Screening report

AstraZeneca Pharmaceuticals LP · Package insert of record

KOSELUGO (SELUMETINIB)

Not on the NIOSH ListDailyMed (opens the full label on DailyMed in a new tab)
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: not found
Carcinogenicity: not found
Developmental: present in the label
Reproductive: not found
Genotoxicity: present in the label
Organ toxicity: present in the label
Genotoxicity / mutagenicity
3 passages in the label

“…micronucleus studies, predominantly via an aneugenic mode of action, but at doses > 160 mg/kg (~38-times the human C max at the clinical dose of 25 mg/m 2 ). In a 6-mon…”

2 more passages

“…in micronucleated immature erythrocytes (chromosome aberrations) in mouse micronucleus studies, predominantly via an aneugenic mode of action, but at doses > 160 mg/kg (~38-times the…”

“…erythrocytes (chromosome aberrations) in mouse micronucleus studies, predominantly via an aneugenic mode of action, but at doses > 160 mg/kg (~38-times the human C max at the clin…”

Developmental / embryo-fetal toxicity
16 passages in the label

“…vitamin E [see Drug Interactions (7.1) ]. 5.7 Embryo-Fetal Toxicity Based on findings from clinical trials, animal studies and its mechanism of action, KOSELUGO can cause fetal h…”

2 more passages

“…agent [see Warnings and Precautions (5.6) ] . Embryo-Fetal Toxicity • Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females…”

“…E. ( 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 ,…”

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

“…Left Ventricular Dysfunction KOSELUGO can cause cardiomyopathy, defined as a decrease in left ventricular ejection fraction (LVEF) ≥ 10% below baseline. KOSELUGO has not been studied…”

1 more passage

“…to immediately report any signs or symptoms of cardiomyopathy to their healthcare provider [see Warnings and Precautions (5.1) ] . Ocular Toxicity Advise patients and caregivers tha…”

Set aside: found but not counted (9)
NegatedCarcinogenicity: “is a substrate of BCRP and P-gp. 13 13.1 Carcinogenicity Selumetinib was not carcinogenic in a 6-month study in rasH2 transgenic mice and in 2-year carcinogenicity study i”
NegatedCarcinogenicity: “13 13.1 Carcinogenicity Selumetinib was not carcinogenic in a 6-month study in rasH2 transgenic mice and in 2-year carcinogenicity study in rats at exposures ≥ 15 times the h”
NegatedCarcinogenicity: “study in rasH2 transgenic mice and in 2-year carcinogenicity study in rats at exposures ≥ 15 times the human exposure (AUC) at the clinical dose of 25 mg/m 2 . Mutagenicity Se”
NegatedGenotoxicity / mutagenicity: “(AUC) at the clinical dose of 25 mg/m 2 . Mutagenicity Selumetinib was not mutagenic or clastogenic in vitro . Selumetinib did result in an increase in micronucleated im”
NegatedGenotoxicity / mutagenicity: “of 25 mg/m 2 . Mutagenicity Selumetinib was not mutagenic or clastogenic in vitro . Selumetinib did result in an increase in micronucleated immature erythrocytes (chromosome a”
NegatedGenotoxicity / mutagenicity: “. Mutagenicity Selumetinib was not mutagenic or clastogenic in vitro . Selumetinib did result in an increase in micronucleated immature erythrocytes (chromosome aberrations) in”
NegatedDevelopmental / embryo-fetal toxicity: “granules do not contain vitamin E. ( 5.6 ) • Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of reproductive potential of the potential risk to a fetus and to use e”
NegatedDevelopmental / embryo-fetal toxicity: “in a patient receiving KOSELUGO. Animal Data In embryo-fetal development studies in mice at doses > 2.5 mg/kg twice daily (~5-times the human exposure based on area under the curve”
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.