RALTITREXED For Colorectal Cancer (Systemic)*

Some commonly used brand names are:

In Canada?

• Tomudex

* Not commercially available in the U.S.

Category

• Antineoplastic

Description

Raltitrexed (ral-ti-TREX-ed) belongs to a group of medicines known asantimetabolites. It is used to treat cancer of the colon and rectum. It mayalso be used to treat other kinds of cancer, as determined by your doctor.

Raltitrexed blocks an enzyme needed by the cell to live. This interfereswith the growth of cancer cells, which are eventually destroyed. Since thegrowth of normal body cells may also be affected by raltitrexed, other effectswill also occur. Some of these may be serious and must be reported to yourdoctor. Other effects, like hair loss, may not be serious but may cause concern.

Before you begin treatment with raltitrexed, you and your doctor shouldtalk about the good this medicine will do as well as the risks of using it.

Raltitrexed is to be administered only by or under the immediate supervisionof your doctor. It is available in the following dosage form:

Parenteral
• Injection (Canada)

Before Using This Medicine

In deciding to use a medicine,the risks of taking the medicine must be weighed against the good it willdo. This is a decision you and your doctor will make. For raltitrexed, thefollowing should be considered:

Allergies?Tell your doctor if you have ever had any unusualor allergic reaction to raltitrexed.

Pregnancy?Tell your doctor if you are pregnant or if youintend to have children. There is a chance that this medicine may cause birthdefects if either the male or female is taking it at the time of conceptionor if it is taken during pregnancy. Raltitrexed causes toxic or harmful effectsin rats. In addition, many cancer medicines may cause sterility which couldbe permanent. Although sterility has not been reported with this medicine,the possibility should be kept in mind.

Be sure that you have discussed this with your doctor before receivingthis medicine. It is best to use some kind of birth control while you arereceiving raltitrexed. Tell your doctor right away if you think you have becomepregnant while receiving raltitrexed. Because raltitrexed may cause seriousside effects, pregnancy is generally not recommended while you are takingit.

Breast-feeding?Tell your doctor if you are breast-feeding orif you intend to breast-feed during treatment with this medicine. Becauseraltitrexed may cause serious side effects, breast-feeding is generally notrecommended while you are taking it.

Children?Studies on this medicine have been done only inadult patients, and there is no specific information comparing use of raltitrexedin children with use in other age groups.

Older adults?Elderly people are especially sensitive to theeffects of raltitrexed. Raltitrexed may be more likely to cause side effectssuch as cracked lips, diarrhea, difficulty in swallowing, sores, ulcers, orwhite spots on the lips, tongue, or inside the mouth in elderly patients.

Other medicines?Although certain medicines should not be usedtogether at all, in other cases two different medicines may be used togethereven if an interaction might occur. In these cases, your doctor may want tochange the dose, or other precautions may be necessary. When you are receivingraltitrexed, it is especially important that your doctor and pharmacist knowif you are taking any of the following:

• Amphotericin B by injection (e.g., Fungizone) or
• Antithyroid agents (medicine for overactive thyroid) or
• Azathioprine (e.g., Imuran) or
• Chloramphenicol (e.g., Chloromycetin) or
• Colchicine or
• Flucytosine (e.g., Ancobon) or
• Ganciclovir (e.g., Cytovene) or
• Interferon (e.g., Intron A, Roferon-A) or
• Mercaptopurine (e.g., Purinethol) or
• Methotrexate (e.g., Rheumatrex) or
• Plicamycin (e.g., Mithracin) or
• Zidovudine (e.g., AZT, Retrovir) or
• If you have ever been treated with radiation or cancer medicines?Raltitrexedmay increase the effects of these medicines or radiation therapy on the blood
• Folic acid or
• Leucovorin (e.g., Wellcovorin) or
• Vitamin preparations containing folic or folinic acid?May interferewith the effectiveness of raltitrexed

Other medical problems?The presence of other medicalproblems may affect the use of raltitrexed. Make sure you tell your doctorif you have any other medical problems, especially:

• Chickenpox (including recent exposure) or
• Herpes zoster (shingles)?Risk of severe disease affecting otherparts of the body

• Infection?Raltitrexed can decrease your body's ability to fightinfection

• Kidney disease or
• Liver disease?Effects of raltitrexed may be increased becauseof slower removal from the body; your doctor may need to change your dose

Proper Use of This Medicine

This medicineis sometimes given together with certain other medicines. If you are usinga combination of medicines, it is important that you receive each one at theproper time. If you are taking some of these medicines by mouth, ask yourhealth care professional to help you plan a way to take them at the righttimes.

This medicine usually causes nausea and vomiting that may be severe. However,it is very important that you continue to receive the medicine, even if youbegin to feel ill. Ask your health care professional for ways to lessen theseeffects, especially if they are severe.

Dosing?The dose of raltitrexed will be differentfor different patients. The dose that is used may depend on a number of things,including what the medicine is being used for, the patient's size, and whetheror not other medicines are also being taken. If you have any questions aboutthe proper dose of raltitrexed, ask your doctor.

• For parenteral dosage form (injection):
  • For colorectal cancer
    • Adults?3 milligrams (mg) per square meter of body surface areagiven over a 15 minute period. The dose may be repeated every 3 weeks.
    • Children?Use and dose must be determined by your doctor.

Missed dose?If you have any questions about this, check withyour doctor.

Precautions While Using This Medicine

It isvery important that your doctor check your progress at regular visitsto make sure that this medicine is working properly and to check for unwantedeffects.

This medicine may cause some people to feel unusually tired or ill. Make sure you know how you react to this medicine before youdrive, use machines, or do anything else that could be dangerous if you areless alert.

While you are being treated with raltitrexed, and after you stop treatmentwith it, do not have any immunizations (vaccinations)without your doctor's approval. Raltitrexed may lower your body's resistanceand there is a chance you might get the infection the immunization is meantto prevent. In addition, other persons living in your household should nottake oral polio vaccine since there is a chance they could pass the poliovirus on to you. Also, avoid persons who have taken oral polio vaccine withinthe last several months. Do not get close to them and do not stay in the sameroom with them for very long. If you cannot take these precautions, you shouldconsider wearing a protective face mask that covers the nose and mouth.

Raltitrexed can temporarily lower the number of white blood cells in yourblood, increasing the chance of getting an infection. It can also lower thenumber of platelets, which are necessary for proper blood clotting. If thisoccurs, there are certain precautions you can take, especially when your bloodcount is low, to reduce the risk of infection or bleeding:

• If you can, avoid people with infections. Checkwith your doctor immediately if you think you are getting an infectionor if you get a fever or chills, cough or hoarseness, lower back or side pain,or painful or difficult urination.
• Check with your doctor immediately ifyou notice any unusual bleeding or bruising; black, tarry stools; blood inurine or stools; or pinpoint red spots on your skin.
• Be careful when using a regular toothbrush, dental floss, or toothpick.Your medical doctor, dentist, or nurse may recommend other ways to clean yourteeth and gums. Check with your medical doctor before having any dental workdone.
• Do not touch your eyes or the inside of your nose unless you havejust washed your hands and have not touched anything else in the meantime.
• Be careful not to cut yourself when you are using sharp objects suchas a safety razor or fingernail or toenail cutters.
• Avoid contact sports or other situations where bruising or injurycould occur.

Side Effects of This Medicine

Along with its needed effects, a medicinemay cause some unwanted effects. Although not all of these side effects mayoccur, if they do occur they may need medical attention.

Check with your doctorimmediately if any of the following side effects occur:

More common

Pale skin, troubled breathing, unusual bleeding or bruising,unusual tiredness or weakness; black, tarry stools,chest pain, chills, cough, fever, painful or difficult urination, shortnessof breath, sore throat, sores, ulcers, or white spots on lips or in mouth,swollen glands; increase in bowel movements, loosestools, soft stools

Less common

Dizziness, fainting, fast, slow, or irregular heartbeat, decreasedurine output, dilated neck veins, extreme fatigue, irregular breathing, swellingof face, fingers, feet, or lower legs, tightness in chest, weight gain, wheezing

Other side effects may occur that usually do not need medical attention.These side effects may go away during treatment as your body adjusts to themedicine. However, check with your doctor if any of the following side effectscontinue or are bothersome.

More common

Stomach or abdomen pain; loss of appetite,weight loss; constipation; nausea and vomiting; lack or loss of strength; general feeling of discomfort or illness, headache, joint pain,muscle aches and pains, runny nose, shivering, sweating, trouble sleeping; rash

Less common

Bloating or swelling of face, arms, hands, lower legs, or feet,rapid weight gain, tingling of hands or feet

Other side effects mayoccur that usually do not need medical attention. These side effects may goaway during treatment as your body adjusts to the medicine. Also, your healthcare professional may be able to tell you about ways to prevent or reducesome of these side effects. Check with your health care professional if anyof the following side effects continue or are bothersome or if you have anyquestions about them:

More common

Hair loss, thinning of hair

Less common

Change in taste, bad unusual or unpleasant (after)taste

Afteryou stop receiving raltitrexed, it may still produce some side effects thatneed attention. During this period of time check with your doctor if you noticeany of the following side effects: