warnings and cautions
5 WARNINGS AND PRECAUTIONS 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 routinely during treatment. ( 5.4 ) Electrolyte Abnormalities : Monitor phosphate and potassium regularly and modify dose as recommended. ( 5.5 ) Hypersensitivity Reactions : Monitor for signs and symptoms of hypersensitivity; interrupt or permanently discontinue OGSIVEO based on severity. ( 2.2 , 5.6 ) Embryo-Fetal Toxicity : Can cause fetal harm. Advise patients of reproductive potential of the potential risk to a fetus and to use effective contraception. ( 5.7 , 8.1 , 8.3 ) 5.1 Diarrhea Diarrhea, sometimes severe, can occur in patients treated with OGSIVEO [see Adverse Reactions ( 6.1 ) ] . In DeFi, diarrhea occurred in 84% of patients treated with OGSIVEO, and included Grade 3 events in 16% of patients. Median time to first diarrhea event for patients treated with OGSIVEO was 9 days (range: 2 to 434 days). Monitor patients and manage using antidiarrheal medications. Modify dose as recommended [ see Dosage and Administration ( 2.2 ) ]. 5. 2 Ovarian Toxicity Female reproductive function and fertility may be impaired in patients being treated with OGSIVEO. Impact on fertility may depend on factors including the duration of therapy and the state of gonadal function at the time of treatment. The long-term effects of OGSIVEO on fertility have not been established. Advise patients on the potential risks for ovarian toxicity before initiating treatment with OGSIVEO [ see Use in Specific Populations ( 8.3 ) ]. Monitor patients for changes in menstrual cycle regularity or the development of symptoms of estrogen deficiency, including hot flashes, night sweats, and vaginal dryness. 5. 3 Hepatotoxicity ALT or AST elevations occurred in 30% and 33% of patients who received OGSIVEO in DeFi, respectively. Grade 3 ALT or AST elevations (> 5 × ULN) occurred in 6% and 2.9% of patients, respectively [see Adverse Reactions ( 6.1 ) ] . Monitor liver function tests regularly and modify dose as recommended [see Dosage and Administration ( 2.2 ) ] . 5. 4 Non-Melanoma Skin Cancers New non-melanoma skin cancers can occur in patients treated with OGSIVEO. In DeFi, cutaneous squamous cell carcinoma and basal cell carcinoma occurred in 2.9% and 1.4% of patients, respectively [see Adverse Reactions ( 6.1 ) ]. Perform dermatologic evaluations prior to initiation of OGSIVEO and routinely during treatment. 5. 5 Electrolyte Abnormalities Electrolyte abnormalities can occur in patients treated with OGSIVEO. In DeFi, these included decreased phosphate (65%) and decreased potassium (22%). Phosphate <2 mg/dL occurred in 20% of patients who received OGSIVEO. Grade 3 decreased potassium occurred in 1.4% of patients [ see A dverse Reactions ( 6.1 ) ] . Monitor phosphate and potassium levels regularly and supplement as necessary. Modify dose as recommended [see Dosage and Administration ( 2.2 ) ]. 5.6 Hypersensitivity Reactions Hypersensitivity reactions, including severe hypersensitivity reactions, have been reported with postmarketing use of OGSIVEO. Monitor patients for signs and symptoms of hypersensitivity during treatment with OGSIVEO and manage as clinically indicated. Interrupt dosing or permanently discontinue OGSIVEO depending on the severity [see Dosage and Administration (2.2) ]. 5. 7 Embryo-Fetal Toxicity Based on findings from animal studies and its mechanism of action, OGSIVEO can cause fetal harm when administered to pregnant women. Oral administration of nirogacestat to pregnant rats during the period of organogenesis resulted in embryo-fetal toxicity and death at maternal exposures below the human exposure at the recommended dose of 150 mg twice daily. Advise pregnant women of the potential risk to a fetus. Advise females and males of reproductive potential to use effective contraception during treatment with OGSIVEO and for 1 week after the last dose [ see Use in Specific Populations ( 8.1 , 8.3 ) ].