Ogsiveo
(nirogacestat)Dosage & Administration
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Ogsiveo Prescribing Information
OGSIVEO is indicated for adult patients with progressing desmoid tumors who require systemic treatment.
2.1 Recommended Dosage
The recommended dosage of OGSIVEO is 150 mg administered orally twice daily until disease progression or unacceptable toxicity. Each 150 mg dose of OGSIVEO consists of three 50 mg tablets or one 150 mg tablet. OGSIVEO may be taken with or without food.
Instruct patients to swallow OGSIVEO tablets whole and not to break, crush, or chew prior to swallowing.
If a patient vomits or misses a dose, instruct the patient to take the next dose at its scheduled time.
2.2 Dosage Modifications for Adverse Reactions
The recommended dose modifications for OGSIVEO for selected severe adverse reactions are summarized in Table 1 [see Warnings and Precautions ( 5), Adverse Reactions ( 6)]. For other severe adverse reactions, life-threatening adverse reactions, or persistent intolerable Grade 2 adverse events, withhold drug until resolved to Grade ≤ 1 or baseline. Only restart at a dose of 100 mg twice daily after considering the potential benefit and likelihood of recurrence of the adverse reaction. Permanently discontinue OGSIVEO for recurrence of severe or life-threatening adverse reaction upon rechallenge at the reduced dose.
| Adverse Reaction | Severity | OGSIVEO Dosage Modifications |
| Diarrhea persisting for ≥ 3 days despite maximal medical therapy [see Warnings and Precautions ( 5.1)] | Grades 3 or 4 | Withhold OGSIVEO until resolved to Grade ≤ 1 or baseline, then restart at a dose of 100 mg twice daily. |
| ALT or AST increased [see Warnings and Precautions ( 5.3)] | Grade 2 (≥ 3 to 5 × ULN) | Withhold OGSIVEO until ALT, AST, or both are resolved to < 3 × ULN or baseline, then restart at a dose of 100 mg twice daily. |
| Grades 3 or 4 (> 5 × ULN) | Permanently discontinue. | |
| Hypophosphatemia persisting for ≥ 3 days despite maximal replacement therapy [see Warnings and Precautions ( 5.5)] | Grades 3 or 4 | Withhold OGSIVEO until resolved to Grade ≤ 1 or baseline, then restart at a dose of 100 mg twice daily. |
| Hypokalemia despite maximal replacement therapy [see Warnings and Precautions ( 5.5)] | Grades 3 or 4 | Withhold OGSIVEO until resolved to Grade ≤ 1 or baseline, then restart at a dose of 100 mg twice daily. |
The 50 mg tablets are round, orange, film-coated, and debossed with “50” on one face. Each 50 mg tablet contains 50 mg nirogacestat.
The 100 mg tablets are round, light orange, film-coated, and debossed with “100” on one face. Each 100 mg tablet contains 100 mg nirogacestat.
The 150 mg tablets are oval, orange yellow, film-coated, and debossed with “150” on one face. Each 150 mg tablet contains 150 mg nirogacestat
8.1 Pregnancy
Risk Summary
Based on findings from animal studies and its mechanism of action, OGSIVEO can cause fetal harm or loss of pregnancy when administered to a pregnant woman [see Clinical Pharmacology ( 12.1)]. Oral administration of nirogacestat to pregnant rats during the period of organogenesis resulted in embryo-fetal toxicity and embryo-fetal death at maternal exposures below the human exposure at the recommended dose of 150 mg twice daily [see Data]. There are no available data on the use of OGSIVEO in pregnant women. Advise pregnant women of the potential risk to a fetus.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data
Animal Data
Daily oral administration of nirogacestat to pregnant rats during the period of organogenesis resulted in decreased fetal body weights, pre- and post-implantation loss, and fetal subcutis edema at doses ≥ 20 mg/kg/day (approximately 0.85 times the recommended dose of 150 mg twice daily based on area under the curve).
8.2 Lactation
Risk Summary
There are no data on the presence of nirogacestat or its metabolites in human milk or the effects of nirogacestat on a breastfed child or milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with OGSIVEO and for 1 week after the last dose.
8.3 Females and Males of Reproductive Potential
OGSIVEO can cause fetal harm when administered to a pregnant woman (see Use in Specific Populations ( 8.1)].
Pregnancy Testing
Verify the pregnancy status of females of reproductive potential prior to initiating OGSIVEO [see Use in Specific Populations ( 8.1)].
Contraception
Females
Advise females of reproductive potential to use effective contraception during treatment with OGSIVEO and for 1 week after the last dose.
Males
Advise males with female partners of reproductive potential to use effective contraception during treatment with OGSIVEO and for 1 week after the last dose.
Infertility
Based on findings in animal studies, OGSIVEO can impair female and male fertility. OGSIVEO has been shown to interfere with folliculogenesis and spermatogenesis in nonclinical studies resulting in changes that included ovarian atrophy [see Nonclinical Toxicology ( 13.1)].
8.4 Pediatric Use
The safety and effectiveness of OGSIVEO have not been established in pediatric patients. Epiphyseal disorder, manifesting as a widening of the epiphyseal growth plate, has been reported in pediatric patients with open growth plates treated with OGSIVEO.
8.5 Geriatric Use
Of the total number of OGSIVEO-treated patients in the DeFi study, 3 (4%) were 65 years of age and older and none were 75 years of age and older. Clinical studies of OGSIVEO did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently than younger adult patients.
None.
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 Adverse 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 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)].