ment epithelial detachments (RPED) can occur during treatment with MEKINIST. In Trial 1, where ophthalmologic examinations including retinal eva luation were performed pretreatment and at regular intervals during treatment, one patient (0.5%) receiving MEKINIST developed RPED and no cases of RPED were identified in chemotherapy-treated patients. Across all clinical trials of MEKINIST, the incidence of RPED was 0.8% (14/1749).
Retinal detachments were often bilateral and multifocal, occurring in the macular region of the retina. RPED led to reduction in visual acuity that resolved after a median of 11.5 days (range: 3 to 71 days) following the interruption of dosing with MEKINIST, although Ocular Coherence Tomography (OCT) abnormalities persisted beyond a month in at least several cases.
Perform ophthalmological eva luation at any time a patient reports visual disturbances and compare to baseline, if available. Withhold MEKINIST if RPED is diagnosed. If resolution of the RPED is documented on repeat ophthalmological eva luation within 3 weeks, resume MEKINIST at a reduced dose [see Dosage and Administration (2.3)].
5.3 Retinal Vein Occlusion (RVO)
Across all clinical trials of MEKINIST, the incidence of RVO was 0.2% (4/1749). An RVO may lead to macular edema, decreased visual function, neovascularization, and glaucoma.
Urgently (within 24 hours) perform ophthalmological eva luation for patient-reported loss of vision or other visual disturbances. Permanently discontinue MEKINIST in patients with documented retinal vein occlusion [see Dosage and Administration (2.3)].
5.4 Interstitial Lung Disease
In clinical trials of MEKINIST at the recommended dose (N = 329), interstitial lung disease (ILD) or pneumonitis occurred in 1.8% of patients. In Trial 1, 2.4% (5/211) of patients treated with MEKINIST developed ILD or pneumonitis; all five patients required hospitalization. The median time to first presentation of ILD or pneumonitis was 160 days (range: 60 to 172 days).
Withhold MEKINIST in patients presenting 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.
5.5 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.
