Everolimus

Everolimus is a prescription medication used to treat certain types of cancer in the pancreas, kidney, brain, and breast. It is also used to prevent organ rejection in adults who have received a kidney or liver transplant.

One form of everolimus is given in combination (as an added treatment) to other seizure medicines in adults and children 2 years of age and older with a genetic condition called tuberous sclerosis complex (TSC) who have certain types of seizures (epilepsy). 

Everolimus belongs to a group of drugs called kinase inhibitors. It works by stopping cancer cells from reproducing and by decreasing blood supply to cancer cells. To prevent organ rejection, this medication works by weakening the immune system to prevent it from attacking the new organ.

Everolimus comes in tablet form and as a tablet to dissolve in water (for oral suspension). Depending on the condition being treated, this medication may be given once or twice a day. 

Common side effects include constipation, mouth ulcers, nausea, vomiting, diarrhea, and headache.

Everolimus is a prescription medicine used to treat:

• postmenopausal women with a type of breast cancer known as advanced hormone receptor-positive, HER2-negative breast cancer, along with Aromasin (exemestane) after treatment with other medication has not worked.
• adults with a type of pancreatic cancer known as pancreatic neuroendocrine tumor (PNET) that has progressed and can not be treated with surgery.  
• adults with a type of advanced kidney cancer known as renal cell carcinoma (RCC) when treatment with other medications has not worked.
• people with the following types of tumors that are seen with a genetic condition called tuberous sclerosis complex (TSC):
  • adults with a type of kidney tumor called renal angiomyolipoma, when the tumor does not need surgery right away.
  • adults and children with a type of brain tumor called subependymal giant cell astrocytoma (SEGA), when the tumor cannot be removed with surgery.

Everolimus is also used with other medicines to prevent transplant rejection in people who have received a kidney or liver transplant. 

Everolimus may be found in some form under the following brand names:

• Afinitor

• Afinitor Disperz

• Zortress

Everolimus can cause serious side effects. See “Drug Precautions”.

Common side effects of everolimus in people with advanced pancreatic neuroendocrine tumors and patients with advanced kidney cancer include:

• Mouth ulcers. Everolimus can cause mouth ulcers and sores. Tell your doctor if you have pain, discomfort, or open sores in your mouth. Your doctor may tell you to use a special mouthwash or mouth gel to reduce the likelihood of developing mouth ulcers or sores as well as to reduce their severity.
• Feeling weak or tired
• Cough, shortness of breath
• Diarrhea
• Rash, dry skin, and itching
• Nausea and vomiting
• Fever
• Loss of appetite
• Swelling of arms, hands, feet, ankles, face or other parts of the body 
• Abnormal taste
• Inflammation of the lining of the digestive system
• Headache
• Nose bleeds
• Pain in arms and legs

Common side effects of everolimus in people who have angiomyolipoma with TSC include:

• Mouth ulcers. Everolimus can cause mouth ulcers and sores. Tell your doctor if you have pain, discomfort, or open sores in your mouth. Your doctor may tell you to use a special mouthwash or mouth gel to reduce the likelihood of developing mouth ulcers or sores as well as to reduce their severity.
• Acne or eczema
• Nausea and vomiting
• Headache
• Cough
• Diarrhea
• Joint pain
• Swelling of your hands, arms, legs, and feet
• Stomach-area (abdomen) pain
• Respiratory tract infection
• Increased blood cholesterol level and certain other blood tests
• Decreased blood phosphate level
• Low red blood cells and white blood cells
• Increased blood sugar levels
• Absence of menstrual periods (menstruation). You may miss one or more menstrual periods. Tell your doctor if this happens.

Common side effects of everolimus in people with SEGA include:

• Infections of the respiratory tract, sinuses and ears
• Mouth ulcers. Everolimus can cause mouth ulcers and sores. Tell your doctor if you have pain, discomfort, or open sores in your mouth. Your doctor may tell you to use a special mouthwash or mouth gel that does not contain alcohol or peroxide.
• Diarrhea and constipation
• Vomiting
• Stomach pain
• Fever
• Seizure
• Headache
• Dizziness
• Skin problems (such as rash, acne, dry skin, or scratching of the skin)
• Cough
• Stuffy or runny nose
• Change in personality
• Low white blood cells (a type of blood cell that fights infection; your doctor will periodically check you for this problem)
• High levels of fats in the blood (raised triglycerides)

These common side effects have been reported in both kidney and liver transplant patients:

• nausea
• swelling of the lower legs, ankles and feet
• high blood pressure

The most common side effects of everolimus in people who have had a kidney transplant include:

• constipation
• low red blood cell count (anemia)
• urinary tract infection
• increased fat in the blood (cholesterol and triglycerides)

The most common side effects of everolimus in people who have had a liver transplant include:

• diarrhea
• headache
• fever
• abdominal pain
• low white blood cells

Tell your doctor if you have any side effect that bothers you or does not go away.

These are not all the possible side effects of everolimus. For more information, ask your doctor or pharmacist.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• St. John’s wort 
• Medicine for: 
        ○  Fungal infections 
        ○  Bacterial infections 
        ○  Tuberculosis
        ○  Seizures 
        ○  HIV-AIDS 
        ○  Heart conditions or high blood pressure
• Medicines that suppress your immune system

This is not a complete list of everolimus drug interactions. Ask your doctor or pharmacist for more information.

Everolimus can cause serious side effects including: 

Lung or breathing problems that may be severe, and can even lead to death. Tell your doctor right away if you have any of these symptoms:

• New or worsening cough
• Shortness of breath
• Chest pain
• Difficulty breathing or wheezing

Increased risk of developing an infection, such as pneumonia, or a bacterial, fungal or viral infection. Viral infections may include active hepatitis B in people who have had hepatitis B in the past (reactivation). In some people, these infections may be severe, and can even lead to death. You may need to be treated as soon as possible. Tell your doctor right away if you have a temperature of 100.5˚F or above, chills, or do not feel well.

Symptoms of hepatitis B or infection may include the following:

• Fever
• Skin rash
• Joint pain and inflammation
• Tiredness
• Loss of appetite
• Nausea
• Pale stool or dark urine
• Yellowing of the skin
• Pain in your upper right side

Kidney failure which may be severe and can even lead to death. Your doctor will likely do tests to check your kidney function before and during your treatment with everolimus.

Severe allergic reactions. Notify your healthcare provider or get medical help right away if you get signs and symptoms of a severe allergic reaction including rash, itching, hives, flushing, trouble breathing or swallowing, chest pain or dizziness.

Harm to your unborn baby. It is recommended women avoid becoming pregnant while taking this medication and for 8 weeks after the last dose. 

Decreased blood cell counts such as red blood cells, white blood cells, and platelets. Your healthcare provider should do blood tests to check your blood cell counts before you start and during treatment.

Everolimus for prevention of transplant rejection (in addition to the above):

Blood clot in the blood vessels of the transplanted kidney. If this happens, it usually occurs within the first 30 days after your kidney transplant. Tell your doctor right away if you:

• have pain in your groin, lower back, side or stomach (abdomen)
• make less urine or you do not pass any urine
• have blood in your urine or dark-colored urine (tea-colored)
• have fever, nausea, or vomiting

Serious problems with the transplanted kidney (nephrotoxicity). You will need to start with a lower dose of cyclosporine when you take it with everolimus. Your Doctor should do regular blood tests to check your levels of both everolimus and cyclosporine.

Increased risk of getting certain cancers. People who take everolimus have a higher chance of getting lymphoma and other cancers, especially skin cancer. Talk to your doctor about your risk for cancer.

Increased risk of death that can be related to infection, in people who have had a heart transplant. You should not take everolimus if you have had a heart transplant without talking to your doctor.

Swelling under your skin especially around your mouth, eyes and in your throat (angioedema). Your chance of having swelling under your skin is higher if you take everolimus along with certain other medicines. Tell your doctor right away or go to the nearest emergency room if you have any of these symptoms of angioedema:

• sudden swelling of your face, mouth, throat, tongue or hands
• hives or welts
• itchy or painful swollen skin
• trouble breathing

Delayed wound healing. Everolimus can cause your incision to heal slowly or not heal well. Call your doctor right away if you have any of the following symptoms:

• your incision is red, warm or painful
• blood, fluid, or pus in your incision
• your incision opens up
• swelling of your incision

Increased cholesterol and triglycerides (fat in your blood). If your cholesterol and triglyceride levels are high your doctor may want to lower them with diet, exercise and certain medicines.

Protein in your urine (proteinuria).

If you have any of the serious side effects listed above, you may need to stop taking everolimus for a while or use a lower dose. Follow your doctor’s instructions.

Do not take everolimus if you are allergic to everolimus or to any of its ingredients. Talk to your doctor before taking this medicine if you are allergic to:

• sirolimus (Rapamune)
• temsirolimus (Torisel)

You should not drink grapefruit juice or eat grapefruit during your treatment with everolimus. It may make the amount of everolimus in your blood increase to a harmful level.

Before taking everolimus, tell your healthcare provider about all of your medical conditions, including if you:

• Have or have had kidney problems
• Have or have had liver problems
• Have diabetes or high blood sugar
• Have high blood cholesterol levels
• Have any infections
• Have skin cancer or if it runs in your family
• Have Lapp lactase deficiency or glucose-galactose malabsorption.
• Previously had hepatitis B
• Are scheduled to receive any vaccinations. You should not receive a live vaccine or be around people who have recently received a live vaccine during your treatment with everolimus. If you are not sure about the type of immunization or vaccine, ask your healthcare provider. 
• are pregnant or planning on becoming pregnant
• are breastfeeding or planning on breastfeeding

Tell your healthcare provider about all of the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.

Tell your doctor if you are pregnant or plan to become pregnant. 

This medication can cause harm to your unborn baby. It is recommended women avoid becoming pregnant while taking this medication. In fact, it is recommended to use effective birth control while using this medication and for 8 weeks after stopping treatment. Talk to your healthcare provider about birth control options while using this medication. 

In regards to male patients with female partners of reproductive potential, it is recommended males use effective contraception during treatment and for 4 weeks after the last dose. 

It is not known if everolimus crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using everolimus.

Take everolimus exactly as your doctor tells you.

• Your healthcare provider will prescribe the dose of everolimus that is right for you.
• Take everolimus exactly as your healthcare provider tells you. Your healthcare provider may change your dose of everolimus if needed.
• Depending on the condition, everolimus may be taken once or twice a day. 
• Regardless of how many times you are to take everolimus, make sure to take everolimus the same way each time, either with food or without food.
• Do not stop taking everolimus or change your dose unless your doctor tells you to.

• Your doctor will order blood tests before you start everolimus and as needed during your treatment. These will include tests to check your blood cell count, kidney and liver function, cholesterol, and blood sugar levels. In addition, when treating certain conditions, your doctor will adjust your dose to reach a specific level of medication in your blood.

If you miss a dose of everolimus, you may still take it up to 6 hours after the time you normally take it. If it is more than 6 hours after you normally take your everolimus, skip the dose for that day. The next day, take everolimus at your usual time. Do not take 2 doses to make up for the one that you missed. If you are not sure about what to do, call your healthcare provider.

Everolimus tablets:

• Swallow everolimus tablets whole with a glass of water. Do not crush or chew everolimus tablets.

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following:

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your weight
• your height
• your age
• your gender

Afinitor (everolimus):

For advanced breast cancer, neuroendocrine tumors (NET), advanced kidney cancer, and renal angiomyolipoma with TSC, the recommended dose of everolimus tablets is 10 mg, to be taken once daily at the same time every day. Take either consistently with food or consistently without food. Everolimus tablets should be swallowed whole with a glass of water. Do not break or crush tablets.

Kidney transplantation: starting dose of 0.75 mg twice daily as soon as possible after transplantation.

Liver transplantation: starting dose of 1.0 mg twice daily starting 30 days after transplantation.

Take consistently with or without food at the same time as cyclosporine or tacrolimus.

Afinitor Disperz (everolimus):

• The recommended dose, when used to treat brain tumor called subependymal giant cell astrocytoma (SEGA), is 4.5 mg/m2 once daily.
• When treating TSC-Associated Partial-Onset Seizures, the recommended dose is 5 mg/m2 orally once daily. 

If you take too much everolimus, call your local Poison Control Center or seek emergency medical attention right away.

• Store everolimus at room temperature, between 68°F to 77°F (20°C to 25°C). 
• Keep everolimus in the package it comes in.
• Open the blister package just before taking everolimus.
• Keep the blister package and tablets dry prior to taking. 
• Keep everolimus out of light.
• Throw away everolimus that is out of date or no longer needed.

Keep everolimus and all medicines out of the reach of children.

WARNING: MALIGNANCIES AND SERIOUS INFECTIONS, KIDNEY GRAFT THROMBOSIS; NEPHROTOXICITY; AND MORTALITY IN HEART TRANSPLANTATION

Malignancies and Serious Infections

• Only physicians experienced in immunosuppressive therapy and management of transplant patients should prescribe everolimus. Patients receiving the drug should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physician responsible for maintenance therapy should have complete information requisite for the follow-up of the patient. 
• Increased susceptibility to infection and the possible development of malignancies such as lymphoma and skin cancer may result from immunosuppression. 

Kidney Graft Thrombosis

• An increased risk of kidney arterial and venous thrombosis, resulting in graft loss, was reported, mostly within the first 30 days post-transplantation. 

Nephrotoxicity

• Increased nephrotoxicity can occur with use of standard doses of cyclosporine in combination with everolimus. Therefore reduced doses of cyclosporine should be used in combination with everolimus in order to reduce renal dysfunction. It is important to monitor the cyclosporine and everolimus whole blood trough concentrations.

Mortality in Heart Transplantation

• Increased mortality, often associated with serious infections, within the first three months post-transplantation was observed in a clinical trial of de novoheart transplant patients receiving immunosuppressive regimens with or without induction therapy. Use in heart transplantation is not recommended.