Drug information of encorafenib

encorafenib


Encorafenib is used in combination with a medicine called binimetinib (Mektovi) to treat melanoma (skin cancer) that cannot be treated with surgery or has spread to other parts of the body.

Encorafenib is used in combination with a medicine called cetuximab (Erbitux) to treat colorectal cancer that has spread to other parts of the body.

Encorafenib is used only if your cancer has a specific genetic marker (an abnormal "BRAF" gene). Your doctor will test you for this gene. encorafenib is not for treating wild-type BRAF cancers.

Mechanism of effect

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).

Pharmacodynamic

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.
Absorption
At least 86% of the dose is absorbed
Metabolism
Primarily via CYP3A4 and to a lesser extent by CYP2C19 (16%) and CYP2D6 (1%).
Time to reach the peak
2 hours
Half life
3.5 hours
Excretion
Feces (47%; 5% as unchanged drug); urine (47%; 2% as unchanged drug)

Drug 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

Dosage

Usual Adult Dose for Melanoma - Metastatic
450 mg orally once a day in combination with binimetinib until disease progression or unacceptable toxicity
Usual Adult Dose for Colorectal Cancer
300 mg orally once a day in combination with cetuximab until disease progression or unacceptable toxicity

Drug contraindications

None
This drug is not recommended for use in children

Side effects

>10%
Central nervous system: Fatigue, headache, dizziness, peripheral neuropathy 
Dermatologic: Hyperkeratosis, alopecia, palmar-plantar erythrodysesthesia, skin rash, xeroderma, pruritus, dermatological reaction, erythema
Endocrine & metabolic: Increased gamma-glutamyl transferase, hyperglycemia, hyponatremia
Gastrointestinal: Nausea, vomiting, abdominal pain, constipation, dysgeusia
Hematologic & oncologic: Anemia, hemorrhage, leukopenia, lymphocytopenia, neutropenia
Hepatic: Increased serum alanine aminotransferase, increased serum aspartate aminotransferase, increased serum alkaline phosphatase
Neuromuscular & skeletal: Arthralgia, myopathy, back pain, limb pain
Renal: Increased serum creatinine
Miscellaneous: Fever
1% 
to 10%
Central nervous system: Facial paresis
Dermatologic: Acneiform eruption
Endocrine & metabolic: Hypermagnesemia
Gastrointestinal: Pancreatitis, hematochezia, hemorrhoidal bleeding
Hypersensitivity: Hypersensitivity
Hematologic & oncologic: Squamous cell carcinoma of skin, malignant melanoma, rectal hemorrhage, keratoacanthoma, basal cell carcinoma
Neuromuscular & skeletal: Panniculitis
Ophthalmic: Uveitis
<1%
postmarketing, and/or case reports: Prolonged QT interval on ECG

Alerts

Although this medicine is used to treat melanoma, using encorafenib may increase your risk of developing other types of skin cancer. Ask your doctor about your specific risk. Tell your doctor if you notice any new skin symptoms

Grapefruit may interact with encorafenib and lead to unwanted side effects. Avoid the use of grapefruit products

Points of recommendation

Encorafenib can harm an unborn baby. Do not use if you are pregnant. Use a non-hormonal form of birth control to prevent pregnancy while using encorafenib and for at least 2 weeks after your last dose

:Tell your doctor if you have ever had
heart problems
(long QT syndrome (in you or a family member
lung disease
liver or kidney disease
(eye problems (especially a problem with your retina
bleeding problems, or a blood clot

Encorafenib can make hormonal birth control less effective, including birth control pills, injections, implants, skin patches, and vaginal rings. To prevent pregnancy while using encorafenib, use a barrier form of birth control: condom, diaphragm, cervical cap, or contraceptive sponge

This medicine may affect fertility (ability to have children) in men.
5-Do not breastfeed while using this medicine, and for at least 2 weeks after your last dose

You may need to take 4 to 6 capsules at one time for a complete dose. Follow your doctor's dosing instructions very carefully

If you vomit shortly after taking encorafenib, do not take another dose. Wait until your next scheduled dose time to take the medicine again

Your doctor will need to check your skin every 2 months while you are using encorafenib, and for up to 6 months after your last dose

Pregnancy level

D

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

Breast feeding warning

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

Related drugs

vandetanib , Nintedanib , Binimetinib

Amisulpride (Oral), Clofazimine, Conivaptan, CYP3A4 Inducers (Moderate), CYP3A4 Inducers (Strong), CYP3A4 Inhibitors (Moderate), CYP3A4 Inhibitors (Strong), Deferasirox, Domperidone,
Dronedarone, Erdafitinib, Estrogen Derivatives (Contraceptive), Fexinidazole [INT], Idelalisib,
Fosaprepitant, Fusidic Acid (Systemic), Haloperidol, Larotrectinib, Lefamulin, MiFEPRIStone,
Ondansetron, Palbociclib, Pentamidine (Systemic), Pimozide, Posaconazole, Progestins (Contraceptive), QT-prolonging Agents (Highest Risk), QT-prolonging Antidepressants (Moderate Risk), QT-prolonging Antipsychotics (Moderate Risk), QT-prolonging Class IC Antiarrhythmics (Moderate Risk), QT-prolonging Kinase Inhibitors (Moderate Risk),
QT-prolonging Miscellaneous Agents (Moderate Risk), QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk), QT-prolonging Quinolone Antibiotics (Moderate Risk), Stiripentol,
QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk), Sarilumab, Siltuximab, Simeprevir,
Tocilizumab

Drug forms

Braftovi

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