Pronunciation:

trye-me-TREX-ate

Brand Names:

• NeuTrexin

Dosage Forms:

• Powder for Solution

Warnings:

Trimetrexate glucuronate for injection must be used with concurrent leucovorin (leucovorin protection) to avoid potentially serious or life-threatening toxicities .

Trimetrexate glucuronate for injection must be used with concurrent leucovorin (leucovorin protection) to avoid potentially serious or life-threatening toxicities .

Classifications:

Therapeutic

Antibiotic

Pharmacologic

Antimetabolite

Uses of This Medicine:

Trimetrexate is used, together with leucovorin, to treat Pneumocystis carinii pneumonia (PCP), a very serious kind of pneumonia. This kind of pneumonia occurs commonly in patients whose immune system is not working normally, such as cancer patients, transplant patients, and patients with acquired immune deficiency syndrome (AIDS).

Trimetrexate may cause some serious, even life-threatening, side effects. To prevent these effects, you must take another medicine, leucovorin, together with trimetrexate and for 3 days after you stop receiving trimetrexate. Before you begin treatment with trimetrexate, you and your doctor should talk about the good this medicine will do as well as the risks of using it.

Trimetrexate is to be administered only by or under the immediate supervision of your doctor.

Products containing trimetrexate were withdrawn from the market by MedImmune in March 2007 .

Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although this use is not included in product labeling, trimetrexate is used in certain patients with the following medical condition:

• Cancer of the colon

Before Using This Medicine:

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 this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Children

This medicine has been tested in a limited number of children younger than 18 years of age. Trimetrexate can cause serious side effects in any patient. However, in effective doses, this medicine did not cause different side effects or problems in the few children who received it than it does in adults.

Older adults

Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults or if they cause different side effects or problems in older people. There is no specific information comparing use of trimetrexate in the elderly with use in other age groups.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	D	Studies in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy in a life threatening situation or a serious disease, may outweigh the potential risk.

Breast-feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Other medicines

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Rotavirus Vaccine, Live

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Bacillus of Calmette and Guerin Vaccine, Live
• Influenza Virus Vaccine, Live
• Measles Virus Vaccine, Live
• Mumps Virus Vaccine, Live
• Poliovirus Vaccine, Live
• Rotavirus Vaccine, Live
• Rubella Virus Vaccine, Live
• Smallpox Vaccine
• Typhoid Vaccine
• Varicella Virus Vaccine
• Yellow Fever Vaccine

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Cimetidine
• Clotrimazole
• Erythromycin
• Fluconazole
• Itraconazole
• Ketoconazole
• Miconazole
• Rifabutin
• Rifampin

Other interactions

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other medical problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Anemia or
• Blood problems or
• Low platelet count or
• Low white blood cell count Trimetrexate may make any blood diseases that you have worse.

• Mouth ulcers or other mouth sores or
• Stomach ulcer or other stomach or intestinal problems Trimetrexate may make these conditions worse.

• Kidney disease or
• Liver disease Kidney or liver disease may increase the chance of side effects from trimetrexate.

Proper Use of This Medicine:

When you take leucovorin:

• Leucovorin must be taken with trimetrexate to help prevent very serious, possibly life-threatening, unwanted side effects. Leucovorin should be taken during trimetrexate treatment and for 3 days after trimetrexate is stopped. It is very important to take this medicine exactly as your doctor told you. Failure to do this can result in very serious side effects.
• Take oral leucovorin exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. Also, do not stop taking this medicine without checking with your doctor first.
• Oral leucovorin works best when there is a constant amount in the blood. To help keep the amount constant, do not miss any doses. If you need help in planning the best times to take your medicine, check with your health care professional.
• If you vomit shortly after taking an oral dose of leucovorin, check with your doctor. You will be told whether to take the dose again or to wait until the next scheduled dose.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For the treatment of Pneumocystis carinii pneumonia:
  • For injection dosage form:
    • Adults 45 milligrams per square meter of body surface area (mg/m2) injected into a vein once a day for twenty-one days. Your doctor will check your blood counts and may change your dose based on these counts. Your doctor may want to give you a dose you based on how much you weigh. Your dose will be determined by your doctor.
    • Children and teenagers Use and dose must be determined by your doctor.

• For the prevention of serious side effects of trimetrexate in the treatment of Pneumocystis carinii pneumonia:
  • For the oral or injection dosage forms:
    • Adults 20 milligrams per square meter of body surface area (mg/m 2) taken by mouth or injected into a vein every six hours for twenty-four days. Your doctor will check your blood counts and may change your dose based on these counts. Your doctor may want to give you a dose you based on how much you weigh. Your dose will be determined by your doctor.
    • Children and teenagers Use and dose must be determined by your doctor.

Missed dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Precautions While Using This Medicine:

If your symptoms do not improve within a few days, or if they become worse, 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.

Trimetrexate can lower the number of white blood cells in your blood temporarily, increasing your 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.
• Be careful not to cut yourself when you are using sharp objects such as a safety razor or fingernail or toenail cutters.

Check with your doctor right away if you experience symptoms of an allergic reaction such as cough, difficulty swallowing, dizziness, fainting or loss of consciousness, fast heartbeat, fast or irregular breathing, hives, itching, puffiness or swelling of the eyelids or around the eyes, face, lips or tongue, shortness of breath, skin rash, swelling of eyes or eyelids, tightness in chest, trouble in breathing, unusual tiredness or weakness, and/or wheezing .

Side Effects of This Medicine:

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

Abdominal pain or tenderness

black, tarry stools

blood in urine or stools

clay-colored stools

dark urine

decreased appetite

fever and sore throat

headache

itching

loss of appetite

nausea and vomiting

pinpoint red spots on skin

skin rash

swelling of feet or lower legs

unusual bleeding or bruising

unusual tiredness or weakness

yellow eyes or skin

Less common

Abdominal cramps

coma

confusion

convulsions

decreased urine output

difficulty in breathing

dizziness

fast or irregular heartbeat

hypocalcemia

increased thirst

mood or mental changes

muscle cramps in hands, arms, feet, legs, or face

muscle pain

mouth sores or ulcers

numbness and tingling around the mouth, fingertips, or feet

skin rash and itching

shortness of breath

tremor

Rare

Cough

difficulty swallowing

fainting or loss of consciousness

fast or irregular breathing

hives

puffiness or swelling of the eyelids or around the eyes, face, lips or tongue

swelling of eyes or eyelids

tightness in chest

trouble in breathing

wheezing

Some 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:

Less common

Fatigue

stomach pain

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

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.