Sirolimus Protein-Bound (Fyarro™)

Sirolimus protein-bound is a kinase inhibitor that inhibits rapamycin kinase (mTOR kinase), an enzyme required for cell growth and survival. By blocking this enzyme, the medication prevents cell division and, in turn, tumor growth. The medication can also interrupt angiogenesis, the development of blood vessels to supply the tumor with nutrients, which they need to grow.

How To Take

This medication is given intravenously (IV, directly into a vein). The dose is based on your size. How often you receive the medication will be determined by your team.

The blood levels of this medication can be affected by certain foods and medications, so they should be avoided. These include: grapefruit, grapefruit juice, verapamil, ketoconazole, rifampin, phenytoin, St. John’s wort, and modafinil, among others. Be sure to tell your healthcare provider about all medications and supplements you take.

You, or anyone you live with, should avoid having live or live-attenuated vaccines while receiving this medication. These include herpes zoster (Zostavax) for shingles prevention, oral polio, measles, nasal flu vaccine (FluMist®), rotavirus, and yellow fever vaccines.

Possible Side Effects

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

Mouth Sores (Stomatitis)

Certain cancer treatments can cause sores or soreness in your mouth and/or throat. Notify your doctor or nurse if your mouth, tongue, inside of your cheek or throat becomes white, ulcerated, or painful. Performing regular mouth care can help prevent or manage mouth sores. If mouth sores become painful, your doctor or nurse can recommend a pain reliever.

• Brush with a soft-bristle toothbrush or cotton swab twice a day.
• Avoid mouthwashes that contain alcohol. A baking soda and/or salt warm water mouth rinse (2 level teaspoons of baking soda or 1 level teaspoon salt in an eight-ounce glass of warm water) is recommended 4 times daily.
• If your mouth becomes dry, eat moist foods, drink plenty of fluids (6-8 glasses), and suck on sugarless hard candy.
• Avoid smoking and chewing tobacco, drinking alcoholic beverages, and citrus juices.

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.

Kidney Problems

This medication can cause kidney problems, including an increased creatinine level, which your oncology care team may monitor for using blood tests. Notify your healthcare provider if you notice decreased urine output, blood in the urine, swelling in the ankles, or loss of appetite.

Fatigue

Fatigue is very common during cancer treatment and is an overwhelming feeling of exhaustion that is not usually relieved by rest. While on cancer treatment, and for a period after, you may need to adjust your schedule to manage fatigue. Plan times to rest during the day and conserve energy for more important activities. Exercise can help combat fatigue; a simple daily walk with a friend can help. Talk to your healthcare team for helpful tips on dealing with this side effect.

Rash

Some patients may develop a rash, scaly skin, or red itchy bumps. Use an alcohol-free moisturizer on your skin and lips; avoid moisturizers with perfumes or scents. Your oncology care team can recommend a topical medication if itching is bothersome. If your skin does crack or bleed, be sure to keep the area clean to avoid infection. Be sure to notify your oncology care team of any rash that develops, as this can be a reaction. They can give you more tips on caring for your skin.

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.

High Cholesterol/Triglyceride Level

This medication can cause high levels of cholesterol and/or triglycerides. You may be monitored for this using blood tests. There are no immediate symptoms of high cholesterol/ triglycerides but when not treated appropriately it can lead to heart attack and stroke.

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.

Peripheral Edema

Peripheral edema is swelling of the extremities caused by the retention of fluid. It can cause swelling of the hands, arms, legs, ankles, and feet. The swelling can become uncomfortable. Notify your oncology care team if you are experiencing any new or worsening swelling.

Diarrhea

Diarrhea can be a serious side effect of this medication. Notify your care provider if you start to have diarrhea to determine which medications you should be taking. Diarrhea can lead to dehydration so it is important to manage this side effect.

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.

Muscle or Joint Pain/Aches and Headache

Your healthcare provider can recommend medications and other strategies to help relieve pain.

Decrease in Appetite or Taste Changes

Nutrition is an important part of your care. Cancer treatment can affect your appetite and, in some cases, the side effects of treatment can make eating difficult. Ask your oncology care team about nutritional counseling services at your treatment center to help with food choices.

• Try to eat five or six small meals or snacks throughout the day, instead of 3 larger meals.
• If you are not eating enough, nutritional supplements may help.
• You may experience a metallic taste or find that food has no taste at all. You may dislike foods or beverages that you liked before receiving cancer treatment. These symptoms can last for several months or longer after treatment ends.
• Avoid any food that you think smells or tastes bad. If red meat is a problem, eat chicken, turkey, eggs, dairy products, and fish without a strong smell. Sometimes cold food has less of an odor.
• Add extra flavor to meat or fish by marinating it in sweet juices, sweet and sour sauce, or dressings. Use seasonings like basil, oregano, or rosemary to add flavor. Bacon, ham, and onion can add flavor to vegetables.

Liver Toxicity

This medication can cause liver toxicity, which your oncology care team may monitor for using blood tests called liver function tests. Notify your healthcare provider if you notice yellowing of the skin or eyes, your urine appears dark or brown, or you have pain in your abdomen, as these can be signs of liver toxicity.

Electrolyte Abnormalities

This medication can affect the normal levels of electrolytes (potassium, sodium, 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.

High Blood Pressure

This medication can cause high blood pressure (hypertension). Patients should have their blood pressure checked regularly during therapy. Any hypertension should be treated appropriately. If hypertension cannot be controlled, the medication may be stopped. Report any headaches, vision changes or dizziness to your oncology care team.

Bleeding/Hemorrhage

This medication can cause serious bleeding in some cases. Let your oncology team know immediately if you have any excess bruising or bleeding, including nose bleeds, bleeding gums, or blood in your urine or stool.

Constipation

There are several things you can do to prevent or relieve constipation. Include fiber in your diet (fruits and vegetables), drink 8-10 glasses of non-alcoholic fluids a day, and keep active. A stool softener once or twice a day may prevent constipation. If you do not have a bowel movement for 2-3 days, you should contact your healthcare team for suggestions to relieve the constipation.

Important but Less Common Side Effects

• Allergic Reactions: In some cases, patients can have an allergic reaction to this medication. Signs of a reaction can include: shortness of breath or difficulty breathing, chest pain, rash, flushing or itching, or a decrease in blood pressure. If you notice any changes in how you feel during the infusion, let your nurse know immediately. The infusion will be slowed or stopped if this occurs. Depending on the severity of your reaction, you may still be able to receive the medication with a pre-medication to prevent a reaction, or if the medication is given at a slower rate.
• Interstitial Lung Disease/ Non-Infectious Pneumonitis: Patients can develop an inflammation of the lungs (called pneumonitis) while taking this medication. Notify your oncology care team right away if you develop any new or worsening symptoms, including shortness of breath, trouble breathing, cough, or fever.
• High Blood Sugar: This medication can cause elevated blood sugar levels in patients with and without diabetes. Your oncology care team will monitor your blood sugar. If you develop increased thirst, urination or hunger, blurry vision, headaches, or your breath smells like fruit, notify your healthcare team. Diabetics should monitor their blood sugar closely and report elevations to the healthcare team.

Sexual & 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. Effective birth control is necessary during treatment and for at least 12 weeks after treatment, even if your menstrual cycle stops or you believe you are not producing sperm. You should not breastfeed while receiving this medication or for 2 weeks after your last dose.