Ogsiveo

OGSIVEO is indicated for adult patients with progressing desmoid tumors who require systemic treatment.  

• The recommended dosage is 150 mg orally twice daily until disease progression or unacceptable toxicity. (
  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.
  )
  
  
• See Full Prescribing Information for dosage modifications due to adverse reactions. (
  2.2

  Dos

  ag

  e 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.

  Table 1. Recommended Dose Modifications for Adverse Reactions

  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

• Lactation: Advise not to breastfeed. (
  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.
  )

• Diarrhea: Severe diarrhea can occur. Monitor and dose modify for Grade 3-4 diarrhea. (
  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

  )

  ].
  )
  
  
• 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. (
  5.000000000000000e+00

  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.
  )
  
  
• Hepatotoxicity: Elevated AST and ALT can occur. Monitor AST and ALT regularly and modify dose as recommended. (
  5.000000000000000e+00

  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

  )

  ]

  .
  )
  
  
• Non-Melanoma Skin Cancers: Perform dermatologic examination prior to initiation of OGSIVEO and routinely during treatment. (
  5.000000000000000e+00

  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.
  )
  
  
• Electrolyte Abnormalities: Monitor phosphate and potassium regularly and modify dose as recommended. (
  5.000000000000000e+00

  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

  )

  ].
  )
  
  
• Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of reproductive potential of the potential risk to a fetus and to use effective contraception. (
  5.000000000000000e+00

  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

  )

  ].
  ,
  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

  C

  linical

  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).
  ,
  8.3

  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

  )

  ].
  )