tudies of Mekinist did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In Trial 1, 49 patients (23%) were 65 years of age and older, and 9 patients (4%) were 75 years of age and older.
Females and Males of Reproductive Potential
Contraception:Females
Mekinist can cause fetal harm when administered during pregnancy. Advise female patients of reproductive potential to use highly effective contraception during treatment and for 4 months after treatment. Advise patients to contact their healthcare provider if they become pregnant, or if pregnancy is suspected, while taking Mekinist [see Use in Specific Populations (8.1)].
Infertility:Females
Trametinib may impair fertility in female patients [see Nonclinical Toxicology (13.1)].
Hepatic Impairment
No formal clinical study has been conducted to eva luate the effect of hepatic impairment on the pharmacokinetics of trametinib. No dose adjustment is recommended in patients with mild hepatic impairment based on a population pharmacokinetic analysis [see Clinical Pharmacology (12.3)].
The appropriate dose of Mekinist has not been established in patients with moderate or severe hepatic impairment.
Renal Impairment
No formal clinical study has been conducted to eva luate the effect of renal impairment on the pharmacokinetics of trametinib. No dose adjustment is recommended in patients with mild or moderate renal impairment based on a population pharmacokinetic analysis [see Clinical Pharmacology (12.3)]. The appropriate dose of Mekinist has not been established in patients with severe renal impairment.
Overdosage
There were no reported cases of inadvertent overdosage with Mekinist. The highest doses of Mekinist eva luated in clinical trials were 4 mg orally once daily and 10 mg administered orally once daily on two consecutive days followed by 3 mg once daily. In seven patients treated on one of these two schedules, there were two cases of retinal pigment epithelial detachments for an incidence of 28%. Since trametinib is highly bound to plasma proteins, hemodialysis is likely to be ineffective in the treatment of overdose with Mekinist.
Mekinist Description
Trametinib dimethyl sulfoxide is a kinase inhibitor. The chemical name is acetamide, N-[3-[3-cyclopropyl-5-[(2-fluoro-4- iodophenyl)amino]-3,4,6,7-tetrahydro-6,8-dimethyl- 2,4,7-trioxopyrido[4,3-d]pyrimidin-1(2H)-yl]phenyl]-, compound with 1,1’-sulfinylbis[methane] (1:1). It has a molecular formula C26H23FIN5O4•C2H6OS with a molecular mass of 693.53.
Trametinib dimethyl sulfoxide has the following chemical structure:
Trametinib dimethyl sulfoxide is a white to almost white powder. It is practically insoluble in the pH range of 2 to 8 in aqueous media.
Mekinist (trametinib) Tablets are supplied as 0.5-mg, 1-mg, and 2-mg tablets for oral administration. Each 0.5-mg tablet contains 0.5635 mg trametinib dimethyl sulfoxide equivalent to 0.5 mg of trametinib non-solvated parent. Each 1-mg tablet contains 1.127 mg trametinib dimethyl sulfoxide equivalent to 1 mg of trametinib non-solvated parent. Each 2-mg tablet contains 2.254 mg trametinib dimethyl sulfoxide equivalent to 2 mg of trametinib non-solvated parent.
The inactive ingredients of Mekinist Tablets are: Tablet Core: mannitol, microcrystalline cellulose, hypromellose, croscarmellose sodium, magnesium stearate (veget |
