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Dabrafenib results in an increased incidence of cutaneous squamous cell carcinoma, keratoacanthoma, and melanoma. In Trial 1, cutaneous squamous cell carcinomas and keratoacanthomas (cuSCC) occurred in 7% (14/187) of patients treated with Dabrafenib and in none of the patients treated with dacarbazine. Across clinical trials of Dabrafenib (n = 586), the incidence of cuSCC was 11%. The median time to first cuSCC was 9 weeks (range: 1 to 53weeks). Of those patients who developed a cuSCC, approximately 33% developed one or more cuSCC with continued Dabrafenib. The median time between diagnosis of the first cuSCC and the second cuSCC was 6 weeks.
In Trial 1, the incidence of new primary malignant melanomas was 2% (3/187) for patients receiving Dabrafenib while no chemotherapy-treated patient was diagnosed with new primary malignant melanoma.
Perform dermatologic evaluations prior to initiation of Dabrafenib, every 2 months while on therapy, and for up to 6 months following discontinuation of Dabrafenib.
In vitro experiments have demonstrated paradoxical activation of MAP-kinase signaling and increased cell proliferation in BRAF wild-type cells which are exposed to BRAF inhibitors. Confirm evidence of BRAF V600E mutation status prior to initiation of Dabrafenib.
In Trial 1, serious febrile drug reactions, defined as serious cases of fever or fever of any severity accompanied by hypotension, rigors or chills, dehydration, or renal failure in the absence of another identifiable cause (e.g., infection) occurred in 3.7% (7/187) of patients treated with Dabrafenib and in none of the patients treated with dacarbazine. The incidence of fever (serious and non-serious) was 28% in patients treated with Dabrafenib and 10% in patients treated with dacarbazine. In patients treated with Dabrafenib, the median time to initial onset of fever (any severity) was 11 days (range: 1 to 202 days) and the median duration of fever was 3 days (range 1 to 129 days).
Withhold Dabrafenib for fever of 101.3ºF or greater or for any serious febrile drug reaction and evaluate for signs and symptoms of infection. Refer to Table 1 for recommended dose modifications for adverse reactions. Prophylaxis with antipyretics may be required when resuming Dabrafenib.
Hyperglycemia requiring an increase in the dose of, or initiation of insulin or oral hypoglycemic agent therapy can occur with Dabrafenib. In Trial 1, five of 12 patients with a history of diabetes required more intensive hypoglycemic therapy while taking Dabrafenib. The incidence of Grade 3 hyperglycemia based on laboratory values was 6% (12/187) in patients treated with Dabrafenib compared to none of the dacarbazine-treated patients.
Monitor serum glucose levels as clinically appropriate during treatment with Dabrafenib in patients with pre-existing diabetes or hyperglycemia. Advise patients to report symptoms of severe hyperglycemia such as excessive thirst or any increase in the volume or frequency of urination.
Uveitis (including iritis) occurred in 1% (6/586) of patients treated with Dabrafenib across clinical trials. Symptomatic treatment employed in clinical trials included steroid and mydriatic ophthalmic drops. Monitor patients for visual signs and symptoms of uveitis (e.g., change in 80 vision, photophobia, and eye pain).
Dabrafenib, which contains a sulfonamide moiety, confers a potential risk of hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Closely observe patients with G6PD deficiency for signs of hemolytic anemia.
Based on its mechanism of action, Dabrafenib can cause fetal harm when administered to a pregnant woman. Dabrafenib was teratogenic and embryotoxic in rats at doses three times greater than 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.
Advise female patients of reproductive potential to use a highly effective non-hormonal method of contraception during treatment and for 4 weeks after treatment since Dabrafenib can render hormonal contraceptives ineffective. Advise patients to contact their healthcare provider if they become pregnant, or if pregnancy is suspected, while taking Dabrafenib.
from FDA,2013.05
Dabrafenib is a drug used to treat specific types of skin cancer, such as melano···【more】
Release date：2025-01-14Recommended：98
