Luciniro Nirogacestat 50mg Tablets 90's

Nirogacestat is an oral gamma-secretase inhibitor used to treat adults with progressing desmoid tumors who require systemic treatment.

Desmoid tumors, also known as aggressive fibromatosis, are rare tumors that arise from connective tissue. Although they do not usually spread to distant organs, they can grow into surrounding tissues and cause pain, functional impairment, or other complications.

Nirogacestat inhibits gamma-secretase, an enzyme involved in Notch signaling. Blocking this pathway can reduce signaling that contributes to the growth and persistence of desmoid tumor cells. Nirogacestat received FDA approval in November 2023 as the first FDA-approved systemic treatment specifically for progressing desmoid tumors.

Adult patients with progressing desmoid tumors who require systemic treatment.

It may be considered when the tumor is progressing and systemic therapy is required rather than immediate surgical management.

Nirogacestat acts as a gamma-secretase inhibitor.

It works by:

• Inhibiting gamma-secretase activity.
• Reducing Notch signaling.
• Interfering with signaling pathways involved in desmoid tumor growth.
• Inhibiting proliferation of tumor cells.
• Helping delay tumor progression.
• Potentially reducing tumor size and tumor-related symptoms.

Nirogacestat is taken orally twice daily.

The recommended dosage is 150 mg twice daily.

Treatment is continued until disease progression or unacceptable toxicity.

It may be taken with or without food.

Swallow tablets whole with water.

Do not break, crush, or chew the tablets.

If vomiting occurs or a dose is missed, take the next dose at its regularly scheduled time; do not take an additional dose to compensate.

The currently marketed tablet strengths are 100 mg and 150 mg. Dose reduction to 100 mg twice daily may be required for certain adverse reactions.

Serious:

• Severe diarrhea
• Ovarian toxicity
• Hepatotoxicity
• Significant electrolyte abnormalities
• Embryo-fetal toxicity
• Non-melanoma skin cancers
• Severe gastrointestinal complications in susceptible patients

Ovarian toxicity is particularly important because nirogacestat may impair ovarian function and fertility in females of reproductive potential.

Common:

• Diarrhea
• Ovarian toxicity
• Rash
• Nausea
• Fatigue
• Stomatitis (mouth sores/inflammation)
• Headache
• Abdominal pain
• Cough
• Hair loss (alopecia)
• Upper respiratory tract infection
• Shortness of breath (dyspnea)

Common laboratory abnormalities include:

• Decreased phosphate
• Increased urine glucose
• Increased urine protein
• Increased AST
• Increased ALT
• Decreased potassium

Patients should inform their healthcare provider about all prescription medicines, over-the-counter medicines, vitamins, and herbal supplements they are taking.

Nirogacestat is metabolized by CYP3A, making several drug interactions clinically important.

Medicines requiring particular attention include:

• Strong CYP3A inhibitors—avoid concomitant use.
• Moderate CYP3A inhibitors—avoid concomitant use.
• Strong CYP3A inducers—avoid concomitant use.
• Moderate CYP3A inducers—avoid concomitant use.
• Proton pump inhibitors (PPIs)—avoid concomitant use.
• H2-receptor antagonists—avoid concomitant use where possible.

If gastric acid-reducing treatment is necessary, antacids may be used with appropriate separation from nirogacestat.

Patients should also avoid grapefruit products, Seville oranges, and starfruit, as these may affect nirogacestat exposure.

• Store at 20°C–25°C (68°F–77°F).
• Temperature excursions between 15°C and 30°C (59°F and 86°F) are permitted.
• Keep tablets in the original packaging.
• Protect from excessive heat and moisture.
• Keep out of reach of children.

• Monitor diarrhea carefully, particularly during the first weeks of treatment. Severe diarrhea may require treatment interruption or dose modification.
• Maintain adequate fluid and electrolyte intake, especially if diarrhea occurs.
• Liver function tests should be monitored during treatment.
• Women of reproductive potential should discuss fertility preservation before starting therapy because ovarian toxicity may occur.
• Report menstrual changes, reduced ovarian function, or fertility concerns promptly.
• Avoid grapefruit, Seville oranges, and starfruit during treatment.
• Avoid strong/moderate CYP3A inhibitors and inducers unless specifically managed by the treating physician.
• Avoid PPIs and H2-receptor antagonists unless an appropriate alternative strategy is established.
• Report new skin lesions or changes promptly because non-melanoma skin cancers have been reported.
• Do not change the dose or discontinue treatment without consulting the treating specialist.
• Regular clinical and laboratory monitoring is important throughout treatment.