Capecitabine is an oral chemotherapy drug that is given as a treatment for many types of cancer.
What capecitabine looks like
Capecitabine is available as peach-coloured tablets of 500mg, and light peach-coloured tablets of 150mg.
How it is given
Your doctor will want you to take a combination of 500mg and 150mg tablets. The correct dose is calculated from your height and weight. You need to make sure that you are taking the right dose.
The tablets should be swallowed whole with a glass of water, within half an hour of the end of a meal, as capecitabine works best if it is broken down in the stomach with food. You should take them in the morning after breakfast, and then again after your evening meal, so that the doses are spaced at least eight hours apart.
If you have trouble swallowing capecitabine tablets, they can be dissolved in a 200ml glass of warm water. The mixture should be stirred with a spoon until the tablets are completely dissolved and drunk immediately. The glass and spoon should be washed and kept separate from your other crockery and cooking utensils.
Capecitabine tablets are usually taken for a number of days, followed by a rest period in which no tablets are taken. This can vary depending upon the type of cancer you have. It is important to follow the instructions carefully and take the tablets as directed by your doctor, nurse or pharmacist.
You should only get the tablets from your hospital. You can’t get a repeat prescription from your GP.
Possible side effects
Each person’s reaction to chemotherapy is different. Some people have very few side effects, while others may experience more. The side effects described in this information will not affect everyone who is given capecitabine, and may be different if you are having more than one chemotherapy drug.
We have outlined the most common side effects and some of the less common ones, so that you can be aware of them if they occur. However, we have not included those that are very rare and therefore extremely unlikely to affect you. If you notice any effects which you think may be due to the drug but which are not listed in this information, please discuss them with your doctor or chemotherapy nurse.
Feeling sick (nausea) and being sick (vomiting)
This is usually mild. Your doctor can prescribe very effective anti-sickness (anti-emetic) drugs to prevent, or greatly reduce this symptom.
Sore mouth and ulcers
Your mouth may become sore or you may notice small ulcers during this treatment. Drinking plenty of fluids, and cleaning your teeth regularly and gently with a soft toothbrush, can help to reduce the risk of this happening. Tell your nurse or doctor if you have any of these problems, as they can prescribe special mouthwashes and medicines, which prevent or clear any mouth infection.
You may notice that your food tastes different. Normal taste will usually return when your treatment finishes.
In my opinion this is the most common side effect of Capecitabine, and in most cases it is controllable. Even if it is quite severe, it can usually be controlled with medicines such as Imodium (Loperamide) or codeine.
Take 2 tablets of imodium (loperamide) immediately if you experience diarrhoea and take a further single tablet with each loose motion, up to a maximum of 8 per day. If you have continuing diarrhoea despite taking imodium, contact the hospital as you can quickly become very dehydrated. You MUST STOP taking capecitabine in this situation, but it is often possible to restart the treatment later at a lower dose once the diarrhoea has settled. It is important to drink plenty of fluids if you have diarrhoea. DO NOT STOP THE CAPECITABINE WITHOUT FIRST SEEKING MEDICAL ADVICE FROM MYSELF, OR THE CHEMOTHERAPY UNIT, OR YOUR SPECIALIST NURSE.
Abdominal pain and constipation
It may help to drink plenty of fluids, eat a high-fibre diet and take gentle exercise. Sometimes you may need to take medicines to stimulate your bowel.
Loss of appetite
Soreness and redness or darkening of the palms of the hands and soles of the feet (sometimes known as palmar plantar syndrome or hand-foot syndrome) can occur. You may be prescribed vitamin B6 (pyridoxine), which can help to reduce this. A rash and dry or itchy skin may also occur. Simple moisturising creams like E45 or ‘Aqueous Cream’ can work well also.
Tiredness and feeling weak
Less common side effects
Lowered resistance to infection
Capecitabine can reduce the production of white blood cells by the bone marrow, making you more prone to infection. This effect can begin seven days after treatment has been given, and your resistance to infection usually reaches its lowest point 10–14 days after chemotherapy. Your blood cells will then increase steadily, and will usually have returned to normal levels before your next course of chemotherapy.
Contact your doctor or the hospital straightaway if:
- your temperature goes above 38ºC (100.5ºF)
- you suddenly feel unwell (even with a normal temperature).
- You will have a blood test before having more chemotherapy to make sure that your cells have recovered. Occasionally it may be necessary to delay your treatment if the number of blood cells (the blood count) is still low.
Bruising or bleeding
Capecitabine can reduce the production of platelets (which help the blood to clot). Let your doctor know if you have any unexplained bruising or bleeding, such as nosebleeds, blood spots or rashes on the skin, or bleeding gums.
Anaemia (low number of red blood cells)
While having treatment with capecitabine you may become anaemic. This may make you feel tired and breathless and pale. Let your doctor or nurse know if you develop these symptoms.
Hair loss is rare with capecitabine, but your hair may thin. If this happens it usually begins about 3–4 weeks after starting treatment, although it may occur earlier. It is temporary and your hair will start to regrow once the treatment ends.
Headaches and dizziness
Changes in the way your heart works
Capecitabine may affect the way your heart works. Some people can experience chest pain and tightening across the centre of the chest while taking capecitabine. This pain is called angina. Chest pain can be caused by many different things other than chemotherapy. If you develop any of these symptoms you should contact your doctor immediately.
Increased production of tears
This may be caused by capecitabine and is temporary. You may also notice that your eyes become sore and inflamed (conjunctivitis). Your doctor can prescribe soothing eye drops if necessary.
Risk of blood clots
Cancer can increase your risk of developing a blood clot (thrombosis), and having chemotherapy may increase this risk further. A blood clot may cause symptoms such as pain, redness and swelling in a leg, or breathlessness and chest pain. Blood clots can be very serious so it is important to tell your doctor straightaway if you have any of these symptoms. However, most clots can usually be successfully treated with drugs to thin the blood. Your doctor or nurse can give you more information.
Some other medicines can be harmful to take when you are having chemotherapy. Capecitabine is known to react with the drugs phenytoin, allopurinol and interferon; you should let your doctor know if you are taking any of these. It is a good idea to tell your doctor about other medications you are taking, including non-prescribed drugs such as complementary therapies and herbal drugs.
Your ability to become pregnant or father a child may be affected by taking this drug. It is important to discuss fertility with your doctor before starting treatment.
It is not advisable to become pregnant or father a child while taking capecitabine, as the developing foetus may be harmed. It is necessary to use effective contraception while taking this drug, and for at least a few months afterwards. Again, discuss this with your doctor.
Interaction with other drugs
Capecitabine may affect the action of some medication given to thin the blood (anti-coagulants), such as warfarin. Let your doctor know if you take warfarin, as they may need to check more often how quickly your blood is clotting.
Let your doctor know if you are taking folic acid because it might increase the side effects of capecitabine.
ADDITIONAL INFORMATION FOR HEALTHCARE PROFESSIONALS ONLY
DOSING: RENAL IMPAIRMENT
Clcr 51-80 mL/minute: No adjustment of initial dose.
Clcr 30-50 mL/minute: Administer 75% of normal dose.
Clcr <30 mL/minute: Use is contraindicated. DOSING: HEPATIC IMPAIRMENT mild-to-moderate impairment: No starting dose adjustment is necessary; however, carefully monitor patients. Severe hepatic impairment: Patients have not been studied.
ADVERSE REACTIONS SIGNIFICANT — Frequency listed derived from monotherapy trials.
Cardiovascular: Edema (9% to 15%)
Central nervous system: Fatigue (16% to 42%), fever (7% to 18%), pain (12%)
Dermatologic: Palmar-plantar erythrodysesthesia (hand-and-foot syndrome) (54% to 60%; grade 3: 11% to 17%; may be dose limiting), dermatitis (27% to 37%)
Gastrointestinal: Diarrhea (47% to 57%; may be dose limiting; grade 3: 12% to 13%; grade 4: 2% to 3%), nausea (34% to 53%), vomiting (15% to 37%), abdominal pain (7% to 35%), stomatitis (22% to 25%), appetite decreased (26%), anorexia (9% to 23%), constipation (9% to 15%)
Hematologic: Lymphopenia (94%; grade 4: 14%), anemia (72% to 80%; grade 4: <1% to 1%), neutropenia (2% to 26%; grade 4: 2%), thrombocytopenia (24%; grade 4: 1%) Hepatic: Bilirubin increased (22% to 48%; grades 3/4: 11% to 23%) Neuromuscular & skeletal: Paresthesia (21%) Ocular: Eye irritation (13% to 15%) Respiratory: Dyspnea (14%) 5% to 10%:
Cardiovascular: Venous thrombosis (8%), chest pain (6%)
Central nervous system: Headache (5% to 10%), lethargy (10%), dizziness (6% to 8%), insomnia (7% to 8%), mood alteration (5%), depression (5%)
Dermatologic: Nail disorder (7%), rash (7%), skin discoloration (7%), alopecia (6%), erythema (6%)
Endocrine & metabolic: Dehydration (7%)
Gastrointestinal: Motility disorder (10%), oral discomfort (10%), dyspepsia (6% to 8%), upper GI inflammatory disorders (colorectal cancer: 8%), hemorrhage (6%), ileus (6%), taste perversion (colorectal cancer: 6%)
Neuromuscular & skeletal: Back pain (10%), weakness (10%), neuropathy (10%), myalgia (9%), arthralgia (8%), limb pain (6%)
Ocular: Abnormal vision (colorectal cancer: 5%), conjunctivitis (5%)
Respiratory: Cough (7%)
Miscellaneous: Viral infection (colorectal cancer: 5%)
<5% (Limited to important or life-threatening):
Angina, ascites, asthma, atrial fibrillation, bradycardia, bronchitis, bronchopneumonia, bronchospasm, cachexia, cardiac arrest, cardiac failure, cardiomyopathy, cerebral vascular accident, cholestasis, coagulation disorder, colitis, deep vein thrombosis, diaphoresis, duodenitis, dysphagia, dysrhythmia, ECG changes, encephalopathy, epistaxis, fungal infection, gastric ulcer, gastroenteritis, hematemesis, hemoptysis, hepatic failure, hepatic fibrosis, hepatitis, hypokalemia, hypomagnesemia, hyper-/hypotension, hypersensitivity, hypertriglyceridemia, idiopathic thrombocytopenia purpura, ileus, infection, intestinal obstruction (~1%), keratoconjunctivitis, lacrimal duct stenosis, leukopenia, loss of consciousness, lymphedema, MI, multifocal leukoencephalopathy, myocardial ischemia, myocarditis, necrotizing enterocolitis (typhlitis), oral candidiasis, pericardial effusion, thrombocytopenic purpura, pancytopenia, photosensitivity reaction, pneumonia, pruritus, pulmonary embolism, radiation recall syndrome, renal impairment, respiratory distress, sedation, sepsis, skin ulceration, tachycardia, thrombophlebitis, toxic megacolon, tremor, ventricular extrasystoles
MECHANISM OF ACTION
Capecitabine is a prodrug of fluorouracil. It undergoes hydrolysis in the liver and tissues to form fluorouracil which is the active moiety. Fluorouracil is a fluorinated pyrimidine antimetabolite that inhibits thymidylate synthetase, blocking the methylation of deoxyuridylic acid to thymidylic acid, interfering with DNA, and to a lesser degree, RNA synthesis. Fluorouracil appears to be phase specific for the G1 and S phases of the cell cycle.
PHARMACODYNAMICS / KINETICS
Absorption: Rapid and extensive
Protein binding: <60%; ~35% to albumin Metabolism:
- Hepatic: Inactive metabolites: 5′-deoxy-5-fluorocytidine, 5′-deoxy-5-fluorouridine
- Tissue: Active metabolite: Fluorouracil
Half-life elimination: 0.5-1 hour
Time to peak: 1.5 hours; Fluorouracil: 2 hours
Excretion: Urine (96%, 57% as alpha-fluoro-ß-alanine); faeces (<3%) [/av_textblock]