Zortress

Zortress is a prescription medication used to prevent organ rejection in adults who have received a kidney or liver transplant. 

Zortress belongs to a group of drugs called kinase inhibitors. To prevent organ rejection, this medication works by weakening the immune system to prevent it from attacking the new organ.

Zortress is a prescription medication used to prevent organ rejection in adults who have received a kidney or liver transplant. 

• Novartis Pharmaceuticals Corporation

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

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

• retaining fluids
• constipation
• high blood pressure
• nausea
• a condition in which the blood does not have enough healthy blood cells (anemia)
• urinary tract infection
• high amount of fats in the blood (cholesterol and triglycerides)

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

• diarrhea
• headache
• retaining fluids
• high blood pressure
• nausea
• fever
• stomach (abdomen) pain
• decrease in white blood cells (leukopenia)

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 Zortress. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

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:

• medications that block a protein in the body (CYP3A4) such as some macrolide antibiotics (clarithromycin, telithromycin, erythromycin), some HIV protease inhibitors (indinavir, nelfinavir, ritonavir, saquinavir), some HCV protease inhibitors (boceprevir, telaprevir), some azole antifungals (ketoconazole, itraconazole, posaconazole, voriconazole), conivaptan (Vaprisol), delavirdine (Rescriptor), and nefazodone
• medications that increase the activity of the enzyme CYP3A4 such as carbamazepine (Tegretol, Equetro, Carbatrol), phenobarbital, phenytoin (Dilantin), rifampin (Rifadin), St John's wort, and nimodipine (Nimotop)
• digoxin
• verapamil 
• heart medicine
• high blood pressure medicine
• a medicine to lower cholesterol or triglycerides
• cyclosporine (Sandimmune, Gengraf, Neoral)
• tuberculosis (TB) medicine
• St. John’s Wort
• seizure (anticonvulsant) medicine

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

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).

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

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

• have liver problems
• have skin cancer or it runs in your family
• have high cholesterol or triglycerides (fat in your blood)
• have Lapp lactase deficiency or glucose-galactose malabsorption. You should not take Zortress if you have this disorder.
• have any other medical conditions
• are pregnant or plan to become pregnant. It is not known if Zortress will harm your unborn baby. Talk with your doctor if you are pregnant or plan to become pregnant. Women who may become pregnant should use effective birth control (contraception) while taking Zortress and for 8 weeks after stopping Zortress.
• are breastfeeding or plan to breastfeed. It is not known if Zortress passes into your breast milk. You and your doctor should decide if you will take Zortress or breastfeed. You should not do both.

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. 

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.

It is not known if Zortress 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 Zortress.

Take Zortress exactly as your doctor tells you.

• Do not stop taking Zortress or change your dose unless your doctor tells you to.
• Take Zortress at the same time as your dose of cyclosporine medicine. 
• Do not stop taking or change your dose of cyclosporine or tacrolimus medicine unless your doctor tells you to.
• If your doctor changes your dose of cyclosporine your dose of Zortress may change.
• Take Zortress 2 times a day about 12 hours apart.
• Swallow Zortress tablets whole with a glass of water. Do not crush or chew Zortress tablets.
• Take Zortress tablets with or without food. If you take Zortress tablets with food, always take Zortress tablets with food. If you take Zortress tablets without food, always take Zortress tablets without food.
• Your doctor will do regular blood tests to check your kidney function while you take Zortress. It is important that you get these tests done when your doctor tells you to. Blood tests will monitor how your kidneys are working and make sure you are getting the right dose of Zortress and other transplant medications they may be on (cyclosporine and tacrolimus). 
• If you take too much Zortress, call your doctor or go to the nearest hospital emergency room right away.
• Avoid receiving any live vaccines while taking Zortress. Some vaccines may not work as well while you are taking Zortress.
• Do not eat grapefruit or drink grapefruit juice while you are taking Zortress. Grapefruit may increase your blood level of Zortress.
• Limit the amount of time you spend in the sunlight. Avoid using tanning beds or sunlamps. People who take Zortress have a higher risk of getting skin cancer. Wear protective clothing when you are in the sun and use a sunscreen with a high protection factor (SPF 30 and above). This is especially important if you have fair skin or if you have a family history of skin cancer.

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
• medication levels in your blood
• your liver function

The recommended dose of Zortress for adults getting a:

• Kidney transplant, the recommended starting dose of Zortress is 0.75 mg twice daily in combination as soon as possible after transplantation.
• Liver transplant, the recommended starting dose of Zortress is 1.0 mg twice daily starting 30 days after transplantation.

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

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

• Store Zortress tablets between 59°F to 86°F (15°C to 30°C).
• Keep Zortress out of the light.
• Keep Zortress tablets dry.

Keep Zortress 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 Zortress. 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 Zortress. Therefore reduced doses of cyclosporine should be used in combination with Zortress in order to reduce renal dysfunction. It is important to monitor the cyclosporine and Zortress 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.