Encorafenib: Drug information

For additional information see "Encorafenib: Patient drug information"

For abbreviations, symbols, and age group definitions show table

Brand Names: US

Braftovi

Brand Names: Canada

Braftovi

Pharmacologic Category

Antineoplastic Agent, BRAF Kinase Inhibitor

Dosing: Adult

Dosage guidance:

Safety: Correct hypokalemia or hypomagnesemia prior to treatment initiation.

Colorectal cancer, metastatic, with BRAF V600E mutation

Colorectal cancer, metastatic, with BRAF V600E mutation: Note: Confirm BRAF V600E mutation status in tumor or plasma specimens prior to initiation; if no mutation detected in plasma specimens, then test tumor tissue.

Encorafenib/Cetuximab: Oral: 300 mg once daily (in combination with cetuximab); continue until disease progression or unacceptable toxicity (Ref).

Encorafenib/Cetuximab/mFOLFOX6: Oral: 300 mg once daily (in combination with cetuximab and mFOLFOX6 [fluorouracil, leucovorin, and oxaliplatin]); continue until disease progression or unacceptable toxicity.

Melanoma, unresectable or metastatic, with BRAF V600E or BRAF V600K mutation

Melanoma, unresectable or metastatic, with BRAF V600E or BRAF V600K mutation: Note: Confirm BRAF V600E or V600K mutation status in tumor specimens prior to initiation.

Oral: 450 mg once daily (in combination with binimetinib); continue until disease progression or unacceptable toxicity (Ref).

Non–small cell lung cancer, metastatic, with BRAF V600E mutation

Non–small cell lung cancer, metastatic, with BRAF V600E mutation: Note: Confirm BRAF V600E mutation status in tumor or plasma specimens prior to initiation; if no mutation detected in plasma specimens, then test tumor tissue.

Oral: 450 mg once daily (in combination with binimetinib); continue until disease progression or unacceptable toxicity (Ref).

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

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

Dosing: Kidney Impairment: Adult

CrCl ≥30 mL/minute: No dosage adjustment necessary.

CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, no need for dosage adjustment is expected (Ref).

Hemodialysis: Not likely dialyzed due to extensive protein binding (Ref). No need for dosage adjustment is expected (Ref).

Dosing: Liver Impairment: Adult

Hepatic impairment prior to treatment initiation:

Mild impairment (Child-Turcotte-Pugh class A): No dosage adjustment necessary.

Moderate to severe impairment (Child-Turcotte-Pugh class B or C): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, additional sources suggest use is not recommended (Ref).

Acute hepatotoxicity during treatment:

Grade 2 AST or ALT elevations: Maintain encorafenib dose; if no improvement within 4 weeks, withhold encorafenib until improvement to grade 0 or 1 or to pretreatment/baseline levels and then resume at the same dose.

Grade 3 AST or ALT elevation: For the first occurrence of grade 3 AST or ALT elevations, withhold encorafenib for up to 4 weeks; if improves to grade 0 or 1 or to pretreatment/baseline level, resume encorafenib at a reduced dose. If no improvement, permanently discontinue encorafenib. For recurrent grade 3 toxicity, consider permanently discontinuing encorafenib.

Grade 4 AST or ALT elevation: For the first occurrence of grade 4 AST or ALT elevations, permanently discontinue encorafenib or withhold encorafenib for up to 4 weeks; if improves to grade 0 or 1 or to pretreatment/baseline level, resume encorafenib at a reduced dose. If no improvement, permanently discontinue encorafenib. For recurrent grade 4 toxicity, permanently discontinue encorafenib.

Dosing: Adjustment for Toxicity: Adult

Note: In unresectable or metastatic melanoma or metastatic non-small cell lung cancer, 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. Other concomitant anticancer medications may also require dosage modification(s).

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, CPK elevation, rhabdomyolysis, and venous thromboembolism.

**Encorafenib** **Dosage Reduction Levels**
Dosage reduction levels	Recommended dosage and schedule (melanoma or non-small cell lung cancer)	Recommended dosage and schedule (colorectal cancer)
Initial (usual) dosage	450 mg once daily	300 mg once daily
First dosage reduction	300 mg once daily	225 mg once daily
Second dosage reduction	225 mg once daily	150 mg once daily
Subsequent modification	If unable to tolerate 225 mg once daily, permanently discontinue encorafenib.	If unable to tolerate 150 mg once daily, permanently discontinue encorafenib.

**Recommended** **Encorafenib Dosage Modifications for Adverse Reactions**
Adverse reaction	Severity	Encorafenib dosage modification
^a LVEF = left ventricular ejection fraction.
Cardiotoxicity	Symptomatic heart failure or absolute decrease in LVEF^a of >20% from baseline and also below LLN	Reduce encorafenib by one dose level. LVEF improves to ≥ LLN and* absolute decrease from baseline is ≤10%:* Continue encorafenib at reduced dose. LVEF does not recover: Withhold encorafenib until LVEF improves to ≥ LLN and absolute decrease from baseline is ≤10%; resume at reduced dose or reduce dose by an additional dose level.
	QTcF >500 msec and ≤60 msec increase from baseline	First occurrence: Withhold encorafenib until QTcF ≤500 msec; resume at reduced dose. If >1 recurrence, permanently discontinue encorafenib.
	QTcF >500 msec and >60 msec increase from baseline	Permanently discontinue encorafenib.
Dermatologic toxicity (excluding hand-foot skin reaction)	Grade 2	No improvement within 2 weeks: Withhold encorafenib until improved to grade 0 or 1; resume at same dose.
	Grade 3	Withhold encorafenib until improved to grade 0 or 1; resume at same dose (if first occurrence) or reduced dose (if recurrent).
	Grade 4	Permanently discontinue encorafenib.
Malignancy, new primary	Noncutaneous malignancy (RAS-mutation positive)	Permanently discontinue encorafenib.
Ocular toxicity	Uveitis (Grade 1 to 2)	If no response to specific ocular therapy: Withhold encorafenib for up to 6 weeks. Improvement within 6 weeks of interruption: Resume encorafenib at same or reduced dose. No improvement within 6 weeks of interruption: Permanently discontinue encorafenib.
	Uveitis (Grade 3)	Withhold encorafenib for up to 6 weeks. Improvement within 6 weeks of interruption: Resume encorafenib at same or reduced dose. No improvement within 6 weeks of interruption: Permanently discontinue encorafenib.
	Uveitis (Grade 4)	Permanently discontinue encorafenib.
Other treatment-related adverse reaction (including hemorrhage and hand-foot skin reaction)	Grade 2 (recurrent) or Grade 3 (first occurrence)	Withhold encorafenib for up to 4 weeks. Improvement to grade 0 or 1 or pretreatment/baseline levels within 4 weeks of interruption: Resume encorafenib at reduced dose. No improvement within 4 weeks of interruption: Permanently discontinue encorafenib.
	Grade 4 (first occurrence)	Permanently discontinue encorafenib or withhold encorafenib for up to 4 weeks. Improvement to grade 0 or 1 or pretreatment/baseline levels within 4 weeks of interruption: Resume encorafenib at reduced dose. No improvement within 4 weeks of interruption: Permanently discontinue encorafenib.
	Grade 3 (recurrent)	Consider permanently discontinuing encorafenib.
	Grade 4 (recurrent)	Permanently discontinue encorafenib.

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Incidence of adverse reactions for encorafenib are for combination therapy with either binimetinib or cetuximab in adults, unless otherwise noted. Encorafenib as a single agent is associated with an increased risk of certain adverse reactions.

>10%:

Cardiovascular: Cardiomyopathy (≤11%), edema (23%), left ventricular dysfunction (≤11%)

Dermatologic: Acneiform eruption (combination therapy: 3% to 32%; single agent: 8%), alopecia (single agent: 56%; combination therapy: 12% to 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 16%), skin rash (single agent: 41%; combination therapy: 22% to 27%), xeroderma (single agent: 38%; combination therapy: 13% to 16%)

Endocrine & metabolic: Hyperglycemia (28% to 48%), hyperkalemia (31%), hypoalbuminemia (32%), hypocalcemia (12%), hypokalemia (12%), hypomagnesemia (19%), hyponatremia (11% to 26%), weight gain (11%)

Gastrointestinal: Abdominal pain (28% to 32%), constipation (15% to 27%), decreased appetite (14% to 27%), diarrhea (33% to 52%; grades 3/4: 2% to 7%), dysgeusia (single agent: 13%; combination therapy: 6%), increased serum amylase (22%), increased serum lipase (40%), nausea (34% to 58%; grades 3/4: 1% to 3%), vomiting (21% to 37%; grades 3/4: 1% to 2%)

Hematologic & oncologic: Anemia (34% to 47%; grades 3/4: 4% to 11%), hemorrhage (12% to 19%; grades 3/4: 2% to 4%), leukopenia (12% to 13%), lymphocytopenia (13% to 24%; grades 3/4: 2% to 7%), neutropenia (12% to 13%; grades 3/4: 1% to 3%), prolonged partial thromboplastin time (13%; grades 3/4: 1%), thrombocytopenia (20%; grades 3/4: 1%)

Hepatic: Increased gamma-glutamyl transferase (45%), increased serum alanine aminotransferase (17% to 34%), increased serum alkaline phosphatase (18% to 31%), increased serum aspartate aminotransferase (15% to 31%)

Nervous system: Dizziness (15% to 17%), fatigue (43% to 61%), headache (11% to 22%), insomnia (10% to 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%), increased creatine phosphokinase in blood specimen (41%), limb pain (10% to 11%), musculoskeletal pain (48%), myopathy (single agent: 33%; combination therapy: 15% to 23%)

Ophthalmic: Visual impairment (29%)

Renal: Increased serum creatinine (91% to 93%)

Respiratory: Cough (26%), dyspnea (27%)

Miscellaneous: Fever (17% to 22%)

1% to 10%:

Cardiovascular: Acute myocardial infarction (2%), cardiac arrhythmia (2%), hypertension (10%), prolonged QT interval on ECG (≤2%)

Dermatologic: Basal cell carcinoma of skin (single agent: 1%; combination therapy: 2%), cutaneous papilloma (2%), skin photosensitivity (<10%), squamous cell carcinoma of skin (single agent: ≤8%; combination therapy: ≤3%)

Endocrine & metabolic: Hypermagnesemia (10%)

Gastrointestinal: Hematochezia (2% to 3%), hemorrhoidal bleeding (1%), pancreatitis (<10%), rectal hemorrhage (2% to 4%)

Hematologic & oncologic: Keratoacanthoma (single agent: ≤8%; combination therapy: ≤3%), malignant melanoma (single agent: 5%; combination therapy: 1%)

Hypersensitivity: Hypersensitivity reaction (<10%)

Nervous system: Facial paresis (<10%)

Neuromuscular & skeletal: Panniculitis (<10%)

Ophthalmic: Uveitis (1% to 4%; including iridocyclitis, iritis)

Respiratory: Epistaxis (7%), pleural effusion (2%), pneumonia (3%)

Frequency not defined:

Gastrointestinal: Gastrointestinal hemorrhage

Renal: Acute kidney injury

Respiratory: Hemothorax

Contraindications

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

Canadian labeling: Hypersensitivity to encorafenib or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Cardiotoxicity: Cardiomyopathy (manifesting as left ventricular dysfunction associated with symptomatic or asymptomatic ejection fraction decreases) has been reported in patients who received the combination of encorafenib and binimetinib. A decrease in left ventricular ejection fraction (LVEF) below the institutional LLN with an absolute decrease in LVEF ≥10% below baseline (detected by echocardiography or multigated acquisition [MUGA] scan) has occurred. Grade 3 left ventricular dysfunction has been reported. The median time to first occurrence of any grade left ventricular dysfunction was 3.6 months (range: up to 21 months). Cardiomyopathy resolved in a majority of patients. Safety has not been established in patients with a baseline ejection fraction that is either <50% or below the institutional LLN. Encorafenib is associated with dose-dependent QTc interval prolongation. QTcF prolongation to >500 msec was reported in a small percentage of patients when used in combination with binimetinib or in combination with cetuximab and mFOLFOX6. Patients at risk for developing QTc prolongation include those with known long QT syndromes, clinically significant bradyarrhythmias, severe or uncontrolled heart failure, or concomitant use of medications associated with QT prolongation.

• 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.

• Hemorrhage: Hemorrhage may occur with the combination of encorafenib with binimetinib or cetuximab (alone or in combination with mFOLFOX6), including ≥ grade 3 hemorrhage. The most frequent hemorrhagic events included epistaxis, rectal/anal hemorrhage, hematochezia, hemorrhoidal hemorrhage, and hemothorax. Fatal intracranial hemorrhage (may occur in the setting of new or progressive brain metastases) was also reported.

• Hepatotoxicity: Hepatotoxicity may occur with the combination of encorafenib with binimetinib or cetuximab and mFOLFOX6; grade 3 or 4 elevations in ALT, AST, and/or alkaline phosphatase have been reported.

• 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, new primary melanoma (including malignant melanoma in situ), and skin papilloma 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. Due to its mechanism of action (activation of RAS through mutation or other mechanisms), other noncutaneous malignancies may develop with encorafenib use.

• Ocular toxicity: Uveitis, including iritis and iridocyclitis, has been observed with the combination of encorafenib and binimetinib.

Concurrent drug therapy issues:

• Combination therapy: Additional toxicities may occur when used in combination with binimetinib or cetuximab (alone or in combination with mFOLFOX6).

Other warnings/precautions:

• Appropriate use: 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 from tumor specimens in melanoma. Prior to initiating therapy, confirm BRAF V600E mutation status with an approved test from plasma or tumor tissue in colorectal cancer; if no mutation detected in plasma specimens, then test tumor tissue. Prior to initiating therapy, confirm BRAF V600E mutation status with an approved test from tumor or plasma specimen non–small cell lung cancer (NSCLC); if no mutation detected in plasma specimen, then test tumor tissue. Information on approved tests for detection of BRAF V600 mutations is available at http://www.fda.gov/companiondiagnostics.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Braftovi: 75 mg

Generic Equivalent Available: US

Pricing: US

Capsules (Braftovi Oral)

75 mg (per each): $163.85

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Braftovi: 75 mg

Prescribing and Access Restrictions

Encorafenib is available through specialty pharmacies and various specialty institutions or accounts. Examples from the manufacturer may be found at https://www.braftovimektovi.com/hcp/.

Administration: Adult

Oral: Administer once daily with or without food.

Hazardous Drugs Handling Considerations

This medication is not on the NIOSH (2024) list; however, it may meet the criteria for a hazardous drug. Encorafenib may cause carcinogenicity and has a structural or toxicity profile similar to existing hazardous agents.

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).

Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/210496s016lbl.pdf#page=31, must be dispensed with this medication.

Use: Labeled Indications

Colorectal cancer, metastatic, with BRAF V600E mutation:

Treatment (in combination with cetuximab and mFOLFOX6) of metastatic colorectal cancer in patients with a BRAF V600E mutation (as detected by an approved test).

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

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

Non–small cell lung cancer, metastatic, with BRAF V600E mutation: Treatment (in combination with binimetinib) of metastatic non–small cell lung cancer (NSCLC) with a BRAF V600E mutation (as detected by an approved test) in adults.

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

Medication Safety Issues

Sound-alike/look-alike issues:

Encorafenib may be confused with binimetinib, cobimetinib, dabrafenib, dasatinib, enasidenib, enfortumab vedotin, ensartinib, entrectinib, erdafitinib, erlotinib, trametinib, vemurafenib

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).

Metabolism/Transport Effects

Substrate of CYP2C19 (Minor), CYP2D6 (Minor), CYP3A4 (Major with inhibitors), CYP3A4 (Minor with inducers), P-glycoprotein (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits BCRP, CYP1A2 (Weak), OATP1B1/1B3; Induces CYP2B6 (Weak), CYP3A4 (Strong);

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Abemaciclib: CYP3A4 Inducers (Strong) may decrease serum concentration of Abemaciclib. Risk X: Avoid

Abiraterone Acetate: CYP3A4 Inducers (Strong) may decrease serum concentration of Abiraterone Acetate. Management: Avoid coadministration with strong CYP3A4 inducers. For patients treated with single-agent abiraterone who require therapy with a strong CYP3A4 inducers, abiraterone frequency may increased to twice daily. See full mono for details. Risk D: Consider Therapy Modification

Acalabrutinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Acalabrutinib. Management: Avoid co-administration of strong CYP3A inducers in patients taking acalabrutinib. If strong CYP3A inducers cannot be avoided, increase the dose of acalabrutinib to 200 mg twice daily. Risk D: Consider Therapy Modification

Acoramidis: CYP3A4 Inducers (Strong) may decrease serum concentration of Acoramidis. Risk X: Avoid

Adagrasib: Encorafenib may increase QTc-prolonging effects of Adagrasib. Encorafenib may decrease serum concentration of Adagrasib. Risk X: Avoid

Alfacalcidol: CYP3A4 Inducers (Strong) may decrease serum concentration of Alfacalcidol. Risk C: Monitor

ALfentanil: CYP3A4 Inducers (Strong) may decrease serum concentration of ALfentanil. Management: If concomitant use of alfentanil and strong CYP3A4 inducers is necessary, consider dosage increase of alfentanil until stable drug effects are achieved. Monitor patients for signs of opioid withdrawal. Risk D: Consider Therapy Modification

Alpelisib: CYP3A4 Inducers (Strong) may decrease serum concentration of Alpelisib. Risk X: Avoid

ALPRAZolam: CYP3A4 Inducers (Strong) may decrease serum concentration of ALPRAZolam. Risk C: Monitor

Amiodarone: Encorafenib may increase QTc-prolonging effects of Amiodarone. Encorafenib may decrease serum concentration of Amiodarone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation, ventricular arrhythmias, and decreased amiodarone concentrations. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider Therapy Modification

Amisulpride (Oral): May increase QTc-prolonging effects of QT-prolonging Agents (Moderate Risk). Risk C: Monitor

AmLODIPine: CYP3A4 Inducers (Strong) may decrease serum concentration of AmLODIPine. Risk C: Monitor

Antihepaciviral Combination Products: CYP3A4 Inducers (Strong) may decrease serum concentration of Antihepaciviral Combination Products. Risk X: Avoid

Apixaban: CYP3A4 Inducers (Strong) may decrease serum concentration of Apixaban. Management: Avoid concurrent use of apixaban with strong CYP3A4 inducers whenever possible. Use of a strong CYP3A4 inducer with apixaban should be strictly avoided in any patient who is using an agent (either the CYP3A4 inducer or a third drug) that induces P-gp. Risk D: Consider Therapy Modification

Apremilast: CYP3A4 Inducers (Strong) may decrease serum concentration of Apremilast. Risk X: Avoid

Aprepitant: CYP3A4 Inducers (Strong) may decrease serum concentration of Aprepitant. Risk X: Avoid

ARIPiprazole Lauroxil: CYP3A4 Inducers (Strong) may decrease active metabolite exposure of ARIPiprazole Lauroxil. Management: Patients taking the 441 mg dose of aripiprazole lauroxil increase their dose to 662 mg if used with a strong CYP3A4 inducer for more than 14 days. No dose adjustment is necessary for patients using the higher doses of aripiprazole lauroxil. Risk D: Consider Therapy Modification

ARIPiprazole: CYP3A4 Inducers (Strong) may decrease serum concentration of ARIPiprazole. Management: For indications other than major depressive disorder: double the oral aripiprazole dose over 1 to 2 weeks and closely monitor. Avoid use of strong CYP3A4 inducers for more than 14 days with extended-release injectable aripiprazole. Risk D: Consider Therapy Modification

Artemether and Lumefantrine: CYP3A4 Inducers (Strong) may decrease serum concentration of Artemether and Lumefantrine. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Artemether and Lumefantrine. Specifically, concentrations of dihydroartemisinin (DHA), the active metabolite of artemether may be decreased. Risk X: Avoid

Atazanavir: Encorafenib may decrease serum concentration of Atazanavir. Atazanavir may increase serum concentration of Encorafenib. Risk X: Avoid

Atogepant: Encorafenib may increase serum concentration of Atogepant. Encorafenib may decrease serum concentration of Atogepant. Management: Consider avoiding this combination if possible, as encorafenib is both a strong CYP3A4 inducer and an OATP1B1/1B3 inhibitor, with unknown net effects on atogepant exposure. Risk D: Consider Therapy Modification

Atorvastatin: Encorafenib may increase serum concentration of Atorvastatin. Encorafenib may decrease serum concentration of Atorvastatin. Risk C: Monitor

Atrasentan: CYP3A4 Inducers (Strong) may decrease serum concentration of Atrasentan. Risk X: Avoid

Avacopan: CYP3A4 Inducers (Strong) may decrease serum concentration of Avacopan. Risk X: Avoid

Avanafil: CYP3A4 Inducers (Strong) may decrease serum concentration of Avanafil. Risk X: Avoid

Avapritinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Avapritinib. Risk X: Avoid

Axitinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Axitinib. Risk X: Avoid

Azithromycin (Systemic): QT-prolonging Kinase Inhibitors (Moderate Risk) may increase QTc-prolonging effects of Azithromycin (Systemic). 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. Risk C: Monitor

Barnidipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Barnidipine. Risk C: Monitor

BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors): Encorafenib may increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor

Bedaquiline: Encorafenib may increase QTc-prolonging effects of Bedaquiline. Encorafenib may decrease active metabolite exposure of Bedaquiline. Encorafenib may decrease serum concentration of Bedaquiline. Risk X: Avoid

Belumosudil: CYP3A4 Inducers (Strong) may decrease serum concentration of Belumosudil. Management: Increase the dose of belumosudil to 200 mg twice daily when coadministered with strong CYP3A4 inducers. Risk D: Consider Therapy Modification

Benidipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Benidipine. Risk C: Monitor

Benperidol: CYP3A4 Inducers (Strong) may decrease serum concentration of Benperidol. Risk C: Monitor

Benzhydrocodone: CYP3A4 Inducers (Strong) may decrease serum concentration of Benzhydrocodone. Specifically, the serum concentrations of hydrocodone may be reduced. Risk C: Monitor

Betamethasone (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Betamethasone (Systemic). Risk C: Monitor

Bictegravir: CYP3A4 Inducers (Strong) may decrease serum concentration of Bictegravir. Risk C: Monitor

Bisoprolol: CYP3A4 Inducers (Strong) may decrease serum concentration of Bisoprolol. Risk C: Monitor

Blonanserin: CYP3A4 Inducers (Strong) may decrease serum concentration of Blonanserin. Risk C: Monitor

Bortezomib: CYP3A4 Inducers (Strong) may decrease serum concentration of Bortezomib. Risk X: Avoid

Bosentan: Encorafenib may increase serum concentration of Bosentan. Bosentan may decrease serum concentration of Encorafenib. Risk C: Monitor

Bosutinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Bosutinib. Risk X: Avoid

Brentuximab Vedotin: CYP3A4 Inducers (Strong) may decrease serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be decreased. Risk C: Monitor

Brexpiprazole: CYP3A4 Inducers (Strong) may decrease serum concentration of Brexpiprazole. Management: If brexpiprazole is used together with a strong CYP3A4 inducer, the brexpiprazole dose should gradually be doubled over the course of 1 to 2 weeks. Decrease brexpiprazole to original dose over 1 to 2 weeks if the strong CYP3A4 inducer is discontinued. Risk D: Consider Therapy Modification

Brigatinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Brigatinib. Risk X: Avoid

Brincidofovir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Brincidofovir. Management: Consider alternatives to OATP1B/1B3 inhibitors in patients treated with brincidofovir. If coadministration is required, administer OATP1B1/1B3 inhibitors at least 3 hours after brincidofovir and increase monitoring for brincidofovir adverse reactions. Risk D: Consider Therapy Modification

Bromocriptine: CYP3A4 Inducers (Strong) may decrease serum concentration of Bromocriptine. Risk C: Monitor

Bromperidol: CYP3A4 Inducers (Strong) may decrease serum concentration of Bromperidol. Risk C: Monitor

Brotizolam: CYP3A4 Inducers (Strong) may decrease serum concentration of Brotizolam. Risk C: Monitor

Buprenorphine: CYP3A4 Inducers (Strong) may decrease serum concentration of Buprenorphine. Risk C: Monitor

BuPROPion: CYP2B6 Inducers (Weak) may decrease serum concentration of BuPROPion. Risk C: Monitor

BusPIRone: CYP3A4 Inducers (Strong) may decrease serum concentration of BusPIRone. Management: Consider alternatives to this combination. If coadministration of these agents is deemed necessary, monitor patients for reduced buspirone effects and increase buspirone doses as needed. Risk D: Consider Therapy Modification

Butorphanol: CYP3A4 Inducers (Strong) may decrease serum concentration of Butorphanol. Risk C: Monitor

Cabazitaxel: CYP3A4 Inducers (Strong) may decrease serum concentration of Cabazitaxel. Risk C: Monitor

Cabozantinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Cabozantinib. Management: Avoid use of strong CYP3A4 inducers with cabozantinib if possible. If combined, increase cabozantinib capsules (Cometriq) by 40 mg from previous dose, max 180 mg daily. Increase cabozantinib tablets (Cabometyx) by 20 mg from previous dose, max 80 mg daily Risk D: Consider Therapy Modification

Calcifediol: CYP3A4 Inducers (Strong) may increase serum concentration of Calcifediol. Risk C: Monitor

Calcitriol (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Calcitriol (Systemic). Risk C: Monitor

Cannabidiol: CYP3A4 Inducers (Strong) may decrease serum concentration of Cannabidiol. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Cannabidiol. Risk C: Monitor

Cannabis: CYP3A4 Inducers (Strong) may decrease serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be decreased. Risk C: Monitor

Capivasertib: CYP3A4 Inducers (Strong) may decrease serum concentration of Capivasertib. Risk X: Avoid

Capmatinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Capmatinib. Risk X: Avoid

Cariprazine: CYP3A4 Inducers (Strong) may decrease serum concentration of Cariprazine. Risk X: Avoid

Ceritinib: Encorafenib may increase QTc-prolonging effects of Ceritinib. Ceritinib may increase serum concentration of Encorafenib. Encorafenib may decrease serum concentration of Ceritinib. Risk X: Avoid

ChlorproPAMIDE: CYP3A4 Inducers (Strong) may decrease serum concentration of ChlorproPAMIDE. Risk C: Monitor

Cilnidipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Cilnidipine. Risk C: Monitor

Citalopram: May increase QTc-prolonging effects of Encorafenib. Encorafenib may decrease serum concentration of Citalopram. Management: Monitor for QTc interval prolongation, ventricular arrhythmias, and reduced citalopram concentrations and efficacy when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor

Cladribine: BCRP/ABCG2 Inhibitors may increase serum concentration of Cladribine. Management: Avoid concomitant use of BCRP inhibitors during the 4 to 5 day oral cladribine treatment cycles whenever possible. If combined, consider dose reduction of the BCRP inhibitor and separation in the timing of administration. Risk D: Consider Therapy Modification

Clarithromycin: May increase QTc-prolonging effects of Encorafenib. Clarithromycin may increase serum concentration of Encorafenib. Encorafenib may decrease serum concentration of Clarithromycin. Encorafenib may increase active metabolite exposure of Clarithromycin. Management: Avoid this combination when possible. If combined, decrease encorafenib from 450 mg to 150 mg; or from 300 mg, 225 mg, or 150 mg to 75 mg. Additionally, monitor for decreased clarithromycin efficacy and for QTc interval prolongation and arrhythmias. Risk D: Consider Therapy Modification

Clindamycin (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Clindamycin (Systemic). Risk C: Monitor

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

ClonazePAM: CYP3A4 Inducers (Strong) may decrease serum concentration of ClonazePAM. Risk C: Monitor

CloZAPine: Encorafenib may increase QTc-prolonging effects of CloZAPine. Encorafenib may decrease serum concentration of CloZAPine. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation, ventricular arrhythmias, and decreased clozapine concentrations. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider Therapy Modification

Cobicistat: May increase serum concentration of Encorafenib. Encorafenib may decrease serum concentration of Cobicistat. Management: Avoid this combination when possible. If combined, decrease encorafenib from 450 mg to 150 mg; or from 300 mg, 225 mg, or 150 mg to 75 mg. Additionally, monitor for reduced cobicistat efficacy and possible development of resistance. Risk D: Consider Therapy Modification

Cobimetinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Cobimetinib. Risk X: Avoid

Codeine: CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Codeine. Risk C: Monitor

Colchicine: CYP3A4 Inducers (Strong) may decrease serum concentration of Colchicine. Risk C: Monitor

Copanlisib: CYP3A4 Inducers (Strong) may decrease serum concentration of Copanlisib. Risk X: Avoid

Crinecerfont: CYP3A4 Inducers (Strong) may decrease serum concentration of Crinecerfont. Management: Double the morning and evening doses of crinecerfont during coadministration with strong CYP3A4 inducers. See full interaction monograph for details. Risk D: Consider Therapy Modification

Crizotinib: May increase QTc-prolonging effects of Encorafenib. Crizotinib may increase serum concentration of Encorafenib. Encorafenib may decrease serum concentration of Crizotinib. Risk X: Avoid

CycloSPORINE (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of CycloSPORINE (Systemic). Management: Monitor closely for reduced cyclosporine concentrations when combined with strong CYP3A4 inducers. Cyclosporine dose increases will likely be required to maintain adequate serum concentrations. Risk D: Consider Therapy Modification

CYP3A4 Inducers (Moderate): May decrease serum concentration of Encorafenib. Risk C: Monitor

CYP3A4 Inducers (Strong): May decrease serum concentration of Encorafenib. Risk X: Avoid

CYP3A4 Inhibitors (Moderate): May increase 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. Risk D: Consider Therapy Modification

CYP3A4 Inhibitors (Strong): May increase 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. Risk D: Consider Therapy Modification

Cyproterone: CYP3A4 Inducers (Strong) may decrease serum concentration of Cyproterone. Risk C: Monitor

Dabrafenib: May increase QTc-prolonging effects of Encorafenib. Dabrafenib may decrease serum concentration of Encorafenib. Encorafenib may decrease serum concentration of Dabrafenib. Management: Monitor for QTc interval prolongation, ventricular arrhythmias, and reduced encorafenib and dabrafenib concentrations and efficacy when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor

Daclatasvir: CYP3A4 Inducers (Strong) may decrease serum concentration of Daclatasvir. Risk X: Avoid

Dapsone (Systemic): May increase adverse/toxic effects of CYP3A4 Inducers (Strong). CYP3A4 Inducers (Strong) may decrease serum concentration of Dapsone (Systemic). Management: Consider alternatives to this combination when possible. Monitor for decreased dapsone efficacy if combined with strong CYP3A4 inducers. Risk D: Consider Therapy Modification

Daridorexant: CYP3A4 Inducers (Strong) may decrease serum concentration of Daridorexant. Risk X: Avoid

Darunavir: May increase serum concentration of Encorafenib. Encorafenib may decrease serum concentration of Darunavir. Management: Avoid this combination when possible. If combined, decrease encorafenib from 450 mg to 150 mg; or from 300 mg, 225 mg, or 150 mg to 75 mg. Additionally, monitor for reduced darunavir efficacy and possible development of resistance. Risk D: Consider Therapy Modification

Dasabuvir: CYP3A4 Inducers (Strong) may decrease serum concentration of Dasabuvir. Risk X: Avoid

Dasatinib: Encorafenib may increase QTc-prolonging effects of Dasatinib. Encorafenib may decrease serum concentration of Dasatinib. Management: Consider alternatives to this drug combination. If combined, consider increasing the dasatinib dose and monitor clinical response and toxicity. Additionally, monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes. Risk D: Consider Therapy Modification

Deflazacort: CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Deflazacort. Risk X: Avoid

Delamanid: Encorafenib may increase QTc-prolonging effects of Delamanid. Encorafenib may decrease serum concentration of Delamanid. Risk X: Avoid

Deuruxolitinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Deuruxolitinib. Risk X: Avoid

DexAMETHasone (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of DexAMETHasone (Systemic). Management: Avoid coadministration of dexamethasone and strong CYP3A4 inducers. If concomitant use cannot be avoided, consider dexamethasone dose increases. Risk D: Consider Therapy Modification

DiazePAM: CYP3A4 Inducers (Strong) may decrease serum concentration of DiazePAM. Risk C: Monitor

Dienogest: CYP3A4 Inducers (Strong) may decrease serum concentration of Dienogest. Risk C: Monitor

Digitoxin: CYP3A4 Inducers (Strong) may decrease serum concentration of Digitoxin. Risk C: Monitor

DilTIAZem: May increase serum concentration of Encorafenib. Encorafenib may decrease serum concentration of DilTIAZem. Management: Avoid use of encorafenib and diltiazem 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. Monitor for reduced diltiazem efficacy. Risk D: Consider Therapy Modification

Disopyramide: Encorafenib may increase QTc-prolonging effects of Disopyramide. Encorafenib may decrease serum concentration of Disopyramide. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation, ventricular arrhythmias, and decreased disopyramide concentrations. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider Therapy Modification

DOCEtaxel: CYP3A4 Inducers (Strong) may decrease serum concentration of DOCEtaxel. Risk C: Monitor

Domperidone: QT-prolonging Agents (Moderate Risk) may increase QTc-prolonging effects of Domperidone. Risk X: Avoid

Doravirine: CYP3A4 Inducers (Strong) may decrease serum concentration of Doravirine. Risk X: Avoid

Doxercalciferol: CYP3A4 Inducers (Strong) may increase active metabolite exposure of Doxercalciferol. Risk C: Monitor

DOXOrubicin (Conventional): CYP3A4 Inducers (Strong) may decrease serum concentration of DOXOrubicin (Conventional). Risk X: Avoid

DroNABinol: CYP3A4 Inducers (Strong) may decrease serum concentration of DroNABinol. Risk C: Monitor

Dronedarone: Encorafenib may increase QTc-prolonging effects of Dronedarone. Dronedarone may increase serum concentration of Encorafenib. Encorafenib may decrease serum concentration of Dronedarone. Risk X: Avoid

Duvelisib: CYP3A4 Inducers (Strong) may decrease serum concentration of Duvelisib. Risk X: Avoid

Dydrogesterone: CYP3A4 Inducers (Strong) may decrease serum concentration of Dydrogesterone. Risk C: Monitor

Ebastine: CYP3A4 Inducers (Strong) may decrease serum concentration of Ebastine. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Ebastine. Risk C: Monitor

Efavirenz: CYP3A4 Inducers (Strong) may decrease serum concentration of Efavirenz. Risk C: Monitor

Elacestrant: CYP3A4 Inducers (Strong) may decrease serum concentration of Elacestrant. Risk X: Avoid

Elagolix, Estradiol, and Norethindrone: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Elagolix, Estradiol, and Norethindrone. Specifically, concentrations of elagolix may be increased. Risk X: Avoid

Elagolix: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Elagolix. Risk X: Avoid

Elbasvir and Grazoprevir: CYP3A4 Inducers (Strong) may decrease serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid

Elbasvir and Grazoprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid

Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inducers (Strong) may decrease serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Risk X: Avoid

Eliglustat: CYP3A4 Inducers (Strong) may decrease serum concentration of Eliglustat. Risk X: Avoid

Eluxadoline: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Eluxadoline. Management: Decrease the eluxadoline dose to 75 mg twice daily if combined with OATP1B1/1B3 inhibitors and monitor patients for increased eluxadoline effects/toxicities. Risk D: Consider Therapy Modification

Enfortumab Vedotin: CYP3A4 Inducers (Strong) may decrease serum concentration of Enfortumab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be decreased. Risk C: Monitor

Ensartinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Ensartinib. Risk X: Avoid

Entrectinib: Encorafenib may increase QTc-prolonging effects of Entrectinib. Encorafenib may decrease serum concentration of Entrectinib. Risk X: Avoid

Enzalutamide: Encorafenib may decrease serum concentration of Enzalutamide. Enzalutamide may decrease serum concentration of Encorafenib. Risk X: Avoid

Eplerenone: CYP3A4 Inducers (Strong) may decrease serum concentration of Eplerenone. Risk C: Monitor

Eravacycline: CYP3A4 Inducers (Strong) may decrease serum concentration of Eravacycline. Management: Increase the eravacycline dose to 1.5 mg/kg every 12 hours when combined with strong CYP3A4 inducers. Risk D: Consider Therapy Modification

Erdafitinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Erdafitinib. Risk X: Avoid

Erlotinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Erlotinib. Management: Avoid the combination of erlotinib and strong CYP3A4 inducers whenever possible. If this combination must be used, increase erlotinib dose by 50 mg increments every 2 weeks as tolerated, to a maximum of 450 mg/day. Risk D: Consider Therapy Modification

Escitalopram: Encorafenib may increase QTc-prolonging effects of Escitalopram. Encorafenib may decrease serum concentration of Escitalopram. Management: Monitor for QTc interval prolongation, ventricular arrhythmias, and reduced citalopram concentrations and efficacy when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor

Esketamine (Injection): CYP3A4 Inducers (Strong) may decrease serum concentration of Esketamine (Injection). Risk C: Monitor

Estazolam: CYP3A4 Inducers (Strong) may decrease serum concentration of Estazolam. Risk C: Monitor

Estrogen Derivatives: CYP3A4 Inducers (Strong) may decrease serum concentration of Estrogen Derivatives. Risk C: Monitor

Eszopiclone: CYP3A4 Inducers (Strong) may decrease serum concentration of Eszopiclone. Risk C: Monitor

Ethosuximide: CYP3A4 Inducers (Strong) may decrease serum concentration of Ethosuximide. Risk C: Monitor

Etizolam: CYP3A4 Inducers (Strong) may decrease serum concentration of Etizolam. Risk C: Monitor

Etoposide Phosphate: CYP3A4 Inducers (Strong) may decrease serum concentration of Etoposide Phosphate. Management: When possible, seek alternatives to strong CYP3A4-inducing medications in patients receiving etoposide phosphate. If these combinations cannot be avoided, monitor patients closely for diminished etoposide phosphate response. Risk D: Consider Therapy Modification

Etoposide: CYP3A4 Inducers (Strong) may decrease serum concentration of Etoposide. Management: When possible, seek alternatives to strong CYP3A4-inducing medications in patients receiving etoposide. If combined, monitor patients closely for diminished etoposide response and need for etoposide dose increases. Risk D: Consider Therapy Modification

Etoricoxib: CYP3A4 Inducers (Strong) may decrease serum concentration of Etoricoxib. Risk C: Monitor

Etravirine: CYP3A4 Inducers (Strong) may decrease serum concentration of Etravirine. Risk X: Avoid

Everolimus: CYP3A4 Inducers (Strong) may decrease serum concentration of Everolimus. Management: Concomitant use of everolimus and strong CYP3A4 inducers is generally not recommended. However, if combined, monitor for decreased everolimus concentrations and effects, and adjust everolimus dose as needed. Risk D: Consider Therapy Modification

Evogliptin: CYP3A4 Inducers (Strong) may decrease serum concentration of Evogliptin. Risk C: Monitor

Exemestane: CYP3A4 Inducers (Strong) may decrease serum concentration of Exemestane. Management: Increase the exemestane dose to 50 mg once daily in patients receiving concurrent strong CYP3A4 inducers. Monitor patients closely for evidence of toxicity or inadequate clinical response. Risk D: Consider Therapy Modification

Fedratinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Fedratinib. Risk X: Avoid

Felbamate: CYP3A4 Inducers (Strong) may decrease serum concentration of Felbamate. Risk C: Monitor

Felodipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Felodipine. Management: Consider alternatives to this combination when possible. If combined, monitor for reduced felodipine efficacy and the need for felodipine dose increases. Risk D: Consider Therapy Modification

Fenfluramine: CYP3A4 Inducers (Strong) may decrease serum concentration of Fenfluramine. Management: Avoid concurrent use of strong CYP3A4 inducers with fenfluramine when possible. If combined use cannot be avoided, consider increasing the fenfluramine dose, but do not exceed the fenfluramine maximum daily dose. Risk D: Consider Therapy Modification

FentaNYL: CYP3A4 Inducers (Strong) may decrease serum concentration of FentaNYL. Risk C: Monitor

Fesoterodine: CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Fesoterodine. Risk C: Monitor

Fexinidazole: May increase QTc-prolonging effects of Encorafenib. Fexinidazole may decrease serum concentration of Encorafenib. Encorafenib may increase active metabolite exposure of Fexinidazole. Risk X: Avoid

Fezolinetant: CYP1A2 Inhibitors (Weak) may increase serum concentration of Fezolinetant. Risk X: Avoid

Finerenone: CYP3A4 Inducers (Strong) may decrease serum concentration of Finerenone. Risk X: Avoid

Flibanserin: CYP3A4 Inducers (Strong) may decrease serum concentration of Flibanserin. Risk X: Avoid

Fludrocortisone: CYP3A4 Inducers (Strong) may decrease serum concentration of Fludrocortisone. Risk C: Monitor

Fluorouracil Products: May increase QTc-prolonging effects 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. Risk C: Monitor

Fosamprenavir: May increase serum concentration of Encorafenib. Encorafenib may decrease serum concentration of Fosamprenavir. Management: Avoid use of encorafenib and fosamprenavir 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. Monitor for reduced fosamprenavir efficacy. Risk D: Consider Therapy Modification

Fosaprepitant: CYP3A4 Inducers (Strong) may decrease serum concentration of Fosaprepitant. Specifically, CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite aprepitant. Risk X: Avoid

Fosnetupitant: CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Fosnetupitant. Risk X: Avoid

Fostamatinib: CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Fostamatinib. Risk X: Avoid

Fostemsavir: CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Fostemsavir. Risk X: Avoid

Fruquintinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Fruquintinib. Risk X: Avoid

Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification

Futibatinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Futibatinib. Risk C: Monitor

Ganaxolone: CYP3A4 Inducers (Strong) may decrease serum concentration of Ganaxolone. Management: Avoid concomitant use of ganaxolone and strong CYP3A4 inducers whenever possible. If combined, consider increasing the dose of ganaxolone, but do not exceed the maximum recommended daily dose. Risk D: Consider Therapy Modification

Gefitinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Gefitinib. Management: In the absence of severe adverse reactions, increase the gefitinib dose to 500 mg daily in patients receiving strong CYP3A4 inducers; resume 250 mg dose 7 days after discontinuation of the strong inducer. Carefully monitor clinical response. Risk D: Consider Therapy Modification

Gemigliptin: CYP3A4 Inducers (Strong) may decrease serum concentration of Gemigliptin. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Gemigliptin. Risk X: Avoid

Gepirone: CYP3A4 Inducers (Strong) may decrease serum concentration of Gepirone. Risk X: Avoid

Gepotidacin: CYP3A4 Inducers (Strong) may decrease serum concentration of Gepotidacin. Risk X: Avoid

Gilteritinib: Encorafenib may increase QTc-prolonging effects of Gilteritinib. Encorafenib may decrease serum concentration of Gilteritinib. Management: Monitor for reduced gilteritinib efficacy as well as for QTc interval prolongation and arrhythmias (including torsades de pointes). Avoid use of gilteritinib and encorafenib if also combined with a P-gp inducer. Risk C: Monitor

Glasdegib: CYP3A4 Inducers (Strong) may decrease serum concentration of Glasdegib. Risk X: Avoid

Glecaprevir and Pibrentasvir: CYP3A4 Inducers (Strong) may decrease serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor

Grapefruit Juice: May increase serum concentration of Encorafenib. Risk X: Avoid

GuanFACINE: CYP3A4 Inducers (Strong) may decrease serum concentration of GuanFACINE. Management: Increase extended-release guanfacine dose by up to double when initiating guanfacine in patients taking CYP3A4 inducers or if initiating a CYP3A4 inducer in a patient already taking extended-release guanfacine. Monitor for reduced guanfacine efficacy. Risk D: Consider Therapy Modification

Haloperidol: Encorafenib may increase QTc-prolonging effects of Haloperidol. Encorafenib may decrease serum concentration of Haloperidol. Management: Monitor for QTc interval prolongation, ventricular arrhythmias, and reduced haloperidol concentrations and efficacy when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor

Hormonal Contraceptives: Encorafenib may decrease serum concentration of Hormonal Contraceptives. Risk X: Avoid

HYDROcodone: CYP3A4 Inducers (Strong) may decrease serum concentration of HYDROcodone. Risk C: Monitor

Hydrocortisone (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Hydrocortisone (Systemic). Risk C: Monitor

Ibrexafungerp: CYP3A4 Inducers (Strong) may decrease serum concentration of Ibrexafungerp. Risk X: Avoid

Ibrutinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Ibrutinib. Risk X: Avoid

Idelalisib: CYP3A4 Inducers (Strong) may decrease serum concentration of Idelalisib. Risk X: Avoid

Ifosfamide: CYP3A4 Inducers (Strong) may increase active metabolite exposure of Ifosfamide. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Ifosfamide. Risk C: Monitor

Imatinib: Encorafenib may decrease serum concentration of Imatinib. Imatinib may increase serum concentration of Encorafenib. Management: Avoid this combination 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. Increase imatinib dose by at least 50% and monitor the patient's clinical response closely. Risk D: Consider Therapy Modification

Indinavir: May increase serum concentration of Encorafenib. Encorafenib may decrease serum concentration of Indinavir. Management: Avoid this combination when possible. If combined, decrease encorafenib from 450 mg to 150 mg; or from 300 mg, 225 mg, or 150 mg to 75 mg. Additionally, monitor for reduced indinavir efficacy and possible development of resistance. Risk D: Consider Therapy Modification

Irinotecan Products: CYP3A4 Inducers (Strong) may decrease serum concentration of Irinotecan Products. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Irinotecan Products. Specifically, serum concentrations of SN-38 may be reduced. Management: Avoid administration of strong CYP3A4 inducers during irinotecan treatment, and substitute non-CYP3A4 inducing agents at least 2 weeks prior to irinotecan initiation, whenever possible. If combined, monitor for reduced irinotecan efficacy. Risk D: Consider Therapy Modification

Isavuconazonium Sulfate: CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Isavuconazonium Sulfate. Specifically, CYP3A4 Inducers (Strong) may decrease isavuconazole serum concentrations. Risk X: Avoid

Isradipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Isradipine. Risk C: Monitor

Istradefylline: CYP3A4 Inducers (Strong) may decrease serum concentration of Istradefylline. Risk X: Avoid

Itraconazole: CYP3A4 Inducers (Strong) may decrease serum concentration of Itraconazole. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Itraconazole. Risk X: Avoid

Ivabradine: CYP3A4 Inducers (Strong) may decrease serum concentration of Ivabradine. Risk X: Avoid

Ivacaftor: CYP3A4 Inducers (Strong) may decrease serum concentration of Ivacaftor. Risk X: Avoid

Ivosidenib: Encorafenib may increase QTc-prolonging effects of Ivosidenib. Encorafenib may decrease serum concentration of Ivosidenib. Risk X: Avoid

Ixabepilone: CYP3A4 Inducers (Strong) may decrease serum concentration of Ixabepilone. Management: Avoid this combination whenever possible. If this combination must be used, a gradual increase in ixabepilone dose from 40 mg/m² to 60 mg/m² (given as a 4-hour infusion), as tolerated, should be considered. Risk D: Consider Therapy Modification

Ixazomib: CYP3A4 Inducers (Strong) may decrease serum concentration of Ixazomib. Risk X: Avoid

Ketamine: CYP3A4 Inducers (Strong) may decrease serum concentration of Ketamine. Risk C: Monitor

Ketoconazole (Systemic): May increase serum concentration of Encorafenib. Encorafenib may decrease serum concentration of Ketoconazole (Systemic). Management: Avoid use of ketoconazole with encorafenib, and for 2 weeks after encorafenib discontinuation. If combined, decrease encorafenib from 450 mg to 150 mg; or from 300 mg, 225 mg, or 150 mg to 75 mg. Additionally, monitor for reduced ketoconazole efficacy. Risk D: Consider Therapy Modification

Lacidipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Lacidipine. Risk C: Monitor

Lapatinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Lapatinib. Management: If concomitant use cannot be avoided, titrate lapatinib gradually from 1,250 mg/day up to 4,500 mg/day (HER2 positive metastatic breast cancer) or 1,500 mg/day up to 5,500 mg/day (hormone receptor/HER2 positive breast cancer) as tolerated. Risk D: Consider Therapy Modification

Larotrectinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Larotrectinib. Management: Avoid use of strong CYP3A4 inducers with larotrectinib. If this combination cannot be avoided, double the larotrectinib dose. Reduced to previous dose after stopping the inducer after a period of 3 to 5 times the inducer's half-life. Risk D: Consider Therapy Modification

Lazertinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Lazertinib. Risk X: Avoid

Lefamulin (Intravenous): CYP3A4 Inducers (Strong) may decrease serum concentration of Lefamulin (Intravenous). Management: Avoid concomitant use of lefamulin intravenous infusion with strong CYP3A4 inducers unless the benefits outweigh the risks. Risk D: Consider Therapy Modification

Lefamulin: Encorafenib may decrease serum concentration of Lefamulin. Lefamulin may increase serum concentration of Encorafenib. Risk X: Avoid

Lemborexant: CYP3A4 Inducers (Strong) may decrease serum concentration of Lemborexant. Risk X: Avoid

Lenacapavir: CYP3A4 Inducers (Strong) may decrease serum concentration of Lenacapavir. Risk X: Avoid

Leniolisib: CYP3A4 Inducers (Strong) may decrease serum concentration of Leniolisib. Risk X: Avoid

Lercanidipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Lercanidipine. Risk C: Monitor

Leuprolide and Norethindrone: CYP3A4 Inducers (Strong) may decrease serum concentration of Leuprolide and Norethindrone. Specifically, norethindrone concentrations may be decreased. Risk C: Monitor

Levamlodipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Levamlodipine. Risk C: Monitor

Levoketoconazole: May increase QTc-prolonging effects of Encorafenib. Encorafenib may decrease serum concentration of Levoketoconazole. Levoketoconazole may increase serum concentration of Encorafenib. Risk X: Avoid

Levomethadone: CYP3A4 Inducers (Strong) may decrease serum concentration of Levomethadone. Risk C: Monitor

Levonorgestrel (IUD): CYP3A4 Inducers (Strong) may decrease therapeutic effects of Levonorgestrel (IUD). CYP3A4 Inducers (Strong) may decrease serum concentration of Levonorgestrel (IUD). Risk C: Monitor

Lidocaine (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Lidocaine (Systemic). Risk C: Monitor

LinaGLIPtin: CYP3A4 Inducers (Strong) may decrease serum concentration of LinaGLIPtin. Management: Strongly consider using an alternative to any strong CYP3A4 inducer in patients who are being treated with linagliptin. If this combination is used, monitor patients closely for evidence of reduced linagliptin effectiveness. Risk D: Consider Therapy Modification

Lonafarnib: May increase QTc-prolonging effects of Encorafenib. Encorafenib may decrease serum concentration of Lonafarnib. Risk X: Avoid

Lopinavir: May increase serum concentration of Encorafenib. Encorafenib may decrease serum concentration of Lopinavir. Management: Avoid this combination when possible. If combined, decrease encorafenib from 450 mg to 150 mg; or from 300 mg, 225 mg, or 150 mg to 75 mg. Additionally, monitor for reduced lopinavir efficacy and possible development of resistance. Risk D: Consider Therapy Modification

Lorlatinib: CYP3A4 Inducers (Strong) may increase hepatotoxic effects of Lorlatinib. CYP3A4 Inducers (Strong) may decrease serum concentration of Lorlatinib. Risk X: Avoid

Lovastatin: Encorafenib may decrease serum concentration of Lovastatin. Encorafenib may increase serum concentration of Lovastatin. Risk C: Monitor

Lumacaftor and Ivacaftor: CYP3A4 Inducers (Strong) may decrease serum concentration of Lumacaftor and Ivacaftor. Specifically, the serum concentration of ivacaftor may be decreased. Risk X: Avoid

Lumateperone: CYP3A4 Inducers (Strong) may decrease serum concentration of Lumateperone. Risk X: Avoid

Lurasidone: CYP3A4 Inducers (Strong) may decrease serum concentration of Lurasidone. Risk X: Avoid

Lurbinectedin: CYP3A4 Inducers (Strong) may decrease serum concentration of Lurbinectedin. Risk X: Avoid

Macimorelin: CYP3A4 Inducers (Strong) may decrease serum concentration of Macimorelin. Risk X: Avoid

Macitentan: CYP3A4 Inducers (Strong) may decrease serum concentration of Macitentan. Risk X: Avoid

Manidipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Manidipine. Management: Consider avoiding concomitant use of manidipine and strong CYP3A4 inducers. If combined, monitor closely for decreased manidipine effects and loss of efficacy. Increased manidipine doses may be required. Risk D: Consider Therapy Modification

Maraviroc: CYP3A4 Inducers (Strong) may decrease serum concentration of Maraviroc. Management: Increase maraviroc adult dose to 600 mg twice/day, but only if not receiving a strong CYP3A4 inhibitor. Not recommended for pediatric patients not also receiving a strong CYP3A4 inhibitor. Contraindicated in patients with CrCl less than 30 mL/min. Risk D: Consider Therapy Modification

Maribavir: CYP3A4 Inducers (Strong) may decrease serum concentration of Maribavir. Risk X: Avoid

Mavacamten: CYP3A4 Inducers (Strong) may decrease serum concentration of Mavacamten. Risk X: Avoid

Mavorixafor: CYP3A4 Inducers (Strong) may decrease serum concentration of Mavorixafor. Risk X: Avoid

Mefloquine: CYP3A4 Inducers (Strong) may decrease serum concentration of Mefloquine. Risk C: Monitor

Meperidine: CYP3A4 Inducers (Strong) may decrease serum concentration of Meperidine. CYP3A4 Inducers (Strong) may increase active metabolite exposure of Meperidine. Specifically, concentrations of normeperidine, the CNS stimulating metabolite, may be increased. Risk C: Monitor

Methadone: Encorafenib may increase QTc-prolonging effects of Methadone. Encorafenib may decrease serum concentration of Methadone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation, ventricular arrhythmias, and decreased methadone effects/withdrawal. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider Therapy Modification

Methylergonovine: CYP3A4 Inducers (Strong) may decrease serum concentration of Methylergonovine. Risk C: Monitor

MethylPREDNISolone: CYP3A4 Inducers (Strong) may decrease serum concentration of MethylPREDNISolone. Management: Consider methylprednisolone dose increases in patients receiving strong CYP3A4 inducers and monitor closely for reduced steroid efficacy. Risk D: Consider Therapy Modification

Mianserin: CYP3A4 Inducers (Strong) may decrease serum concentration of Mianserin. Risk C: Monitor

Midazolam: CYP3A4 Inducers (Strong) may decrease serum concentration of Midazolam. Risk C: Monitor

Midostaurin: Encorafenib may increase QTc-prolonging effects of Midostaurin. Encorafenib may decrease serum concentration of Midostaurin. Risk X: Avoid

MiFEPRIStone: May increase serum concentration of Encorafenib. Encorafenib may decrease serum concentration of MiFEPRIStone. Management: Avoid this combination when possible, especially when using mifepristone for Cushing's disease. If combined, decrease encorafenib from 450 mg to 150 mg; or from 300 mg, 225 mg, or 150 mg to 75 mg. Monitor for reduced mifepristone efficacy. Risk D: Consider Therapy Modification

Mirabegron: CYP3A4 Inducers (Strong) may decrease serum concentration of Mirabegron. Risk C: Monitor

Mirodenafil: CYP3A4 Inducers (Strong) may decrease serum concentration of Mirodenafil. Management: Consider avoiding the concomitant use of mirodenafil and strong CYP3A4 inducers. If combined, monitor for decreased mirodenafil effects. Mirodenafil dose increases may be required to achieve desired effects. Risk D: Consider Therapy Modification

Mirtazapine: CYP3A4 Inducers (Strong) may decrease serum concentration of Mirtazapine. Risk C: Monitor

Mitapivat: CYP3A4 Inducers (Strong) may decrease serum concentration of Mitapivat. Risk X: Avoid

Mobocertinib: Encorafenib may increase QTc-prolonging effects of Mobocertinib. Encorafenib may decrease serum concentration of Mobocertinib. Risk X: Avoid

Momelotinib: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Momelotinib. Risk C: Monitor

Montelukast: CYP3A4 Inducers (Strong) may decrease serum concentration of Montelukast. Risk C: Monitor

Naldemedine: CYP3A4 Inducers (Strong) may decrease serum concentration of Naldemedine. Risk X: Avoid

Naloxegol: CYP3A4 Inducers (Strong) may decrease serum concentration of Naloxegol. Risk X: Avoid

Nateglinide: CYP3A4 Inducers (Strong) may decrease serum concentration of Nateglinide. Risk C: Monitor

Nelfinavir: Encorafenib may decrease serum concentration of Nelfinavir. Nelfinavir may increase serum concentration of Encorafenib. Management: Avoid this combination when possible. If combined, decrease encorafenib from 450 mg to 150 mg; or from 300 mg, 225 mg, or 150 mg to 75 mg. Additionally, monitor for reduced nelfinavir efficacy and possible development of resistance. Risk D: Consider Therapy Modification

Neratinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Neratinib. Risk X: Avoid

Netupitant: CYP3A4 Inducers (Strong) may decrease serum concentration of Netupitant. Risk X: Avoid

Nevirapine: CYP3A4 Inducers (Strong) may decrease serum concentration of Nevirapine. Management: Consider alternatives to this combination when possible. If combined, monitor for reduced nevirapine efficacy. Risk D: Consider Therapy Modification

NiCARdipine: CYP3A4 Inducers (Strong) may decrease serum concentration of NiCARdipine. Risk C: Monitor

NIFEdipine (Topical): CYP3A4 Inducers (Strong) may decrease serum concentration of NIFEdipine (Topical). Risk C: Monitor

NIFEdipine: CYP3A4 Inducers (Strong) may decrease serum concentration of NIFEdipine. Management: Avoid coadministration of nifedipine with strong CYP3A4 inducers when possible and if combined, monitor patients closely for clinical signs of diminished nifedipine response. Risk D: Consider Therapy Modification

Nilotinib: Encorafenib may increase QTc-prolonging effects of Nilotinib. Nilotinib may increase serum concentration of Encorafenib. Encorafenib may decrease serum concentration of Nilotinib. Risk X: Avoid

Nilvadipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Nilvadipine. Risk C: Monitor

NiMODipine: CYP3A4 Inducers (Strong) may decrease serum concentration of NiMODipine. Risk X: Avoid

Nintedanib: CYP3A4 Inducers (Strong) may decrease serum concentration of Nintedanib. Risk C: Monitor

Nirmatrelvir and Ritonavir: CYP3A4 Inducers (Strong) may decrease serum concentration of Nirmatrelvir and Ritonavir. Risk X: Avoid

Nirogacestat: CYP3A4 Inducers (Strong) may decrease serum concentration of Nirogacestat. Risk X: Avoid

Nisoldipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Nisoldipine. Risk X: Avoid

Nitrazepam: CYP3A4 Inducers (Strong) may decrease serum concentration of Nitrazepam. Risk C: Monitor

OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors): Encorafenib may increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor

OLANZapine: May increase QTc-prolonging effects 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. Risk C: Monitor

Olaparib: CYP3A4 Inducers (Strong) may decrease serum concentration of Olaparib. Risk X: Avoid

Oliceridine: CYP3A4 Inducers (Strong) may decrease serum concentration of Oliceridine. Risk C: Monitor

Olmutinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Olmutinib. Risk C: Monitor

Olutasidenib: CYP3A4 Inducers (Strong) may decrease serum concentration of Olutasidenib. Risk X: Avoid

Omaveloxolone: CYP3A4 Inducers (Strong) may decrease serum concentration of Omaveloxolone. Risk X: Avoid

Ondansetron: CYP3A4 Inducers (Strong) may decrease serum concentration of Ondansetron. Risk C: Monitor

Ondansetron: May increase QTc-prolonging effects 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. Risk C: Monitor

Osilodrostat: CYP3A4 Inducers (Strong) may decrease serum concentration of Osilodrostat. Risk C: Monitor

Osimertinib: May increase QTc-prolonging effects of Encorafenib. Encorafenib may decrease serum concentration of Osimertinib. Management: Avoid coadministration of osimertinib and encorafenib if possible. If coadministration is unavoidable, increase osimertinib to 160 mg daily. Reduce osimertinib to 80 mg daily 3 weeks after encorafenib discontinuation. Monitor for QTc interval prolongation Risk D: Consider Therapy Modification

OXcarbazepine: CYP3A4 Inducers (Strong) may decrease serum concentration of OXcarbazepine. Specifically, the concentrations of the 10-monohydroxy active metabolite of oxcarbazepine may be decreased. Risk C: Monitor

OxyCODONE: CYP3A4 Inducers (Strong) may decrease serum concentration of OxyCODONE. Risk C: Monitor

PACLitaxel (Conventional): CYP3A4 Inducers (Strong) may decrease serum concentration of PACLitaxel (Conventional). Risk C: Monitor

PACLitaxel (Protein Bound): CYP3A4 Inducers (Strong) may decrease serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor

Pacritinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Pacritinib. Risk X: Avoid

Palbociclib: CYP3A4 Inducers (Strong) may decrease serum concentration of Palbociclib. Risk X: Avoid

Paliperidone: CYP3A4 Inducers (Strong) may decrease serum concentration of Paliperidone. Management: Avoid coadministration of extended-release injectable paliperidone and strong CYP3A4 inducers. If coadministration is required consider use of paliperidone extended-release tablets, monitor for reduced effects, and increase the dose as needed. Risk D: Consider Therapy Modification

Palovarotene: CYP3A4 Inducers (Strong) may decrease serum concentration of Palovarotene. Risk X: Avoid

Panobinostat: CYP3A4 Inducers (Strong) may decrease serum concentration of Panobinostat. Risk X: Avoid

PAZOPanib: Encorafenib may increase QTc-prolonging effects of PAZOPanib. Encorafenib may increase serum concentration of PAZOPanib. Risk X: Avoid

Pemigatinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Pemigatinib. Risk X: Avoid

Pentamidine (Systemic): May increase QTc-prolonging effects 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. Risk C: Monitor

Perampanel: CYP3A4 Inducers (Strong) may decrease serum concentration of Perampanel. Management: Increase perampanel starting dose to 4 mg/day if used with strong CYP3A4 inducers. Increase perampanel dose by 2 mg/day no more than once weekly based on response and tolerability. Dose adjustments may be needed if the inducer is discontinued. Risk D: Consider Therapy Modification

Perazine: CYP3A4 Inducers (Strong) may decrease serum concentration of Perazine. Risk C: Monitor

Pexidartinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Pexidartinib. Risk X: Avoid

Pimavanserin: CYP3A4 Inducers (Strong) may decrease serum concentration of Pimavanserin. Risk X: Avoid

Pimozide: May increase QTc-prolonging effects of QT-prolonging Agents (Moderate Risk). Risk X: Avoid

Piperaquine: May increase QTc-prolonging effects of Encorafenib. Encorafenib may decrease serum concentration of Piperaquine. Risk X: Avoid

Pirtobrutinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Pirtobrutinib. Risk X: Avoid

Pitolisant: CYP3A4 Inducers (Strong) may decrease serum concentration of Pitolisant. Management: If on a stable pitolisant dose of 8.9 mg or 17.8 mg/day and starting a strong CYP3A4 inducer, double the pitolisant dose over 7 days (ie, to either 17.8 mg/day or 35.6 mg/day, respectively). Reduce pitolisant dose by 50% when the inducer is discontinued. Risk D: Consider Therapy Modification

Polatuzumab Vedotin: CYP3A4 Inducers (Strong) may decrease serum concentration of Polatuzumab Vedotin. Exposure to unconjugated MMAE, the cytotoxic small molecule component of polatuzumab vedotin, may be decreased. Risk C: Monitor

PONATinib: CYP3A4 Inducers (Strong) may decrease serum concentration of PONATinib. Management: Avoid coadministration of ponatinib with strong CYP3A4 inducers unless the potential benefit of concomitant treatment outweighs the risk of reduced ponatinib exposure. Monitor patients for reduced ponatinib efficacy if combined. Risk D: Consider Therapy Modification

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

Pralsetinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Pralsetinib. Management: Avoid concomitant use of pralsetinib with strong CYP3A4 inducers when possible. If combined, increase the starting dose of pralsetinib to double the current pralsetinib dosage starting on day 7 of coadministration. Risk D: Consider Therapy Modification

Praziquantel: CYP3A4 Inducers (Strong) may decrease serum concentration of Praziquantel. Risk X: Avoid

PrednisoLONE (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of PrednisoLONE (Systemic). Risk C: Monitor

PredniSONE: CYP3A4 Inducers (Strong) may decrease serum concentration of PredniSONE. Risk C: Monitor

Pretomanid: CYP3A4 Inducers (Strong) may decrease serum concentration of Pretomanid. Risk X: Avoid

Propafenone: Encorafenib may increase QTc-prolonging effects of Propafenone. Encorafenib may decrease serum concentration of Propafenone. Management: Monitor for QTc interval prolongation, ventricular arrhythmias, and reduced propafenone concentrations and efficacy when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor

Pyrimethamine: CYP3A4 Inducers (Strong) may decrease serum concentration of Pyrimethamine. Risk C: Monitor

QT-prolonging Agents (Highest Risk): Encorafenib may increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). 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. Risk D: Consider Therapy Modification

QT-prolonging Antidepressants (Moderate Risk): Encorafenib may increase QTc-prolonging effects of QT-prolonging Antidepressants (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. Risk C: Monitor

QT-prolonging Antipsychotics (Moderate Risk): Encorafenib may increase QTc-prolonging effects of QT-prolonging Antipsychotics (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. Risk C: Monitor

QT-prolonging Class IC Antiarrhythmics (Moderate Risk): Encorafenib may increase QTc-prolonging effects of QT-prolonging Class IC Antiarrhythmics (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. Risk C: Monitor

QT-Prolonging Inhalational Anesthetics (Moderate Risk): QT-prolonging Kinase Inhibitors (Moderate Risk) may increase QTc-prolonging effects of QT-Prolonging Inhalational Anesthetics (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. Risk C: Monitor

QT-prolonging Miscellaneous Agents (Moderate Risk): Encorafenib may increase QTc-prolonging effects 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. Risk C: Monitor

QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): Encorafenib may increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase 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. Risk D: Consider Therapy Modification

QT-prolonging Quinolone Antibiotics (Moderate Risk): May increase QTc-prolonging effects 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. Risk C: Monitor

QUEtiapine: Encorafenib may increase QTc-prolonging effects of QUEtiapine. Encorafenib may decrease serum concentration of QUEtiapine. Management: An increase in quetiapine dose (as much as 5 times the regular dose) may be required to maintain therapeutic benefit. Additionally, monitor for QTc interval prolongation and ventricular arrhythmias. Risk D: Consider Therapy Modification

QuiNIDine: Encorafenib may increase QTc-prolonging effects of QuiNIDine. Encorafenib may decrease serum concentration of QuiNIDine. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation, ventricular arrhythmias, and decreased quinidine concentrations. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider Therapy Modification

QuiNINE: Encorafenib may increase QTc-prolonging effects of QuiNINE. Encorafenib may decrease serum concentration of QuiNINE. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation, ventricular arrhythmias, and decreased quinine concentrations. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider Therapy Modification

Quizartinib: Encorafenib may increase QTc-prolonging effects of Quizartinib. Encorafenib may decrease serum concentration of Quizartinib. Risk X: Avoid

Radotinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Radotinib. Management: Consider alternatives to this combination when possible as the risk of radotinib treatment failure may be increased. Risk D: Consider Therapy Modification

Ramelteon: CYP3A4 Inducers (Strong) may decrease serum concentration of Ramelteon. Risk C: Monitor

Ranolazine: CYP3A4 Inducers (Strong) may decrease serum concentration of Ranolazine. Risk X: Avoid

Reboxetine: CYP3A4 Inducers (Strong) may decrease serum concentration of Reboxetine. Risk C: Monitor

Regorafenib: CYP3A4 Inducers (Strong) may decrease serum concentration of Regorafenib. CYP3A4 Inducers (Strong) may increase active metabolite exposure of Regorafenib. Risk X: Avoid

Repaglinide: CYP3A4 Inducers (Strong) may decrease serum concentration of Repaglinide. Risk C: Monitor

Repotrectinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Repotrectinib. Risk X: Avoid

Resmetirom: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Resmetirom. Risk X: Avoid

Revefenacin: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase active metabolite exposure of Revefenacin. Risk X: Avoid

Revumenib: Encorafenib may increase QTc-prolonging effects of Revumenib. Encorafenib may decrease serum concentration of Revumenib. Encorafenib may also increase concentrations of the M1 metabolite, which may contribute to the QT-prolonging effect of Revumenib. Risk X: Avoid

Ribociclib: May increase QTc-prolonging effects of Encorafenib. Encorafenib may decrease serum concentration of Ribociclib. Ribociclib may increase serum concentration of Encorafenib. Risk X: Avoid

Rifabutin: CYP3A4 Inducers (Strong) may decrease serum concentration of Rifabutin. Risk C: Monitor

Rilpivirine: CYP3A4 Inducers (Strong) may decrease serum concentration of Rilpivirine. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for reduced rilpivirine efficacy (eg, loss of virologic response or resistance). Risk X: Avoid

Rimegepant: CYP3A4 Inducers (Strong) may decrease serum concentration of Rimegepant. Risk X: Avoid

Riociguat: CYP3A4 Inducers (Strong) may decrease serum concentration of Riociguat. Risk C: Monitor

Ripretinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Ripretinib. Risk X: Avoid

RisperiDONE: May increase QTc-prolonging effects of Encorafenib. Encorafenib may decrease serum concentration of RisperiDONE. Management: Careful monitoring for reduced risperidone efficacy and possible dose adjustment are recommended when combined with encorafenib. Additionally, monitor for increased QTc interval prolongation and arrhythmias. See full interaction monograph for details. Risk D: Consider Therapy Modification

Ritlecitinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Ritlecitinib. Risk X: Avoid

Ritonavir: CYP3A4 Inducers (Strong) may decrease serum concentration of Ritonavir. Risk X: Avoid

Rivaroxaban: CYP3A4 Inducers (Strong) may decrease serum concentration of Rivaroxaban. Management: Consider alternatives to use of rivaroxaban with strong CYP3A4 inducers. Use of a strong CYP3A4 inducer with rivaroxaban should be strictly avoided in any patient who is using an agent (either the CYP3A4 inducer or a third drug) that induces P-gp. Risk D: Consider Therapy Modification

Roflumilast (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Roflumilast (Systemic). CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Roflumilast (Systemic). Risk X: Avoid

Rolapitant: CYP3A4 Inducers (Strong) may decrease serum concentration of Rolapitant. Risk X: Avoid

RomiDEPsin: CYP3A4 Inducers (Strong) may decrease serum concentration of RomiDEPsin. Risk X: Avoid

Rosuvastatin: BCRP/ABCG2 Inhibitors may increase serum concentration of Rosuvastatin. Risk C: Monitor

Ruxolitinib (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Ruxolitinib (Systemic). CYP3A4 Inducers (Strong) may increase active metabolite exposure of Ruxolitinib (Systemic). Risk C: Monitor

Samidorphan: CYP3A4 Inducers (Strong) may decrease serum concentration of Samidorphan. Risk X: Avoid

Saquinavir: Encorafenib may increase QTc-prolonging effects of Saquinavir. Saquinavir may increase serum concentration of Encorafenib. Encorafenib may decrease serum concentration of Saquinavir. Management: Avoid this combination when possible. If combined, decrease encorafenib from 450 mg to 150 mg; or from 300 mg, 225 mg, or 150 mg to 75 mg. Additionally, monitor for decreased saquinavir efficacy and for QTc interval prolongation and arrhythmias. Risk D: Consider Therapy Modification

SAXagliptin: CYP3A4 Inducers (Strong) may decrease serum concentration of SAXagliptin. Risk C: Monitor

Seladelpar: BCRP/ABCG2 Inhibitors may increase serum concentration of Seladelpar. Risk C: Monitor

Selpercatinib: Encorafenib may increase QTc-prolonging effects of Selpercatinib. Encorafenib may decrease serum concentration of Selpercatinib. Risk X: Avoid

Selumetinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Selumetinib. Risk X: Avoid

Sertindole: May increase QTc-prolonging effects of QT-prolonging Agents (Moderate Risk). Risk X: Avoid

Sertraline: CYP3A4 Inducers (Strong) may decrease serum concentration of Sertraline. Risk C: Monitor

Sildenafil: CYP3A4 Inducers (Strong) may decrease serum concentration of Sildenafil. Risk C: Monitor

Simeprevir: CYP3A4 Inducers (Strong) may decrease serum concentration of Simeprevir. Risk X: Avoid

Simvastatin: Encorafenib may increase serum concentration of Simvastatin. Encorafenib may decrease serum concentration of Simvastatin. Risk C: Monitor

Sirolimus (Conventional): CYP3A4 Inducers (Strong) may decrease serum concentration of Sirolimus (Conventional). Management: Avoid concomitant use of strong CYP3A4 inducers and sirolimus if possible. If combined, monitor for reduced serum sirolimus concentrations. Sirolimus dose increases will likely be necessary to prevent subtherapeutic sirolimus levels. Risk D: Consider Therapy Modification

Sirolimus (Protein Bound): CYP3A4 Inducers (Strong) may decrease serum concentration of Sirolimus (Protein Bound). Risk X: Avoid

Solifenacin: CYP3A4 Inducers (Strong) may decrease serum concentration of Solifenacin. Risk C: Monitor

Sonidegib: CYP3A4 Inducers (Strong) may decrease serum concentration of Sonidegib. Risk X: Avoid

SORAfenib: CYP3A4 Inducers (Strong) may decrease serum concentration of SORAfenib. Risk X: Avoid

Sotorasib: CYP3A4 Inducers (Strong) may decrease serum concentration of Sotorasib. Risk X: Avoid

Sparsentan: CYP3A4 Inducers (Strong) may decrease serum concentration of Sparsentan. Risk X: Avoid

Stiripentol: CYP3A4 Inducers (Strong) may decrease serum concentration of Stiripentol. Management: Avoid concomitant use of stiripentol and strong CYP3A4 inducers when possible. If combined, monitor for reduced stiripentol efficacy and increase the stiripentol dose as needed. Risk D: Consider Therapy Modification

SUFentanil: CYP3A4 Inducers (Strong) may decrease serum concentration of SUFentanil. Management: If a strong CYP3A4 inducer is initiated in a patient on sufentanil, consider a sufentanil dose increase and monitor for decreased sufentanil effects and opioid withdrawal symptoms. Risk D: Consider Therapy Modification

SUNItinib: Encorafenib may increase QTc-prolonging effects of SUNItinib. Encorafenib may decrease serum concentration of SUNItinib. Management: Avoid when possible. If combined, increase sunitinib dose to a max of 87.5 mg daily when treating GIST or RCC. Increase sunitinib dose to a max of 62.5 mg daily when treating PNET. Monitor QTc interval, for reduced efficacy, and for other toxicities. Risk D: Consider Therapy Modification

Suvorexant: CYP3A4 Inducers (Strong) may decrease serum concentration of Suvorexant. Risk C: Monitor

Suzetrigine: CYP3A4 Inducers (Strong) may decrease serum concentration of Suzetrigine. Risk X: Avoid

Tacrolimus (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Tacrolimus (Systemic). Management: Tacrolimus dose increases will likely be needed during concomitant use with strong CYP3A4 inducers. Monitor more closely and frequently for decreased tacrolimus concentrations and effects when combined. Risk D: Consider Therapy Modification

Tadalafil: CYP3A4 Inducers (Strong) may decrease serum concentration of Tadalafil. Management: Erectile dysfunction or benign prostatic hypertrophy: monitor for decreased effectiveness - no standard dose adjustment is recommended. Avoid use of tadalafil for pulmonary arterial hypertension in patients receiving a strong CYP3A4 inducer. Risk D: Consider Therapy Modification

Talazoparib: BCRP/ABCG2 Inhibitors may increase serum concentration of Talazoparib. Risk C: Monitor

Tamoxifen: CYP3A4 Inducers (Strong) may decrease serum concentration of Tamoxifen. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Tamoxifen. Risk X: Avoid

Tasimelteon: CYP3A4 Inducers (Strong) may decrease serum concentration of Tasimelteon. Risk X: Avoid

Taurursodiol: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Taurursodiol. Risk X: Avoid

Tazemetostat: CYP3A4 Inducers (Strong) may decrease serum concentration of Tazemetostat. Risk X: Avoid

Temsirolimus: CYP3A4 Inducers (Strong) may decrease serum concentration of Temsirolimus. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Temsirolimus. Specifically, concentrations of sirolimus may be decreased. Management: Avoid concomitant use of temsirolimus and strong CYP3A4 inducers. If coadministration is unavoidable, increase temsirolimus dose to 50 mg per week. Resume previous temsirolimus dose after discontinuation of the strong CYP3A4 inducer. Risk D: Consider Therapy Modification

Teniposide: CYP3A4 Inducers (Strong) may decrease serum concentration of Teniposide. Risk C: Monitor

Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inducers (Strong) may decrease serum concentration of Tetrahydrocannabinol and Cannabidiol. Management: Avoid use of the tetrahydrocannabinol/cannabidiol oromucosal spray and strong CYP3A4 inducers when possible. If combined use is necessary, careful titration is recommended, notably within the two weeks following discontinuation of the inducer. Risk D: Consider Therapy Modification

Tetrahydrocannabinol: CYP3A4 Inducers (Strong) may decrease serum concentration of Tetrahydrocannabinol. Risk C: Monitor

Tezacaftor and Ivacaftor: CYP3A4 Inducers (Strong) may decrease serum concentration of Tezacaftor and Ivacaftor. Risk X: Avoid

Theophylline Derivatives: CYP1A2 Inhibitors (Weak) may increase serum concentration of Theophylline Derivatives. Risk C: Monitor

Thioridazine: QT-prolonging Agents (Moderate Risk) may increase QTc-prolonging effects of Thioridazine. Risk X: Avoid

Thiotepa: CYP3A4 Inducers (Strong) may increase active metabolite exposure of Thiotepa. CYP3A4 Inducers (Strong) may decrease serum concentration of Thiotepa. Management: Thiotepa prescribing information recommends avoiding concomitant use of thiotepa and strong CYP3A4 inducers. If concomitant use is unavoidable, monitor for adverse effects. Risk D: Consider Therapy Modification

TiaGABine: CYP3A4 Inducers (Strong) may decrease serum concentration of TiaGABine. Risk C: Monitor

Ticagrelor: CYP3A4 Inducers (Strong) may decrease serum concentration of Ticagrelor. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Ticagrelor. Risk X: Avoid

Tipranavir: CYP3A4 Inducers (Strong) may decrease serum concentration of Tipranavir. Risk C: Monitor

Tivozanib: CYP3A4 Inducers (Strong) may decrease serum concentration of Tivozanib. Risk X: Avoid

TiZANidine: CYP1A2 Inhibitors (Weak) may increase serum concentration of TiZANidine. Management: Avoid the use of tizanidine with weak CYP1A2 inhibitors when possible. If combined, monitor closely for increased tizanidine toxicities (eg, hypotension, bradycardia, drowsiness). Tizanidine dose reduction or discontinuation may be necessary. Risk D: Consider Therapy Modification

Tofacitinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Tofacitinib. Risk X: Avoid

Tolvaptan: CYP3A4 Inducers (Strong) may decrease serum concentration of Tolvaptan. Risk X: Avoid

Topotecan: BCRP/ABCG2 Inhibitors may increase serum concentration of Topotecan. Risk X: Avoid

Toremifene: May increase QTc-prolonging effects of Encorafenib. Encorafenib may decrease active metabolite exposure of Toremifene. Encorafenib may decrease serum concentration of Toremifene. Risk X: Avoid

Trabectedin: CYP3A4 Inducers (Strong) may decrease serum concentration of Trabectedin. Risk X: Avoid

TraMADol: CYP3A4 Inducers (Strong) may decrease serum concentration of TraMADol. Risk C: Monitor

TraZODone: CYP3A4 Inducers (Strong) may decrease serum concentration of TraZODone. Management: Consider increasing the trazodone dose during coadministration with strong CYP3A4 inducers. Risk D: Consider Therapy Modification

Tretinoin (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Tretinoin (Systemic). Management: Avoid use of tretinoin and strong CYP3A4 inducers when possible. If combined, monitor for reduced tretinoin concentrations and efficacy. Risk D: Consider Therapy Modification

Triamcinolone (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Triamcinolone (Systemic). Risk C: Monitor

Triazolam: CYP3A4 Inducers (Strong) may decrease serum concentration of Triazolam. Management: Consider alternatives to this combination when possible. If combined, monitor for reduced triazolam efficacy. Substantial triazolam dose increases will likely be required. Risk D: Consider Therapy Modification

Tropisetron: CYP3A4 Inducers (Strong) may decrease serum concentration of Tropisetron. Risk C: Monitor

Tucatinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Tucatinib. Risk X: Avoid

Ubrogepant: CYP3A4 Inducers (Strong) may decrease serum concentration of Ubrogepant. Risk X: Avoid

Udenafil: CYP3A4 Inducers (Strong) may decrease serum concentration of Udenafil. Risk C: Monitor

Ulipristal: CYP3A4 Inducers (Strong) may decrease serum concentration of Ulipristal. Risk X: Avoid

Upadacitinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Upadacitinib. Risk X: Avoid

Valbenazine: CYP3A4 Inducers (Strong) may decrease serum concentration of Valbenazine. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Valbenazine. Risk X: Avoid

Vandetanib: Encorafenib may increase QTc-prolonging effects of Vandetanib. Encorafenib may decrease serum concentration of Vandetanib. Encorafenib may increase active metabolite exposure of Vandetanib. Risk X: Avoid

Vanzacaftor, Tezacaftor, and Deutivacaftor: CYP3A4 Inducers (Strong) may decrease serum concentration of Vanzacaftor, Tezacaftor, and Deutivacaftor. Risk X: Avoid

Velpatasvir: CYP3A4 Inducers (Strong) may decrease serum concentration of Velpatasvir. Risk X: Avoid

Vemurafenib: Encorafenib may increase QTc-prolonging effects of Vemurafenib. Encorafenib may decrease serum concentration of Vemurafenib. Management: Avoid use of vemurafenib and encorafenib if possible. If combined increase the vemurafenib dose by 240 mg as tolerated. Resume prior vemurafenib dose 2 weeks after encorafenib discontinuation. Monitor for QTc interval prolongation and arrhythmias. Risk D: Consider Therapy Modification

Venetoclax: CYP3A4 Inducers (Strong) may decrease serum concentration of Venetoclax. Risk X: Avoid

Verapamil: May increase serum concentration of Encorafenib. Encorafenib may decrease serum concentration of Verapamil. Management: Avoid use of encorafenib and verapamil 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. Monitor for reduced verapamil efficacy. Risk D: Consider Therapy Modification

Vilazodone: CYP3A4 Inducers (Strong) may decrease serum concentration of Vilazodone. Management: Consider increasing vilazodone dose by as much as 2-fold (do not exceed 80 mg/day), based on response, in patients receiving strong CYP3A4 inducers for > 14 days. Reduce to the original vilazodone dose over 1 to 2 weeks after inducer discontinuation. Risk D: Consider Therapy Modification

VinCRIStine: CYP3A4 Inducers (Strong) may decrease serum concentration of VinCRIStine. Risk X: Avoid

Vinflunine: CYP3A4 Inducers (Strong) may decrease serum concentration of Vinflunine. Risk X: Avoid

Vinorelbine: CYP3A4 Inducers (Strong) may decrease serum concentration of Vinorelbine. Risk C: Monitor

Voclosporin: CYP3A4 Inducers (Strong) may decrease serum concentration of Voclosporin. Risk X: Avoid

Vonoprazan: CYP3A4 Inducers (Strong) may decrease serum concentration of Vonoprazan. Risk X: Avoid

Vorapaxar: CYP3A4 Inducers (Strong) may decrease serum concentration of Vorapaxar. Risk X: Avoid

Voriconazole: Encorafenib may increase QTc-prolonging effects of Voriconazole. Voriconazole may increase serum concentration of Encorafenib. Encorafenib may decrease serum concentration of Voriconazole. Management: Avoid this combination when possible. If combined, decrease encorafenib from 450 mg to 150 mg; or from 300 mg, 225 mg, or 150 mg to 75 mg. Additionally, monitor for decreased voriconazole efficacy and for QTc interval prolongation and arrhythmias. Risk D: Consider Therapy Modification

Vortioxetine: CYP3A4 Inducers (Strong) may decrease serum concentration of Vortioxetine. Management: Consider increasing the vortioxetine dose to no more than 3 times the original dose when used with a strong drug metabolism inducer for more than 14 days. The vortioxetine dose should be returned to normal within 14 days of stopping the strong inducer. Risk D: Consider Therapy Modification

Voxelotor: CYP3A4 Inducers (Strong) may decrease serum concentration of Voxelotor. Management: Avoid concomitant use of voxelotor and strong CYP3A4 inducers. If unavoidable, increase the voxelotor dose to 2,500 mg once daily. For children ages 4 to less than 12 years, weight-based dose adjustments are required. See full monograph for details. Risk D: Consider Therapy Modification

Voxilaprevir: CYP3A4 Inducers (Strong) may decrease serum concentration of Voxilaprevir. Risk X: Avoid

Voxilaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Voxilaprevir. Risk X: Avoid

Zaleplon: CYP3A4 Inducers (Strong) may decrease serum concentration of Zaleplon. Management: Consider the use of an alternative hypnotic that is not metabolized by CYP3A4 in patients receiving strong CYP3A4 inducers. If zaleplon is combined with a strong CYP3A4 inducer, monitor for decreased effectiveness of zaleplon. Risk D: Consider Therapy Modification

Zanubrutinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Zanubrutinib. Risk X: Avoid

Zavegepant: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Zavegepant. Risk X: Avoid

Ziprasidone: Encorafenib may increase QTc-prolonging effects of Ziprasidone. Encorafenib may decrease serum concentration of Ziprasidone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation, ventricular arrhythmias, and decreased ziprasidone concentrations. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider Therapy Modification

Zolpidem: CYP3A4 Inducers (Strong) may decrease serum concentration of Zolpidem. Risk C: Monitor

Zonisamide: CYP3A4 Inducers (Strong) may decrease serum concentration of Zonisamide. Risk C: Monitor

Zopiclone: CYP3A4 Inducers (Strong) may decrease serum concentration of Zopiclone. Risk C: Monitor

Zuclopenthixol: CYP3A4 Inducers (Strong) may decrease serum concentration of Zuclopenthixol. Risk C: Monitor

Zuranolone: CYP3A4 Inducers (Strong) may decrease serum concentration of Zuranolone. Risk X: Avoid

Food Interactions

Coadministration with a grapefruit or grapefruit juice may increase encorafenib concentrations. Management: Avoid grapefruit or grapefruit juice while taking encorafenib.

Reproductive Considerations

Verify pregnancy status prior to initiating encorafenib therapy in patients who could become pregnant. Patients who could become pregnant should use a highly effective nonhormonal contraceptive during therapy and for 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, in utero exposure to encorafenib may cause fetal harm.

Breastfeeding Considerations

It is not known if encorafenib is present in breast milk.

Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during treatment and for 2 weeks after the last encorafenib dose.

Monitoring Parameters

BRAF mutation status: BRAF V600K or V600E mutation status in tumor specimens prior to treatment in melanoma. BRAF V600E mutation status in plasma or tumor tissue prior to treatment in colorectal cancer; if no mutation detected in plasma specimens, then test tumor tissue. BRAF V600E mutation status in tumor or plasma specimens prior to treatment for non–small cell lung cancer (NSCLC); if no mutation detected in plasma specimens, then test tumor tissue.

Monitor LFTs prior to treatment initiation, monthly during treatment, and as clinically indicated; monitor electrolytes. Verify pregnancy status prior to treatment initiation in patients who could become pregnant. Assess ejection fraction (by echocardiogram or multigated acquisition [MUGA] scan) prior to treatment initiation, one month after initiation, and then every 2 to 3 months during treatment; monitor closely in patients with cardiovascular risk factors. Monitor for QT prolongation in patients with or at risk for developing QTc prolongation (eg, patients with known long QT syndromes, clinically significant bradyarrhythmias, severe or uncontrolled heart failure, or concomitant QT prolonging medications). Conduct dermatologic evaluations prior to treatment initiation, every 2 months during therapy, and for up to 6 months following discontinuation to assess for new cutaneous malignancies. Evaluate visual symptoms at each visit; perform an ophthalmologic examination at regular intervals and for new or worsening visual disturbances (and to follow new or persistent ophthalmologic findings). Monitor for signs/symptoms of hemorrhage, dermatologic toxicity (conduct dermatopathologic evaluations for suspicious lesions), new noncutaneous malignancy, and/or ocular toxicity (eg, uveitis including eye pain, photophobia, vision changes). Monitor adherence.

The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

Cardiovascular monitoring specifics: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking (ASCO [Armenian 2017]). Assess BP at baseline and each clinical visit (as well as outpatient monitoring weekly for initial 3 months, then monthly thereafter), obtain a baseline echocardiography in high- and very-high risk patients scheduled to receive BRAF-MEK inhibitor combination therapy (consider repeating every 4 months during the first year); consider echocardiography in low- and moderate-risk patients scheduled to receive BRAF-MEK inhibitor combination therapy (ESC [Lyon 2022]).

Mechanism of Action

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). In animal models, the combination of encorafenib and binimetinib had an anti-tumor effect greater than binimetinib alone. In BRAF mutant non-small cell lung cancer animal models, after dosing cessation, increased tumor growth delays were also observed with the encorafenib/binimetinib combination (compared to either drug alone).

Pharmacokinetics (Adult Data Unless Noted)

Absorption: At least 86% of the dose is absorbed.

Distribution: 164 L.

Protein binding: 86% to plasma proteins.

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

Half-life elimination: 3.5 hours.

Time to peak: 2 hours.

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

Clearance: 14 L/hour (450 mg; day 1); 32 L/hour (450 mg; steady state).

Brand Names: International

International Brand Names by Country

For country code abbreviations (show table)

(AE) United Arab Emirates: Braftovi;
(AT) Austria: Braftovi;
(AU) Australia: Braftovi;
(BE) Belgium: Braftovi;
(BG) Bulgaria: Braftovi;
(CH) Switzerland: Braftovi;
(CZ) Czech Republic: Braftovi;
(DE) Germany: Braftovi;
(EC) Ecuador: Braftovi;
(EE) Estonia: Braftovi;
(ES) Spain: Braftovi;
(FI) Finland: Braftovi;
(FR) France: Braftovi;
(GB) United Kingdom: Braftovi;
(HK) Hong Kong: Braftovi;
(IE) Ireland: Braftovi;
(IT) Italy: Braftovi;
(JP) Japan: Braftovi;
(NL) Netherlands: Braftovi;
(NO) Norway: Braftovi;
(PE) Peru: Braftovi;
(PL) Poland: Braftovi;
(PR) Puerto Rico: Braftovi;
(PT) Portugal: Braftovi;
(QA) Qatar: Braftovi;
(RO) Romania: Braftovi;
(SA) Saudi Arabia: Braftovi;
(SE) Sweden: Braftovi;
(SK) Slovakia: Braftovi;
(TR) Turkey: Braftovi;
(TW) Taiwan: Braftovi;
(ZA) South Africa: Braftovi

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Braftovi (encorafenib) [prescribing information]. Boulder, CO: Array BioPharma Inc; December 2024.
Braftovi (encorafenib) [product monograph]. Kirkland, Quebec, Canada: Pfizer Canada ULC; February 2024.
Dummer R, Ascierto PA, Gogas HJ, et al. Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicenter, open-label, randomized phase 3 trial. Lancet Oncol. 2018;19(5):603-615. doi:10.1016/S1470-2045(18)30142-6 [PubMed 29573941]
Dummer R, Flaherty KT, Robert C, et al. COLUMBUS 5-year update: a randomized, open-label, phase III trial of encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF V600-mutant melanoma. J Clin Oncol. 2022;40(36):4178-4188. doi:10.1200/JCO.21.02659 [PubMed 35862871]
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Lyon AR, López-Fernández T, Couch LS, et al. 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J. 2022;43(41):4229-4361. doi:10.1093/eurheartj/ehac244 [PubMed 36017568]
Ovesen JL, Sammons D, Connor TH, et al; US Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health. NIOSH list of hazardous drugs in healthcare settings, 2024. https://doi.org/10.26616/NIOSHPUB2025103. Updated December 18, 2024. Accessed December 20, 2024.
Refer to manufacturer’s labeling.
Riely GJ, Smit EF, Ahn MJ, et al. Phase II, open-label study of encorafenib plus binimetinib in patients with BRAF ^V600-mutant metastatic non-small-cell lung cancer. J Clin Oncol. 2023;41(21):3700-3711. doi:10.1200/JCO.23.00774 [PubMed 37270692]
Tabernero J, Grothey A, Van Cutsem E, et al. Encorafenib plus cetuximab as a new standard of care for previously treated BRAFV600E-mutant metastatic colorectal cancer: updated survival results and subgroup analyses from the BEACON study. J Clin Oncol, 2021;39(4):273-284. doi:10.1200/JCO.20.02088 [PubMed 33503393]
United States Pharmacopeia. <800> Hazardous Drugs—Handling in Healthcare Settings. In: USP-NF. United States Pharmacopeia; July 1, 2020. Accessed January 16, 2025. doi:10.31003/USPNF_M7808_07_01
Van Cutsem E, Huijberts S, Grothey A, et al. Binimetinib, encorafenib, and cetuximab triplet therapy for patients with BRAF V600E-mutant metastatic colorectal cancer: safety lead-in results from the phase III BEACON colorectal cancer study. J Clin Oncol. 2019;37(17):1460-1469. doi: 10.1200/JCO.18.02459. [PubMed 30892987]

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Encorafenib: Drug information