Xeloda (Capecitabine) is a prodrug that is converted to the active drug fluorouracil. It inhibits RNA and DNA synthesis and is used as a chemotherapeutic agent in the treatment of the following disorders:

• Treatment of metastatic Breast cancer resistant to both paclitaxel and an anthracycline-containing regimen or resistant to paclitaxel in patients for whom further anthracycline therapy is not indicated as monotherapy or in combination with docetaxel after the failure of a prior anthracycline-containing regimen.
• As a first-line treatment of Colorectal cancer when treatment with a fluoropyrimidine monotherapy is preferred or as adjuvant therapy of Dukes' C colon cancer after complete resection of the primary tumor.

  ---

Off Label Uses of Xeloda (Capecitabine) in Adults include:

• Anal cancer
• Breast cancer as adjuvant therapy
• Esophageal and gastric cancers
• Hepatobiliary cancer as adjuvant therapy
• Advanced Hepatobiliary Cancers
• Metastatic or unresectable Neuroendocrine islet cell tumors
• Refractory Ovarian, fallopian tube, or peritoneal cancers
• Pancreatic cancer as adjuvant therapy
• Locally advanced or metastatic Pancreatic cancer
• Unknown primary cancer

Xeloda (Capecitabine) Dose in Adults

Xeloda use in the treatment of metastatic Breast cancer:

• 1,250 mg/m2 orally twice a day for 2 weeks, every 21 days (as monotherapy or in combination with docetaxel).

Off-label dose in metastatic Breast cancer:

• Adults 65 years or older:
  • 1,000 mg/m2 orally twice a day on days 1 - 14 of a 21-day treatment cycle for a minimum of 2 and up to 6 cycles or longer.

    ---

As off-label combination therapy in metastatic Breast cancer:

• 1,000 mg/m2 orally twice a day (in combination with ixabepilone) on days 1 - 14 of a 3-week cycle until disease progression or unacceptable toxicity.

As off-label combination therapy in HER2+ metastatic breast cancer:

• 1,000 mg/m2 orally twice a day in combination with lapatinib on days 1 - 14 of a 3-week cycle until disease progression or unacceptable toxicity or
• 1,250 mg/m2 orally twice a day in combination with trastuzumab on days 1 - 14 of a 3-week cycle.

  ---

As off-label first-line combination therapy in HER 2+ breast cancer with brain metastasis. 

• 1,000 mg/m2 orally twice a day in combination with lapatinib on days 1 - 14 of a 3-week cycle until disease progression or unacceptable toxicity.

As off-label adjuvant therapy in HER2 negative breast cancer patients with residual disease after neoadjuvant therapy and surgery.

• 1,250 mg/m2 orally twice a day on days 1 - 14 of a 21-day treatment cycle for 6 -  8 cycles.

Xeloda use in the treatment of metastatic Colorectal cancer:

• 1,250 mg/m2 orally twice a day for 2 weeks, every 21 days.

As off-label combination therapy in Colorectal cancer:

• 1,000 mg/m2 orally twice a day in combination with oxaliplatin on days 1 - 14 of a 3-week cycle for 8 or 16 cycles.

Adjuvant therapy in Dukes' C colon cancer:

• 1,250 mg/m2 orally twice a day for 2 weeks, every 21 days, for a recommended total duration of 24 weeks (8 cycles of 2 weeks each of drug administration and 1 week rest period).

Off label use in the treatment of Anal carcinoma:

• 825 mg/m2 orally twice a day 5 days per week (Monday through Friday) (in combination with mitomycin [on day 1 only]) during radiation therapy or
• 825 mg/m2 orally twice a day on radiation therapy days (in combination with mitomycin [on day 1 only] and radiation therapy)

  ---

Off Label Use in the treatment of Esophageal and gastric cancers:

• Preoperative or definitive chemoradiation:
  • 800 mg/m2 orally twice a day on days 1 to 5 weekly for 5 weeks in combination with cisplatin and radiation or
  • 625 mg/m2 orally twice a day on days 1 to 5 weekly for 5 weeks in combination with oxaliplatin and radiation.
• Postoperative chemoradiation:
  • 625 to 825 mg/m2 orally twice a day during radiation therapy
• Locally advanced or metastatic (chemoradiation not indicated):
  • 1,000 to 1,250 mg/m2 orally twice a day on days 1 to 14 of a 3-week cycle as monotherapy or in combination with cisplatin with or without trastuzumab) or
  • 625 mg/m2 orally twice a day on days 1 - 21 of a 3-week cycle for up to 8 cycles in combination with epirubicin and cisplatin or oxaliplatin.

    ---

Off label use as adjuvant therapy in the treatment of Hepatobiliary cancer:

• 1,250 mg/m2 orally twice a day on days 1 - 14 of a 21-day treatment cycle for 8 cycles.

Off label use in the treatment of advanced Hepatobiliary cancers:

• 650 mg/m2 orally twice a day on days 1 to 14 of a 3-week cycle in combination with gemcitabine or
• 1,000 mg/m2 orally twice a day on days 1 to 14 of a 3-week cycle in combination with oxaliplatin or
• 1,250 mg/m2 orally twice a day on days 1 to 14 of a 3-week cycle in combination with cisplatin
• all regimens should be continued until disease progression or unacceptable toxicity develops

  ---

Off label use in the treatment of metastatic or unresectable Neuroendocrine pancreatic or islet cell tumors:

• 750 mg/m2 orally twice a day on days 1 to 14 of a 4-week cycle in combination with temozolomide

Off label use in the treatment of platinum-refractory Ovarian, fallopian tube, or peritoneal cancer:

• 1,000 mg/m2 orally twice a day on days 1 - 14 of a 3-week cycle until disease progression or unacceptable toxicity.

Off label use as adjuvant therapy in the treatment of Pancreatic cancer:

• 1,660 mg/m2 /day in 2 divided doses on days 1 - 21 every 28 days for 6 cycles beginning within 12 weeks of resection in combination with gemcitabine.
• Therapy should be initiated within 8 weeks of resection of the tumor according to the recommendations by the American Society of Clinical Oncology guidelines.

  ---

Off label use in treatment of metastatic Pancreatic cancer:

• 1,250 mg/m2 orally twice a day on days 1 - 14 of a 3-week cycle or
• 830 mg/m2 orally twice a day on days 1 to 21 of a 4-week cycle in combination with gemcitabine until disease progression or unacceptable toxicity.

  ---

Off label use in the treatment of Unknown primary cancer:

• 1,000 mg/m2 orally twice a day on days 1 to 14 of a 3-week cycle for up to 6 cycles or until disease progression in combination with oxaliplatin or
• 800 mg/m2 orally twice a day on days 1 to 14 of a 3-week cycle for up to 8 cycles or until disease progression or unacceptable toxicity in combination with carboplatin and gemcitabine.

Pregnancy Risk Factor D

• Significant fetal harm has been reported with its use based on animal reproduction studies.
• Prior to initiating therapy, a pregnancy test should be performed.
• Females of reproductive age group should use effective contraception during its use and up to six months after the last dose.
• Males with female partners of reproductive age groups should also use effective contraception and up to 3 months after the last dose.

Xeloda (Capecitabine) use during breastfeeding:

• It is unknown whether xeloda can be found in breastmilk. 
• The manufacturer suggests that you stop breastfeeding during therapy and for up to two weeks after your last dose 

Xeloda dose in patients with Renal impairment at treatment initiation:

• CrCl of 51 mL/minute or more: No dosage adjustment necessary.
• CrCl of 30 - 50 mL/minute: Reduce the dose by 25% of the usual dose.
• CrCl of less than 30 mL/minute: Use is contraindicated

Xeloda dose in patients with hepatic impairment at treatment initiation:

• Mild to moderate impairment: No dose adjustment is necessary however, the patient should be carefully monitored.
• Severe hepatic impairment: The manufacturer has not recommended any dose adjustment (not studied in patients with liver disease).
• Hepatotoxicity during therapy: Interrupt therapy in patients with grade 3 or 4 hyperbilirubinemia unless bilirubin levels are less than 3 times the upper limit of normal.

Common Side Effects Of Xeloda (Capecitabine) Include:

• Cardiovascular:
  • Edema
• Central nervous system:
  • Fatigue
  • Paresthesia
  • Pain
• Dermatologic:
  • Palmar-plantar erythrodysesthesia
  • Dermatitis
• Gastrointestinal:
  • Diarrhea
  • Nausea
  • Vomiting
  • Abdominal pain
  • Decreased appetite
  • Stomatitis
  • Anorexia
  • Constipation
• Hematologic & oncologic:
  • Lymphocytopenia
  • Anemia
  • Neutropenia
  • Thrombocytopenia
• Hepatic:
  • Hyperbilirubinemia
• Neuromuscular & skeletal:
  • Asthenia
• Ophthalmic:
  • Eye irritation
• Miscellaneous:
  • Fever

Less Common Side Effects of capecitabine:

• Cardiovascular:
  • Venous thrombosis
  • Chest pain
  • Atrial fibrillation
  • Bradycardia
  • Cerebrovascular accident
  • Collapse
  • Extrasystoles
  • Hypertension
  • Hypotension
  • Myocarditis
  • Pericardial effusion
  • Pulmonary embolism
  • Tachycardia
  • Ventricular premature contractions
• Central nervous system:
  • Lethargy
  • Peripheral sensory neuropathy
  • Headache
  • Insomnia
  • Dizziness
  • Ataxia
  • Confusion
  • Depression
  • Mood changes
  • Abnormal gait
  • Dysarthria
  • Dysphasia
  • Encephalopathy
  • Equilibrium disturbance
  • Irritability
  • Loss of consciousness
  • Myasthenia
  • Sedated state
  • Vertigo
• Dermatologic:
  • Nail disease
  • Skin discoloration
  • Skin rash
  • Alopecia
  • Erythema of skin
  • Dermal ulcer
  • Pruritus
• Endocrine & metabolic:
  • Dehydration
  • Cachexia
  • Hot flash
  • Hypertriglyceridemia
  • Hypokalemia
  • Hypomagnesemia
  • Increased thirst
  • Weight gain
  • Decreased or increased serum calcium
• Gastrointestinal:
  • Gastrointestinal motility disorder
  • Upper Gastrointestinal inflammation
  • Oral discomfort
  • Dyspepsia
  • Upper abdominal pain
  • Intestinal obstruction
  • Dysgeusia
  • Gastrointestinal hemorrhage
  • Abdominal distention
  • Dysphagia
  • Gastric ulcer
  • Gastroenteritis
  • Rectal pain
  • Toxic megacolon
  • Sore throat
• Hematologic & oncologic:
  • Disorder of hemostatic components of blood
  • Hemorrhage
  • Leukopenia
  • Lymphedema
  • Pancytopenia
  • Granulocytopenia
  • Immune thrombocytopenia
• Hepatic:
  • Abnormal hepatic function tests
  • Ascites
  • Cholestatic hepatitis
  • Hepatic fibrosis
  • Hepatitis
  • Increased serum alanine aminotransferase
• Hypersensitivity:
  • Drug-induced hypersensitivity reaction
• Infection:
  • Viral infection
  • Fungal infection
  • Sepsis
• Neuromuscular & skeletal:
  • Back pain
  • Myalgia
  • Arthralgia
  • Limb pain
  • Arthritis
  • Ostealgia
  • Tremor
• Ophthalmic:
  • Visual disturbance
  • Conjunctivitis
  • Keratoconjunctivitis
• Renal:
  • Renal insufficiency
• Respiratory:
  • Cough
  • Pharyngeal disease
  • Asthma
  • Bronchitis
  • Bronchopneumonia
  • Dyspnea
  • Flu-like symptoms
  • Hemoptysis
  • Hoarseness
  • Pneumonia
  • Respiratory distress
  • Epistaxis
  • Laryngitis
• Miscellaneous:
  • Radiation recall phenomenon

Frequency not defined:

• Cardiovascular:
  • Angina pectoris
  • Cardiac arrhythmia
  • Cardiac failure
  • Cardiomyopathy
  • ECG changes
  • Ischemic heart disease
  • Myocardial infarction
• Gastrointestinal:
  • Necrotizing enterocolitis

Contraindications to Xeloda (capecitabine)

• Allergy to any drug, fluorouracil or component of the formulation
• Severe renal impairment (CrCl >30 mL/minute).
• Complete deficiency in dihydropyrimidine (DPD) activity is known
• Concomitant administration of the drug sorivudine and other chemically related analogues, such as brivudine.

Warnings and Precautions

• Suppression of bone marrow
  • Patients who have a lower baseline platelet count than 100000/mm3 or a lower neutrophil count than 1500/mm3 shouldn't be given Xeloda.
  • If grade 3 or 4 hematologic toxicities develop during therapy, it is important to withhold treatment.
  • Patients receiving combination therapy are more likely to experience bone marrow suppression.
• Cardiotoxicity
  • Xeloda (capecitabine therapy) has been shown to cause cardiotoxicity.
  • Cardiac toxicity is more common in patients with an underlying history of coronary heart disease.
• Dermatologic toxicities:
  • It has been linked to severe mucocutaneous reactions, including fatal cases of Stevens Johnson syndrome and toxic epidermal Necrolysis (TEN).
  • In severe reactions, therapy should be stopped immediately
• Gastrointestinal toxicities:
  • This is often associated with severe diarrhea. You should suspend treatment while you are undergoing treatment. Then, start antidiarrheal medications like loperamide and intravenous and oral hydration.
  • It has been reported that it can cause necrotizing enterocolitis.
• Hand-and-foot syndrome
  • Capecitabine is often used to treat the hand-and foot syndrome. Also known as palmar-plantar or chemotherapy-induced Acral Erythema, it has been linked to capecitabine.
  • It can cause numbness, paresthesia, tingling and painless or painful swelling.
  • In grade 3 or 4, therapy should be stopped. You may also need to adjust the doses in subsequent doses.
• Hepatotoxicity
  • Patients can develop hyperbilirubinemias of Grade 3 or 4 and raised transaminases and alkalinephosphatase.
  • The treatment should be stopped until the bilirubin levels are below 3 times the normal upper limit.
• Deficiency in dihydropyrimidine hydrogenase
  • Patients who have complete or partial dihydropyrimidine-dehydrogenase enzyme (DPD), are at greater risk of severe and fatal toxicities.
  • Toxicity can include stomatitis and mucositis as well as diarrhea, neutropenia, neurotoxicity, and respiratory distress.
  • Based on the severity and extent of toxic effects, it is worth considering dosing adjustment or complete withdrawal.
• Hepatic impairment
  • Patients with liver disease should use it with caution.
• Renal impairment
  • It is possible for acute renal failure to occur if the medication is used. Patients with impaired baseline renal function and those taking concomitant drugs such as nephrotoxic substances are more likely to develop kidney failure.
  • In mild to moderate renal impairment, adjust the dose. It is contraindicated in severe renal impairment. 

Capecitabine: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• Baseline renal function is used to determine the initial dose, and then it is used periodically throughout therapy.
• During therapy, monitor CBC with differential counts.
• You should monitor the patient for any adverse drug reactions such as diarrhea, Stevens-Johnson Syndrome, toxic epidermal Necrolysis, hand foot syndrome, stomatitis and cardiotoxicity.
• If the patient is receiving concomitant warfarin, monitor compliance to therapy and INR.
• Before initiating therapy, perform a pregnancy test on females in the reproductive age group.

How to administer Xeloda (Capecitabine)?

• It should be administered with water within 30 minutes after a meal in two divided doses 12 hours apart.
• Avoid cutting or crushing the tablets. Swallow the tablets whole.

Mechanism of action of Xeloda (Capecitabine):

• Xeloda (Capecitabine), is a prodrug for fluorouracil. 
• Hydrolysis converts it into fluorouracil, the active drug in the liver.
• Fluorouracil blocks thymidylate synthesise and, to a lesser extent, interferes with DNA and RNA synthesis in G and S phases.

It is growing rapidlyIntakeAnd less than 60% are actually prescription drugsProtein-bound It isMetabolizedThe liver converts inactive metabolites 5’-deoxy-5–fluorocytidine to 5'-deoxy-5–fluorouridine.It has a half life elimination time of approximately 0.75 hours. It takes time to get therePeak plasma concentrationIt takes between 1.5 and 2 hours. It isExcretedPrimarily via urine.  

International brands of Xeloda (Capecitabine):

• ACH-Capecitabine
• SANDOZ Capecitabine
• TARO-Capecitabine
• TEVA-Capecitabine
• Xeloda
• Aceda
• Ai Bin
• Apecitab
• Arxeda
• Capebina
• Capecitabina
• Capeda
• Capetero
• Capibine
• Capit
• Caponko
• Captabine
• Capvex
• Catacibin
• Caxeta
• Celabin
• Cipatin
• Coloxet
• Ecansya
• Intacape
• Naprocap
• Taceral
• Tutabin
• Xalvobin
• Xelcip
• Xelobig
• Xelocan
• Xeloda
• Xeltabine
• Xitabin
• Zapecine

Xeloda Brands in Pakistan