OGSIVEO (nirogacestat hydrobromide)

Nirogacestat pharmacokinetic parameters in patients with desmoid tumors are summarized in Table 6 . Table 6. Pharmacokinetic Parameters and Characteristics of Nirogacestat General Information Steady state exposure [Mean (%CV)] C max 508 (62) ng/mL AUC 0- tau 3370 (58) ng·h/mL Time to steady-state Approximately 6 days Accumulation ratio [Median (Min, Max)] 1.6 (1.3, 4.6) Absorption T max [Median (Min, Max)] 1.5 (0.5, 6.5) hours Absolute bioavailability 19% Food effect [dose-normalized GMR% (90% C...

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of OGSIVEO was evaluated in 69 patients enrolled in DeFi with progressing desmoid tumor [see Clinical Studies ( 14 ) ]. Patients received OGSIVEO 150 mg orally twice daily or placebo orally twice daily until disease progression or unacceptable toxicity. The median duration of exposure to OGSIV...

The following serious adverse reactions are described elsewhere in the labeling: Diarrhea [see Warnings and Precautions ( 5.1 )] Ovarian Toxicity [see Warnings and Precautions ( 5.2 )] Hepatotoxicity [see Warnings and Precautions ( 5.3 )] Non-Melanoma Skin Cancers [see Warnings and Precautions ( 5.4 )] Electrolyte Abnormalities [see Warnings and Precautions ( 5.5 )] The most common ( > 15 %) adverse reactions are diarrhea, ovarian toxicity, rash, nausea, fatigue, stomatitis, headache, abdomin...

None. None. ( 4 )

Diarrhea: Severe diarrhea can occur. Monitor and dose modify for Grade 3-4 diarrhea. ( 5.1 ) Ovarian Toxicity: Female reproductive function and fertility may be impaired. Advise females of reproductive potential of the potential risk prior to treatment and monitor routinely. ( 5.2 ) Hepatotoxicity: Elevated AST and ALT can occur. Monitor AST and ALT regularly and modify dose as recommended. ( 5.3 ) Non-Melanoma Skin Cancers: Perform dermatologic examination prior to initiation of OGSIVEO and rou...

7 DRUG INTERACTIONS Strong or moderate CYP3A inhibitors: Avoid concomitant use. ( 7.1 ) Strong or moderate CYP3A inducers: Avoid concomitant use. ( 7.1 ) Gastric acid reducing agents: Avoid concomitant use with proton pump inhibitors and H2-receptor antagonists. If concomitant use cannot be avoided, OGSIVEO administration can be staggered with antacids. ( 7.1 ) 7.1 Effect s of Other Drugs on OGSIV...