encorafenib

Contraindicated in:

Wild-type BRAF melanoma (may ↑ proliferation)
Long QT syndrome, bradyarrhythmias, severe or decompensated HF, hypokalemia, or hypomagnesemia (↑ risk of QT interval prolongation)
Concurrent use of QT-interval prolonging medications
Baseline QTc interval >500 msec
OB: Pregnancy
Lactation: Lactation.

Use Cautiously in:

Moderate or severe hepatic impairment
Severe renal impairment
Rep: Women of reproductive potential
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: QT interval prolongation.

Derm: alopecia, dry skin, hyperkeratosis, pruritus, rash, BASAL CELL CARCINOMA, CUTANEOUS SQUAMOUS CELL CARCINOMA, nodule formation.

EENT: uveitis.

Endo: hyperglycemia.

F and E: hypermagnesemia, hyponatremia.

GI: ↑liver enzymes, abdominal pain, constipation, nausea, vomiting, GI HEMORRHAGE, PANCREATITIS.

GU: ↑serum creatinine, ↓ fertility (males).

Hemat: anemia, bleeding, leukopenia, lymphopenia, neutropenia.

MS: arthralgia, myalgia.

Neuro: dizziness, fatigue, headache, peripheral neuropathy, facial paralysis, INTRACRANIAL HEMORRHAGE.

Misc: fever, HYPERSENSITIVITY REACTIONS, MALIGNANCY.

Interactions ⬆ ⬇

Drug-Drug:

QT interval prolonging drugs may ↑ the risk of QT interval prolongation and torsades de pointes; avoid concurrent use.
Strong or moderate CYP3A4 inhibitors, including diltiazem and posaconazole may ↑ levels and risk of toxicity; avoid concurrent use, if possible (if must use concurrently, ↓ encorafenib dose).
Strong or moderate CYP3A4 inducers may ↓ levels and effectiveness; avoid concurrent use.
May ↓ effectiveness of hormonal contraceptives; avoid concurrent use.
May ↑ levels and risk of toxicity of OATP1B1 substrates, OATP1B3 substrates, or BRCP substrates.

Drug-Natural Products:

St. John's wort may ↓ levels and effectiveness; avoid concurrent use.

Drug-Food:

Grapefruit juicemay ↑ levels and risk of toxicity; avoid concurrent use.

Availability ⬆ ⬇

Capsules: 75 mg;

Route/Dosage ⬆ ⬇

BRAF V600E or V600K Mutation-Positive Unresectable or Metastatic Melanoma

PO (Adults): 450 mg once daily until disease progression or unacceptable toxicity. Concurrent use of moderate CYP3A4 inhibitor: 225 mg once daily (if planned dose 450 mg once daily); 150 mg once daily (if planned dose 300 mg once daily); 75 mg once daily (if planned dose 225 mg once daily); Concurrent use of strong CYP3A4 inhibitor: 150 mg once daily (if planned dose 450 mg once daily); 75 mg once daily (if planned dose 300 mg once daily or 225 mg once daily).

BRAF V600E Mutation-Positive Metastatic CRC

PO (Adults): 300 mg once daily until disease progression or unacceptable toxicity. Concurrent use of moderate CYP3A4 inhibitor: 150 mg once daily (if planned dose 300 mg once daily); 75 mg once daily (if planned dose 225 mg once daily or 150 mg once daily); Concurrent use of strong CYP3A4 inhibitor: 75 mg once daily (if planned dose 300 mg once daily, 225 mg once daily, or 150 mg once daily).

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Kinase inhibitor that targets BRAF V600E, a mutated enzyme that promotes tumor cell proliferation.

Therapeutic Effects:

Improvement in progression-free survival and overall survival in patients with melanoma and CRC.

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: kinase inhibitors

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed (86%) following oral administration.

Distribution: Extensively distributed to tissues.

Metabolism/Excretion: Primarily metabolized by the liver via the CYP3A4 and CYP2C19 isoenzymes. Primarily excreted as metabolites in feces (42%) and urine (45%).

Half-life: 3.5 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	2 hr	24 hr

Patient/Family Teaching ⬆ ⬇

Instruct patient to take encorafenib as directed. Take missed dose within 12 hr of missed dose; do not take dose within 12 hr of next dose. If vomiting occurs, skip dose; continue with next scheduled dose. Advise patient to read Medication Guide before starting therapy and with each Rx refill in case of changes.
Inform patient that grapefruit products may increase amount of encorafenib in the body. Avoid grapefruit and grapefruit juice during therapy.
Inform patient that encorafenib increases risk of developing new cutaneous malignancies. Notify health care professional immediately if new lesions (wart, skin sore or reddish bump that bleeds or does not heal) or changes in size or color of existing moles or lesions occur.
Advise patient to notify health care professional immediately if signs and symptoms of bleeding (headaches, dizziness, weakness, coughing up blood or blood clots, vomiting blood or vomit looks like "coffee grounds," red or black stools that look like tar); liver dysfunction (yellow skin or whites of eyes, feeling tired, urine turns dark or brown, nausea or vomiting, loss of appetite, pain on right side of stomach), changes in heart rhythm (feeling faint, lightheaded, dizzy, heart beating irregularly or fast); or eye problems (blurred vision, loss of vision, other vision changes, seeing colored dots, seeing halos or blurred outline around objects, eye pain, swelling, redness) occur.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially St. John's wort.
Rep: May cause fetal harm. Encorafenib may decrease effectiveness of hormonal contraceptives. Advise female patient to use a highly effective nonhormonal form of contraception during and for 2 wk after last dose. Advise patient to notify health care professional if pregnancy is suspected and to avoid breastfeeding during and for at least 2 wk after last dose. May impair fertility in males.
Inform patient that regular assessments of skin and assessments for signs and symptoms of other malignancies must be done every 2 mo during and for up to 6 mo after therapy. Advise patient to notify health care professional immediately if any changes in skin occur.

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Indications ⬇

Contraind./Precautions ⬆ ⬇