdose. In a clinical study of 98 patients who received uridine triacetate for fluorouracil toxicity (due to overdose, accidental capecitabine ingestion, or possible DPD deficiency), 96 patients recovered fully. Of 17 patients receiving uridine triacetate beginning within 8 to 96 hours after fluorouracil overdose, all patients fully recovered. An additional case report describes accidental capecitabine ingestion by a 22-month-old child; uridine triacetate was initiated approximately 7 hours after exposure. The patient received uridine triacetate every 6 hours for a total of 20 doses through nasogastric tube administration; he was asymptomatic throughout his course and was discharged with normal laboratory values.
Hazardous agent: Use appropriate precautions for receiving, handling, administration, and disposal. (NIOSH 2016 [group 1]).
Renal function impairment: Dehydration may occur, resulting in acute renal failure (may be fatal); concomitant use with nephrotoxic agents and baseline renal dysfunction may increase the risk. Use with caution in patients with mild to moderate renal impairment; reduce dose with moderate impairment (exposure to capecitabine and metabolites is increased) and carefully monitor and reduce subsequent dose (with any grade 2 or higher adverse effect) with mild to moderate impairment. Use is contraindicated in severe impairment.
Hepatic impairment: Use with caution in patients with mild to moderate hepatic impairment due to liver metastases. The effect of severe hepatic impairment has not been studied.
Monitoring: Renal function should be estimated at baseline to determine initial dose. During therapy, complete blood cell count (CBC) with differential, hepatic function, and renal function should be monitored. Monitor INR closely if receiving concomitant warfarin. Pregnancy test prior to treatment initiation (in females of reproductive potential). Monitor for diarrhea, dehydration, hand-foot syndrome, Stevens-Johnson syndrome, toxic epidermal necrolysis, stomatitis, and cardiotoxicity.
Use in the Elderly: Use with caution in patients ≥60 years of age; the incidence of treatment-related adverse events may be higher.