Irinotecan is a chemotherapy drug that is given as a treatment for some types of cancer. It is most commonly used to treat bowel cancer, but is also used in stomach cancer, small cell lung cancer, cervix cancer and brain tumours. This information describes irinotecan, how it is given and some of its possible side effects.
What irinotecan looks like
Irinotecan is a clear yellow fluid.
How it is given
Irinotecan may be given:
- as a drip (infusion) through a fine tube (cannula) inserted into a vein
- through a central line (Hickman / Portacath), which is inserted under the skin into a vein near the collarbone, or into a PICC line, which is inserted into a vein in the crook of your arm.
It is normally given over 30 – 60 minutes as an infusion.
Chemotherapy is usually given as a course of several sessions (or cycles) of treatment over a few months. The length of your treatment and the number of cycles you have will depend on the type of cancer for which you are being treated. Irinotecan is commonly given alongside other chemotherapy drugs as part of a combination regimen.
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 irinotecan, and may be different if you are having more than one chemotherapy drug.
We have outlined the most common side effects as well as some less common ones, so that you can be aware of them if they occur. However, we have not included those which 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.
Increased sweating, production of saliva, stomach cramps and diarrhoea
This is a particular group of side effects that are known as ‘acute cholinergic syndrome’. They happen because irinotecan can cause the cells in the body to release too much of a chemical called acetylcholine. The side effects tend to occur during, or within the first 24 hours after an infusion of irinotecan.
These symptoms can usually be prevented or controlled by a drug called atropine. The atropine is given as an injection under the skin (subcutaneously), which can be repeated if necessary.
If diarrhoea occurs as a delayed side effect (occurring more than 24 hours after an infusion) it can usually be easily controlled, but may occasionally be severe. If you get diarrhoea and abdominal cramps, start taking the anti-diarrhoea medicine (usually loperamide) that you have been given. You should take these medicines exactly as you have been instructed by the hospital treating you, which may be different from the instructions on any printed leaflets provided by the manufacturer.
Normally your doctor will tell you to take two tablets or capsules to start with and then one every two hours until you have not had a loose bowel movement for 12 hours. If loperamide does not work quickly (certainly if you still have diarrhoea after 48 hours) it is important that you contact the hospital. You may become dehydrated if you have a lot of diarrhoea. In some situations you may be asked to take liquids to re-hydrate you and replace any salts that you have lost. Antibiotics are also sometimes given if diarrhoea occurs.
Feeling sick (nausea) and being sick (vomiting)
If you do feel sick this may begin a few hours after the treatment is given and last for up to a day. Your doctor can prescribe very effective anti-sickness (anti-emetic) drugs to prevent, or greatly reduce this. If the sickness is not controlled, or continues, tell your doctor; they can prescribe other anti-sickness drugs which may be more effective.
Loss of appetite
This is usually mild and may last a day or so. A dietitian or specialist nurse at your hospital can give advice on nutritional supplements.
Lowered resistance to infection
Irinotecan can reduce the production of white blood cells by the bone marrow, making you more prone to infection. This effect can begin a few days after treatment has been given and your resistance to infection usually reaches its lowest point in the second week after chemotherapy. Your blood cells will then increase steadily and will usually have returned to normal before your next course of chemotherapy is due.
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
Irinotecan 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 irinotecan you may become anaemic. This may make you feel pale, tired and short of breath on exertion. Let your doctor or nurse know if these effects are a problem.
Hair loss is fairly common with Irinotecan. This usually starts 3–4 weeks after the first dose of irinotecan, although it may happen earlier. Hair may completely fall out. You may also have thinning and loss of eyelashes, eyebrows and other body hair. Hair loss is temporary and all your hair will grow again once the treatment ends.
Tiredness and a general feeling of weakness
It is important to allow yourself plenty of time to rest.
Less common side effects
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 special mouthwashes and medicines to prevent or clear any mouth infection can be prescribed.
You may notice that your food tastes different. Normal taste will usually come back after the treatment finishes.
Tell your doctor if you have muscle cramps, so that they can prescribe suitable painkillers.
Temporary effect on liver function
Irinotecan may cause changes in the way that your liver works, though your liver will return to normal when the treatment is finished. You are very unlikely to notice any problems but your doctor will check your liver is working properly before each treatment.
Irinotecan can cause a rash which may be itchy. Your doctor can prescribe medicines to help with this.
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 medicines can be harmful to take when you are having chemotherapy. Let your doctor know about any 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 irinotecan, as the developing foetus may be harmed. It is important to use effective contraception while taking this drug, and for at least a few months afterwards. Again, discuss this with your doctor.
ADDITIONAL INFORMATION FOR HEALTHCARE PROFESSIONALS
ADVERSE REACTIONS SIGNIFICANT
Frequency of adverse reactions reported for single-agent use of irinotecan only.
- Cardiovascular: Vasodilation (9% to 11%)
- Central nervous system: Cholinergic toxicity (47% – includes rhinitis, increased salivation, miosis, lacrimation, diaphoresis, flushing and intestinal hyperperistalsis); fever (44% to 45%), pain (23% to 24%), dizziness (15% to 21%), insomnia (19%), headache (17%), chills (14%)
- Dermatologic: Alopecia (46% to 72%), rash (13% to 14%)
- Endocrine & metabolic: Dehydration (15%)
- Gastrointestinal: Diarrhea, late (83% to 88%; grade 3/4: 5% to 31%), diarrhea, early (43% to 51%; grade 3/4: 6% to 22%), nausea (70% to 86%), abdominal pain (57% to 68%), vomiting (62% to 67%), cramps (57%), anorexia (44% to 55%), constipation (30% to 32%), mucositis (30%), weight loss (30%), flatulence (12%), stomatitis (12%)
- Hematologic: Anemia (60% to 97%; grades 3/4: 5% to 22%), leukopenia (63% to 96%, grades 3/4: 14% to 28%), thrombocytopenia (96%, grades 3/4: 1% to 4%), neutropenia (30% to 96%; grades 3/4: 14% to 31%)
- Hepatic: Bilirubin increased (84%), alkaline phosphatase increased (13%)
- Neuromuscular & skeletal: Weakness (69% to 76%), back pain (14%)
- Respiratory: Dyspnea (22%), cough (17% to 20%), rhinitis (16%)
- Miscellaneous: Diaphoresis (16%), infection (14%)
1% to 10%:
- Cardiovascular: Edema (10%), hypotension (6%), thromboembolic events (5%)
- Central nervous system: Somnolence (9%), confusion (3%)
- Gastrointestinal: Abdominal fullness (10%), dyspepsia (10%)
- Hematologic: Neutropenic fever (grades 3/4: 2% to 6%), hemorrhage (grades 3/4: 1% to 5%), neutropenic infection (grades 3/4: 1% to 2%)
- Hepatic: AST increased (10%), ascites and/or jaundice (grades 3/4: 9%)
- Respiratory: Pneumonia (4%)
ALT increased, amylase increased, anaphylactoid reaction, anaphylaxis, angina, arterial thrombosis, bleeding, bradycardia, cardiac arrest, cerebral infarct, cerebrovascular accident, circulatory failure, colitis, deep thrombophlebitis, dysrhythmia, embolus, gastrointestinal bleeding, gastrointestinal obstruction, hepatomegaly, hiccups, hyperglycemia, hypersensitivity, hyponatremia, ileus, interstitial lung disease, intestinal perforation, ischemic colitis, lipase increased, lymphocytopenia, megacolon, MI, muscle cramps, myocardial ischemia, pancreatitis, paresthesia, peripheral vascular disorder, pulmonary embolus; pulmonary toxicity (dyspnea, fever, reticulonodular infiltrates on chest x-ray); renal failure (acute), renal impairment, syncope, thrombophlebitis, thrombosis, typhlitis, ulceration, ulcerative colitis, vertigo
MECHANISM OF ACTION
Irinotecan and its active metabolite (SN-38) bind reversibly to topoisomerase I-DNA complex preventing religation of the cleaved DNA strand. This results in the accumulation of cleavable complexes and double-strand DNA breaks. As mammalian cells cannot efficiently repair these breaks, cell death consistent with S-phase cell cycle specificity occurs, leading to termination of cellular replication.
PHARMACODYNAMICS / KINETICS
- Distribution: Vd: 33-150 L/m2
- Protein binding, plasma: Predominantly albumin; Parent drug: 30% to 68%, SN-38 (active metabolite): ~95%
- Metabolism: Primarily hepatic to SN-38 (active metabolite) by carboxylesterase enzymes; SN-38 undergoes conjugation by UDP- glucuronosyl transferase 1A1 (UGT1A1) to form a glucuronide metabolite. Conversion of irinotecan to SN-38 is decreased and glucuronidation of SN-38 is increased patients who smoke cigarettes, resulting in lower levels of the metabolite and overall decreased systemic exposure. SN-38 is increased by UGT1A1*28 polymorphism (10% of North Americans are homozygous for UGT1A1*28 allele). The lactones of both irinotecan and SN-38 undergo hydrolysis to inactive hydroxy acid forms.
- Half-life elimination: SN-38: Mean terminal: 10-20 hours
- Time to peak: SN-38: Following 90-minute infusion: ~1 hour
- Excretion: Within 24 hours: Urine: Irinotecan (11% to 20%), metabolites (SN-38 <1%, SN-38 glucuronide, 3%)