Zortress

What is Zortress?

• Zortress (Everolimus) is an mTOR inhibitor immunosuppressant used with other drugs to keep the body from rejecting a kidney or liver transplant.
• It lowers the body’s immune response.
• Zortress contains the active ingredient everolimus.
• It is a type of immunosuppressant and a type of kinase inhibitor.

Everolimus

Everolimus ball-and-stick

What are the uses of this medicine?

• Zortress(Everolimus) is a prescription medicine used to prevent transplant rejection (antirejection medicine) in people who have received a kidney transplant or liver transplant.
• Transplant rejection happens when the body’s immune system perceives the new transplanted kidney as “foreign” and attacks it.
• Zortress is used with other medicines called cyclosporine, corticosteroids and certain other transplant medicines to prevent rejection of your transplanted kidney.
• ZORTRESS is used with other medicines called tacrolimus and corticosteroids to prevent rejection of your transplanted liver.

Limitations of Use:

• It is not known if ZORTRESS is safe and effective in transplanted organs other than the kidney and liver.
• It is not known if ZORTRESS is safe and effective in children under 18 years of age.
• It is not known if ZORTRESS is safe and effective in kidney transplant patients at high immunologic risk.

How does this medicine work?

• Everolimus inhibits antigenic and interleukin (IL-2 and IL-15) stimulated activation and proliferation of T and B lymphocytes.
• In cells, everolimus binds to a cytoplasmic protein, the FK506 Binding Protein-12 (FKBP-12), to form an immunosuppressive complex (everolimus: FKBP-12) that binds to and inhibits the mammalian target of rapamycin (mTOR), a key regulatory kinase.
• In the presence of everolimus phosphorylation of p70 S6 ribosomal protein kinase (p70S6K), a substrate of mTOR, is inhibited.
• Consequently, phosphorylation of the ribosomal S6 protein and subsequent protein synthesis and cell proliferation are inhibited.
• The everolimus: FKBP-12 complex has no effect on calcineurin activity.

Who Should Not Use this medicine ?

This medicine cannot be used in patients:

• with known hypersensitivity to everolimus, sirolimus, or to components of the drug product.

What drug interactions can this medicine cause?

• Coadministration of Zortress with strong CYP3A4-inhibitors (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir, boceprevir, telaprevir) and strong CYP3A4 inducers (e.g., rifampin, rifabutin) is not recommended without close monitoring of everolimus whole blood trough concentrations.

Is this medicine FDA approved?

• Initial U.S. Approval: 2009

How should this medicine be used?

Recommended dosage: Dosage in Adult Kidney Transplant Patients:

• An initial Zortress dose of 0.75 mg orally twice daily (1.5 mg per day) is recommended for adult kidney transplant patients in combination with reduced dose cyclosporine, administered as soon as possible after transplantation.
• Oral prednisone should be initiated once oral medication is tolerated.

Dosage in Adult Liver Transplant Patients:

• Start Zortress at least 30 days posttransplant.
• An initial dose of 1 mg orally twice daily (2 mg per day) is recommended for adult liver transplant patients in combination with reduced dose tacrolimus.
• Steroid doses may be further tapered on an individualized basis depending on the clinical status of patient and function of graft.

• Adjust maintenance dose to achieve trough concentrations within the 3 to 8 ng/mL target range using LC/MS/MS assay method.
• Administer consistently with or without food at the same time as cyclosporine or tacrolimus.

• Mild Hepatic Impairment: Reduce initial daily dose by one-third
• Moderate or Severe Hepatic Impairment: Reduce initial daily dose by one-half

Administration:

• Take ZORTRESS exactly as your doctor tells you to.
• 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.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As 0.25 mg, 0.5 mg, 0.75 mg, and 1 mg tablets

This medicine is available in fallowing brand namesː

• ZORTRESS

What side effects can this medication cause?

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 ZORTRESS 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 ZORTRESS in people who have had a liver transplant include:

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

ZORTRESS may cause serious side effects, including:

• Increased risk of getting certain cancers
• Increased risk of serious infections
• Blood clot in the blood vessels of your transplanted kidney
• Serious problems with your transplanted kidney (nephrotoxicity)
• angioedema
• delayed wound healing
• lung or breathing problems
• increased cholesterol and triglycerides (fat in your blood)
• protein in your urine (proteinuria)
• change in kidney function

What special precautions should I follow?

• 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.
• Patients receiving immunosuppressants, including Zortress, are at increased risk of developing lymphomas and other malignancies, particularly of the skin. 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.
• Only physicians experienced in management of systemic immunosuppressant therapy in transplantation should prescribe Zortress.
• Patients receiving immunosuppressants, including Zortress, are at increased risk of developing bacterial, viral, fungal, and protozoal infections, including opportunistic infections. Antimicrobial prophylaxis for Pneumocystis jiroveci (carinii) pneumonia and prophylaxis for cytomegalovirus (CMV) is recommended in transplant recipients.
• Mammalian target of rapamycin (mTOR) inhibitors are associated with an increase in hepatic artery thrombosis (HAT). Therefore, Zortress should not be administered earlier than 30 days after liver transplant.
• In kidney transplant recipients, Zortress with standard dose cyclosporine increases the risk of nephrotoxicity resulting in a lower glomerular filtration rate. Renal function should be monitored during the administration of Zortress. Consider switching to other immunosuppressive therapies if renal function does not improve after dose adjustments or if the dysfunction is thought to be drug related. Caution should be exercised when using other drugs which are known to impair renal function.
• Zortress has been associated with the development of angioedema. The concomitant use of Zortress with other drugs known to cause angioedema, such as angiotensin converting enzyme (ACE) inhibitors may increase the risk of developing [[angioedema.
• Zortress increases the risk of delayed wound healing and increases the occurrence of wound-related complications.
• Cases of ILD, implying lung intraparenchymal inflammation (pneumonitis) and/or fibrosis of non-infectious etiology, some reported with pulmonary hypertension [including pulmonary arterial hypertension (PAH)] as a secondary event, have occurred in patients receiving rapamycins and their derivatives, including Zortress. Most cases generally resolve on drug interruption with or without glucocorticoid therapy.
• Increased serum cholesterol and triglycerides, requiring the need for anti-lipid therapy, have been reported to occur following initiation of Zortress. Any patient who is administered Zortress should be monitored for hyperlipidemia. Zortress has not been studied in patients with baseline cholesterol levels greater than 350 mg/dL.
• The use of Zortress in transplant patients has been associated with increased proteinuria. Patients receiving Zortress should be monitored for proteinuria.
• Patients receiving immunosuppressants, including Zortress, are at increased risk for opportunistic infections; including polyoma virus infections.
• The concomitant use of Zortress with cyclosporine may increase the risk of thrombotic microangiopathy (TMA)/thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic syndrome (HUS). Monitor hematologic parameters.
• Zortress has been shown to increase the risk of new onset diabetes mellitus after transplant. Blood glucose concentrations should be monitored closely in patients using Zortress.
• Zortress may cause fetal harm when administered to a pregnant woman. Advise female patients of reproductive potential to avoid becoming pregnant and to use effective contraception while using Zortress and for 8 weeks after ending treatment.
• Azospermia or oligospermia may be observed.
• Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take Zortress as this may result in diarrhea and malabsorption.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• Reported experience with overdose in humans is very limited.

Treatment of overdosage:

• General supportive measures should be followed in all cases of overdose.
• Everolimus is not considered dialyzable to any relevant degree.

Can this medicine be used in pregnancy?

• Based on animal studies and the mechanism of action, Zortress can cause fetal harm when administered to a pregnant woman.

Can this medicine be used in children?

• The safe and effective use of Zortress in kidney or liver transplant patients younger than 18 years of age has not been established.

What are the active and inactive ingredients in this medicine?

• Active ingredient: everolimus
• Inactive ingredients: butylated hydroxytoluene, magnesium stearate, lactose monohydrate, hypromellose, crospovidone and lactose anhydrous.

Who manufactures and distributes this medicine?

• Distributed by:

Novartis Pharmaceuticals Corporation East Hanover, New Jersey

What should I know about storage and disposal of this medication?

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

• Dailymed label info on Zortress
• FDA Zortress

Zortress Resources
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