Braftovi

/ Medison

BRAF V600E or V600K Mutation-Positive Unresectable or Metastatic Melanoma and for BRAF V600E Mutation-Positive Metastatic Non-Small Cell Lung Cancer (NSCLC)- The recommended dosage of this medical product is 450 mg (six 75 mg capsules) orally once daily in combination with binimetinib until disease progression or unacceptable toxicity.
Recommended Dosage for BRAF V600E Mutation-Positive Metastatic Colorectal Cancer (CRC)– The recommended dosage of this medical product is 300 mg (four 75 mg capsules) orally once daily in combination with cetuximab until disease progression or unacceptable toxicity.
For full details see prescribing information

BRAF V600E or V600K Mutation-Positive Unresectable or Metastatic Melanoma
BRAF V600E Mutation-Positive Metastatic Colorectal Cancer (CRC)– treatment of adult patients, detected by an -approved test, after prior therapy.
BRAF V600E Mutation-Positive metastatic non-small cell lung cancer (NSCLC)– in combination with binimetinib, for the treatment of adult patients, with mutation, as detected by an approved test.
Limitations of Use
Is not indicated for treatment of patients with wild-type BRAF melanoma, wild-type BRAF CRC, or wild-type BRAF NSCLC

Hypersensitivity to the active substance or to any of the excipients

New Primary Malignancies
New primary malignancies, cutaneous and non-cutaneous, have been observed in patients treated with BRAF inhibitors.
Cutaneous Malignancies
In clinical studied, cutaneous squamous cell carcinoma (cuSCC), including keratoacanthoma (KA), occurred in 2.6%, and basal cell carcinoma occurred in 1.6% of patients who received this medical product in combination with binimetinib. Median time to first occurrence of cuSCC/KA was 5.8 months (range 1 to 9 months).
For patients who received this medical product as a single agent, cuSCC/KA was reported in 8%, basal cell carcinoma in 1%, and a new primary melanoma in 5% of patients.
cuSCC/KA occurred in 1.4% of patients with CRC, and a new primary melanoma occurred in 1.4% of patients who received this medical product in combination with cetuximab.
cuSCC and skin papilloma, each occurred in 2% of patients who received encorafenib in combination with binimetinib.
Perform dermatologic evaluations prior to initiating treatment, every 2 months during treatment, and for up to 6 months following discontinuation of treatment. Manage suspicious skin lesions with excision and dermatopathologic evaluation. Dose modification is not recommended for new primary cutaneous malignancies.
Non-Cutaneous Malignancies
Based on its mechanism of action, encorafenib may promote malignancies associated with activation of RAS through mutation or other mechanisms. Monitor patients receiving encorafenib for signs and symptoms of non-cutaneous malignancies. Discontinue encorafenib for RAS mutation-positive non-cutaneous malignancies.
Hepatotoxicity
Hepatotoxicity can occur when encorafenib is administered in combination with binimetinib. Monitor liver laboratory tests before initiation of this medical product, monthly during treatment, and as clinically indicated. Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction.
Hemorrhage
Across clinical studies, hemorrhage was reported in 12% to 19% of patients receiving this medical product, with Grade 3 or higher events. Fatal events, including intracranial and gastrointestinal hemorrhage, have been observed. The most frequent hemorrhagic events included gastrointestinal bleeding such as rectal hemorrhage (up to 4.2%), hematochezia (up to 3.1%), and hemorrhoidal hemorrhage (1%); nasal bleeding/epistaxis (6.9%); anal hemorrhage (2%); and hemothorax (2%).
Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction.
Uveitis
Uveitis, including iritis and iridocyclitis, has been reported in patients treated with encorafenib in combination with binimetinib. Assess for visual symptoms at each visit. Perform an ophthalmologic evaluation at regular intervals and for new or worsening visual disturbances, and to follow new or persistent ophthalmologic findings. Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction.
QT Prolongation
This medical product is associated with dose-dependent QTc interval prolongation in some patients. Across clinical studies, an increase in QTcF interval to >500 ms was observed in 0.5% to 2.1% of patients receiving encorafenib in combination with binimetinib. Monitor patients who already have or who are at significant risk of developing QTc prolongation, including patients with known long QT syndromes, clinically significant bradyarrhythmias, severe or uncontrolled heart failure and those taking other medicinal products associated with QT prolongation. Correct hypokalemia and hypomagnesemia prior to and during administration. Withhold, reduce dose, or permanently discontinue for QTc > 500 ms.
Embryo-Fetal Toxicity
Based on its mechanism of action, encorafenib can cause fetal harm when administered to a pregnant woman.
For full details see prescribing information.

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.
For full details see prescribing information.

Effect of Other Drugs on encorafenib
Strong or Moderate CYP3A4 Inhibitors
Coadministration of encorafenib with a strong or moderate CYP3A4 inhibitor increases encorafenib plasma concentrations. and may increase encorafenib adverse reactions. Avoid coadministration of encorafenib with strong or moderate CYP3A4 inhibitors, including grapefruit juice. If coadministration is unavoidable, reduce the dose of this medical product.
Strong CYP3A4 Inducers
Coadministration of encorafenib with a strong CYP3A4 inducer may decrease encorafenib plasma concentrations and may decrease encorafenib efficacy. Avoid coadministration of encorafenib with strong CYP3A4 inducers.
Effect of encorafenib on Other Drugs
Sensitive CYP3A4 Substrates
encorafenib is a strong CYP3A4 inducer at steady-state. Concomitant use of encorafenib may decrease the plasma concentrations of CYP3A4 substrates (including hormonal contraceptives), which may reduce the efficacy of these substrates. Avoid the coadministration of encorafenib with CYP3A4 substrates for which a decrease in plasma concentration may lead to reduced efficacy of the substrate.
OATP1B1, OATP1B3, or BCRP Substrates
Coadministration of encorafenib with OATP1B1, OATP1B3, or BCRP substrates can result in increased concentrations of the substrates, and may increase toxicity of these agents. When used in combination, monitor patients closely for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.
Drugs That Prolong the QT Interval
encorafenib is associated with dose-dependent QTc interval prolongation. Avoid coadministration of encorafenib with drugs known to prolong the QT/QTc interval.
For full details see prescribing information.

Pregnancy: Based on its mechanism of action, encorafenib can cause fetal harm when administered to a pregnant woman. There are no available clinical data on the use of encorafenib during pregnancy. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to initiating this medical product. Advise females of reproductive potential to use effective contraception during treatment with encorafenib and for 2 weeks after the last dose. Counsel patients to use a non-hormonal method of contraception since encorafenib has the potential to render hormonal contraceptives ineffective.
Lactation: There are no data on the presence of encorafenib or its metabolites in human milk or the effects of encorafenib on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child from encorafenib, advise women not to breastfeed during treatment with encorafenib and for 2 weeks after the last dose.

Since encorafenib is 86% bound to plasma proteins, hemodialysis is likely to be ineffective in the treatment of overdose with encorafenib.