AFINITOR DISPERZ – Treatment for Tuberous Sclerosis Complex Seizures and Tumors

AFINITOR DISPERZ is an oral suspension formulation of everolimus, used primarily as a targeted kinase inhibitor for managing several tumor types and neurological conditions associated with tuberous sclerosis complex (TSC). It provides treatment options for seizures and certain brain tumors when surgery is not feasible.

• Adjunctive treatment of TSC-associated partial-onset seizures in adult and pediatric patients aged 2 years and older.
• Treatment of TSC-associated subependymal giant cell astrocytoma (SEGA) requiring therapy in adult and pediatric patients aged 1 year and older when surgical resection is not an option.

everolimus

AFINITOR DISPERZ works by inhibiting kinases involved in cellular growth and proliferation pathways. By blocking these kinases, it helps slow or stop the growth of tumors and decreases abnormal neurological activity linked to seizures in tuberous sclerosis complex.

Dosing

• SEGA (TSC-associated): Start with 4.5 mg/m2 orally once daily; adjust dose based on blood trough concentrations aiming for 5–15 ng/mL.
• Partial-Onset Seizures (TSC-associated): Start with 5 mg/m2 orally once daily; titrate dose to maintain 5–15 ng/mL trough levels.

Administration

• Do not combine AFINITOR and AFINITOR DISPERZ to achieve total daily dose; select dosage form based on indication.
• Prepare suspension by placing dose into water only; administer immediately after preparation.
• Use an oral syringe or a small glass for preparation, following specified mixing and administration steps.
• If a dose is missed, it can be taken within 6 hours; otherwise, skip dose and resume next day at usual time. Do not double doses.

Dose Adjustments and Monitoring

• Regularly monitor whole blood trough concentrations at initiation, dose changes, or interacting medication changes.
• Titrate dose using the formula: New dose = current dose × (target concentration ÷ current concentration), with increments ≤5 mg.
• Modify doses according to liver function impairment and drug interactions (see Warnings and Interactions).

Important Safety Information

• Non-infectious pneumonitis: Monitor for pulmonary symptoms; withhold or discontinue based on severity.
• Severe infections: Increased risk; monitor closely.
• Stomatitis: Manage symptoms; dose modification may be required.
• Metabolic disturbances: Hyperglycemia and dyslipidemia have occurred; monitor and treat accordingly.
• Hematologic abnormalities: Thrombocytopenia and neutropenia can occur; dose adjustments based on severity.
• Monitor liver function and adjust dosing for hepatic impairment.
• Avoid combination with strong CYP3A and P-glycoprotein inhibitors; adjust dosage or discontinue as needed.

Side Effects

• Common: Stomatitis, infections, rash, diarrhea, fatigue.
• Serious: Non-infectious pneumonitis, severe infections, thrombocytopenia, neutropenia, metabolic disturbances (such as hyperglycemia and dyslipidemia).

Drug Interactions

• Strong CYP3A and P-glycoprotein inhibitors: Avoid coadministration; can increase everolimus levels.
• Moderate CYP3A inhibitors: Reduce everolimus dose appropriately.
• Strong CYP3A and P-glycoprotein inducers: Avoid if possible; may require doubling everolimus dose with careful monitoring.
• Cannabidiol oral solution: Reduce everolimus dose by approximately 50% when coadministered; monitor everolimus levels closely.

Pregnancy and Lactation

• Pregnancy: Safety during pregnancy has not been established; avoid use unless potential benefit justifies risk.
• Breastfeeding: Unknown if excreted in human milk; breastfeeding is generally not recommended while receiving everolimus.

Manifestations of overdose may include increased incidence and severity of adverse reactions commonly seen with AFINITOR DISPERZ. Management is supportive. Monitor closely and provide symptomatic treatment.

Store AFINITOR DISPERZ suspension as directed on the product label. Prepare suspension immediately before use and discard if not administered within 60 minutes. Store tablets and prepared suspensions at recommended temperatures; avoid moisture and direct light according to instructions.