Zortress

Dosage Forms And Strengths

Zortress is available as 0.25 mg, 0.5 mg, and 0.75 mg tablets.

Table 1: Description of Zortress (everolimus) Tablets

Storage And Handling

Zortress (everolimus) Tablets are packed in child-resistant blisters.

Table 11: Description of Zortress (everolimus) Tablets

Each strength is available in boxes of 60 tablets (6 blister strips of 10 tablets each).

Store at 25°C (77°F); excursions permitted to 15°C-30°C (59°F-86°F) [see USP Controlled Room Temperature].

Protect from light and moisture.

Distributed by: Novartis Pharmaceuticals Corporation East Hanover, New Jersey 07936. Revised: Oct 2016  

Serious side effects have been reported with Zortress including the following:

• Increased risk of getting certain cancers. People who take Zortress 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 serious infections. Zortress weakens the body’s immune system and affects your ability to fight infections. Serious infections can happen with Zortress that may lead to death. People taking Zortress have a higher chance of getting infections caused by viruses, bacteria, and fungi (yeast). Call your doctor if you have symptoms of infection including fever or chills. Certain viruses can live in your body and cause active infections when your immune system is weak. Viral infections that can happen with Zortress include BK virus-associated nephropathy. BK virus can affect how your kidney works and cause your transplanted kidney to fail.
• Blood clot in the blood vessels of your 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 your transplanted kidney (nephrotoxicity). You will need to start with a lower dose of cyclosporine when you take it with Zortress. Your Doctor should do regular blood tests to check your levels of both Zortress and cyclosporine.
• Increased risk of death that can be related to infection, in people who have had a heart transplant. You should not take Zortress if you have had a heart transplant without talking to your doctor.
• Your chance of having swelling under your skin is higher if you take Zortress 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. Zortress 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
• Lung or breathing problems. Tell your doctor right away if you have new or worsening cough, shortness of breath, difficulty breathing or wheezing. In some patients lung or breathing problems have been severe, and can even lead to death. Your doctor may need to stop Zortress or lower your dose.
• 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). 
• Change in kidney function. Zortress may cause kidney problems when taken along with a standard dose of cyclosporine medicine instead of a lower dose.

Your doctor should do blood and urine tests to monitor your cholesterol, triglycerides and kidney function.

• Blood clotting problems. 
• Diabetes. Tell your doctor if you have frequent urination, increased thirst or hunger.
• Male infertility (low or no sperm count).

Do not take Zortress 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).

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

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy. 

Zortress falls into category C. No well-controlled studies have been done in humans. Therefore, this medication may be used if the potential benefits to the mother outweigh the potential risks to the unborn child.

Women who may become pregnant should use effective birth control (contraception) while taking Zortress and for 8 weeks after stopping Zortress.

Zortress is usually taken twice daily (every 12 hours). Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger or smaller amounts or for longer than recommended.

You may take the medicine with or without food, but take it the same way each time. If you also take cyclosporine or tacrolimus, take both medications at the same time.

Do not stop taking Zortress or change your dose without first talking to your doctor.

Take this medication with a full glass (8 ounces) of water.

Do not crush or chew an everolimus tablet. Swallow the pill whole.

While using Zortress, you will need frequent blood and urine tests at your doctor's office.

Store at room temperature in the original container, away from moisture, heat, and light. Keep each tablet in its blister pack until you are ready to take it.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Get emergency medical help if you have signs of an allergic reaction: hives; chest pain, difficult breathing; swelling of your face, lips, tongue, or throat.

Serious and sometimes fatal infections may occur during treatment with Zortress. Stop using this medicine and call your doctor right away if you have signs of infection such as: fever, chills, swollen glands, or flu symptoms.

Zortress can cause a blood clot in the blood vessels of your transplanted organ, especially within 30 days after transplant. Tell your doctor right away if you have: fever with nausea or vomiting, blood in your urine, dark colored urine, little or no urination, jaundice (yellowing of your skin or eyes), or pain in your stomach, groin, lower back, or side.

Call your doctor at once if you have:

• changes in your vision;

• pain or burning when you urinate, red or brown colored urine;

• redness, warmth, swelling, oozing, or slow healing of a wound or surgical incision;

• new or worsening cough, wheezing, breathing problems;

• muscle pain or weakness;

• easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin;

• rapid weight gain, especially in your face and midsection;

• fluid build-up in the lungs--pain when you breathe, feeling short of breath while lying down, wheezing, gasping for breath, cough with foamy mucus;

• low red blood cells (anemia)--pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating; or

• high blood sugar--increased thirst, increased urination, hunger, dry mouth, fruity breath odor, drowsiness, dry skin, blurred vision, weight loss.

Common side effects may include:

• swelling in your legs, ankles, or feet;

• anemia, infections;

• urination problems;

• high blood pressure, increased cholesterol or triglycerides;

• stomach pain, nausea, diarrhea, constipation; or

• headache.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Many drugs can interact with Zortress. Not all possible interactions are listed here. Tell your doctor about all your current medicines and any you start or stop using, especially:

• cyclosporine or others medicine to prevent organ transplant rejection;

• St. John's wort;

• an antibiotic or antifungal medicine;

• cholesterol medication;

• heart or blood pressure medicine;

• HIV/AIDS medication;

• seizure medicine; or

• tuberculosis medication.

This list is not complete and many other drugs can interact with Zortress. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Give a list of all your medicines to any healthcare provider who treats you.

It is very important that your doctor check your progress at regular visits to make sure that this medicine is working properly. Blood and urine tests may be needed to check for unwanted effects.

Using this medicine while you are pregnant can harm your unborn baby. Use an effective form of birth control while you are using this medicine and for at least 8 weeks after stopping treatment. If you think you have become pregnant while using the medicine, tell your doctor right away.

If you are planning to have children, talk with your doctor before using this medicine. This medicine may decrease fertility in men and women.

This medicine may cause a serious lung problem called noninfectious pneumonitis. Check with your doctor right away if you have chest pain, chills, a cough, a fever, shortness of breath, or trouble breathing.

Check with your doctor right away if you have agitation, confusion, decreased urine amount, dizziness, headache, irritability, muscle twitching, nausea, rapid weight gain, swelling of the face, ankles, or hands, or unusual tiredness or weakness. These may be symptoms of a serious kidney problem.

While you are being treated with everolimus, and after you stop treatment with it, do not have any immunizations (vaccines) without your doctor's approval. Everolimus may lower your body's resistance and the vaccine may not work as well or you might get the infection the vaccine is meant to prevent. In addition, you should not be around other persons living in your household who receive live virus vaccines because there is a chance they could pass the virus on to you. Some examples of live virus vaccines include measles, mumps, influenza (nasal flu vaccine), poliovirus (oral form), rotavirus, and rubella. Do not get close to them and do not stay in the same room with them for very long. If you have questions about this, talk to your doctor.

Everolimus can temporarily lower the number of white blood cells in your blood, which increases the chance of getting an infection. It can also lower the number of platelets, which are necessary for proper blood clotting. If this occurs, there are certain precautions you can take, especially when your blood count is low, to reduce the risk of infection or bleeding:

• If you can, avoid people with infections. Check with your doctor immediately if you think you are getting an infection or if you get a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.
• Check with your doctor immediately if you notice any unusual bleeding or bruising, black, tarry stools, blood in the urine or stools, or pinpoint red spots on your skin.
• Be careful when using a regular toothbrush, dental floss, or toothpick. Your medical doctor, dentist, or nurse may recommend other ways to clean your teeth and gums. Check with your medical doctor before having any dental work done.
• Do not touch your eyes or the inside of your nose unless you have just washed your hands and have not touched anything else in the meantime.
• Be careful not to cut yourself when you are using sharp objects such as a safety razor or fingernail or toenail cutters.
• Avoid contact sports or other situations where bruising or injury could occur.

This medicine may increase your risk for getting skin cancer. When you begin taking this medicine:

• Stay out of direct sunlight, especially between the hours of 10:00 AM and 3:00 PM, if possible.
• Wear protective clothing, including a hat and sunglasses.
• Apply a sunblock product that has a sun protection factor (SPF) of at least 15, or higher if you have a fair complexion.
• Apply a sunblock lipstick that has an SPF of at least 15 to protect your lips.
• Do not use sunlamps, tanning beds, or tanning booths.
• If you have any questions about this, check with your doctor.

Everolimus may cause a serious type of allergic reaction called angioedema. This may occur more often when it is used with certain heart and blood pressure medicines called ACE inhibitors (eg, captopril [Capoten®], enalapril [Vasotec®], fosinopril [Monopril®], quinapril [Accupril®], ramipril [Altace®]). Check with your doctor right away if you have a rash, itching, a large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs, trouble breathing, or chest tightness while you are using this medicine.

If you have a kidney transplant, this medicine may increase your risk for having a blood clot in the new kidney. This usually occurs within the first 30 days after the kidney transplant. Check with your doctor right away if you are making less urine, or if you have pain in your groin, lower back, side, or stomach, dark-colored urine, a fever, or nausea or vomiting.

This medicine may also prevent you from healing correctly after an injury. Call your doctor right away if you have blood, fluid, or pus in your incision, your incision opens up, or it is red, warm, painful, or swollen.

If you are taking this medicine after a kidney transplant, it may increase your risk for developing rare and serious virus infections, such as polyoma virus-associated nephropathy (PVAN), progressive multiple leukoencephalopathy (PML), and BK virus-associated nephropathy (BKVAN). The BK virus may affect how your kidneys work and cause a transplanted kidney to fail. Check with your doctor right away if you have bloody urine, a decreased frequency or amount of urine, increased thirst, loss of appetite, lower back or side pain, nausea, swelling of the face, fingers, or lower legs, trouble breathing, unusual tiredness or weakness, vomiting, or weight gain.

Everolimus may cause mouth ulcers and sores in some patients. Tell your doctor right away if you have pain, discomfort, or open sores in your mouth while you are using this medicine. You may use a special mouthwash or mouth gel to treat these ulcers. Ask your doctor what type of products to use.

This medicine may affect blood sugar levels. If you have diabetes, check with your doctor if you notice a change in your blood or urine sugar tests.

Tell your doctor if you are taking a corticosteroid or another medicine that may weaken your immune system. This may increase your risk for developing a serious infection.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal (eg, St. John's Wort) or vitamin supplements.

• Tell all of your health care providers that you take this medicine (Zortress). This includes your doctors, nurses, pharmacists, and dentists.
• You may have more of a chance of getting an infection. Wash hands often. Stay away from people with infections, colds, or flu. Some infections have been very bad and even deadly.
• Check your blood sugar as you have been told by your doctor.
• Tell your doctor if you have signs of high blood sugar like confusion, feeling sleepy, more thirst, more hungry, passing urine more often, flushing, fast breathing, or breath that smells like fruit.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• Avoid grapefruit and grapefruit juice.
• Talk with your doctor before getting any vaccines. Use with this medicine may either raise the chance of an infection or make the vaccine not work as well.
• If you have mouth irritation or mouth sores, do not use mouth rinses that have alcohol, peroxide, iodine, or thyme in them. Talk with your doctor.
• This medicine may affect how wounds heal. Sometimes, people with wound healing problems have needed surgery. Call your doctor right away if you have a wound that is red, warm, painful, or swollen. Call your doctor right away if your wound opens up or if there is blood, fluid, or pus in a wound.
• Very bad and sometimes deadly lung problems have happened with this medicine (Zortress). Call your doctor right away if you have lung or breathing problems like trouble breathing, shortness of breath, or a cough that is new or worse.
• If you are 65 or older, use this medicine with care. You could have more side effects.
• This medicine may affect sperm in men. This may affect being able to father a child. Talk with the doctor.
• This medicine may cause harm to the unborn baby if you take it while you are pregnant.
• Use birth control that you can trust during care and for 2 months after care ends.
• If you get pregnant while taking this medicine (Zortress) or within 2 months after your last dose, call your doctor right away.
• This medicine may raise the chance of high blood sugar (diabetes). Talk with the doctor.
• There is a chance of skin cancer. Avoid sun, sunlamps, and tanning beds. Use sunscreen and wear clothing and eyewear that protects you from the sun.
• In people who have had a liver transplant, the risk of a blood clot in the liver transplant may be raised. This may lead to loss of the liver or death. Most of the time, this has happened within the first 30 days after the liver transplant. Talk with the doctor.
• Some people treated with this medicine have had very bad kidney problems caused by a certain viral infection (BK virus). In people who have had a kidney transplant, BK virus infection may cause loss of the kidney. Call your doctor right away if you have signs of kidney problems like change in the amount of urine passed, difficulty or pain when passing urine, or blood in the urine.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time this medicine is refilled. If you have any questions about this medicine (Zortress), please talk with the doctor, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine (Zortress). It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine (Zortress).

Review Date: October 4, 2017

Administration

Inform patients that Zortress should be taken orally twice a day approximately 12 hours apart consistently either with or without food.

Inform patients to avoid grapefruit and grapefruit juice which increase blood drug concentrations of Zortress [see Warnings and Precautions (5.19)].

Advise patients that Zortress should be used concurrently with reduced doses of cyclosporine and that any change in doses of these medications should be made under physician supervision. A change in the cyclosporine dose may also require a change in the dosage of Zortress. 

Inform patients of the necessity of repeated laboratory tests according to physician recommendations while they are taking Zortress.

Development of Lymphomas and Other Malignancies

Inform patients they are at risk of developing lymphomas and other malignancies, particularly of the skin, due to immunosuppression. Advise patients to limit exposure to sunlight and ultraviolet (UV) light by wearing protective clothing and using a sunscreen with a high protection factor [see Warnings and Precautions (5.2)]. 

Increased Risk of Infection 

Inform patients they are at increased risk of developing a variety of infections, including opportunistic infections, due to immunosuppression. Advise patients to contact their physician if they develop any symptoms of infection [see Warnings and Precautions (5.3, 5.13)]. 

Kidney Graft Thrombosis

Inform patients that Zortress has been associated with an increased risk of kidney arterial and venous thrombosis, resulting in graft loss, usually within the first 30 days posttransplantation [see Warnings and Precautions (5.4)].

Zortress and Calcineurin Inhibitor-Induced Nephrotoxicity

Advise patients of the risks of impaired kidney function with the combination of Zortress and cyclosporine as well as the need for routine blood concentration monitoring for both drugs. Advise patients of the importance of serum creatinine monitoring [see Warnings and Precautions (5.6)].

Angioedema

Inform patients of the risk of angioedema and that concomitant use of ACE inhibitors may increase this risk. Advise patients to seek prompt medical attention if symptoms occur [see Warnings and Precautions (5.8)].

Wound Healing Complications and Fluid Accumulation

Inform patients the use of Zortress has been associated with impaired or delayed wound healing, fluid accumulation and the need for careful observation of their incision site [see Warnings and Precautions (5.9)]. 

Interstitial Lung Disease/Non-Infectious Pneumonitis

Inform patients the use of Zortress may increase the risk of noninfectious pneumonitis. Advise patients to seek medical attention if they develop clinical symptoms consistent with pneumonia [see Warnings and Precautions (5.10)].

Hyperlipidemia

Inform patients the use of Zortress has been associated with increased serum cholesterol and triglycerides that may require treatment and the need for monitoring of blood lipid concentrations [see Warnings and Precautions (5.11)].

Proteinuria

Inform patients the use of Zortress has been associated with an increased risk of proteinuria [see Warnings and Precautions (5.12)].

Pregnancy

Advise women of childbearing age to avoid becoming pregnant throughout treatment and for 8 weeks after Zortress therapy has stopped.

Medications that Interfere with Zortress

Some medications can increase or decrease blood concentrations of Zortress. Advise patients to inform their physician if they are taking any of the following: antifungals, antibiotics, antivirals, anti-epileptic medicines including carbamazepine, phenytoin and barbiturates, herbal/dietary supplements (St. John’s Wort), and/or rifampin [see Warnings and Precautions (5.14)].

New Onset Diabetes

Inform patients the use of Zortress may increase the risk of diabetes mellitus and to contact their physician if they develop symptoms [see Warnings and Precautions (5.16)].

Immunizations

Inform patients that vaccinations may be less effective while they are being treated with Zortress. Advise patients live vaccines should be avoided [see Warnings and Precautions (5.18)].

Patient with Hereditary Disorders

Advise patients to inform their physicians that if they have hereditary disorders of galactose intolerance (Lapp-lactase deficiency or glucose-galactose malabsorption) not to take Zortress [see Warnings and Precautions (5.20)].

Distributed by:
Novartis Pharmaceuticals Corporation
East Hanover, New Jersey 07936

© Novartis

T2016-87
October 2016

Zortress may increase your risk of infection or certain cancer by changing the way your immune system works.

Serious and sometimes fatal infections may occur during treatment with Zortress. Stop using this medicine and call your doctor right away if you have signs of infection such as: fever, chills, body aches, or flu symptoms.

Zortress can cause a blood clot in the blood vessels of your transplanted organ. Tell your doctor right away if you have: fever with nausea or vomiting, blood in your urine, dark colored urine, little or no urination, jaundice (yellowing of your skin or eyes), or pain in your stomach, groin, lower back, or side.