Methotrexate. About This Drug. Possible Side Effects. Warnings and Precautions

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Methotrexate About This Drug Methotrexate is used to treat cancer. This drug is given in the vein (IV). Possible Side Effects Soreness of the mouth and throat. You may have red areas, white patches, or sores that hurt. Tiredness Confusion Nausea and throwing up (vomiting) Fever and chills Decrease in the number of white blood cells. This may raise your risk of infection. Feeling dizzy General discomfort, feeling unwell (malaise) Pain in the abdomen Changes in your liver function Changes in your kidney function Changes in lung function. You may have a dry cough or trouble breathing. Note: Not all possible side effects are included above. Warnings and Precautions Severe bone marrow depression, which is a decrease in the number of white blood cells, red blood cells, and platelets, which can very rarely be life-threatening. This may raise your risk of infection, make you tired and weak (fatigue), and raise your risk of bleeding. Severe kidney or liver problems may occur Sores in your mouth may become severe Severe diarrhea and inflammation (swelling) of your intestines, or stomach may occur, which can very rarely be lifethreatening. This drug may raise your risk of getting a second cancer such as lymphoma. http://hillman.upmc.com/patients/community-support/education/chemotherapy-drugs/methotrexate 1/5

Inflammation (swelling) of your lungs, which can very rarely be life-threatening. Tumor lysis syndrome may occur as a result of this drug acting on the cancer cells very quickly. This may affect how your kidneys work. Increased risk of infection, which may very rarely be life-threatening. Changes in your central nervous system can happen. The central nervous system is made up of your brain and spinal cord. You could feel extreme tiredness, agitation, confusion, hallucinations (see or hear things that are not there), trouble understanding or speaking, loss of control of your bowels or bladder, eyesight changes, numbness or lack of strength to your arms, legs, face, or body, and coma. If you start to have any of these symptoms call your doctor right away. Seizure. Common symptoms of a seizure can include confusion, blacking out, passing out, loss of hearing or vision, blurred vision, unusual smells or tastes (such as burning rubber), trouble talking, tremors or shaking in parts or all of the body, repeated body movements, tense muscles that do not relax, and loss of control of urine and bowels. There are other less common symptoms of seizures. If you or your family member suspects you are having a seizure, call 911 right away. Severe allergic skin reaction, which may very rarely be life-threatening. You may develop blisters on your skin that are filled with fluid or a severe red rash all over your body that may be painful. Allergic reactions, including anaphylaxis are rare but may happen in some patients. Signs of allergic reaction to this drug may be swelling of the face, feeling like your tongue or throat are swelling, trouble breathing, rash, itching, fever, chills, feeling dizzy, and/or feeling that your heart is beating in a fast or not normal way. If this happens, do not take another dose of this drug. You should get urgent medical treatment. Note: Some of the side effects above are very rare. If you have concerns and/or questions, please discuss them with your medical team. Important Information This drug may be present in the saliva, tears, sweat, urine, stool, vomit, semen, and vaginal secretions. Talk to your doctor and/or your nurse about the necessary precautions to take during this time. Talk to your doctor before receiving any vaccinations during your treatment. Some vaccinations are not recommended while receiving methotrexate. If you are getting this drug by injection into the fluid that surrounds the brain and spinal cord (intrathecal), your side effects might be different than those listed above. Please talk to your doctor about these side effects. These side effects may be more severe if you are receiving high doses of this medication. When receiving high doses of methotrexate, you may also receive a medication called leucovorin, which helps decrease the side effects of methotrexate. Please follow the administration instructions from your medical team very closely. Treating Side Effects To decrease your risk of infection, wash your hands regularly. Avoid close contact with people who have a cold, the flu, or other infections. http://hillman.upmc.com/patients/community-support/education/chemotherapy-drugs/methotrexate 2/5

Take your temperature as your doctor or nurse tells you, and whenever you feel like you may have a fever. Mouth care is very important. Your mouth care should consist of routine, gentle cleaning of your teeth or dentures and rinsing your mouth with a mixture of ½ teaspoon of salt in 8 ounces of water or ½ teaspoon of baking soda in 8 ounces of water. This should be done at least after each meal and at bedtime. If you have mouth sores, avoid mouthwash that has alcohol. Also avoid alcohol and smoking because they can bother your mouth and throat. Drink plenty of fluids (a minimum of eight glasses per day is recommended). This is very important if you are receiving high doses of methotrexate. If you throw up or have loose bowel movements, you should drink more fluids so that you do not become dehydrated (lack water in the body from losing too much fluid). To help with nausea and vomiting, eat small, frequent meals instead of three large meals a day. Choose foods and drinks that are at room temperature. Ask your nurse or doctor about other helpful tips and medicine that is available to help or stop lessen these symptoms. If you get diarrhea, eat low-fiber foods that are high in protein and calories and avoid foods that can irritate your digestive tracts or lead to cramping. Ask your nurse or doctor about medicine that can lessen or stop your diarrhea. Manage tiredness by pacing your activities for the day. Be sure to include periods of rest between energy-draining activities. If you are dizzy, get up slowly after sitting or lying. Keeping your pain under control is important to your well-being. Please tell your doctor or nurse if you are experiencing pain. Food and Drug Interactions There are no known interactions of methotrexate with food. Folic acid supplements may interfere with how methotrexate works. Avoid use of folic acid supplements while taking this drug. Folic acid may be in your multivitamin. This drug may also interact with other medicines. Tell your doctor and pharmacist about all the medicines and dietary supplements (vitamins, minerals, herbs and others) that you are taking at this time. The safety and use of dietary supplements and alternative diets are often not known. Using these might affect your cancer or interfere with your treatment. Until more is known, you should not use dietary supplements or alternative diets without your cancer doctor's help. Drugs that treat heartburn and stomach upset such Protonix, Nexium, Prilosec, Pepcid, Tagamet, and Zantac may interact with methotrexate and cause serious harm. Call your doctor to find out what drug you may take to help with heartburn or stomach upset. Non-steroidal anti-inflammatory drugs (NSAIDs) e.g., ibuprofen and naproxen and salicylates e.g., aspirin, can interact with methotrexate and cause serious harm, or fatality. Avoid the use of these drugs with methotrexate. Do not drink alcohol while taking this medicine. Alcohol may increase your risk of changes in your liver function. http://hillman.upmc.com/patients/community-support/education/chemotherapy-drugs/methotrexate 3/5

When to Call the Doctor Call your doctor or nurse if you have any of these symptoms and/or any new or unusual symptoms: Fever of 100.5 F (38 C) or higher Chills Pain in your chest Dry cough Trouble breathing Easy bleeding or bruising (platelets) Pain in your mouth or throat that makes it hard to eat or drink Loose bowel movements (diarrhea) 4 times a day or loose bowel movements with lack of strength or a feeling of being dizzy Nausea that stops you from eating or drinking and/or is not relieved by prescribed medicines Throwing up more than 3 times a day Feeling dizzy or lightheaded Pain that does not go away or is not relieved by prescribed medicine Flu-like symptoms: fever, headache, muscle and joint aches, and fatigue (low energy, feeling weak) Decreased urine A new rash or a rash that is not relieved by prescribed medicines Signs of possible liver problems: dark urine, pale bowel movements, bad stomach pain, feeling very tired and weak, unusual itching, or yellowing of the eyes or skin Signs of tumor lysis: Confusion or agitation, decreased urine, nausea/vomiting, diarrhea, muscle cramping, numbness and/or tingling, seizures Signs of allergic reaction: swelling of the face, feeling like your tongue or throat are swelling, trouble breathing, rash, itching, fever, chills, feeling dizzy, and/or feeling that your heart is beating in a fast or not normal way Symptoms of a seizure such as confusion, blacking out, passing out, loss of hearing or vision, blurred vision, unusual smells or tastes (such as burning rubber), trouble talking, tremors or shaking in parts or all of the body, repeated body movements, tense muscles that do not relax, and loss of control of urine and bowels. If you or your family member suspects you are having a seizure, call 911 right away. If you think you are pregnant or may have impregnated your partner Reproduction Warnings Pregnancy warning: This drug can have harmful effects on the unborn baby. Women of child bearing potential should use effective methods of birth control during your cancer treatment and for at least one ovulatory cycle after treatment. Men with female partners of child bearing potential should use effective methods of birth control during your cancer treatment and for at least 3 months after your cancer treatment. Let your doctor know right away if you think you may be pregnant (or may have impregnated your partner). http://hillman.upmc.com/patients/community-support/education/chemotherapy-drugs/methotrexate 4/5

Breastfeeding warning: Women should not breast feed during treatment because this drug can enter the breast milk and cause harm to a breast feeding baby. Fertility warning: In men and women both, this drug may affect your ability to have children in the future. Talk with your doctor or nurse if you plan to have children. Ask for information on sperm or egg banking. In women, menstrual bleeding may become irregular or stop while you are getting this drug. Do not assume that you cannot become pregnant if you do not have a menstrual period. Revised November 2017 This information is intended to provide helpful health information to the general public and is not to be used in place of any medical, health, psychological, or any other kind of personal professional services. The information herein does not cover all possible uses, actions, precautions, side effects, or interactions of the medicines mentioned, nor is the information intended as medical advice for individual problems or for making an evaluation as to the risks and benefits of taking a particular medication. The dose, method of administration and contraindications for any administered medication should be confirmed before use. UPMC specifically disclaims all responsibility for any liability, loss or risk, personal or otherwise, which is incurred as a consequence, directly or indirectly, of the use and application of any medication mentioned herein. http://hillman.upmc.com/patients/community-support/education/chemotherapy-drugs/methotrexate 5/5