Capecitabine Tablet IP 500mg Capnat

[Drug Name]

Generic Name: Capecitabine Tablets

Brand Name: Capecitabine Tablets (Aibin)

English Name: Capecitabine Tablets

Full Pinyin Code: KaPeiTaBinPian (AiBin)

[Main Ingredient] Capecitabine.

[Composition]

Chemical Name: 5’-deoxy-5-fluoro-N-[(pentyloxy)carbonyl]cytidine

Molecular Formula: C15H22FN3O6

[Description] This product consists of peach-colored film-coated tablets; when the coating is removed, the tablets appear off-white.

[Indications/Functions] Adjuvant Chemotherapy for Colon Cancer: Capecitabine is indicated as monotherapy for the adjuvant treatment of patients with Dukes’ C stage colon cancer who have undergone curative resection of the primary tumor and are suitable for single-agent fluoropyrimidine therapy. The disease-free survival (DFS) achieved with this treatment is non-inferior to that of the combination regimen of 5-fluorouracil and folinic acid (5-FU/LV). Neither Capecitabine monotherapy nor Capecitabine in combination chemotherapy regimens has been shown to prolong overall survival (OS); however, clinical trial data indicate that within combination chemotherapy regimens, Capecitabine may improve disease-free survival compared to 5-FU/LV. Physicians prescribing Capecitabine monotherapy for the adjuvant treatment of Dukes’ C stage colon cancer may refer to the aforementioned study results. The data supporting this indication are derived from international clinical studies (see the [Clinical Trials] section). Colorectal Cancer: Capecitabine monotherapy, or Capecitabine in combination with oxaliplatin (XELOX), is indicated for the first-line treatment of metastatic colorectal cancer. Combination Chemotherapy for Breast Cancer: Capecitabine, in combination with docetaxel, is indicated for the treatment of metastatic breast cancer that has failed prior chemotherapy regimens containing an anthracycline. Breast Cancer Monotherapy: Capecitabine may also be used alone for the treatment of metastatic breast cancer patients whose disease is refractory to both paclitaxel and anthracycline-containing chemotherapy regimens, or whose disease is refractory to paclitaxel and for whom further anthracycline-based treatment is contraindicated (e.g., patients who have already received a cumulative dose of 400 mg/m² of doxorubicin or a doxorubicin analog). Refractoriness is defined as continued disease progression during treatment (with or without an initial response), or relapse within 6 months of completing anthracycline-containing adjuvant chemotherapy. Gastric Cancer: Capecitabine is indicated for the first-line treatment of unresectable advanced or metastatic gastric cancer.

[Specifications] 0.5 g × 100 tablets

[Dosage and Administration] 2.5 g/m² daily, administered for 2 weeks, followed by a 1-week rest period. The total daily dose should be divided into two equal doses, taken orally with water approximately 30 minutes after meals—one in the morning and one in the evening. Treatment should be discontinued if the patient's condition continues to deteriorate or if intolerable toxicity develops.

[Adverse Reactions] Adverse reactions associated with this product may include the following: Gastrointestinal System: The most common adverse reactions are reversible gastrointestinal disturbances, such as diarrhea, nausea, vomiting, abdominal pain, stomatitis, etc. Severe (Grade 3–4) adverse reactions are relatively uncommon. Skin: Hand-foot syndrome occurs in nearly half of the patients treated with this product; it manifests as numbness, hypoesthesia, paresthesia, tingling sensations, absence of pain sensation or actual pain, skin swelling or erythema, desquamation, blistering, or severe pain. Dermatitis and alopecia are relatively common, though severe cases are rare. Systemic Adverse Reactions: Fatigue is frequently observed, but severe cases are extremely rare. Other common adverse reactions include mucositis, fever, weakness, somnolence, etc., none of which are typically severe. Nervous System: Headache, paresthesia, dysgeusia (taste disturbance), dizziness, insomnia, etc., are relatively common, though severe cases are rare. Cardiovascular System: Edema of the lower extremities is mild and uncommon. No other cardiovascular adverse effects have been reported to date. Hematologic System: Neutropenia is uncommon, and anemia is extremely rare; neither is typically severe. Other: Anorexia and dehydration are commonly observed, though severe cases are rare.

[Contraindications] This product is contraindicated in patients with a history of severe adverse reactions to the drug, those with a history of hypersensitivity to fluoropyrimidines (metabolites of capecitabine), and pregnant women.

[Precautions] Dose-limiting toxicities include: diarrhea, abdominal pain, nausea, gastritis, and hand-foot syndrome. Diarrhea occurs in nearly half of the patients treated with this product; patients experiencing severe diarrhea accompanied by dehydration should be closely monitored and treated with fluid replacement therapy. Diarrhea occurring 4 to 6 times daily, or involving nocturnal diarrhea, is classified as Grade 2; diarrhea occurring 7 to 9 times daily, or involving fecal incontinence or malabsorption, is classified as Grade 3; and diarrhea occurring 10 or more times daily, or involving gross bloody stools or a requirement for intravenous fluid replacement, is classified as Grade 4. If Grade 2, 3, or 4 diarrhea occurs, use of this product should be discontinued until the diarrhea resolves or decreases to Grade 1, at which point treatment may be resumed. Upon resuming treatment following Grade 3 or 4 diarrhea, the dosage should be reduced. Hand-foot syndrome occurs in nearly half of the patients using this product; however, most cases are Grade 1 or 2, while Grade 3 syndrome is uncommon. Most adverse reactions are reversible; while they may necessitate temporary interruption of treatment or dosage reduction, they rarely require permanent discontinuation of therapy. Please read the package insert carefully and use this product strictly according to physician's instructions.

[Pediatric Use] The efficacy and safety of this product have not been established in pediatric patients.

[Geriatric Use] No dosage adjustment is required. However, elderly patients (aged 65 years and older) may be more susceptible to the toxic effects of capecitabine than younger patients; therefore, they should be closely monitored.

[Use in Pregnant and Lactating Women] Clinical studies regarding the use of this product in pregnant women have not been conducted; however, it must be assumed that if this product is administered to such patients, it carries the potential to cause fetal harm. Animal studies have demonstrated that capecitabine can cause fetal death or malformations. These findings suggest that capecitabine derivatives may exert similar effects; therefore, this product must not be used in pregnant women. If this product is used during pregnancy, or if pregnancy occurs while using this product, the potential risk of fetal harm or teratogenicity associated with the drug must be taken into consideration. Women of childbearing potential must use effective contraception while taking this product. Although it is not known whether this product is excreted in human milk, because many drugs are excreted in human milk and have the potential to cause serious adverse reactions in nursing infants, it is recommended that women taking this product discontinue nursing.

【Drug Interactions】 Combination Therapy: No clinically significant adverse effects have been observed when this product is used in combination with a wide range of drugs, such as antihistamines, non-steroidal anti-inflammatory drugs (NSAIDs), morphine, paracetamol, aspirin, antiemetics, H2 receptor antagonists, etc. Protein Binding: The protein binding rate of capecitabine to serum proteins is low (64%); therefore, the potential for displacement interactions with drugs that bind tightly to proteins cannot be predicted. Interactions with Cytochrome P450 Enzymes: *In vitro* studies have shown that capecitabine has no effect on human hepatic microsomal P450 enzymes.

【Overdosage】 No adverse reactions attributed to drug overdose were observed during clinical trials of this product. However, in animal studies (in monkeys treated at a dose of 25.679 g/m²/day) and in human studies involving treatment at the maximum tolerated dose (3.514 g/m²/day), manifestations of drug overdose included nausea, vomiting, diarrhea, gastrointestinal irritation, gastrointestinal hemorrhage, and bone marrow suppression. Management of overdose should include dehydration therapy using diuretics, and dialysis if necessary.

【Pharmacology and Toxicology】 Capecitabine is an oral cytotoxic agent with selective activity against tumor cells. Capecitabine itself is not cytotoxic; however, it is converted into the cytotoxic agent 5-fluorouracil. This conversion occurs specifically at the tumor site—mediated by the tumor-associated angiogenic factor thymidine phosphorylase—thereby minimizing the damage caused by 5-fluorouracil to normal human cells. [Pharmacokinetics] Pharmacokinetic studies of capecitabine, conducted within a dose range of 502 to 3514 mg/m²/day, demonstrated that the pharmacokinetic parameters for capecitabine, 5'-deoxy-5-fluorocytidine, and 5'-deoxy-5-fluorouridine remained consistent between Day 1 and Day 14 of administration. On Day 14, the plasma concentration of 5-fluorouracil was 30% higher than that on Day 1; however, no further increase in concentration was observed by Day 22. At therapeutic doses, with the exception of 5-fluorouracil, the pharmacokinetic parameters of capecitabine and its metabolites are dose-proportional. Absorption: Following oral administration, capecitabine is rapidly and completely absorbed by the body, crossing the intestinal mucosa as an intact molecule; it is subsequently and completely converted into 5'-deoxy-5-fluorocytidine and 5'-deoxy-5-fluorouridine. Taking capecitabine with food affects its rate of absorption, but has a negligible effect on the Area Under the Curve (AUC) of 5'-deoxy-5-fluorouridine and its secondary metabolite, 5-fluorouracil. Distribution: *In vitro* studies using human serum indicate that the protein binding rates (primarily to albumin) for capecitabine, 5'-deoxy-5-fluorocytidine, and 5'-deoxy-5-fluorouridine are 54%, 10%, and 62%, respectively. Metabolism: Capecitabine is primarily metabolized within the liver and tumor tissues. It is first converted into 5'-deoxy-5-fluorocytidine via carboxylesterase, and subsequently into 5'-deoxy-5-fluorouridine via cytidine deaminase. Within tumor cells, under the catalytic action of the tumor-associated angiogenic factor thymidine phosphorylase, it is finally converted into 5-fluorouracil, thereby minimizing the potential damage of 5-fluorouracil to normal tissues. When administered at the recommended dosage, the mean serum Area Under the Curve (AUC) values for capecitabine, 5'-deoxy-5-fluorocytidine, 5'-deoxy-5-fluorouridine, and 5-fluorouracil are 7.40 mg·h/mL, 5.21 mg·h/mL, 21.7 mg·h/mL, and 1.63 mg·h/mL, respectively. The serum AUC for 5-fluorouracil is approximately 10-fold lower than that observed following intravenous administration (at a dose of 600 mg/m²). No cytotoxic activity distinct from that of 5-fluorouracil has been identified. Serum concentrations of capecitabine, 5'-deoxy-5-fluorocytidine, and 5'-deoxy-5-fluorouridine reach peak levels approximately 2 hours after administration. Subsequently, concentrations decline exponentially with a half-life ranging from 0.7 to 1.14 hours. Approximately 3 hours after administration, the 5-fluorouracil degradation product, α-fluoro-β-alanine, reaches its peak concentration, with a half-life of 3 to 4 hours. Elimination: Capecitabine metabolites are primarily eliminated via the kidneys; 71% of the administered dose is recovered in the urine, with α-fluoro-β-alanine constituting the major metabolite (52%).

[Storage] Store in a cool, dry place.

[Packaging] 0.5 g × 100 tablets per box.

[Shelf Life] 24 months.

Product Specifications

Product Name: Capecitabine Tablets (Xeloda) 500 mg × 100 tablets | Capecitabine Tablet IP 500 mg (Natco)

Common Name: Capecitabine Tablets

Active Ingredient: Capecitabine

Dosage Form: Tablets

Specification: 500 mg × 100 tablets

Manufacturer: Natco Pharma (India)

Indications: Adjuvant Chemotherapy for Colon Cancer: Capecitabine is indicated as monotherapy for the adjuvant treatment of patients with Dukes’ C stage colon cancer who have undergone curative resection of the primary tumor and are suitable candidates for single-agent fluoropyrimidine therapy. Its disease-free survival (DFS) is non-inferior to that of the combination regimen of 5-fluorouracil and leucovorin (5-FU/LV). Neither capecitabine monotherapy nor its use in combination chemotherapy regimens has been shown to prolong overall survival (OS); however, trial data indicate that, within combination chemotherapy regimens, capecitabine may improve disease-free survival compared to 5-FU/LV. Physicians may refer to the aforementioned study results when prescribing capecitabine monotherapy for the adjuvant treatment of Dukes’ C stage colon cancer. The data supporting this indication are derived from international clinical studies (see the [Clinical Trials] section). Colorectal Cancer: Capecitabine monotherapy or its combination with oxaliplatin (XELOX) is indicated for the first-line treatment of metastatic colorectal cancer. Breast Cancer (Combination Chemotherapy): Capecitabine may be used in combination with docetaxel for the treatment of metastatic breast cancer that has failed prior chemotherapy regimens containing anthracyclines. Breast Cancer (Monotherapy): Capecitabine may also be used as a single agent for the treatment of patients with metastatic breast cancer who are resistant to both paclitaxel and anthracycline-containing chemotherapy regimens, or who are resistant to paclitaxel and for whom further anthracycline treatment is contraindicated (e.g., having already received a cumulative dose of 400 mg/m² of doxorubicin or its equivalents). Resistance is defined as disease progression during treatment (with or without an initial response), or relapse occurring within 6 months of completing adjuvant chemotherapy containing anthracyclines. Gastric Cancer: Capecitabine is indicated for the first-line treatment of advanced or metastatic gastric cancer that is not amenable to surgery.

Dosage and Administration: 2.5 g/m² daily, administered for 2 weeks, followed by a 1-week rest period. The total daily dose should be divided into two equal doses, taken orally with water approximately 30 minutes after a meal—one in the morning and one in the evening. Treatment should be discontinued if the patient's condition continues to deteriorate or if intolerable toxicity develops.