Screening report

SpringWorks Therapeutics, Inc. · Package insert of record

OGSIVEO (NIROGACESTAT)

Not on the NIOSH ListDailyMed (opens the full label on DailyMed in a new tab)
Developmental / reproductive language
The label notes developmental and/or reproductive toxicity. Many drugs carry this language and are not classified as hazardous.
3 / 6NIOSH hazard criteria present in this label
Special handling: not found
Carcinogenicity: not found
Developmental: present in the label
Reproductive: present in the label
Genotoxicity: not found
Organ toxicity: present in the label
Developmental / embryo-fetal toxicity
20 passages in the label

“…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…”

2 more passages

“…[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 administe…”

“…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…”

Reproductive / fertility toxicity
4 passages in the label

“…that OGSIVEO can cause ovarian toxicity and impair fertility, and that these effects may continue following discontinuation of OGSIVEO. Advise patients to tell their healthcare pro…”

2 more passages

“…shown to interfere with folliculogenesis and spermatogenesis in nonclinical studies resulting in changes that included ovarian atrophy [ see ( 13.1 ) ]. 8.4 Pediatric Use The saf…”

Animal study“…micronucleus study. Nirogacestat resulted in reduced fertility when administered to male and female rats at doses ≥ 5 mg/kg/day (approximately 0.16 times the recommended dose of 150…”

Organ toxicity (verify at low doses)
2 passages in the label

“…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…”

1 more passage

“…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…”

Set aside: found but not counted (7)
NegatedCarcinogenicity: “significant neoplastic findings occurred. The carcinogenic potential of nirogacestat in rats has not been assessed. Mutagenesis Nirogacestat was not mutagenic in a bacterial re”
Supporting onlyCarcinogenicity: “OATP1B3, OAT1, OAT2 and OAT3. 13 13.1 Carcinogenesis In a 6-month carcinogenicity study, transgenic rasH2 mice received up to 100 mg/kg/day of oral nirogacestat, result”
NegatedGenotoxicity / mutagenicity: “of nirogacestat in rats has not been assessed. Mutagenesis Nirogacestat was not mutagenic in a bacterial reverse mutation (Ames) assay and was not clastogenic in an in vitro”
NegatedGenotoxicity / mutagenicity: “been assessed. Mutagenesis Nirogacestat was not mutagenic in a bacterial reverse mutation (Ames) assay and was not clastogenic in an in vitro chromosome aberration assay in hu”
NegatedGenotoxicity / mutagenicity: “reverse mutation (Ames) assay and was not clastogenic in an in vitro chromosome aberration assay in human lymphocytes or in vivo rat bone marrow micronucleus study. Niro”
NegatedGenotoxicity / mutagenicity: “assay and was not clastogenic in an in vitro chromosome aberration assay in human lymphocytes or in vivo rat bone marrow micronucleus study. Nirogacestat resulted in reduced fertility”
NegatedGenotoxicity / mutagenicity: “in human lymphocytes or in vivo rat bone marrow micronucleus study. Nirogacestat resulted in reduced fertility when administered to male and female rats at doses ≥ 5 mg/kg/day (a”
These matched a hazard term but the text negates the finding, or names a test, a disease or a drug class rather than a finding about this drug. Shown so you can review them yourself.

For information only. This is a count of how many of the six NIOSH hazard-criteria appear in this label after negated and supporting-only statements are set aside. Findings from animal studies count, as NIOSH’s definition counts them, and are tagged “Animal data”. It is not a hazard determination, and the drug-class hint is not counted.