Capecitabine

Brand Names: Capecitabine

Drug Class: Nucleoside Metabolic Inhibitor

Overview

11 DESCRIPTION Capecitabine, USP is a nucleoside metabolic inhibitor. The chemical name is 5’-deoxy-5-fluoro-N-[(pentyloxy) carbonyl]-cytidine and has a molecular weight of 359.35. Capecitabine, USP has the following structural formula: Capecitabine, USP is a white to off-white crystalline powder. Freely soluble in methanol, soluble in acetonitrile and in ethanol. Sparingly soluble in water.

Mechanism of Action

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Capecitabine is metabolized to fluorouracil in vivo. Both normal and tumor cells metabolize fluorouracil to 5-fluoro-2’-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). These metabolites cause cell injury by two different mechanisms. First, FdUMP and the folate cofactor, N 5-10 -methylenetetrahydrofolate, bind to thymidylate synthase (TS) to form a covalently bound ternary complex. This binding inhibits the formation of thymidylate from 2’-deoxyuridylate. Thymidylate is the necessary precursor of thymidine triphosphate, which is essential for the synthesis of DNA, so that a deficiency of this compound can inhibit cell division.

Indications

  • 1 INDICATIONS AND USAGE Capecitabine tablet is a nucleoside metabolic inhibitor indicated for: Colorectal Cancer • adjuvant treatment of patients with Stage III colon cancer as a single agent or as a component of a combination chemotherapy regimen. ( 1.1 ) • perioperative treatment of adults with locally advanced rectal cancer as a component of chemoradiotherapy. ( 1.1 ) • treatment of patients with unresectable or metastatic colorectal cancer as a single agent or as a component of a combination chemotherapy regimen. ( 1.

Common Doses

  • 250 mg
  • 000 mg
  • 130 mg
  • 825 mg

Dosage

2 DOSAGE AND ADMINISTRATION Adjuvant Treatment of Colon Cancer • Single agent: 1,250 mg/m 2 twice daily orally for the first 14 days of each 21-day cycle for a maximum of 8 cycles. ( 2.1 ) In combination with Oxaliplatin-Containing Regimens: 1,000 mg/m 2 orally twice daily for the first 14 days of each 21-day cycle for a maximum of 8 cycles in combination with oxaliplatin 130 mg/m 2 administered intravenously on day 1 of each cycle. ( 2.2) Perioperative Treatment of Rectal Cancer • With Concomitant Radiation Therapy: 825 mg/m 2 orally twice daily ( 2.

Black Box Warning

WARNING: SERIOUS ADVERSE REACTIONS OR DEATH IN PATIENTS WITH COMPLETE DPD DEFICIENCY and BLEEDING WITH CONCOMITANT USE OF VITAMIN K ANTAGONISTS Increased risk of serious adverse reactions or death in patients with complete DPD deficiency Test patients for genetic variants of DPYD prior to initiating capecitabine tablets unless immediate treatment is necessary. Avoid use of capecitabine tablets in patients with certain homozygous or compound heterozygous DPYD variants that result in complete DPD deficiency [see Warnings and Precautions ( 5.1 )].

Contraindications

  • 4 CONTRAINDICATIONS Capecitabine tablets are contraindicated in patients with history of severe hypersensitivity reaction to fluorouracil or capecitabine [see Adverse Reactions ( 6.1 )]. History of severe hypersensitivity reactions to fluorouracil or capecitabine (4)

Side Effects

  • 6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Cardiotoxicity [see Warnings and Precautions ( 5.3 )] Diarrhea [see Warnings and Precautions ( 5.4 )] Dehydration [see Warnings and Precautions ( 5.5 )] Renal Toxicity [see Warnings and Precautions ( 5.6 )] Serious Skin Toxicities [see Warnings and Precautions ( 5.7 )] Palmar-Plantar Erythrodysesthesia Syndrome [see Warnings and Precautions ( 5.8 )] Myelosuppression [see Warnings and Precautions ( 5.9 )] Hyperbilirubinemia [see Warnings and Precautions ( 5.

Interactions

  • 7 DRUG INTERACTIONS • Allopurinol: Avoid concomitant use of allopurinol with capecitabine tablets. ( 7.1 ) • Leucovorin : Closely monitor for toxicities when capecitabine tablets is coadministered with leucovorin. ( 7.1 ) • CYP2C9 substrates : Closely monitor for adverse reactions when CYP2C9 substrates are coadministered with capecitabine tablets. ( 7.2 ) • Vitamin K antagonists : Monitor INR more frequently and dose adjust oral vitamin K antagonist as appropriate • Phenytoin : Closely monitor phenytoin levels in patients taking capecitabine tablets concomitantly with phenytoin and adjust...