Nat-Everolimus: Uses, Side Effects and Dosage

• NAT-EVEROLIMUS should only be prescribed and managed by healthcare professionals who are experienced in:

  • Anticancer medicines.
  • Treating patients with Tuberous Sclerosis Complex (TSC).

• If you are taking NAT-EVEROLIMUS for the treatment of Subependymal Giant Cell Astrocytoma (SEGA) associated with TSC:

  • Your healthcare professional will monitor the level of everolimus in your blood during treatment.
  • The ideal length of treatment is not known.
  • Your condition may reappear once you stop taking NAT-EVEROLIMUS.
  • There is a risk for developmental delays and delayed puberty in patients taking everolimus.
  • NAT-EVEROLIMUS is not to be used in children and adolescents (below 18 years of age) who have liver problems.
  • Risk of Medication Errors: NAT-EVEROLIMUS and everolimus tablets for oral suspension are not interchangeable. The doses and the way you should be taking these two drugs are not the same. Taking everolimus for oral suspension instead of NAT-EVEROLIMUS could lead to the medicine not working properly or to more side effects.

• If you are taking NAT-EVEROLIMUS for the treatment of angiomyolipoma of the kidney associated with TSC:

  • The ideal start and length of treatment is not known.
  • Female patients who were having periods may experience secondary amenorrhea when taking everolimus. This is when periods stop happening.

• NAT-EVEROLIMUS can cause serious side effects including:

  • Lung problems: NAT-EVEROLIMUS can cause:

    • Non-infectious pneumonitis (inflammation of the lungs)
    • Interstitial lung disease (inflammation or scarring of the lungs)

These lung problems can lead to death. Tell your healthcare professional right away if you have any new or worsening lung problems.

• Infections: NAT-EVEROLIMUS can make you more likely to get an infection. Some cases have resulted in death in both adults and children. Any infections should be treated and fully healed before starting therapy with NAT-EVEROLIMUS. Tell your healthcare professional right away if you experience signs of infection when taking NAT-EVEROLIMUS.

• Kidney failure (kidney problems): Cases of kidney failure (including severe kidney failure) have been reported in patients taking everolimus. Some have resulted in death. Your healthcare professional will monitor your kidney function before you start NAT-EVEROLIMUS and regularly during treatment.

See the Serious side effects and what to do about them table, below, for more information on these and other serious side effects.

• Adult women with hormone receptor-positive, HER2-negative advanced breast cancer:

  • Who are in menopause; and
  • In whom letrozole or anastrozole no longer keep their disease under control.

• Adults with a type of pancreatic cancer known as Pancreatic Neuroendocrine Tumour (PNET) in patients whose disease cannot be treated with surgery. For these patients their disease will:

  • Be advanced, or
  • Have spread outside the pancreas, or
  • Have worsened in the last 12 months.

• Adults with a type of cancer known as Neuroendocrine Tumour (NET) that originates from the gastrointestinal (GI) tract or lungs. For these patients, their disease:

  • Cannot be treated with surgery,
  • Will be advanced or spread outside the GI tract or lung, and
  • Will have progressed.
• Adults with metastatic kidney cancer. This means their disease has spread outside of the kidney to other parts of the body. These patients will have received previous treatment with sunitinib or sorafenib, which did not work.
• Adults with an angiomyolipoma of the kidney (a kidney tumour) that is linked to a genetic condition called Tuberous Sclerosis Complex (TSC). These patients will not need immediate surgery.
• Children (1 year of age or older) and adults with Subependymal Giant Cell Astrocytoma (SEGA), a brain tumour seen with a genetic condition called Tuberous Sclerosis Complex (TSC). For these patients, their disease will have progressed and cannot be treated with surgery. As well, they will not need immediate surgery.

• Slow down the growth and spread of:

  • Kidney cancer cells.
  • Pancreatic neuroendocrine cells.
  • Breast cancer cells when taken with exemestane.
• Reduce the size of brain tumours (SEGA) and kidney tumours (angiomyolipomas) that are associated with TSC.

• You are allergic to:

  • Everolimus or any other ingredients in NAT-EVEROLIMUS.
  • Sirolimus.
  • Temsirolimus.
• You have seizures (of any type).

• Are taking other medicines.
• Have any problems with your liver or have previously had any liver disease.
• Have any infections. All infections must be treated and fully healed before starting NAT-EVEROLIMUS.
• Have had hepatitis B, because it may be reactivated during your treatment with NAT-EVEROLIMUS.
• Are going to have or have recently had surgery, or still have an unhealed wound following surgery. NAT-EVEROLIMUS might affect the way your wound heals.
• Have received or are about to receive radiation treatment.
• Have kidney problems.
• Are pregnant, think you may be pregnant, or are planning to become pregnant.

• Diabetes, worsening of diabetes, or high blood sugar: Everolimus, the active ingredient in NAT-EVEROLIMUS, may cause a high level of sugar in the blood, including type II diabetes. Your healthcare professional will monitor your blood sugar level before you start NAT-EVEROLIMUS and regularly during treatment. More monitoring may be required if you take other medicines. If you have diabetes, closely monitor your blood sugar while taking NAT-EVEROLIMUS.
• Stomatitis (mouth sores): Mouth sores may appear in your mouth when taking NAT-EVEROLIMUS. Stomatitis mostly occurs within the first 8 weeks of treatment. If you experience stomatitis, you might need treatment with a mouthwash or gel. Some mouthwashes and gels can make your stomatitis worse. Do not try anything without checking with your healthcare professional first.

• Bleeding problems: Some patients taking everolimus have reported various types of bleeding problems, including:

  • Hemoptysis (coughing up blood)
  • Hematuria (blood in the urine)
  • Gastrointestinal (GI) bleeding (bleeding anywhere along the GI tract between mouth and anus)
  • Intracerebral hemorrhage (bleeding in the brain)

• Have an effect on blood clotting.
• Increase the risk of bleeding.

• Rhabdomyolysis (breakdown of damaged muscle): Some cases of rhabdomyolysis have been reported in patients taking everolimus. Your healthcare professional will monitor you for signs of rhabdomyolysis during therapy with NAT-EVEROLIMUS. Stop taking NAT-EVEROLIMUS and tell your healthcare professional right away if you experience symptoms of rhabdomyolysis.

• Radiation sensitization and radiation recall (severe reactions at sites of radiation): Severe radiation reactions have been observed in some patients taking everolimus. These reactions happened during or shortly after radiation therapy. Tell your healthcare professional if you:

  • Have received radiation therapy in the past.
  • Are receiving radiation therapy at the present time.
  • Will receive radiation therapy.

• Receiving live vaccines.
• Close contact with those who have received live vaccines.

• Unusual levels of reproductive hormones required for the development of sperm.
• Absence of sperm.

• NAT-EVEROLIMUS could harm an unborn baby.
• Use a highly effective birth control method during your treatment with NAT-EVEROLIMUS and for at least 8 weeks after your last dose.
• Continue using this method of birth control even if your periods have stopped. Your periods may stop during your treatment with NAT-EVEROLIMUS; however, it could still be possible for you to become pregnant.
• Patients who have not yet had their first period should also use effective birth control.

• Contact your healthcare professional if you:

  • Become pregnant.
  • Experience irregular or delayed periods.
  • Experience absence of periods.

• During treatment with NAT-EVEROLIMUS.
• For two weeks after the last dose of NAT-EVEROLIMUS.

• The amount of blood cells in your body.
• That your liver or kidneys are working properly.
• The level of electrolytes in your body.
• The amount of cholesterol or triglycerides (types of fat) in your blood.
• Your blood sugar level.

• Height and weight
• Reproductive development (puberty)

• Ketoconazole, itraconazole, voriconazole, fluconazole – used to treat fungal infections.
• Clarithromycin, telithromycin, erythromycin – used to treat bacterial infections.
• Rifampicin, rifabutin – used to treat bacterial infections, primarily tuberculosis.
• St. John’s Wort – an herbal remedy used mainly for depression.
• Phenytoin, carbamazepine, oxcarbazepine, phenobarbital, clobazam – used to treat seizures and epilepsy.
• Ritonavir, amprenavir, fosamprenavir, efavirenz, nevirapine, atazanavir, nelfinavir – used to treat viral infections, primarily HIV.
• Verapamil, diltiazem – used to treat heart conditions or high blood pressure.
• Angiotensin-converting enzyme (ACE) inhibitors – used to treat high blood pressure and other cardiovascular problems.
• Statins e.g. atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, simvastatin – used to lower blood cholesterol levels.
• Cyclosporine – used to suppress the immune system.
• Aprepitant – used to prevent nausea and vomiting.
• Midazolam – used to produce sleepiness and drowsiness.
• Pimozide – used to treat mental disorders.
• Quinidine – used to treat certain types of irregular heartbeats.
• Ergotamine – used to treat migraines and headaches.

• Take NAT-EVEROLIMUS exactly as your healthcare professional tells you.
• Take your tablets at about the same time each day (preferably in the morning).
• Take with or without food. Be consistent in how you take NAT-EVEROLIMUS either always on an empty stomach or always with food.
• Place the tablet in your mouth and swallow whole with a glass of water. Do not chew or crush the tablets. This may affect how quickly the medicine gets into your body.

• The type of disease you have.
• Any other condition you have.
• Any other medications you are taking.
• Blood test results.
• Your height and weight.

Leukopenia, lymphopenia, neutropenia (decreased white blood cells): infections, fatigue, fever, aches, pains and flu-like

symptoms

Cellulitis (skin infection): pain,

tenderness, swelling, redness of the skin

Convulsion: seizure, spasms,

shaking or fits

Lymphoedema (build-up of lymph in tissues):

Swelling of part or all of your arm (including fingers) or leg (including toes), feeling of heaviness, restricted movement, discomfort

Herpes Zoster virus (shingles): a painful skin rash of fluid-filled blisters, blisters appear along a

strip of skin, itching

Palmar-plantar

erythrodysaesthesia syndrome (also called Hand-Foot syndrome): red or swollen palms, thick calluses and blisters of the hands and soles of the feet, tingling or burning, tightness of the skin

Pleural effusion (fluid around

the lungs): chest pain, difficult or painful breathing, cough

Pneumonitis, pulmonary

embolism, acute respiratory syndrome (lung or breathing

problems): cough, chest pain, shortness of breath

Thrombocytopenia (low blood

platelets): bruising or bleeding for longer than usual if you hurt

yourself, fatigue and weakness

Intestinal obstruction (partial

or complete blockage of the small intestine): abdominal cramps or pain, loss of appetite, constipation, vomiting, inability to have a bowel movement or pass gas, swelling of the abdomen

Liver failure (serious disturbance of liver function, hepatic failure): yellow colour to skin, whites of the eyes (jaundice), bleeding easily, swollen abdomen, mental disorientation or confusion,

sleepiness, coma

Radiation sensitization and radiation recall (severe reactions at sites of radiation) including:

• Severe skin reactions: skin rash, blistering, peeling or discoloration of the skin
• Pneumonitis (inflammation of lung tissue): shortness of breath, which may be accompanied by a cough, fever or chills
• Esophagitis (inflammation of the esophagus): difficulty or pain when swallowing, chest pain, heartburn or acid reflux