Drug Detail:Everolimus (Everolimus)
Drug Class: MTOR inhibitors Selective immunosuppressants
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
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
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
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
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
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.
- See DOSE ADJUSTMENTS for therapeutic drug monitoring and dose titration.
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
Usual Adult Dose for Seizures
5 mg/m2 orally once a day until disease progression or unacceptable toxicity
Comments:
- Not all trade name products are approved for the same indications. Refer to the manufacturer product information for indications.
- See DOSE ADJUSTMENTS for therapeutic drug monitoring and dose titration.
Use: For adjunctive treatment of TSC-associated partial-onset seizures
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.
- See DOSE ADJUSTMENTS for therapeutic drug monitoring and dose titration.
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
Usual Pediatric Dose for Seizures
5 mg/m2 orally once a day until disease progression or unacceptable toxicity
Comments:
- Not all trade name products are approved for the same indications. Refer to the manufacturer product information for indications.
- See DOSE ADJUSTMENTS for therapeutic drug monitoring and dose titration.
Use: For adjunctive treatment of pediatric patients 2 years and older with TSC-associated partial-onset seizures
Renal Dose Adjustments
No adjustment recommended.
Liver Dose Adjustments
DOSE MODIFICATIONS IN BREAST CANCER, NET, RCC, AND TSC-ASSOCIATED RENAL ANGIOMYOLIPOMA:
- Mild hepatic impairment (Child-Pugh A): 7.5 mg orally once a day; the dose may be reduced to 5 mg a day if not well tolerated
- Moderate hepatic impairment (Child-Pugh B): 5 mg orally once a day; the dose may be decreased to 2.5 mg a day if not well tolerated
- Severe hepatic impairment (Child-Pugh C): 2.5 mg orally once a day if the benefit outweighs the risk; do not exceed 2.5 mg once a day
DOSE MODIFICATIONS IN TSC-ASSOCIATED SEGA AND TSC-ASSOCIATED PARTIAL-ONSET SEIZURES:
- Severe hepatic impairment (Child-Pugh C): 2.5 mg/m2 orally once a day; assess trough concentrations of this drug as recommended in DOSE ADJUSTMENTS
DOSE MODIFICATIONS FOR ORGAN TRANSPLANT-REJECTION PROPHYLAXIS:
- Mild hepatic impairment (Child-Pugh A): The initial daily dose should be reduced by one-third of the normally recommended initial dose.
- Moderate hepatic impairment (Child-Pugh B) or severe hepatic impairment (Child-Pugh 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
THERAPEUTIC DRUG MONITORING AND DOSE TITRATION FOR TUBEROUS SCLEROSIS COMPLEX (TSC)-ASSOCIATED SUBEPENDYMAL GIANT CELL ASTROCYTOMA (SEGA) AND TSC-ASSOCIATED PARTIAL-ONSET SEIZURES:
- Monitor whole blood trough concentrations of this drug at time points (see manufacturer recommended time points below).
- Titrate the dose to attain trough concentrations of 5 ng/mL to 15 ng/mL.
- Adjust the dose using the following equation: New dose = current dose x (target concentration divided by current concentration). The maximum dose increment at any titration should not exceed 5 mg. Multiple dose titrations may be required to attain the target trough concentration. When possible, use the same assay and laboratory for therapeutic drug monitoring throughout therapy.
- Initiation of therapy: Assess trough concentrations 1 to 2 weeks after event.
- Modification of the dose: Assess trough concentrations 1 to 2 weeks after event.
- Switch between oral tablets and tablets for suspension: Assess trough concentrations 1 to 2 weeks after event.
- Initiation or discontinuation of P-gp and moderate CYP450 3A inhibitor: Assess trough concentrations 2 weeks after event.
- Initiation or discontinuation of P-gp and strong CYP450 3A inhibitor: Assess trough concentrations 2 weeks after event.
- Change in hepatic function: Assess trough concentrations 2 weeks after event.
- Stable dose with changing body surface area: Assess trough concentrations every 3 to 6 months after event.
- Stable dose with stable body surface area: Assess trough concentrations every 6 to 12 months after event.
DOSE MODIFICATIONS IN BREAST CANCER, NET, RCC, AND TSC-ASSOCIATED RENAL ANGIOMYOLIPOMA:
---NON-INFECTIOUS PNEUMONITIS---
- Grade 2: Interrupt therapy until improvement to Grade 0 or 1; resume at 50% of previous dose; change to every other day dosing if the reduced dose is lower than the lowest available strength; permanently discontinue therapy if toxicity does not resolve or improve to Grade 1 within 4 weeks
- Grade 3: Interrupt therapy until improvement to Grade 0 or 1; resume at 50% of previous dose; change to every other day dosing if the reduced dose is lower than the lowest available strength; if toxicity recurs at Grade 3, permanently discontinue therapy
- Grade 4: Permanently discontinue therapy
- Grade 2: Interrupt therapy until recovery to Grade 0 or 1; reinitiate therapy at the same dose; if stomatitis recurs at Grade 2, interrupt therapy until recovery to Grade 0 or 1; reinitiate therapy at 50% of previous dose; change to every other day dosing if the reduced dose is lower than the lowest available strength
- Grade 3: Interrupt therapy until recovery to Grade 0 or 1; reinitiate therapy at 50% of the previous dose; change to every other day dosing if the reduced dose is lower than the lowest available strength
- Grade 4: Permanently discontinue therapy
- Grade 3: Interrupt therapy until recovery to Grade 0, 1, or 2; reinitiate therapy at 50% of the previous dose; change to every other day dosing if the reduced dose is lower than the lowest available strength
- Grade 4: Permanently discontinue therapy
- 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 0 or 1; reinitiate therapy at the same dose; if toxicity recurs at Grade 2, interrupt therapy until recovery to Grade 0 or 1; reinitiate therapy at 50% of the previous dose; change to every other day dosing if the reduced dose is lower than the lowest available strength
Grade 4: Permanently discontinue therapy
----THROMBOCYTOPENIA----
- Grade 2: Interrupt therapy until recovery to Grade 0 or 1; resume therapy at same dose
- Grade 3 or 4: Interrupt therapy until recovery to Grade 0 or 1; reinitiate therapy at 50% of the previous dose; change to every other day dosing if the reduced dose is lower than the lowest available strength
- Grade 3: Interrupt therapy until recovery to Grade 0, 1, or 2; reinitiate therapy at the same dose
- Grade 4: Interrupt therapy until recovery to Grade 0, 1, or 2; reinitiate therapy at 50% of the previous dose; change to every other day dosing if the reduced dose
- Grade 3: Interrupt therapy until recovery to Grade 0, 1, or 2 and no fever; reinitiate therapy at 50% of the previous dose; change to every other day dosing if the reduced dose
- Grade 4: Permanently discontinue therapy
DOSAGE MODIFICATIONS FOR P-GP AND CYP450 3A4 INHIBITORS:
- Avoid the concomitant use of P-gp and strong CYP450 3A4 inhibitors.
- Avoid ingesting grapefruit or grapefruit juice.
- Reduce the dose for patients taking this drug with a P-gp and moderate CYP450 3A4 inhibitors.
- Reduce dose to 2.5 mg orally once a day.
- May increase dose to 5 mg orally once a day if tolerated.
- Resume dose administered prior to inhibitor initiation when the inhibitor has been discontinued for 3 days.
- Reduce the daily dose by 50%.
- Change to every other day dosing if the reduced dose is lower than the lowest available strength.
- Resume dose administered prior to inhibitor initiation when the inhibitor has been discontinued for 3 days.
- Assess trough concentrations when initiating and discontinuing the inhibitor.
DOSAGE MODIFICATIONS FOR P-GP AND CYP450 3A4 INDUCERS:
- Avoid concomitant use of St. John's Wort (Hypericum perforatum).
- Increase the dose for patients taking this drug with a P-gp and strong CYP450 3A4 inducer.
- Avoid coadministration where alternatives exist.
- If coadministration cannot be avoided, double the daily dose using increments of 5 mg or less. Multiple increments may be required.
- Resume the dose administered prior to inducer initiation when an inducer is discontinued for 5 days.
ASSOCIATED SEGA AND TSC-ASSOCIATED PARTIAL-ONSET SEIZURES:
- Double the daily dose using increments of 5 mg or less. Multiple increments may be required.
- Addition of another strong CYP450 3A4 inducer in a patient already receiving treatment with a strong CYP450 3A4 inducer may not require additional dosage modification.
- Assess trough concentrations when initiating and discontinuing the inducer.
- Resume the dose administered before starting any inducer when all inducers are discontinued for 5 days.
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.
Precautions
US BOXED WARNINGS:
Zortress (R):
- MANAGEMENT OF IMMUNOSUPPRESSION: Only physicians experienced in immunosuppressive therapy and management of transplant patients should use Zortress(R).
- INFECTION AND MALIGNANCIES: Increased susceptibility to infection and the possible development of malignancies 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.
- ZORTRESS AND CALCINEURIN INHIBITOR-INDUCED NEPHROTOXICITY: Reduced doses of cyclosporine are required for use in combination with Zortress(R) in order to reduce nephrotoxicity.
- HEART TRANSPLANTATION: Increased mortality in a heart transplant clinical trial. Use in heart transplantation is not recommended.
CONTRAINDICATIONS:
- Hypersensitivity to the active component or any of the ingredients
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.
Consult WARNINGS section for additional precautions.
Dialysis
Data not available
Other Comments
Administration advice:
- Take consistently with or without food.
- Maintain consistency in time of administration.
- Tablets should be taken with a full glass of water.
- Tablets should not be broken or crushed.
- Do not combine the 2 dosage forms (Afinitor(R) tablets and Afinitor Disperz(R)) to achieve the desired total dose for patients with SEGA with TSC.
- If a dose is missed, continue normal dosing schedule. Do not take 2 doses to make up for the missed dose.
- Zortress(R) should be taken 12 hours apart with or without food and at the same times each day.
General:
- 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.
- St. John's Wort (Hypericum perforatum) may decrease everolimus exposure unpredictably and should be avoided.
- AFINITOR (R) is available in 2 dosage forms: tablets (Afinitor) and tablets for oral suspension (Afinitor Disperz); Afinitor tablets may be used for all approved indications; Afinitor Disperz is approved for the treatment of patients with subependymal giant cell astrocytoma (SEGA) and tuberous sclerosis complex (TSC).
Storage requirements:
- Store in original container away from light and moisture.
Reconstitution/preparation techniques:
Afinitor Disperz(R):
- Wear gloves to avoid possible contact with the drug when preparing suspensions for another person.
- Administer as a suspension only within 60 minutes of preparation. If not used within 60 minutes, discard suspension.
- Prepare suspension in water only.
Frequently asked questions
- How much does Afinitor cost per month?
- How long can you take Afinitor for?
- How long can you take everolimus?
- What is everolimus used for and how does it work?
- How does Afinitor work?
