CAPECITABINE tablet, film coated

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

CAPECITABINE (UNII: 6804DJ8Z9U) (CAPECITABINE - UNII:6804DJ8Z9U)

Available from:

American Health Packaging

INN (International Name):

CAPECITABINE

Composition:

CAPECITABINE 500 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Capecitabine tablets are indicated for the: - adjuvant treatment of patients with Stage III colon cancer as a single agent or as a component of a combination chemotherapy regimen. - perioperative treatment of adults with locally advanced rectal cancer as a component of chemoradiotherapy. - treatment of patients with unresectable or metastatic colorectal cancer as a single agent or as a component of a combination chemotherapy regimen. Capecitabine tablets are indicated for the: - treatment of patients with advanced or metastatic breast cancer as a single agent if an anthracycline- or taxane-containing chemotherapy is not indicated. - treatment of patients with advanced or metastatic breast cancer in combination with docetaxel after disease progression on prior anthracycline-containing chemotherapy. Capecitabine tablets are indicated for the: - treatment of adults with unresectable or metastatic gastric, esophageal, or gastroesophageal junction cancer as a component of a combination chemotherapy regimen. - treatment of adults with HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma who have not received prior treatment for metastatic disease as a component of a combination regimen. Capecitabine tablets are indicated for the adjuvant treatment of adults with pancreatic adenocarcinoma as a component of a combination chemotherapy regimen. Capecitabine is contraindicated in patients with history of severe hypersensitivity reaction to fluorouracil or capecitabine [see Adverse Reactions (6.1) ] . Risk Summary Based on findings in animal reproduction studies and its mechanism of action [see Clinical Pharmacology (12.1)] , capecitabine can cause fetal harm when administered to a pregnant woman. Available human data with capecitabine use in pregnant women is not sufficient to inform the drug-associated risk. In animal reproduction studies, administration of capecitabine to pregnant animals during the period of organogenesis caused embryolethality and teratogenicity in mice and embryolethality in monkeys at 0.2 and 0.6 times the exposure (AUC) in patients receiving the recommended dose of 1,250 mg/m 2 twice daily, respectively (see Data) . Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Oral administration of capecitabine to pregnant mice during the period of organogenesis at a dose of 198 mg/kg/day caused malformations and embryo lethality. In separate pharmacokinetic studies, this dose in mice produced 5’-DFUR AUC values that were approximately 0.2 times the AUC values in patients administered the recommended daily dose. Malformations in mice included cleft palate, anophthalmia, microphthalmia, oligodactyly, polydactyly, syndactyly, kinky tail and dilation of cerebral ventricles. Oral administration of capecitabine to pregnant monkeys during the period of organogenesis at a dose of 90 mg/kg/day, caused fetal lethality. This dose produced 5’-DFUR AUC values that were approximately 0.6 times the AUC values in patients administered the recommended daily dose. Risk Summary There is no information regarding the presence of capecitabine or its metabolites in human milk, or on its effects on milk production or the breastfed child. Capecitabine metabolites were present in the milk of lactating mice (see Data) . Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with capecitabine and for 1 week after the last dose. Data Lactating mice given a single oral dose of capecitabine excreted significant amounts of capecitabine metabolites into the milk. Capecitabine can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. Pregnancy Testing Verify pregnancy status in females of reproductive potential prior to initiating capecitabine. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with capecitabine and for 6 months after the last dose. Males Based on genotoxicity findings, advise males with female partners of reproductive potential to use effective contraception during treatment with capecitabine and for 3 months after the last dose [see Nonclinical Toxicology (13.1)]. Infertility Based on animal studies, capecitabine may impair fertility in females and males of reproductive potential [see Nonclinical Toxicology (13.1)]. The safety and effectiveness of capecitabine in pediatric patients have not been established. Safety and effectiveness were assessed, but not established in two single arm studies in 56 pediatric patients aged 3 months to <17 years with newly diagnosed gliomas. In both trials, pediatric patients received an investigational pediatric formulation of capecitabine concomitantly with and following completion of radiation therapy (total dose of 5580 cGy in 180 cGy fractions). The relative bioavailability of the investigational formulation to capecitabine was similar. The adverse reaction profile was consistent with that of adults, with the exception of laboratory abnormalities which occurred more commonly in pediatric patients. The most frequently reported laboratory abnormalities (per-patient incidence ≥ 40%) were increased ALT (75%), lymphocytopenia (73%), hypokalemia (68%), thrombocytopenia (57%), hypoalbuminemia (55%), neutropenia (50%), low hematocrit (50%), hypocalcemia (48%), hypophosphatemia (45%) and hyponatremia (45%). Of 7,938 patients with colorectal cancer who were treated with capecitabine, 33% were older than 65 years. Of the 4,536 patients with metastatic breast cancer who were treated with capecitabine, 18% were older than 65 years. Of 1,951 patients with gastric, esophageal, or gastrointestinal junction cancer who were treated with capecitabine, 26% were older than 65 years. Of 364 patients with pancreatic cancer who received adjuvant treatment with capecitabine, 47% were 65 years or older. No overall differences in efficacy were observed comparing older versus younger patients with colorectal cancer, gastric, esophageal or gastrointestinal junction cancer, or pancreatic cancer using the approved recommended dosages and treatment regimens. Older patients experience increased gastrointestinal toxicity due to capecitabine compared to younger patients. Deaths from severe enterocolitis, diarrhea, and dehydration have been reported in elderly patients receiving weekly leucovorin and fluorouracil [see Drug Interactions (7.1)] . The exposure of capecitabine and its inactive metabolites (5-DFUR and FBAL) increases in patients with CLcr <50 mL/min as determined by Cockcroft-Gault [see Clinical Pharmacology (12.3)] . Reduce the dosage for patients with CLcr of 30 to 50 mL/min [see Dosage and Administration (2.6)] . There is limited experience with capecitabine in patients with CLcr <30 mL/min, and a dosage has not been established in those patients. If no treatment alternative exists, capecitabine could be administered to such patients on an individual basis applying a reduced starting dose, close monitoring of a patient's clinical and biochemical data and dose modifications guided by observed adverse reactions. The exposure of capecitabine increases in patients with mild to moderate hepatic impairment. The effect of severe hepatic impairment on the safety and pharmacokinetics of capecitabine is unknown [see Clinical Pharmacology (12.3)] . Monitor patients with hepatic impairment more frequently for adverse reactions.

Product summary:

Capecitabine tablets, USP are available as follows: 500 mg: Peach to light peach, oblong, film-coated, biconvex, unscored tablets debossed with 191 on one side and 77 on the other side. Available in unit dose packages of 20 (2 x 10) NDC 60687-149-94. Storage and Handling Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. FOR YOUR PROTECTION: Do not use if blister is torn or broken. Keep this and all medications out of the reach of children. Capecitabine is a hazardous drug. Follow applicable special handling and disposal procedures. 1

Authorization status:

Abbreviated New Drug Application

Patient Information leaflet

American Health Packaging
----------
PATIENT INFORMATION
8414994/0917
Capecitabine (KAP e SYE ta been) Tablets USP, Film Coated
What is the most important information I should know about
capecitabine tablets?
Capecitabine tablets can cause serious side effects, including:
•
Capecitabine tablets can interact with blood thinner medicines, such
as warfarin (COUMADIN
®). Taking capecitabine tablets with these medicines can cause
changes in how fast your blood
clots, and can cause bleeding that can lead to death. This can happen
as soon as a few days after
you start taking capecitabine tablets, or later during treatment, and
possibly even within 1 month
after you stop taking capecitabine tablets. Your risk may be higher
because you have cancer, and
if you are over 60 years of age.
•
Before taking capecitabine tablets, tell your doctor if you are taking
warfarin
(COUMADIN) or another blood thinner medicine.
•
If you take warfarin (COUMADIN) or another blood thinner that is like
warfarin
(COUMADIN) during treatment with capecitabine tablets, your doctor
should do blood
tests often, to check how fast your blood clots during and after you
stop treatment with
capecitabine tablets. Your doctor may change your dose of the blood
thinner medicine if
needed.
See “What are the possible side effects of capecitabine tablets?”
for more information about side effects.
What are capecitabine tablets?
Capecitabine tablets are a prescription medicine used to treat people
with:
•
cancer of the colon that has spread to lymph nodes in the area close
to the colon (Dukes’ C stage),
after they have surgery.
•
cancer of the colon or rectum (colorectal) that has spread to other
parts of the body (metastatic).
•
breast cancer that has spread to other parts of the body (metastatic)
together with another medicine
called docetaxel after treatment with certain other anti-cancer
medicines have not worked.
•
breast cancer that has spread to other parts of the body and has not
improved after treatment with
paclitaxel and certain ot

Summary of Product characteristics

CAPECITABINE- CAPECITABINE TABLET, FILM COATED
AMERICAN HEALTH PACKAGING
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
CAPECITABINE TABLETS
SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
CAPECITABINE TABLETS.
CAPECITABINE TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 1998
WARNING: INCREASED RISK OF BLEEDING WITH CONCOMITANT USE OF VITAMIN K
ANTAGONISTS
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
ALTERED COAGULATION PARAMETERS AND/OR BLEEDING, INCLUDING DEATH, HAVE
BEEN REPORTED
IN PATIENTS TAKING CAPECITABINE CONCOMITANTLY WITH ORAL VITAMIN K
ANTAGONISTS. (5.1,
7.2)
MONITOR INTERNATIONAL NORMALIZED RATIO (INR) MORE FREQUENTLY AND
ADJUST THE DOSE OF THE
VITAMIN K ANTAGONIST AS APPROPRIATE. (7.2)
RECENT MAJOR CHANGES
Boxed Warning         
                  (12/2022)
Indications and Usage, Colorectal Cancer (1.1)  
           (12/2022)
Indications and Usage, Breast Cancer (1.2)  
            (12/2022)
Indications and Usage, Gastric, Esophageal, or
Gastroesophageal Junction Cancer (1.3)     
           (12/2022)
Indications and Usage, Pancreatic Cancer (1.4)     
        (12/2022)
Dosage and Administration (2.1 to 2.7)         
        (12/2022)
Contraindications (4)               
         (12/2022)
Warnings and Precautions (5.1 to 5.12)       
         (12/2022)
INDICATIONS AND USAGE
Capecitabine 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 unresectabl