Torpenz Dosage

Generic name: EVEROLIMUS 2.5mg
Dosage form: tablet

Medically reviewed by Drugs.com. Last updated on Jun 18, 2024.

Important Dosage Information

TORPENZ tablets and AFINITOR DISPERZ are two different dosage forms. Select the recommended dosage form based on the indication [see Indications and Usage (1)] . Do not combine TORPENZ tablets and AFINITOR DISPERZ to achieve the total dose.
Modify the dosage for patients with hepatic impairment or for patients taking drugs that inhibit or induce P-glycoprotein (P-gp) and CYP3A4 [see Dosage and Administration (2.10, 2.11, 2.12)] .

Recommended Dosage for Hormone Receptor-Positive, HER2-Negative Breast Cancer

The recommended dosage of TORPENZ tablets is 10 mg orally once daily until disease progression or unacceptable toxicity.

Recommended Dosage for Tuberous Sclerosis Complex (TSC)-Associated Renal Angiomyolipoma

The recommended dosage of TORPENZ tablets is 10 mg orally once daily until disease progression or unacceptable toxicity.

Recommended Dosage for Tuberous Sclerosis Complex (TSC)-Associated Subependymal Giant Cell Astrocytoma (SEGA)

The recommended starting dosage of TORPENZ tablets is 4.5 mg/m 2orally once daily until disease progression or unacceptable toxicity [see Dosage and Administration (2.8)] .

Therapeutic Drug Monitoring (TDM) and Dose Titration for Tuberous Sclerosis Complex (TSC)-Associated Subependymal Giant Cell Astrocytoma (SEGA)

Monitor everolimus whole blood trough concentrations at time points recommended in Table 1.
Titrate the dose to attain trough concentrations of 5 ng/mL to 15 ng/mL.
Adjust the dose using the following equation:
- New dose 1= current dose × (target concentration divided by current concentration)
When possible, use the same assay and laboratory for TDM throughout treatment.

Table 1: Recommended Timing of Therapeutic Drug Monitoring
Event	When to Assess Trough Concentrations After Event
Abbreviation: P-gp, P-glycoprotein
Initiation of TORPENZ	1 to 2 weeks
Modification of TORPENZ dose	1 to 2 weeks
Switch between TORPENZ tablets and AFINITOR DISPERZ	1 to 2 weeks
Initiation or discontinuation of P-gp and moderate CYP3A4 inhibitor	2 weeks
Initiation or discontinuation of P-gp and strong CYP3A4 inducer	2 weeks
Change in hepatic function	2 weeks
Stable dose with changing body surface area (BSA)	Every 3 to 6 months
Stable dose with stable BSA	Every 6 to 12 months

1: The maximum dose increment at any titration must not exceed 5 mg. Multiple dose titrations may be required to attain the target trough concentration.

Dosage Modifications for Adverse Reactions

Table 2 summarizes recommendations for dosage modifications of TORPENZ tablets for the management of adverse reactions.

Table 2: Recommended Dosage Modifications for TORPENZ for Adverse Reactions
Adverse Reaction	Severity	Dosage modification
Non-infectious pneumonitis [see Warnings and Precautions (5.1)]	Grade 2	Withhold 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 if toxicity does not resolve or improve to Grade 1 within 4 weeks.
	Grade 3	Withhold 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.
	Grade 4	Permanently discontinue.
Stomatitis [see Warnings and Precautions (5.5)]	Grade 2	Withhold until improvement to Grade 0 or 1. Resume at same dose. If recurs at Grade 2, withhold 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.
	Grade 3	Withhold 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.
	Grade 4	Permanently discontinue.
Metabolic events (e.g., hyperglycemia, dyslipidemia) [see Warnings and Precautions (5.9)]	Grade 3	Withhold until improvement to Grade 0, 1, or 2. Resume at 50% of previous dose; change to every other day dosing if the reduced dose is lower than the lowest available strength.
	Grade 4	Permanently discontinue.
Other non-hematologic toxicities	Grade 2	If toxicity becomes intolerable, withhold until improvement to Grade 0 or 1. Resume at same dose. If toxicity recurs at Grade 2, withhold 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.
	Grade 3	Withhold until improvement to Grade 0 or 1. Consider resuming at 50% of previous dose; change to every other day dosing if the reduced dose is lower than the lowest available strength. If recurs at Grade 3, permanently discontinue.
	Grade 4	Permanently discontinue.
Thrombocytopenia [see Warnings and Precautions (5.10)]	Grade 2	Withhold until improvement to Grade 0 or 1. Resume at same dose.
Thrombocytopenia [see Warnings and Precautions (5.10)]	Grade 3 OR Grade 4	Withhold 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.
Neutropenia [see Warnings and Precautions (5.10)]	Grade 3	Withhold until improvement to Grade 0, 1, or 2. Resume at same dose.
Neutropenia [see Warnings and Precautions (5.10)]	Grade 4	Withhold until improvement to Grade 0, 1, or 2. Resume at 50% of previous dose; change to every other day dosing if the reduced dose is lower than the lowest available strength.
Febrile neutropenia [see Warnings and Precautions (5.10)]	Grade 3	Withhold until improvement to Grade 0, 1, or 2 and no fever. Resume at 50% of previous dose; change to every other day dosing if the reduced dose is lower than the lowest available strength.
Febrile neutropenia [see Warnings and Precautions (5.10)]	Grade 4	Permanently discontinue.

Dosage Modifications for Hepatic Impairment

The recommended dosages of TORPENZ tablets for patients with hepatic impairment are described in Table 3 [see Use in Specific Populations (8.6)] :

Table 3: Recommended Dosage Modifications for Patients with Hepatic Impairment
Indication	Dose Modification for TORPENZ
Abbreviations: SEGA, Subependymal Giant Cell Astrocytoma; TSC, Tuberous Sclerosis Complex.
Breast Cancer and TSC-Associated Renal Angiomyolipoma	Mild hepatic impairment (Child-Pugh class A) – 7.5 mg orally once daily; decrease the dose to 5 mg orally once daily if a dose of 7.5 mg once daily is not tolerated. Moderate hepatic impairment (Child-Pugh class B) – 5 mg orally once daily; decrease the dose to 2.5 mg orally once daily if a dose of 5 mg once daily is not tolerated. Severe hepatic impairment (Child-Pugh class C) – 2.5 mg orally once daily if the desired benefit outweighs the risk; do not exceed a dose of 2.5 mg once daily.
TSC-Associated SEGA	Severe hepatic impairment (Child-Pugh class C) – 2.5 mg/m 2orally once daily. Adjust dose based on everolimus trough concentrations as recommended [see Dosage and Administration (2.8)] .

Dosage Modifications for P-gp and CYP3A4 Inhibitors

Avoid the concomitant use of P-gp and strong CYP3A4 inhibitors [see Drug Interactions (7.1)].
Avoid ingesting grapefruit and grapefruit juice.
Reduce the dose for patients taking TORPENZ tablets with a P-gp and moderate CYP3A4 inhibitor as recommended in Table 4 [see Drug Interactions (7.1), Clinical Pharmacology (12.3)].

Table 4: Recommended Dosage Modifications for Concurrent Use of TORPENZ with a P-gp and Moderate CYP3A4 Inhibitor
Indication	Dose Modification for TORPENZ
Breast Cancer and TSC-Associated Renal Angiomyolipoma	Reduce dose to 2.5 mg once daily. May increase dose to 5 mg once daily if tolerated. Resume dose administered prior to inhibitor initiation, once the inhibitor is discontinued for 3 days.
TSC-Associated SEGA	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, once the inhibitor is discontinued for 3 days. Assess trough concentrations when initiating and discontinuing the inhibitor [see Dosage and Administration (2.8)].

Dosage Modifications for P-gp and CYP3A4 Inducers

Avoid concomitant use of St. John's Wort (Hypericum perforatum).
Increase the dose for patients taking TORPENZ tablets with a P-gp and strong CYP3A4 inducer as recommended in Table 5 [see Drug Interactions (7.1), Clinical Pharmacology (12.3)].

Table 5: Recommended Dosage Modifications for Concurrent Use of TORPENZ with P-gp and Strong CYP3A4 Inducers
Indication	Dose Modification for TORPENZ
Breast Cancer and TSC-Associated Renal Angiomyolipoma	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, once an inducer is discontinued for 5 days.
TSC-Associated SEGA	Double the daily dose using increments of 5 mg or less. Multiple increments may be required. Addition of another strong CYP3A4 inducer in a patient already receiving treatment with a strong CYP3A4 inducer may not require additional dosage modification. Assess trough concentrations when initiating and discontinuing the inducer [see Dosage and Administration (2.8)] . Resume the dose administered before starting any inducer, once all inducers are discontinued for 5 days.

Administration and Preparation

Administer TORPENZ tablets at the same time each day.
Administer TORPENZ tablets consistently either with or without food [see Clinical Pharmacology (12.3)] .
If a dose of TORPENZ tablets is missed, it can be administered up to 6 hours after the time it is normally administered. After more than 6 hours, the dose should be skipped for that day. The next day, TORPENZ tablets should be administered at its usual time. Double doses should not be administered to make up for the dose that was missed.
TORPENZ tablets should be swallowed whole with a glass of water. Do not break or crush tablets.