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Tafinlar
Classes
Small Molecule Antineoplastic BRAF kinase Inhibitors
Administration
Hazardous Drugs Classification
NIOSH 2016 List: Group 1
NIOSH (Draft) 2020 List: Table 2
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use gloves. Cutting, crushing, or otherwise manipulating tablets/capsules will increase exposure.[
Emetic Risk
Moderate/High
Administer routine antiemetic prophylaxis prior to treatment.
Take dabrafenib at the same time each day, approximately 12 hours apart.
Take at least 1 hour before or 2 hours after a meal.
If a dose is missed, take it as soon as possible. If it is less than 6 hours before the next scheduled dose, skip the missed dose and take the next dose at the regular time.
If vomiting occurs after a dose, do not take an additional dose and take the next dose at the regular time.
Swallow whole; do not open, crush, or break capsules.
Do not use the capsules in those who weigh less than 26 kg or in children not able to swallow dabrafenib capsules whole.
Refer caregivers to the Instructions for Use provided with the medication on how to correctly prepare the tablets for oral suspension and give a dose of the oral suspension.
Tablets must be dissolved in water prior to administration; do not swallow whole, chew, or crush the tablets for oral suspension.
Preparation:
Calculate the number of tablets required to make the appropriate dose; add approximately 5 mL of water for 1 to 4 tablets and approximately 10 mL of water for 5 to 15 tablets in the provided cup.
Gently stir with the handle of a teaspoon until the tablets are fully dissolved; it may take at least 3 minutes for the tablets to dissolve.
The resulting suspension will be cloudy white.
Administration:
Give the suspension orally immediately after preparation using the cup or an oral dosing syringe; the suspension may also be given via a feeding tube.
Discard the suspension if it is not administered within 30 minutes after preparation.
Adverse Reactions
neutropenia / Delayed / 6.0-20.0
hyponatremia / Delayed / 0-17.0
lymphopenia / Delayed / 0-14.0
new primary malignancy / Delayed / 0-11.0
GI perforation / Delayed / 0-10.0
pancreatitis / Delayed / 0-10.0
interstitial nephritis / Delayed / 0-10.0
anemia / Delayed / 0-10.0
hyperglycemia / Delayed / 0-9.0
cardiomyopathy / Delayed / 0-9.0
leukopenia / Delayed / 0-8.0
hypophosphatemia / Delayed / 0-7.0
weight gain / Delayed / 0-7.0
elevated hepatic enzymes / Delayed / 0-6.0
fever / Early / 0-6.0
dyspnea / Early / 0-5.0
malaise / Early / 0-5.0
asthenia / Delayed / 0-5.0
fatigue / Early / 0-5.0
hyperkalemia / Delayed / 0-4.2
hypocalcemia / Delayed / 0-4.1
hypomagnesemia / Delayed / 0-4.1
rash / Early / 0-3.2
vomiting / Early / 0-3.2
back pain / Delayed / 0-3.0
bleeding / Early / 0-3.0
GI bleeding / Delayed / 0-3.0
diarrhea / Early / 0-2.2
hyperbilirubinemia / Delayed / 0-2.1
hypokalemia / Delayed / 0-2.1
hypoalbuminemia / Delayed / 2.1-2.1
uveitis / Delayed / 1.0-2.0
palmar-plantar erythrodysesthesia (hand and foot syndrome) / Delayed / 0-2.0
constipation / Delayed / 0-2.0
headache / Early / 0-1.5
xerosis / Delayed / 0-1.1
chills / Rapid / 0.5-1.1
hyperkeratosis / Delayed / 0-1.0
arthralgia / Delayed / 0-1.0
myalgia / Early / 0-1.0
nausea / Early / 0-1.0
renal failure (unspecified) / Delayed / 0-1.0
rhabdomyolysis / Delayed / 0-1.0
peripheral edema / Delayed / 0-0.7
thrombocytopenia / Delayed / 0-0.7
intracranial bleeding / Delayed / 0-0.6
dizziness / Early / 0-0.2
erythema multiforme / Delayed / Incidence not known
exfoliative dermatitis / Delayed / Incidence not known
retroperitoneal bleeding / Delayed / Incidence not known
heart failure / Delayed / Incidence not known
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
hemophagocytic lymphohistiocytosis / Delayed / Incidence not known
hypermagnesemia / Delayed / 0-32.0
edema / Delayed / 0-28.0
hypernatremia / Delayed / 0-27.0
lymphocytosis / Delayed / 0-24.0
bullous rash / Early / 0-10.0
colitis / Delayed / 0-10.0
stomatitis / Delayed / 0-10.0
sarcoidosis / Delayed / 0-10.0
peripheral neuropathy / Delayed / 0-7.0
blurred vision / Early / 0-6.0
hypotension / Rapid / 0-4.0
QT prolongation / Rapid / 0.8-3.8
dehydration / Delayed / 0-3.0
iritis / Delayed / Incidence not known
photophobia / Early / Incidence not known
bone pain / Delayed / Incidence not known
glossitis / Early / Incidence not known
oral ulceration / Delayed / Incidence not known
hematuria / Delayed / Incidence not known
hematoma / Early / Incidence not known
hemoptysis / Delayed / Incidence not known
cough / Delayed / 0-44.0
musculoskeletal pain / Early / 0-36.0
anorexia / Delayed / 0-29.0
abdominal pain / Early / 0-24.0
acneiform rash / Delayed / 0-23.0
infection / Delayed / 0-23.0
alopecia / Delayed / 0-22.0
epistaxis / Delayed / 0-16.0
pharyngitis / Delayed / 0-12.0
panniculitis / Delayed / 0-10.0
syncope / Early / 0-2.0
anxiety / Delayed / 0-1.4
ocular pain / Early / Incidence not known
maculopapular rash / Early / Incidence not known
vesicular rash / Delayed / Incidence not known
hypoesthesia / Delayed / Incidence not known
paresthesias / Delayed / Incidence not known
cheilitis / Delayed / Incidence not known
purpura / Delayed / Incidence not known
petechiae / Delayed / Incidence not known
Common Brand Names
Tafinlar
Dea Class
Rx
Description
Oral BRAF kinase inhibitor
Used in adults as a single agent for advanced melanoma and in combination with trametinib for melanoma, NSCLC, and anaplastic thyroid cancer and for other BRAF V600 mutation-positive solid tumors (1 year and older); used in pediatric patients 1 year and older for low-grade glioma
Monitor patients who have glucose-6-phosphate dehydrogenase deficiency for hemolytic anemia
Dosage And Indications
NOTE: Confirm the BRAF V600E or V600K mutation prior to starting therapy. Information on FDA-approved tests for the detection of BRAF V600 mutations is available at www.fda.gov/CompanionDiagnostics.
NOTE: Dabrafenib is not indicated in patients with wild-type BRAF melanoma.
NOTE: Dabrafenib has been designated as an orphan drug for the treatment of BRAF V600 mutation-positive melanoma by the FDA as a single-agent or in combination with trametinib. For the treatment of unresectable or metastatic malignant melanoma in patients with the BRAF V600E mutation, as a single agent. Oral dosage Adults
150 mg orally twice daily until disease progression. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Interruption of therapy and/or a dosage reduction may be necessary in patients who develop toxicity or intolerable side effects.[54802] Patients with previously untreated BRAF V600-mutated unresectable stage III or metastatic melanoma received oral dabrafenib (n = 187) or dacarbazine 1,000 mg/m2 IV every 3 weeks (n = 63) in a multinational, randomized, phase 3 study; prior therapy with interleukin-2 was permitted. At a median follow-up time of 5 months, the progression-free survival (PFS) time assessed by investigator review (IR) (primary endpoint) was significantly improved with dabrafenib compared with dacarbazine (5.1 months vs. 2.7 months; hazard ratio = 0.3; 95% CI, 0.18 to 0.51; p less than 0.0001); PFS results were confirmed on independent radiologic review (IRR).[54812] Dabrafenib was also studied in melanoma patients who had previously untreated brain metastases (cohort A) or progressive brain disease following prior local treatment for metastases (cohort B) in a multinational, phase 2 study. In cohort A, the overall intracranial response rates (OIRR) assessed by IR (primary endpoint) or IRR, respectively, were 39.2% or 20% in patients with a valine for glutamate substitution at position 600 BRAF mutation (BRAF V600glu; n = 74) and 6.7% or 0% in patients with a valine for lysine substitution at position 600 BRAF mutation (BRAF V600lys; n = 15); duration of responses were 20.1 months (BRAF V600glu) and 12.4 months (BRAF V600lys) by IR review. In cohort B, the OIRR assessed by IR or IRR, respectively, were 30.8% or 19% in patients with a BRAF V600glu mutation (n = 65) and 22.2% or 11% in patients with a BRAF V600lys mutation (n = 18); duration of responses were 28.1 months (BRAF V600glu) and 16.6 months (BRAF V600lys) by IR review. A third party blinded adjudication confirmed the IR assessments in 68% of cases. In patients with the BRAF V600glu mutation, the estimated 6-month overall survival (OS) rates were 61% in both cohort A and B. In patients with the BRAF V600lys mutation, the 6-month OS rates were 27% in cohort A and 41% in cohort B.[54811]
150 mg orally twice daily in combination with trametinib 2 mg orally once daily until disease progression. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Interruption of therapy and/or a dosage reduction may be necessary in patients who develop toxicity or intolerable side effects.[54802] Treatment with dabrafenib plus trametinib resulted in significantly improved median progression-free survival (PFS; 11.4 months vs. 7.3 months; hazard ratio (HR) = 0.56; 95% CI, 0.46 to 0.69; p less than 0.001) and overall survival (OS; median not reached vs. 17.2 months; HR = 0. 69; 95% CI, 0.53 to 0.89; p = 0.005) times compared with single-agent vemurafenib in previously untreated patients with unresectable stage IIIC or stage IV melanoma and BRAF V600E or V600K mutations in a planned interim analysis of a randomized, phase 3 study (n = 704; the COMBI-v study). This trial was stopped early based on the significantly improved OS data with combination therapy; cross-over from the vemurafenib to the combination arm was not allowed prior to the interim analysis.[58760] The median PFS (11 months vs. 8.8 months; HR = 0.67; 95% CI, 0.53 to 0.84; p = 0.0004) and OS (25.1 months vs. 18.7 months; HR = 0.71; 95% CI, 0.55 to 0.92; p = 0.0107) times were significantly improved with dabrafenib plus trametinib compared with dabrafenib plus placebo in previously untreated patients with unresectable stage IIIC or stage IV melanoma with BRAF V600E or V600K mutations in a randomized, double-blind, phase 3 study (n = 423; the COMBI-d study). Cross-over from the dabrafenib plus placebo arm to the combination therapy arm was not permitted at the primary analysis.[59946] At a median follow-up time of 22 months (range, 0 to 76 months), the median PFS and OS times were 11.1 months and 25.9 months, respectively, in a pooled analysis of patients with advanced melanoma who received dabrafenib and trametinib in the COMBI-d and COMBI-v trials (n = 563); the 5-year PFS and OS rates were 19% and 37%, respectively.[64436]
150 mg orally twice daily in combination with trametinib 2 mg orally once daily until disease progression was evaluated in a cohort of 76 patients in a multicenter, phase 2 trial. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Interruption of therapy and/or a dosage reduction may be necessary in patients who develop toxicity or intolerable side effects.
150 mg orally twice daily in combination with trametinib 2 mg orally once daily until disease recurrence or for up to 1 year was evaluated in a multinational, randomized, double-blind, placebo-controlled, phase 3 trial (n = 870; the COMBI-AD trial). Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Interruption of therapy and/or a dosage reduction may be necessary in patients who develop toxicity or intolerable side effects.
NOTE: Confirm the BRAF V600E mutation prior to starting therapy. Information on FDA-approved tests for the detection of BRAF V600 mutations is available at www.fda.gov/CompanionDiagnostics.
NOTE: Dabrafenib is not indicated in patients with wild-type BRAF NSCLC.
NOTE: Dabrafenib has been designated as an orphan drug for the treatment of BRAF mutation-positive NSCLC by the FDA as a single-agent or in combination with trametinib. For the treatment of metastatic BRAF V600E mutation-positive NSCLC, in combination with trametinib. Oral dosage Adults
150 mg PO twice daily in combination with trametinib (2 mg PO once daily) until disease progression. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Interruption of therapy and/or a dosage reduction may be necessary in patients who develop toxicity or intolerable side effects. The investigator-assessed overall response rate (ORR) was 61% (complete response [CR], 5%) following treatment with dabrafenib and trametinib in a cohort of patients with previously treated stage IV BRAF V600E-mutant NSCLC (n = 57) in a multinational, nonrandomized, 3-cohort, phase 2 trial; the ORR in previously untreated patients (n = 36) was 61% (CR, 8%). The median duration of response was 9 months.
NOTE: Confirm the BRAF V600E mutation prior to starting therapy. An FDA-approved test for the detection of BRAF V600E mutation in ATC is not currently available.
NOTE: Dabrafenib is not indicated in patients with wild-type BRAF ATC.
NOTE: Dabrafenib has been designated as an orphan drug for the treatment of BRAF mutation-positive ATC by the FDA in combination with trametinib. Oral dosage Adults
150 mg orally twice daily in combination with trametinib 2 mg orally once daily until disease progression was evaluated in a subgroup of patients with ATC in a multicenter, nonrandomized phase 2 clinical trial. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Interruption of therapy and/or a dosage reduction may be necessary in patients who develop toxicity or intolerable side effects. In a multicenter, noncomparative, 9-cohort, open-label trial, patients with advanced anaplastic thyroid cancer with a BRAF V600E mutation had an overall response rate of 53% (complete response, 6%) when treated with dabrafenib plus trametinib. The median duration of response was 13.6 months; 68% had a duration of response of at least 6 months, and 53% had a duration of response of at least 12 months.
NOTE: Trametinib is not indicated for treatment of patients with colorectal cancer due to known intrinsic resistance to BRAF inhibition.
For the treatment of unresectable or metastatic BRAF V600E-mutation positive solid tumors that have progressed after prior treatment and have no satisfactory alternative treatment options, in combination with trametinib.
NOTE: Patients should be selected based on the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment. An FDA-approved test for this mutation in solid tumors other than melanoma and NSCLC is not currently available.
Oral dosage (capsules)
NOTE: The recommended dosage of dabrafenib capsules has not been established in pediatric patients who weigh less than 26 kg.
150 mg PO twice daily in combination with trametinib 2 mg PO once daily until disease progression. Interruption of therapy, a dosage reduction, or discontinuation of therapy may be necessary in patients who develop toxicity. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Patients with selected BRAF V600E mutation-positive tumors (n = 137) in 2 single-arm, open-label, clinical trials (BRF117019 and NCI-MATCH) were treated with trametinib plus dabrafenib. Response rates varied widely depending on indication including biliary tract cancer (n = 48; 46%); high grade gliomas (n = 48; 33%) including glioblastoma (n = 32; 25%), anaplastic pleomorphic xanthoastrocytoma (n = 6; 67%), anaplastic astrocytoma (n = 5; 20%), and astroblastoma (n = 2; 100%); low grade gliomas (n = 14; 50%); low grade serous ovarian cancer (n = 5; 80%); and others.
Dosage is based on weight as follows: 26 to 37 kg, give 75 mg PO twice daily; 38 to 50 kg, give 100 mg PO twice daily; and 51 kg or more, give 150 mg PO twice daily. Administer in combination with trametinib until disease progression. Interruption of therapy, a dosage reduction, or discontinuation of therapy may be necessary in patients who develop toxicity. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In 2 cohorts of a multicenter, multicohort, open-label clinical trial (Study X2101), pediatric patients with refractory or recurrent BRAF V600E mutation-positive solid tumors were treated with dabrafenib (n = 48), including 34 patients with low-grade glioma and 2 patients with high grade glioma. The objective response rate was 25%, with a duration of at least 6 months for 78% of patients and at least 24 months for 44% of patients.
150 mg PO twice daily in combination with trametinib 2 mg PO once daily until disease progression. Interruption of therapy, a dosage reduction, or discontinuation of therapy may be necessary in patients who develop toxicity. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Patients with selected BRAF V600E mutation-positive tumors (n = 137) in 2 single-arm, open-label, clinical trials (BRF117019 and NCI-MATCH) were treated with trametinib plus dabrafenib. Response rates varied widely depending on indication including biliary tract cancer (n = 48; 46%); high grade gliomas (n = 48; 33%) including glioblastoma (n = 32; 25%), anaplastic pleomorphic xanthoastrocytoma (n = 6; 67%), anaplastic astrocytoma (n = 5; 20%), and astroblastoma (n = 2; 100%); low grade gliomas (n = 14; 50%); low grade serous ovarian cancer (n = 5; 80%); and others.
Dosage is based on weight as follows: 14 to 17 kg, give 40 mg twice daily; 18 to 21 kg, give 50 mg twice daily; 22 to 25 kg, give 60 mg twice daily; 26 to 29 kg, give 70 mg twice daily; 30 to 33 kg, give 80 mg twice daily; 34 to 37 kg, give 90 mg twice daily; 38 to 41 kg, give 100 mg twice daily; 42 to 45 kg, give 110 mg twice daily; 46 to 50 kg, give 130 mg twice daily; and 51 kg or more, give 150 mg twice daily. Administer in combination with trametinib until disease progression. Interruption of therapy, a dosage reduction, or discontinuation of therapy may be necessary in patients who develop toxicity. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In 2 cohorts of a multicenter, multicohort, open-label clinical trial (Study X2101), pediatric patients with refractory or recurrent BRAF V600E mutation-positive solid tumors were treated with dabrafenib (n = 48), including 34 patients with low-grade glioma and 2 patients with high grade glioma. The objective response rate was 25%, with a duration of at least 6 months for 78% of patients and at least 24 months for 44% of patients.
NOTE: Dabrafenib is designated as an orphan drug by the FDA for this indication.
For the treatment of BRAF V600E mutation-positive low-grade gliomas (LGG) in pediatric patients who require systemic therapy, in combination with trametinib.
NOTE: Patients should be selected based on the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment. An FDA-approved test for this mutation in LGG is not currently available.
Oral dosage (capsules)
NOTE: The recommended dosage of dabrafenib capsules has not been established in pediatric patients who weigh less than 26 kg.
Dosage is based on weight as follows: 26 to 37 kg, give 75 mg PO twice daily; 38 to 50 kg, give 100 mg PO twice daily; and 51 kg or more, give 150 mg PO twice daily. Administer in combination with trametinib until disease progression. Interruption of therapy, a dosage reduction, or discontinuation of therapy may be necessary in patients who develop toxicity. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. The overall response rate (primary endpoint evaluated by an independent review committee) was significantly improved (46.6% vs. 10.8%; p-value less than 0.001) in pediatric patients aged 1 to less than 18 years (median age, 9.5 years) with WHO grades 1 and 2 LGG who received dabrafenib plus trametinib (n = 73) compared with carboplatin plus vincristine (n = 37) as first systemic therapy in a randomized (2:1), phase 2/3 (TADPOLE) trial. The complete response rate was 2.7% in each treatment arm. The median duration of response was 23.7 months in the dabrafenib plus trametinib arm and not estimable in the carboplatin plus vincristine arm. At the primary analysis when all patients had completed at least 32 weeks of therapy, the median progression-free survival time was significantly improved in patients who received dabrafenib plus trametinib compared with carboplatin plus vincristine (20.1 months vs. 7.4 months; hazard ratio = 0.31; 95% CI, 0.17 to 0.55).
Dosage is based on weight as follows: 8 to 9 kg, give 20 mg twice daily; 10 to 13 kg, give 30 mg twice daily; 14 to 17 kg, give 40 mg twice daily; 18 to 21 kg, give 50 mg twice daily; 22 to 25 kg, give 60 mg twice daily; 26 to 29 kg, give 70 mg twice daily; 30 to 33 kg, give 80 mg twice daily; 34 to 37 kg, give 90 mg twice daily; 38 to 41 kg, give 100 mg twice daily; 42 to 45 kg, give 110 mg twice daily; 46 to 50 kg, give 130 mg twice daily; and 51 kg or more, give 150 mg twice daily. Administer in combination with trametinib until disease progression. Interruption of therapy, a dosage reduction, or discontinuation of therapy may be necessary in patients who develop toxicity. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. The overall response rate (primary endpoint evaluated by an independent review committee) was significantly improved (46.6% vs. 10.8%; p-value less than 0.001) in pediatric patients aged 1 to less than 18 years (median age, 9.5 years) with WHO grades 1 and 2 LGG who received dabrafenib plus trametinib (n = 73) compared with carboplatin plus vincristine (n = 37) as first systemic therapy in a randomized (2:1), phase 2/3 (TADPOLE) trial. The complete response rate was 2.7% in each treatment arm. The median duration of response was 23.7 months in the dabrafenib plus trametinib arm and not estimable in the carboplatin plus vincristine arm. At the primary analysis when all patients had completed at least 32 weeks of therapy, the median progression-free survival time was significantly improved in patients who received dabrafenib plus trametinib compared with carboplatin plus vincristine (20.1 months vs. 7.4 months; hazard ratio = 0.31; 95% CI, 0.17 to 0.55).
Dosing Considerations
No dabrafenib dosage adjustment is necessary in patients with mild hepatic impairment (bilirubin level at the upper limit of normal (ULN) or less and AST level greater than the ULN OR bilirubin level greater than 1- to 1.5-times the ULN and any AST level). Dabrafenib has not been studied in patients with moderate (bilirubin level greater than 1.5- to 3-times the ULN and any AST level) to severe (bilirubin level greater than 3- to 10-times the ULN and any AST level) hepatic impairment; hepatic and biliary secretion are the primary routes of dabrafenib elimination and exposure may be increased in these patients.[54802]
Renal ImpairmentNo dabrafenib dosage adjustment is necessary in patients with mild to moderate renal impairment (glomerular filtration rate (GFR), 30 to 89 mL/min/1.73 m2). Dabrafenib has not been studied in patients with severe renal impairment (GFR less than 30 mL/min/1.73 m2). Dabrafenib is highly bound to plasma proteins and is unlikely to be removed by hemodialysis.[54802]
Drug Interactions
Abemaciclib: (Major) Avoid coadministration of dabrafenib with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Abemaciclib is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer. Coadministration with other moderate CYP3A inducers is predicted to decrease the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 29% to 53%.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with dabrafenib can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If coadministration is necessary, monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal; consider increasing the dose of dihydrocodeine as needed. If dabrafenib is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Dabrafenib is a moderate inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with dabrafenib can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If dabrafenib is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Dabrafenib is a moderate CYP3A4 inducer.
Acetaminophen; Hydrocodone: (Moderate) Concomitant use of hydrocodone with dabrafenib can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If dabrafenib is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and dabrafenib is a moderate CYP3A4 inducer.
Acetaminophen; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with dabrafenib is necessary; consider increasing the dose of oxycodone as needed. If dabrafenib is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and dabrafenib is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Adagrasib: (Major) Avoid coadministration of dabrafenib and adagrasib due to increased dabrafenib exposure. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for dabrafenib adverse reactions including skin toxicity, ocular toxicity, and cardiotoxicity. Dabrafenib is a CYP3A substrate; adagrasib is a strong CYP3A inhibitor. In a drug interaction study, coadministration of a strong CYP3A inhibitor increased the dabrafenib AUC by 71%, hydroxy-dabrafenib AUC by 82%, and desmethyl-dabrafenib AUC by 68%.
Albuterol; Budesonide: (Major) The concomitant use of dabrafenib and budesonide may lead to decreased budesonide concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of budesonide efficacy. Dabrafenib is a moderate CYP3A4 inducer and budesonide is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
Alfentanil: (Major) The concomitant use of dabrafenib and alfentanil may lead to decreased alfentanil concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of alfentanil efficacy. Dabrafenib is a moderate CYP3A4 inducer and alfentanil is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
Alogliptin; Pioglitazone: (Major) The concomitant use of dabrafenib and pioglitazone may lead to decreased pioglitazone exposure and loss of efficacy. Use of an alternative agent is recommended. If concomitant use is unavoidable, monitor patients for loss of pioglitazone efficacy. A change in diabetes treatment may be needed based upon clinical response if dabrafenib is started or stopped during treatment with pioglitazone; do not exceed the maximum recommended dose of 45 mg/day. In vitro, dabrafenib is an inducer of CYP2C isoenzymes via activation of the pregnane X receptor and constitutive androstane receptor nuclear receptors. Pioglitazone is a moderately sensitive CYP2C8 substrate. Administration of Rifampin 600 mg/day for 5 days with a single 30 mg dose of pioglitazone decreased the AUC of pioglitazone by 54% in a drug interaction study (n = 10).
Amlodipine: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as dabrafenib, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Amlodipine; Atorvastatin: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as dabrafenib, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Amlodipine; Benazepril: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as dabrafenib, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Amlodipine; Celecoxib: (Major) The concomitant use of dabrafenib and celecoxib may lead to decreased celecoxib concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents is unavoidable, monitor patients for loss of celecoxib efficacy; a celecoxib dose adjustment may be necessary. Dabrafenib is a weak CYP2C9 inducer and celecoxib is a sensitive CYP2C9 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP2C9 substrate decreased the AUC value of the sensitive CYP2C9 substrate by 37%. (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as dabrafenib, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Amlodipine; Olmesartan: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as dabrafenib, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Amlodipine; Valsartan: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as dabrafenib, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as dabrafenib, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Amoxicillin; Clarithromycin; Omeprazole: (Major) The concomitant use of dabrafenib, a CYP3A4 substrate and moderate CYP3A4 inducer, and clarithromycin, a strong CYP3A4 inhibitor and CYP3A4 substrate, may result in altered levels of either agent; avoid concomitant use if possible. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for dabrafenib adverse reactions including skin toxicity, ocular toxicity, and cardiotoxicity and for loss of clarithromycin efficacy.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with dabrafenib can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If dabrafenib is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Dabrafenib is a moderate CYP3A4 inducer.
Aspirin, ASA; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with dabrafenib is necessary; consider increasing the dose of oxycodone as needed. If dabrafenib is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and dabrafenib is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Atazanavir: (Major) Coadministration of atazanavir with dabrafenib is not recommended as there is a potential for elevated dabrafenib concentrations and decreased concentrations of atazanavir. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Atazanavir is metabolized by CYP3A4; dabrafenib is a moderate CYP3A4 inducer. In addition, darbrafenib is a substrate for CYP2C8; atazanavir is a weak CYP2C8 inhibitor.
Atazanavir; Cobicistat: (Major) Avoid coadministration of dabrafenib and cobicistat due to the potential for decreased cobicistat concentrations and increased dabrafenib exposure. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for reduced antiretroviral efficacy and dabrafenib adverse reactions including skin toxicity, ocular toxicity, and cardiotoxicity. Both drugs are CYP3A4 substrates. Darafenib is a moderate CYP3A4 inducer, while cobicistat is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration of a strong CYP3A4 inhibitor increased the dabrafenib AUC by 71%, hydroxy-dabrafenib AUC by 82%, and desmethyl-dabrafenib AUC by 68%. (Major) Coadministration of atazanavir with dabrafenib is not recommended as there is a potential for elevated dabrafenib concentrations and decreased concentrations of atazanavir. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Atazanavir is metabolized by CYP3A4; dabrafenib is a moderate CYP3A4 inducer. In addition, darbrafenib is a substrate for CYP2C8; atazanavir is a weak CYP2C8 inhibitor.
Atogepant: (Major) Avoid use of atogepant and dabrafenib when atogepant is used for chronic migraine. Use an atogepant dose of 30 or 60 mg PO once daily for episodic migraine if coadministered with dabrafenib. Concurrent use may decrease atogepant exposure and reduce efficacy. Atogepant is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer.
Avacopan: (Major) Avoid concomitant use of avacopan and dabrafenib due to the risk of decreased avacopan exposure which may reduce its efficacy. Avacopan is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer.
Avanafil: (Major) Avoid the concomitant use of dabrafenib and avanafil; decreased avanafil concentrations and loss of efficacy may occur. Use of an alternative agent is recommended. Dabrafenib is a moderate CYP3A4 inducer and avanafil is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
Avapritinib: (Major) Avoid coadministration of avapritinib with dabrafenib due to the risk of decreased avapritinib efficacy. Avapritinib is a CYP3A4 substrate and dabrafenib is a moderate CYP3A4 inducer. Coadministration with another moderate CYP3A4 inducer is predicted to decrease the AUC and Cmax of avapritinib by 62% and 55%, respectively.
Axitinib: (Major) Avoid coadministration of axitinib with dabrafenib if possible due to the risk of decreased efficacy of axitinib. Selection of a concomitant medication with no or minimal CYP3A4 induction potential is recommended. Axitinib is a CYP3A4/5 substrate and dabrafenib is a moderate CYP3A4 inducer.
Azilsartan: (Moderate) The concomitant use of dabrafenib, a CYP29 inducer, and azilsartan, a CYP2C9 substrate, may result in decreased levels of azilsartan; avoid concomitant use if possible. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for loss of azilsartan efficacy.
Azilsartan; Chlorthalidone: (Moderate) The concomitant use of dabrafenib, a CYP29 inducer, and azilsartan, a CYP2C9 substrate, may result in decreased levels of azilsartan; avoid concomitant use if possible. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for loss of azilsartan efficacy.
Bedaquiline: (Major) Avoid concurrent use of dabrafenib with bedaquiline. Dabrafenib is a CYP3A4 inducer, which may result in decreased bedaquiline systemic exposure (AUC) and possibly reduced therapeutic effect.
Benzhydrocodone; Acetaminophen: (Moderate) Concurrent use of benzhydrocodone with dabrafenib may decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. If concomitant use is necessary, consider increasing the benzhydrocodone dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Discontinuation of dabrafenib may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. If dabrafenib is discontinued, consider a benzhydrocodone dosage reduction and monitor patients for respiratory depression and sedation at frequent intervals. Benzhydrocodone is a prodrug of hydrocodone. Dabrafenib is an inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of hydrocodone.
Brigatinib: (Major) Avoid coadministration of brigatinib with dabrafenib due to decreased plasma exposure to brigatinib which may result in decreased efficacy. If concomitant use is unavoidable, after 7 days of concomitant treatment with dabrafenib, increase the dose of brigatinib as tolerated in 30 mg increments to a maximum of twice the original brigatinib dose. After discontinuation of dabrafenib, resume the brigatinib dose that was tolerated prior to initiation of dabrafenib. Brigatinib is a CYP3A4 substrate and dabrafenib is a moderate CYP3A4 inducer. Coadministration with a moderate CYP3A inducer is predicted to decrease the AUC of brigatinib by approximately 50%.
Bromocriptine: (Moderate) Caution and close monitoring are advised if bromocriptine and dabrafenib are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; dabrafenib is a moderate inducer of CYP3A4.
Budesonide: (Major) The concomitant use of dabrafenib and budesonide may lead to decreased budesonide concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of budesonide efficacy. Dabrafenib is a moderate CYP3A4 inducer and budesonide is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
Budesonide; Formoterol: (Major) The concomitant use of dabrafenib and budesonide may lead to decreased budesonide concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of budesonide efficacy. Dabrafenib is a moderate CYP3A4 inducer and budesonide is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
Budesonide; Glycopyrrolate; Formoterol: (Major) The concomitant use of dabrafenib and budesonide may lead to decreased budesonide concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of budesonide efficacy. Dabrafenib is a moderate CYP3A4 inducer and budesonide is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
Bupivacaine; Lidocaine: (Moderate) Concomitant use of systemic lidocaine and dabrafenib may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; dabrafenib induces CYP3A4.
Bupivacaine; Meloxicam: (Moderate) The concomitant use of dabrafenib, a CYP29 inducer, and meloxicam, a CYP2C9 substrate, may result in decreased levels of meloxicam; avoid concomitant use if possible. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for loss of meloxicam efficacy. In addition, an increased risk of bleeding may occur when NSAIDs are used with agents that cause clinically significant thrombocytopenia. Patients should be monitored closely for bleeding.
Bupropion: (Major) The concomitant use of dabrafenib and bupropion may lead to decreased bupropion concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents is unavoidable, monitor patients for loss of bupropion efficacy. In vitro, dabrafenib is an inducer of CYP2B6 via activation of the pregnane X receptor and constitutive androstane receptor nuclear receptors. Bupropion is a sensitive CYP2B6 substrate.
Bupropion; Naltrexone: (Major) The concomitant use of dabrafenib and bupropion may lead to decreased bupropion concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents is unavoidable, monitor patients for loss of bupropion efficacy. In vitro, dabrafenib is an inducer of CYP2B6 via activation of the pregnane X receptor and constitutive androstane receptor nuclear receptors. Bupropion is a sensitive CYP2B6 substrate.
Buspirone: (Major) The concomitant use of dabrafenib and buspirone may lead to decreased buspirone concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of buspirone efficacy. If a patient has been titrated to a stable dosage on buspirone, a dose adjustment of buspirone may be necessary to maintain anxiolytic effect. Dabrafenib is a moderate CYP3A4 inducer and buspirone is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of codeine with dabrafenib can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If dabrafenib is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Dabrafenib is a moderate CYP3A4 inducer.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Concomitant use of codeine with dabrafenib can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If dabrafenib is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Dabrafenib is a moderate CYP3A4 inducer.
Cabotegravir; Rilpivirine: (Major) The concomitant use of dabrafenib and rilpivirine may lead to decreased rilpivirine concentrations and loss of virologic response. Consider use of an alternative agent. If concomitant use of these agents is unavoidable, monitor patients for loss of rilpivirine efficacy. Dabrafenib is a moderate CYP3A4 inducer and rilpivirine is a moderately sensitive CYP3A4 substrate.
Cannabidiol: (Moderate) Consider a dose reduction of dabrafenib as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased dabrafenib exposure is possible. Dabrafenib is a CYP2C8 substrate. In vitro data predicts inhibition of CYP2C8 by cannabidiol potentially resulting in clinically significant interactions.
Capivasertib: (Major) Avoid coadministration of capivasertib with dabrafenib due to decreased capivasertib exposure and risk of decreased efficacy. Capivasertib is a CYP3A substrate; dabrafenib is a moderate CYP3A inducer. Coadministration of another moderate CYP3A inducer is predicted to decrease the capivasertib overall exposure by 60%.
Capmatinib: (Major) Avoid coadministration of capmatinib and dabrafenib due to the risk of decreased capmatinib exposure, which may reduce its efficacy. Capmatinib is a CYP3A substrate and dabrafenib is a moderate CYP3A4 inducer. Coadministration with another moderate CYP3A4 inducer decreased capmatinib exposure by 44%.
Carbamazepine: (Major) Use dabrafenib and carbamazepine together with caution; concentrations of either agent may be decreased resulting in loss of efficacy. Use of an alternate agent in place of carbamazepine is recommended. If concomitant use cannot be avoided, monitor patients for loss of carbamazepine efficacy. Carbamazepine is a CYP3A4 substrate and a strong CYP3A4 inducer; dabrafenib is a CYP3A4 substrate and a moderate CYP3A4 inducer. The AUC values of dabrafenib and its metabolite desmethyl-dabrafenib were decreased by 34% and 30%, respectively, when dabrafenib was coadministered with another strong CYP3A4 inducer for 10 days in a drug interaction study.
Celecoxib: (Major) The concomitant use of dabrafenib and celecoxib may lead to decreased celecoxib concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents is unavoidable, monitor patients for loss of celecoxib efficacy; a celecoxib dose adjustment may be necessary. Dabrafenib is a weak CYP2C9 inducer and celecoxib is a sensitive CYP2C9 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP2C9 substrate decreased the AUC value of the sensitive CYP2C9 substrate by 37%.
Celecoxib; Tramadol: (Major) The concomitant use of dabrafenib and celecoxib may lead to decreased celecoxib concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents is unavoidable, monitor patients for loss of celecoxib efficacy; a celecoxib dose adjustment may be necessary. Dabrafenib is a weak CYP2C9 inducer and celecoxib is a sensitive CYP2C9 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP2C9 substrate decreased the AUC value of the sensitive CYP2C9 substrate by 37%.
Ceritinib: (Major) Avoid coadministration of dabrafenib and ceritinib due to increased dabrafenib exposure. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for dabrafenib adverse reactions including skin toxicity, ocular toxicity, and cardiotoxicity. Dabrafenib is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration of a strong CYP3A4 inhibitor increased the dabrafenib AUC by 71%, hydroxy-dabrafenib AUC by 82%, and desmethyl-dabrafenib AUC by 68%.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with dabrafenib can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If dabrafenib is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Dabrafenib is a moderate CYP3A4 inducer.
Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with dabrafenib can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If dabrafenib is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and dabrafenib is a moderate CYP3A4 inducer.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Clarithromycin: (Major) The concomitant use of dabrafenib, a CYP3A4 substrate and moderate CYP3A4 inducer, and clarithromycin, a strong CYP3A4 inhibitor and CYP3A4 substrate, may result in altered levels of either agent; avoid concomitant use if possible. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for dabrafenib adverse reactions including skin toxicity, ocular toxicity, and cardiotoxicity and for loss of clarithromycin efficacy.
Cobicistat: (Major) Avoid coadministration of dabrafenib and cobicistat due to the potential for decreased cobicistat concentrations and increased dabrafenib exposure. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for reduced antiretroviral efficacy and dabrafenib adverse reactions including skin toxicity, ocular toxicity, and cardiotoxicity. Both drugs are CYP3A4 substrates. Darafenib is a moderate CYP3A4 inducer, while cobicistat is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration of a strong CYP3A4 inhibitor increased the dabrafenib AUC by 71%, hydroxy-dabrafenib AUC by 82%, and desmethyl-dabrafenib AUC by 68%.
Cobimetinib: (Major) Avoid the concomitant use of dabrafenib and cobimetinib; decreased cobimetinib concentrations and loss of efficacy may occur. Use of an alternative agent is recommended. Dabrafenib is a moderate CYP3A4 inducer and cobimetinib is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
Codeine: (Moderate) Concomitant use of codeine with dabrafenib can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If dabrafenib is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Dabrafenib is a moderate CYP3A4 inducer.
Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with dabrafenib can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If dabrafenib is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Dabrafenib is a moderate CYP3A4 inducer.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with dabrafenib can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If dabrafenib is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Dabrafenib is a moderate CYP3A4 inducer.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of codeine with dabrafenib can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If dabrafenib is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Dabrafenib is a moderate CYP3A4 inducer.
Codeine; Promethazine: (Moderate) Concomitant use of codeine with dabrafenib can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If dabrafenib is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Dabrafenib is a moderate CYP3A4 inducer.
Daclatasvir: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be increased to 90 mg PO once daily when administered in combination with moderate CYP3A4 inducers, such as dabrafenib. Taking these drugs together may decrease daclatasvir serum concentrations, potentially resulting in reduced antiviral efficacy and antimicrobial resistance.
Dapsone: (Moderate) Closely monitor for a reduction in dapsone efficacy and signs of hemolytic anemia if coadministration with dabrafenib is necessary. Dapsone is a CYP3A4 substrate and dabrafenib is a moderate CYP3A4 inducer. Coadministration may decrease plasma concentrations of dapsone and increase the formation of dapsone hydroxylamine (a metabolite associated with hemolysis).
Daridorexant: (Major) Avoid concomitant use of daridorexant and dabrafenib. Coadministration may decrease daridorexant exposure which may reduce its efficacy. Daridorexant is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer. Concomitant use of another moderate CYP3A inducer decreased daridorexant overall exposure by over 50%.
Darunavir: (Major) The concomitant use of dabrafenib and darunavir may lead to altered concentrations of either drug. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of darunavir efficacy. Dabrafenib is a CYP3A4 substrate and moderate CYP3A4 inducer; darunavir is a sensitive CYP3A4 substrate and a moderate CYP3A4 inhibitor.
Darunavir; Cobicistat: (Major) Avoid coadministration of dabrafenib and cobicistat due to the potential for decreased cobicistat concentrations and increased dabrafenib exposure. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for reduced antiretroviral efficacy and dabrafenib adverse reactions including skin toxicity, ocular toxicity, and cardiotoxicity. Both drugs are CYP3A4 substrates. Darafenib is a moderate CYP3A4 inducer, while cobicistat is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration of a strong CYP3A4 inhibitor increased the dabrafenib AUC by 71%, hydroxy-dabrafenib AUC by 82%, and desmethyl-dabrafenib AUC by 68%. (Major) The concomitant use of dabrafenib and darunavir may lead to altered concentrations of either drug. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of darunavir efficacy. Dabrafenib is a CYP3A4 substrate and moderate CYP3A4 inducer; darunavir is a sensitive CYP3A4 substrate and a moderate CYP3A4 inhibitor.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid coadministration of dabrafenib and cobicistat due to the potential for decreased cobicistat concentrations and increased dabrafenib exposure. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for reduced antiretroviral efficacy and dabrafenib adverse reactions including skin toxicity, ocular toxicity, and cardiotoxicity. Both drugs are CYP3A4 substrates. Darafenib is a moderate CYP3A4 inducer, while cobicistat is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration of a strong CYP3A4 inhibitor increased the dabrafenib AUC by 71%, hydroxy-dabrafenib AUC by 82%, and desmethyl-dabrafenib AUC by 68%. (Major) The concomitant use of dabrafenib and darunavir may lead to altered concentrations of either drug. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of darunavir efficacy. Dabrafenib is a CYP3A4 substrate and moderate CYP3A4 inducer; darunavir is a sensitive CYP3A4 substrate and a moderate CYP3A4 inhibitor.
Deflazacort: (Major) Avoid concomitant use of deflazacort and dabrafenib. Concurrent use may significantly decrease concentrations of 21-desDFZ, the active metabolite of deflazacort, resulting in loss of efficacy. Deflazacort is a CYP3A4 substrate; dabrafenib is a moderate inducer of CYP3A4. Administration of deflazacort with multiple doses of rifampin (a strong CYP3A4 inducer) resulted in geometric mean exposures that were approximately 95% lower compared to administration alone.
Delavirdine: (Major) The concomitant use of dabrafenib, a CYP3A4 substrate and a moderate CYP3A4 inducer, and delavirdine, a strong CYP3A4 inhibitor and a CYP3A4 substrate, may result in altered levels of either agent; avoid concomitant use if possible. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for dabrafenib adverse reactions including skin toxicity, ocular toxicity, and cardiotoxicity and for loss of delavirdine efficacy.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Desogestrel; Ethinyl Estradiol: (Major) Avoid concomitant use of dabrafenib and hormonal contraceptives; decreased hormonal contraceptive concentrations and loss of efficacy may occur. Use of an alternative non-hormonal contraceptive method of birth control is recommended during treatment for 2 weeks after the last dose of dabrafenib. Dabrafenib is a moderate CYP3A4 inducer and many hormonal contraceptive are CYP3A4 substrates.
Dextromethorphan; Bupropion: (Major) The concomitant use of dabrafenib and bupropion may lead to decreased bupropion concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents is unavoidable, monitor patients for loss of bupropion efficacy. In vitro, dabrafenib is an inducer of CYP2B6 via activation of the pregnane X receptor and constitutive androstane receptor nuclear receptors. Bupropion is a sensitive CYP2B6 substrate.
Diclofenac: (Moderate) The concomitant use of dabrafenib, a CYP29 inducer, and diclofenac, a CYP2C9 substrate, may result in decreased levels of diclofenac; avoid concomitant use if possible. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for loss of diclofenac efficacy. In addition, an increased risk of bleeding may occur when NSAIDs are used with agents that cause clinically significant thrombocytopenia. Patients should be monitored closely for bleeding.
Diclofenac; Misoprostol: (Moderate) The concomitant use of dabrafenib, a CYP29 inducer, and diclofenac, a CYP2C9 substrate, may result in decreased levels of diclofenac; avoid concomitant use if possible. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for loss of diclofenac efficacy. In addition, an increased risk of bleeding may occur when NSAIDs are used with agents that cause clinically significant thrombocytopenia. Patients should be monitored closely for bleeding.
Dienogest; Estradiol valerate: (Major) Avoid concomitant use of dabrafenib and hormonal contraceptives; decreased hormonal contraceptive concentrations and loss of efficacy may occur. Use of an alternative non-hormonal contraceptive method of birth control is recommended during treatment for 2 weeks after the last dose of dabrafenib. Dabrafenib is a moderate CYP3A4 inducer and many hormonal contraceptive are CYP3A4 substrates.
Diphenhydramine; Naproxen: (Moderate) Use dabrafenib and naproxen together with caution; naproxen exposure may be decreased. Use an alternate agent in place of naproxen if possible. If concomitant use with cannot be avoided, monitor patients for loss of naproxen efficacy. Dabrafenib is a weak CYP29 inducer and naproxen is a CYP2C9 substrate. When a single-dose of a sensitive CYP2C9 substrate was administered after 15 days of dabrafenib 150 mg twice daily, the AUC value of the CYP2C9 substrate was decreased by 37%.
Dolutegravir; Rilpivirine: (Major) The concomitant use of dabrafenib and rilpivirine may lead to decreased rilpivirine concentrations and loss of virologic response. Consider use of an alternative agent. If concomitant use of these agents is unavoidable, monitor patients for loss of rilpivirine efficacy. Dabrafenib is a moderate CYP3A4 inducer and rilpivirine is a moderately sensitive CYP3A4 substrate.
Doravirine: (Moderate) Concurrent administration of doravirine and dabrafenib may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; dabrafenib is a moderate CYP3A4 inducer.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Concurrent administration of doravirine and dabrafenib may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; dabrafenib is a moderate CYP3A4 inducer.
Doxorubicin Liposomal: (Major) Dabrafenib is a CYP3A4 inducer and doxorubicin is a major substrate of CYP3A4. Inducers of CYP3A4 may decrease the concentration of doxorubicin and compromise the efficacy of chemotherapy. Avoid coadministration of dabrafenib and doxorubicin if possible. If not possible, monitor doxorubicin closely for efficacy.
Doxorubicin: (Major) Dabrafenib is a CYP3A4 inducer and doxorubicin is a major substrate of CYP3A4. Inducers of CYP3A4 may decrease the concentration of doxorubicin and compromise the efficacy of chemotherapy. Avoid coadministration of dabrafenib and doxorubicin if possible. If not possible, monitor doxorubicin closely for efficacy.
Dronabinol: (Moderate) Use caution if coadministration of dronabinol with dabrafenib is necessary, and monitor for a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; dabrafenib is a moderate inducer of CYP3A4 and a weak CYP2C9 inducer. Concomitant use may result in decreased plasma concentrations of dronabinol.
Dronedarone: (Major) The concomitant use of dabrafenib and dronedarone may lead to decreased dronedarone concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of dronedarone efficacy. Dabrafenib is a moderate CYP3A4 inducer and dronedarone is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
Drospirenone: (Major) Avoid concomitant use of dabrafenib and hormonal contraceptives; decreased hormonal contraceptive concentrations and loss of efficacy may occur. Use of an alternative non-hormonal contraceptive method of birth control is recommended during treatment for 2 weeks after the last dose of dabrafenib. Dabrafenib is a moderate CYP3A4 inducer and many hormonal contraceptive are CYP3A4 substrates.
Drospirenone; Estetrol: (Major) Avoid concomitant use of dabrafenib and hormonal contraceptives; decreased hormonal contraceptive concentrations and loss of efficacy may occur. Use of an alternative non-hormonal contraceptive method of birth control is recommended during treatment for 2 weeks after the last dose of dabrafenib. Dabrafenib is a moderate CYP3A4 inducer and many hormonal contraceptive are CYP3A4 substrates.
Drospirenone; Estradiol: (Major) Avoid concomitant use of dabrafenib and hormonal contraceptives; decreased hormonal contraceptive concentrations and loss of efficacy may occur. Use of an alternative non-hormonal contraceptive method of birth control is recommended during treatment for 2 weeks after the last dose of dabrafenib. Dabrafenib is a moderate CYP3A4 inducer and many hormonal contraceptive are CYP3A4 substrates.
Drospirenone; Ethinyl Estradiol: (Major) Avoid concomitant use of dabrafenib and hormonal contraceptives; decreased hormonal contraceptive concentrations and loss of efficacy may occur. Use of an alternative non-hormonal contraceptive method of birth control is recommended during treatment for 2 weeks after the last dose of dabrafenib. Dabrafenib is a moderate CYP3A4 inducer and many hormonal contraceptive are CYP3A4 substrates.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Major) Avoid concomitant use of dabrafenib and hormonal contraceptives; decreased hormonal contraceptive concentrations and loss of efficacy may occur. Use of an alternative non-hormonal contraceptive method of birth control is recommended during treatment for 2 weeks after the last dose of dabrafenib. Dabrafenib is a moderate CYP3A4 inducer and many hormonal contraceptive are CYP3A4 substrates.
Duvelisib: (Major) Avoid concomitant use of duvelisib with dabrafenib. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. If concomitant use is necessary, increase the dose of duvelisib on day 12 of coadministration from 25 mg PO twice daily to 40 mg PO twice daily; or from 15 mg PO twice daily to 25 mg PO twice daily. When dabrafenib has been discontinued for at least 14 days, resume duvelisib at the dose taken prior to initiating treatment with dabrafenib. Duvelisib is a CYP3A substrate; dabrafenib is a moderate CYP3A inducer. Coadministration of duvelisib with another moderate CYP3A inducer for 12 days decreased duvelisib exposure by 35%.
Elacestrant: (Major) Avoid concurrent use of elacestrant and dabrafenib due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced elacestrant overall exposure by 55% to 73%.
Elagolix; Estradiol; Norethindrone acetate: (Major) Avoid concomitant use of dabrafenib and hormonal contraceptives; decreased hormonal contraceptive concentrations and loss of efficacy may occur. Use of an alternative non-hormonal contraceptive method of birth control is recommended during treatment for 2 weeks after the last dose of dabrafenib. Dabrafenib is a moderate CYP3A4 inducer and many hormonal contraceptive are CYP3A4 substrates.
Elbasvir; Grazoprevir: (Major) If possible, avoid concurrent administration of elbasvir with dabrafenib. Dabrafenib is a moderate CYP3A inducer, while elbasvir is a substrate of CYP3A. Use of these drugs together is expected to decrease the plasma concentrations of elbasvir, and may result in decreased virologic response. (Major) If possible, avoid concurrent administration of grazoprevir with dabrafenib. Dabrafenib is a moderate CYP3A inducer, while grazoprevir is a substrate of CYP3A. Use of these drugs together is expected to decrease the plasma concentrations of grazoprevir, and may result in decreased virologic response. Conversely, concentrations of dabrafenib (also a CYP3A substrate) may be increased when given with grazoprevir (a weak CYP3A inhibitor).
Eletriptan: (Major) The concomitant use of dabrafenib and eletriptan may lead to decreased eletriptan concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of eletriptan efficacy. Dabrafenib is a moderate CYP3A4 inducer and eletriptan is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid coadministration of dabrafenib and cobicistat due to the potential for decreased cobicistat concentrations and increased dabrafenib exposure. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for reduced antiretroviral efficacy and dabrafenib adverse reactions including skin toxicity, ocular toxicity, and cardiotoxicity. Both drugs are CYP3A4 substrates. Darafenib is a moderate CYP3A4 inducer, while cobicistat is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration of a strong CYP3A4 inhibitor increased the dabrafenib AUC by 71%, hydroxy-dabrafenib AUC by 82%, and desmethyl-dabrafenib AUC by 68%. (Major) Coadministration of elvitegravir with dabrafenib is not recommended as there is a potential for decreased elvitegravir concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Elvitegravir is metabolized by CYP3A4; dabrafenib is a moderate CYP3A4 inducer.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of dabrafenib and cobicistat due to the potential for decreased cobicistat concentrations and increased dabrafenib exposure. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for reduced antiretroviral efficacy and dabrafenib adverse reactions including skin toxicity, ocular toxicity, and cardiotoxicity. Both drugs are CYP3A4 substrates. Darafenib is a moderate CYP3A4 inducer, while cobicistat is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration of a strong CYP3A4 inhibitor increased the dabrafenib AUC by 71%, hydroxy-dabrafenib AUC by 82%, and desmethyl-dabrafenib AUC by 68%. (Major) Coadministration of elvitegravir with dabrafenib is not recommended as there is a potential for decreased elvitegravir concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Elvitegravir is metabolized by CYP3A4; dabrafenib is a moderate CYP3A4 inducer.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) The concomitant use of dabrafenib and rilpivirine may lead to decreased rilpivirine concentrations and loss of virologic response. Consider use of an alternative agent. If concomitant use of these agents is unavoidable, monitor patients for loss of rilpivirine efficacy. Dabrafenib is a moderate CYP3A4 inducer and rilpivirine is a moderately sensitive CYP3A4 substrate.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Major) The concomitant use of dabrafenib and rilpivirine may lead to decreased rilpivirine concentrations and loss of virologic response. Consider use of an alternative agent. If concomitant use of these agents is unavoidable, monitor patients for loss of rilpivirine efficacy. Dabrafenib is a moderate CYP3A4 inducer and rilpivirine is a moderately sensitive CYP3A4 substrate.
Entrectinib: (Major) Avoid coadministration of entrectinib with dabrafenib due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; dabrafenib is a moderate CYP3A4 inducer. Coadministration of a moderate CYP3A4 inducer is predicted to reduce the entrectinib AUC by 56%.
Eplerenone: (Major) The concomitant use of dabrafenib and eplerenone may lead to decreased eplerenone concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of eplerenone efficacy. Dabrafenib is a moderate CYP3A4 inducer and eplerenone is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
Erdafitinib: (Major) If coadministration of erdafitinib and dabrafenib is necessary at the initiation of erdafitinib therapy, administer the dose of erdafitinib as recommended (8 mg once daily with potential to increase the dose to 9 mg on days 14 to 21 based on phosphate levels and tolerability). If dabrafenib must be added to erdafitinib therapy after the initial dose increase period (days 14 to 21), increase the dose of erdafitinib up to 9 mg. If dabrafenib is discontinued, continue erdafitinib at the same dose in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and dabrafenib is a moderate CYP3A4 inducer.
Erlotinib: (Major) There may be a risk of reduced erlotinib efficacy when coadministered with dabrafenib; however, the risk has not been clearly defined. If coadministration is necessary, consider increasing the erlotinib dose by 50 mg increments at 2-week intervals as tolerated, to a maximum of 450 mg. Erlotinib is a CYP3A4 substrate, and dabrafenib is a moderate CYP3A4 inducer.
Estradiol; Levonorgestrel: (Major) Avoid concomitant use of dabrafenib and hormonal contraceptives; decreased hormonal contraceptive concentrations and loss of efficacy may occur. Use of an alternative non-hormonal contraceptive method of birth control is recommended during treatment for 2 weeks after the last dose of dabrafenib. Dabrafenib is a moderate CYP3A4 inducer and many hormonal contraceptive are CYP3A4 substrates.
Estradiol; Norethindrone: (Major) Avoid concomitant use of dabrafenib and hormonal contraceptives; decreased hormonal contraceptive concentrations and loss of efficacy may occur. Use of an alternative non-hormonal contraceptive method of birth control is recommended during treatment for 2 weeks after the last dose of dabrafenib. Dabrafenib is a moderate CYP3A4 inducer and many hormonal contraceptive are CYP3A4 substrates.
Estradiol; Norgestimate: (Major) Avoid concomitant use of dabrafenib and hormonal contraceptives; decreased hormonal contraceptive concentrations and loss of efficacy may occur. Use of an alternative non-hormonal contraceptive method of birth control is recommended during treatment for 2 weeks after the last dose of dabrafenib. Dabrafenib is a moderate CYP3A4 inducer and many hormonal contraceptive are CYP3A4 substrates.
Ethinyl Estradiol; Norelgestromin: (Major) Avoid concomitant use of dabrafenib and hormonal contraceptives; decreased hormonal contraceptive concentrations and loss of efficacy may occur. Use of an alternative non-hormonal contraceptive method of birth control is recommended during treatment for 2 weeks after the last dose of dabrafenib. Dabrafenib is a moderate CYP3A4 inducer and many hormonal contraceptive are CYP3A4 substrates.
Ethinyl Estradiol; Norethindrone Acetate: (Major) Avoid concomitant use of dabrafenib and hormonal contraceptives; decreased hormonal contraceptive concentrations and loss of efficacy may occur. Use of an alternative non-hormonal contraceptive method of birth control is recommended during treatment for 2 weeks after the last dose of dabrafenib. Dabrafenib is a moderate CYP3A4 inducer and many hormonal contraceptive are CYP3A4 substrates.
Ethinyl Estradiol; Norgestrel: (Major) Avoid concomitant use of dabrafenib and hormonal contraceptives; decreased hormonal contraceptive concentrations and loss of efficacy may occur. Use of an alternative non-hormonal contraceptive method of birth control is recommended during treatment for 2 weeks after the last dose of dabrafenib. Dabrafenib is a moderate CYP3A4 inducer and many hormonal contraceptive are CYP3A4 substrates.
Ethynodiol Diacetate; Ethinyl Estradiol: (Major) Avoid concomitant use of dabrafenib and hormonal contraceptives; decreased hormonal contraceptive concentrations and loss of efficacy may occur. Use of an alternative non-hormonal contraceptive method of birth control is recommended during treatment for 2 weeks after the last dose of dabrafenib. Dabrafenib is a moderate CYP3A4 inducer and many hormonal contraceptive are CYP3A4 substrates.
Etonogestrel: (Major) Avoid concomitant use of dabrafenib and hormonal contraceptives; decreased hormonal contraceptive concentrations and loss of efficacy may occur. Use of an alternative non-hormonal contraceptive method of birth control is recommended during treatment for 2 weeks after the last dose of dabrafenib. Dabrafenib is a moderate CYP3A4 inducer and many hormonal contraceptive are CYP3A4 substrates.
Etonogestrel; Ethinyl Estradiol: (Major) Avoid concomitant use of dabrafenib and hormonal contraceptives; decreased hormonal contraceptive concentrations and loss of efficacy may occur. Use of an alternative non-hormonal contraceptive method of birth control is recommended during treatment for 2 weeks after the last dose of dabrafenib. Dabrafenib is a moderate CYP3A4 inducer and many hormonal contraceptive are CYP3A4 substrates.
Everolimus: (Moderate) Monitor everolimus whole blood trough concentrations as appropriate if coadministration with dabrafenib is necessary. The dose of everolimus may need to be increased. Everolimus is a sensitive CYP3A4 substrate and dabrafenib is a moderate CYP3A4 inducer. Coadministration with CYP3A4 inducers may increase the metabolism of everolimus and decrease everolimus blood concentrations.
Ezetimibe; Simvastatin: (Major) The concomitant use of dabrafenib and simvastatin may lead to decreased simvastatin concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of simvastatin efficacy. Dabrafenib is a moderate CYP3A4 inducer and simvastatin is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
Fedratinib: (Major) Avoid coadministration of fedratinib with dabrafenib as concurrent use may decrease fedratinib exposure which may result in decreased therapeutic response. Fedratinib is a CYP3A4 substrate; dabrafenib is a moderate CYP3A4 inducer. Coadministration of fedratinib with another moderate CYP3A4 inducer decreased the overall exposure of fedratinib by 47%.
Felodipine: (Major) The concomitant use of dabrafenib and felodipine may lead to decreased felodipine concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of felodipine efficacy. Dabrafenib is a moderate CYP3A4 inducer and felodipine is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
Fentanyl: (Moderate) Consider an increased dose of fentanyl and monitor for evidence of opioid withdrawal if concurrent use of dabrafenib is necessary. If dabrafenib is discontinued, consider reducing the fentanyl dosage and monitor for evidence of respiratory depression. Coadministration of a CYP3A4 inducer like dabrafenib with fentanyl, a CYP3A4 substrate, may decrease exposure to fentanyl resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to fentanyl. Fentanyl plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Finerenone: (Major) Avoid concurrent use of finerenone and dabrafenib due to the risk for decreased finerenone exposure which may reduce its efficacy. Finerenone
Fosamprenavir: (Moderate) Monitor for decreased fosamprenavir efficacy if coadministered with dabrafenib. Concurrent use may decrease the plasma concentrations of fosamprenavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Fosamprenavir is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer.
Fosphenytoin: (Major) Use dabrafenib and fosphenytoin together with caution; concentrations of either agent may be decreased. Use an alternate agent in place of fosphenytoin if possible. If concomitant use cannot be avoided, monitor patients for loss of fosphenytoin efficacy. Fosphenytoin is a strong CYP3A4 inducer and a substrate of CYP2C9 and CYP2C19; dabrafenib is a CYP3A4 substrate and a CYP2C9 and CYP2C19 inducer.
Fruquintinib: (Major) Avoid coadministration of fruquintinib with dabrafenib if possible due to decreased fruquintinib exposure and risk of decreased efficacy. If concomitant use of fruquintinib and dabrafenib is necessary, monitor for decreased efficacy. Fruquintinib is a CYP3A substrate; dabrafenib is a strong CYP3A inducer. Coadministration of a moderate CYP3A inducer is predicted to decrease fruquintinib exposure by 32%.
Ganaxolone: (Major) Avoid concurrent use of ganaxolone and dabrafenib due to the risk of decreased ganaxolone efficacy. If concomitant use is unavoidable, consider increasing ganaxolone dose without exceeding the maximum daily dose. Ganaxolone is a CYP3A4 substrate and dabrafenib is a moderate CYP3A4 inducer.
Gemfibrozil: (Major) Avoid the concomitant use of dabrafenib and gemfibrozil; dabrafenib exposure increased by 47% when these drugs were administered together in a drug interaction study. Use of an alternate agent in place of gemfibrozil is recommended. If concomitant use cannot be avoided, monitor patients for dabrafenib toxicity (e.g., skin toxicity, ocular toxicity, and cardiotoxicity). Dabrafenib is a CYP2C8 substrate; gemfibrozil is a strong CYP2C8 inhibitor. The dabrafenib AUC value increased by 47% when dabrafenib 75 mg PO twice daily was administered with gemfibrozil 600 mg twice daily for 4 days in a drug interaction study; there were no change in the AUC values of the metabolites, hydroxy-dabrafenib and desmethyl-dabrafenib.
Glasdegib: (Major) Avoid coadministration of glasdegib and dabrafenib due to the potential for decreased glasdegib exposure and risk of decreased efficacy. If concurrent use cannot be avoided, increase the glasdegib dosage (i.e., from 100 mg PO daily to 200 mg PO daily; or from 50 mg PO daily to 100 mg PO daily). Resume the previous dose of glasdegib after dabrafenib has been discontinued for 7 days. Glasdegib is a CYP3A4 substrate; dabrafenib is a moderate CYP3A4 inducer. Coadministration with another moderate CYP3A4 inducer was predicted to decrease the glasdegib AUC value by 55%.
Glimepiride: (Major) The concomitant use of dabrafenib and glimepiride may lead to decreased glimepiride concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents is unavoidable, monitor patients for loss of glimepiride efficacy. Dabrafenib is a weak CYP2C9 inducer and glimepiride is a moderately sensitive CYP2C9 substrate.
Grapefruit juice: (Major) Avoid the concomitant use of dabrafenib, a CYP3A4 substrate, and grapefruit juice, a CYP3A4 inhibitor, as dabrafenib levels may increase.
Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with dabrafenib can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If dabrafenib is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and dabrafenib is a moderate CYP3A4 inducer.
Homatropine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with dabrafenib can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If dabrafenib is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and dabrafenib is a moderate CYP3A4 inducer.
Hydrocodone: (Moderate) Concomitant use of hydrocodone with dabrafenib can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If dabrafenib is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and dabrafenib is a moderate CYP3A4 inducer.
Hydrocodone; Ibuprofen: (Moderate) Concomitant use of hydrocodone with dabrafenib can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If dabrafenib is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and dabrafenib is a moderate CYP3A4 inducer.
Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with dabrafenib can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If dabrafenib is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and dabrafenib is a moderate CYP3A4 inducer.
Ibrexafungerp: (Major) Avoid concurrent administration of ibrexafungerp with dabrafenib. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer.
Ibrutinib: (Major) The concomitant use of dabrafenib and ibrutinib may lead to decreased ibrutinib concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of ibrutinib efficacy. Dabrafenib is a moderate CYP3A4 inducer and ibrutinib is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%. Additionally, simulations using physiologically-based pharmacokinetic (PBPK) models suggest that moderate CYP3A4 inducers may decrease ibrutinib exposure up to 3-fold.
Ibuprofen; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with dabrafenib is necessary; consider increasing the dose of oxycodone as needed. If dabrafenib is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and dabrafenib is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with dabrafenib, a CYP3A substrate, as dabrafenib toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Ifosfamide: (Moderate) Closely monitor for increased ifosfamide-related toxicities (e.g., neurotoxicity, nephrotoxicity) if coadministration with dabrafenib is necessary; consider adjusting the dose of ifosfamide as clinically appropriate. Ifosfamide is metabolized to its active alkylating metabolites by CYP3A4; dabrafenib is a moderate CYP3A4 inducer. Concomitant use may increase the formation of the neurotoxic/nephrotoxic ifosfamide metabolite, chloroacetaldehyde.
Indinavir: (Major) Avoid the concomitant use of dabrafenib and indinavir; altered levels of either drug may occur. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients closely for dabrafenib adverse reactions (e.g., skin toxicity, ocular toxicity, and cardiotoxicity) and for loss of indinavir efficacy. Dabrafenib is a CYP3A4 substrate and moderate CYP3A4 inducer; indinavir is a strong CYP3A4 inhibitor and a sensitive CYP3A4 substrate.
Infigratinib: (Major) Avoid concurrent use of infigratinib and dabrafenib. Coadministration may decrease infigratinib exposure resulting in decreased efficacy. Infigratinib is a CYP3A4 substrate and dabrafenib is a moderate CYP3A4 inducer.
Isavuconazonium: (Major) The concomitant use of dabrafenib and isavuconazonium may lead to decreased isavuconazonium concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of isavuconazonium efficacy. Dabrafenib is a CYP3A4 substrate and a moderate CYP3A4 inducer; isavuconazonium is a sensitive CYP3A4 substrate and a moderate inhibitor of CYP3A4. The use of isavuconazonium is contraindicated with strong CYP3A4 inducers; however, the manufacturer does not provide guidance for moderate inducers. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
Itraconazole: (Major) Avoid dabrafenib use during and for 2 weeks after discontinuation of itraconazole treatment. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for dabrafenib adverse reactions including skin toxicity, ocular toxicity, and cardiotoxicity and for loss of itraconazole efficacy. The concomitant use of dabrafenib, a CYP3A4 substrate and moderate CYP3A4 inducer, and itraconazole, a strong CYP3A4 inhibitor and a CYP3A4 substrate, may result in altered levels of either agent.
Ketoconazole: (Major) Avoid coadministration of dabrafenib and ketoconazole due to increased dabrafenib exposure. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for dabrafenib adverse reactions including skin toxicity, ocular toxicity, and cardiotoxicity. Dabrafenib is a CYP3A4 substrate and ketoconazole is a strong CYP3A4 inhibitor. Coadministration with ketoconazole increased the dabrafenib AUC by 71%, hydroxy-dabrafenib AUC by 82%, and desmethyl-dabrafenib AUC by 68%.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) The concomitant use of dabrafenib, a CYP3A4 substrate and moderate CYP3A4 inducer, and clarithromycin, a strong CYP3A4 inhibitor and CYP3A4 substrate, may result in altered levels of either agent; avoid concomitant use if possible. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for dabrafenib adverse reactions including skin toxicity, ocular toxicity, and cardiotoxicity and for loss of clarithromycin efficacy.
Larotrectinib: (Major) Avoid concurrent use of larotrectinib and dabrafenib due to the risk of decreased larotrectinib exposure which may reduce its efficacy. If concomitant use is necessary, double the dose of larotrectinib and monitor response. If dabrafenib is discontinued, resume the original larotrectinib dose after 3 to 5 elimination half-lives of dabrafenib. Larotrectinib is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer. Coadministration with a moderate CYP3A inducer is predicted to decrease larotrectinib exposure by 72%.
Lefamulin: (Major) Avoid coadministration of lefamulin with dabrafenib unless the benefits outweigh the risks as concurrent use may decrease lefamulin exposure and efficacy. Lefamulin is a CYP3A4 substrate; dabrafenib is a moderate CYP3A4 inducer.
Lemborexant: (Major) Avoid coadministration of lemborexant and dabrafenib as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; dabrafenib is a moderate CYP3A4 inducer.
Lenacapavir: (Major) Avoid concurrent use of lenacapavir and dabrafenib due to the risk of decreased lenacapavir exposure which may result in loss of therapeutic effect and development of resistance. Lenacapavir is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced lenacapavir overall exposure by 56%.
Leniolisib: (Major) Avoid concomitant use of leniolisib and dabrafenib. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced leniolisib overall exposure by 58%.
Lesinurad: (Moderate) Dabrafenib may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Dabrafenib is a mild CYP2C9 inducer, and lesinurad is a CYP2C9 substrate.
Lesinurad; Allopurinol: (Moderate) Dabrafenib may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Dabrafenib is a mild CYP2C9 inducer, and lesinurad is a CYP2C9 substrate.
Letermovir: (Moderate) Administering letermovir with dabrafenib may increase dabrafenib concentration and risk for adverse events. Avoid coadministration in patients who are also receiving cyclosporine because the magnitude of this interaction may be increased. Closely monitor the patient for adverse reactions if coadministration of dabrafenib with both letermovir and cyclosporine cannot be avoided. Dabrafenib is primarily metabolized by CYP3A4 and CYP2C8. Letermovir is a moderate inhibitor of CYP3A4 and inhibits CYP2C8 in vitro. When given with cyclosporine, the combined effect of letermovir and cyclosporine on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. Concurrent administration with a strong CYP3A4 inhibitor resulted in the exposure of dabrafenib, hydroxy-dabrafenib, and desmethyl-dabrafenib to be increased by 71%, 82%, and 68%, respectively. Administration with a strong CYP2C8 inhibitor increased dabrafenib exposure by 47%, but did not change the exposure of dabrafenib metabolites.
Leuprolide; Norethindrone: (Major) Avoid concomitant use of dabrafenib and hormonal contraceptives; decreased hormonal contraceptive concentrations and loss of efficacy may occur. Use of an alternative non-hormonal contraceptive method of birth control is recommended during treatment for 2 weeks after the last dose of dabrafenib. Dabrafenib is a moderate CYP3A4 inducer and many hormonal contraceptive are CYP3A4 substrates.
Levamlodipine: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as dabrafenib, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Levoketoconazole: (Major) Avoid coadministration of dabrafenib and ketoconazole due to increased dabrafenib exposure. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for dabrafenib adverse reactions including skin toxicity, ocular toxicity, and cardiotoxicity. Dabrafenib is a CYP3A4 substrate and ketoconazole is a strong CYP3A4 inhibitor. Coadministration with ketoconazole increased the dabrafenib AUC by 71%, hydroxy-dabrafenib AUC by 82%, and desmethyl-dabrafenib AUC by 68%.
Levonorgestrel: (Major) Avoid concomitant use of dabrafenib and hormonal contraceptives; decreased hormonal contraceptive concentrations and loss of efficacy may occur. Use of an alternative non-hormonal contraceptive method of birth control is recommended during treatment for 2 weeks after the last dose of dabrafenib. Dabrafenib is a moderate CYP3A4 inducer and many hormonal contraceptive are CYP3A4 substrates.
Levonorgestrel; Ethinyl Estradiol: (Major) Avoid concomitant use of dabrafenib and hormonal contraceptives; decreased hormonal contraceptive concentrations and loss of efficacy may occur. Use of an alternative non-hormonal contraceptive method of birth control is recommended during treatment for 2 weeks after the last dose of dabrafenib. Dabrafenib is a moderate CYP3A4 inducer and many hormonal contraceptive are CYP3A4 substrates.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Major) Avoid concomitant use of dabrafenib and hormonal contraceptives; decreased hormonal contraceptive concentrations and loss of efficacy may occur. Use of an alternative non-hormonal contraceptive method of birth control is recommended during treatment for 2 weeks after the last dose of dabrafenib. Dabrafenib is a moderate CYP3A4 inducer and many hormonal contraceptive are CYP3A4 substrates.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Major) Avoid concomitant use of dabrafenib and hormonal contraceptives; decreased hormonal contraceptive concentrations and loss of efficacy may occur. Use of an alternative non-hormonal contraceptive method of birth control is recommended during treatment for 2 weeks after the last dose of dabrafenib. Dabrafenib is a moderate CYP3A4 inducer and many hormonal contraceptive are CYP3A4 substrates.
Lidocaine: (Moderate) Concomitant use of systemic lidocaine and dabrafenib may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; dabrafenib induces CYP3A4.
Lidocaine; Epinephrine: (Moderate) Concomitant use of systemic lidocaine and dabrafenib may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; dabrafenib induces CYP3A4.
Lidocaine; Prilocaine: (Moderate) Concomitant use of systemic lidocaine and dabrafenib may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; dabrafenib induces CYP3A4.
Lomitapide: (Major) The concomitant use of dabrafenib and lomitapide may lead to decreased lomitapide concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of lomitapide efficacy. Dabrafenib is a moderate CYP3A4 inducer and lomitapide is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
Lonafarnib: (Contraindicated) Coadministration of lonafarnib and dabrafenib is contraindicated; concurrent use may decrease lonafarnib exposure, which may reduce its efficacy. The exposure of dabrafenib may also be increased, increasing the risk for dabrafenib-related adverse reactions including skin toxicity, ocular toxicity, and cardiotoxicity. Lonafarnib is a sensitive CYP3A4 substrate and strong CYP3A4 inhibitor; dabrafenib is a CYP3A4 substrate and moderate CYP3A4 inducer.
Lopinavir; Ritonavir: (Major) The concomitant use of dabrafenib, a CYP3A4 substrate and a moderate CYP3A4 inducer, and ritonavir, a strong CYP3A4 inhibitor and a CYP3A4 substrate and inducer, may result in altered levels of either agent; avoid concomitant use if possible. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for dabrafenib or ritonavir adverse effects and/or reduced efficacy. (Moderate) Concomitant use of dabrafenib, a moderate CYP3A4 inducer, and lopinavir, a CYP3A4 substrate, may result in decreased lopinavir plasma concentrations. If these drugs are used together, monitor patients closely for reduced antiretroviral efficacy.
Lorlatinib: (Major) Avoid concomitant use of lorlatinib and dabrafenib due to decreased plasma concentrations of lorlatinib, which may reduce its efficacy. If concomitant use is necessary, increase the dose of lorlatinib to 125 mg PO once daily. Lorlatinib is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer. Administration with another moderate CYP3A inducer decreased lorlatinib exposure by 23%.
Losartan: (Moderate) The concomitant use of dabrafenib, a CYP29 inducer and losartan, a CYP2C9 substrate, may result in decreased levels of losartan; avoid concomitant use if possible. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for loss of losartan efficacy.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) The concomitant use of dabrafenib, a CYP29 inducer and losartan, a CYP2C9 substrate, may result in decreased levels of losartan; avoid concomitant use if possible. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for loss of losartan efficacy.
Lovastatin: (Major) The concomitant use of dabrafenib and lovastatin may lead to decreased lovastatin concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of lovastatin efficacy. Dabrafenib is a moderate CYP3A4 inducer and lovastatin is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
Lumacaftor; Ivacaftor: (Major) Avoid the concomitant administration of dabrafenib and lumacaftor; ivacaftor. If concomitant use is unavoidable, monitor patients closely for loss of dabrafenib efficacy. Dabrafenib is primarily metabolized by CYP3A4 and CYP2C8. Lumacaftor is a strong CYP3A inducer; in vitro data also suggest that lumacaftor may induce and/or inhibit CYP2C8.
Lumacaftor; Ivacaftor: (Major) Avoid the concomitant administration of dabrafenib and lumacaftor; ivacaftor. If concomitant use is unavoidable, monitor patients closely for loss of dabrafenib efficacy. Dabrafenib is primarily metabolized by CYP3A4 and CYP2C8. Lumacaftor is a strong CYP3A inducer; in vitro data also suggest that lumacaftor may induce and/or inhibit CYP2C8.
Lumateperone: (Major) Avoid coadministration of lumateperone and dabrafenib as concurrent use may decrease lumateperone exposure which may reduce efficacy. Lumateperone is a CYP3A4 substrate; dabrafenib is a moderate CYP3A4 inducer.
Lurasidone: (Moderate) If lurasidone is used with dabrafenib, it may be necessary to increase the lurasidone dose after chronic treatment (7 days or more) with dabrafenib. Concurrent use may lead to a decrease in efficacy of lurasidone. Dabrafenib is a moderate CYP3A inducer; lurasidone is a CYP3A substrate.
Maraviroc: (Major) The concomitant use of dabrafenib and maraviroc may lead to decreased maraviroc concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of maraviroc efficacy. Dabrafenib is a moderate CYP3A4 inducer and maraviroc is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
Mavacamten: (Contraindicated) Mavacamten is contraindicated for use with dabrafenib due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer.
Meloxicam: (Moderate) The concomitant use of dabrafenib, a CYP29 inducer, and meloxicam, a CYP2C9 substrate, may result in decreased levels of meloxicam; avoid concomitant use if possible. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for loss of meloxicam efficacy. In addition, an increased risk of bleeding may occur when NSAIDs are used with agents that cause clinically significant thrombocytopenia. Patients should be monitored closely for bleeding.
Metformin; Repaglinide: (Major) The concomitant use of dabrafenib and repaglinide may lead to decreased repaglinide concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents is unavoidable, monitor patients for loss of repaglinide efficacy. In vitro, dabrafenib is an inducer of CYP2C isoenzymes via activation of the pregnane X receptor and constitutive androstane receptor nuclear receptors. Repaglinide is a sensitive CYP2C8 substrate.
Midazolam: (Major) The concomitant use of dabrafenib and midazolam led to significantly decreased midazolam concentrations in a drug interaction study. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of midazolam efficacy. Dabrafenib is a moderate CYP3A4 inducer and midazolam is a sensitive CYP3A4 substrate. Administration of dabrafenib 150 mg twice daily for 15 days with a single 3 mg dose of midazolam decreased the AUC of midazolam by 65% in a drug interaction study.
Mitapivat: (Major) Avoid coadministration of mitapivat with dabrafenib, if possible, due to decreased mitapivat efficacy. Coadministration decreases mitapivat concentrations. If concomitant use is necessary, up-titration of mitapivat may be required. Monitor hemoglobin and titrate the mitapivat dose based on response; do not exceed 100 mg PO twice daily. Mitapivat is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased mitapivat overall exposure by 55% to 60%.
Mobocertinib: (Major) Avoid concomitant use of mobocertinib and dabrafenib. Coadministration may decrease mobocertinib exposure resulting in decreased efficacy. Mobocertinib is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer. Use of a moderate CYP3A inducer is predicted to decrease the overall exposure of mobocertinib and its active metabolites by 58%.
Naloxegol: (Major) The concomitant use of dabrafenib and naloxegol may lead to decreased naloxegol concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of naloxegol efficacy. Dabrafenib is a moderate CYP3A4 inducer and naloxegol is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with dabrafenib is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and dabrafenib is a moderate CYP3A4 inducer.
Nanoparticle Albumin-Bound Sirolimus: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with dabrafenib. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer.
Naproxen: (Moderate) Use dabrafenib and naproxen together with caution; naproxen exposure may be decreased. Use an alternate agent in place of naproxen if possible. If concomitant use with cannot be avoided, monitor patients for loss of naproxen efficacy. Dabrafenib is a weak CYP29 inducer and naproxen is a CYP2C9 substrate. When a single-dose of a sensitive CYP2C9 substrate was administered after 15 days of dabrafenib 150 mg twice daily, the AUC value of the CYP2C9 substrate was decreased by 37%.
Naproxen; Esomeprazole: (Moderate) Use dabrafenib and naproxen together with caution; naproxen exposure may be decreased. Use an alternate agent in place of naproxen if possible. If concomitant use with cannot be avoided, monitor patients for loss of naproxen efficacy. Dabrafenib is a weak CYP29 inducer and naproxen is a CYP2C9 substrate. When a single-dose of a sensitive CYP2C9 substrate was administered after 15 days of dabrafenib 150 mg twice daily, the AUC value of the CYP2C9 substrate was decreased by 37%.
Naproxen; Pseudoephedrine: (Moderate) Use dabrafenib and naproxen together with caution; naproxen exposure may be decreased. Use an alternate agent in place of naproxen if possible. If concomitant use with cannot be avoided, monitor patients for loss of naproxen efficacy. Dabrafenib is a weak CYP29 inducer and naproxen is a CYP2C9 substrate. When a single-dose of a sensitive CYP2C9 substrate was administered after 15 days of dabrafenib 150 mg twice daily, the AUC value of the CYP2C9 substrate was decreased by 37%.
Nateglinide: (Moderate) The concomitant use of dabrafenib, a CYP2C9 inducer, and nateglinide, a CYP2C9 substrate, may result in decreased levels of nateglinide; avoid concomitant use if possible. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for loss of nateglinide efficacy.
Nefazodone: (Major) The concomitant use of dabrafenib, a CYP3A4 substrate and moderate CYP3A4 inducer, and nefazodone, a strong CYP3A4 inhibitor and a CYP3A4 substrate, may result in altered levels of either agent; avoid concomitant use if possible. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for dabrafenib adverse reactions including skin toxicity, ocular toxicity, and cardiotoxicity and for loss of nefazodone efficacy.
Neratinib: (Major) Avoid concomitant use of dabrafenib with neratinib due to decreased efficacy of neratinib. Neratinib is a CYP3A4 substrate and dabrafenib is a moderate CYP3A4 inducer. Simulations using physiologically based pharmacokinetic (PBPK) models suggest that another moderate CYP3A4 inducer may decrease neratinib exposure by 52%.
Netupitant, Fosnetupitant; Palonosetron: (Moderate) Netupitant is a moderate inhibitor of CYP3A4 and the plasma concentrations of medications that are primarily metabolized through CYP3A4, such as dabrafenib, can increase with coadministration. The inhibitory effect on CYP3A4 can last for multiple days. In addition, netupitant is mainly metabolized by CYP3A4. Coadministration of netupitant in patients who are chronically using a strong CYP3A4 inducer should be avoided since a strong CYP3A inducer can decrease the efficacy of netupitant by substantially reducing plasma concentrations of netupitant. Dabrafenib is a CYP3A4 inducer. If coadministration is necessary, no dosage adjustment is necessary for single dose administration of netupitant; palonosetron.
Nirmatrelvir; Ritonavir: (Major) The concomitant use of dabrafenib, a CYP3A4 substrate and a moderate CYP3A4 inducer, and ritonavir, a strong CYP3A4 inhibitor and a CYP3A4 substrate and inducer, may result in altered levels of either agent; avoid concomitant use if possible. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for dabrafenib or ritonavir adverse effects and/or reduced efficacy. (Moderate) Monitor for a diminished response to nirmatrelvir if concomitant use of dabrafenib is necessary. Concomitant use of nirmatrelvir and dabrafenib may reduce the therapeutic effect of nirmatrelvir. Nirmatrelvir is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer.
Nirogacestat: (Major) Avoid concomitant use of nirogacestat and dabrafenib. Concurrent use may decrease nirogacestat exposure which may reduce its efficacy. Nirogacestat is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer is predicted to reduce nirogacestat overall exposure by 67%.
Nisoldipine: (Major) Avoid the concomitant use of dabrafenib and nisoldipine; decreased nisoldipine concentrations and loss of efficacy may occur. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of nisoldipine efficacy. Dabrafenib is a moderate CYP3A4 inducer and nisoldipine is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
Non-oral combination contraceptives: (Major) Avoid concomitant use of dabrafenib and hormonal contraceptives; decreased hormonal contraceptive concentrations and loss of efficacy may occur. Use of an alternative non-hormonal contraceptive method of birth control is recommended during treatment for 2 weeks after the last dose of dabrafenib. Dabrafenib is a moderate CYP3A4 inducer and many hormonal contraceptive are CYP3A4 substrates.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Major) Avoid concomitant use of dabrafenib and hormonal contraceptives; decreased hormonal contraceptive concentrations and loss of efficacy may occur. Use of an alternative non-hormonal contraceptive method of birth control is recommended during treatment for 2 weeks after the last dose of dabrafenib. Dabrafenib is a moderate CYP3A4 inducer and many hormonal contraceptive are CYP3A4 substrates.
Norethindrone: (Major) Avoid concomitant use of dabrafenib and hormonal contraceptives; decreased hormonal contraceptive concentrations and loss of efficacy may occur. Use of an alternative non-hormonal contraceptive method of birth control is recommended during treatment for 2 weeks after the last dose of dabrafenib. Dabrafenib is a moderate CYP3A4 inducer and many hormonal contraceptive are CYP3A4 substrates.
Norethindrone; Ethinyl Estradiol: (Major) Avoid concomitant use of dabrafenib and hormonal contraceptives; decreased hormonal contraceptive concentrations and loss of efficacy may occur. Use of an alternative non-hormonal contraceptive method of birth control is recommended during treatment for 2 weeks after the last dose of dabrafenib. Dabrafenib is a moderate CYP3A4 inducer and many hormonal contraceptive are CYP3A4 substrates.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Major) Avoid concomitant use of dabrafenib and hormonal contraceptives; decreased hormonal contraceptive concentrations and loss of efficacy may occur. Use of an alternative non-hormonal contraceptive method of birth control is recommended during treatment for 2 weeks after the last dose of dabrafenib. Dabrafenib is a moderate CYP3A4 inducer and many hormonal contraceptive are CYP3A4 substrates.
Norgestimate; Ethinyl Estradiol: (Major) Avoid concomitant use of dabrafenib and hormonal contraceptives; decreased hormonal contraceptive concentrations and loss of efficacy may occur. Use of an alternative non-hormonal contraceptive method of birth control is recommended during treatment for 2 weeks after the last dose of dabrafenib. Dabrafenib is a moderate CYP3A4 inducer and many hormonal contraceptive are CYP3A4 substrates.
Norgestrel: (Major) Avoid concomitant use of dabrafenib and hormonal contraceptives; decreased hormonal contraceptive concentrations and loss of efficacy may occur. Use of an alternative non-hormonal contraceptive method of birth control is recommended during treatment for 2 weeks after the last dose of dabrafenib. Dabrafenib is a moderate CYP3A4 inducer and many hormonal contraceptive are CYP3A4 substrates.
Olaparib: (Major) Avoid coadministration of olaparib with dabrafenib due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and dabrafenib is a moderate CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with a moderate CYP3A inducer is predicted to decrease the olaparib Cmax by 31% and the AUC by 60%.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as dabrafenib, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Olutasidenib: (Major) Avoid concurrent use of olutasidenib and dabrafenib due to the risk of decreased olutasidenib exposure which may reduce its efficacy. Olutasidenib is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer.
Omaveloxolone: (Major) Avoid concurrent use of omaveloxolone and dabrafenib. Concurrent use may decrease omaveloxolone exposure which may reduce its efficacy. Omaveloxolone is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer.
Oral Contraceptives: (Major) Avoid concomitant use of dabrafenib and hormonal contraceptives; decreased hormonal contraceptive concentrations and loss of efficacy may occur. Use of an alternative non-hormonal contraceptive method of birth control is recommended during treatment for 2 weeks after the last dose of dabrafenib. Dabrafenib is a moderate CYP3A4 inducer and many hormonal contraceptive are CYP3A4 substrates.
Ospemifene: (Moderate) The concomitant use of dabrafenib, a CYP2C9 inducer, and ospemifene, a CYP2C9 substrate, may result in decreased levels of ospemiphene, which may decrease the clinical effect. Monitor patients for reduced ospemiphene efficacy.
Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with dabrafenib is necessary; consider increasing the dose of oxycodone as needed. If dabrafenib is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and dabrafenib is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Pacritinib: (Major) Avoid concurrent use of pacritinib with dabrafenib due to the risk of decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer.
Palovarotene: (Major) Avoid concomitant use of palovarotene and dabrafenib. Concurrent use may decrease palovarotene exposure which may reduce its efficacy. Palovarotene is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer.
Pemigatinib: (Major) Avoid coadministration of pemigatinib and dabrafenib due to the risk of decreased pemigatinib exposure which may reduce its efficacy. Pemigatinib is a CYP3A4 substrate and dabrafenib is a moderate CYP3A4 inducer. Coadministration with a moderate CYP3A4 inducer is predicted to decrease pemigatinib exposure by more than 50%.
Perampanel: (Major) Consider alternative therapy or start perampanel at a higher initial dose of 4 mg once daily at bedtime when using concurrently with dabrafenib due to a potential reduction in perampanel plasma concentration. If introduction or withdrawal of dabrafenib occurs during perampanel therapy, closely monitor patient response; a dosage adjustment may be necessary. Dabrafenib is a moderate CYP3A4 inducer, and perampanel is a CYP3A4 substrate.
Perindopril; Amlodipine: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as dabrafenib, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Phenobarbital: (Major) Use dabrafenib and phenobarbital together with caution; concentrations of either agent may be decreased. Use an alternate agent in place of phenobarbital if possible. If concomitant use cannot be avoided, monitor patients for loss of phenobarbital efficacy. Phenobarbital is a strong CYP3A4 inducer and a substrate of CYP2C9 and CYP2C19; dabrafenib is a CYP3A4 substrate and a CYP2C9 and CYP2C19 inducer.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Use dabrafenib and phenobarbital together with caution; concentrations of either agent may be decreased. Use an alternate agent in place of phenobarbital if possible. If concomitant use cannot be avoided, monitor patients for loss of phenobarbital efficacy. Phenobarbital is a strong CYP3A4 inducer and a substrate of CYP2C9 and CYP2C19; dabrafenib is a CYP3A4 substrate and a CYP2C9 and CYP2C19 inducer.
Phenytoin: (Major) Use dabrafenib and phenytoin together with caution; concentrations of either agent may be decreased. Use an alternate agent in place of phenytoin if possible. If concomitant use cannot be avoided, monitor patients for loss of phenytoin efficacy. Phenytoin is a strong CYP3A4 inducer and a substrate of CYP2C9 and CYP2C19; dabrafenib is a CYP3A4 substrate and a CYP2C9 and CYP2C19 inducer.
Pimavanserin: (Major) Because pimavanserin is primarily metabolized by CYP3A4 and CYP3A5, the manufacturer recommends avoiding concomitant use of pimavanserin with moderate CYP3A4 inducers, such as dabrafenib. Moderate inducers of CYP3A4 can reduce pimavanserin exposure, potentially decreasing the effectiveness of pimavanserin.
Pioglitazone: (Major) The concomitant use of dabrafenib and pioglitazone may lead to decreased pioglitazone exposure and loss of efficacy. Use of an alternative agent is recommended. If concomitant use is unavoidable, monitor patients for loss of pioglitazone efficacy. A change in diabetes treatment may be needed based upon clinical response if dabrafenib is started or stopped during treatment with pioglitazone; do not exceed the maximum recommended dose of 45 mg/day. In vitro, dabrafenib is an inducer of CYP2C isoenzymes via activation of the pregnane X receptor and constitutive androstane receptor nuclear receptors. Pioglitazone is a moderately sensitive CYP2C8 substrate. Administration of Rifampin 600 mg/day for 5 days with a single 30 mg dose of pioglitazone decreased the AUC of pioglitazone by 54% in a drug interaction study (n = 10).
Pioglitazone; Glimepiride: (Major) The concomitant use of dabrafenib and glimepiride may lead to decreased glimepiride concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents is unavoidable, monitor patients for loss of glimepiride efficacy. Dabrafenib is a weak CYP2C9 inducer and glimepiride is a moderately sensitive CYP2C9 substrate. (Major) The concomitant use of dabrafenib and pioglitazone may lead to decreased pioglitazone exposure and loss of efficacy. Use of an alternative agent is recommended. If concomitant use is unavoidable, monitor patients for loss of pioglitazone efficacy. A change in diabetes treatment may be needed based upon clinical response if dabrafenib is started or stopped during treatment with pioglitazone; do not exceed the maximum recommended dose of 45 mg/day. In vitro, dabrafenib is an inducer of CYP2C isoenzymes via activation of the pregnane X receptor and constitutive androstane receptor nuclear receptors. Pioglitazone is a moderately sensitive CYP2C8 substrate. Administration of Rifampin 600 mg/day for 5 days with a single 30 mg dose of pioglitazone decreased the AUC of pioglitazone by 54% in a drug interaction study (n = 10).
Pioglitazone; Metformin: (Major) The concomitant use of dabrafenib and pioglitazone may lead to decreased pioglitazone exposure and loss of efficacy. Use of an alternative agent is recommended. If concomitant use is unavoidable, monitor patients for loss of pioglitazone efficacy. A change in diabetes treatment may be needed based upon clinical response if dabrafenib is started or stopped during treatment with pioglitazone; do not exceed the maximum recommended dose of 45 mg/day. In vitro, dabrafenib is an inducer of CYP2C isoenzymes via activation of the pregnane X receptor and constitutive androstane receptor nuclear receptors. Pioglitazone is a moderately sensitive CYP2C8 substrate. Administration of Rifampin 600 mg/day for 5 days with a single 30 mg dose of pioglitazone decreased the AUC of pioglitazone by 54% in a drug interaction study (n = 10).
Pirtobrutinib: (Major) Avoid concurrent use of pirtobrutinib and dabrafenib due to the risk of decreased pirtobrutinib exposure which may reduce its efficacy. If concomitant use is necessary, an empiric pirtobrutinib dosage increase is required. If the current dosage is 200 mg once daily, increase the dose to 300 mg; if the current dosage is 50 mg or 100 mg once daily, increase the dose by 50 mg. Pirtobrutinib is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer. Concomitant use with other moderate CYP3A inducers reduced pirtobrutinib overall exposure by 27% and 49%.
Posaconazole: (Major) Avoid the concomitant use of dabrafenib, a CYP3A4 substrate, and posaconazole, a strong CYP3A4 inhibitor, as dabrafenib levels may increase. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for dabrafenib adverse reactions including skin toxicity, ocular toxicity, and cardiotoxicity.
Pralsetinib: (Major) Avoid concurrent use of dabrafenib and pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the current dose of pralsetinib (400 mg to 600 mg; 300 mg to 500 mg; 200 mg to 300 mg) starting on day 7 of coadministration. Pralsetinib is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased the pralsetinib overall exposure by 45%.
Praziquantel: (Major) Avoid concomitant use of praziquantel and dabrafenib. Concurrent use may decrease praziquantel exposure which may reduce its efficacy. If concomitant use is necessary, monitor for reduced response to praziquantel. Praziquantel is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer. When praziquantel was administered after 13 days of treatment with a moderate CYP3A inducer, the mean praziquantel AUC was 77% lower than when praziquantel was given alone.
Pretomanid: (Major) Avoid coadministration of pretomanid with dabrafenib as concurrent use may decrease pretomanid exposure which may lead to decreased efficacy. Pretomanid is a CYP3A4 substrate; dabrafenib is a moderate CYP3A4 inducer. Coadministration with another moderate CYP3A4 inducer decreased pretomanid exposure by 35%.
Quetiapine: (Major) The concomitant use of dabrafenib and quetiapine may lead to decreased quetiapine concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of quetiapine efficacy. Dabrafenib is a moderate CYP3A4 inducer and quetiapine is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
Quizartinib: (Major) Avoid concomitant use of dabrafenib with quizartinib due to the risk of decreased quizartinib exposure which may reduce its efficacy. Quizartinib is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased the quizartinib overall exposure by 90%.
Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid concomitant use of dabrafenib and hormonal contraceptives; decreased hormonal contraceptive concentrations and loss of efficacy may occur. Use of an alternative non-hormonal contraceptive method of birth control is recommended during treatment for 2 weeks after the last dose of dabrafenib. Dabrafenib is a moderate CYP3A4 inducer and many hormonal contraceptive are CYP3A4 substrates.
Repaglinide: (Major) The concomitant use of dabrafenib and repaglinide may lead to decreased repaglinide concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents is unavoidable, monitor patients for loss of repaglinide efficacy. In vitro, dabrafenib is an inducer of CYP2C isoenzymes via activation of the pregnane X receptor and constitutive androstane receptor nuclear receptors. Repaglinide is a sensitive CYP2C8 substrate.
Repotrectinib: (Major) Avoid coadministration of repotrectinib with dabrafenib due to decreased repotrectinib exposure and risk of decreased efficacy. Repotrectinib is a CYP3A substrate; dabrafenib is a moderate CYP3A inducer.
Ribociclib: (Major) Avoid coadministration of dabrafenib and ribociclib due to increased dabrafenib exposure. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for dabrafenib adverse reactions including skin toxicity, ocular toxicity, and cardiotoxicity. Dabrafenib is a CYP3A4 substrate; ribociclib is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration of a strong CYP3A4 inhibitor increased the dabrafenib AUC by 71%, hydroxy-dabrafenib AUC by 82%, and desmethyl-dabrafenib AUC by 68%.
Ribociclib; Letrozole: (Major) Avoid coadministration of dabrafenib and ribociclib due to increased dabrafenib exposure. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for dabrafenib adverse reactions including skin toxicity, ocular toxicity, and cardiotoxicity. Dabrafenib is a CYP3A4 substrate; ribociclib is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration of a strong CYP3A4 inhibitor increased the dabrafenib AUC by 71%, hydroxy-dabrafenib AUC by 82%, and desmethyl-dabrafenib AUC by 68%.
Rilpivirine: (Major) The concomitant use of dabrafenib and rilpivirine may lead to decreased rilpivirine concentrations and loss of virologic response. Consider use of an alternative agent. If concomitant use of these agents is unavoidable, monitor patients for loss of rilpivirine efficacy. Dabrafenib is a moderate CYP3A4 inducer and rilpivirine is a moderately sensitive CYP3A4 substrate.
Rimegepant: (Major) Avoid coadministration of rimegepant with dabrafenib; concurrent use may significantly decrease rimegepant exposure which may result in loss of efficacy. Rimegepant is a CYP3A4 substrate and dabrafenib is a moderate CYP3A4 inducer.
Ripretinib: (Major) Avoid coadministration of ripretinib with dabrafenib. If concomitant use is unavoidable, increase the frequency of ripretinib dosing from 150 mg once daily to 150 mg twice daily; monitor for clinical response and tolerability. Resume once daily dosing of ripretinib 14 days after discontinuation of dabrafenib. Coadministration is predicted to decrease the exposure of ripretinib and its active metabolite (DP-5439), which may decrease ripretinib anti-tumor activity. Ripretinib and DP-5439 are metabolized by CYP3A and dabrafenib is a moderate CYP3A inducer. Drug interaction modeling studies suggest coadministration with a moderate CYP3A inducer may decrease ripretinib exposure by 56%.
Ritonavir: (Major) The concomitant use of dabrafenib, a CYP3A4 substrate and a moderate CYP3A4 inducer, and ritonavir, a strong CYP3A4 inhibitor and a CYP3A4 substrate and inducer, may result in altered levels of either agent; avoid concomitant use if possible. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for dabrafenib or ritonavir adverse effects and/or reduced efficacy.
Rosiglitazone: (Major) The concomitant use of dabrafenib and rosiglitazone may lead to decreased rosiglitazone exposure and loss of efficacy. Use of an alternative agent is recommended. If concomitant use is unavoidable, monitor patients for loss of rosiglitazone efficacy. A change in diabetes treatment may be needed based upon clinical response if dabrafenib is started or stopped during treatment with rosiglitazone. In vitro, dabrafenib is an inducer of CYP2C isoenzymes via activation of the pregnane X receptor and constitutive androstane receptor nuclear receptors. Rosiglitazone is a moderately sensitive CYP2C8 substrate. Administration of rifampin 600 mg/day for 6 days with a single 8 mg dose of rosiglitazone decreased the AUC of rosiglitazone by 66% in a drug interaction study.
Saquinavir: (Major) Avoid the concomitant use of dabrafenib and saquinavir; altered levels of either drug may occur. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients closely for dabrafenib adverse reactions (e.g., skin toxicity, ocular toxicity, and cardiotoxicity) and for loss of saquinavir efficacy. Dabrafenib is a CYP3A4 substrate and moderate CYP3A4 inducer; saquinavir is a strong CYP3A4 inhibitor and a sensitive CYP3A4 substrate.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Segesterone Acetate; Ethinyl Estradiol: (Major) Avoid concomitant use of dabrafenib and hormonal contraceptives; decreased hormonal contraceptive concentrations and loss of efficacy may occur. Use of an alternative non-hormonal contraceptive method of birth control is recommended during treatment for 2 weeks after the last dose of dabrafenib. Dabrafenib is a moderate CYP3A4 inducer and many hormonal contraceptive are CYP3A4 substrates.
Selpercatinib: (Major) Avoid coadministration of selpercatinib and dabrafenib due to the risk of decreased selpercatinib exposure which may reduce its efficacy. Selpercatinib is a CYP3A4 substrate and dabrafenib is a moderate CYP3A4 inducer. Coadministration with other moderate CYP3A4 inducers is predicted to decrease selpercatinib exposure by 40% to 70%.
Selumetinib: (Major) Avoid coadministration of selumetinib and dabrafenib due to the risk of decreased selumetinib exposure which may reduce its efficacy. Selumetinib is a CYP3A4 substrate and dabrafenib is a moderate CYP3A4 inducer. Coadministration with a moderate CYP3A4 inducer is predicted to decrease selumetinib exposure by 38%.
Sildenafil: (Major) The concomitant use of dabrafenib and sildenafil may lead to decreased sildenafil concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of sildenafil efficacy. Dabrafenib is a moderate CYP3A4 inducer and sildenafil is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
Simvastatin: (Major) The concomitant use of dabrafenib and simvastatin may lead to decreased simvastatin concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of simvastatin efficacy. Dabrafenib is a moderate CYP3A4 inducer and simvastatin is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
Siponimod: (Moderate) Concomitant use of siponimod and dabrafenib is not recommended for patients with CYP2C9*1/*3 and *2/*3 genotypes due to a significant decrease in siponimod exposure. Siponimod is a CYP2C9 and CYP3A4 substrate; dabrafenib is a moderate CYP3A4 inducer. Across different CYP2C9 genotypes, a moderate CYP3A4 inducer decreased the exposure of siponimod by up to 52% according to in silico evaluation.
Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of dabrafenib. Concomitant use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer.
Sofosbuvir; Velpatasvir: (Major) Avoid coadministration of velpatasvir with dabrafenib. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a CYP3A4 substrate; dabrafenib is an inducer of CYP3A4.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Avoid coadministration of velpatasvir with dabrafenib. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a CYP3A4 substrate; dabrafenib is an inducer of CYP3A4. (Major) Avoid coadministration of voxilaprevir (a CYP3A4 substrate) with moderate to strong inducers of CYP3A4, such as dabrafenib. Taking these drugs together may significantly decrease voxilaprevir plasma concentrations, potentially resulting in loss of antiviral efficacy.
Sonidegib: (Major) Avoid the concomitant use of sonidegib and dabrafenib; sonidegib levels may be significantly decreased and its efficacy reduced. Sonidegib is a CYP3A4 substrate and dabrafenib is a moderate CYP3A4 inducer. Physiologic-based pharmacokinetics (PBPK) simulations indicate that a moderate CYP3A4 inducer would decrease the sonidegib AUC by 56% if administered for 14 days and by 69% if the moderate CYP3A inducer is administered for more than 14 days.
Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if dabrafenib must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with dabrafenib is necessary; consider increasing the dose of sufentanil injection as needed. If dabrafenib is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and dabrafenib is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Sumatriptan; Naproxen: (Moderate) Use dabrafenib and naproxen together with caution; naproxen exposure may be decreased. Use an alternate agent in place of naproxen if possible. If concomitant use with cannot be avoided, monitor patients for loss of naproxen efficacy. Dabrafenib is a weak CYP29 inducer and naproxen is a CYP2C9 substrate. When a single-dose of a sensitive CYP2C9 substrate was administered after 15 days of dabrafenib 150 mg twice daily, the AUC value of the CYP2C9 substrate was decreased by 37%.
Tacrolimus: (Major) The concomitant use of dabrafenib and tacrolimus may lead to decreased tacrolimus concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor tacrolimus levels and for loss of tacrolimus efficacy. Dabrafenib is a moderate CYP3A4 inducer and tacrolimus is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
Tasimelteon: (Moderate) Caution is recommended during concurrent use of tasimelteon and dabrafenib. Because tasimelteon is partially metabolized via CYP3A4, use with CYP3A4 inducers, such as dabrafenib, may reduce the efficacy of tasimelteon.
Tazemetostat: (Major) Avoid coadministration of tazemetostat with dabrafenib as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and dabrafenib is a moderate CYP3A4 inducer.
Telmisartan; Amlodipine: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as dabrafenib, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Ticagrelor: (Major) The concomitant use of dabrafenib and ticagrelor may lead to decreased ticagrelor concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of ticagrelor efficacy. Dabrafenib is a moderate CYP3A4 inducer and ticagrelor is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
Tipranavir: (Major) Avoid the concomitant use of dabrafenib and tipranavir; altered levels of either drug may occur. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients closely for dabrafenib adverse reactions (e.g., skin toxicity, ocular toxicity, and cardiotoxicity) and for loss of tipranavir efficacy. Dabrafenib is a CYP3A4 substrate and moderate CYP3A4 inducer; tipranavir is a strong CYP3A4 inhibitor and a sensitive CYP3A4 substrate.
Tucatinib: (Major) Avoid coadministration of dabrafenib and tucatinib due to increased dabrafenib exposure. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for dabrafenib adverse reactions including skin toxicity, ocular toxicity, and cardiotoxicity. Dabrafenib is a CYP3A4 substrate; tucatinib is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration of a strong CYP3A4 inhibitor increased the dabrafenib AUC by 71%, hydroxy-dabrafenib AUC by 82%, and desmethyl-dabrafenib AUC by 68%.
Ubrogepant: (Major) Increase the initial and second dose of ubrogepant to 100 mg if coadministered with dabrafenib as concurrent use may decrease ubrogepant exposure and reduce its efficacy. Ubrogepant is a CYP3A4 substrate; dabrafenib is a moderate CYP3A4 inducer.
Ulipristal: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and dabrafenib is a CYP3A4 inducer. Concomitant use is expected to decrease the plasma concentration of ulipristal and may decrease its effectiveness.
Venetoclax: (Major) Avoid the concomitant use of venetoclax and dabrafenib; venetoclax levels may be decreased and its efficacy reduced. Venetoclax is a CYP3A4 substrate and dabrafenib is a moderate CYP3A4 inducer. Consider alternative agents. In a drug interaction study (n = 11), the venetoclax Cmax and AUC values were decreased by 42% and 71%, respectively, following the co-administration of multiple doses of a strong CYP3A4 inducer. Use of venetoclax with a moderate CYP3A4 inducer has not been evaluated.
Vincristine Liposomal: (Moderate) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP3A4 may increase the metabolism of vincristine and decrease the efficacy of drug, including dabrafenib. Patients receiving these drugs concurrently with vincristine should be monitored for possible loss of vincristine efficacy.
Vincristine: (Moderate) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP3A4 may increase the metabolism of vincristine and decrease the efficacy of drug, including dabrafenib. Patients receiving these drugs concurrently with vincristine should be monitored for possible loss of vincristine efficacy.
Voclosporin: (Major) Avoid coadministration of voclosporin with dabrafenib. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and dabrafenib is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease voclosporin exposure by 70%.
Vonoprazan: (Major) Avoid concomitant use of vonoprazan and dabrafenib due to decreased plasma concentrations of vonoprazan, which may reduce its efficacy. Vonoprazan is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer. Vonoprazan exposures are predicted to be 50% lower when coadministered with a moderate CYP3A4 inducer.
Vonoprazan; Amoxicillin: (Major) Avoid concomitant use of vonoprazan and dabrafenib due to decreased plasma concentrations of vonoprazan, which may reduce its efficacy. Vonoprazan is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer. Vonoprazan exposures are predicted to be 50% lower when coadministered with a moderate CYP3A4 inducer.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid concomitant use of vonoprazan and dabrafenib due to decreased plasma concentrations of vonoprazan, which may reduce its efficacy. Vonoprazan is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer. Vonoprazan exposures are predicted to be 50% lower when coadministered with a moderate CYP3A4 inducer. (Major) The concomitant use of dabrafenib, a CYP3A4 substrate and moderate CYP3A4 inducer, and clarithromycin, a strong CYP3A4 inhibitor and CYP3A4 substrate, may result in altered levels of either agent; avoid concomitant use if possible. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for dabrafenib adverse reactions including skin toxicity, ocular toxicity, and cardiotoxicity and for loss of clarithromycin efficacy.
Vorapaxar: (Moderate) Use caution during concurrent use of vorapaxar and dabrafenib. Decreased serum concentrations of vorapaxar and thus decreased efficacy are possible when vorapaxar, a CYP3A4 substrate, is coadministered with dabrafenib, a CYP3A inducer.
Voriconazole: (Major) The concomitant use of dabrafenib and voriconazole may result in altered levels of either agent. Use of an alternative agent is recommended. If concomitant use of these agents is unavoidable, monitor patients for dabrafenib toxicity (e.g., skin toxicity, ocular toxicity, and cardiotoxicity) and loss of voriconazole efficacy. Dabrafenib is a CYP3A4 substrate, a moderate CYP3A4 inducer, and an inducer of CYP2C isoenzymes via activation of the pregnane X receptor and constitutive androstane receptor nuclear receptors. Voriconazole is a strong CYP3A4 inhibitor and a substrate of CYP3A4, CYP2C9, and CYP2C19.
Voxelotor: (Major) Avoid coadministration of voxelotor and dabrafenib as concurrent use may decrease voxelotor exposure and lead to reduced efficacy. If coadministration is unavoidable, increase voxelotor dosage to 2,000 mg PO once daily in patients 12 years and older. In patients 4 to 11 years old, weight-based dosage adjustments are recommended; consult product labeling for specific recommendations. Voxelotor is a substrate of CYP3A; dabrafenib is a moderate CYP3A inducer. Coadministration of voxelotor with a moderate CYP3A inducer is predicted to decrease voxelotor exposure by up to 24%.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with dabrafenib is necessary as concurrent use may decrease the exposure of warfarin leading to reduced efficacy. Dabrafenib is a weak CYP2C9 and moderate CYP3A4 inducer and the enantiomers of warfarin are substrates of CYP2C9/CYP3A4. In a drug interaction study, administration of dabrafenib 150 mg twice daily for 15 days with a single 15 mg-dose of warfarin decreased the AUC of S-warfarin (a CYP2C9 substrate) by 37% and decreased the AUC of R-warfarin (a CYP3A4 substrate) by 33%.
Zanubrutinib: (Major) Avoid concurrent use of zanubrutinib and dabrafenib due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the zanubrutinib dose to 320 mg twice daily and monitor response. Resume the previous dose of zanubrutinib if dabrafenib is discontinued. Zanubrutinib is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer decreased zanubrutinib exposure by 44%.
Zolpidem: (Moderate) It is advisable to closely monitor for reductions in zolpidem efficacy during co-administration of moderate CYP3A4 inducers, such as dabrafenib. CYP3A4 is the primary isoenzyme responsible for zolpidem metabolism, and there is evidence of significant decreases in systemic exposure and pharmacodynamic effects of zolpidem during co-administration of rifampin, a potent CYP3A4 inducer.
How Supplied
Dabrafenib Oral Tab for Susp: 10mg
Tafinlar Oral Cap: 50mg, 75mg
Maximum Dosage
150 mg PO twice daily.
Geriatric150 mg PO twice daily.
AdolescentsCapsules:
Less than 26 kg: Safety and efficacy have not been established.26 to 37 kg: 75 mg PO twice daily.38 to 50 kg: 100 mg PO twice daily.51 kg or more: 150 mg PO twice daily.
Oral Suspension:26 to 29 kg: 70 mg twice daily.30 to 33 kg: 80 mg twice daily.34 to 37 kg: 90 mg twice daily.38 to 41 kg: 100 mg twice daily.42 to 45 kg: 110 mg twice daily.46 to 50 kg: 130 mg twice daily.51 kg or more: 150 mg twice daily.
Capsules:
Less than 26 kg: Safety and efficacy have not been established.26 to 37 kg: 75 mg PO twice daily.38 to 50 kg: 100 mg PO twice daily.51 kg or more: 150 mg PO twice daily.
Oral Suspension:
8 to 9 kg: 20 mg twice daily.10 to 13 kg: 30 mg twice daily. 14 to 17 kg: 40 mg twice daily. 18 to 21 kg: 50 mg twice daily. 22 to 25 kg: 60 mg twice daily. 26 to 29 kg: 70 mg twice daily. 30 to 33 kg: 80 mg twice daily. 34 to 37 kg: 90 mg twice daily. 38 to 41 kg: 100 mg twice daily. 42 to 45 kg: 110 mg twice daily. 46 to 50 kg: 130 mg twice daily. 51 kg or more: 150 mg twice daily.
Safety and efficacy have not been established.
NeonatesSafety and efficacy have not been established.
Mechanism Of Action
Dabrafenib is a kinase inhibitor that has demonstrated activity against some mutated forms of BRAF kinases including BRAF V600E, BRAF V600K, and BRAF V600D in melanoma cells in vitro and in vivo. Dabrafenib inhibits wild-type BRAF and CRAF kinases in vitro. Approximately 40-50% of melanomas have BRAF mutations. Some BRAF mutations (e.g., BRAF V600 mutations) signal mitogen activated protein kinase (MAPK) pathways resulting in the hyperactivation of MEK and extracellular receptor kinase (ERK) leading to melanoma cell proliferation in the absence of growth factors that would normally be required for cell proliferation.
Potential mechanisms of resistance to dabrafenib include upregulation of MAPK signaling, phosphatase tensin homologue (PTEN) loss, hepatocyte growth factor (HGF)/MET signaling, amplified cyclin D1 (CCND1), and amplified receptor tyrosine kinase (RTK) signaling through PI3K and mTOR.
Induction of EGFR-mediated MAPK pathway reactivation has been identified as a mechanism of intrinsic resistance to BRAF inhibitors in the setting of BRAF mutation-positive colorectal cancer.
Pharmacokinetics
Dabrafenib is administered orally. It is highly bound to plasma proteins (99.7%) and has an apparent volume of distribution of 70.3 L. Dabrafenib is metabolized by CYP3A4 and CYP2C8 isoenzymes to hydroxy-dabrafenib which is further oxidized to carboxy-dabrafenib and excreted in the bile and urine. Carboxy-dabrafenib is decarboxylated to form desmethyl-dabrafenib which may be reabsorbed from the gut. Both the hydroxy- and desmethyl-dabrafenib metabolites are likely to contribute to the clinical activity of dabrafenib. Desmethyl-dabrafenib is metabolized by CYP3A4 to oxidative metabolites. The mean terminal half-life is 8 hours for dabrafenib, 10 hours for hydroxy-dabrafenib, and 21 to 22 hours for carboxy-dabrafenib and desmethyl-dabrafenib. The apparent clearance is 17 L/hour after a single dabrafenib dose and 34 L/hour after twice-daily dosing for 2 weeks. The fecal route is the main route of dabrafenib excretion. Following a radioactive dabrafenib dose, 71% of the dose was recovered in the feces and 23% of the total reactivity was recovered as metabolites only in the urine.
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A, CYP2C8, CYP2C9
Dabrafenib is a substrate of CYP3A and CYP2C8, a moderate CYP3A inducer, and a weak CYP2C9 inducer. In vitro, dabrafenib and its metabolites are substrates of human P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) and inhibitors of organic anion transporter (OAT)1 and OAT3. Dabrafenib and desmethyl-dabrafenib are inhibitors of organic cation transporter (OCT)2 and BCRP.
The mean absolute oral bioavailability is 95% for dabrafenib capsules and 76% for the dabrafenib tablets for oral suspension. The median time to peak plasma concentration (Tmax) after oral administration is 2 hours. Dabrafenib capsules exhibit dose proportional exposure over a dosage range of 12 mg to 300 mg following a single dose. The mean accumulation ratio was 0.7 (coefficient of variance, 38%) following 150 mg twice daily dosing; the mean metabolite-to-parent AUC ratios were 0.9 for hydroxy-dabrafenib, 11 for carboxy-dabrafenib, and 0.7 for desmethyl-dabrafenib.
Effects of Food: Administering dabrafenib capsules with a high-fat meal decreases the Cmax by 51%, decreases the AUC by 31%, and delays the median Tmax by 3.6 hours when compared to the fasted state. Take the dabrafenib dose at least 1 hour before or at least 2 hours after a meal.
Pregnancy And Lactation
Dabrafenib may cause fetal harm when administered to a pregnant woman, based on its mechanism of action and findings from animal studies. Advise females of reproductive potential to avoid pregnancy while taking dabrafenib. Discuss the potential hazard to the fetus if dabrafenib is used during pregnancy or if a patient becomes pregnant while taking this drug. Embryo-fetal toxicity was observed in pregnant rats who received dabrafenib doses that resulted in drug exposures that were about 3 times the recommended human exposure including embryo-lethality, ventricular septal defects, and variation in thymic shape. Additionally, fetal skeletal development delay and reduced fetal body weight occurred with dabrafenib doses that achieved exposure equivalent to the recommended human dose.
Patients should discontinue breast-feeding during dabrafenib therapy and for 2 weeks after the last dose because of the potential for serious adverse reactions in a nursing child. It is not known if dabrafenib is secreted in human milk or if it affects the breastfed child or milk production.