Overview
Encoraf 75 mg contains Encorafenib, a highly potent, oral small-molecule kinase inhibitor that specifically targets mutated BRAF proteins. Manufactured by Everest Pharmaceuticals Ltd. and supplied globally by Saif Pharma, Encoraf is a precision oncology therapy designed to interrupt the uncontrolled growth signals in tumor cells. It is primarily used in targeted combination regimens to treat advanced skin and gastrointestinal cancers that harbor specific genetic alterations, specifically the BRAF V600E mutation.
Therapeutic Applications
Encoraf 75 mg is indicated for use in combination with specific companion therapies for the following conditions:
Unresectable or Metastatic Melanoma: For adult patients with advanced skin cancer carrying a confirmed BRAF V600E or V600K mutation (administered in combination with the MEK inhibitor Binimetinib).
Metastatic Colorectal Cancer (mCRC): For adult patients with BRAF V600E-mutated metastatic colorectal cancer who have progressed on or after prior systemic therapies (administered in combination with Cetuximab).
Mechanism of Action
Encorafenib targets the MAPK kinase signaling pathway, a primary cellular communication route that regulates cell division:
Inhibiting Mutated BRAF: In tumors with BRAF V600 mutations, the BRAF kinase is locked in an “on” position, driving rapid cellular growth. Encoraf selectively binds to and blocks this mutated kinase (V600E, V600D, and V600K variants).
Extended Target Residence: Encorafenib is engineered with a long “off-rate” (dissociation half-life), meaning it stays bound to the target mutated enzyme much longer than early-generation BRAF inhibitors, delivering sustained pathway inhibition.
Synergistic Blockade: When paired with a MEK inhibitor (like Binimetinib) or an anti-EGFR antibody (like Cetuximab), it forms a dual-point blockade that prevents the cancer cell from bypassing the drug, inducing tumor shrinkage and apoptosis (programmed cell death).
Pharmacokinetic Profile
Absorption: Rapidly absorbed after oral administration, reaching maximum plasma concentration ($T_{max}$) within approximately 2 hours.
Distribution: Moderately bound to human plasma proteins (~86%), with stable systemic distribution.
Metabolism: Primarily metabolized in the liver via the CYP3A4 enzyme system, making it sensitive to strong CYP3A inhibitors or inducers.
Elimination: Displays a terminal elimination half-life of approximately 3.5 hours, cleared from the body via both fecal and urinary pathways.
Dosage & Administration
Standard Melanoma Dose: The recommended dose is 450 mg (six 75 mg capsules/tablets) taken orally once daily when paired with Binimetinib.
Standard Colorectal Cancer Dose: The recommended dose is 300 mg (four 75 mg capsules/tablets) taken orally once daily when paired with Cetuximab.
Instructions: Must be swallowed whole with a glass of water. Do not break, crush, dissolve, or split the pills. It can be taken with or without food.
Missed Dose Window: If a dose is missed by more than 12 hours, skip that dose and take the next scheduled dose at the normal time. Do not take a double dose to compensate.
Clinical Considerations & Safety
New Primary Malignancies: BRAF inhibitors can paradoxically activate the MAPK pathway in healthy cells, potentially causing new skin cancers (cutaneous squamous cell carcinomas). Regular dermatologic screenings are necessary.
Hemorrhage Risk: Severe bleeding events have occurred during therapy. Monitor patients carefully for unusual bruising or bleeding signs.
Uveitis & Ocular Toxicities: Can cause eye inflammation, blurred vision, or photophobia. Any new visual changes require immediate ophthalmologic evaluation.
QT Prolongation: Periodic ECG monitoring and electrolyte checks (potassium, magnesium) are recommended to maintain stable cardiac rhythms.
Hepatotoxicity: Liver transaminase levels (ALT/AST) must be monitored before treatment initiation and periodically during therapy.
Special Populations
Pregnancy & Contraception: Encorafenib can cause severe embryo-fetal harm. Females of childbearing potential must use effective, non-hormonal contraception during treatment and for at least 30 days following the final dose.
Hepatic Impairment: Use with caution. Patients with moderate-to-severe liver dysfunction may require careful monitoring or adjustment, as the drug is cleared primarily through the liver.