Augtyro (REPOTRECTINIB): 3 of 6 NIOSH criteria in the label

Screening report

E.R. Squibb & Sons, L.L.C. · Package insert of record

Augtyro (REPOTRECTINIB)

Not on the NIOSH ListDailyMed

Carcinogenic / genotoxic findings in the label

The label reports carcinogenicity and/or genotoxicity findings — among the criteria NIOSH uses to identify hazardous drugs.

3 / 6NIOSH hazard criteria present in this label

Special handling

Carcinogenicity

Developmental

Reproductive

Genotoxicity

Organ toxicity

Genotoxicity / mutagenicity

4 passages in the label

“…[see Drug Interactions (7.2) ]. Males Based on genotoxicity findings, advise male patients with female partners of childbearing potential to use effective contraception durin…”

2 more passages

“…were not conducted. Repotrectinib was genotoxic in an in vitro assay in human lymphoblastoid TK6 cells and in an in vivo rat bone marrow micronucleus assay via an an…”

“…vivo rat bone marrow micronucleus assay via an aneugenic mechanism of action. Repotrectinib was not mutagenic in vitro in the bacterial reverse mutation (Ames) assay. Dedicat…”

Developmental / embryo-fetal toxicity

21 passages in the label

“…in mobility, deformity) of fractures. ( 5.6 ) • Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use an…”

2 more passages

“…fractures and risk of future fractures. 5.7 Embryo-Fetal Toxicity Based on literature reports in humans with congenital mutations leading to changes in tropomyosin receptor tyr…”

“…to pain, and anhidrosis. Animal Data In an embryo-fetal development study, once daily oral administration of repotrectinib to pregnant rats during the period of organogenesis…”

Organ toxicity (verify at low doses)

31 passages in the label

“…discontinue if ILD/pneumonitis is confirmed. Hepatotoxicity [see Warnings and Precautions (5.3) ] Grade 3 • Withhold AUGTYRO until ≤Grade 1 or baseline. • Resume at same dose i…”

2 more passages

“…if ILD/pneumonitis is confirmed. ( 5.2 ) • Hepatotoxicity: Monitor liver function tests every 2 weeks during the first month of treatment, and as clinically indicated thereaf…”

“…[see Dosage and Administration (2.5) ] . 5.3 Hepatotoxicity AUGTYRO can cause hepatotoxicity. Among the 426 patients treated with AUGTYRO, increased alanine transaminase (ALT)…”

Drug-class hint

Context only · not counted

“…patients who received up to 1 prior line of platinum-based chemotherapy and/or immunotherapy and 56 patients who received 1 prior ROS1 TKI with no prior platinum-based chemothera…”

Set aside: found but not counted (4)

NegatedCarcinogenicity: “is a substrate for P-gp. 13 13.1 Carcinogenicity studies with repotrectinib were not conducted. Repotrectinib was genotoxic in an in vitro assay in human lymphobla”

Supporting onlyCarcinogenicity: “that include ROS1 or TRK domains can drive tumorigenic potential through hyperactivation of downstream signaling pathways leading to unconstrained cell proliferation. Repot”

NegatedGenotoxicity / mutagenicity: “mechanism of action. Repotrectinib was not mutagenic in vitro in the bacterial reverse mutation (Ames) assay. Dedicated fertility studies were not conducted with repotrec”

NegatedDevelopmental / embryo-fetal toxicity: “dose of 160 mg twice daily based on BSA]. No embryolethality was observed. 8.2 Lactation Risk Summary There are no data on the presence of AUGTYRO in human milk or its effects o”

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.