encorafenib

High Alert

Metastatic or unresectable melanoma in patients with a BRAF V600E or V600K mutation (in combination with binimetinib).
Metastatic colorectal cancer in patients with a BRAF V600E mutation (in combination with cetuximab and mFOLFOX6).
Metastatic colorectal cancer in patients with a BRAF V600E mutation (in combination with cetuximab).
Metastatic non-small cell lung cancer (NSCLC) in patients with a BRAF V600E mutation (in combination with binimetinib).

Contraind./Precautions ⬆ ⬇

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:

Left ventricular ejection fraction (LVEF) <50%;
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: cardiomyopathy, QT interval prolongation

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

EENT: uveitis

Endo: hyperglycemia

F and E: hypermagnesemia, hyponatremia

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

GU: ↑serum creatinine, ↓fertility (men)

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 concurrent use unavoidable, ↓ encorafenib dose.
Strong 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 BCRP substrates.

Drug-Natural Products:

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

Drug-Food:

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

Availability ⬆ ⬇

Route/Dosage ⬆ ⬇

BRAF V600E or V600K Mutation-Positive Unresectable or Metastatic Melanoma and BRAF V600E Mutation-Positive Metastatic NSCLC

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 Colorectal Cancer

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 colorectal cancer.
Decreased progression of NSCLC.

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 ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy. Instruct patient to take 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 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.
Inform patient to avoid grapefruit and grapefruit juice during therapy.
Instruct patient to notify health care professional promptly if new onset or worsening shortness of breath; cough; swelling of the ankles, legs, or face; palpitations; or weight gain of >5 pounds in 24 hr occur.
Inform patient of the ↑ 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 tarry stools), liver dysfunction (yellow skin or whites of eyes, feeling tired, dark or brown urine, nausea or vomiting, loss of appetite, pain on right side of stomach), changes in heart rhythm (feeling faint, light-headed, or 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.
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.
Rep: May cause fetal harm, and may ↓ effectiveness of hormonal contraceptives. Advise women 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 therapy and for >2 wk after last dose. May impair fertility in men.

Pronunciation ⬆ ⬇

Code ⬆

NDC Code

11014- Catalent Pharma Solutions, LLC
- 11014-0344-
  - 11014-0344-1- 1 BAG in 1 CONTAINER (11014-0344-1) / 7000 CAPSULE in 1 BAG

11014- Catalent Pharma Solutions, LLC
- 11014-0345-
  - 11014-0345-1- 1 BAG in 1 CONTAINER (11014-0345-1) / 7000 CAPSULE in 1 BAG

11014- Catalent Pharma Solutions, LLC
- 11014-0577-
  - 11014-0577-1- 1 BAG in 1 DRUM (11014-0577-1) / 7000 CAPSULE in 1 BAG

11014- Catalent Pharma Solutions, LLC
- 11014-0582-
  11014-0582-1- 1 BAG in 1 DRUM (11014-0582-1) / 7000 CAPSULE in 1 BAG

54893- MSN Laboratories Private Limited
- 54893-0114-
  54893-0114-2- 30 kg in 1 DRUM (54893-0114-2)

59651- Aurobindo Pharma Limited
- 59651-641-
  59651-641-37- 50 kg in 1 DRUM (59651-641-37)

62009- Finorga
- 62009-1913-
  62009-1913-1- 20 kg in 1 DRUM (62009-1913-1)

70255- Array BioPharma Inc.
- 70255-025- BRAFTOVI
  70255-025-01- 2 BOTTLE in 1 CARTON (70255-025-01) / 90 CAPSULE in 1 BOTTLE (70255-025-02)

70255- Array BioPharma Inc.
- 70255-025- BRAFTOVI
  - 70255-025-03- 2 BOTTLE in 1 CARTON (70255-025-03) / 60 CAPSULE in 1 BOTTLE (70255-025-04)

70255- Array BioPharma Inc.
- 70255-025- BRAFTOVI
  - 70255-025-05- 90 CAPSULE in 1 BOTTLE (70255-025-05)

70255- Array BioPharma Inc.
- 70255-025- BRAFTOVI
  - 70255-025-06- 60 CAPSULE in 1 BOTTLE (70255-025-06)

81955- VALARY LAB PRIVATE LIMITED
- 81955-0026-
  - 81955-0026-1- 10 kg in 1 DRUM (81955-0026-1)

85247- Ardena US, LLC
- 85247-0002-
  85247-0002-1- 1 BAG in 1 CONTAINER (85247-0002-1) / 7000 CAPSULE in 1 BAG

85247- Ardena US, LLC
- 85247-0003-
  85247-0003-1- 1 BAG in 1 CONTAINER (85247-0003-1) / 7000 CAPSULE in 1 BAG

85247- Ardena US, LLC
- 85247-0004-
  85247-0004-1- 1 BAG in 1 DRUM (85247-0004-1) / 7000 CAPSULE in 1 BAG

85247- Ardena US, LLC
- 85247-0005-
  85247-0005-1- 1 BAG in 1 DRUM (85247-0005-1) / 7000 CAPSULE in 1 BAG

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Indications ⬇