In Canada—

• Antineoplastic

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

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

Before you begin treatment with raltitrexed, you and your doctor should talk 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 supervision of your doctor. It is available in the following dosage form:

Parenteral
• Injection (Canada)

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

Allergies—Tell your doctor if you have ever had any unusual or allergic reaction to raltitrexed.

Pregnancy—Tell your doctor if you are pregnant or if you intend to have children. There is a chance that this medicine may cause birth defects if either the male or female is taking it at the time of conception or if it is taken during pregnancy. Raltitrexed causes toxic or harmful effects in rats. In addition, many cancer medicines may cause sterility which could be 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 receiving this medicine. It is best to use some kind of birth control while you are receiving raltitrexed. Tell your doctor right away if you think you have become pregnant while receiving raltitrexed. Because raltitrexed may cause serious side effects, pregnancy is generally not recommended while you are taking it.

Breast-feeding—Tell your doctor if you are breast-feeding or if you intend to breast-feed during treatment with this medicine. Because raltitrexed may cause serious side effects, breast-feeding is generally not recommended while you are taking it.

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

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

Other medicines—Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are receiving raltitrexed, it is especially important that your doctor and pharmacist know if 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—Raltitrexed may 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 interfere with the effectiveness of raltitrexed

• Chickenpox (including recent exposure) or
• Herpes zoster (shingles)—Risk of severe disease affecting other parts of the body

• Infection—Raltitrexed can decrease your body's ability to fight infection

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

This medicine is sometimes given together with certain other medicines. If you are using a combination of medicines, it is important that you receive each one at the proper time. If you are taking some of these medicines by mouth, ask your health care professional to help you plan a way to take them at the right times.

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 you begin to feel ill. Ask your health care professional for ways to lessen these effects, especially if they are severe.

Dosing—

The dose of raltitrexed will be different for 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 whether or not other medicines are also being taken. If you have any questions about the 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 area given 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 with your doctor.

It is very important that your doctor check your progress at regular visits to make sure that this medicine is working properly and to check for unwanted effects.

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

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

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

• If you can, avoid people with infections. Check with your doctor immediately if you think you are getting an infection or 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 if you notice any unusual bleeding or bruising; black, tarry stools; blood in urine 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 your teeth and gums. Check with your medical doctor before having any dental work done.
• Do not touch your eyes or the inside of your nose unless you have just washed your hands and have not touched anything else in the meantime.
• Be careful not to cut yourself when you are using sharp objects such as a safety razor or fingernail or toenail cutters.
• Avoid contact sports or other situations where bruising or injury could occur.

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

Check with your doctor immediately 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, shortness of breath, sore throat, sores, ulcers, or white spots on lips or in mouth, swollen glands;  increase in bowel movements, loose stools, soft stools 
  
  

• Less common
  • Dizziness, fainting, fast, slow, or irregular heartbeat, decreased urine output, dilated neck veins, extreme fatigue, irregular breathing, swelling of 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 the medicine. However, check with your doctor if any of the following side effects continue 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 may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• More common
  • Hair loss, thinning of hair 
  
  

• Less common
  • Change in taste, bad unusual or unpleasant (after)taste 
  
  

After you stop receiving raltitrexed, it may still produce some side effects that need attention. During this period of time check with your doctor if you notice any of the following side effects:

• Black, tarry stools, blood in urine or stools, cough or hoarseness, fever or chills, lower back or side pain, painful or difficult urination, pinpoint red spots on skin, unusual bleeding or bruising 

Other side effects not listed above may also occur in some patients. If you notice any other effects, check with your doctor.