ing with new or progressive pulmonary symptoms and findings including cough, dyspnea, hypoxia, pleural effusion, or infiltrates, pending clinical investigations. Permanently discontinue Mekinist for patients diagnosed with treatment-related ILD or pneumonitis.
Serious Skin Toxicity
In Trial 1, the overall incidence of skin toxicity including rash, dermatitis, acneiform rash, palmar-plantar erythrodysesthesia syndrome, and erythema was 87% in patients treated with Mekinist and 13% in chemotherapy-treated patients. Severe skin toxicity occurred in 12% of patients treated with Mekinist. Skin toxicity requiring hospitalization occurred in 6% of patients treated with Mekinist, most commonly for secondary infections of the skin requiring intravenous antibiotics or severe skin toxicity without secondary infection. In comparison, no patients treated with chemotherapy required hospitalization for severe skin toxicity or infections of the skin. The median time to onset of skin toxicity in patients treated with Mekinist was 15 days (range: 1 to 221 days) and median time to resolution of skin toxicity was 48 days (range: 1 to 282 days). Reductions in the dose of Mekinist were required in 12% and permanent discontinuation of Mekinist was required in 1% of patients with skin toxicity.
Monitor patients receiving Mekinist for skin toxicities and for secondary infections [see Dosage and Administration (2.3)].
Embryofetal Toxicity
Based on its mechanism of action, Mekinist can cause fetal harm when administered to a pregnant woman. Mekinist 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 a fetus. [See Use in Specific Populations (8.1).]
Advise female patients of reproductive potential to use highly effective contraception during treatment with Mekinist 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, 8.6).]
Adverse Reactions
The following adverse reactions are discussed in greater detail in another section of the label:
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Cardiomyopathy [see Warnings and Precautions (5.1)]
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Retinal pigment epithelial detachment [see Warnings and Precautions (5.2)]
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Retinal vein occlusion [see Warnings and Precautions (5.3)]
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Interstitial lung disease [see Warnings and Precautions (5.4)]
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Serious skin toxicity [see Warnings and Precautions (5.5)]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The data described in the Warnings and Precautions section and below reflect exposure to Mekinist in 329 patients including 107 (33%) exposed for greater than or equal to 6 months and 30 (9%) exposed for greater than or equal to one year. Mekinist was studied in open-label, single-arm trials (N = 118) or in an open-label, randomized, active-controlled trial (N = 211). The median age was 54, 60% were male, >99% were white |
