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Trimetrexate (Systemic)

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Trimetrexate (Systemic)

US Brand Names

• Neutrexin

Canadian Brand Names

• Neutrexin


Trimetrexate (tri-me-TREX-ate) is used, together with leucovorin (loo-koe-VOR-in) , to treatPneumocystis carinii ((noo-moe-SISS-tis)) 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. It is available in the following dosage form:


    • Injection (U.S. and Canada)

Before Receiving This Medicine

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


Tell your doctor if you have ever had any unusual or allergic reaction to trimetrexate, methotrexate, or leucovorin. Also tell your health care professional if you are allergic to any other substances, such as foods, preservatives, or dyes.


Use of trimetrexate during pregnancy should be avoided whenever possible since trimetrexate has caused birth defects and death of the fetus in animal studies. The use of birth control is recommended during trimetrexate therapy. Tell your doctor immediately if you think you may be pregnant or if you need advice about birth control.


It is not known if trimetrexate passes into breast milk. However, breast-feeding should be stopped during treatment with this medicine because trimetrexate may cause serious unwanted effects in nursing babies.


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.

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 taking trimetrexate, it is especially important that your health care professional know if you are taking any of the following:

    • Acetaminophen (e.g., Tylenol) (with long-term, high-dose use) or

    • Amiodarone (e.g., Cordarone) or

    • Anabolic steroids (nandrolone [e.g., Anabolin], oxandrolone [e.g., Anavar], oxymetholone [e.g., Anadrol], stanozolol [e.g., Winstrol]) or

    • Androgens (male hormones) or

    • Carbamazepine (e.g., Tegretol) or

    • Chloroquine (e.g., Aralen) or

    • Dantrolene (e.g., Dantrium) or

    • Daunorubicin (e.g., Cerubidine) or

    • Estrogens (female hormones) or

    • Etretinate (e.g., Tegison) or

    • Hydroxychloroquine (e.g., Plaquenil) or

    • Methyldopa (e.g., Aldomet) or

    • Naltrexone (e.g., Trexan) (with long-term, high-dose use) or

    • Phenothiazines (acetophenazine [e.g., Tindal], chlorpromazine [e.g., Thorazine], fluphenazine [e.g., Prolixin], mesoridazine [e.g., Serentil], perphenazine [e.g., Trilafon], prochlorperazine [e.g., Compazine], promazine [e.g., Sparine], promethazine [e.g., Phenergan], thioridazine [e.g., Mellaril], trifluoperazine [e.g., Stelazine], triflupromazine [e.g., Vesprin], trimeprazine [e.g., Temaril]) or

    • Phenytoin (e.g., Dilantin)-Use of these medicines while you are taking trimetrexate may decrease the breakdown of trimetrexate in the liver and increase the chance of trimetrexate side effects

    • Alcohol or

    • Cimetidine (e.g., Tagamet) or

    • Diltiazem (e.g., Cardizem) or

    • Erythromycins (medicine for infection) or

    • Isoniazid (e.g., INH, Nydrazid) or

    • Quinine (e.g., Quinamm) or

    • Ranitidine (e.g., Zantac) or

    • Verapamil (e.g., Calan)-Use of these medicines with trimetrexate may increase the chance of trimetrexate side effects

    • Amphotericin B by injection (e.g., Fungizone) or

    • Antineoplastics (cancer medicine) or

    • Azathioprine (e.g., Imuran) or

    • Colchicine or

    • Cyclophosphamide (e.g., Cytoxan) or

    • Flucytosine (e.g., Ancobon) or

    • Ganciclovir (e.g., Cytovene) or

    • Interferon (e.g., Intron A, Roferon-A) or

    • Zidovudine (e.g., AZT, Retrovir)-Receiving trimetrexate while you are using these medicines may make side effects affecting the blood worse

    • Cisplatin (e.g., Platinol) or

    • Combination pain medicine containing acetaminophen and aspirin (e.g., Excedrin) or other salicylates (with large amounts taken regularly) or

    • Cyclosporine (e.g., Sandimmune) or

    • Deferoxamine (e.g., Desferal) (with long-term use) or

    • Foscarnet (e.g., Foscavir) or

    • Inflammation or pain medicine (except narcotics) or

    • Lithium (e.g., Lithane) or

    • Penicillamine (e.g., Cuprimine) or

    • Streptozocin (e.g., Zanosar) or

    • Tiopronin (e.g., Thiola)-Use of these medicines while you are taking trimetrexate may decrease the elimination of trimetrexate through the kidneys and increase the chance of trimetrexate toxicity

    • Antithyroid agents (medicine for overactive thyroid) or

    • Carmustine (e.g., BiCNU) or

    • Chloramphenicol (e.g., Chloromycetin) or

    • Disulfiram (e.g., Antabuse) or

    • Divalproex (e.g., Depakote) or

    • Gold salts (medicine for arthritis) or

    • Mercaptopurine (e.g., Purinethol) or

    • Methotrexate (e.g., Mexate) or

    • Oral contraceptives (birth control pills) containing estrogen or

    • Other anti-infectives (medicine for infection) by mouth or by injection or

    • Plicamycin (e.g., Mithracin) or

    • Valproic acid (e.g., Depakene)-Use of these medicines with trimetrexate may increase the chance of side effects from trimetrexate

Other medical problems

The presence of other medical problems may affect the use of trimetrexate. 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 that you have worse

    • Kidney disease or

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


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.


The doses of trimetrexate and of leucovorin 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 trimetrexate and leucovorin. If your doses are different, do not change them unless your doctor tells you to do so.

    For trimetrexate

    • For the treatment ofPneumocystis cariniipneumonia:

      o For injection dosage form:

        Adults- 45 milligrams per square meter of body surface area (mg/m) 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 leucovorin

    • For the prevention of serious side effects of trimetrexate in the treatment ofPneumocystis cariniipneumonia:

      o For the oral or injection dosage forms:

        Adults-20 milligrams per square meter of body surface area (mg/m) 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 leucovorin, take it as soon as possible. This will help to keep a constant amount of medicine in the blood. 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.


To store leucovorin:

    • Keep out of the reach of children.

    • Store away from heat and direct light.

    • Do not store in the bathroom, near the kitchen sink, or in other damp places. Heat or moisture may cause the medicine to break down.

    • Do not keep outdated medicine or medicine no longer needed. Be sure that any discarded medicine is out of the reach of children.


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.

Side Effects

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.

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:

Less common

Fatigue; stomach pain.

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

Additional Information

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

Other than the above information, there is no additional information relating to proper use, precautions, or side effects for this use.

October 28, 2003

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