Safety

Aromasin (exemestane) tablets

Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER) 

July 2016

Summary View

WARNINGS AND PRECAUTIONS

2 subsections added:

Use in Premenopausal Women
  • AROMASIN is not indicated for the treatment of breast cancer in premenopausal women.
Embryo-Fetal Toxicity
  • Based on findings from animal studies and its mechanism of action, AROMASIN can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of exemestane to pregnant rats and rabbits caused increased incidence of abortions and embryo-fetal toxicity. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with AROMASIN and for 1 month after the last dose.

USE IN SPECIFIC POPULATIONS

PLLR conversion:

Pregnancy
Risk Summary
  • Based on findings in animal studies and its mechanism of action, AROMASIN can cause fetal harm when administered to a pregnant woman. Limited human data from case reports are insufficient to inform a drug-associated risk. In animal reproduction studies, administration of exemestane to pregnant rats and rabbits caused increased incidence of abortions, embryo-fetal toxicity, and prolonged gestation with abnormal or difficult labor. Advise pregnant women of the potential risk to a fetus.
  • The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Data
Animal Data
  • In animal reproduction studies in rats and rabbits, exemestane caused embryo-fetal toxicity, and was abortifacient. Radioactivity related to 14C-exemestane crossed the placenta of rats following oral administration of 1 mg/kg exemestane. The concentration of exemestane and its metabolites was approximately equivalent in maternal and fetal blood. When rats were administered exemestane from 14 days prior to mating until either days 15 or 20 of gestation, and resuming for the 21 days of lactation, an increase in placental weight was seen at 4 mg/kg/day (approximately 1.5 times the recommended human daily dose on a mg/m2 basis). Increased resorptions, reduced number of live fetuses, decreased fetal weight, retarded ossification, prolonged gestation and abnormal or difficult labor was observed at doses equal to or greater than 20 mg/kg/day (approximately 7.5 times the recommended human daily dose on a mg/m2 basis). Daily doses of exemestane, given to rabbits during organogenesis, caused a decrease in placental weight at 90 mg/kg/day (approximately 70 times the recommended human daily dose on a mg/m2 basis) and in the presence of maternal toxicity, abortions, an increase in resorptions, and a reduction in fetal body weight were seen at 270 mg/kg/day. No malformations were noted when exemestane was administered to pregnant rats or rabbits during the organogenesis period at doses up to 810 and 270 mg/kg/day, respectively (approximately 320 and 210 times the recommended human dose on a mg/m2 basis, respectively).
Lactation
Risk Summary
  • There is no information on the presence of exemestane in human milk, or on its effects on the breastfed infant or milk production. Exemestane is present in rat milk at concentrations similar to maternal plasma. Because of the potential for serious adverse reactions in breast-fed infants from AROMASIN, advise a woman not to breastfeed during treatment with AROMASIN and for 1 month after the final dose.
Data
  • Radioactivity related to exemestane appeared in rat milk within 15 minutes of oral administration of radiolabeled exemestane. Concentrations of exemestane and its metabolites were approximately equivalent in the milk and plasma of rats for 24 hours after a single oral dose of 1 mg/kg 14C-exemestane.
Females and Males of Reproductive Potential
Pregnancy Testing
  • Pregnancy testing is recommended for females of reproductive potential within seven days prior to initiating AROMASIN.
Contraception
Females
  • AROMASIN can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with AROMASIN and for 1 month after the final dose.
Infertility
  • Based on findings in animals, male and female fertility may be impaired by treatment with AROMASIN.

PATIENT COUNSELING INFORMATION

  • Advise the patient to read the FDA-approved patient labeling (Patient Information).
Embryo-Fetal Toxicity (addition)
  • Advise pregnant women and females of reproductive potential that exposure during pregnancy or within 1 month prior to conception can result in fetal harm. Advise females to inform their healthcare provider of a known or suspected pregnancy.
  • Advise females of reproductive potential to use effective contraception while taking AROMASIN and for 1 month after the last dose.
Lactation (addition)
  • Advise women not to breastfeed during treatment with AROMASIN and for 1 month after the last dose.

 

May 2014

Summary View

5 WARNINGS AND PRECAUTIONS

5.3 Reductions in Bone Mineral Density (BMD)
  • risk of osteoporosis added

6 ADVERSE REACTIONS

6.2 Post-Marketing Experiences
  • ...include hypersensitivity, paresthesia, cholestatic hepatitis, and acute generalized exanthematous pustulosis, urticaria, and pruritus. 

 

February 2013

Summary View 

WARNINGS AND PRECAUTIONS

Vitamin D Assessment
  • Routine assessment of 25-hydroxy vitamin D levels prior to the start of aromatase inhibitor treatment should be performed, due to the high prevalence of vitamin D deficiency in women with early breast cancer (EBC). Women with vitamin D deficiency should receive supplementation with vitamin D.
 

ADVERSE REACTIONS

Postmarketing Experience
  • hypersensitivity
  • urticaria
  • pruritis

 

March 2011 

Summary View 

ADVERSE REACTION

  • adverse event information to the labeling based on 52 months of median follow-up in study 96-OEXE 031
Post-Marketing Experience
  • addition of information cholestatic hepatitis
     

 

Page Last Updated: 08/15/2016
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