Skip to Content

Encorafenib

Medically reviewed by Drugs.com. Last updated on Jun 27, 2020.

Pronunciation

(en koe RAF e nib)

Index Terms

  • LGX 818

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, Oral:

Braftovi: 50 mg [DSC], 75 mg

Brand Names: U.S.

  • Braftovi

Pharmacologic Category

  • Antineoplastic Agent, BRAF Kinase Inhibitor

Pharmacology

Encorafenib is an ATP-competitive inhibitor of protein kinase B-raf (BRAF) which suppresses the MAPK pathway (Dummer 2018). Encorafenib targets BRAF V600E, V600 D, and V600 K, and has a longer dissociation half-life than other BRAF inhibitors, allowing for sustained inhibition (Dummer 2018). BRAF V600 mutations result in constitutive activation of the BRAF pathway (which may stimulate tumor growth); BRAF inhibition inhibits tumor cell growth. The combination of encorafenib and binimetinib allows for greater antitumor activity in BRAF V600 mutant cell lines; in animal studies, the combination also delayed the emergence of resistance in BRAF V600E mutant cells compared to either drug alone. In BRAF-mutant colorectal cancer, EGFR-mediated MAPK pathway activation is a resistance mechanism to BRAF inhibitors; the combination of a BRAF inhibitor and anti-EGFR agents has been shown to overcome this resistance mechanism (in nonclinical models). The combination of encorafenib and cetuximab had an anti-tumor effect greater than either agent alone (in an animal model).

Absorption

At least 86% of the dose is absorbed

Distribution

164 L

Metabolism

Primarily via CYP3A4 and to a lesser extent by CYP2C19 (16%) and CYP2D6 (1%).

Excretion

Feces (47%; 5% as unchanged drug); urine (47%; 2% as unchanged drug)

Time to Peak

2 hours

Half-Life Elimination

3.5 hours

Protein Binding

86% to plasma proteins

Use: Labeled Indications

Colorectal cancer, metastatic: Treatment of metastatic colorectal cancer in adults with a BRAF V600E mutation (in combination with cetuximab) as detected by an approved test, after prior therapy.

Melanoma, unresectable or metastatic: Treatment of unresectable or metastatic melanoma with a BRAF V600E or V600K mutation (in combination with binimetinib) as detected by an approved test.

Limitations of use: Encorafenib is not indicated for treatment of wild-type BRAF melanoma or wild-type BRAF colorectal cancer.

Contraindications

There are no contraindications listed in the manufacturer's labeling.

Dosing: Adult

Note: Confirm BRAF V600 mutation status prior to treatment initiation. Encorafenib is associated with a moderate emetic potential; antiemetics may be recommended to prevent nausea and vomiting.

Colorectal cancer, metastatic (with BRAF V600E mutation): Oral: 300 mg once daily (in combination with cetuximab) until disease progression or unacceptable toxicity (Kopetz 2019). The BEACON CRC trial also studied the triplet combination of encorafenib, binimetinib, and cetuximab; both the doublet (encorafenib and cetuximab) and triplet (encorafenib, binimetinib, and cetuximab) combinations resulted in similarly improved overall survival rates compared to the control group (Kopetz 2019). A quality of life analysis for the BEACON CRC trial demonstrated no overall differences between triplet and doublet therapy across four quality of life measures (Kopetz 2020).

Melanoma, unresectable or metastatic (with BRAF V600E or BRAF V600K mutation): Oral: 450 mg once daily (in combination with binimetinib) until disease progression or unacceptable toxicity (Dummer 2018).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Missed doses: Do not administer a missed dose if <12 hours until the next dose. Do not take an additional dose if vomiting occurs after encorafenib administration; resume with the next scheduled dose.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Adjustment for Toxicity

Note: In metastatic melanoma, if encorafenib is permanently discontinued, discontinue binimetinib. If binimetinib is withheld, reduce encorafenib dose to a maximum of 300 mg once daily until binimetinib therapy is resumed. In metastatic colorectal cancer, if cetuximab is discontinued, discontinue encorafenib. Refer to the Binimetinib or Cetuximab monographs for recommended dose reductions.

When used in combination with binimetinib or cetuximab, encorafenib dosage modification is not recommended for new primary cutaneous malignancies, ocular events (other than uveitis, iritis, and iridocyclitis), interstitial lung disease/pneumonitis, cardiac dysfunction (other than QTc prolongation), creatine phosphokinase elevation, rhabdomyolysis, and venous thromboembolism.

Recommended encorafenib dose reductions for toxicity:

Colorectal cancer, metastatic:

Initial dose: 300 mg once daily.

First dose reduction: 225 mg once daily.

Second dose reduction: 150 mg once daily.

Subsequent modifications (if unable to tolerate 150 mg once daily): Permanently discontinue encorafenib.

Melanoma, unresectable or metastatic:

Initial dose: 450 mg once daily.

First dose reduction: 300 mg once daily.

Second dose reduction: 225 mg once daily.

Subsequent modifications (if unable to tolerate 225 mg once daily): Permanently discontinue encorafenib.

Dermatologic toxicity (excluding hand-foot skin reaction):

Grade 2 toxicity: If no improvement within 2 weeks, withhold encorafenib until ≤ grade 1, then resume at the same dose.

Grade 3 toxicity: Withhold encorafenib until ≤ grade 1; resume at the same dose if first occurrence, or reduce the dose if recurrent grade 3 toxicity.

Grade 4 toxicity: Permanently discontinue encorafenib.

Ocular toxicity:

Uveitis including iritis and iridocyclitis: If grade 1 or 2 uveitis does not respond to specific ocular therapy (or for grade 3 uveitis), interrupt encorafenib therapy for up to 6 weeks. If improves within 6 weeks following therapy interruption, resume at the same dose or a lower dose. If does not improve, permanently discontinue encorafenib. Permanently discontinue for grade 4 uveitis.

QTc prolongation:

QTcF >500 msec and ≤60 msec increase from baseline: Withhold encorafenib until QTcF is ≤500 msec; then resume at a reduced dose. If more than 1 recurrence, permanently discontinue encorafenib.

QTcF >500 msec and >60 msec increase from baseline: Permanently discontinue encorafenib.

Other toxicity (including hemorrhage and hand-foot skin reaction):

Recurrent grade 2 or first occurrence of any grade 3 toxicity: Interrupt encorafenib therapy for up to 4 weeks; if improves to ≤ grade 1 or to pretreatment/baseline level, resume at a reduced dose. If no improvement, permanently discontinue encorafenib.

Grade 3 toxicity (recurrent): Consider permanently discontinuing encorafenib.

Grade 4 toxicity (first occurrence): Permanently discontinue encorafenib or withhold encorafenib therapy for up to 4 weeks until improvement to ≤ grade 1 or to pretreatment/baseline level, then resume at a reduced dose (permanently discontinue if no improvement).

Grade 4 toxicity (recurrent): Permanently discontinue encorafenib.

New primary noncutaneous malignancy (RAS mutation-positive): Permanently discontinue encorafenib.

Administration

Oral: Administer once daily with or without food. Encorafenib is associated with a moderate emetic potential; antiemetics may be recommended to prevent nausea and vomiting.

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Dispense in original bottle; do not remove desiccant. Protect from moisture.

Drug Interactions

Abametapir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Amisulpride (Oral): May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

CloZAPine: May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Encorafenib. Avoid combination

CYP3A4 Inducers (Strong): May decrease the serum concentration of Encorafenib. Avoid combination

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Encorafenib. Management: Avoid use of encorafenib and moderate CYP3A4 inhibitors when possible. If combined, decrease the encorafenib dose from 450 mg to 225 mg; 300 mg to 150 mg; and 225 mg or 150 mg to 75 mg. Resume prior dose once inhibitor discontinued for 3 to 5 half-lives. Consider therapy modification

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Encorafenib. Management: Avoid use of encorafenib and strong CYP3A4 inhibitors when possible. If combined, decrease encorafenib from 450 mg to 150 mg; or from 300 mg, 225 mg, or 150 mg to 75 mg. Once the CYP3A4 inhibitor is discontinued for 3 to 5 half-lives, resume prior dose. Exceptions: Ceritinib; Clarithromycin; Saquinavir; Voriconazole. Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Domperidone: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Domperidone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification

Dronedarone: Encorafenib may enhance the QTc-prolonging effect of Dronedarone. Dronedarone may increase the serum concentration of Encorafenib. Management: Avoid use of dronedarone and encorafenib if possible. If combined, reduce the encorafenib dose (if 450 mg, decrease to 225 mg; if 300 mg decrease to 150 mg; if 225 mg or 150 mg decrease to 75 mg) and monitor the QT interval. Consider therapy modification

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Estrogen Derivatives (Contraceptive): Encorafenib may decrease the serum concentration of Estrogen Derivatives (Contraceptive). Avoid combination

Fexinidazole [INT]: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Avoid combination

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Haloperidol: QT-prolonging Kinase Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Haloperidol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Lefamulin: May enhance the QTc-prolonging effect of QT-prolonging CYP3A4 Substrates. Management: Do not use lefamulin tablets with QT-prolonging CYP3A4 substrates. Lefamulin prescribing information lists this combination as contraindicated. Avoid combination

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification

Ondansetron: May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Pentamidine (Systemic): May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

Pimozide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Avoid combination

Posaconazole: May increase the serum concentration of QT-prolonging CYP3A4 Substrates. Such increases may lead to a greater risk for proarrhythmic effects and other similar toxicities. Avoid combination

Progestins (Contraceptive): Encorafenib may decrease the serum concentration of Progestins (Contraceptive). Avoid combination

QT-prolonging Agents (Highest Risk): Encorafenib may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Exceptions: Dronedarone. Consider therapy modification

QT-prolonging Antidepressants (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

QT-prolonging Antipsychotics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: CloZAPine; Pimozide. Monitor therapy

QT-prolonging Class IC Antiarrhythmics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

QT-prolonging Kinase Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of other QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

QT-prolonging Miscellaneous Agents (Moderate Risk): QT-prolonging Kinase Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Domperidone. Monitor therapy

QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): Encorafenib may enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Encorafenib. Management: Avoid use of encorafenib and moderate CYP3A4 inhibitors when possible. If combined, decrease encorafenib dose from 450 mg to 225 mg; 300 mg to 150 mg; and 225 mg or 150 mg to 75 mg. Monitor closely for QT interval prolongation. Consider therapy modification

QT-prolonging Quinolone Antibiotics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): Encorafenib may enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Encorafenib. Management: Avoid use of encorafenib and strong CYP3A4 inhibitors when possible. If combined, decrease encorafenib dose from 450 mg to 150 mg; or from 300 mg, 225 mg, or 150 mg to 75 mg. Monitor closely for QT interval prolongation. Consider therapy modification

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Adverse Reactions

Incidence of adverse reactions for encorafenib are in combination therapy with either binimetinib or cetixumab, unless otherwise noted. Encorafenib as a single agent is associated with an increased risk of certain adverse reactions.

>10%:

Dermatologic: Acneiform eruption (combination therapy: 3% to 32%; single agent: 8%), alopecia (single agent: 56%; combination therapy: 14%), dermatological reaction (grades 3/4: single agent: 21%; combination therapy: 2%), erythema of skin (single agent: 16%; combination therapy: 7%), hyperkeratosis (single agent: 57%; combination therapy: 23%), melanocytic nevus (14%), palmar-plantar erythrodysesthesia (single agent: 51%; combination therapy: 7%), pruritus (single agent: 31%; combination therapy: 13% to 14%), skin rash (single agent: 41%; combination therapy: 22% to 26%), xeroderma (single agent: 38%; combination therapy: 13% to 16%)

Endocrine & metabolic: Hyperglycemia (28%), hypokalemia (12%), hypomagnesemia (19%), hyponatremia (11% to 18%), increased gamma-glutamyl transferase (45%)

Gastrointestinal: Abdominal pain (28% to 30%), constipation (15% to 22%), decreased appetite (27%), diarrhea (33%), dysgeusia (single agent: 13%, combination therapy: 6%), nausea (34% to 41%), vomiting (21% to 30%)

Hematologic & oncologic: Anemia (34% to 36%; grades 3/4: 4%), hemorrhage (19%; grades 3/4: 2% to 3%), leukopenia (13%), lymphocytopenia (13% to 24%; grades 3/4: 2% to 7%), neutropenia (13%; grades 3/4: 3%), prolonged partial thromboplastin time (13%; grades 3/4: 1%)

Hepatic: Increased serum alanine aminotransferase (17% to 29%), increased serum alkaline phosphatase (18% to 21%), increased serum aspartate aminotransferase (15% to 27%)

Nervous system: Dizziness (15%), fatigue (43% to 51%), headache (20% to 22%), insomnia (13%), peripheral neuropathy (12%; grades 3/4: 1%)

Neuromuscular & skeletal: Arthralgia (single agent: 44%; combination therapy: 26% to 27%), back pain (single agent: 15%; combination therapy: 9%), limb pain (10% to 11%), myopathy (single agent: 33%; combination therapy: 15% to 23%)

Renal: Increased serum creatinine (93%)

Miscellaneous: Fever (17% to 18%)

1% to 10%:

Endocrine & metabolic: Hypermagnesemia (10%)

Gastrointestinal: Hematochezia (2% to 3%), hemorrhoidal bleeding (1% to 2%), pancreatitis (<10%)

Hematologic & oncologic: Basal cell carcinoma of skin (combination therapy: 2%; single agent: 1%), keratoacanthoma (single agent: ≤8%; combination therapy: ≤3%), malignant melanoma (single agent: 5%; combination therapy: 1%), rectal hemorrhage (4%), squamous cell carcinoma of skin (single agent: ≤8%; combination therapy: ≤3%)

Hypersensitivity: Hypersensitivity reaction (<10%)

Nervous system: Facial paresis (<10%)

Neuromuscular & skeletal: Panniculitis (<10%)

Ophthalmic: Uveitis (4%, including iritis and iridocyclitis)

Respiratory: Epistaxis (7%)

<1%: Cardiovascular: Prolonged QT interval on ECG

Frequency not defined:

Gastrointestinal: Gastrointestinal hemorrhage

Nervous system: Intracranial hemorrhage

Warnings/Precautions

Concerns related to adverse effects:

• Dermatologic toxicity: Grade 3 or 4 dermatologic toxicity occurred in ~20% of patients receiving encorafenib as a single agent, compared to 2% of patients receiving the combination of encorafenib and binimetinib.

• GI toxicity: Encorafenib is associated with a moderate emetic potential; antiemetics may be recommended to prevent nausea and vomiting.

• Hemorrhage: Hemorrhage, including ≥ grade 3 events, may occur when administered in combination with other agents. The most frequent hemorrhagic events in melanoma patients were GI in nature, including rectal hemorrhage, hematochezia, and hemorrhoidal hemorrhage. Fatal intracranial hemorrhage (in the setting of new or progressive brain metastases) was also reported. In a study of metastatic colorectal cancer, epistaxis, hematochezia, and rectal hemorrhage occurred most frequently; fatal GI hemorrhage also was reported (rarely). May require treatment interruption, dosage reduction, and/or permanent discontinuation based on the severity of the hemorrhage.

• Malignancy: New primary malignancies (cutaneous and noncutaneous) have been observed in patients treated with BRAF inhibitors and may occur with encorafenib. Cutaneous squamous cell carcinoma (cuSCC), including keratoacanthoma (KA), as well as basal cell carcinoma and new primary melanoma occurred in patients receiving encorafenib in combination with other agents; the median time to first onset of cuSCC/KA in patients with melanoma was ~6 months (range: 1 to 9 months). Cases of cuSCC/KA, basal cell carcinoma, and new primary melanoma were also observed in patients receiving encorafenib monotherapy. Dermatologic evaluations should be performed prior to initiating therapy, every 2 months during therapy, and for up to 6 months post discontinuation. Suspicious skin lesions may be managed with excision and dermatopathologic evaluation; dose modification is not recommended for new primary cutaneous malignancies. Due to its mechanism of action (activation of RAS through mutation or other mechanisms), other noncutaneous malignancies may develop with encorafenib use; monitor for signs/symptoms of noncutaneous malignancies. Discontinue encorafenib for RAS mutation-positive noncutaneous malignancies.

• Ocular toxicity: Uveitis, including iritis and iridocyclitis, has been observed with the combination of encorafenib and binimetinib. Monitor for ocular toxicity at each visit; perform an ophthalmologic evaluation regularly and for new or worsening visual disturbances (and to follow new or persistent ophthalmologic findings). May require treatment interruption, dosage reduction, and/or permanent discontinuation based on the severity of the toxicity.

• QT prolongation: Encorafenib is associated with dose dependent QTc interval prolongation. In a clinical trial, QTcF prolongation to >500 msec was reported (rare) when used in combination with binimetinib. Monitor patients with or at risk for developing QTc prolongation, including those with known long QT syndromes, clinically significant bradyarrhythmias, severe or uncontrolled heart failure, or concomitant use of medications associated with QT prolongation. Correct hypokalemia or hypomagnesemia prior to treatment initiation. QT prolongation may require treatment interruption, dosage reduction, and/or permanent discontinuation based on the severity of the toxicity.

Concurrent drug therapy issues:

• Combination therapy: Additional toxicities may occur when used in combination with binimetinib or cetuximab. Refer to the Binimetinib and Cetuximab monographs for further information on warnings/precautions or dosage modifications. In metastatic melanoma treatment, if binimetinib therapy is withheld or permanently discontinued, the encorafenib dose should also be reduced (see Dosing: Adjustment for Toxicity). In metastatic colorectal cancer, if cetuximab is discontinued, encorafenib should also be discontinued.

Other warnings/precautions:

• Appropriate use: Encorafenib is not indicated for treatment of patients with wild-type BRAF melanoma or wild-type BRAF colorectal cancer. Exposing BRAF wild-type cells to BRAF inhibitors such as encorafenib may result in paradoxical activation of MAP-kinase signaling and increased cell proliferation. Prior to initiating therapy, confirm BRAF V600E or BRAF V600K mutation status with an approved test. Information on approved tests for detection of BRAF V600 mutations is available at http://www.fda.gov/companiondiagnostics.

Monitoring Parameters

BRAFV600K or V600E mutation status (prior to treatment); electrolytes; verify pregnancy status in females of reproductive potential prior to treatment initiation; dermatologic evaluations prior to initiation, every 2 months during therapy, and for up to 6 months following discontinuation to assess for new cutaneous malignancies; monitor for signs/symptoms of uveitis (eg, eye pain, photophobia, vision changes), hemorrhage, and dermatologic toxicity, and for noncutaneous malignancies. Monitor adherence.

Reproductive Considerations

Verify pregnancy status in females of reproductive potential prior to initiating encorafenib therapy. Females of reproductive potential should use a highly effective nonhormonal contraceptive during therapy and for at least 2 weeks after the last encorafenib dose; hormonal contraceptives may not be effective.

Pregnancy Considerations

Based on its mechanism of action and on findings in animal reproduction studies, encorafenib may cause fetal harm if administered during pregnancy.

Patient Education

What is this drug used for?

• It is used to treat a type of skin cancer (melanoma).

• It is used to treat colorectal cancer.

• This drug is taken with other drugs. Be sure you know about the warnings, benefits, and risks of these other drugs. Talk with the doctor if you have questions or concerns about any of the drugs.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Dizziness

• Loss of strength and energy

• Fatigue

• Nausea

• Vomiting

• Abdominal pain

• Lack of appetite

• Joint pain

• Back pain

• Muscle pain

• Constipation

• Diarrhea

• Painful extremities

• Hard or thick skin

• Dry skin

• Acne

• Hair loss

• Change in taste

• Trouble sleeping

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Bleeding like vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding

• Electrolyte problems like mood changes, confusion, muscle pain or weakness, abnormal heartbeat, seizures, lack of appetite, or severe nausea or vomiting

• High blood sugar like confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit

• Change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or vision changes

• Chills

• Vision changes

• Eye pain

• Severe eye irritation

• Seeing colored dots

• Seeing halos or bright colors around lights

• Burning or numbness feeling

• Redness or irritation of palms of hands or soles of feet

• Fast heartbeat

• Abnormal heartbeat

• Passing out

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Related questions