ibrutinib (Rx)

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Also indicated for CLL/SLL in patients with 17p deletion

Monotherapy or in combination with rituximab or obinutuzumab, or with bendamustine and rituximab (BR) combination: 420 mg PO qDay

Continue until unacceptable toxicity or disease progression

Mantle Cell Lymphoma

Indicated in patients who have received at least 1 previous therapy

560 mg PO qDay

Continue until disease progression or unacceptable toxicity

Waldenström Macroglobulinemia

Indicated as monotherapy or in combination with rituximab

420 mg PO qDay

Continue until disease progression or unacceptable toxicity

Marginal Zone Lymphoma

Indicated in patients who require systemic therapy and have received at least one prior anti-CD20-based therapy

560 mg PO qDay

Continue until disease progression or unacceptable toxicity

Chronic Graft vs Host Disease

Indicated for chronic graft versus host disease (cGVHD) in adults who failed >1 lines of systemic therapy

420 mg PO qDay

Continue until cGVHD progression, recurrence of an underlying malignancy, or unacceptable toxicity

If therapy is no longer required, consider discontinuing therapy based on medical assessment of individual patient

Dosage Modifications

Grade 2 cardiac failure

• Evaluate benefit-risk before resuming treatment

• MCL and MZL

  • First occurrence: Restart at 420 mg qDay
  • Second occurrence: Restart at 280 mg qDay
  • Third occurrence: Discontinue therapy

• CLL/SLL, WM, and cGVHD

  • First occurrence: Restart at 280 mg qDay
  • Second occurrence: Restart at 140 mg qDay
  • Third occurrence: Discontinue therapy

Grade 3 cardiac arrhythmias

• MCL and MZL

  • First occurrence: Restart at 420 mg qDay
  • Second occurrence: Discontinue therapy

• CLL/SLL, WM, and cGVHD

  • First occurrence: Restart at 280 mg qDay
  • Second occurrence: Discontinue therapy

Grade ≥3 cardiac failure or Grade 4 cardiac arrhythmias

• First occurrence: Discontinue therapy

Nonhematological and hematologic toxicities

• Other Grade 3 or 4 nonhematological toxicities
• Grade 3 or 4 neutropenia with infection or fever
• Grade 4 hematological toxicities

• MCL and MZL

  • First occurrence: Restart at 420 mg qDay
  • Second occurrence: Restart at 280 mg qDay
  • Third occurrence: Discontinue therapy

• CLL/SLL, WM, and cGVHD

  • First occurrence: Restart at 280 mg qDay
  • Second occurrence: Restart at 140 mg qDay
  • Third occurrence: Discontinue therapy

Coadministration with CYP3A inhibitors

• Moderate CYP3A4 inhibitor: Reduce ibrutinib to 420 mg qDay; modify dose as recommended

• Reduce ibrutinib dose to 280 mg qDay when coadministered with the following

  • Voriconazole 200 mg BID
  • Posaconazole suspension 100 mg qDay, 100 mg BID, or 200 mg BID
  • Modify dose as recommended

• Reduce ibrutinib dose to 140 mg qDay when coadministered with the following

  • Posaconazole suspension 200 mg TID or 400 mg BID
  • Posaconazole IV injection 300 mg qDay
  • Posaconazole delayed-release tablets 300 mg qDay

• Avoid coadministration

  • Other strong CYP3A inhibitors (boceprevir, clarithromycin, cobicistat conivaptan, danoprevir and ritonavir, diltiazem, elvitegravir and ritonavir, idelalisib, indinavir and ritonavir, itraconazole, ketoconazole, lopinavir and ritonavir, nefazodone, nelfinavir, paritaprevir and ritonavir and [ombitasvir and/or dasabuvir], ritonavir, saquinavir and ritonavir, tipranavir and ritonavir, and troleandomycin)
  • If these inhibitors will be used short term (eg, anti-infectives for <7 days), interrupt ibrutinib
  • After discontinuation of a CYP3A inhibitor, resume previous dose of ibrutinib

Hepatic impairment

• Modify dose based on following ULN unless of non-hepatic origin or due to Gilbert’s syndrome

• Total bilirubin (TB) level >1.5 to 3x ULN

  • ≥1 to <12 years: Reduce to 80 mg/m² PO qDay
  • ≥12 years: Reduce to 140 mg PO qDay
  • TB >3x ULN: Avoid use

Renal impairment

Mild-to-moderate (eCrCl ≥25 mL/min): No dosage adjustment necessary

Severe (eCrCl <25 mL/min) or patients on dialysis: Not studied

Dosing Considerations

Available via a limited distributed system from specialty pharmacies

Orphan Designations

Diffuse large B-cell lymphoma

Follicular lymphoma

Multiple myeloma

Pancreatic cancer

Gastric cancer, including gastroesophageal junction adenocarcinoma

Sponsor

• Pharmacyclics, Inc.; 995 E. Arques Avenue; Sunnyvale, CA 94085

Chronic Graft versus Host Disease

Indicated for chronic graft versus host disease (cGVHD) in adult and pediatric patients aged ≥1 year who failed >1 lines of systemic therapy

1 to <12 years: 1 to <12 years: 240 mg/m2 PO qDay (not to exceed 420 mg/dose)  

≥12 years: 420 mg PO qDay

Continue until cGVHD progression, recurrence of an underlying malignancy, or unacceptable toxicity

If therapy is no longer required, consider discontinuing therapy based on medical assessment of individual patient

Dosage Modifications

Grade 2 cardiac failure

• Evaluate the benefit-risk before resuming treatment

• ≥1 to <12 years

  • First occurrence: Restart at 160 mg/m² qDay
  • Second occurrence: Restart at 80 mg/m² qDay
  • Third occurrence: Discontinue therapy

• ≥12 years

  • First occurrence: Restart at 280 mg qDay
  • Second occurrence: Restart at 140 mg qDay
  • Third occurrence: Discontinue therapy

Grade 3 cardiac arrhythmias

• ≥1 to <12 years

  • First occurrence: Restart at 160 mg/m² qDay
  • Second occurrence: Discontinue therapy

• ≥12 years

  • First occurrence: Restart at 280 mg qDay
  • Second occurrence: Discontinue therapy

Grade ≥3 cardiac failure or Grade 4 cardiac arrhythmias

• First occurrence: Discontinue therapy

Nonhematological and hematologic toxicities

• Other Grade 3 or 4 nonhematological toxicities
• Grade 3 or 4 neutropenia with infection or fever
• Grade 4 hematological toxicities

• ≥1 to <12 years

  • First occurrence: Restart at 160 mg/m² qDay
  • Second occurrence: Restart at 80 mg/m² qDay
  • Third occurrence: Discontinue therapy

• ≥12 years

  • First occurrence: Restart at 280 mg qDay
  • Second occurrence: Restart at 140 mg qDay
  • Third occurrence: Discontinue therapy

CYP3A inducers

• Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold
• Avoid coadministration of strong CYP3A inducers (eg, carbamazepine, rifampin, phenytoin, St. John’s Wort, enzalutamide, mitotane)

Coadministration with CYP3A inhibitors for ≥1 to <12 years

• Moderate CYP3A4 inhibitor: Reduce ibrutinib 160 mg/m2 qDay; modify dose as recommended
• Posaconazole at any dosage: Reduce ibrutinib 80 mg/m2 qDay

Avoid coadministration

• Other strong CYP3A inhibitors (boceprevir, clarithromycin, cobicistat conivaptan, danoprevir and ritonavir, diltiazem, elvitegravir and ritonavir, idelalisib, indinavir and ritonavir, itraconazole, ketoconazole, lopinavir and ritonavir, nefazodone, nelfinavir, paritaprevir and ritonavir and [ombitasvir and/or dasabuvir], ritonavir, saquinavir and ritonavir, tipranavir and ritonavir, and troleandomycin)
• If these inhibitors will be used short term (eg, anti-infectives for <7 days), interrupt ibrutinib
• After discontinuation of a CYP3A inhibitor, resume previous dose of ibrutinib

Coadministration with CYP3A inhibitors for ≥12 years

• Moderate CYP3A4 inhibitor: Reduce ibrutinib to 420 mg qDay; modify dose as recommended

• Reduce ibrutinib dose to 280 mg qDay when coadministered with the following

  • Voriconazole 200 mg BID
  • Posaconazole suspension 100 mg qDay, 100 mg BID, or 200 mg BID
  • Modify dose as recommended

• Reduce ibrutinib dose to 140 mg qDay when coadministered with the following

  • Posaconazole suspension 200 mg TID or 400 mg BID
  • Posaconazole IV injection 300 mg qDay
  • Posaconazole delayed-release tablets 300 mg qDay

• Avoid coadministration

  • Other strong CYP3A inhibitors (boceprevir, clarithromycin, cobicistat conivaptan, danoprevir and ritonavir, diltiazem, elvitegravir and ritonavir, idelalisib, indinavir and ritonavir, itraconazole, ketoconazole, lopinavir and ritonavir, nefazodone, nelfinavir, paritaprevir and ritonavir and [ombitasvir and/or dasabuvir], ritonavir, saquinavir and ritonavir, tipranavir and ritonavir, and troleandomycin)
  • If these inhibitors will be used short term (eg, anti-infectives for <7 days), interrupt ibrutinib
  • After discontinuation of a CYP3A inhibitor, resume previous dose of ibrutinib

Hepatic impairment

• Modify dose based on following ULN unless of non-hepatic origin or due to Gilbert’s syndrome

• Total bilirubin (TB) level >1.5 to 3x ULN

  • ≥1 to <12 years: Reduce to 80 mg/m² PO qDay
  • ≥12 years: Reduce to 140 mg PO qDay
  • TB >3x ULN: Avoid use

Renal impairment

Mild-to-moderate (eCrCl ≥25 mL/min): No dosage adjustment necessary

Severe (eCrCl <25 mL/min) or patients on dialysis: Not studied

Contraindicated (16)

• adenovirus types 4 and 7 live, oral

  ibrutinib decreases effects of adenovirus types 4 and 7 live, oral by pharmacodynamic antagonism. Contraindicated. Immunosuppressives may diminish therapeutic effects of vaccines and increase risk of adverse effects (increased risk of infection). Live-attenuated vaccines should be avoided for at least 3 mo after cessation of immunosuppressive therapy.

• BCG vaccine live

  ibrutinib decreases effects of BCG vaccine live by pharmacodynamic antagonism. Contraindicated. Immunosuppressives may diminish therapeutic effects of vaccines and increase risk of adverse effects (increased risk of infection). Live-attenuated vaccines should be avoided for at least 3 mo after cessation of immunosuppressive therapy.

• cholera vaccine

  ibrutinib decreases effects of cholera vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressives may diminish therapeutic effects of vaccines and increase risk of adverse effects (increased risk of infection). Live-attenuated vaccines should be avoided for at least 3 mo after cessation of immunosuppressive therapy.

• influenza virus vaccine quadrivalent, intranasal

  ibrutinib decreases effects of influenza virus vaccine quadrivalent, intranasal by pharmacodynamic antagonism. Contraindicated. Immunosuppressives may diminish therapeutic effects of vaccines and increase risk of adverse effects (increased risk of infection). Live-attenuated vaccines should be avoided for at least 3 mo after cessation of immunosuppressive therapy.

• measles (rubeola) vaccine

  ibrutinib decreases effects of measles (rubeola) vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressives may diminish therapeutic effects of vaccines and increase risk of adverse effects (increased risk of infection). Live-attenuated vaccines should be avoided for at least 3 mo after cessation of immunosuppressive therapy.

• measles mumps and rubella vaccine, live

  ibrutinib decreases effects of measles mumps and rubella vaccine, live by pharmacodynamic antagonism. Contraindicated. Immunosuppressives may diminish therapeutic effects of vaccines and increase risk of adverse effects (increased risk of infection). Live-attenuated vaccines should be avoided for at least 3 mo after cessation of immunosuppressive therapy.

• measles, mumps, rubella and varicella vaccine, live

  ibrutinib decreases effects of measles, mumps, rubella and varicella vaccine, live by pharmacodynamic antagonism. Contraindicated. Immunosuppressives may diminish therapeutic effects of vaccines and increase risk of adverse effects (increased risk of infection). Live-attenuated vaccines should be avoided for at least 3 mo after cessation of immunosuppressive therapy.

• ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)

  ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• rotavirus oral vaccine, live

  ibrutinib decreases effects of rotavirus oral vaccine, live by pharmacodynamic antagonism. Contraindicated. Immunosuppressives may diminish therapeutic effects of vaccines and increase risk of adverse effects (increased risk of infection). Live-attenuated vaccines should be avoided for at least 3 mo after cessation of immunosuppressive therapy.

• rubella vaccine

  ibrutinib decreases effects of rubella vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressives may diminish therapeutic effects of vaccines and increase risk of adverse effects (increased risk of infection). Live-attenuated vaccines should be avoided for at least 3 mo after cessation of immunosuppressive therapy.

• smallpox (vaccinia) vaccine, live

  ibrutinib decreases effects of smallpox (vaccinia) vaccine, live by pharmacodynamic antagonism. Contraindicated. Immunosuppressives may diminish therapeutic effects of vaccines and increase risk of adverse effects (increased risk of infection). Live-attenuated vaccines should be avoided for at least 3 mo after cessation of immunosuppressive therapy.

• typhoid polysaccharide vaccine

  ibrutinib decreases effects of typhoid polysaccharide vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressives may diminish therapeutic effects of vaccines and increase risk of adverse effects (increased risk of infection). Live-attenuated vaccines should be avoided for at least 3 mo after cessation of immunosuppressive therapy.

• typhoid vaccine live

  ibrutinib decreases effects of typhoid vaccine live by pharmacodynamic antagonism. Contraindicated. Immunosuppressives may diminish therapeutic effects of vaccines and increase risk of adverse effects (increased risk of infection). Live-attenuated vaccines should be avoided for at least 3 mo after cessation of immunosuppressive therapy.

• varicella virus vaccine live

  ibrutinib decreases effects of varicella virus vaccine live by pharmacodynamic antagonism. Contraindicated. Immunosuppressives may diminish therapeutic effects of vaccines and increase risk of adverse effects (increased risk of infection). Live-attenuated vaccines should be avoided for at least 3 mo after cessation of immunosuppressive therapy.

• yellow fever vaccine

  ibrutinib decreases effects of yellow fever vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressives may diminish therapeutic effects of vaccines and increase risk of adverse effects (increased risk of infection). Live-attenuated vaccines should be avoided for at least 3 mo after cessation of immunosuppressive therapy.

• zoster vaccine live

  ibrutinib decreases effects of zoster vaccine live by pharmacodynamic antagonism. Contraindicated. Immunosuppressives may diminish therapeutic effects of vaccines and increase risk of adverse effects (increased risk of infection). Live-attenuated vaccines should be avoided for at least 3 mo after cessation of immunosuppressive therapy.

Serious - Use Alternative (73)

• amobarbital

  amobarbital decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• apalutamide

  apalutamide will decrease the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

• aprepitant

  aprepitant increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• atazanavir

  atazanavir increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• bosentan

  bosentan decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• carbamazepine

  carbamazepine decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• chloramphenicol

  chloramphenicol will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• ciprofloxacin

  ciprofloxacin increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• clarithromycin

  clarithromycin increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• cobicistat

  cobicistat will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• conivaptan

  conivaptan increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• dabrafenib

  dabrafenib decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• darunavir

  darunavir increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• deferiprone

  deferiprone, ibrutinib. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid use of deferiprone with other drugs known to be associated with neutropenia or agranulocytosis; if an alternative is not possible, monitor absolute neutrophil count more frequently.

• dexamethasone

  dexamethasone decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• diltiazem

  diltiazem increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• edoxaban

  ibrutinib will increase the level or effect of edoxaban by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Dose adjustment may be required with strong P-gp inhibitors. DVT/PE treatment: Decrease dose to 30 mg PO once daily. NVAF: No dose reduction recommended

• efavirenz

  efavirenz decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• enzalutamide

  enzalutamide decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• erythromycin ethylsuccinate

  erythromycin ethylsuccinate increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• erythromycin stearate

  erythromycin stearate increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• eslicarbazepine acetate

  eslicarbazepine acetate will decrease the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold

• etravirine

  etravirine decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• fexinidazole

  fexinidazole will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

• fluconazole

  fluconazole increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• fosamprenavir

  fosamprenavir increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• fosaprepitant

  fosaprepitant increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• fosphenytoin

  fosphenytoin decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• grapefruit

  grapefruit increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• idelalisib

  idelalisib will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• imatinib

  imatinib increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• indinavir

  indinavir increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• isoniazid

  isoniazid increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• itraconazole

  itraconazole increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• ivosidenib

  ivosidenib will decrease the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

• ketoconazole

  ketoconazole increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• levoketoconazole

  levoketoconazole increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• lopinavir

  lopinavir increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• mifepristone

  mifepristone will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• nafcillin

  nafcillin decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• nefazodone

  nefazodone increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• nelfinavir

  nelfinavir increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• nevirapine

  nevirapine decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• nicardipine

  nicardipine increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• nirmatrelvir

  nirmatrelvir will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• nirmatrelvir/ritonavir

  nirmatrelvir/ritonavir will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• oxcarbazepine

  oxcarbazepine decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• palifermin

  palifermin increases toxicity of ibrutinib by Other (see comment). Avoid or Use Alternate Drug. Comment: Palifermin should not be administered within 24 hr before, during infusion of, or within 24 hr after administration of antineoplastic agents. Coadministration of palifermin within 24 hr of chemotherapy resulted in increased severity and duration of oral mucositis.

• pentobarbital

  pentobarbital decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• phenobarbital

  phenobarbital decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• phenytoin

  phenytoin decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• ponesimod

  ponesimod, ibrutinib. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Consult cardiologist if considering treatment. Generally, should not be initiated in patients who are concurrently taking QT prolonging drugs with known arrhythmogenic properties, such as HR-lowering calcium channel blockers (eg, verapamil, diltiazem).

• posaconazole

  posaconazole increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with posaconazole suspension at doses of 100 mg qDay, 100 mg BID, or 200 mg BID, reduce ibrutinib dose to 140 mg qDay (B-cell malignancies) or 280 mg qDay (graft versus host disease [GvHD]). Coadministration with posaconazole suspension at doses of 200 mg TID, 400 mg BID , posaconazole 300 mg IV qDay, posaconazole delayed-release tablets 300 mg qDay reduce ibrutinib dose to 70 mg qDay (B-cell malignancies) or 140 mg qDay (GvHD). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• primidone

  primidone decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• quinidine

  quinidine increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• quinupristin/dalfopristin

  quinupristin/dalfopristin increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• rifabutin

  rifabutin decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• rifampin

  rifampin decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• rifapentine

  rifapentine decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• rimegepant

  ibrutinib will increase the level or effect of rimegepant by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

• ritonavir

  ritonavir increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• ropeginterferon alfa 2b

  ropeginterferon alfa 2b, ibrutinib. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Myelosuppressive agents can produce additive myelosuppression. Avoid use and monitor patients receiving the combination for effects of excessive myelosuppression.

• saquinavir

  saquinavir increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• secobarbital

  secobarbital decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• sertraline

  sertraline increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• St John's Wort

  St John's Wort decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• tipranavir

  tipranavir increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• tucatinib

  tucatinib will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

• venetoclax

  ibrutinib will increase the level or effect of venetoclax by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If a P-gp inhibitor must be used, reduce the venetoclax dose by at least 50%. Monitor more closely for signs of venetoclax toxicities.

• verapamil

  verapamil increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• voriconazole

  voriconazole increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with voriconazole 200 mg PO BID, reduce ibrutinib dose to 140 mg qDay (B-cell malignancies) or 280 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• voxelotor

  voxelotor will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

Monitor Closely (138)

• abciximab

  ibrutinib will increase the level or effect of abciximab by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• alteplase

  ibrutinib will increase the level or effect of alteplase by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• anagrelide

  ibrutinib will increase the level or effect of anagrelide by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• anthrax vaccine adsorbed

  ibrutinib decreases effects of anthrax vaccine adsorbed by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• antithrombin alfa

  ibrutinib will increase the level or effect of antithrombin alfa by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• antithrombin III

  ibrutinib will increase the level or effect of antithrombin III by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• apixaban

  ibrutinib will increase the level or effect of apixaban by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• argatroban

  ibrutinib will increase the level or effect of argatroban by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• aspirin

  ibrutinib will increase the level or effect of aspirin by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• aspirin rectal

  ibrutinib will increase the level or effect of aspirin rectal by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• belzutifan

  belzutifan will decrease the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.

• berotralstat

  ibrutinib increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

• betrixaban

  ibrutinib increases levels of betrixaban by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Decrease betrixaban dose to 80 mg PO once, then 40 mg PO qDay if coadministered with a P-gp inhibitor.
  
  ibrutinib will increase the level or effect of betrixaban by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• bicalutamide

  bicalutamide increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• bivalirudin

  ibrutinib will increase the level or effect of bivalirudin by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• cangrelor

  ibrutinib will increase the level or effect of cangrelor by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• celecoxib

  ibrutinib will increase the level or effect of celecoxib by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• cenobamate

  cenobamate will decrease the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

• ceritinib

  ceritinib increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• cilostazol

  ibrutinib will increase the level or effect of cilostazol by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• citalopram

  ibrutinib will increase the level or effect of citalopram by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• clopidogrel

  ibrutinib will increase the level or effect of clopidogrel by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• clotrimazole

  clotrimazole increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• crizotinib

  crizotinib increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• cyclosporine

  cyclosporine increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• dabigatran

  ibrutinib will increase the level or effect of dabigatran by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Atrial fibrillation: Avoid coadministering dabigatran with P-gp inhibitors if CrCl <30 mL/min. DVT/PE treatment: Avoid coadministering dabigatran with P-gp inhibitors if CrCl <50 mL/min
  
  ibrutinib will increase the level or effect of dabigatran by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• dalteparin

  ibrutinib will increase the level or effect of dalteparin by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• defibrotide

  ibrutinib will increase the level or effect of defibrotide by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• desipramine

  desipramine increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• desirudin

  ibrutinib will increase the level or effect of desirudin by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• desvenlafaxine

  ibrutinib will increase the level or effect of desvenlafaxine by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• diclofenac

  ibrutinib will increase the level or effect of diclofenac by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• diflunisal

  ibrutinib will increase the level or effect of diflunisal by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• dipyridamole

  ibrutinib will increase the level or effect of dipyridamole by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• doxycycline

  doxycycline increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• dronedarone

  dronedarone increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• duloxetine

  ibrutinib will increase the level or effect of duloxetine by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• duvelisib

  duvelisib will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with duvelisib increases AUC of a sensitive CYP3A4 substrate which may increase the risk of toxicities of these drugs. Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the coadministered sensitive CYP3A substrate.

• edoxaban

  ibrutinib will increase the level or effect of edoxaban by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• elagolix

  elagolix decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

• encorafenib

  encorafenib, ibrutinib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

• enoxaparin

  ibrutinib will increase the level or effect of enoxaparin by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• epoprostenol

  ibrutinib will increase the level or effect of epoprostenol by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• eptifibatide

  ibrutinib will increase the level or effect of eptifibatide by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• erythromycin base

  erythromycin base increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• erythromycin lactobionate

  erythromycin lactobionate increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• escitalopram

  ibrutinib will increase the level or effect of escitalopram by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• etodolac

  ibrutinib will increase the level or effect of etodolac by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• fedratinib

  fedratinib will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

• fenoprofen

  ibrutinib will increase the level or effect of fenoprofen by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• fish oil triglycerides

  fish oil triglycerides will increase the level or effect of ibrutinib by anticoagulation. Use Caution/Monitor. Prolonged bleeding reported in patients taking antiplatelet agents or anticoagulants and oral omega-3 fatty acids. Periodically monitor bleeding time in patients receiving fish oil triglycerides and concomitant antiplatelet agents or anticoagulants.

• fluoxetine

  ibrutinib will increase the level or effect of fluoxetine by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• flurbiprofen

  ibrutinib will increase the level or effect of flurbiprofen by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• fluvoxamine

  ibrutinib will increase the level or effect of fluvoxamine by anticoagulation. Use Caution/Monitor. Ibrutinib may increase risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding

• fondaparinux

  ibrutinib will increase the level or effect of fondaparinux by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• glecaprevir/pibrentasvir

  ibrutinib will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• haemophilus influenzae type b vaccine

  ibrutinib decreases effects of haemophilus influenzae type b vaccine by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Avoid vaccination during chemotherapy or radiation therapy if possible because antibody response might be suboptimal. Patients vaccinated within a 14-day period before starting or during immunosuppressive therapy should be revaccinated =3 months after therapy is discontinued if immune competence has been restored. .

• haloperidol

  haloperidol increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• heparin

  ibrutinib will increase the level or effect of heparin by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• hepatitis A vaccine inactivated

  ibrutinib decreases effects of hepatitis A vaccine inactivated by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• hepatitis a/b vaccine

  ibrutinib decreases effects of hepatitis a/b vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• hepatitis b vaccine

  ibrutinib decreases effects of hepatitis b vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• HIV vaccine

  ibrutinib decreases effects of HIV vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• human papillomavirus vaccine, nonavalent

  ibrutinib decreases effects of human papillomavirus vaccine, nonavalent by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• human papillomavirus vaccine, quadrivalent

  ibrutinib decreases effects of human papillomavirus vaccine, quadrivalent by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• ibuprofen

  ibrutinib will increase the level or effect of ibuprofen by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• ibuprofen IV

  ibrutinib will increase the level or effect of ibuprofen IV by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• iloperidone

  iloperidone increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• iloprost

  ibrutinib will increase the level or effect of iloprost by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• indomethacin

  ibrutinib will increase the level or effect of indomethacin by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• influenza A (H5N1) vaccine

  ibrutinib decreases effects of influenza A (H5N1) vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• influenza virus vaccine (H5N1), adjuvanted

  ibrutinib decreases effects of influenza virus vaccine (H5N1), adjuvanted by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• influenza virus vaccine quadrivalent

  ibrutinib decreases effects of influenza virus vaccine quadrivalent by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• influenza virus vaccine quadrivalent, adjuvanted

  ibrutinib decreases effects of influenza virus vaccine quadrivalent, adjuvanted by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• influenza virus vaccine quadrivalent, cell-cultured

  ibrutinib decreases effects of influenza virus vaccine quadrivalent, cell-cultured by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• influenza virus vaccine quadrivalent, recombinant

  ibrutinib decreases effects of influenza virus vaccine quadrivalent, recombinant by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• influenza virus vaccine trivalent

  ibrutinib decreases effects of influenza virus vaccine trivalent by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• influenza virus vaccine trivalent, adjuvanted

  ibrutinib decreases effects of influenza virus vaccine trivalent, adjuvanted by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• influenza virus vaccine trivalent, recombinant

  ibrutinib decreases effects of influenza virus vaccine trivalent, recombinant by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• istradefylline

  istradefylline will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

• Japanese encephalitis virus vaccine

  ibrutinib decreases effects of Japanese encephalitis virus vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• ketoprofen

  ibrutinib will increase the level or effect of ketoprofen by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• ketorolac

  ibrutinib will increase the level or effect of ketorolac by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• lapatinib

  lapatinib increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• lenacapavir

  lenacapavir will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.

• letermovir

  letermovir increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• levomilnacipran

  ibrutinib will increase the level or effect of levomilnacipran by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• lorlatinib

  lorlatinib will decrease the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• meclofenamate

  ibrutinib will increase the level or effect of meclofenamate by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• mefenamic acid

  ibrutinib will increase the level or effect of mefenamic acid by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• meloxicam

  ibrutinib will increase the level or effect of meloxicam by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• meningococcal A C Y and W-135 diphtheria conjugate vaccine

  ibrutinib decreases effects of meningococcal A C Y and W-135 diphtheria conjugate vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• meningococcal A C Y and W-135 polysaccharide vaccine combined

  ibrutinib decreases effects of meningococcal A C Y and W-135 polysaccharide vaccine combined by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• meningococcal group B vaccine

  ibrutinib decreases effects of meningococcal group B vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• metronidazole

  metronidazole increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• milnacipran

  ibrutinib will increase the level or effect of milnacipran by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• mitotane

  mitotane decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.

• nabumetone

  ibrutinib will increase the level or effect of nabumetone by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• naldemedine

  ibrutinib increases levels of naldemedine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor naldemedine for potential adverse effects if coadministered with P-gp inhibitors.

• naproxen

  ibrutinib will increase the level or effect of naproxen by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• netupitant/palonosetron

  netupitant/palonosetron increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• ofatumumab SC

  ofatumumab SC, ibrutinib. Either increases effects of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Consider the risk of additive immune system effects when coadministering immunosuppressive therapies with coadministration. When switching from therapies with immune effects, take into account the duration and mechanism of action of these therapies when initiating ofatumumab SC.

• oxaprozin

  ibrutinib will increase the level or effect of oxaprozin by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• paroxetine

  ibrutinib will increase the level or effect of paroxetine by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• piroxicam

  ibrutinib will increase the level or effect of piroxicam by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• pneumococcal vaccine 13-valent

  ibrutinib decreases effects of pneumococcal vaccine 13-valent by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• pneumococcal vaccine heptavalent

  ibrutinib decreases effects of pneumococcal vaccine heptavalent by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• pneumococcal vaccine polyvalent

  ibrutinib decreases effects of pneumococcal vaccine polyvalent by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• poliovirus vaccine inactivated

  ibrutinib decreases effects of poliovirus vaccine inactivated by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Avoid vaccination during chemotherapy or radiation therapy if possible because antibody response might be suboptimal. Patients vaccinated within a 14-day period before starting or during immunosuppressive therapy should be revaccinated =3 months after therapy is discontinued if immune competence has been restored. .

• prasugrel

  ibrutinib will increase the level or effect of prasugrel by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• protein C concentrate

  ibrutinib will increase the level or effect of protein C concentrate by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• rabies vaccine

  ibrutinib decreases effects of rabies vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• rabies vaccine chick embryo cell derived

  ibrutinib decreases effects of rabies vaccine chick embryo cell derived by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• ribociclib

  ribociclib increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• rivaroxaban

  ibrutinib will increase the level or effect of rivaroxaban by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• rucaparib

  rucaparib will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

• schisandra

  schisandra increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• sertraline

  ibrutinib will increase the level or effect of sertraline by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• siponimod

  siponimod and ibrutinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

• stiripentol

  stiripentol, ibrutinib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.

• sulindac

  ibrutinib will increase the level or effect of sulindac by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• talazoparib

  ibrutinib will increase the level or effect of talazoparib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Talazoparib is a P-glycoprotein (P-gp) substrate; coadministration with P-gp inhibitors may increase talazoparib systemic exposure.

• tazemetostat

  tazemetostat will decrease the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tecovirimat

  tecovirimat will decrease the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

• tenecteplase

  ibrutinib will increase the level or effect of tenecteplase by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• tetanus toxoid adsorbed or fluid

  ibrutinib decreases effects of tetanus toxoid adsorbed or fluid by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• ticagrelor

  ibrutinib will increase the level or effect of ticagrelor by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• ticlopidine

  ibrutinib will increase the level or effect of ticlopidine by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• tirofiban

  ibrutinib will increase the level or effect of tirofiban by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• tolmetin

  ibrutinib will increase the level or effect of tolmetin by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• trastuzumab

  trastuzumab, ibrutinib. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

• trastuzumab deruxtecan

  trastuzumab deruxtecan, ibrutinib. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

• treprostinil

  ibrutinib will increase the level or effect of treprostinil by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• venlafaxine

  ibrutinib will increase the level or effect of venlafaxine by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• vilazodone

  ibrutinib will increase the level or effect of vilazodone by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• vorapaxar

  ibrutinib will increase the level or effect of vorapaxar by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• vortioxetine

  ibrutinib will increase the level or effect of vortioxetine by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• zoster vaccine recombinant

  ibrutinib decreases effects of zoster vaccine recombinant by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

Minor (4)

• acetazolamide

  acetazolamide will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• anastrozole

  anastrozole will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• cyclophosphamide

  cyclophosphamide will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• larotrectinib

  larotrectinib will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• abciximab

  Monitor Closely (1)ibrutinib will increase the level or effect of abciximab by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• acetazolamide

  Minor (1)acetazolamide will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• adenovirus types 4 and 7 live, oral

  Contraindicated (1)ibrutinib decreases effects of adenovirus types 4 and 7 live, oral by pharmacodynamic antagonism. Contraindicated. Immunosuppressives may diminish therapeutic effects of vaccines and increase risk of adverse effects (increased risk of infection). Live-attenuated vaccines should be avoided for at least 3 mo after cessation of immunosuppressive therapy.

• alteplase

  Monitor Closely (1)ibrutinib will increase the level or effect of alteplase by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• amobarbital

  Serious - Use Alternative (1)amobarbital decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• anagrelide

  Monitor Closely (1)ibrutinib will increase the level or effect of anagrelide by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• anastrozole

  Minor (1)anastrozole will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• anthrax vaccine adsorbed

  Monitor Closely (1)ibrutinib decreases effects of anthrax vaccine adsorbed by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• antithrombin alfa

  Monitor Closely (1)ibrutinib will increase the level or effect of antithrombin alfa by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• antithrombin III

  Monitor Closely (1)ibrutinib will increase the level or effect of antithrombin III by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• apalutamide

  Serious - Use Alternative (1)apalutamide will decrease the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

• apixaban

  Monitor Closely (1)ibrutinib will increase the level or effect of apixaban by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• aprepitant

  Serious - Use Alternative (1)aprepitant increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• argatroban

  Monitor Closely (1)ibrutinib will increase the level or effect of argatroban by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• aspirin

  Monitor Closely (1)ibrutinib will increase the level or effect of aspirin by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• aspirin rectal

  Monitor Closely (1)ibrutinib will increase the level or effect of aspirin rectal by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• atazanavir

  Serious - Use Alternative (1)atazanavir increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• BCG vaccine live

  Contraindicated (1)ibrutinib decreases effects of BCG vaccine live by pharmacodynamic antagonism. Contraindicated. Immunosuppressives may diminish therapeutic effects of vaccines and increase risk of adverse effects (increased risk of infection). Live-attenuated vaccines should be avoided for at least 3 mo after cessation of immunosuppressive therapy.

• belzutifan

  Monitor Closely (1)belzutifan will decrease the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.

• berotralstat

  Monitor Closely (1)ibrutinib increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

• betrixaban

  Monitor Closely (2)ibrutinib increases levels of betrixaban by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Decrease betrixaban dose to 80 mg PO once, then 40 mg PO qDay if coadministered with a P-gp inhibitor.
  
  ibrutinib will increase the level or effect of betrixaban by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• bicalutamide

  Monitor Closely (1)bicalutamide increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• bivalirudin

  Monitor Closely (1)ibrutinib will increase the level or effect of bivalirudin by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• bosentan

  Serious - Use Alternative (1)bosentan decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• cangrelor

  Monitor Closely (1)ibrutinib will increase the level or effect of cangrelor by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• carbamazepine

  Serious - Use Alternative (1)carbamazepine decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• celecoxib

  Monitor Closely (1)ibrutinib will increase the level or effect of celecoxib by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• cenobamate

  Monitor Closely (1)cenobamate will decrease the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

• ceritinib

  Monitor Closely (1)ceritinib increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• chloramphenicol

  Serious - Use Alternative (1)chloramphenicol will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• cholera vaccine

  Contraindicated (1)ibrutinib decreases effects of cholera vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressives may diminish therapeutic effects of vaccines and increase risk of adverse effects (increased risk of infection). Live-attenuated vaccines should be avoided for at least 3 mo after cessation of immunosuppressive therapy.

• cilostazol

  Monitor Closely (1)ibrutinib will increase the level or effect of cilostazol by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• ciprofloxacin

  Serious - Use Alternative (1)ciprofloxacin increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• citalopram

  Monitor Closely (1)ibrutinib will increase the level or effect of citalopram by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• clarithromycin

  Serious - Use Alternative (1)clarithromycin increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• clopidogrel

  Monitor Closely (1)ibrutinib will increase the level or effect of clopidogrel by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• clotrimazole

  Monitor Closely (1)clotrimazole increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• cobicistat

  Serious - Use Alternative (1)cobicistat will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• conivaptan

  Serious - Use Alternative (1)conivaptan increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• crizotinib

  Monitor Closely (1)crizotinib increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• cyclophosphamide

  Minor (1)cyclophosphamide will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• cyclosporine

  Monitor Closely (1)cyclosporine increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• dabigatran

  Monitor Closely (2)ibrutinib will increase the level or effect of dabigatran by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Atrial fibrillation: Avoid coadministering dabigatran with P-gp inhibitors if CrCl <30 mL/min. DVT/PE treatment: Avoid coadministering dabigatran with P-gp inhibitors if CrCl <50 mL/min
  
  ibrutinib will increase the level or effect of dabigatran by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• dabrafenib

  Serious - Use Alternative (1)dabrafenib decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• dalteparin

  Monitor Closely (1)ibrutinib will increase the level or effect of dalteparin by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• darunavir

  Serious - Use Alternative (1)darunavir increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• deferiprone

  Serious - Use Alternative (1)deferiprone, ibrutinib. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid use of deferiprone with other drugs known to be associated with neutropenia or agranulocytosis; if an alternative is not possible, monitor absolute neutrophil count more frequently.

• defibrotide

  Monitor Closely (1)ibrutinib will increase the level or effect of defibrotide by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• desipramine

  Monitor Closely (1)desipramine increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• desirudin

  Monitor Closely (1)ibrutinib will increase the level or effect of desirudin by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• desvenlafaxine

  Monitor Closely (1)ibrutinib will increase the level or effect of desvenlafaxine by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• dexamethasone

  Serious - Use Alternative (1)dexamethasone decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• diclofenac

  Monitor Closely (1)ibrutinib will increase the level or effect of diclofenac by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• diflunisal

  Monitor Closely (1)ibrutinib will increase the level or effect of diflunisal by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• diltiazem

  Serious - Use Alternative (1)diltiazem increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• dipyridamole

  Monitor Closely (1)ibrutinib will increase the level or effect of dipyridamole by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• doxycycline

  Monitor Closely (1)doxycycline increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• dronedarone

  Monitor Closely (1)dronedarone increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• duloxetine

  Monitor Closely (1)ibrutinib will increase the level or effect of duloxetine by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• duvelisib

  Monitor Closely (1)duvelisib will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with duvelisib increases AUC of a sensitive CYP3A4 substrate which may increase the risk of toxicities of these drugs. Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the coadministered sensitive CYP3A substrate.

• edoxaban

  Monitor Closely (1)ibrutinib will increase the level or effect of edoxaban by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding. Serious - Use Alternative (1)ibrutinib will increase the level or effect of edoxaban by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Dose adjustment may be required with strong P-gp inhibitors. DVT/PE treatment: Decrease dose to 30 mg PO once daily. NVAF: No dose reduction recommended

• efavirenz

  Serious - Use Alternative (1)efavirenz decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• elagolix

  Monitor Closely (1)elagolix decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  Serious - Use Alternative (1)elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• encorafenib

  Monitor Closely (1)encorafenib, ibrutinib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

• enoxaparin

  Monitor Closely (1)ibrutinib will increase the level or effect of enoxaparin by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• enzalutamide

  Serious - Use Alternative (1)enzalutamide decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• epoprostenol

  Monitor Closely (1)ibrutinib will increase the level or effect of epoprostenol by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• eptifibatide

  Monitor Closely (1)ibrutinib will increase the level or effect of eptifibatide by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• erythromycin base

  Monitor Closely (1)erythromycin base increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• erythromycin ethylsuccinate

  Serious - Use Alternative (1)erythromycin ethylsuccinate increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• erythromycin lactobionate

  Monitor Closely (1)erythromycin lactobionate increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• erythromycin stearate

  Serious - Use Alternative (1)erythromycin stearate increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• escitalopram

  Monitor Closely (1)ibrutinib will increase the level or effect of escitalopram by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• eslicarbazepine acetate

  Serious - Use Alternative (1)eslicarbazepine acetate will decrease the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold

• etodolac

  Monitor Closely (1)ibrutinib will increase the level or effect of etodolac by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• etravirine

  Serious - Use Alternative (1)etravirine decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• fedratinib

  Monitor Closely (1)fedratinib will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

• fenoprofen

  Monitor Closely (1)ibrutinib will increase the level or effect of fenoprofen by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• fexinidazole

  Serious - Use Alternative (1)fexinidazole will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

• fish oil triglycerides

  Monitor Closely (1)fish oil triglycerides will increase the level or effect of ibrutinib by anticoagulation. Use Caution/Monitor. Prolonged bleeding reported in patients taking antiplatelet agents or anticoagulants and oral omega-3 fatty acids. Periodically monitor bleeding time in patients receiving fish oil triglycerides and concomitant antiplatelet agents or anticoagulants.

• fluconazole

  Serious - Use Alternative (1)fluconazole increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• fluoxetine

  Monitor Closely (1)ibrutinib will increase the level or effect of fluoxetine by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• flurbiprofen

  Monitor Closely (1)ibrutinib will increase the level or effect of flurbiprofen by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• fluvoxamine

  Monitor Closely (1)ibrutinib will increase the level or effect of fluvoxamine by anticoagulation. Use Caution/Monitor. Ibrutinib may increase risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding

• fondaparinux

  Monitor Closely (1)ibrutinib will increase the level or effect of fondaparinux by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• fosamprenavir

  Serious - Use Alternative (1)fosamprenavir increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• fosaprepitant

  Serious - Use Alternative (1)fosaprepitant increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• fosphenytoin

  Serious - Use Alternative (1)fosphenytoin decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• glecaprevir/pibrentasvir

  Monitor Closely (1)ibrutinib will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• grapefruit

  Serious - Use Alternative (1)grapefruit increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• haemophilus influenzae type b vaccine

  Monitor Closely (1)ibrutinib decreases effects of haemophilus influenzae type b vaccine by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Avoid vaccination during chemotherapy or radiation therapy if possible because antibody response might be suboptimal. Patients vaccinated within a 14-day period before starting or during immunosuppressive therapy should be revaccinated =3 months after therapy is discontinued if immune competence has been restored. .

• haloperidol

  Monitor Closely (1)haloperidol increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• heparin

  Monitor Closely (1)ibrutinib will increase the level or effect of heparin by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• hepatitis A vaccine inactivated

  Monitor Closely (1)ibrutinib decreases effects of hepatitis A vaccine inactivated by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• hepatitis a/b vaccine

  Monitor Closely (1)ibrutinib decreases effects of hepatitis a/b vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• hepatitis b vaccine

  Monitor Closely (1)ibrutinib decreases effects of hepatitis b vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• HIV vaccine

  Monitor Closely (1)ibrutinib decreases effects of HIV vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• human papillomavirus vaccine, nonavalent

  Monitor Closely (1)ibrutinib decreases effects of human papillomavirus vaccine, nonavalent by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• human papillomavirus vaccine, quadrivalent

  Monitor Closely (1)ibrutinib decreases effects of human papillomavirus vaccine, quadrivalent by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• ibuprofen

  Monitor Closely (1)ibrutinib will increase the level or effect of ibuprofen by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• ibuprofen IV

  Monitor Closely (1)ibrutinib will increase the level or effect of ibuprofen IV by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• idelalisib

  Serious - Use Alternative (1)idelalisib will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• iloperidone

  Monitor Closely (1)iloperidone increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• iloprost

  Monitor Closely (1)ibrutinib will increase the level or effect of iloprost by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• imatinib

  Serious - Use Alternative (1)imatinib increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• indinavir

  Serious - Use Alternative (1)indinavir increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• indomethacin

  Monitor Closely (1)ibrutinib will increase the level or effect of indomethacin by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• influenza A (H5N1) vaccine

  Monitor Closely (1)ibrutinib decreases effects of influenza A (H5N1) vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• influenza virus vaccine (H5N1), adjuvanted

  Monitor Closely (1)ibrutinib decreases effects of influenza virus vaccine (H5N1), adjuvanted by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• influenza virus vaccine quadrivalent

  Monitor Closely (1)ibrutinib decreases effects of influenza virus vaccine quadrivalent by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• influenza virus vaccine quadrivalent, adjuvanted

  Monitor Closely (1)ibrutinib decreases effects of influenza virus vaccine quadrivalent, adjuvanted by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• influenza virus vaccine quadrivalent, cell-cultured

  Monitor Closely (1)ibrutinib decreases effects of influenza virus vaccine quadrivalent, cell-cultured by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• influenza virus vaccine quadrivalent, intranasal

  Contraindicated (1)ibrutinib decreases effects of influenza virus vaccine quadrivalent, intranasal by pharmacodynamic antagonism. Contraindicated. Immunosuppressives may diminish therapeutic effects of vaccines and increase risk of adverse effects (increased risk of infection). Live-attenuated vaccines should be avoided for at least 3 mo after cessation of immunosuppressive therapy.

• influenza virus vaccine quadrivalent, recombinant

  Monitor Closely (1)ibrutinib decreases effects of influenza virus vaccine quadrivalent, recombinant by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• influenza virus vaccine trivalent

  Monitor Closely (1)ibrutinib decreases effects of influenza virus vaccine trivalent by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• influenza virus vaccine trivalent, adjuvanted

  Monitor Closely (1)ibrutinib decreases effects of influenza virus vaccine trivalent, adjuvanted by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• influenza virus vaccine trivalent, recombinant

  Monitor Closely (1)ibrutinib decreases effects of influenza virus vaccine trivalent, recombinant by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• isoniazid

  Serious - Use Alternative (1)isoniazid increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• istradefylline

  Monitor Closely (1)istradefylline will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

• itraconazole

  Serious - Use Alternative (1)itraconazole increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• ivosidenib

  Serious - Use Alternative (1)ivosidenib will decrease the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

• Japanese encephalitis virus vaccine

  Monitor Closely (1)ibrutinib decreases effects of Japanese encephalitis virus vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• ketoconazole

  Serious - Use Alternative (1)ketoconazole increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• ketoprofen

  Monitor Closely (1)ibrutinib will increase the level or effect of ketoprofen by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• ketorolac

  Monitor Closely (1)ibrutinib will increase the level or effect of ketorolac by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• lapatinib

  Monitor Closely (1)lapatinib increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• larotrectinib

  Minor (1)larotrectinib will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• lenacapavir

  Monitor Closely (1)lenacapavir will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.

• letermovir

  Monitor Closely (1)letermovir increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• levoketoconazole

  Serious - Use Alternative (1)levoketoconazole increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• levomilnacipran

  Monitor Closely (1)ibrutinib will increase the level or effect of levomilnacipran by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• lopinavir

  Serious - Use Alternative (1)lopinavir increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• lorlatinib

  Monitor Closely (1)lorlatinib will decrease the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• measles (rubeola) vaccine

  Contraindicated (1)ibrutinib decreases effects of measles (rubeola) vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressives may diminish therapeutic effects of vaccines and increase risk of adverse effects (increased risk of infection). Live-attenuated vaccines should be avoided for at least 3 mo after cessation of immunosuppressive therapy.

• measles mumps and rubella vaccine, live

  Contraindicated (1)ibrutinib decreases effects of measles mumps and rubella vaccine, live by pharmacodynamic antagonism. Contraindicated. Immunosuppressives may diminish therapeutic effects of vaccines and increase risk of adverse effects (increased risk of infection). Live-attenuated vaccines should be avoided for at least 3 mo after cessation of immunosuppressive therapy.

• measles, mumps, rubella and varicella vaccine, live

  Contraindicated (1)ibrutinib decreases effects of measles, mumps, rubella and varicella vaccine, live by pharmacodynamic antagonism. Contraindicated. Immunosuppressives may diminish therapeutic effects of vaccines and increase risk of adverse effects (increased risk of infection). Live-attenuated vaccines should be avoided for at least 3 mo after cessation of immunosuppressive therapy.

• meclofenamate

  Monitor Closely (1)ibrutinib will increase the level or effect of meclofenamate by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• mefenamic acid

  Monitor Closely (1)ibrutinib will increase the level or effect of mefenamic acid by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• meloxicam

  Monitor Closely (1)ibrutinib will increase the level or effect of meloxicam by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• meningococcal A C Y and W-135 diphtheria conjugate vaccine

  Monitor Closely (1)ibrutinib decreases effects of meningococcal A C Y and W-135 diphtheria conjugate vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• meningococcal A C Y and W-135 polysaccharide vaccine combined

  Monitor Closely (1)ibrutinib decreases effects of meningococcal A C Y and W-135 polysaccharide vaccine combined by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• meningococcal group B vaccine

  Monitor Closely (1)ibrutinib decreases effects of meningococcal group B vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• metronidazole

  Monitor Closely (1)metronidazole increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• mifepristone

  Serious - Use Alternative (1)mifepristone will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• milnacipran

  Monitor Closely (1)ibrutinib will increase the level or effect of milnacipran by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• mitotane

  Monitor Closely (1)mitotane decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.

• nabumetone

  Monitor Closely (1)ibrutinib will increase the level or effect of nabumetone by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• nafcillin

  Serious - Use Alternative (1)nafcillin decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• naldemedine

  Monitor Closely (1)ibrutinib increases levels of naldemedine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor naldemedine for potential adverse effects if coadministered with P-gp inhibitors.

• naproxen

  Monitor Closely (1)ibrutinib will increase the level or effect of naproxen by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• nefazodone

  Serious - Use Alternative (1)nefazodone increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• nelfinavir

  Serious - Use Alternative (1)nelfinavir increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• netupitant/palonosetron

  Monitor Closely (1)netupitant/palonosetron increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• nevirapine

  Serious - Use Alternative (1)nevirapine decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• nicardipine

  Serious - Use Alternative (1)nicardipine increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• nirmatrelvir

  Serious - Use Alternative (1)nirmatrelvir will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• nirmatrelvir/ritonavir

  Serious - Use Alternative (1)nirmatrelvir/ritonavir will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ofatumumab SC

  Monitor Closely (1)ofatumumab SC, ibrutinib. Either increases effects of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Consider the risk of additive immune system effects when coadministering immunosuppressive therapies with coadministration. When switching from therapies with immune effects, take into account the duration and mechanism of action of these therapies when initiating ofatumumab SC.

• ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)

  Contraindicated (1)ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• oxaprozin

  Monitor Closely (1)ibrutinib will increase the level or effect of oxaprozin by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• oxcarbazepine

  Serious - Use Alternative (1)oxcarbazepine decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• palifermin

  Serious - Use Alternative (1)palifermin increases toxicity of ibrutinib by Other (see comment). Avoid or Use Alternate Drug. Comment: Palifermin should not be administered within 24 hr before, during infusion of, or within 24 hr after administration of antineoplastic agents. Coadministration of palifermin within 24 hr of chemotherapy resulted in increased severity and duration of oral mucositis.

• paroxetine

  Monitor Closely (1)ibrutinib will increase the level or effect of paroxetine by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• pentobarbital

  Serious - Use Alternative (1)pentobarbital decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• phenobarbital

  Serious - Use Alternative (1)phenobarbital decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• phenytoin

  Serious - Use Alternative (1)phenytoin decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• piroxicam

  Monitor Closely (1)ibrutinib will increase the level or effect of piroxicam by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• pneumococcal vaccine 13-valent

  Monitor Closely (1)ibrutinib decreases effects of pneumococcal vaccine 13-valent by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• pneumococcal vaccine heptavalent

  Monitor Closely (1)ibrutinib decreases effects of pneumococcal vaccine heptavalent by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• pneumococcal vaccine polyvalent

  Monitor Closely (1)ibrutinib decreases effects of pneumococcal vaccine polyvalent by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• poliovirus vaccine inactivated

  Monitor Closely (1)ibrutinib decreases effects of poliovirus vaccine inactivated by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Avoid vaccination during chemotherapy or radiation therapy if possible because antibody response might be suboptimal. Patients vaccinated within a 14-day period before starting or during immunosuppressive therapy should be revaccinated =3 months after therapy is discontinued if immune competence has been restored. .

• ponesimod

  Serious - Use Alternative (1)ponesimod, ibrutinib. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Consult cardiologist if considering treatment. Generally, should not be initiated in patients who are concurrently taking QT prolonging drugs with known arrhythmogenic properties, such as HR-lowering calcium channel blockers (eg, verapamil, diltiazem).

• posaconazole

  Serious - Use Alternative (1)posaconazole increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with posaconazole suspension at doses of 100 mg qDay, 100 mg BID, or 200 mg BID, reduce ibrutinib dose to 140 mg qDay (B-cell malignancies) or 280 mg qDay (graft versus host disease [GvHD]). Coadministration with posaconazole suspension at doses of 200 mg TID, 400 mg BID , posaconazole 300 mg IV qDay, posaconazole delayed-release tablets 300 mg qDay reduce ibrutinib dose to 70 mg qDay (B-cell malignancies) or 140 mg qDay (GvHD). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• prasugrel

  Monitor Closely (1)ibrutinib will increase the level or effect of prasugrel by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• primidone

  Serious - Use Alternative (1)primidone decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• protein C concentrate

  Monitor Closely (1)ibrutinib will increase the level or effect of protein C concentrate by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• quinidine

  Serious - Use Alternative (1)quinidine increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• quinupristin/dalfopristin

  Serious - Use Alternative (1)quinupristin/dalfopristin increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• rabies vaccine

  Monitor Closely (1)ibrutinib decreases effects of rabies vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• rabies vaccine chick embryo cell derived

  Monitor Closely (1)ibrutinib decreases effects of rabies vaccine chick embryo cell derived by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• ribociclib

  Monitor Closely (1)ribociclib increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• rifabutin

  Serious - Use Alternative (1)rifabutin decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• rifampin

  Serious - Use Alternative (1)rifampin decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• rifapentine

  Serious - Use Alternative (1)rifapentine decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• rimegepant

  Serious - Use Alternative (1)ibrutinib will increase the level or effect of rimegepant by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

• ritonavir

  Serious - Use Alternative (1)ritonavir increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• rivaroxaban

  Monitor Closely (1)ibrutinib will increase the level or effect of rivaroxaban by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• ropeginterferon alfa 2b

  Serious - Use Alternative (1)ropeginterferon alfa 2b, ibrutinib. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Myelosuppressive agents can produce additive myelosuppression. Avoid use and monitor patients receiving the combination for effects of excessive myelosuppression.

• rotavirus oral vaccine, live

  Contraindicated (1)ibrutinib decreases effects of rotavirus oral vaccine, live by pharmacodynamic antagonism. Contraindicated. Immunosuppressives may diminish therapeutic effects of vaccines and increase risk of adverse effects (increased risk of infection). Live-attenuated vaccines should be avoided for at least 3 mo after cessation of immunosuppressive therapy.

• rubella vaccine

  Contraindicated (1)ibrutinib decreases effects of rubella vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressives may diminish therapeutic effects of vaccines and increase risk of adverse effects (increased risk of infection). Live-attenuated vaccines should be avoided for at least 3 mo after cessation of immunosuppressive therapy.

• rucaparib

  Monitor Closely (1)rucaparib will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

• saquinavir

  Serious - Use Alternative (1)saquinavir increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• schisandra

  Monitor Closely (1)schisandra increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• secobarbital

  Serious - Use Alternative (1)secobarbital decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• sertraline

  Monitor Closely (1)ibrutinib will increase the level or effect of sertraline by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding. Serious - Use Alternative (1)sertraline increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• siponimod

  Monitor Closely (1)siponimod and ibrutinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

• smallpox (vaccinia) vaccine, live

  Contraindicated (1)ibrutinib decreases effects of smallpox (vaccinia) vaccine, live by pharmacodynamic antagonism. Contraindicated. Immunosuppressives may diminish therapeutic effects of vaccines and increase risk of adverse effects (increased risk of infection). Live-attenuated vaccines should be avoided for at least 3 mo after cessation of immunosuppressive therapy.

• St John's Wort

  Serious - Use Alternative (1)St John's Wort decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• stiripentol

  Monitor Closely (1)stiripentol, ibrutinib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.

• sulindac

  Monitor Closely (1)ibrutinib will increase the level or effect of sulindac by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• talazoparib

  Monitor Closely (1)ibrutinib will increase the level or effect of talazoparib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Talazoparib is a P-glycoprotein (P-gp) substrate; coadministration with P-gp inhibitors may increase talazoparib systemic exposure.

• tazemetostat

  Monitor Closely (1)tazemetostat will decrease the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tecovirimat

  Monitor Closely (1)tecovirimat will decrease the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

• tenecteplase

  Monitor Closely (1)ibrutinib will increase the level or effect of tenecteplase by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• tetanus toxoid adsorbed or fluid

  Monitor Closely (1)ibrutinib decreases effects of tetanus toxoid adsorbed or fluid by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .

• ticagrelor

  Monitor Closely (1)ibrutinib will increase the level or effect of ticagrelor by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• ticlopidine

  Monitor Closely (1)ibrutinib will increase the level or effect of ticlopidine by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• tipranavir

  Serious - Use Alternative (1)tipranavir increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• tirofiban

  Monitor Closely (1)ibrutinib will increase the level or effect of tirofiban by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• tolmetin

  Monitor Closely (1)ibrutinib will increase the level or effect of tolmetin by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• trastuzumab

  Monitor Closely (1)trastuzumab, ibrutinib. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

• trastuzumab deruxtecan

  Monitor Closely (1)trastuzumab deruxtecan, ibrutinib. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

• treprostinil

  Monitor Closely (1)ibrutinib will increase the level or effect of treprostinil by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• tucatinib

  Serious - Use Alternative (1)tucatinib will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

• typhoid polysaccharide vaccine

  Contraindicated (1)ibrutinib decreases effects of typhoid polysaccharide vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressives may diminish therapeutic effects of vaccines and increase risk of adverse effects (increased risk of infection). Live-attenuated vaccines should be avoided for at least 3 mo after cessation of immunosuppressive therapy.

• typhoid vaccine live

  Contraindicated (1)ibrutinib decreases effects of typhoid vaccine live by pharmacodynamic antagonism. Contraindicated. Immunosuppressives may diminish therapeutic effects of vaccines and increase risk of adverse effects (increased risk of infection). Live-attenuated vaccines should be avoided for at least 3 mo after cessation of immunosuppressive therapy.

• varicella virus vaccine live

  Contraindicated (1)ibrutinib decreases effects of varicella virus vaccine live by pharmacodynamic antagonism. Contraindicated. Immunosuppressives may diminish therapeutic effects of vaccines and increase risk of adverse effects (increased risk of infection). Live-attenuated vaccines should be avoided for at least 3 mo after cessation of immunosuppressive therapy.

• venetoclax

  Serious - Use Alternative (1)ibrutinib will increase the level or effect of venetoclax by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If a P-gp inhibitor must be used, reduce the venetoclax dose by at least 50%. Monitor more closely for signs of venetoclax toxicities.

• venlafaxine

  Monitor Closely (1)ibrutinib will increase the level or effect of venlafaxine by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• verapamil

  Serious - Use Alternative (1)verapamil increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

• vilazodone

  Monitor Closely (1)ibrutinib will increase the level or effect of vilazodone by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• vorapaxar

  Monitor Closely (1)ibrutinib will increase the level or effect of vorapaxar by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• voriconazole

  Serious - Use Alternative (1)voriconazole increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with voriconazole 200 mg PO BID, reduce ibrutinib dose to 140 mg qDay (B-cell malignancies) or 280 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

• vortioxetine

  Monitor Closely (1)ibrutinib will increase the level or effect of vortioxetine by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• voxelotor

  Serious - Use Alternative (1)voxelotor will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

• yellow fever vaccine

  Contraindicated (1)ibrutinib decreases effects of yellow fever vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressives may diminish therapeutic effects of vaccines and increase risk of adverse effects (increased risk of infection). Live-attenuated vaccines should be avoided for at least 3 mo after cessation of immunosuppressive therapy.

• zoster vaccine live

  Contraindicated (1)ibrutinib decreases effects of zoster vaccine live by pharmacodynamic antagonism. Contraindicated. Immunosuppressives may diminish therapeutic effects of vaccines and increase risk of adverse effects (increased risk of infection). Live-attenuated vaccines should be avoided for at least 3 mo after cessation of immunosuppressive therapy.

• zoster vaccine recombinant

  Monitor Closely (1)ibrutinib decreases effects of zoster vaccine recombinant by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Coadministration with immunosuppressant therapy reduced efficacy of the vaccine may occur. If possible, complete all age-appropriate vaccinations at least 2 weeks prior to initiation of immunosuppressant therapy. Patients vaccinated <14 days before initiation or during immunosuppressive therapy should be revaccinated at least 3 months after therapy is discontinued. .