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Another NameMekinist,CE-Trametinib,Mekinisuto,二甲基亚砜曲美替尼,迈吉宁
IndicationsTrametinib is a broad-spectrum anti-cancer drug.
Reg No.09 L 1010/23
Inspection NO.
The original manufacturer of Trametinib is GlaxoSmithKline (GSK), which was approved for listing by the US FDA on May 29, 2013 under the trade name Mekinist.
Trimetinib is an oral tablet primarily used to treat specific types of cancer, such as tumors associated with BRAF mutations.
Trametinib is a reversible inhibitor of mitogen activated extracellular signal regulated kinase 1 (MEK1) and MEK2. It inhibits the proliferation and metastasis of cancer cells by inhibiting the activity of MEK protein and blocking the signaling pathway of MAPK.
Trametinib
Trametinib is a broad-spectrum anti-cancer drug.
Based on its mechanism of action and findings from animal reproduction studies, Trametinib can cause fetal harm when administered to a pregnant woman. There is insufficient data in pregnant women exposed to Trametinib to assess the risks. 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 adult clinical dose. Advise pregnant women of the potential risk to a fetus.
There are no data on the presence of trametinib in human milk, or the effects of trametinib on the breastfed child or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with Trametinib and for 4 months following the last dose.
Pregnancy Testing
Verify pregnancy status in females of reproductive potential prior to initiating Trametinib.
Females
Advise female patients of reproductive potential to use effective contraception during treatment with Trametinib and for 4 months after the last dose.
Males
To avoid potential drug exposure to pregnant partners and female partners of reproductive potential, advise male patients (including those who have had vasectomies) with female partners of reproductive potential to use condoms during treatment with Trametinib and for 4 months after the last dose.
Infertility
Females
Advise female patients of reproductive potential that Trametinib may impair fertility. Increased follicular cysts and decreased corpora lutea were observed in female rats at dose exposures equivalent to 0.3 times the human exposure at the recommended adult dose.
BRAF V600E Mutation-Positive Unresectable or Metastatic Solid Tumors and LGG.
The safety and effectiveness of Trametinib in combination with dabrafenib have been established in pediatric patients 1 year of age and older with unresectable or metastatic solid tumors with BRAF V600E mutation who have progressed following prior treatment and have no satisfactory alternative treatment options; or with LGG with BRAF V600E mutation who require systemic therapy.
The safety and effectiveness of Trametinib in combination with dabrafenib have not been established for these indications in pediatric patients less than 1 year old.
The safety and effectiveness of Trametinib as a single agent in pediatric patients have not been established.
Of the 214 patients with melanoma who received single agent Trametinib in the METRIC study, 27% were aged 65 years and older and 4% were over 75 years old. This study of single agent Trametinib in melanoma did not include sufficient numbers of geriatric patients to determine whether they respond differently from younger adults.
Of the 994 patients with melanoma who received Trametinib plus dabrafenib in the COMBI-d, COMBI-v, and COMBI-AD studies, 21% were aged 65 years and older and 5% were aged 75 years and older. No overall differences in the effectiveness of Trametinib plus dabrafenib were observed in geriatric patients as compared to younger adults across these melanoma studies. The incidences of peripheral edema (26% vs. 12%) and anorexia (21% vs. 9%) increased in geriatric patients as compared to younger adults in these studies.
Of the 93 patients with NSCLC who received Trametinib in Study BRF113928, there were insufficient numbers of geriatric patients aged 65 and older to determine whether they respond differently from younger adults.
Of the 26 patients with ATC who received Trametinib in Study BRF117019, 77% were aged 65 years and older and 31% were aged 75 years and older. This study in ATC did not include sufficient numbers of younger adults to determine whether they respond differently compared to geriatric patients.
No dose adjustment is recommended in patients with mild (bilirubin ≤ upper limit of normal (ULN) and aspartate aminotransferase (AST) > ULN or bilirubin > 1x to 1.5x ULN and any AST) hepatic impairment.
A recommended dosage of Trametinib has not been established for patients with moderate (bilirubin > 1.5x to 3x ULN and any AST) or severe (bilirubin > 3x to 10x ULN and any AST) hepatic impairment. Consider the risk-benefit profile of Trametinib related to dosing prior to determining whether to administer Trametinib to patients with moderate or severe hepatic impairment.
In patients with moderate hepatic impairment, 3 patients who received a starting dose of 1.5 mg orally once daily and two patients who received a starting dose of 2 mg orally once daily did not experience dose limiting toxicities (DLTs) during the first cycle of therapy.
In patients with severe hepatic impairment, 3 patients who received a starting dose of 1 mg orally once daily did not experience DLTs during the first cycle; one patient who received a starting dose of 1.5 mg orally once daily experienced a DLT (grade 3 acneiform rash).
Compared to patients with normal hepatic function, there was no increase in exposure of trametinib in patients with moderate or severe hepatic impairment.
The highest doses of Trametinib evaluated in clinical trials were 4 mg orally once daily and 10 mg administered orally once daily on 2 consecutive days followed by 3 mg once daily. In seven patients treated on one of these two schedules, there were two cases of RPEDs 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 Trametinib.
Store refrigerated at 2°C to 8°C (36°F to 46°F). Dispense in original bottle. Do not remove desiccant. Protect from moisture and light. Do not place medication in pill boxes.
The median time to achieve peak plasma concentrations (Tmax) is 1.5 hours post-dose. The mean absolute bioavailability of Trametinib tablets is 72% and Trametinib for oral solution is 81%.
from FDA，2024.03
