Zortress (everolimus)

By Medically reviewed by hellodoktor

Generic Name: Zortress (everolimus) Brand Name(s): Generics only. No brands available. Avability: Rx Pregnancy Category: N

Uses

What is Zortress (everolimus) used for?

Zortress (everolimus) lowers your body’s immune system. The immune system helps your body fight infections. The immune system can also fight or “reject” a transplanted organ such as a liver or kidney. This is because the immune system treats the new organ as an invader.

The Zortress brand of everolimus is used to prevent organ rejection after a kidney or liver transplant. Zortress is used together with cyclosporine, steroids, and other medications.

Afinitor is another brand of everolimus used to treat certain types of cancer.

How should I take Zortress (everolimus)?

Take this medication by mouth as directed by your doctor, usually every 12 hours with your cyclosporine dose, beginning immediately after a kidney transplant. Zortress (everolimus) is usually started 30 days after a liver transplant and is usually taken every 12 hours with your tacrolimus dose. You may take this medication with or without food, but it is important to choose one way and take this medication the same way with every dose. Swallow this medication whole with a glass of water. Do not crush, chew, or break the tablets.

The dosage is based on your medical condition, response to treatment, laboratory tests, and other medications you may be taking. Be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

Use this medication regularly to get the most benefit from it. To help you remember, take it at the same times each day.

Do not increase your dose or use this medication more often or for longer than prescribed. Your condition will not improve any faster, and your risk of side effects will increase.

Since this drug can be absorbed through the skin and lungs and may harm an unborn baby, women who are pregnant or who may become pregnant should not handle this medication or breathe the dust from the tablets.

How do I store Zortress (everolimus)?

Zortress (everolimus) is best stored at room temperature away from direct light and moisture. To prevent drug damage, you should not store Everolimus in the bathroom or the freezer. There may be different brands of Everolimus that may have different storage needs. It is important to always check the product package for instructions on storage, or ask your pharmacist. For safety, you should keep all medicines away from children and pets.

You should not flush Everolimus down the toilet or pour them into a drain unless instructed to do so. It is important to properly discard this product when it is expired or no longer needed. Consult your pharmacist for more details about how to safely discard your product.

Precautions & warnings

What should I know before using Zortress (everolimus)?

Before taking Zortress (everolimus), tell your doctor or pharmacist if you are allergic to it; or to sirolimus or temsirolimus; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: high cholesterol/triglyceride levels, any recent/current infections, diabetes, liver disease, certain hereditary enzyme problems (galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption).

Zortress (everolimus) can make you more likely to get infections or may worsen any current infections. Therefore, wash your hands well to prevent the spread of infection. Avoid contact with people who have infections that may spread to others (such as chickenpox, measles, flu). Consult your doctor if you have been exposed to an infection or for more details.

Do not have immunizations/vaccinations without the consent of your doctor. Avoid contact with people who have recently received live vaccines (such as flu vaccine inhaled through the nose).

To lower the chance of getting cut, bruised, or injured, use caution with sharp objects like razors and nail cutters, and avoid activities such as contact sports.

Since this medication may increase your risk of developing skin cancer, limit your time in the sun. Avoid tanning booths and sunlamps. Use sunscreen and wear protective clothing when outdoors.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

Tell your doctor if you are pregnant or plan to become pregnant. You should not become pregnant while using Zortress (everolimus). Zortress (everolimus) may harm an unborn baby. Female patients should ask about reliable forms of birth control while using this medication and for 8 weeks after stopping treatment. Male patients with female partners should ask about reliable forms of birth control while using this medication and for 4 weeks after stopping treatment. If you or your partner become pregnant, talk to your doctor right away about the risks and benefits of this medication.

Since this drug can be absorbed through the skin and lungs and may harm an unborn baby, women who are pregnant or who may become pregnant should not handle this medication or breathe the dust from the tablets.

It is unknown if this medication passes into breast milk. Because of the possible risk to the infant, breast-feeding while using this drug and for 2 weeks after stopping treatment is not recommended. Consult your doctor before breast-feeding.

Is it safe during pregnancy or breast-feeding?

There are no adequate studies in women for determining risk when using this Everolimus during pregnancy or while breastfeeding. Please always consult with your doctor to weigh the potential benefits and risks before taking Everolimus. Everolimus is pregnancy risk category N according to the US Food and Drug Administration (FDA).

FDA pregnancy risk category reference below:

  • A=No risk,
  • B=No risk in some studies,
  • C=There may be some risk,
  • D=Positive evidence of risk,
  • X=Contraindicated,
  • N=Unknown

Side effects

What side effects can occur from Everolimus?

Constipation, headache, nausea, and sores in the mouth/throat may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

People using this medication may have serious side effects. However, your doctor has prescribed this drug because he or she has judged that the benefit to you is greater than the risk ofside effects. Careful monitoring by your doctor may decrease your risk.

Tell your doctor right away if you have any serious side effects, including: swelling hands/ankles/feet, wound problems (such as infection, slow wound healing, opening of wound), decreased sexual ability (in men), chest pain/pressure, shortness of breath, unusual bruising/bleeding.

This medication has caused very serious (rarely fatal) lung problems. Get medical help right away if you have symptoms of lung problems, such as shortness of breath, chest pain.

This medication may increase your risk of getting a rare but very serious (sometimes fatal) brain infection (progressive multifocal leukoencephalopathy-PML). Get medical help right away if any of these rare but very serious side effects occur: clumsiness, loss of coordination, weakness, sudden change in your thinking (such as confusion, difficulty concentrating), difficulty moving your muscles, problems with speech, seizure, vision changes.

Everolimus may cause your cholesterol/triglycerides or blood sugar to increase. You may be required to have your cholesterol/triglycerides or blood sugar checked periodically. You may need medication to control your cholesterol/triglycerides or blood sugar. Tell your doctor or pharmacist if you experience symptoms of high blood sugar, including increased thirst/hunger, frequent urination.

This medication may affect male and female fertility. Consult your doctor for more details.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

Not everyone experiences these side effects. There may be some side effects not listed above. If you have any concerns about a side-effect, please consult your doctor or pharmacist.

Interactions

What drugs may interact with Zortress (everolimus)?

Some products that may interact with this drug include: other drugs that weaken the immune system/increase the risk of infection (such as natalizumab, rituximab), ACE inhibitors (such as captopril, lisinopril).

Other medications can affect the removal of Zortress (everolimus) from your body, which may affect how everolimus works. Examples include azole antifungals (such as itraconazole, ketoconazole), cobicistat, macrolide antibiotics (such as clarithromycin, erythromycin), HIV and HCV protease inhibitors (such as atazanavir, boceprevir, ritonavir, telaprevir), rifamycins (such as rifabutin, rifampin), St. John’s wort, telithromycin, among others.

Zortress (everolimus) may interact with other drugs that you are currently taking, which can change how your drug works or increase your risk for serious side effects. To avoid any potential drug interactions, you should keep a list of all the drugs you are using (including prescription drugs, nonprescription drugs and herbal products) and share it with your doctor and pharmacist. For your safety, do not start, stop, or change the dosage of any drugs without your doctor’s approval.

Does food or alcohol interact with Zortress (everolimus)?

Zortress (everolimus) may interact with food or alcohol by altering the way the drug works or increase the risk for serious side effects. Please discuss with your doctor or pharmacist any potential food or alcohol interactions before using this drug.

Grapefruit, grapefruit juice, and other foods that are known to inhibit CYP450 and PgP activity may increase everolimus exposures and should be avoided during therapy.

What health conditions may interact with Zortress (everolimus)?

Everolimus may interact with your health condition. This interaction may worsen your health condition or alter the way the drug works. It is important to always let your doctor and pharmacist know all the health conditions you currently have.

Dosage

The information provided is not a substitute for any medical advice. You should ALWAYS consult with your doctor or pharmacist before using this Everolimus.

What is the dose of Zortress (everolimus) for an adult?

Usual Adult Dose for Breast Cancer

10 mg orally once a day

Duration of therapy: Continue until disease progression or unacceptable toxicity occurs.

Comments:

-Not all trade name products are approved for the same indications. Refer to the manufacturer product information for indications.

-Dose should be taken at the same time each day.

-Dose should be taken consistently with or without food.

-Tablets should be swallowed whole with a glass of water and not chewed, broken, or crushed.

-Do not combine Afinitor(R) tablets and Afinitor Disperz(R) to achieve the desired total dose; use one or the other.

Uses:

1) Advanced Hormone Receptor-Positive, HER2-Negative Breast Cancer (Advanced HR+ BC): For postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer (advanced HR+ BC) in combination with exemestane, after failure of treatment with letrozole or anastrozole

2) Advanced Neuroendocrine Tumors (NET):

-For progressive neuroendocrine tumors of pancreatic origin (PNET) with unresectable, locally advanced or metastatic disease

-For progressive, well-differentiated, non-functional neuroendocrine tumors (NET) of GI or lung origin with unresectable, locally advanced or metastatic disease

3) Advanced Renal Cell Carcinoma (RCC): For advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib

4) For Renal Angiomyolipoma with Tuberous Sclerosis Complex (TSC): For renal angiomyolipoma and TSC, not requiring immediate surgery

Usual Adult Dose for Renal Cell Carcinoma

10 mg orally once a day

Duration of therapy: Continue until disease progression or unacceptable toxicity occurs.

Comments:

-Not all trade name products are approved for the same indications. Refer to the manufacturer product information for indications.

-Dose should be taken at the same time each day.

-Dose should be taken consistently with or without food.

-Tablets should be swallowed whole with a glass of water and not chewed, broken, or crushed.

-Do not combine Afinitor(R) tablets and Afinitor Disperz(R) to achieve the desired total dose; use one or the other.

Uses:

1) Advanced Hormone Receptor-Positive, HER2-Negative Breast Cancer (Advanced HR+ BC): For postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer (advanced HR+ BC) in combination with exemestane, after failure of treatment with letrozole or anastrozole

2) Advanced Neuroendocrine Tumors (NET):

-For progressive neuroendocrine tumors of pancreatic origin (PNET) with unresectable, locally advanced or metastatic disease

-For progressive, well-differentiated, non-functional neuroendocrine tumors (NET) of GI or lung origin with unresectable, locally advanced or metastatic disease

3) Advanced Renal Cell Carcinoma (RCC): For advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib

4) For Renal Angiomyolipoma with Tuberous Sclerosis Complex (TSC): For renal angiomyolipoma and TSC, not requiring immediate surgery

Usual Adult Dose for Pancreatic Cancer

10 mg orally once a day

Duration of therapy: Continue until disease progression or unacceptable toxicity occurs.

Comments:

-Not all trade name products are approved for the same indications. Refer to the manufacturer product information for indications.

-Dose should be taken at the same time each day.

-Dose should be taken consistently with or without food.

-Tablets should be swallowed whole with a glass of water and not chewed, broken, or crushed.

-Do not combine Afinitor(R) tablets and Afinitor Disperz(R) to achieve the desired total dose; use one or the other.

Uses:

1) Advanced Hormone Receptor-Positive, HER2-Negative Breast Cancer (Advanced HR+ BC): For postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer (advanced HR+ BC) in combination with exemestane, after failure of treatment with letrozole or anastrozole

2) Advanced Neuroendocrine Tumors (NET):

-For progressive neuroendocrine tumors of pancreatic origin (PNET) with unresectable, locally advanced or metastatic disease

-For progressive, well-differentiated, non-functional neuroendocrine tumors (NET) of GI or lung origin with unresectable, locally advanced or metastatic disease

3) Advanced Renal Cell Carcinoma (RCC): For advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib

4) For Renal Angiomyolipoma with Tuberous Sclerosis Complex (TSC): For renal angiomyolipoma and TSC, not requiring immediate surgery

Usual Adult Dose for Renal Angiomyolipoma

10 mg orally once a day

Duration of therapy: Continue until disease progression or unacceptable toxicity occurs.

Comments:

-Not all trade name products are approved for the same indications. Refer to the manufacturer product information for indications.

-Dose should be taken at the same time each day.

-Dose should be taken consistently with or without food.

-Tablets should be swallowed whole with a glass of water and not chewed, broken, or crushed.

-Do not combine Afinitor(R) tablets and Afinitor Disperz(R) to achieve the desired total dose; use one or the other.

Uses:

1) Advanced Hormone Receptor-Positive, HER2-Negative Breast Cancer (Advanced HR+ BC): For postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer (advanced HR+ BC) in combination with exemestane, after failure of treatment with letrozole or anastrozole

2) Advanced Neuroendocrine Tumors (NET):

-For progressive neuroendocrine tumors of pancreatic origin (PNET) with unresectable, locally advanced or metastatic disease

-For progressive, well-differentiated, non-functional neuroendocrine tumors (NET) of GI or lung origin with unresectable, locally advanced or metastatic disease

3) Advanced Renal Cell Carcinoma (RCC): For advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib

4) For Renal Angiomyolipoma with Tuberous Sclerosis Complex (TSC): For renal angiomyolipoma and TSC, not requiring immediate surgery

Usual Adult Dose for Neuroendocrine Carcinoma

10 mg orally once a day

Duration of therapy: Continue until disease progression or unacceptable toxicity occurs.

Comments:

-Not all trade name products are approved for the same indications. Refer to the manufacturer product information for indications.

-Dose should be taken at the same time each day.

-Dose should be taken consistently with or without food.

-Tablets should be swallowed whole with a glass of water and not chewed, broken, or crushed.

-Do not combine Afinitor(R) tablets and Afinitor Disperz(R) to achieve the desired total dose; use one or the other.

Uses:

1) Advanced Hormone Receptor-Positive, HER2-Negative Breast Cancer (Advanced HR+ BC): For postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer (advanced HR+ BC) in combination with exemestane, after failure of treatment with letrozole or anastrozole

2) Advanced Neuroendocrine Tumors (NET):

-For progressive neuroendocrine tumors of pancreatic origin (PNET) with unresectable, locally advanced or metastatic disease

-For progressive, well-differentiated, non-functional neuroendocrine tumors (NET) of GI or lung origin with unresectable, locally advanced or metastatic disease

3) Advanced Renal Cell Carcinoma (RCC): For advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib

4) For Renal Angiomyolipoma with Tuberous Sclerosis Complex (TSC): For renal angiomyolipoma and TSC, not requiring immediate surgery

Usual Adult Dose for Brain/Intracranial Tumor

4.5 mg/m2 orally once a day

Duration of therapy: Continue until disease progression or unacceptable toxicity occurs. The optimal duration of therapy is unknown.

Comments:

-Not all trade name products are approved for the same indications. Refer to the manufacturer product information for indications.

-Dose should be taken at the same time each day.

-Dose should be taken consistently with or without food.

-Afinitor(R) tablets should be swallowed whole with a glass of water and not chewed, broken, or crushed.

-Do not combine Afinitor(R) tablets and Afinitor Disperz(R) to achieve the desired total dose; use one or the other.

-Use therapeutic drug monitoring to guide subsequent dosing.

-Adjust dose at 2 week intervals as needed to achieve and maintain trough concentrations of 5 to 15 ng/mL.

Use: Subependymal Giant Cell Astrocytoma (SEGA) with Tuberous Sclerosis Complex (TSC): For tuberous sclerosis complex (TSC) for the treatment of SEGA that requires therapeutic intervention but cannot be curatively resected

Usual Adult Dose for Organ Transplant – Rejection Prophylaxis

KIDNEY transplant: 0.75 mg orally twice a day

Comments:

-Not all trade name products are approved for the same indications. Refer to the manufacturer product information for indications.

-This drug should be administered in combination with reduced dose cyclosporine as soon as possible after transplantation.

-Oral prednisone should be initiated once oral medication is tolerated. Doses may be further individualized based on the clinical status of the patient and function of the graft.

LIVER transplant: 1 mg orally twice a day

Comments:

-Not all trade name products are approved for the same indications. Refer to the manufacturer product information for indications.

-Start therapy at least 30 days after transplant.

-Use this drug in combination with reduced dose tacrolimus.

-Steroid doses may be individualized based on the clinical status of the patient and function of the graft.

Uses:

-Prophylaxis of organ rejection in patients at low-moderate immunologic risk receiving a kidney transplant and in combination with basiliximab induction and concurrently with reduced doses of cyclosporine and with corticosteroids

-Prophylaxis of allograft rejection in adult patients receiving a liver transplant to be administered no earlier than 30 days post-transplant concurrently with reduced doses of tacrolimus and with corticosteroids

Renal Dose Adjustments

No adjustment recommended.

Liver Dose Adjustments

—-DOSE MODIFICATIONS IN ADVANCED HORMONE RECEPTOR-POSITIVE, HER2-NEGATIVE BREAST CANCER, ADVANCED NET, ADVANCED RCC, AND RENAL ANGIOMYOLIPOMA WITH TSC—-

-Mild hepatic impairment (Child-Pugh class A): The recommended dose is 7.5 mg a day. The dose may be reduced to 5 mg a day if not well tolerated.

-Moderate hepatic impairment (Child-Pugh class B): The recommended dose is 5 mg a day. The dose may be decreased to 2.5 mg a day if not well tolerated.

-Severe hepatic impairment (Child-Pugh class C): If the desired benefit outweighs the risk, a dose of 2.5 mg a day may be used but must not be exceeded.

-Dose adjustments should occur if a patient’s hepatic status changes during therapy.

—-DOSE MODIFICATIONS IN SEGA WITH TSC—-

-Mild hepatic impairment (Child-Pugh class A): No dose adjustment recommended.

-Moderate hepatic impairment (Child-Pugh class B): No dose adjustment recommended.

-Severe hepatic impairment (Child-Pugh class C): Reduce the starting dose by approximately 50%.

-Assess everolimus trough concentrations approximately 2 weeks after commencing therapy, a change in dose, or any change in hepatic function.

DOSE MODIFICATIONS FOR ORGAN TRANSPLANT-REJECTION PROPHYLAXIS:

-Mild hepatic impairment (Child-Pugh class A): The initial daily dose should be reduced by one-third of the normally recommended initial dose.

-Moderate hepatic impairment (Child-Pugh class B) or severe hepatic impairment (Child-Pugh class C): Initial daily dose should be reduced to one-half of the normally recommended initial dose; further dose adjustment and/or dose titration should be made if the patient whole blood trough concentration of this drug is not within the target trough concentration range of 3 to 8 ng/mL

Dose Adjustments

DOSE MODIFICATIONS IN ADVANCED HORMONE RECEPTOR-POSITIVE, HER2-NEGATIVE BREAST CANCER, ADVANCED NET, ADVANCED RCC, AND RENAL ANGIOMYOLIPOMA WITH TSC:

—-NON-INFECTIOUS PNEUMONITIS—-

-Grade 1: No dose adjustment recommended; monitor closely

-Grade 2: Consider interrupting therapy; rule out infection; consider treatment with corticosteroids until symptoms improve to Grade 1 or less; reinitiate therapy at a lower dose; discontinue therapy if failure to recover within 4 weeks

-Grade 3: Interrupt therapy until symptoms resolve to Grade 1 or less; rule out infection; consider treatment with corticosteroids; consider reinitiating therapy at a lower dose; if toxicity recurs at Grade 3, consider discontinuing therapy

-Grade 4: Discontinue therapy; rule out infection; consider treatment with corticosteroids

—-STOMATITIS—-

-Grade 1: No dose adjustment recommended; manage with nonalcoholic or salt water (0.9%) mouthwash several times a day

-Grade 2: Interrupt therapy until recovery to Grade 1 or less; reinitiate therapy at the same dose; if stomatitis recurs at Grade 2, interrupt therapy until recovery to Grade 1 or less; reinitiate therapy at a lower dose; manage with topical analgesic mouth treatments (e.g., benzocaine, butyl aminobenzoate, tetracaine hydrochloride, menthol, phenol) with or without topical corticosteroids (i.e., triamcinolone oral paste)

-Grade 3: Interrupt therapy until recovery to Grade 1 or less; reinitiate therapy at a lower dose; manage with topical analgesic mouth treatments (e.g., benzocaine,

butyl aminobenzoate, tetracaine hydrochloride, menthol, phenol) with or without topical corticosteroids (i.e., triamcinolone oral paste)

-Grade 4: Discontinue therapy and treat medically

—-OTHER NONHEMATOLOGIC TOXICITIES (EXCLUDING METABOLIC EVENTS)—-

-Grade 1: If toxicity is tolerable, no dose adjustment is recommended; initiate medical therapy and monitor

-Grade 2: If toxicity is tolerable, no dose adjustment is recommended; initiate medical therapy and monitor; if toxicity becomes intolerable, interrupt therapy until recovery to Grade 1 or less; reinitiate therapy at the same dose; if toxicity recurs at Grade 2, interrupt therapy until recovery to Grade 1 or less; reinitiate therapy at a lower dose

Grade 3: Interrupt therapy until recovery to Grade 1 or less; initiate medical therapy and monitor; consider reinitiating therapy at a lower dose; if toxicity recurs at Grade 3, consider discontinuing therapy

Grade 4: Discontinue therapy and treat medically

—-METABOLIC EVENTS (e.g., HYPERGLYCEMIA, DYSLIPIDEMIA)—-

-Grade 1: No dose adjustment recommended; initiate medical therapy and monitor

-Grade 2: No dose adjustment recommended; initiate medical therapy and monitor

-Grade 3: Interrupt therapy temporarily; reinitiate therapy at a lower dose; treat medically and monitor

-Grade 4: Discontinue therapy; treat medically and monitor

—-THROMBOCYTOPENIA—-

-Grade 1: No dose adjustment recommended

-Grade 2: Interrupt therapy until recovery to Grade 1 or less; reinitiate therapy at the same dose

-Grade 3 or 4: Interrupt therapy until recovery to Grade 1 or less; reinitiate therapy at a lower dose

—-NEUTROPENIA—-

-Grade 1 or 2: No dose adjustment recommended

-Grade 3: Interrupt therapy until recovery to Grade 2 or less; reinitiate therapy at the same dose

-Grade 4: Interrupt therapy until recovery to Grade 2 or less; reinitiate therapy at a lower dose

—-FEBRILE NEUTROPENIA—-

-Grade 3: Interrupt therapy until recovery to Grade 2 or less and no fever; reinitiate therapy at a lower dose

-Grade 4: Discontinue therapy

—-CYP450 3A4/P-GLYCOPROTEIN (PGP) INHIBITORS—-

-Strong CYP450 3A4/PgP inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole): Avoid use

-Moderate CYP450 3A4/PgP inhibitors (e.g., amprenavir, fosamprenavir, aprepitant, erythromycin, fluconazole, verapamil, diltiazem): Use with caution; if patients require coadministration of a moderate CYP450 3A4/PgP inhibitor, reduce the Afinitor (R) dose to 2.5 mg daily; an Afinitor (R) dose increase from 2.5 mg to 5 mg may be considered based on patient tolerance; if the moderate inhibitor is discontinued, a washout period of approximately 2 to 3 days should be allowed before the Afinitor (R) dose is increased; if the moderate inhibitor is discontinued, the Afinitor (R) dose should be returned to the dose used prior to initiation of the moderate CYP450 3A4/PgP inhibitor

-Grapefruit, grapefruit juice, and other foods that are known to inhibit CYP450 and PgP activity may increase everolimus exposures and should be avoided during therapy

—-STRONG CYP450 3A4/PGP INDUCERS—-

Avoid the use of concomitant strong CYP450 3A4/PgP inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital); if patients require coadministration of a strong CYP450 3A4/PgP inducer, consider doubling the daily dose of Afinitor (R) using increments of 5 mg or less; if the strong inducer is discontinued, consider a washout period of 3 to 5 days, before the Afinitor (R) dose is returned to the dose used prior to initiation of the strong CYP450 3A4/PgP inducer

-St. John’s Wort (Hypericum perforatum) may decrease everolimus exposure unpredictably and should be avoided.

THERAPEUTIC DRUG MONITORING IN SEGA WITH TSC:

-Monitor everolimus whole blood trough levels routinely in all patients.

-Assess trough concentrations approximately 2 weeks after initiation of therapy, a change in dose, a change in coadministration of CYP450 3A4/P-gp inducers and/or inhibitors, a change in hepatic function, or a change in dosage form from Afinitor(R) to Afinitor Disperz(R).

-Once a stable dose is attained, monitor trough levels every 3 to 6 months in patients with changing body surface area or every 6 to 12 months in patients with a stable body surface area.

—-Titrate the dose to attain trough concentrations of 5 to 15 ng/mL—-

-For trough concentrations less than 5 ng/mL, increase the daily dose by 2.5 mg (Afinitor (R) tablets) or 2 mg (Afinitor (R) Disperz)

-For trough concentrations greater than 15 ng/mL, reduce the daily dose by 2.5 mg (Afinitor (R) tablets) or 2 mg (Afinitor (R) Disperz)

-If dose reduction is required for patients taking the lowest available strength, administer every other day

DOSE MODIFICATIONS IN SEGA WITH TSC:

—-ADVERSE REACTIONS—-

-Temporarily interrupt or permanently discontinue therapy for severe or intolerable adverse reactions

-If dose reduction is required when reinitiating therapy, reduce the dose by approximately 50%

-If dose reduction is required for patients receiving the lowest available strength, administer every other day

—-CYP450 3A4/P-GLYCOPROTEIN (PGP) INHIBITORS—-

-Strong CYP450 3A4/PgP inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole): Avoid use

-Moderate CYP450 3A4/PgP inhibitors (e.g., amprenavir, fosamprenavir, aprepitant, erythromycin, fluconazole, verapamil, diltiazem): Reduce the Afinitor (R) or Afinitor (R) Disperz dose by approximately 50%; administer every other day if dose reduction is required for patients receiving the lowest available strength and maintain trough concentrations of 5 to 15 ng/mL.

-Assess everolimus trough concentrations approximately 2 weeks after dose reduction.

-Resume the dose that was used prior to initiating the CYP450 3A4/PgP inhibitor 2 to 3 days after discontinuation of a moderate inhibitor; assess the everolimus trough concentration approximately 2 weeks later.

-Do not ingest foods or nutritional supplements (e.g., grapefruit, grapefruit juice) that are known to inhibit CYP450 or PgP activity.

—-STRONG CYP450 3A4/PGP INDUCERS—-

Avoid the use of concomitant strong CYP450 3A4/PgP inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital) if alternative therapy is available; for patients who require treatment with a strong CYP450 3A4/PgP inducer:

-Double the dose of Afinitor (R) Tablets or Afinitor (R) Disperz and assess tolerability.

-Assess the everolimus trough concentration approximately 2 weeks after doubling the dose and adjust the dose if necessary to maintain a trough concentration of 5 to 15 ng/mL.

-Return the dose to that used prior to initiating the strong CYP450 3A4/PgP inducer if the strong inducer is discontinued, and assess the everolimus trough concentrations approximately 2 weeks later.

-Do not ingest foods or nutritional supplements (e.g., St. John’s Wort (Hypericum perforatum)) that are known to induce CYP450 activity.

DOSE MODIFICATIONS IN KIDNEY OR LIVER TRANSPLANT:

Patients may require dose adjustments based on everolimus blood concentrations achieved, tolerability, individual response, change in concomitant medications and the clinical situation. Dose adjustments should be based on trough concentrations taken 4 or 5 days after a previous dosing change. Dose adjustment is required if the trough concentration is below 3 ng/mL. The total daily dose should be doubled using the available tablet strengths (0.25 mg, 0.5 mg or 0.75 mg). Dose adjustment is also required if the trough concentration is greater than 8 ng/mL on 2 consecutive measures; the dose should be decreased by 0.25 mg twice daily.

What is the dose of Zortress (everolimus) for a child?

Usual Pediatric Dose for Brain/Intracranial Tumor

One year and older:

4.5 mg/m2 orally once a day

Duration of therapy: Continue until disease progression or unacceptable toxicity occurs. The optimal duration of therapy is unknown.

Comments:

-Not all trade name products are approved for the same indications. Refer to the manufacturer product information for indications.

-Dose should be taken at the same time each day.

-Dose should be taken consistently with or without food.

-Afinitor (R) tablets should be swallowed whole with a glass of water and not chewed, broken, or crushed.

-Do not combine Afinitor (R) tablets and Afinitor Disperz (R) to achieve the desired total dose; use one or the other.

-Use therapeutic drug monitoring to guide subsequent dosing.

-Adjust dose at 2 week intervals as needed to achieve and maintain trough concentrations of 5 to 15 ng/mL.

Use: Subependymal Giant Cell Astrocytoma (SEGA) with Tuberous Sclerosis Complex (TSC): For tuberous sclerosis complex (TSC) for the treatment of SEGA that requires therapeutic intervention but cannot be curatively resected in pediatric patients 1 year and older

Precautions

Afinitor (R): Safety and efficacy have not been established in patients younger than 1 year.

Zortress (R): Safety and efficacy have not been established in patients younger than 18 years.

How is Zortress (everolimus) available?

Everolimus is available in the following dosage forms and strengths:

  • Oral tablet,
  • Oral tablet, dispersible.

What should I do in case of an emergency or overdose?

In case of an emergency or an overdose, call your local emergency services or go to your nearest emergency room.

What should I do if I miss a dose?

If you miss a dose of Everolimus, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and take your regular dose as scheduled. Do not take a double dose.

Hello Health Group does not provide medical advice, diagnosis or treatment.

Review Date: August 23, 2018 | Last Modified: September 12, 2019

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