Version May 2024
Dosage guidance:
Safety: Correct hypokalemia or hypomagnesemia prior to treatment initiation.
Colorectal cancer, metastatic, with BRAF V600E mutation: Note: Confirm BRAF V600E mutation status in tumor specimens prior to initiation.
Oral: 300 mg once daily (in combination with cetuximab); continue until disease progression or unacceptable toxicity (Ref).
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: 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.
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).
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.
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. Refer to the binimetinib or cetuximab monographs for recommended dose reductions.
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.
|
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. |
|
Adverse reaction |
Severity |
Encorafenib dosage modification |
|---|---|---|
|
a LVEF = left ventricular ejection fraction. | ||
|
Cardiotoxicity |
Symptomatic heart failure or absolute decrease in LVEFa 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. | |
Refer to adult dosing.
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%), increased gamma-glutamyl transferase (45%), 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: 7%), dysgeusia (single agent: 13%, combination therapy: 6%), increased serum amylase (22%), increased serum lipase (40%), nausea (34% to 58%; grades 3/4: 2% 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 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: Cutaneous papilloma (2%)
Endocrine & metabolic: Hypermagnesemia (10%)
Gastrointestinal: Hematochezia (2% to 3%), hemorrhoidal bleeding (1%), pancreatitis (<10%)
Hematologic & oncologic: Basal cell carcinoma of skin (combination therapy: 2%; single agent: 1%), keratoacanthoma (single agent: ≤8%; combination therapy: ≤3%), malignant melanoma (single agent: 5%; combination therapy: 1%), rectal hemorrhage (2% to 4%), squamous cell carcinoma of skin (single agent: ≤8%; combination therapy: ≤3%)
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
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to encorafenib or any component of the formulation.
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. In a clinical trial, QTcF prolongation to >500 msec was reported in a small percentage of patients when used in combination with binimetinib. 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 binimetinib and encorafenib, including ≥ grade 3 hemorrhage. The most frequent hemorrhagic events were gastrointestinal in nature, including 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 and binimetinib; grade 3 or 4 elevations in ALT, AST, and/or alkaline phosphatase have been reported, although grade 3 or 4 total bilirubin elevations were not 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, 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.
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 colorectal cancer and melanoma, and from tumor or plasma specimens in non-small cell lung cancer (NSCLC); if no mutation detected in plasma specimens, then test tumor tissue (NSCLC only). Information on approved tests for detection of BRAF V600 mutations is available at http://www.fda.gov/companiondiagnostics.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Braftovi: 75 mg
No
Capsules (Braftovi Oral)
75 mg (per each): $159.08
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Braftovi: 75 mg
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/.
Oral: Administer once daily with or without food.
This medication is not on the NIOSH (2016) 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 2016; 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.
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/210496s015lbl.pdf#page=30, must be dispensed with this medication.
Colorectal cancer, metastatic, with BRAF V600E mutation: Treatment of metastatic colorectal cancer in adults with a BRAF V600E mutation (in combination with cetuximab) after prior therapy. Select patients for therapy based on the presence of a BRAF V600E mutation in tumor specimens as detected by an approved test.
Melanoma, unresectable or metastatic, with BRAF V600E or V600K mutation: Treatment of unresectable or metastatic melanoma with a BRAF V600E or V600K mutation (in combination with binimetinib). Select patients for therapy based on the presence of a BRAF V600E or BRAF V600K mutation in tumor specimens as detected by an approved test.
Non-small cell lung cancer, metastatic, with BRAF V600E mutation: Treatment of metastatic non-small cell lung cancer (NSCLC) with a BRAF V600E mutation (in combination with binimetinib) in adults. Select patients for therapy based on the presence of a BRAF V600E mutation in tumor or plasma specimens as detected by an approved test.
Limitations of use: Encorafenib is not indicated for treatment of wild-type BRAF melanoma, wild-type BRAF colorectal cancer, or wild-type BRAF NSCLC.
Encorafenib may be confused with binimetinib, cobimetinib, dabrafenib, dasatinib, enasidenib, enfortumab vedotin, entrectinib, erdafitinib, erlotinib, trametinib, vemurafenib
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
Substrate of CYP2C19 (minor), CYP2D6 (minor), CYP3A4 (major), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits BCRP/ABCG2, OATP1B1/1B3 (SLCO1B1/1B3); Induces CYP3A4 (strong)
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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Abemaciclib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Abemaciclib. Risk X: Avoid combination
Abiraterone Acetate: CYP3A4 Inducers (Strong) may decrease the serum concentration of Abiraterone Acetate. Management: Avoid when possible. If the combination cannot be avoided, increase abiraterone acetate dosing frequency from once daily to twice daily during combined use. Reduce abiraterone dose back to the prior dose and frequency once strong inducer is discontinued. Risk D: Consider therapy modification
Acalabrutinib: CYP3A4 Inducers (Strong) may decrease the 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
Adagrasib: Encorafenib may enhance the QTc-prolonging effect of Adagrasib. Encorafenib may decrease the serum concentration of Adagrasib. Risk X: Avoid combination
Alfacalcidol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Alfacalcidol. Risk C: Monitor therapy
ALfentanil: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Alpelisib. Risk X: Avoid combination
ALPRAZolam: CYP3A4 Inducers (Strong) may decrease the serum concentration of ALPRAZolam. Risk C: Monitor therapy
Amiodarone: Encorafenib may enhance the QTc-prolonging effect of Amiodarone. Encorafenib may decrease the 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 enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk C: Monitor therapy
AmLODIPine: CYP3A4 Inducers (Strong) may decrease the serum concentration of AmLODIPine. Risk C: Monitor therapy
Antihepaciviral Combination Products: CYP3A4 Inducers (Strong) may decrease the serum concentration of Antihepaciviral Combination Products. Risk X: Avoid combination
Apixaban: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Apremilast. Risk X: Avoid combination
Aprepitant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Aprepitant. Risk X: Avoid combination
ARIPiprazole: CYP3A4 Inducers (Strong) may decrease the 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
ARIPiprazole Lauroxil: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) 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
Artemether and Lumefantrine: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Artemether and Lumefantrine. Specifically, concentrations of dihydroartemisinin (DHA), the active metabolite of artemether may be decreased. CYP3A4 Inducers (Strong) may decrease the serum concentration of Artemether and Lumefantrine. Risk X: Avoid combination
Asunaprevir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Asunaprevir. Risk X: Avoid combination
Atazanavir: Encorafenib may decrease the serum concentration of Atazanavir. Atazanavir may increase the serum concentration of Encorafenib. Risk X: Avoid combination
Atogepant: Encorafenib may increase the serum concentration of Atogepant. Encorafenib may decrease the 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 the serum concentration of Atorvastatin. Encorafenib may decrease the serum concentration of Atorvastatin. Risk C: Monitor therapy
Avacopan: CYP3A4 Inducers (Strong) may decrease the serum concentration of Avacopan. Risk X: Avoid combination
Avanafil: CYP3A4 Inducers (Strong) may decrease the serum concentration of Avanafil. Risk X: Avoid combination
Avapritinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Avapritinib. Risk X: Avoid combination
Axitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Axitinib. Risk X: Avoid combination
Azithromycin (Systemic): QT-prolonging Kinase Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect 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 therapy
Barnidipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Barnidipine. Risk C: Monitor therapy
BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors): Encorafenib may increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Bedaquiline: Encorafenib may enhance the QTc-prolonging effect of Bedaquiline. Encorafenib may decrease serum concentrations of the active metabolite(s) of Bedaquiline. Encorafenib may decrease the serum concentration of Bedaquiline. Risk X: Avoid combination
Belumosudil: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Benidipine. Risk C: Monitor therapy
Benperidol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Benperidol. Risk C: Monitor therapy
Benzhydrocodone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Benzhydrocodone. Specifically, the serum concentrations of hydrocodone may be reduced. Risk C: Monitor therapy
Berotralstat: May increase the serum concentration of Encorafenib. Encorafenib may increase the serum concentration of Berotralstat. Management: Avoid use of encorafenib and berotralstat 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. Decrease berotralstat to 110 mg daily. Risk D: Consider therapy modification
Betamethasone (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Betamethasone (Systemic). Risk C: Monitor therapy
Bictegravir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Bictegravir. Risk C: Monitor therapy
Bisoprolol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Bisoprolol. Risk C: Monitor therapy
Blonanserin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Blonanserin. Risk C: Monitor therapy
Bortezomib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Bortezomib. Risk X: Avoid combination
Bosentan: Encorafenib may increase the serum concentration of Bosentan. Bosentan may decrease the serum concentration of Encorafenib. Risk C: Monitor therapy
Bosutinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Bosutinib. Risk X: Avoid combination
Brentuximab Vedotin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be decreased. Risk C: Monitor therapy
Brexpiprazole: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Brigatinib. Risk X: Avoid combination
Brincidofovir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the 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 the serum concentration of Bromocriptine. Risk C: Monitor therapy
Bromperidol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Bromperidol. Risk C: Monitor therapy
Brotizolam: CYP3A4 Inducers (Strong) may decrease the serum concentration of Brotizolam. Risk C: Monitor therapy
Buprenorphine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Buprenorphine. Risk C: Monitor therapy
BusPIRone: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Butorphanol. Risk C: Monitor therapy
Cabazitaxel: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cabazitaxel. Risk C: Monitor therapy
Cabozantinib: CYP3A4 Inducers (Strong) may decrease the 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 decrease the serum concentration of Calcifediol. Risk C: Monitor therapy
Calcitriol (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Calcitriol (Systemic). Risk C: Monitor therapy
Cannabidiol: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Cannabidiol. CYP3A4 Inducers (Strong) may decrease the serum concentration of Cannabidiol. Risk C: Monitor therapy
Cannabis: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be decreased. Risk C: Monitor therapy
Capivasertib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Capivasertib. Risk X: Avoid combination
Capmatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Capmatinib. Risk X: Avoid combination
Cariprazine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cariprazine. Risk X: Avoid combination
Ceritinib: Encorafenib may enhance the QTc-prolonging effect of Ceritinib. Ceritinib may increase the serum concentration of Encorafenib. Encorafenib may decrease the serum concentration of Ceritinib. Risk X: Avoid combination
ChlorproPAMIDE: CYP3A4 Inducers (Strong) may decrease the serum concentration of ChlorproPAMIDE. Risk C: Monitor therapy
Cilnidipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cilnidipine. Risk C: Monitor therapy
Citalopram: May enhance the QTc-prolonging effect of Encorafenib. Encorafenib may decrease the 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 therapy
Cladribine: BCRP/ABCG2 Inhibitors may increase the 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 enhance the QTc-prolonging effect of Encorafenib. Encorafenib may increase serum concentrations of the active metabolite(s) of Clarithromycin. Clarithromycin may increase the serum concentration of Encorafenib. Encorafenib may decrease the serum concentration 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 the serum concentration of Clindamycin (Systemic). Risk C: Monitor therapy
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
ClonazePAM: CYP3A4 Inducers (Strong) may decrease the serum concentration of ClonazePAM. Risk C: Monitor therapy
CloZAPine: Encorafenib may enhance the QTc-prolonging effect of CloZAPine. Encorafenib may decrease the 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 the serum concentration of Encorafenib. Encorafenib may decrease the 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 the serum concentration of Cobimetinib. Risk X: Avoid combination
Codeine: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Codeine. Risk C: Monitor therapy
Colchicine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Colchicine. Risk C: Monitor therapy
Copanlisib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Copanlisib. Risk X: Avoid combination
Crizotinib: May enhance the QTc-prolonging effect of Encorafenib. Crizotinib may increase the serum concentration of Encorafenib. Encorafenib may decrease the serum concentration of Crizotinib. Risk X: Avoid combination
CycloSPORINE (Systemic): CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Encorafenib. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Encorafenib. Risk X: Avoid combination
CYP3A4 Inhibitors (Moderate): May increase the 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 the 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 the serum concentration of Cyproterone. Risk C: Monitor therapy
Dabrafenib: May enhance the QTc-prolonging effect of Encorafenib. Encorafenib may decrease the serum concentration of Dabrafenib. Dabrafenib may decrease the serum concentration of Encorafenib. 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 therapy
Daclatasvir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Daclatasvir. Risk X: Avoid combination
Dapsone (Systemic): May enhance the adverse/toxic effect of CYP3A4 Inducers (Strong). CYP3A4 Inducers (Strong) may decrease the serum concentration of Dapsone (Systemic). Risk C: Monitor therapy
Daridorexant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Daridorexant. Risk X: Avoid combination
Darunavir: May increase the serum concentration of Encorafenib. Encorafenib may decrease the 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 the serum concentration of Dasabuvir. Risk X: Avoid combination
Dasatinib: Encorafenib may enhance the QTc-prolonging effect of Dasatinib. Encorafenib may decrease the 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 serum concentrations of the active metabolite(s) of Deflazacort. Risk X: Avoid combination
Delamanid: Encorafenib may enhance the QTc-prolonging effect of Delamanid. Encorafenib may decrease the serum concentration of Delamanid. Risk X: Avoid combination
Delavirdine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Delavirdine. Management: Consider avoiding this combination if possible. If concomitant use is necessary, monitor for decreased delavirdine concentrations and effects if coadministered with strong CYP3A4 inducers. Risk D: Consider therapy modification
DexAMETHasone (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of DexAMETHasone (Systemic). Management: Consider dexamethasone dose increases in patients receiving strong CYP3A4 inducers and monitor closely for reduced dexamethasone efficacy. Consider avoiding this combination when treating life threatening conditions (ie, multiple myeloma). Risk D: Consider therapy modification
DiazePAM: CYP3A4 Inducers (Strong) may decrease the serum concentration of DiazePAM. Risk C: Monitor therapy
Dienogest: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dienogest. Risk C: Monitor therapy
DilTIAZem: May increase the serum concentration of Encorafenib. Encorafenib may decrease the 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 enhance the QTc-prolonging effect of Disopyramide. Encorafenib may decrease the 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 the serum concentration of DOCEtaxel. Risk C: Monitor therapy
Domperidone: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Domperidone. 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
Doravirine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Doravirine. Risk X: Avoid combination
Doxercalciferol: CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Doxercalciferol. Risk C: Monitor therapy
DOXOrubicin (Conventional): CYP3A4 Inducers (Strong) may decrease the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination
DroNABinol: CYP3A4 Inducers (Strong) may decrease the serum concentration of DroNABinol. Risk C: Monitor therapy
Dronedarone: Encorafenib may enhance the QTc-prolonging effect of Dronedarone. Encorafenib may decrease the serum concentration of Dronedarone. Dronedarone may increase the serum concentration of Encorafenib. Risk X: Avoid combination
Duvelisib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Duvelisib. Risk X: Avoid combination
Dydrogesterone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dydrogesterone. Risk C: Monitor therapy
Ebastine: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Ebastine. CYP3A4 Inducers (Strong) may decrease the serum concentration of Ebastine. Risk C: Monitor therapy
Efavirenz: CYP3A4 Inducers (Strong) may decrease the serum concentration of Efavirenz. Risk C: Monitor therapy
Elacestrant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Elacestrant. Risk X: Avoid combination
Elagolix: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elagolix. Risk X: Avoid combination
Elagolix, Estradiol, and Norethindrone: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elagolix, Estradiol, and Norethindrone. Specifically, concentrations of elagolix may be increased. Risk X: Avoid combination
Elbasvir and Grazoprevir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid combination
Elbasvir and Grazoprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid combination
Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inducers (Strong) may decrease the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Risk X: Avoid combination
Eliglustat: CYP3A4 Inducers (Strong) may decrease the serum concentration of Eliglustat. Risk X: Avoid combination
Eluxadoline: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the 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
Elvitegravir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Elvitegravir. Management: Consider alternatives to this combination when possible. If combined, monitor for reduced elvitegravir efficacy. Risk D: Consider therapy modification
Enfortumab Vedotin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Enfortumab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be decreased. Risk C: Monitor therapy
Entrectinib: Encorafenib may enhance the QTc-prolonging effect of Entrectinib. Encorafenib may decrease the serum concentration of Entrectinib. Risk X: Avoid combination
Enzalutamide: Encorafenib may decrease the serum concentration of Enzalutamide. Enzalutamide may decrease the serum concentration of Encorafenib. Risk X: Avoid combination
Eplerenone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Eplerenone. Risk C: Monitor therapy
Eravacycline: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Erdafitinib. Risk X: Avoid combination
Erlotinib: CYP3A4 Inducers (Strong) may decrease the 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 enhance the QTc-prolonging effect of Escitalopram. Encorafenib may decrease the 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 therapy
Estazolam: CYP3A4 Inducers (Strong) may decrease the serum concentration of Estazolam. Risk C: Monitor therapy
Estrogen Derivatives: CYP3A4 Inducers (Strong) may decrease the serum concentration of Estrogen Derivatives. Risk C: Monitor therapy
Eszopiclone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Eszopiclone. Risk C: Monitor therapy
Ethosuximide: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ethosuximide. Risk C: Monitor therapy
Etizolam: CYP3A4 Inducers (Strong) may decrease the serum concentration of Etizolam. Risk C: Monitor therapy
Etoposide: CYP3A4 Inducers (Strong) may decrease the 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
Etoposide Phosphate: CYP3A4 Inducers (Strong) may decrease the 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
Etoricoxib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Etoricoxib. Risk C: Monitor therapy
Etravirine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Etravirine. Risk X: Avoid combination
Everolimus: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Evogliptin. Risk C: Monitor therapy
Exemestane: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Fedratinib. Risk X: Avoid combination
Felbamate: CYP3A4 Inducers (Strong) may decrease the serum concentration of Felbamate. Risk C: Monitor therapy
Felodipine: CYP3A4 Inducers (Strong) may decrease the 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 the 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 the serum concentration of FentaNYL. Risk C: Monitor therapy
Fesoterodine: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Fesoterodine. Risk C: Monitor therapy
Fexinidazole: May enhance the QTc-prolonging effect of Encorafenib. Encorafenib may increase serum concentrations of the active metabolite(s) of Fexinidazole. Risk X: Avoid combination
Finerenone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Finerenone. Risk X: Avoid combination
Flibanserin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Flibanserin. Risk X: Avoid combination
Fluorouracil Products: May enhance the QTc-prolonging effect 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 therapy
Fosamprenavir: May increase the serum concentration of Encorafenib. Encorafenib may decrease the 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 the serum concentration of Fosaprepitant. Specifically, CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite aprepitant. Risk X: Avoid combination
Fosnetupitant: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Fosnetupitant. Risk X: Avoid combination
Fostamatinib: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Fostamatinib. Risk X: Avoid combination
Fostemsavir: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Fostemsavir. Risk X: Avoid combination
Fruquintinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Fruquintinib. Risk X: Avoid combination
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Futibatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Futibatinib. Risk C: Monitor therapy
Ganaxolone: CYP3A4 Inducers (Strong) may decrease the 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 the 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 concentrations of the active metabolite(s) of Gemigliptin. CYP3A4 Inducers (Strong) may decrease the serum concentration of Gemigliptin. Risk X: Avoid combination
Gepirone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Gepirone. Risk X: Avoid combination
Gilteritinib: Encorafenib may enhance the QTc-prolonging effect of Gilteritinib. Encorafenib may decrease the 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 therapy
Glasdegib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Glasdegib. Risk X: Avoid combination
Glecaprevir and Pibrentasvir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor therapy
Grapefruit Juice: May increase the serum concentration of Encorafenib. Risk X: Avoid combination
GuanFACINE: CYP3A4 Inducers (Strong) may decrease the 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 enhance the QTc-prolonging effect of Haloperidol. Encorafenib may decrease the 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 therapy
Hormonal Contraceptives: Encorafenib may decrease the serum concentration of Hormonal Contraceptives. Risk X: Avoid combination
HYDROcodone: CYP3A4 Inducers (Strong) may decrease the serum concentration of HYDROcodone. Risk C: Monitor therapy
Hydrocortisone (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Hydrocortisone (Systemic). Risk C: Monitor therapy
Ibrexafungerp: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ibrexafungerp. Risk X: Avoid combination
Ibrutinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ibrutinib. Risk X: Avoid combination
Idelalisib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Idelalisib. Risk X: Avoid combination
Ifosfamide: CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Ifosfamide. CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. Risk C: Monitor therapy
Imatinib: Encorafenib may decrease the serum concentration of Imatinib. Imatinib may increase the 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 the serum concentration of Encorafenib. Encorafenib may decrease the 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
Infigratinib: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Infigratinib. CYP3A4 Inducers (Strong) may decrease the serum concentration of Infigratinib. Risk X: Avoid combination
Irinotecan Products: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, serum concentrations of SN-38 may be reduced. CYP3A4 Inducers (Strong) may decrease the serum concentration of Irinotecan Products. 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 serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inducers (Strong) may decrease isavuconazole serum concentrations. Risk X: Avoid combination
Isradipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Isradipine. Risk C: Monitor therapy
Istradefylline: CYP3A4 Inducers (Strong) may decrease the serum concentration of Istradefylline. Risk X: Avoid combination
Itraconazole: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Itraconazole. CYP3A4 Inducers (Strong) may decrease the serum concentration of Itraconazole. Risk X: Avoid combination
Ivabradine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ivabradine. Risk X: Avoid combination
Ivacaftor: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ivacaftor. Risk X: Avoid combination
Ivosidenib: Encorafenib may enhance the QTc-prolonging effect of Ivosidenib. Encorafenib may decrease the serum concentration of Ivosidenib. Risk X: Avoid combination
Ixabepilone: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Ixazomib. Risk X: Avoid combination
Ketamine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ketamine. Risk C: Monitor therapy
Ketoconazole (Systemic): May increase the serum concentration of Encorafenib. Encorafenib may decrease the 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 the serum concentration of Lacidipine. Risk C: Monitor therapy
Lapatinib: CYP3A4 Inducers (Strong) may decrease the 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 the 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
Lefamulin: Encorafenib may decrease the serum concentration of Lefamulin. Lefamulin may increase the serum concentration of Encorafenib. Risk X: Avoid combination
Lefamulin (Intravenous): CYP3A4 Inducers (Strong) may decrease the 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
Lemborexant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lemborexant. Risk X: Avoid combination
Lenacapavir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lenacapavir. Risk X: Avoid combination
Leniolisib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Leniolisib. Risk X: Avoid combination
Lercanidipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lercanidipine. Risk C: Monitor therapy
Leuprolide and Norethindrone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Leuprolide and Norethindrone. Specifically, norethindrone concentrations may be decreased. Risk C: Monitor therapy
Levamlodipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Levamlodipine. Risk C: Monitor therapy
Levoketoconazole: May enhance the QTc-prolonging effect of Encorafenib. Encorafenib may decrease the serum concentration of Levoketoconazole. Levoketoconazole may increase the serum concentration of Encorafenib. Risk X: Avoid combination
Levomethadone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Levomethadone. Risk C: Monitor therapy
Levonorgestrel (IUD): CYP3A4 Inducers (Strong) may diminish the therapeutic effect of Levonorgestrel (IUD). CYP3A4 Inducers (Strong) may decrease the serum concentration of Levonorgestrel (IUD). Risk C: Monitor therapy
Lidocaine (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Lidocaine (Systemic). Risk C: Monitor therapy
LinaGLIPtin: CYP3A4 Inducers (Strong) may decrease the 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: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lonafarnib. Risk X: Avoid combination
Lopinavir: May increase the serum concentration of Encorafenib. Encorafenib may decrease the 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 enhance the hepatotoxic effect of Lorlatinib. CYP3A4 Inducers (Strong) may decrease the serum concentration of Lorlatinib. Risk X: Avoid combination
Lovastatin: Encorafenib may decrease the serum concentration of Lovastatin. Encorafenib may increase the serum concentration of Lovastatin. Risk C: Monitor therapy
Lumacaftor and Ivacaftor: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lumacaftor and Ivacaftor. Specifically, the serum concentration of ivacaftor may be decreased. Risk X: Avoid combination
Lumateperone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lumateperone. Risk X: Avoid combination
Lurasidone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lurasidone. Risk X: Avoid combination
Lurbinectedin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lurbinectedin. Risk X: Avoid combination
Macimorelin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Macimorelin. Risk X: Avoid combination
Macitentan: CYP3A4 Inducers (Strong) may decrease the serum concentration of Macitentan. Risk X: Avoid combination
Manidipine: CYP3A4 Inducers (Strong) may decrease the 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 the 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 the serum concentration of Maribavir. Risk X: Avoid combination
Mavacamten: CYP3A4 Inducers (Strong) may decrease the serum concentration of Mavacamten. Risk X: Avoid combination
Mefloquine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Mefloquine. Risk C: Monitor therapy
Meperidine: CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Meperidine. Specifically, concentrations of normeperidine, the CNS stimulating metabolite, may be increased. CYP3A4 Inducers (Strong) may decrease the serum concentration of Meperidine. Risk C: Monitor therapy
Methadone: Encorafenib may enhance the QTc-prolonging effect of Methadone. Encorafenib may decrease the 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 the serum concentration of Methylergonovine. Risk C: Monitor therapy
MethylPREDNISolone: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Mianserin. Risk C: Monitor therapy
Midazolam: CYP3A4 Inducers (Strong) may decrease the serum concentration of Midazolam. Risk C: Monitor therapy
Midostaurin: Encorafenib may enhance the QTc-prolonging effect of Midostaurin. Encorafenib may decrease the serum concentration of Midostaurin. Risk X: Avoid combination
MiFEPRIStone: May increase the serum concentration of Encorafenib. Encorafenib may decrease the 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 the serum concentration of Mirabegron. Risk C: Monitor therapy
Mirodenafil: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Mirtazapine. Risk C: Monitor therapy
Mitapivat: CYP3A4 Inducers (Strong) may decrease the serum concentration of Mitapivat. Risk X: Avoid combination
Mobocertinib: Encorafenib may enhance the QTc-prolonging effect of Mobocertinib. Encorafenib may decrease the serum concentration of Mobocertinib. Risk X: Avoid combination
Momelotinib: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Momelotinib. Risk C: Monitor therapy
Naldemedine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Naldemedine. Risk X: Avoid combination
Naloxegol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Naloxegol. Risk X: Avoid combination
Nateglinide: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nateglinide. Risk C: Monitor therapy
Nelfinavir: Encorafenib may decrease the serum concentration of Nelfinavir. Nelfinavir may increase the 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 the serum concentration of Neratinib. Risk X: Avoid combination
Netupitant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Netupitant. Risk X: Avoid combination
Nevirapine: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of NiCARdipine. Risk C: Monitor therapy
NIFEdipine: CYP3A4 Inducers (Strong) may decrease the 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 enhance the QTc-prolonging effect of Nilotinib. Nilotinib may increase the serum concentration of Encorafenib. Encorafenib may decrease the serum concentration of Nilotinib. Risk X: Avoid combination
Nilvadipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nilvadipine. Risk C: Monitor therapy
NiMODipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of NiMODipine. Risk X: Avoid combination
Nintedanib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nintedanib. Risk C: Monitor therapy
Nirmatrelvir and Ritonavir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nirmatrelvir and Ritonavir. Risk X: Avoid combination
Nirogacestat: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nirogacestat. Risk X: Avoid combination
Nisoldipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nisoldipine. Risk X: Avoid combination
Nitrazepam: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nitrazepam. Risk C: Monitor therapy
Nitrendipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nitrendipine. Risk C: Monitor therapy
OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors): Encorafenib may increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
OLANZapine: May enhance the QTc-prolonging effect 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 therapy
Olaparib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Olaparib. Risk X: Avoid combination
Oliceridine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Oliceridine. Risk C: Monitor therapy
Olmutinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Olmutinib. Risk C: Monitor therapy
Olutasidenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Olutasidenib. Risk X: Avoid combination
Omaveloxolone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Omaveloxolone. Risk X: Avoid combination
Ondansetron: May enhance the QTc-prolonging effect 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 therapy
Ondansetron: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ondansetron. Risk C: Monitor therapy
Orelabrutinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Orelabrutinib. Risk X: Avoid combination
Osilodrostat: CYP3A4 Inducers (Strong) may decrease the serum concentration of Osilodrostat. Risk C: Monitor therapy
Osimertinib: May enhance the QTc-prolonging effect of Encorafenib. Encorafenib may decrease the 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 the serum concentration of OXcarbazepine. Specifically, the concentrations of the 10-monohydroxy active metabolite of oxcarbazepine may be decreased. Risk C: Monitor therapy
OxyCODONE: CYP3A4 Inducers (Strong) may decrease the serum concentration of OxyCODONE. Risk C: Monitor therapy
PACLitaxel (Conventional): CYP3A4 Inducers (Strong) may decrease the serum concentration of PACLitaxel (Conventional). Risk C: Monitor therapy
PACLitaxel (Protein Bound): CYP3A4 Inducers (Strong) may decrease the serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor therapy
Pacritinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pacritinib. Risk X: Avoid combination
Palbociclib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Palbociclib. Risk X: Avoid combination
Palovarotene: CYP3A4 Inducers (Strong) may decrease the serum concentration of Palovarotene. Risk X: Avoid combination
Panobinostat: CYP3A4 Inducers (Strong) may decrease the serum concentration of Panobinostat. Risk X: Avoid combination
PAZOPanib: Encorafenib may enhance the QTc-prolonging effect of PAZOPanib. Encorafenib may increase the serum concentration of PAZOPanib. Risk X: Avoid combination
Pemigatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pemigatinib. Risk X: Avoid combination
Pentamidine (Systemic): May enhance the QTc-prolonging effect 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 therapy
Perampanel: CYP3A4 Inducers (Strong) may decrease the 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
Pexidartinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pexidartinib. Risk X: Avoid combination
Pimavanserin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pimavanserin. Risk X: Avoid combination
Pimozide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination
Piperaquine: May enhance the QTc-prolonging effect of Encorafenib. Encorafenib may decrease the serum concentration of Piperaquine. Risk X: Avoid combination
Pirtobrutinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pirtobrutinib. Risk X: Avoid combination
Pitolisant: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Polatuzumab Vedotin. Exposure to unconjugated MMAE, the cytotoxic small molecule component of polatuzumab vedotin, may be decreased. Risk C: Monitor therapy
PONATinib: CYP3A4 Inducers (Strong) may decrease the 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 the 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 combination
Pralsetinib: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Praziquantel. Risk X: Avoid combination
PrednisoLONE (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of PrednisoLONE (Systemic). Risk C: Monitor therapy
PredniSONE: CYP3A4 Inducers (Strong) may decrease the serum concentration of PredniSONE. Risk C: Monitor therapy
Pretomanid: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pretomanid. Risk X: Avoid combination
Propafenone: Encorafenib may enhance the QTc-prolonging effect of Propafenone. Encorafenib may decrease the 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 therapy
QT-prolonging Agents (Highest Risk): Encorafenib may enhance the QTc-prolonging effect 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 enhance the QTc-prolonging effect 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 therapy
QT-prolonging Antipsychotics (Moderate Risk): Encorafenib may enhance the QTc-prolonging effect 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 therapy
QT-prolonging Class IC Antiarrhythmics (Moderate Risk): Encorafenib may enhance the QTc-prolonging effect 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 therapy
QT-Prolonging Inhalational Anesthetics (Moderate Risk): QT-prolonging Kinase Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect 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 therapy
QT-prolonging Miscellaneous Agents (Moderate Risk): Encorafenib may enhance the QTc-prolonging effect 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 therapy
QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): Encorafenib may enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the 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 enhance the QTc-prolonging effect 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 therapy
QUEtiapine: Encorafenib may enhance the QTc-prolonging effect of QUEtiapine. Encorafenib may decrease the 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 enhance the QTc-prolonging effect of QuiNIDine. Encorafenib may decrease the 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 enhance the QTc-prolonging effect of QuiNINE. Encorafenib may decrease the 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 enhance the QTc-prolonging effect of Quizartinib. Encorafenib may decrease the serum concentration of Quizartinib. Risk X: Avoid combination
Radotinib: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Ramelteon. Risk C: Monitor therapy
Ranolazine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ranolazine. Risk X: Avoid combination
Reboxetine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Reboxetine. Risk C: Monitor therapy
Regorafenib: CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Regorafenib. CYP3A4 Inducers (Strong) may decrease the serum concentration of Regorafenib. Risk X: Avoid combination
Repaglinide: CYP3A4 Inducers (Strong) may decrease the serum concentration of Repaglinide. Risk C: Monitor therapy
Repotrectinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Repotrectinib. Risk X: Avoid combination
Revefenacin: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentrations of the active metabolite(s) of Revefenacin. Risk X: Avoid combination
Ribociclib: May enhance the QTc-prolonging effect of Encorafenib. Encorafenib may decrease the serum concentration of Ribociclib. Ribociclib may increase the serum concentration of Encorafenib. Risk X: Avoid combination
Rifabutin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Rifabutin. Risk C: Monitor therapy
Rilpivirine: CYP3A4 Inducers (Strong) may decrease the 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 combination
Rimegepant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Rimegepant. Risk X: Avoid combination
Riociguat: CYP3A4 Inducers (Strong) may decrease the serum concentration of Riociguat. Risk C: Monitor therapy
Ripretinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ripretinib. Risk X: Avoid combination
RisperiDONE: May enhance the QTc-prolonging effect of Encorafenib. Encorafenib may decrease the 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 the serum concentration of Ritlecitinib. Risk X: Avoid combination
Ritonavir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ritonavir. Risk X: Avoid combination
Rivaroxaban: CYP3A4 Inducers (Strong) may decrease the 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 concentrations of the active metabolite(s) of Roflumilast (Systemic). CYP3A4 Inducers (Strong) may decrease the serum concentration of Roflumilast (Systemic). Risk X: Avoid combination
Rolapitant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Rolapitant. Risk X: Avoid combination
RomiDEPsin: CYP3A4 Inducers (Strong) may decrease the serum concentration of RomiDEPsin. Risk X: Avoid combination
Rosuvastatin: BCRP/ABCG2 Inhibitors may increase the serum concentration of Rosuvastatin. Risk C: Monitor therapy
Ruxolitinib (Systemic): CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Ruxolitinib (Systemic). CYP3A4 Inducers (Strong) may decrease the serum concentration of Ruxolitinib (Systemic). Risk C: Monitor therapy
Samidorphan: CYP3A4 Inducers (Strong) may decrease the serum concentration of Samidorphan. Risk X: Avoid combination
Saquinavir: Encorafenib may enhance the QTc-prolonging effect of Saquinavir. Saquinavir may increase the serum concentration of Encorafenib. Encorafenib may decrease the 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 the serum concentration of SAXagliptin. Risk C: Monitor therapy
Selpercatinib: Encorafenib may enhance the QTc-prolonging effect of Selpercatinib. Encorafenib may decrease the serum concentration of Selpercatinib. Risk X: Avoid combination
Selumetinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Selumetinib. Risk X: Avoid combination
Sertindole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination
Sertraline: CYP3A4 Inducers (Strong) may decrease the serum concentration of Sertraline. Risk C: Monitor therapy
Sildenafil: CYP3A4 Inducers (Strong) may decrease the serum concentration of Sildenafil. Risk C: Monitor therapy
Simeprevir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Simeprevir. Risk X: Avoid combination
Simvastatin: Encorafenib may increase the serum concentration of Simvastatin. Encorafenib may decrease the serum concentration of Simvastatin. Risk C: Monitor therapy
Sirolimus (Conventional): CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Sirolimus (Protein Bound). Risk X: Avoid combination
Solifenacin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Solifenacin. Risk C: Monitor therapy
Sonidegib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Sonidegib. Risk X: Avoid combination
SORAfenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of SORAfenib. Risk X: Avoid combination
Sotorasib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Sotorasib. Risk X: Avoid combination
Sparsentan: CYP3A4 Inducers (Strong) may decrease the serum concentration of Sparsentan. Risk X: Avoid combination
Stiripentol: CYP3A4 Inducers (Strong) may decrease the 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 the 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 enhance the QTc-prolonging effect of SUNItinib. Encorafenib may decrease the 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 the serum concentration of Suvorexant. Risk C: Monitor therapy
Tacrolimus (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Tacrolimus (Systemic). Management: Monitor for decreased tacrolimus concentrations and effects when combined with strong CYP3A4 inducers. Tacrolimus dose increases will likely be needed during concomitant use. Risk D: Consider therapy modification
Tadalafil: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Talazoparib. Risk C: Monitor therapy
Tamoxifen: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Tamoxifen. CYP3A4 Inducers (Strong) may decrease the serum concentration of Tamoxifen. Risk X: Avoid combination
Tasimelteon: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tasimelteon. Risk X: Avoid combination
Taurursodiol: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Taurursodiol. Risk X: Avoid combination
Tazemetostat: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tazemetostat. Risk X: Avoid combination
Temsirolimus: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Temsirolimus. Specifically, concentrations of sirolimus may be decreased. CYP3A4 Inducers (Strong) may decrease the serum concentration of Temsirolimus. 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 the serum concentration of Teniposide. Risk C: Monitor therapy
Tetrahydrocannabinol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tetrahydrocannabinol. Risk C: Monitor therapy
Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inducers (Strong) may decrease the 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
Tezacaftor and Ivacaftor: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tezacaftor and Ivacaftor. Risk X: Avoid combination
Thiotepa: CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Thiotepa. CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of TiaGABine. Risk C: Monitor therapy
Ticagrelor: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inducers (Strong) may decrease the serum concentration of Ticagrelor. Risk X: Avoid combination
Tipranavir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tipranavir. Risk C: Monitor therapy
Tivozanib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tivozanib. Risk X: Avoid combination
Tofacitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tofacitinib. Risk X: Avoid combination
Tolvaptan: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tolvaptan. Risk X: Avoid combination
Topotecan: BCRP/ABCG2 Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination
Toremifene: May enhance the QTc-prolonging effect of Encorafenib. Encorafenib may decrease serum concentrations of the active metabolite(s) of Toremifene. Encorafenib may decrease the serum concentration of Toremifene. Risk X: Avoid combination
Trabectedin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Trabectedin. Risk X: Avoid combination
TraMADol: CYP3A4 Inducers (Strong) may decrease the serum concentration of TraMADol. Risk C: Monitor therapy
TraZODone: CYP3A4 Inducers (Strong) may decrease the serum concentration of TraZODone. Management: Consider increasing the trazodone dose during coadministration with strong CYP3A4 inducers. Risk D: Consider therapy modification
Triamcinolone (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Triamcinolone (Systemic). Risk C: Monitor therapy
Triazolam: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Tropisetron. Risk C: Monitor therapy
Tucatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tucatinib. Risk X: Avoid combination
Ubrogepant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ubrogepant. Risk X: Avoid combination
Udenafil: CYP3A4 Inducers (Strong) may decrease the serum concentration of Udenafil. Risk C: Monitor therapy
Ulipristal: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ulipristal. Risk X: Avoid combination
Upadacitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Upadacitinib. Risk X: Avoid combination
Valbenazine: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Valbenazine. CYP3A4 Inducers (Strong) may decrease the serum concentration of Valbenazine. Risk X: Avoid combination
Vandetanib: Encorafenib may enhance the QTc-prolonging effect of Vandetanib. Encorafenib may increase serum concentrations of the active metabolite(s) of Vandetanib. Encorafenib may decrease the serum concentration of Vandetanib. Risk X: Avoid combination
Velpatasvir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Velpatasvir. Risk X: Avoid combination
Vemurafenib: Encorafenib may enhance the QTc-prolonging effect of Vemurafenib. Encorafenib may decrease the 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 the serum concentration of Venetoclax. Risk X: Avoid combination
Verapamil: May increase the serum concentration of Encorafenib. Encorafenib may decrease the 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 the 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 the serum concentration of VinCRIStine. Risk C: Monitor therapy
VinCRIStine (Liposomal): CYP3A4 Inducers (Strong) may decrease the serum concentration of VinCRIStine (Liposomal). Risk X: Avoid combination
Vinflunine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vinflunine. Risk X: Avoid combination
Vinorelbine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vinorelbine. Risk C: Monitor therapy
Voclosporin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Voclosporin. Risk X: Avoid combination
Vonoprazan: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vonoprazan. Risk X: Avoid combination
Vorapaxar: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vorapaxar. Risk X: Avoid combination
Voriconazole: Encorafenib may enhance the QTc-prolonging effect of Voriconazole. Voriconazole may increase the serum concentration of Encorafenib. Encorafenib may decrease the 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 the 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 the 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 the serum concentration of Voxilaprevir. Risk X: Avoid combination
Voxilaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Voxilaprevir. Risk X: Avoid combination
Zaleplon: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Zanubrutinib. Risk X: Avoid combination
Zavegepant: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Zavegepant. Risk X: Avoid combination
Ziprasidone: Encorafenib may enhance the QTc-prolonging effect of Ziprasidone. Encorafenib may decrease the 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 the serum concentration of Zolpidem. Risk C: Monitor therapy
Zonisamide: CYP3A4 Inducers (Strong) may decrease the serum concentration of Zonisamide. Risk C: Monitor therapy
Zopiclone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Zopiclone. Risk C: Monitor therapy
Zuclopenthixol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Zuclopenthixol. Risk C: Monitor therapy
Zuranolone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Zuranolone. Risk X: Avoid combination
Coadministration with a grapefruit or grapefruit juice may increase encorafenib concentrations. Management: Avoid grapefruit or grapefruit juice while taking encorafenib.
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.
Based on its mechanism of action and on findings in animal reproduction studies, in utero exposure to encorafenib may cause fetal harm.
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.
BRAF mutation status: BRAF V600K or V600E mutation status in tumor specimens prior to treatment in melanoma. BRAF V600E mutation status in tumor specimens prior to treatment in colorectal cancer. 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]).
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).
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).
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