Note: Confirm BRAF V600 mutation status (in tumor specimens) prior to dabrafenib treatment initiation.
Melanoma, adjuvant treatment (with BRAF V600E or BRAF V600K mutation): Oral: 150 mg twice daily, approximately every 12 hours (in combination with trametinib); continue for up to 1 year in the absence of disease recurrence or unacceptable toxicity (Long 2017).
Melanoma, metastatic or unresectable (with BRAF V600E mutation): Oral: 150 mg twice daily, approximately every 12 hours (single-agent therapy); continue until disease progression or unacceptable toxicity.
Melanoma, metastatic or unresectable (with BRAF V600E or BRAF V600K mutation): Oral: 150 mg twice daily, approximately every 12 hours (in combination with trametinib); continue until disease progression or unacceptable toxicity.
Non-small cell lung cancer, metastatic (with BRAF V600E mutation): Oral: 150 mg twice daily, approximately every 12 hours (in combination with trametinib); continue until disease progression or unacceptable toxicity (Planchard 2016).
Thyroid cancer, anaplastic, locally advanced or metastatic (with BRAF V600E mutation): Oral: 150 mg twice daily, approximately every 12 hours (in combination with trametinib); continue until disease progression or unacceptable toxicity (Subbiah 2018).
Missed doses: A missed dose may be administered up to 6 hours prior to the next dose; do not administer if <6 hours until the next dose (do not make up for the missed dose).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
eGFR ≥15 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer’s labeling; however, pharmacokinetic differences with eGFR ≥15 mL/minute/1.73 m2 are not considered clinically relevant.
eGFR <15 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer’s labeling.
Mild impairment (bilirubin ≤ ULN and AST > ULN or bilirubin >1 to 1.5 times ULN and any AST): No dosage adjustment necessary.
Moderate (bilirubin >1.5 to 3 times ULN and any AST) to severe (bilirubin >3 to 10 times ULN and any AST) impairment: There are no dosage adjustments provided in the manufacturer's labeling (an appropriate dose has not been established); however, hepatic metabolism and biliary excretion are the primary elimination routes for dabrafenib, and exposure may be increased in patients with moderate to severe impairment.
Refer to adult dosing.
Note: If using combination therapy, refer to Trametinib monograph for recommended trametinib dose modifications.
|
Usual (initial) dose |
150 mg twice daily |
|
First dose reduction |
100 mg twice daily |
|
Second dose reduction |
75 mg twice daily |
|
Third dose reduction |
50 mg twice daily |
|
If unable to tolerate 50 mg twice daily, permanently discontinue dabrafenib. | |
Cardiotoxicity:
>20% absolute decrease in left ventricular ejection fraction (LVEF) from baseline and LVEF is below institutional lower limit of normal (LLN): Interrupt dabrafenib therapy until improved to at least the institutional LLN and absolute decrease to ≤10% (compared to baseline), then resume at the same dose.
Symptomatic heart failure: Interrupt dabrafenib therapy until improved to at least the institutional LLN and absolute decrease to ≤10% (compared to baseline), then resume at the same dose.
Dermatologic toxicity:
Intolerable grade 2 toxicity or grade 3 or 4 toxicity: Interrupt dabrafenib therapy for up to 3 weeks. If toxicity improves within 3 weeks, resume dabrafenib at a lower dose. If toxicity does not improve within 3 weeks following therapy interruption, permanently discontinue dabrafenib.
New primary cutaneous malignancy: No dabrafenib dosage modification is necessary.
Severe cutaneous adverse reactions: Permanently discontinue dabrafenib.
Fever:
Fever of 38°C to 40°C (100.4°F to 104°F), or first symptoms in case of recurrence: Interrupt dabrafenib therapy until fever resolves and then resume at the same or lower dose.
Fever >40°C (104°F) and/or fever complicated by rigors, hypotension, dehydration, or renal failure: Interrupt dabrafenib therapy until febrile reaction resolves for at least 24 hours. Resume at a lower dose or permanently discontinue. Administer secondary prophylactic antipyretics (secondary prophylaxis) upon dabrafenib resumption. Administer corticosteroids (eg, prednisone 10 mg daily or equivalent) for at least 5 days for second or subsequent pyrexia if temperature does not return to baseline within 3 days of onset of fever, or for fever associated with complications (eg, dehydration, renal failure, hypotension, or severe chills/rigors with no evidence of active infection).
Hemorrhage:
Grade 3 hemorrhage: Interrupt dabrafenib therapy. If hemorrhage improves, resume dabrafenib at a lower dose. If hemorrhage does not improve following therapy interruption, permanently discontinue dabrafenib.
Grade 4 hemorrhage: Permanently discontinue dabrafenib.
Hyperglycemia: Hyperglycemia may require initiation or optimization of insulin or oral hypoglycemic agent therapy (as clinically indicated).
Ocular toxicity:
Uveitis including iritis and iridocyclitis: Manage symptomatically with local ophthalmic therapy (steroid and mydriatic drops were used in clinical trials) while continuing dabrafenib. If mild or moderate uveitis does not respond to local ocular therapy (or for severe uveitis), interrupt dabrafenib therapy for up to 6 weeks. If improves to ≤ grade 1 within 6 weeks following therapy interruption, resume dabrafenib at the same or lower dose. If does not improve, or for persistent grade 2 or higher uveitis of >6-week duration, permanently discontinue dabrafenib.
Retinal pigment epithelial detachment: No dabrafenib dosage modification is necessary.
Retinal vein occlusion: No dabrafenib dosage modification is necessary.
Pulmonary toxicity: Interstitial lung disease or pneumonitis: No dabrafenib dosage modification is necessary.
Venous thromboembolism: Uncomplicated: No dabrafenib dosage modification is necessary.
Other toxicity:
Intolerable grade 2 or any grade 3 toxicity: Interrupt dabrafenib therapy until resolution to ≤ grade 1, then resume dabrafenib at a lower dose. If toxicity does not improve following therapy interruption, permanently discontinue dabrafenib.
Grade 4 toxicity (first occurrence): Interrupt dabrafenib therapy until resolution to ≤ grade 1, then resume dabrafenib at a lower dose or permanently discontinue
Grade 4 toxicity (recurrent after dosage reduction): Permanently discontinue dabrafenib.
New primary noncutaneous malignancy (RAS mutation-positive): Permanently discontinue dabrafenib.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Tafinlar: 50 mg, 75 mg
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Tafinlar: 50 mg, 75 mg
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/202806s019lbl.pdf#page=33, must be dispensed with this medication.
Oral: Administer at least 1 hour before or 2 hours after a meal; doses should be ~12 hours apart. Do not open, crush, or break capsules. When administered in combination with trametinib, take the once-daily dose of trametinib at the same time each day with either the morning or evening dose of dabrafenib.
Hazardous agent (NIOSH 2016 [group 1]).
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).
Melanoma:
Adjuvant treatment of melanoma (in combination with trametinib) in patients with a BRAF V600E or BRAF V600K mutation (as detected by an approved test), and lymph node involvement, following complete resection.
Treatment of unresectable or metastatic melanoma in patients with a BRAF V600E mutation (single agent therapy) or in patients with BRAF V600E or BRAF V600K mutations (in combination with trametinib); confirm BRAF V600E or BRAF V600K mutation status with an approved test prior to treatment.
Non-small cell lung cancer, metastatic: Treatment of metastatic non-small cell lung cancer (NSCLC) in patients with BRAF V600E mutation as detected by an approved test (in combination with trametinib).
Thyroid cancer, anaplastic, locally advanced or metastatic: Treatment of locally advanced or metastatic anaplastic thyroid cancer (ATC) (in combination with trametinib) in patients with BRAF V600E mutation and with no satisfactory locoregional treatment options.
Limitations of use: Dabrafenib is not indicated for treatment of wild-type BRAF melanoma, wild-type BRAF NSCLC, or wild-type BRAF ATC.
Dabrafenib may be confused with cobimetinib, dacomitinib, dasatinib, duvelisib, encorafenib, 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.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Dermatologic: Alopecia (22%), hyperkeratosis (37%), palmar-plantar erythrodysesthesia (20%), skin rash (17% to 27%), xeroderma (16%)
Endocrine & metabolic: Hyperglycemia (50% to 57%), hyponatremia (8% to 14%), hypophosphatemia (35% to 37%)
Gastrointestinal: Constipation (10% to 11%)
Hematologic & oncologic: Papilloma (27%), squamous cell carcinoma of skin (7% to 11%; grade 3: 4%)
Hepatic: Increased serum alkaline phosphatase (19% to 25%)
Nervous system: Chills (17%), headache (30% to 32%)
Neuromuscular & skeletal: Arthralgia (27% to 31%), back pain (12%), myalgia (11% to 13%)
Respiratory: Cough (12% to 21%)
Miscellaneous: Fever (28% to 33%)
1% to 10%:
Dermatologic: Bullous rash (<10%)
Gastrointestinal: Pancreatitis (<10%)
Hematologic & oncologic: Basal cell carcinoma of skin (4%), keratoacanthoma (4%), malignant melanoma (new primary: 1%), malignant neoplasm (≤1%)
Nervous system: Dizziness (7%)
Ophthalmic: Uveitis (1%)
Renal: Interstitial nephritis (<10%)
Respiratory: Nasopharyngitis (10%)
Miscellaneous: Febrile reaction (serious: 6%)
Frequency not defined: Nervous system: Fatigue
Postmarketing: Hematologic & oncologic: Kaposi's sarcoma (Parakh 2016)
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to dabrafenib or any component of the formulation.
Concerns related to adverse effects:
• Cardiomyopathy: Cardiomyopathy (a decrease in left ventricular ejection fraction [LVEF] ≥10% from baseline and below the institutional lower limit of normal) has occurred when used in combination with trametinib. Cardiomyopathy resolved in most patients receiving dabrafenib in combination with trametinib following dose adjustments, treatment interruption, and/or permanent discontinuation.
• Dermatologic toxicity: Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS), may occur when dabrafenib is administered with trametinib and could be life-threatening or fatal. Other serious skin toxicities have also occurred (rare).
• Febrile reactions: Serious febrile reactions and fever (any severity) complicated by hypotension, rigors or chills, dehydration, or renal failure were observed during dabrafenib single-agent therapy and when used in combination with trametinib. The incidence and severity of fevers were increased when dabrafenib was used in combination with trametinib. Some patients experienced multiple discrete episodes.
• Hemorrhage: Hemorrhage, defined as symptomatic bleeding in a critical area/organ, may occur with dabrafenib in combination with trametinib. Major bleeding events (some fatal) included intracranial, cerebral, brainstem, or GI hemorrhage.
• Hyperglycemia: Hyperglycemia may occur in patients with a history of diabetes while on therapy (either as a single agent or in combination with trametinib).
• Malignancy: Cutaneous squamous cell carcinoma (cuSCC) and keratoacanthoma and new primary melanoma were observed during single-agent dabrafenib therapy at an increased incidence compared with control therapy in clinical trials. When used in combination with trametinib, cuSCCs (including keratoacanthomas) were reported. Basal cell carcinoma (BCC) may also occur with combination or single-agent therapy. There are case reports of noncutaneous malignancies with monotherapy and combination therapy.
• Ocular toxicity: Uveitis, including iritis and iridocyclitis, has been reported with dabrafenib single-agent therapy and when used in combination with trametinib. Retinal pigment epithelial detachments (RPED) were seen in clinical trials when used in combination with trametinib (a known complication of trametinib single-agent therapy). Detachments may be bilateral and multifocal, and occurred in the central macular area or elsewhere in the retina.
• QT prolongation: QTcF prolongation >60 msec above baseline or to >500 msec was reported (rare), both as a single agent or when used in combination with trametinib.
• Venous thromboembolism: Venous thromboembolism events such as deep venous thrombosis (DVT) and pulmonary embolism (PE) (some fatal) may occur (rare) when dabrafenib is used in combination with trametinib. Patients should seek immediate medical attention with symptoms of DVT or PE (shortness of breath, chest pain, arm/leg swelling).
Concurrent drug therapy issues:
• Combination therapy with trametinib: Serious adverse reactions that occur with single-agent trametinib may also occur when dabrafenib is administered in combination with trametinib.
Special populations:
• Glucose-6-phosphate dehydrogenase deficiency: Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency may be at risk for hemolytic anemia when administered dabrafenib.
Other warnings/precautions:
• Appropriate use: Not indicated for treatment of patients with wild-type BRAF melanoma, NSCLC, or anaplastic thyroid cancer. Exposing wild-type cells to BRAF inhibitors such as dabrafenib 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 (in tumor specimens) with an approved test. Information on approved tests for detection of BRAF V600 mutations is available at http://www.fda.gov/CompanionDiagnostics. An approved test for BRAF V600E mutation detection in anaplastic thyroid cancer is not available.
Substrate of BCRP/ABCG2, CYP2C8 (major), CYP3A4 (major), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Induces CYP2C9 (weak), CYP3A4 (moderate)
Abemaciclib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Abemaciclib. Risk X: Avoid combination
Abiraterone Acetate: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Abiraterone Acetate. Risk C: Monitor therapy
Acalabrutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Acalabrutinib. Risk C: Monitor therapy
Alfentanil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Alfentanil. Management: If concomitant use of alfentanil and moderate 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
ALPRAZolam: CYP3A4 Inducers (Moderate) may decrease the serum concentration of ALPRAZolam. Risk C: Monitor therapy
AmLODIPine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of AmLODIPine. Risk C: Monitor therapy
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Antihepaciviral Combination Products: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Antihepaciviral Combination Products. Risk X: Avoid combination
Apremilast: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Apremilast. Risk C: Monitor therapy
Aprepitant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Aprepitant. Risk C: Monitor therapy
ARIPiprazole: CYP3A4 Inducers (Moderate) may decrease the serum concentration of ARIPiprazole. Risk C: Monitor therapy
ARIPiprazole Lauroxil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of ARIPiprazole Lauroxil. Risk C: Monitor therapy
Artemether and Lumefantrine: CYP3A4 Inducers (Moderate) 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 (Moderate) may decrease the serum concentration of Artemether and Lumefantrine. Risk C: Monitor therapy
Asunaprevir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Asunaprevir. Risk X: Avoid combination
Atogepant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Atogepant. Management: The recommended dose of atogepant is 30 mg once daily or 60 mg once daily when combined with strong or moderate CYP3A4 inducers. Risk D: Consider therapy modification
AtorvaSTATin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of AtorvaSTATin. Risk C: Monitor therapy
Avacopan: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Avacopan. Risk X: Avoid combination
Avanafil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Avanafil. Risk X: Avoid combination
Avapritinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Avapritinib. Risk X: Avoid combination
Axitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Axitinib. Risk X: Avoid combination
Bedaquiline: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Bedaquiline. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bedaquiline. Risk X: Avoid combination
Belumosudil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Belumosudil. Risk C: Monitor therapy
Benzhydrocodone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Benzhydrocodone. Specifically, the serum concentrations of hydrocodone may be reduced. Risk C: Monitor therapy
Bortezomib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bortezomib. Risk C: Monitor therapy
Bosutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bosutinib. Risk X: Avoid combination
Brexpiprazole: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Brexpiprazole. Risk C: Monitor therapy
Brigatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Brigatinib. Management: Avoid concurrent use of brigatinib with moderate CYP3A4 inducers when possible. If combined, increase the daily dose of brigatinib in 30 mg increments after 7 days of treatment with the current brigatinib dose, up to maximum of twice the dose. Risk D: Consider therapy modification
Buprenorphine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Buprenorphine. Risk C: Monitor therapy
BusPIRone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of BusPIRone. Risk C: Monitor therapy
Cabozantinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Cabozantinib. Risk C: Monitor therapy
Cannabis: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be decreased. Risk C: Monitor therapy
Capmatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Capmatinib. Risk X: Avoid combination
CarBAMazepine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of CarBAMazepine. Risk C: Monitor therapy
Clarithromycin: CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Clarithromycin. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Clarithromycin. Management: Consider alternative antimicrobial therapy for patients receiving a CYP3A4 inducer. Drugs that enhance the metabolism of clarithromycin into 14-hydroxyclarithromycin may alter the clinical activity of clarithromycin and impair its efficacy. Risk D: Consider therapy modification
Clindamycin (Systemic): CYP3A4 Inducers (Moderate) 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
CloZAPine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of CloZAPine. Risk C: Monitor therapy
Cobimetinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Cobimetinib. Risk X: Avoid combination
Codeine: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Codeine. Risk C: Monitor therapy
Copanlisib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Copanlisib. Risk C: Monitor therapy
Crizotinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Crizotinib. Risk C: Monitor therapy
CycloSPORINE (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
CYP2C8 Inhibitors (Moderate): May increase the serum concentration of Dabrafenib. Risk C: Monitor therapy
CYP2C8 Inhibitors (Strong): May increase the serum concentration of Dabrafenib. Management: Consider alternatives to strong CYP2C8 inhibitors in patients being treated with dabrafenib. If such a combination cannot be avoided, monitor closely for evidence of dabrafenib-related adverse effects. Risk D: Consider therapy modification
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Dabrafenib. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Dabrafenib. Management: Consider alternatives to any strong CYP3A4 inhibitor for patients being treated with dabrafenib. If such a combination cannot be avoided, monitor closely for evidence of dabrafenib-related adverse effects. Risk D: Consider therapy modification
Daclatasvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Daclatasvir. Management: Increase the daclatasvir dose to 90 mg once daily if used with a moderate CYP3A4 inducer. Risk D: Consider therapy modification
Dapsone (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Dapsone (Systemic). Risk C: Monitor therapy
Daridorexant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Daridorexant. Risk X: Avoid combination
Dasabuvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Dasabuvir. Risk X: Avoid combination
Deflazacort: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Deflazacort. Risk X: Avoid combination
Delavirdine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Delavirdine. Risk C: Monitor therapy
DexAMETHasone (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of DexAMETHasone (Systemic). Risk C: Monitor therapy
DiazePAM: CYP3A4 Inducers (Moderate) may decrease the serum concentration of DiazePAM. Risk C: Monitor therapy
DilTIAZem: CYP3A4 Inducers (Moderate) may decrease the serum concentration of DilTIAZem. Risk C: Monitor therapy
Disopyramide: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Disopyramide. Risk C: Monitor therapy
Doravirine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Doravirine. Risk C: Monitor therapy
DOXOrubicin (Conventional): CYP3A4 Inducers (Moderate) may decrease the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination
Dronabinol: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Dronabinol. Risk C: Monitor therapy
Dronedarone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Dronedarone. Risk C: Monitor therapy
Duvelisib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Duvelisib. Management: Avoid if possible. If used, on day 12 of combination increase duvelisib from 25 mg twice daily to 40 mg twice daily or from 15 mg twice daily to 25 mg twice daily. Resume prior duvelisib dose 14 days after stopping moderate CYP3A4 inducer. Risk D: Consider therapy modification
Dydrogesterone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Dydrogesterone. Risk C: Monitor therapy
Efavirenz: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Efavirenz. Risk C: Monitor therapy
Elbasvir and Grazoprevir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid combination
Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Risk C: Monitor therapy
Eliglustat: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Eliglustat. Risk C: Monitor therapy
Elvitegravir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Elvitegravir. Risk C: Monitor therapy
Encorafenib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Encorafenib. Risk X: Avoid combination
Entrectinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Entrectinib. Risk X: Avoid combination
Enzalutamide: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Enzalutamide. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Enzalutamide. Risk C: Monitor therapy
Erdafitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Erdafitinib. Management: Dose modifications of erdafitinib may be required. See full monograph for details. Risk D: Consider therapy modification
Erlotinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Erlotinib. Risk C: Monitor therapy
Estrogen Derivatives: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Estrogen Derivatives. Risk C: Monitor therapy
Etoposide: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Etoposide. Risk C: Monitor therapy
Etoposide Phosphate: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Etoposide Phosphate. Risk C: Monitor therapy
Etravirine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Etravirine. Risk C: Monitor therapy
Everolimus: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Everolimus. Risk C: Monitor therapy
Exemestane: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Exemestane. Risk C: Monitor therapy
Fedratinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Fedratinib. Risk X: Avoid combination
Felodipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Felodipine. Risk C: Monitor therapy
FentaNYL: CYP3A4 Inducers (Moderate) may decrease the serum concentration of FentaNYL. Risk C: Monitor therapy
Fexinidazole: CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Fexinidazole. Risk X: Avoid combination
Finerenone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Finerenone. Risk X: Avoid combination
Flibanserin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Flibanserin. Risk X: Avoid combination
Fosamprenavir: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Fosamprenavir. Risk C: Monitor therapy
Fosaprepitant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Fosaprepitant. Specifically, CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite aprepitant. Risk C: Monitor therapy
Fosnetupitant: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Fosnetupitant. Risk C: Monitor therapy
Fostamatinib: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Fostamatinib. Risk C: Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Gefitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Gefitinib. Risk C: Monitor therapy
Gemigliptin: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Gemigliptin. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Gemigliptin. Risk C: Monitor therapy
Glasdegib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Glasdegib. Management: Avoid use of glasdegib and moderate CYP3A4 inducers whenever possible. If combined, increase glasdegib dose from 100 mg daily to 200 mg daily or from 50 mg daily to 100 mg daily. Resume previous glasdegib dose 7 days after discontinuation of the inducer. Risk D: Consider therapy modification
Glecaprevir and Pibrentasvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor therapy
GuanFACINE: CYP3A4 Inducers (Moderate) 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: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy
Hormonal Contraceptives: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing a moderate CYP3A4 inducer to ensure contraceptive reliability. Risk D: Consider therapy modification
HYDROcodone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of HYDROcodone. Risk C: Monitor therapy
Hydrocortisone (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Hydrocortisone (Systemic). Risk C: Monitor therapy
Ibrexafungerp: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ibrexafungerp. Risk X: Avoid combination
Ibrutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ibrutinib. Risk C: Monitor therapy
Ifosfamide: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Ifosfamide. Risk C: Monitor therapy
Imatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Imatinib. Risk C: Monitor therapy
Indinavir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Indinavir. Management: Consider avoiding the combination of indinavir and moderate CYP3A4 inducers whenever possible due to the risk for decreased indinavir concentrations, reduced efficacy, and development of resistance. If combined, monitor for indinavir treatment failure. Risk D: Consider therapy modification
Infigratinib: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Infigratinib. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Infigratinib. Risk X: Avoid combination
Irinotecan Products: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, concentrations of SN-38 may be reduced. Risk C: Monitor therapy
Isavuconazonium Sulfate: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inducers (Moderate) may decrease isavuconazole serum concentrations. Risk C: Monitor therapy
Isradipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Isradipine. Risk C: Monitor therapy
Istradefylline: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Istradefylline. Risk C: Monitor therapy
Ivabradine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ivabradine. Risk X: Avoid combination
Ivacaftor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ivacaftor. Risk C: Monitor therapy
Ixabepilone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ixabepilone. Risk C: Monitor therapy
Ixazomib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ixazomib. Risk C: Monitor therapy
Ketamine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ketamine. Risk C: Monitor therapy
Lapatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lapatinib. Risk C: Monitor therapy
Larotrectinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Larotrectinib. Risk C: Monitor therapy
Lefamulin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin with moderate CYP3A4 inducers unless the benefits outweigh the risks. Risk D: Consider therapy modification
Lefamulin (Intravenous): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lefamulin (Intravenous). Management: Avoid concomitant use of lefamulin (intravenous) with moderate CYP3A4 inducers unless the benefits outweigh the risks. Risk D: Consider therapy modification
Lemborexant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lemborexant. Risk X: Avoid combination
Lercanidipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lercanidipine. Risk C: Monitor therapy
Levamlodipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Levamlodipine. Risk C: Monitor therapy
Levomethadone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Levomethadone. Risk C: Monitor therapy
LinaGLIPtin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of LinaGLIPtin. Risk C: Monitor therapy
Lonafarnib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lonafarnib. Risk X: Avoid combination
Lorlatinib: CYP3A4 Inducers (Moderate) may enhance the hepatotoxic effect of Lorlatinib. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lorlatinib. Management: Avoid use of lorlatinib with moderate CYP3A4 inducers. If such a combination must be used, increase lorlatinib to 125 mg daily. Risk D: Consider therapy modification
Lumacaftor and Ivacaftor: May decrease the serum concentration of CYP2C8 Substrates (High Risk with Inhibitors or Inducers). Lumacaftor and Ivacaftor may increase the serum concentration of CYP2C8 Substrates (High Risk with Inhibitors or Inducers). Risk C: Monitor therapy
Lumacaftor and Ivacaftor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lumacaftor and Ivacaftor. Risk C: Monitor therapy
Lumateperone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lumateperone. Risk X: Avoid combination
Lurasidone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lurasidone. Management: Monitor for decreased lurasidone effects if combined with moderate CYP3A4 inducers and consider increasing the lurasidone dose if coadministered with a moderate CYP3A4 inducer for 7 or more days. Risk D: Consider therapy modification
Lurbinectedin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lurbinectedin. Risk X: Avoid combination
Macitentan: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Macitentan. Risk C: Monitor therapy
Maraviroc: CYP3A4 Inducers (Moderate) 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 (Moderate) may decrease the serum concentration of Maribavir. Risk C: Monitor therapy
Mefloquine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Mefloquine. Risk C: Monitor therapy
Meperidine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Meperidine. Risk C: Monitor therapy
Methadone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Methadone. Risk C: Monitor therapy
MethylPREDNISolone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of MethylPREDNISolone. Risk C: Monitor therapy
Mianserin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Mianserin. Risk C: Monitor therapy
Midazolam: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Midazolam. Risk C: Monitor therapy
Midostaurin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Midostaurin. Risk C: Monitor therapy
Mirodenafil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Mirodenafil. Risk C: Monitor therapy
Mobocertinib: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Mobocertinib. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Mobocertinib. Risk X: Avoid combination
Naldemedine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Naldemedine. Risk C: Monitor therapy
Naloxegol: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Naloxegol. Risk C: Monitor therapy
Neratinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Neratinib. Risk X: Avoid combination
Netupitant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Netupitant. Risk C: Monitor therapy
Nevirapine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Nevirapine. Risk C: Monitor therapy
NIFEdipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of NIFEdipine. Risk C: Monitor therapy
Nilotinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Nilotinib. Risk C: Monitor therapy
Nilvadipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Nilvadipine. Risk C: Monitor therapy
NiMODipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of NiMODipine. Risk C: Monitor therapy
Nirmatrelvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Nirmatrelvir. Risk C: Monitor therapy
Nisoldipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Nisoldipine. Risk X: Avoid combination
Olaparib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Olaparib. Risk X: Avoid combination
Oliceridine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Oliceridine. Risk C: Monitor therapy
Olmutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Olmutinib. Risk C: Monitor therapy
Osimertinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Osimertinib. Risk C: Monitor therapy
OxyCODONE: CYP3A4 Inducers (Moderate) may decrease the serum concentration of OxyCODONE. Risk C: Monitor therapy
PACLitaxel (Conventional): CYP3A4 Inducers (Moderate) may decrease the serum concentration of PACLitaxel (Conventional). Risk C: Monitor therapy
PACLitaxel (Protein Bound): CYP3A4 Inducers (Moderate) may decrease the serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor therapy
Palbociclib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Palbociclib. Risk C: Monitor therapy
PAZOPanib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of PAZOPanib. Risk C: Monitor therapy
Pemigatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pemigatinib. Risk X: Avoid combination
Perampanel: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Perampanel. Management: Increase perampanel starting dose to 4 mg/day if used with moderate 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 (Moderate) may decrease the serum concentration of Pexidartinib. Risk C: Monitor therapy
Pimavanserin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pimavanserin. Risk X: Avoid combination
Piperaquine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Piperaquine. Risk C: Monitor therapy
PONATinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of PONATinib. Risk C: Monitor therapy
Pralsetinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pralsetinib. Risk C: Monitor therapy
Praziquantel: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Praziquantel. Management: Consider alternatives to this combination when possible. If combined, monitor for reduced praziquantel efficacy if combined with moderate CYP3A4 inducers. Risk D: Consider therapy modification
PrednisoLONE (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of PrednisoLONE (Systemic). Risk C: Monitor therapy
PredniSONE: CYP3A4 Inducers (Moderate) may decrease the serum concentration of PredniSONE. Risk C: Monitor therapy
Pretomanid: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pretomanid. Risk X: Avoid combination
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest 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: CYP3A4 Inducers (Moderate) may decrease the serum concentration of QUEtiapine. Risk C: Monitor therapy
QuiNIDine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of QuiNIDine. Risk C: Monitor therapy
QuiNINE: CYP3A4 Inducers (Moderate) may decrease the serum concentration of QuiNINE. Risk C: Monitor therapy
Ranolazine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ranolazine. Risk X: Avoid combination
Regorafenib: CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Regorafenib. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Regorafenib. Risk C: Monitor therapy
Repaglinide: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Repaglinide. Risk C: Monitor therapy
Ribociclib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ribociclib. Risk C: Monitor therapy
Rilpivirine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Rilpivirine. Risk C: Monitor therapy
Rimegepant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Rimegepant. Risk X: Avoid combination
Ripretinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ripretinib. Management: Avoid this combination if possible. If concomitant use is required, increase ripretinib to 150 mg twice daily. Decrease ripretinib to 150 mg once daily 14 days after stopping a moderate CYP3A4 inducer. Monitor patients for ripretinib response and toxicity Risk D: Consider therapy modification
RisperiDONE: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of RisperiDONE. CYP3A4 Inducers (Moderate) may decrease the serum concentration of RisperiDONE. Risk C: Monitor therapy
Roflumilast: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Roflumilast. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Roflumilast. Risk C: Monitor therapy
Rolapitant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Rolapitant. Risk C: Monitor therapy
Samidorphan: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Samidorphan. Risk C: Monitor therapy
Selpercatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Selpercatinib. Risk X: Avoid combination
Selumetinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Selumetinib. Risk X: Avoid combination
Sertraline: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Sertraline. Risk C: Monitor therapy
Sildenafil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Sildenafil. Risk C: Monitor therapy
Simeprevir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Simeprevir. Risk X: Avoid combination
Sirolimus (Conventional): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Sirolimus (Conventional). Risk C: Monitor therapy
Sirolimus (Protein Bound): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Sirolimus (Protein Bound). Risk C: Monitor therapy
Sonidegib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Sonidegib. Risk X: Avoid combination
SORAfenib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of SORAfenib. Risk C: Monitor therapy
Sotorasib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Sotorasib. Risk C: Monitor therapy
SUNItinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of SUNItinib. Risk C: Monitor therapy
Suvorexant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Suvorexant. Risk C: Monitor therapy
Tacrolimus (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Tadalafil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tadalafil. Risk C: Monitor therapy
Tamoxifen: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Tamoxifen. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tamoxifen. Risk C: Monitor therapy
Tasimelteon: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tasimelteon. Risk C: Monitor therapy
Tazemetostat: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tazemetostat. Risk X: Avoid combination
Temsirolimus: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Temsirolimus. Specifically, sirolimus concentrations may be decreased. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Temsirolimus. Risk C: Monitor therapy
Tetrahydrocannabinol: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tetrahydrocannabinol. Risk C: Monitor therapy
Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tetrahydrocannabinol and Cannabidiol. Risk C: Monitor therapy
Tezacaftor and Ivacaftor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tezacaftor and Ivacaftor. Risk C: Monitor therapy
Thiotepa: CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Thiotepa. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Thiotepa. Risk C: Monitor therapy
Ticagrelor: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ticagrelor. Risk C: Monitor therapy
Tivozanib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tivozanib. Risk C: Monitor therapy
Tofacitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tofacitinib. Risk C: Monitor therapy
Tolvaptan: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tolvaptan. Risk C: Monitor therapy
Toremifene: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Toremifene. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Toremifene. Risk C: Monitor therapy
Trabectedin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Trabectedin. Risk C: Monitor therapy
TraMADol: CYP3A4 Inducers (Moderate) may decrease the serum concentration of TraMADol. Risk C: Monitor therapy
Trametinib: May enhance the adverse/toxic effect of Dabrafenib. Risk C: Monitor therapy
TraZODone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of TraZODone. Risk C: Monitor therapy
Triazolam: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Triazolam. Risk C: Monitor therapy
Ubrogepant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 100 mg and second dose (if needed) of 100 mg when used with a moderate CYP3A4 inducer. Risk D: Consider therapy modification
Ulipristal: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ulipristal. Risk X: Avoid combination
Upadacitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Upadacitinib. Risk C: Monitor therapy
Valbenazine: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Valbenazine. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Valbenazine. Risk C: Monitor therapy
Vandetanib: CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Vandetanib. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vandetanib. Risk C: Monitor therapy
Velpatasvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Velpatasvir. Risk X: Avoid combination
Vemurafenib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vemurafenib. Risk C: Monitor therapy
Venetoclax: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Venetoclax. Risk X: Avoid combination
Verapamil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Verapamil. Risk C: Monitor therapy
Vilazodone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vilazodone. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): CYP2C9 Inducers (Weak) may decrease the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy
Voclosporin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Voclosporin. Risk X: Avoid combination
Vorapaxar: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vorapaxar. Risk X: Avoid combination
Vortioxetine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vortioxetine. Risk C: Monitor therapy
Voxelotor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Voxelotor. Management: Avoid concomitant use of voxelotor and moderate CYP3A4 inducers. If unavoidable, increase the voxelotor dose to 2,000 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 (Moderate) may decrease the serum concentration of Voxilaprevir. Risk X: Avoid combination
Zaleplon: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Zaleplon. Risk C: Monitor therapy
Zanubrutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Zanubrutinib. Risk X: Avoid combination
Zolpidem: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Zolpidem. Risk C: Monitor therapy
Zopiclone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Zopiclone. Risk C: Monitor therapy
Administration with a high-fat meal decreased Cmax and AUC by 51% and 31%, respectively, and delayed median Tmax by ~4 hours. Management: Administer 1 hour before or 2 hours after a meal.
Verify pregnancy status prior to treatment initiation in patients who could become pregnant. Dabrafenib may cause hormonal contraceptives to be ineffective. Patients who could become pregnant should use a highly effective nonhormonal contraceptive during dabrafenib therapy and for 2 weeks after the last dabrafenib dose. Males (including those with vasectomies) with pregnant partners or partners who could become pregnant should use condoms during dabrafenib treatment and for at least 2 weeks after the last dabrafenib dose.
Based on its mechanism of action and on findings in animal reproduction studies, in utero exposure to dabrafenib may cause fetal harm.
It is not known if dabrafenib 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 dabrafenib treatment and for 2 weeks after the last dabrafenib dose.
BRAFV600K or V600E mutation status (prior to treatment); serum glucose at baseline and as clinically necessary (particularly in patients with preexisting diabetes mellitus or hyperglycemia); electrolytes; renal function. Verify pregnancy status prior to treatment initiation (in patients who could become pregnant). Perform dermatologic evaluations prior to initiation, every 2 months during therapy, and for up to 6 months following discontinuation to assess for new cutaneous malignancies. Monitor for febrile drug reactions and signs/symptoms of infections; monitor serum creatinine and other evidence of renal function during and after serious fever. Monitor for signs/symptoms of uveitis (eg, eye pain, photophobia, vision changes). Monitor for signs/symptoms of hemolytic anemia in patients with glucose-6-phosphate dehydrogenase deficiency, new or worsening dermatologic toxicity (including severe cutaneous adverse reactions), and for noncutaneous malignancies.
For patients receiving combination therapy with trametinib: Hepatic function; CBC (baseline and periodically during therapy); assess left ventricular ejection fraction (by echocardiogram or multigated acquisition scan [MUGA] scan) at baseline, 1 month after therapy initiation, and then at 2- to 3-month intervals. Monitor for signs/symptoms of hemorrhage, venous thromboembolism, and interstitial lung disease. Monitor for signs/symptoms of retinal pigment epithelial detachment or retinal vein occlusion; promptly (within 24 hours) refer patients for ophthalmological evaluations if loss of vision or other visual disturbances occur; ophthalmic exams (including retinal evaluation) should be performed periodically during treatment with combination therapy.
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.
Dabrafenib selectively inhibits some mutated forms of the protein kinase B-raf (BRAF). BRAF V600 mutations result in constitutive activation of the BRAF pathway; through BRAF inhibition, dabrafenib inhibits tumor cell growth. The combination of dabrafenib and trametinib allows for greater inhibition of the MAPK pathway, resulting in BRAF V600 melanoma cell death (Flaherty 2012). Dabrafenib plus trametinib has been reported to synergistically inhibit cell growth in lung cancer cell lines which are BRAF V600E-mutant (Planchard 2016).
Absorption: Decreased with a high-fat meal (~1,000 calories; 58 to 75 grams of fat).
Distribution: 70.3 L.
Protein binding: 99.7% to plasma proteins.
Metabolism: Hepatic via CYP2C8 and CYP3A4 to hydroxy-dabrafenib (active) which is further metabolized via CYP3A4 oxidation to desmethyl-dabrafenib (active).
Bioavailability: 95%.
Half-life elimination: Parent drug: 8 hours; Hydroxy-dabrafenib (active metabolite): 10 hours; Desmethyl-dabrafenib (active metabolite): 21 to 22 hours; Carboxy-dabrafenib (21 to 22 hours).
Time to peak: 2 hours; delayed with a high-fat meal (~1,000 calories; 58 to 75 grams of fat).
Excretion: Feces (71%); urine (23%; metabolites only).
Clearance: 17 L/hour (single dose); 34.4 L/hour (after 2 weeks of twice-daily dosing).
Hepatic function impairment: Patients with moderate (bilirubin >1.5 to 3 times ULN and any AST) or severe (bilirubin >3 to 10 times ULN and any AST) hepatic impairment may have increased dabrafenib exposure.
Capsules (Tafinlar Oral)
50 mg (per each): $95.01
75 mg (per each): $122.44
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