continuation [see Dosage and Administration (2.2)].
5.6 Photosensitivity
Mild to severe photosensitivity was reported in patients treated with ZELBORAF in clinical trials [see Adverse Reactions (6.1)]. All patients should be advised to avoid sun exposure while taking ZELBORAF. While taking the drug, patients should be advised to wear protective clothing and use a broad spectrum UVA/UVB sunscreen and lip balm (SPF ≥ 30) when outdoors to help protect against sunburn.
For intolerable grade 2 (tender erythema covering 10 - 30% body surface area) or greater photosensitivity, dose modifications are recommended [see Dosage and Administration (2.2)].
5.7 Ophthalmologic Reactions
In Trial 1, five cases of uveitis have been reported in patients treated with ZELBORAF. Treatment with steroid and mydriatic ophthalmic drops may be required to manage uveitis. Patients should be routinely monitored for signs and symptoms of uveitis. Additionally, there were five patients with blurry vision, five patients with iritis and six patients with photophobia. There was one case of retinal vein occlusion in Trial 2.
5.8 New Primary Malignant Melanoma
There were eight skin lesions in seven patients reported as new primary malignant melanoma in Trial 1. Cases were managed with excision, and patients continued treatment without dose adjustment. Monitoring for skin lesions should occur as outlined above [see Warnings and Precautions (5.1)].
5.9 Use in Pregnancy
Pregnancy Category D
ZELBORAF may cause fetal harm when administered to a pregnant woman based on its mechanism of action. There are no adequate and well-controlled studies in pregnant women. 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)].
5.10 BRAFV600E Testing
Confirmation of BRAFV600E mutation-positive melanoma as detected by an FDA-approved test is required for selection of patients for ZELBORAF therapy because these are the only patients studied and for whom benefit has been shown. For patients in ZELBORAF clinical studies, including Trial 1 and Trial 2, all enrolled patients tested positive when their tumor tissue was assessed with the cobas® 4800 BRAF V600 Mutation Test [see Clinical Studies (14)]. This test is designed to detect BRAFV600E mutations in DNA isolated from formalin-fixed, paraffin-embedded human melanoma tissue. The safety and efficacy of ZELBORAF have not been eva luated in patients whose melanoma tested negative by the cobas® 4800 BRAF V600 Mutation Test. Refer to the package inserts of FDA approved test kits, for detailed information.
6 ADVERSE REACTIONS
The following adverse reactions are discussed in greater detail in another section of the label:
Cutaneous Squamous Cell Carcinoma [see Warnings and Precautions (5.1)]
Hypersensitivity Reactions [see Warnings and Precautions (5.2)]
Dermatologic Reactions [see Warnings and Precautions (5.3)]
QT Prolongation [see Warnings and Precautions (5.4)]
Liver Laboratory Abnormalities [see Warnings and Precautions (5.5)]
Photosensitivity [see Warnings and Precautions (5.6)]
Ophthalmologic Reactions [see Warnings and Precautions (5.7)]
New Primary Malignant Melanoma [see Warnings and Precautions (5.8)]
6.1 Clinical Trials Experience
Because clinical studies are conducted under widely varying conditions, adverse rea |
