29) treated with Mekinist were:
Nervous System Disorders: Dizziness, dysgeusia.
Ocular Disorders: Vision blurred, dry eye.
Infections and Infestations: Folliculitis, rash pustular, cellulitis.
Cardiac Disorders: Bradycardia.
Gastrointestinal Disorders: Xerostomia.
Musculoskeletal and Connective Tissue Disorders: Rhabdomyolysis.
Table 3. Percent-Patient Incidence of Laboratory Abnormalities Occurring at a Higher Incidence in Patients Treated With Mekinist in Trial 1 [Between Arm Difference of ≥5% (All Grades) or ≥2% (Grades 3 or 4)a] Preferred Term
Mekinist
Chemotherapy
(N = 211)
(N = 99)
All Grades
Grades
3 and 4
All Grades
Grade
3 and 4
Increased Aspartate aminotransferase (AST)
60
2
16
1
Increased Alanine aminotransferase (ALT)
39
3
20
3
Hypoalbuminemia
42
2
23
1
Anemia
38
2
26
3
Increased Alkaline phosphatase
24
2
18
3
aNo Grade 4 events were reported in either treatment arm.
Drug Interactions
No formal clinical studies have been conducted to eva luate human cytochrome P450 (CYP) enzyme-mediated drug interactions with trametinib [see Clinical Pharmacology (12.3)].
USE IN SPECIFIC POPULATIONS
Pregnancy
Pregnancy Category D
Risk Summary: Mekinist can cause fetal harm when administered to a pregnant woman. Trametinib was embryotoxic and abortifacient in rabbits at doses greater than or equal to those resulting in exposures approximately 0.3 times the human exposure at the recommended clinical dose. 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 hazard to the fetus [see Warnings and Precautions (5.6)].
Animal Data: In reproductive toxicity studies, administration of trametinib to rats during the period of organogenesis resulted in decreased fetal weights at doses greater than or equal to 0.031 mg/kg/day (approximately 0.3 times the human exposure based on AUC at the recommended dose). In rats, at a dose resulting in exposures 1.8-fold higher than the human exposure at the recommended dose, there was maternal toxicity and an increase in post-implantation loss.
In pregnant rabbits, administration of trametinib during the period of organogenesis resulted in decreased fetal body weight and increased incidence of variations in ossification at doses greater than or equal to 0.039 mg/kg/day (approximately 0.08 times the human exposure at the recommended dose based on AUC). In rabbits administered trametinib at 0.15 mg/kg/day (approximately 0.3 times the human exposure at the recommended dose based on AUC) there was an increase in post-implantation loss, including total loss of pregnancy, compared to control animals.
Nursing Mothers
It is not known whether this drug is present in human milk. Because many drugs are present in human milk and because of the potential for serious adverse reactions in nursing infants from Mekinist, a decision should be made whether to discontinue nursing or to discontinue the drug taking into account the importance of the drug to the mother.
Pediatric Use
The safety and effectiveness of Mekinist have not been established in pediatric patients.
Geriatric Use
Clinical s |
