Cyclophosphamide IV Formulation (Cytoxan®, Neosar®, Endoxan®)

Cyclophosphamide kills cancer cells through a process called alkylation. Alkylation damages the DNA of cells, which prevents them from dividing and causes them to die. Since cancer cells tend to divide faster and with less error correcting than healthy cells, cancer cells are more sensitive to this damage.

How to Take Cyclophosphamide

Cyclophosphamide can be given by intravenous (IV, into a vein) infusion or taken orally (by mouth) in a pill form. This information is about the IV formulation. Your dose and schedule are determined by your size and type of cancer being treated.

This medication can interact with a number of medications including: metronidazole, tamoxifen, warfarin, cyclosporine amiodarone, Echinacea, and thiazide diuretics, among others. Be sure to tell your healthcare provider about all medications and supplements you take.

Possible Side Effects

There are a number of things you can do to manage the side effects of cyclophosphamide. Talk to your care team about these recommendations. They can help you decide what will work best for you. There are some of the most common or important side effects:

Infection and Low White Blood Cell Count (Leukopenia or Neutropenia)

This medication can cause life threatening infections, with or without a decrease in white blood cell counts.

White blood cells (WBC) are important for fighting infection. While receiving treatment, your WBC count can drop, putting you at a higher risk of getting an infection. You should let your doctor or nurse know right away if you have a fever (temperature greater than 100.4°F or 38°C), sore throat or cold, shortness of breath, cough, burning with urination, or a sore that doesn't heal.

Tips to preventing infection:

• Washing hands, both yours and your visitors, is the best way to prevent the spread of infection.
• Avoid large crowds and people who are sick (i.e.: those who have a cold, fever or cough or live with someone with these symptoms).
• When working in your yard, wear protective clothing including long pants and gloves.
• Do not handle pet waste.
• Keep all cuts or scratches clean.
• Shower or bathe daily and perform frequent mouth care.
• Do not cut cuticles or ingrown nails. You may wear nail polish, but not fake nails.
• Ask your oncology care team before scheduling dental appointments or procedures.
• Ask your oncology care team before you, or someone you live with, has any vaccinations.

Low Red Blood Cell Count (Anemia)

Your red blood cells are responsible for carrying oxygen to the tissues in your body. When the red cell count is low, you may feel tired or weak. You should let your oncology care team know if you experience any shortness of breath, difficulty breathing or pain in your chest. If the count gets too low, you may receive a blood transfusion.

Low Platelet Count (Thrombocytopenia)

Platelets help your blood clot, so when the count is low you are at a higher risk of bleeding. Let your oncology care team know if you have any excess bruising or bleeding, including nose bleeds, bleeding gums or blood in your urine or stool. If the platelet count becomes too low, you may receive a transfusion of platelets.

• Do not use a razor (an electric razor is fine).
• Avoid contact sports and activities that can result in injury or bleeding.
• Do not take aspirin (salicylic acid), non-steroidal, anti-inflammatory medications (NSAIDs) such as Motrin/Advil (ibuprofen), Aleve (naproxen), Celebrex (celecoxib) etc. as these can all increase the risk of bleeding. Please consult with your healthcare team regarding use of these agents and all over the counter medications/supplements while on therapy.
• Do not floss or use toothpicks and use a soft-bristle toothbrush to brush your teeth.

Nausea and/or Vomiting

Talk to your oncology care team so they can prescribe medications to help you manage nausea and vomiting. In addition, dietary changes may help. Avoid things that may worsen the symptoms, such as heavy or greasy/fatty, spicy or acidic foods (lemons, tomatoes, oranges). Try saltines, or ginger ale to lessen symptoms.

Call your oncology care team if you are unable to keep fluids down for more than 12 hours or if you feel lightheaded or dizzy at any time.

Diarrhea

Your oncology care team can recommend medications to relieve diarrhea. Also, try eating low-fiber, bland foods, such as white rice and boiled or baked chicken. Avoid raw fruits, vegetables, whole grain breads, cereals and seeds. Soluble fiber is found in some foods and absorbs fluid, which can help relieve diarrhea. Foods high in soluble fiber include: applesauce, bananas (ripe), canned fruit, orange sections, boiled potatoes, white rice, products made with white flour, oatmeal, cream of rice, cream of wheat, and farina. Drink 8-10 glasses of non-alcoholic, un-caffeinated fluid a day to prevent dehydration.

Loss or Thinning of Scalp and Body Hair (Alopecia)

Your hair may become thin, brittle, or may fall out. This typically begins two to three weeks after treatment starts. This hair loss can be all body hair, including pubic, underarm, legs/arms, eyelashes, and nose hairs. The use of scarves, wigs, hats and hairpieces may help. Hair generally starts to regrow soon after treatment is completed. Remember your hair helps keep you warm in cold weather, so a hat is particularly important in cold weather or to protect you from the sun.

Nail and Skin Changes

Your fingernails/toenails may become dark, brittle or fall off. You may notice dry skin or changes in the color or tone of your skin. Your skin may be more sensitive to the sun, which can result in severe sunburn or rash. Sun sensitivity can last even after chemotherapy is completed. Avoid the sun between 10-2pm, when it is strongest. Wear sunscreen (at least SPF 15) everyday, wear sunglasses and long sleeves/pants to protect your skin. Keep your fingernails and toenails clean and dry. You may use nail polish, but do not wear fake nails. If any nails fall off, clean the nail bed well with soap and water and cover with a band aid.

Important but Less Common Side Effects

• Bladder Irritation: Cyclophosphamide may irritate your bladder and can cause blood in your urine or pain with urination. Drink at least 6 to 8 glasses of fluid per day to flush out your bladder. You may be given IV fluids along with this medication to help lower the chance of bladder irritation. Let your care team know if you have a hard time urinating, have pain or pink/red urine, or bleed with urination. When given in high doses, your provider may give you a mediation to protect your bladder.
• Secondary Malignancies: There is a very low risk of developing leukemia or another type of cancer due to treatment with this medication, which can happen many years after treatment. This is most often linked to repeated treatments or high doses.
• Electrolyte Abnormalities: This medication can affect the normal levels of electrolytes (sodium, potassium, magnesium, calcium, etc.) in your body. Your levels will be monitored using blood tests. If your levels become too low, your care team may prescribe specific electrolytes to be given by IV or taken by mouth. Do not take any supplements without first consulting with your care team.
• Lung Changes: This medication may cause lung changes, including pneumonitis (irritation of the lung tissue) and pulmonary fibrosis (a scarring and stiffening of the lung tissue). These problems can develop during treatment, or months to years after treatment is completed. Call your provider right away if you have new or worsening shortness of breath, cough, wheezing or difficulty breathing.
• Heart Problems: This medication can affect your heart function and can cause abnormal heartbeats or an abnormal heart rhythm called QT prolongation. Call your provider right away if you develop swelling of the feet or ankles, shortness of breath, have rapid weight gain, feel abnormal heartbeats, or if you feel dizzy or faint.
• Wound Healing: This medication can lead to slower or incomplete wound healing, such as a surgical wound not healing or staying closed. Be sure to inform the team performing the surgical procedure that you are taking this drug. You should also inform your oncology team that a surgical procedure is planned. It is recommended that this medication be discontinued prior to any surgery. In addition, any surgical incision should be fully healed prior to starting or restarting the medication. If you have a surgical wound that has not healed or begins to have signs of infection (redness, swelling, warmth), report this to your healthcare team.
• Veno-occlusive Liver Disease: This medication can cause blood clots in the small veins of your liver. This can lead to liver failure. If you feel like there is fluid in your belly or notice that your skin or the whites of your eyes are yellowing, contact your care team right away.

Reproductive Concerns

This medication may affect your reproductive system, resulting in the menstrual cycle or sperm production becoming irregular or stopping permanently. Women may experience menopausal effects including hot flashes and vaginal dryness. In addition, the desire for sex may decrease during treatment. You may want to consider sperm banking or egg harvesting if you may wish to have a child in the future. Discuss these options with your oncology team.

Exposure of an unborn child to this medication could cause birth defects, so you should not become pregnant or father a child while on this medication. For women, effective birth control is necessary during treatment and for at least 1 year after treatment. For men, effective birth control is necessary during treatment and for at least 4 months after treatment. Even if your menstrual cycle stops or you believe you are not producing sperm, you could still be fertile and conceive. You should not breastfeed during treatment and for at least 1 week after your last dose.