Encorafenib

Encorafenib is a prescription medication used to treat the symptoms of Melanoma and Metastatic Colorectal Cancer. 

• Encorafenib is available under the following different brand names: Braftovi

Common side effects of Encorafenib include:

• Nausea,
• Vomiting,
• Stomach pain,
• Tiredness, and
• Joint pain or swelling

Serious side effects of Encorafenib include:

• Hives,
• Difficulty breathing,
• Swelling of the face, lips, tongue, or throat,
• Eye pain,
• Swelling of the eye,
• Vision changes,
• Seeing halos around lights,
• Seeing color “dots” in your vision,
• Severe skin rash,
• Skin pain or swelling,
• Redness and peeling skin on the hands or feet,
• Fast or pounding heartbeats,
• Fluttering in the chest,
• Shortness of breath,
• Sudden dizziness,
• Weakness,
• Dizziness,
• Headache,
• Nosebleeds,
• Rectal bleeding,
• Bloody or tarry stools,
• Coughing up blood, and
• Vomit that looks like coffee grounds

Rare side effects of Encorafenib include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Capsule

• 75 mg

Melanoma

Adult dosage

• 450 mg orally once a day in combination with binimetinib
• Continue until disease progression or unacceptable toxicity
• See the binimetinib drug monograph for recommended dosing information

Metastatic Colorectal Cancer

Adult dosage

• 300 mg orally once a day in combination with cetuximab
• Continue until disease progression or unacceptable toxicity
• See the cetuximab drug monograph for recommended dosing information

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Encorafenib has severe interactions with the following drugs
  • doravirine
  • dronedarone
  • elagolix
  • isavuconazonium sulfate
  • lonafarnib
  • mavacamten
  • pacritinib
  • voriconazole
• Encorafenib has serious interactions with at least 220 other drugs.
• Encorafenib has moderate interactions with at least 344 other drugs.
• Encorafenib has minor interactions with the following drugs
  • erdafitinib
  • nitrofurantoin

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Encorafenib?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Encorafenib?”

Cautions

• Confirm evidence of BRAF V600E or V600K mutation before initiating treatment; 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; not indicated for wild-type BRAF melanoma
• Hemorrhage can occur; hemorrhagic events include GI, hemorrhoidal, rectal, and intracranial hemorrhage and hematochezia
• Uveitis (. g, iritis, iridocyclitis) reported; assess for visual symptoms at each visit; perform an ophthalmologic evaluation regularly and for new or worsening visual disturbances, and follow new or persistent ophthalmologic findings
• Dose-dependent QTc interval prolongation reported; monitor patients who already have or who are at significant risk of developing QTc prolongation (. g, patients with known long QT syndromes, clinically significant bradyarrhythmias, severe or uncontrolled heart failure, those taking medications associated with QT prolongation); correct hypokalemia and hypomagnesemia before and during the administration
• Based on its mechanism of action, fetal harm may occur when administered to a pregnant woman
• Grade 3 or 4 dermatologic reactions occurred in 21% of patients treated with encorafenib as a single agent compared with 2% of patients treated with encorafenib in combination with binimetinib
• Refer to the binimetinib or cetuximab prescribing information for additional risk information that applies to combination use treatment
• New primary malignancies
  • New primary malignancies, cutaneous and no cutaneous, observed
  • Cutaneous squamous cell carcinoma
  • In the COLUMBUS trial, cutaneous squamous cell carcinoma (SCC), including keratoacanthoma (KA) and basal cell carcinoma occurred in patients who received sorafenib in combination with binimetinib
  • Perform dermatologic evaluations before initiating treatment, every 2 months during treatment, and for up to 6 months following discontinuation of treatment
  • Manage suspicious skin lesions with excision and dermatopathology evaluation
  • Dose modification is not recommended for new primary cutaneous malignancies
• Noncutaneous malignancies
  • Based on its mechanism of action, encorafenib may promote malignancies associated with the activation of RAS through mutation or other mechanisms
  • Monitor for signs and symptoms of noncutaneous malignancies
  • Discontinue treatment for RAS mutation-positive noncutaneous malignancies
• Drug interaction overview
  • Reversible inhibitor of UGT1A1, CYP1A2, CYP2B6, CYP2C8/9, CYP2D6, and CYP3A, and a time-dependent inhibitor of CYP3A4 at clinically relevant plasma concentrations
  • Inhibitor of OATP1B1, OATP1B3, and BCRP
  • Induces CYP2B6, CYP2C9, and CYP3A4 at clinically relevant plasma concentrations
  • Substrate of CYP3A4 and P-glycoprotein (P-GP)
  • Strong or moderate CYP3A4 inhibitors
  • Avoid coadministration
    • Strong or moderate CYP3A4 inhibitor increases encorafenib plasma concentrations and the risk of toxicities
    • If coadministration is unavoidable, modify the dose as recommended
    • Strong or moderate CYP3A4 inducers
  • Avoid coadministration
    • Strong or moderate CYP3A4 inducers may decrease encorafenib plasma concentrations and efficacy
    • Sensitive CYP3A4 substrates
    • Coadministration with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents
    • Encorafenib can decrease the concentrations and efficacy of hormonal contraceptives; avoid hormonal contraceptives
  • Drugs that prolong the QT interval
    • Avoid the use of drugs known to prolong QT/QTc
    • Encorafenib is associated with dose-dependent QTc interval prolongation
    • OATP1B1, OATP1B3, or BCRP substrates
    • Closely monitor signs and symptoms of toxicities of OATP1B1, OATP1B3, or BCRP substrates; consider a dosage adjustment of these substrates
    • Encorafenib can result in increased concentrations of OATP1B1, OATP1B3, or BCRP substrates, and may increase the toxicity of these agents

Pregnancy and Lactation

• Based on its mechanism of action, fetal harm may occur when administered to pregnant women
• There are no available clinical data on the use of encorafenib during pregnancy
• Advise pregnant women of the potential risk to a fetus
• Contraception
  • Verify the pregnancy status of females of reproductive potential before initiating treatment
  • Advise females of reproductive potential to use effective contraception during treatment and for 2 weeks after the final dose
  • Nonhormonal contraceptives should be used during treatment and for at least 30 days after the final dose for patients taking encorafenib and binimetinib (see Drug Interactions)
• Infertility
  • Based on findings in male rats at doses approximately 13 times the human exposure at the 450-mg clinical dose, the use of encorafenib may impact fertility in males
• Lactation
  • The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for the drug and any potential adverse effects on the breastfed child or from the underlying maternal condition