Animal studies have revealed teratogenicity and embryotoxicity at doses 3 times greater than the human exposure at the recommended dose based on AUC. At does equivalent to the human exposure, animals demonstrated delays in skeletal development and reduced fetal body weight. Findings in animals also indicate this drug may impair female and male fertility. In female animals, reduction in fertility (at dose exposures equivalent to the human exposure) and a reduced number of ovarian corpora lutea (at dose exposures 3 times the human exposure) were noted; testicular degeneration/depletion was observed in male animals in repeat-dose studies. There is insufficient data in human pregnancy to assess the risks.

AU TGA pregnancy category D: Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details.

US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D and X are being phased out.

Use is not recommended unless the potential benefit to the mother outweighs the possible risk to the fetus.

AU TGA pregnancy category: D
US FDA pregnancy category: Not assigned.

Risk Summary: Based on findings from animal reproduction studies and its mechanism of action, this drug can cause fetal harm when administered to a pregnant woman.

Comments:
-Based on animal studies, this drug may cause fetal harm and impair fertility.
-This drug may decrease the efficacy of hormonal contraceptives; counsel female patients of reproductive potential to use an effective non-hormonal method of contraception during therapy and for 2 to 4 weeks after the last dose of this drug and 4 months after the last dose of trametinib when given in combination with this drug.
-Advise male patients of the potential risk for impaired spermatogenesis, which may be irreversible.
-Adequate methods of contraception should be encouraged.
-If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential harm to the fetus.

See references

Use is not recommended.

Excreted into human milk: Unknown
Excreted into animal milk: Data not available

Comments:
-No information is available on the use of this drug during breastfeeding. Because it is more than 99% bound to plasma proteins, the amount in milk is likely to be low and absorption is unlikely because it is probably destroyed in the infant GI tract.
-The effects in the nursing infant are unknown.
-The manufacturer recommends that breastfeeding be discontinued during therapy and for 2 weeks after the last dose.

See references