Capecitabine

Introduction

Capecitabine is an oral chemotherapy medication used in the treatment of various cancers, including breast cancer, colorectal cancer, and gastric cancer. It is a prodrug that is converted into the active drug 5-fluorouracil (5-FU) in the body, which inhibits cancer cell growth and proliferation.

Uses

Capecitabine is primarily used for:

Adjuvant therapy for stage III colon cancer following surgery.
First-line treatment of metastatic colorectal cancer, either alone or in combination with other drugs.
Advanced or metastatic breast cancer, often in combination with docetaxel.
Gastric cancer as part of combination therapy.

It is used when other treatments are not suitable or have failed. Its oral administration provides an alternative to intravenous chemotherapy.

Brand Name	Capecitabine
Type
Weight
Generic	Capecitabine
Manufacturer
Available in	English বাংলা

Mechanism of Action

Capecitabine is a prodrug that is converted into 5-fluorouracil (5-FU) in the liver and tumor tissues. 5-FU interferes with DNA synthesis by inhibiting thymidylate synthase, an enzyme crucial for the synthesis of thymidine, a DNA building block. This inhibition leads to the disruption of DNA replication and repair, ultimately inducing cancer cell death.

How Long Does It Take to Work?

Patients may start to see clinical improvement within a few weeks of starting capecitabine therapy. However, the full therapeutic effect can take several cycles of treatment to become apparent, with tumor response often assessed after 8 to 12 weeks of therapy.

Absorption

Capecitabine is well absorbed from the gastrointestinal tract. Peak plasma concentrations are typically reached within 1 to 2 hours after oral administration. The drug’s bioavailability is about 70%, and it is rapidly converted to 5-FU in the liver and tumor tissues.

Route of Elimination

Capecitabine and its metabolites are primarily eliminated through the kidneys. Approximately 90% of the drug is excreted in the urine, with less than 5% of the dose excreted in feces. The metabolism to 5-FU is also a significant pathway for elimination.

Dosage

Monotherapy: 1250 mg/m2 twice daily orally for 2 weeks followed by a one-week rest period in 3-week cycles

Adjuvant treatment: Is recommended for a total of 6 months (8 cycles)

In combination with docetaxel: The recommended dose of Capecitabine is 1250 mg/m2 twice daily for 2 weeks followed by a 7-day rest period, combined with docetaxel at 75 mg/m2 as a 1-hour IV infusion every 3 weeks. Capecitabine dosage may need to be individualized to optimize patient management. Capecitabine dosage has to be reduced by 25% in patients with moderate renal impairment.

Example: A person whose body weight is 64 kg and height is 1.64 m has a body surface area of 1.7 m2 and should take 4 tablets of 500 mg and 1 tablet of 150 mg two times daily.

The tablets should be taken in morning and evening as prescribed by doctor. The tablets should be taken within 30 minutes after the end of a meal (breakfast and dinner) and swallowed whole with water. Tablets should not be cut or crushed. Capecitabine should only be prescribed by a doctor experienced in the use of anticancer medicines.

The standard dosage of capecitabine is:

For colon cancer: 1,250 mg/m² twice daily for 14 days followed by 7 days of rest, in combination with oxaliplatin.
For metastatic breast cancer: 1,250 mg/m² twice daily for 14 days, followed by 7 days of rest, often in combination with docetaxel.
For gastric cancer: 1,000 mg/m² twice daily for 14 days, followed by 7 days of rest, usually in combination with cisplatin and an intravenous fluoropyrimidine.

Dosage adjustments may be necessary based on the patient’s renal function, liver function, and tolerance to the medication.

Administration

Capecitabine is administered orally in the form of tablets. It should be taken with water within 30 minutes after a meal, typically twice daily. The exact dosing schedule may vary based on the specific cancer being treated and the patient’s overall health.

Side Effects

Common side effects of capecitabine include:

Gastrointestinal symptoms such as nausea, vomiting, diarrhea, and mucositis.
Hand-foot syndrome, characterized by redness, swelling, and pain in the palms of the hands and soles of the feet.
Fatigue and weakness.
Myelosuppression, including anemia, leukopenia, and thrombocytopenia.

Serious side effects may include severe gastrointestinal symptoms, liver dysfunction, and infections due to immunosuppression.

Toxicity

Toxicity can manifest as severe gastrointestinal distress, dehydration, and significant myelosuppression. The primary management of toxicity involves dose reduction or discontinuation of therapy, supportive care, and symptomatic treatment. Monitoring blood counts and liver function is essential during treatment.

Precautions

Precautions include:

Regular monitoring of blood counts and liver function tests to detect adverse effects early.
Caution in patients with renal impairment, as dose adjustments may be necessary.
Monitoring for hand-foot syndrome and gastrointestinal toxicity.

Patients should be advised to report any severe side effects or signs of infection promptly.

Interaction

Capecitabine may interact with other medications, including:

Anticoagulants such as warfarin, which may increase the risk of bleeding.
Drugs affecting hepatic metabolism, which may alter capecitabine levels.
Phenytoin, which may affect capecitabine metabolism.

It is important to inform healthcare providers of all other medications being taken to manage potential interactions.

Disease Interaction

Use capecitabine with caution in patients with:

Pre-existing liver disease or significant hepatic impairment.
Renal impairment, which may require dose adjustment.
History of gastrointestinal disease, especially if it affects absorption or function.

Regular monitoring and dose adjustments may be needed based on the patient's condition.

Drug Interaction

Drug interactions include:

Increased risk of bleeding when used with anticoagulants or antiplatelet agents.
Possible alterations in the efficacy or metabolism of other concurrently administered drugs.

Close monitoring is recommended to avoid or manage drug interactions.

Food Interactions

Capecitabine should be taken with food, within 30 minutes of a meal, to reduce gastrointestinal irritation. Food intake does not significantly affect the absorption of capecitabine, but taking it with food may help minimize side effects.

Pregnancy Use

Capecitabine is classified as a Category D drug for pregnancy, indicating that there is evidence of risk to the fetus based on human studies. It should be used during pregnancy only if the potential benefit justifies the potential risk. Women of childbearing potential should use effective contraception during treatment.

Lactation Use

Capecitabine is excreted in breast milk. It is generally advised to avoid breastfeeding during capecitabine treatment due to potential risk to the infant. Women should consult their healthcare provider regarding alternatives or the need to discontinue breastfeeding.

Acute Overdose

In the case of acute overdose, symptoms may include severe gastrointestinal toxicity, dehydration, and signs of significant myelosuppression. Treatment involves supportive care, including hydration, symptomatic management, and monitoring for adverse effects. There is no specific antidote for capecitabine overdose.

Contraindication

Capecitabine is contraindicated in patients with:

Known hypersensitivity to capecitabine or any of its components.
Severe hepatic impairment or active liver disease.
Severe renal impairment, as it may affect drug clearance.

Caution should be used in patients with a history of significant adverse reactions to other chemotherapy agents.

Use Direction

Take capecitabine as prescribed by your healthcare provider. Adhere to the dosing schedule and administration instructions, typically taking the medication twice daily with food. Complete the full course of therapy and consult your healthcare provider if you have any questions or experience severe side effects.

Storage Conditions

Store capecitabine at room temperature, away from moisture and heat. Keep it in its original container and out of reach of children. Check the expiration date and do not use the medication past its expiry date.

Volume of Distribution

The volume of distribution of capecitabine is approximately 1.2 L/kg, indicating the extent to which the drug distributes into body tissues. This distribution helps in understanding the drug's effectiveness and its ability to reach target tissues.

Half Life

The terminal half-life of capecitabine is approximately 1 hour. The short half-life contributes to the need for multiple daily doses to maintain effective therapeutic levels and ensure optimal drug exposure.

Clearance

Capecitabine clearance is primarily renal, with around 90% of the drug excreted in the urine. The drug's clearance rate may be influenced by renal function and may require adjustment in patients with renal impairment to avoid toxicity.

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