larotrectinib (Rx)

Solid Tumors

Indicated for adults and pediatric patients with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have no alternative treatments or have progressed following treatment

100 mg PO BID

Continue until disease progression or until unacceptable toxicity

Dosage Modifications

Dosage modifications for adverse reactions

• Body Surface Area (BSA) ≥1 m2

  • First occurrence: 75 mg BID
  • Second occurrence: 50 mg BID
  • Third occurrence: 100 mg qDay
  • Unable to tolerate 100 mg qDay: Permanently discontinue

Grade ≥3 adverse reactions

• Withhold until reaction resolves or improves to baseline or Grade ≤1
• Resolved within 4 weeks: Resume at next dosage modification
• Unresolved within 4 weeks: Permanently discontinue

Strong CYP3A4 inhibitors

• Avoid coadministration
• If unavoidable, reduce larotrectinib dose by 50%
• Once strong CYP3A4 inhibitor is discontinued for 3-5 elimination half-lives, resume larotrectinib at dose taken before initiating CYP3A4 inhibitor

Strong CYP3A4 inducers

• Avoid coadministration
• If unavoidable, double larotrectinib dose
• Once strong CYP3A4 inducer is discontinued for 3-5 elimination half-lives, resume larotrectinib at dose taken prior to initiating CYP3A4 inducer

Hepatic impairment

• Mild (Child-Pugh A): No dosage adjustment necessary
• Moderate to severe (Child-Pugh B or C): Reduce starting dose by 50%

Renal impairment

• Mild to severe: No dosage adjustment necessary

Dosing Considerations

Verify pregnancy status in females of reproductive potential before initiation

Patient selection

• Select patients based on presence of a NTRK gene fusion in tumor specimens
• Information on FDA-approved tests is available at http://www.fda.gov/companiondiagnostics

Solid Tumors

ndicated for adults and pediatric patients with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have no alternative treatments or have progressed following treatment

Body surface area (BSA) <1 m2: 100 mg/m2 PO BID  

BSA ≥1 m²: 100 mg PO BID

Continue until disease progression or until unacceptable toxicity

Dosage Modifications

Dosage modifications for adverse reactions

• BSA <1 m2

  • First occurrence: 75 mg/m² BID
  • Second occurrence: 50 mg/m² BID
  • Third occurrence: Not to exceed 25 mg/m² BID; remain on 25 mg/m² BID even if BSA becomes >1 m² during treatment
  • Unable to tolerate 25 mg/m² BID: Permanently discontinue

  BSA ≥1 m2

  • First occurrence: 75 mg BID
  • Second occurrence: 50 mg BID
  • Third occurrence: 100 mg qDay
  • Unable to tolerate 100 mg qDay: Permanently discontinue

Grade ≥3 adverse reactions

• Withhold until reaction resolves or improves to baseline or Grade ≤1
• Resolved within 4 weeks: Resume at next dosage modificatio
• Unresolved within 4 weeks: Permanently discontinue

Strong CYP3A4 inhibitors

• Avoid coadministration
• If unavoidable, reduce larotrectinib dose by 50%
• Once strong CYP3A4 inhibitor is discontinued for 3-5 elimination half-lives, resume larotrectinib at dose taken before initiating CYP3A4 inhibitor

Strong CYP3A4 inducers

• Avoid coadministration
• If unavoidable, double larotrectinib dose
• Once strong CYP3A4 inducer is discontinued for 3-5 elimination half-lives, resume larotrectinib at dose taken before initiating CYP3A4 inducer

Hepatic impairment

• Mild (Child-Pugh A): No dosage adjustment necessary
• Moderate to severe (Child-Pugh B or C): Reduce starting dose by 50%

Renal impairment

• Mild to severe: No dosage adjustment necessary

Dosing Considerations

Verify pregnancy status in females of reproductive potential before initiation

Patient selection

• Select patients based on presence of a NTRK gene fusion in tumor specimens
• Information on FDA-approved tests is available at http://www.fda.gov/companiondiagnostics

Contraindicated (1)

• lonafarnib

  larotrectinib will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lonafarnib is a sensitive CYP3A4 substrate. Coadministration with strong or moderate CYP3A4 inhibitors is contraindicated.

Serious - Use Alternative (81)

• abametapir

  abametapir will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

• amobarbital

  amobarbital will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives.

• apalutamide

  apalutamide will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives.

• atazanavir

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

• bosentan

  bosentan will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives.

• butabarbital

  butabarbital will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives.

• butalbital

  butalbital will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives.

• carbamazepine

  carbamazepine will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• ceritinib

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

• chloramphenicol

  chloramphenicol will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.

• clarithromycin

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

• cobicistat

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

• conivaptan

  conivaptan will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.

• crizotinib

  crizotinib will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• dabrafenib

  dabrafenib will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• darunavir

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

• delavirdine

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

• dexamethasone

  dexamethasone will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• doxorubicin

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

• doxorubicin liposomal

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

• efavirenz

  efavirenz will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• elacestrant

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

• enzalutamide

  enzalutamide will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• erdafitinib

  erdafitinib will increase the level or effect of larotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If coadministration unavoidable, separate administration by at least 6 hr before or after administration of P-gp substrates with narrow therapeutic index.

• etravirine

  etravirine will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• fedratinib

  larotrectinib will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

• fexinidazole

  fexinidazole will increase the level or effect of larotrectinib 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.

• fosphenytoin

  fosphenytoin will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• grapefruit

  grapefruit will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.

• idelalisib

  idelalisib will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.

• indinavir

  indinavir will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.

• infigratinib

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

• itraconazole

  itraconazole will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.

• ivacaftor

  ivacaftor will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ivosidenib

  ivosidenib will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• ketoconazole

  ketoconazole will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.

• lemborexant

  larotrectinib will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lemborexant with moderate or strong CYP3A inhibitors.

• levoketoconazole

  levoketoconazole will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.

• lomitapide

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

• lopinavir

  lopinavir will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.

• lorlatinib

  lorlatinib will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• lumacaftor/ivacaftor

  lumacaftor/ivacaftor will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• lurbinectedin

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

• mifepristone

  mifepristone will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.

• mitotane

  mitotane will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• mobocertinib

  larotrectinib will increase the level or effect of mobocertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use of moderate CYP3A4 inhibitor unavoidable, reduce mobocertinib dose by ~50% (eg, 160 to 80 mg); closely monitor QTc interval.

• nafcillin

  nafcillin will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• nefazodone

  nefazodone will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.

• nelfinavir

  nelfinavir will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.

• nisoldipine

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

• omaveloxolone

  larotrectinib will increase the level or effect of omaveloxolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unavoidable, reduce omaveloxolone dose to 100 mg/day. Closely monitor for adverse effects. If adverse effects emerge, further reduce to 50 mg/day.

• oxycodone

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

• pacritinib

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

• pemigatinib

  larotrectinib will increase the level or effect of pemigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors is unavoidable, reduce pemigatinib dose (refer to drug monograph dosage modifications). After discontinuing the CYP3A4 inhibitor for 3 elimination half-lives, may resume previous pemigatinib dose.

• pentobarbital

  pentobarbital will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• pexidartinib

  pexidartinib will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• phenobarbital

  phenobarbital will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• phenytoin

  phenytoin will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• posaconazole

  posaconazole will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.

• primidone

  primidone will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• ribociclib

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

• rifabutin

  rifabutin will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• rifampin

  rifampin will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• rifapentine

  rifapentine will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• ritonavir

  ritonavir will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.

• saquinavir

  saquinavir will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.

• secobarbital

  secobarbital will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• selumetinib

  larotrectinib will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.

• siponimod

  larotrectinib will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

• sirolimus

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

• sotorasib

  sotorasib will decrease the level or effect of larotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the P-gp substrate for dosage modifications.

• St John's Wort

  St John's Wort will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• stiripentol

  stiripentol will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.

• tazemetostat

  larotrectinib will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of tazemetostat with moderate CYP3A4 inhibitors. If coadministration is unavoidable, reduce tazemetostat current dose (see drug monograph Dosage Modifications).

• tepotinib

  tepotinib will increase the level or effect of larotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If concomitant use unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.

• tipranavir

  tipranavir will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.

• tucatinib

  tucatinib will increase the level or effect of larotrectinib 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.

• ubrogepant

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

• verapamil

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

• voriconazole

  voriconazole will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.

• voxelotor

  voxelotor will increase the level or effect of larotrectinib 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 (71)

• alfentanil

  larotrectinib will increase the level or effect of alfentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• amiodarone

  larotrectinib will increase the level or effect of amiodarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• apixaban

  larotrectinib will increase the level or effect of apixaban by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• aprepitant

  larotrectinib will increase the level or effect of aprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• aripiprazole

  larotrectinib will increase the level or effect of aripiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• artemether/lumefantrine

  larotrectinib will decrease the level or effect of artemether/lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• atogepant

  larotrectinib will increase the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• berotralstat

  berotralstat will increase the level or effect of larotrectinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

• bosentan

  larotrectinib will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• carbamazepine

  larotrectinib will increase the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cenobamate

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

• colchicine

  larotrectinib will increase the level or effect of colchicine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• conivaptan

  larotrectinib will increase the level or effect of conivaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• crizotinib

  larotrectinib will increase the level or effect of crizotinib by aldehyde dehydrogenase inhibition. Use Caution/Monitor.

• cyclosporine

  larotrectinib will increase the level or effect of cyclosporine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• daridorexant

  larotrectinib will increase the level or effect of daridorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Daridorexant dose should not exceed 25 mg per night when coadministered with moderate CYP3A4 inhibitors.

• diazepam

  larotrectinib will increase the level or effect of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong or moderate CYP3A4 inhibitors may decrease rate of diazepam elimination, thereby increasing adverse reactions to diazepam.

• diazepam intranasal

  larotrectinib will increase the level or effect of diazepam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong or moderate CYP3A4 inhibitors may decrease rate of diazepam elimination, thereby increasing adverse reactions to diazepam.

• dihydroergotamine

  larotrectinib will increase the level or effect of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• dihydroergotamine intranasal

  larotrectinib will increase the level or effect of dihydroergotamine intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• diltiazem

  diltiazem will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• disopyramide

  larotrectinib will increase the level or effect of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• elagolix

  elagolix decreases levels of larotrectinib 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.

• ergonovine

  larotrectinib will increase the level or effect of ergonovine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ergotamine

  larotrectinib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• erythromycin base

  erythromycin base will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• erythromycin ethylsuccinate

  erythromycin ethylsuccinate will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• erythromycin lactobionate

  erythromycin lactobionate will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• erythromycin stearate

  erythromycin stearate will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fedratinib

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

• felodipine

  larotrectinib will increase the level or effect of felodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fentanyl

  larotrectinib will increase the level or effect of fentanyl by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fentanyl intranasal

  larotrectinib will increase the level or effect of fentanyl intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved

• fentanyl transdermal

  larotrectinib will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved

• fentanyl transmucosal

  larotrectinib will increase the level or effect of fentanyl transmucosal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved

• finerenone

  larotrectinib will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or moderate CYP3A4 inhibitors. Adjust finererone dosage as needed.

• flibanserin

  larotrectinib will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fosamprenavir

  fosamprenavir will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fosaprepitant

  larotrectinib will increase the level or effect of fosaprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• hydrocodone

  larotrectinib will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• imatinib

  imatinib will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• isavuconazonium sulfate

  larotrectinib will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• istradefylline

  istradefylline will increase the level or effect of larotrectinib 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.

• ixabepilone

  larotrectinib will increase the level or effect of ixabepilone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• lefamulin

  larotrectinib will increase the level or effect of lefamulin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for adverse effects if lefamulin is coadministered with moderate CYP3A inhibitors.

• lenacapavir

  lenacapavir will increase the level or effect of larotrectinib 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.

• levamlodipine

  larotrectinib will increase the level or effect of levamlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate and strong CYP3A inhibitors results in increased systemic exposure to amlodipine and may require dose reduction. Monitor for symptoms of hypotension and edema when amlodipine is coadministered with CYP3A inhibitors to determine the need for dose adjustment.

• lumateperone

  larotrectinib will increase the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce lumateperone dose to 21 mg/day if coadministered with moderate CYP3A4 inhibitors.

• lumefantrine

  larotrectinib will increase the level or effect of lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• mavacamten

  larotrectinib will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

• methadone

  larotrectinib will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• netupitant/palonosetron

  netupitant/palonosetron will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nilotinib

  nilotinib will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nimodipine

  larotrectinib will increase the level or effect of nimodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• oliceridine

  larotrectinib will increase the level or effect of oliceridine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If concomitant use is necessary, may require less frequent oliceridine dosing. Closely monitor for respiratory depression and sedation and titrate subsequent doses accordingly. If inhibitor is discontinued, consider increase oliceridine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.

• ospemifene

  larotrectinib will increase the level or effect of ospemifene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rucaparib

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

• siponimod

  siponimod and larotrectinib 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.

• sparsentan

  larotrectinib will increase the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No dosage adjustment needed. Monitor blood pressure, serum potassium, edema, and kidney function regularly if sparsentan is coadministered with moderate CYP3A4 inhibitors.

• sufentanil

  larotrectinib will increase the level or effect of sufentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• sufentanil SL

  larotrectinib will increase the level or effect of sufentanil SL by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tacrolimus

  larotrectinib will increase the level or effect of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tacrolimus ointment

  larotrectinib will increase the level or effect of tacrolimus ointment by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tamsulosin

  larotrectinib will increase the level or effect of tamsulosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tazemetostat

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

• tramadol

  larotrectinib will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• triazolam

  larotrectinib will increase the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tucatinib

  tucatinib will increase the level or effect of larotrectinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.

• vardenafil

  larotrectinib will increase the level or effect of vardenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Vardenafil dose may need to be reduced if coadministered with moderate or strong CYP3A4 inhibitors

• voclosporin

  larotrectinib will increase the level or effect of voclosporin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce voclosporin daily dosage to 15.8 mg PO in AM and 7.9 mg PO in PM.

• zanubrutinib

  larotrectinib will increase the level or effect of zanubrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce zanubrutinib (a CYP3A4 substrate) to 80 mg PO BID to when coadministered with a moderate CYP3A4 inhibitor. Interrupt dose as recommended for adverse reactions. After discontinuing the CYP3A4 inhibitor, resume previous dose of zanubrutinib.

Minor (251)

• abemaciclib

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

• abiraterone

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

• acalabrutinib

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

• acetazolamide

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

• ado-trastuzumab emtansine

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

• alfuzosin

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

• alpelisib

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

• alprazolam

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

• ambrisentan

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

• amlodipine

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

• anastrozole

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

• apalutamide

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

• apomorphine

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

• apremilast

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

• armodafinil

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

• aspirin

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

• astemizole

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

• atorvastatin

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

• avanafil

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

• avapritinib

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

• avatrombopag

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

• axitinib

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

• bedaquiline

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

• benzhydrocodone/acetaminophen

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

• benzphetamine

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

• bortezomib

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

• bosutinib

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

• brentuximab vedotin

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

• brexpiprazole

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

• brigatinib

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

• bromocriptine

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

• budesonide

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

• buprenorphine

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

• buprenorphine transdermal

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

• buspirone

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

• busulfan

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

• cabozantinib

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

• calcifediol

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

• calcitriol

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

• capmatinib

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

• cariprazine

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

• chlordiazepoxide

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

• chloroquine

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

• chlorpheniramine

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

• ciclesonide inhaled

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

• cilostazol

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

• cisapride

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

• citalopram

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

• clonazepam

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

• clorazepate

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

• cobimetinib

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

• cocaine topical

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

• conjugated estrogens

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

• copanlisib

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

• cyclophosphamide

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

• daclatasvir

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

• dantrolene

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

• dapsone

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

• darifenacin

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

• dasatinib

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

• deflazacort

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

• dexlansoprazole

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

• docetaxel

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

• doravirine

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

• doxepin cream

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

• dronabinol

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

• dronedarone

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

• duvelisib

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

• efavirenz

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

• elagolix

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

• elbasvir/grazoprevir

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

• eletriptan

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

• eliglustat

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

• elvitegravir

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

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  larotrectinib will increase the level or effect of elvitegravir/cobicistat/emtricitabine/tenofovir DF by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• encorafenib

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

• enfortumab vedotin

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

• entrectinib

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

• enzalutamide

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

• eplerenone

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

• ergoloid mesylates

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

• erlotinib

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

• escitalopram

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

• esomeprazole

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

• estradiol

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

• estrogens conjugated synthetic

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

• estrogens esterified

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

• estropipate

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

• eszopiclone

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

• ethinylestradiol

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

• ethosuximide

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

• etoposide

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

• everolimus

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

• exemestane

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

• felbamate

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

• fenofibrate

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

• fenofibrate micronized

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

• fenofibric acid

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

• flunisolide inhaled

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

• flurazepam

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

• flutamide

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

• fluticasone furoate

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

• fluticasone inhaled

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

• fostamatinib

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

• gefitinib

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

• glasdegib

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

• glecaprevir/pibrentasvir

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

• guanfacine

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

• haloperidol

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

• hydroxyprogesterone caproate (DSC)

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

• ibrutinib

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

• ifosfamide

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

• irinotecan

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

• irinotecan liposomal

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

• isosorbide dinitrate

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

• isosorbide mononitrate

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

• isradipine

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

• istradefylline

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

• ivosidenib

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

• ixazomib

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

• ketamine

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

• lacosamide

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

• lansoprazole

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

• lapatinib

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

• levomilnacipran

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

• levonorgestrel intrauterine

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

• levonorgestrel oral

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

• linagliptin

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

• lopinavir

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

• losartan

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

• lovastatin

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

• lumacaftor/ivacaftor

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

• lurasidone

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

• macimorelin

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

• maraviroc

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

• marijuana

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

• medroxyprogesterone

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

• mefloquine

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

• mestranol

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

• metaxalone

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

• methylergonovine

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

• methylprednisolone

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

• miconazole oral

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

• midazolam

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

• midazolam intranasal

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

• midostaurin

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

• mirtazapine

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

• modafinil

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

• montelukast

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

• naldemedine

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

• naloxegol

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

• nevirapine

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

• nicardipine

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

• nifedipine

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

• norethindrone

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

• norgestrel

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

• olaparib

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

• ombitasvir/paritaprevir/ritonavir

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

• ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)

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

• omeprazole

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

• ondansetron

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

• osilodrostat

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

• osimertinib

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

• paclitaxel

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

• paclitaxel protein bound

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

• palbociclib

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

• panobinostat

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

• paricalcitol

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

• pazopanib

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

• perampanel

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

• pimavanserin

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

• pimozide

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

• pitolisant

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

• polatuzumab vedotin

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

• pomalidomide

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

• ponatinib

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

• praziquantel

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

• primaquine

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

• progesterone intravaginal gel

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

• progesterone micronized

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

• progesterone, natural

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

• quazepam

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

• quetiapine

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

• quinidine

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

• quinine

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

• rabeprazole

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

• ranolazine

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

• regorafenib

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

• repaglinide

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

• rimegepant

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

• riociguat

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

• rivaroxaban

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

• roflumilast

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

• rolapitant

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

• romidepsin

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

• ropivacaine

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

• ruxolitinib

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

• ruxolitinib topical

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

• salmeterol

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

• saxagliptin

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

• selpercatinib

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

• sildenafil

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

• simvastatin

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

• sofosbuvir/velpatasvir

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

• solifenacin

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

• sonidegib

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

• sorafenib

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

• stiripentol

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

• sunitinib

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

• suvorexant

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

• tadalafil

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

• tamoxifen

  larotrectinib decreases effects of tamoxifen by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• tasimelteon

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

• temsirolimus

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

• teniposide

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

• tetracycline

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

• tezacaftor

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

• theophylline

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

• tiagabine

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

• ticagrelor

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

• ticlopidine

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

• tinidazole

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

• tofacitinib

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

• tolterodine

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

• tolvaptan

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

• toremifene

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

• trabectedin

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

• trazodone

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

• trimethoprim

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

• trimipramine

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

• ulipristal

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

• umeclidinium bromide/vilanterol inhaled

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

• upadacitinib

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

• valbenazine

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

• vandetanib

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

• velpatasvir

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

• vemurafenib

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

• venetoclax

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

• venlafaxine

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

• vilanterol/fluticasone furoate inhaled

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

• vilazodone

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

• vinblastine

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

• vincristine

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

• vincristine liposomal

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

• vinorelbine

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

• vorapaxar

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

• vortioxetine

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

• voxilaprevir

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

• warfarin

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

• zolpidem

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

• zonisamide

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

• abametapir

  Serious - Use Alternative (1)abametapir will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

• abemaciclib

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

• abiraterone

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

• acalabrutinib

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

• acetazolamide

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

• ado-trastuzumab emtansine

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

• alfentanil

  Monitor Closely (1)larotrectinib will increase the level or effect of alfentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• alfuzosin

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

• alpelisib

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

• alprazolam

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

• ambrisentan

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

• amiodarone

  Monitor Closely (1)larotrectinib will increase the level or effect of amiodarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• amlodipine

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

• amobarbital

  Serious - Use Alternative (1)amobarbital will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives.

• anastrozole

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

• apalutamide

  Serious - Use Alternative (1)apalutamide will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives.Minor (1)larotrectinib will increase the level or effect of apalutamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• apixaban

  Monitor Closely (1)larotrectinib will increase the level or effect of apixaban by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• apomorphine

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

• apremilast

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

• aprepitant

  Monitor Closely (1)larotrectinib will increase the level or effect of aprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• aripiprazole

  Monitor Closely (1)larotrectinib will increase the level or effect of aripiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• armodafinil

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

• artemether/lumefantrine

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

• aspirin

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

• astemizole

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

• atazanavir

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

• atogepant

  Monitor Closely (1)larotrectinib will increase the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• atorvastatin

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

• avanafil

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

• avapritinib

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

• avatrombopag

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

• axitinib

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

• bedaquiline

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

• benzhydrocodone/acetaminophen

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

• benzphetamine

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

• berotralstat

  Monitor Closely (1)berotralstat will increase the level or effect of larotrectinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

• bortezomib

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

• bosentan

  Monitor Closely (1)larotrectinib will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)bosentan will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives.

• bosutinib

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

• brentuximab vedotin

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

• brexpiprazole

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

• brigatinib

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

• bromocriptine

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

• budesonide

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

• buprenorphine

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

• buprenorphine transdermal

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

• buspirone

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

• busulfan

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

• butabarbital

  Serious - Use Alternative (1)butabarbital will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives.

• butalbital

  Serious - Use Alternative (1)butalbital will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives.

• cabozantinib

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

• calcifediol

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

• calcitriol

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

• capmatinib

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

• carbamazepine

  Monitor Closely (1)larotrectinib will increase the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)carbamazepine will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• cariprazine

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

• cenobamate

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

• ceritinib

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

• chloramphenicol

  Serious - Use Alternative (1)chloramphenicol will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.

• chlordiazepoxide

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

• chloroquine

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

• chlorpheniramine

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

• ciclesonide inhaled

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

• cilostazol

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

• cisapride

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

• citalopram

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

• clarithromycin

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

• clonazepam

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

• clorazepate

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

• cobicistat

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

• cobimetinib

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

• cocaine topical

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

• colchicine

  Monitor Closely (1)larotrectinib will increase the level or effect of colchicine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• conivaptan

  Monitor Closely (1)larotrectinib will increase the level or effect of conivaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)conivaptan will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.

• conjugated estrogens

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

• copanlisib

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

• crizotinib

  Monitor Closely (1)larotrectinib will increase the level or effect of crizotinib by aldehyde dehydrogenase inhibition. Use Caution/Monitor.Serious - Use Alternative (1)crizotinib will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• cyclophosphamide

  Minor (2)larotrectinib will increase the level or effect of cyclophosphamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  cyclophosphamide will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• cyclosporine

  Monitor Closely (1)larotrectinib will increase the level or effect of cyclosporine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• dabrafenib

  Serious - Use Alternative (1)dabrafenib will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• daclatasvir

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

• dantrolene

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

• dapsone

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

• daridorexant

  Monitor Closely (1)larotrectinib will increase the level or effect of daridorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Daridorexant dose should not exceed 25 mg per night when coadministered with moderate CYP3A4 inhibitors.

• darifenacin

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

• darunavir

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

• dasatinib

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

• deflazacort

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

• delavirdine

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

• dexamethasone

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

• dexlansoprazole

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

• diazepam

  Monitor Closely (1)larotrectinib will increase the level or effect of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong or moderate CYP3A4 inhibitors may decrease rate of diazepam elimination, thereby increasing adverse reactions to diazepam.

• diazepam intranasal

  Monitor Closely (1)larotrectinib will increase the level or effect of diazepam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong or moderate CYP3A4 inhibitors may decrease rate of diazepam elimination, thereby increasing adverse reactions to diazepam.

• dihydroergotamine

  Monitor Closely (1)larotrectinib will increase the level or effect of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• dihydroergotamine intranasal

  Monitor Closely (1)larotrectinib will increase the level or effect of dihydroergotamine intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• diltiazem

  Monitor Closely (1)diltiazem will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• disopyramide

  Monitor Closely (1)larotrectinib will increase the level or effect of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• docetaxel

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

• doravirine

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

• doxepin cream

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

• doxorubicin

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

• doxorubicin liposomal

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

• dronabinol

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

• dronedarone

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

• duvelisib

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

• efavirenz

  Serious - Use Alternative (1)efavirenz will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-livesMinor (1)larotrectinib will increase the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• elacestrant

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

• elagolix

  Monitor Closely (1)elagolix decreases levels of larotrectinib 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.Minor (1)larotrectinib will increase the level or effect of elagolix by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• elbasvir/grazoprevir

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

• eletriptan

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

• eliglustat

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

• elvitegravir

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

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  Minor (1)larotrectinib will increase the level or effect of elvitegravir/cobicistat/emtricitabine/tenofovir DF by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• encorafenib

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

• enfortumab vedotin

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

• entrectinib

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

• enzalutamide

  Serious - Use Alternative (1)enzalutamide will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-livesMinor (1)larotrectinib will increase the level or effect of enzalutamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• eplerenone

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

• erdafitinib

  Serious - Use Alternative (1)erdafitinib will increase the level or effect of larotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If coadministration unavoidable, separate administration by at least 6 hr before or after administration of P-gp substrates with narrow therapeutic index.

• ergoloid mesylates

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

• ergonovine

  Monitor Closely (1)larotrectinib will increase the level or effect of ergonovine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ergotamine

  Monitor Closely (1)larotrectinib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• erlotinib

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

• erythromycin base

  Monitor Closely (1)erythromycin base will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• erythromycin ethylsuccinate

  Monitor Closely (1)erythromycin ethylsuccinate will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• erythromycin lactobionate

  Monitor Closely (1)erythromycin lactobionate will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• erythromycin stearate

  Monitor Closely (1)erythromycin stearate will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• escitalopram

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

• esomeprazole

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

• estradiol

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

• estrogens conjugated synthetic

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

• estrogens esterified

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

• estropipate

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

• eszopiclone

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

• ethinylestradiol

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

• ethosuximide

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

• etoposide

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

• etravirine

  Serious - Use Alternative (1)etravirine will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• everolimus

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

• exemestane

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

• fedratinib

  Monitor Closely (1)fedratinib will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.Serious - Use Alternative (1)larotrectinib will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

• felbamate

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

• felodipine

  Monitor Closely (1)larotrectinib will increase the level or effect of felodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fenofibrate

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

• fenofibrate micronized

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

• fenofibric acid

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

• fentanyl

  Monitor Closely (1)larotrectinib will increase the level or effect of fentanyl by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fentanyl intranasal

  Monitor Closely (1)larotrectinib will increase the level or effect of fentanyl intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved

• fentanyl transdermal

  Monitor Closely (1)larotrectinib will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved

• fentanyl transmucosal

  Monitor Closely (1)larotrectinib will increase the level or effect of fentanyl transmucosal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved

• fexinidazole

  Serious - Use Alternative (1)fexinidazole will increase the level or effect of larotrectinib 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.

• finerenone

  Monitor Closely (1)larotrectinib will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or moderate CYP3A4 inhibitors. Adjust finererone dosage as needed.

• flibanserin

  Monitor Closely (1)larotrectinib will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• flunisolide inhaled

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

• flurazepam

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

• flutamide

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

• fluticasone furoate

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

• fluticasone inhaled

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

• fosamprenavir

  Monitor Closely (1)fosamprenavir will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fosaprepitant

  Monitor Closely (1)larotrectinib will increase the level or effect of fosaprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fosphenytoin

  Serious - Use Alternative (1)fosphenytoin will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• fostamatinib

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

• gefitinib

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

• glasdegib

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

• glecaprevir/pibrentasvir

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

• grapefruit

  Serious - Use Alternative (1)grapefruit will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.

• guanfacine

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

• haloperidol

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

• hydrocodone

  Monitor Closely (1)larotrectinib will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• hydroxyprogesterone caproate (DSC)

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

• ibrutinib

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

• idelalisib

  Serious - Use Alternative (1)idelalisib will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.

• ifosfamide

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

• imatinib

  Monitor Closely (1)imatinib will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• indinavir

  Serious - Use Alternative (1)indinavir will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.

• infigratinib

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

• irinotecan

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

• irinotecan liposomal

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

• isavuconazonium sulfate

  Monitor Closely (1)larotrectinib will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• isosorbide dinitrate

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

• isosorbide mononitrate

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

• isradipine

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

• istradefylline

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

• itraconazole

  Serious - Use Alternative (1)itraconazole will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.

• ivacaftor

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

• ivosidenib

  Serious - Use Alternative (1)ivosidenib will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-livesMinor (1)larotrectinib will increase the level or effect of ivosidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ixabepilone

  Monitor Closely (1)larotrectinib will increase the level or effect of ixabepilone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ixazomib

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

• ketamine

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

• ketoconazole

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.

• lacosamide

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

• lansoprazole

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

• lapatinib

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

• lefamulin

  Monitor Closely (1)larotrectinib will increase the level or effect of lefamulin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for adverse effects if lefamulin is coadministered with moderate CYP3A inhibitors.

• lemborexant

  Serious - Use Alternative (1)larotrectinib will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lemborexant with moderate or strong CYP3A inhibitors.

• lenacapavir

  Monitor Closely (1)lenacapavir will increase the level or effect of larotrectinib 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.

• levamlodipine

  Monitor Closely (1)larotrectinib will increase the level or effect of levamlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate and strong CYP3A inhibitors results in increased systemic exposure to amlodipine and may require dose reduction. Monitor for symptoms of hypotension and edema when amlodipine is coadministered with CYP3A inhibitors to determine the need for dose adjustment.

• levoketoconazole

  Serious - Use Alternative (1)levoketoconazole will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.

• levomilnacipran

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

• levonorgestrel intrauterine

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

• levonorgestrel oral

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

• linagliptin

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

• lomitapide

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

• lonafarnib

  Contraindicated (1)larotrectinib will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lonafarnib is a sensitive CYP3A4 substrate. Coadministration with strong or moderate CYP3A4 inhibitors is contraindicated.

• lopinavir

  Serious - Use Alternative (1)lopinavir will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.Minor (1)larotrectinib will increase the level or effect of lopinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• lorlatinib

  Serious - Use Alternative (1)lorlatinib will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• losartan

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

• lovastatin

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

• lumacaftor/ivacaftor

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-livesMinor (1)larotrectinib will increase the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• lumateperone

  Monitor Closely (1)larotrectinib will increase the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce lumateperone dose to 21 mg/day if coadministered with moderate CYP3A4 inhibitors.

• lumefantrine

  Monitor Closely (1)larotrectinib will increase the level or effect of lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• lurasidone

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

• lurbinectedin

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

• macimorelin

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

• maraviroc

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

• marijuana

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

• mavacamten

  Monitor Closely (1)larotrectinib will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

• medroxyprogesterone

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

• mefloquine

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

• mestranol

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

• metaxalone

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

• methadone

  Monitor Closely (1)larotrectinib will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• methylergonovine

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

• methylprednisolone

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

• miconazole oral

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

• midazolam

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

• midazolam intranasal

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

• midostaurin

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

• mifepristone

  Serious - Use Alternative (1)mifepristone will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.

• mirtazapine

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

• mitotane

  Serious - Use Alternative (1)mitotane will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• mobocertinib

  Serious - Use Alternative (1)larotrectinib will increase the level or effect of mobocertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use of moderate CYP3A4 inhibitor unavoidable, reduce mobocertinib dose by ~50% (eg, 160 to 80 mg); closely monitor QTc interval.

• modafinil

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

• montelukast

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

• nafcillin

  Serious - Use Alternative (1)nafcillin will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• naldemedine

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

• naloxegol

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

• nefazodone

  Serious - Use Alternative (1)nefazodone will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.

• nelfinavir

  Serious - Use Alternative (1)nelfinavir will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.

• netupitant/palonosetron

  Monitor Closely (1)netupitant/palonosetron will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nevirapine

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

• nicardipine

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

• nifedipine

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

• nilotinib

  Monitor Closely (1)nilotinib will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nimodipine

  Monitor Closely (1)larotrectinib will increase the level or effect of nimodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nisoldipine

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

• norethindrone

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

• norgestrel

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

• olaparib

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

• oliceridine

  Monitor Closely (1)larotrectinib will increase the level or effect of oliceridine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If concomitant use is necessary, may require less frequent oliceridine dosing. Closely monitor for respiratory depression and sedation and titrate subsequent doses accordingly. If inhibitor is discontinued, consider increase oliceridine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.

• omaveloxolone

  Serious - Use Alternative (1)larotrectinib will increase the level or effect of omaveloxolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unavoidable, reduce omaveloxolone dose to 100 mg/day. Closely monitor for adverse effects. If adverse effects emerge, further reduce to 50 mg/day.

• ombitasvir/paritaprevir/ritonavir

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

• ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)

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

• omeprazole

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

• ondansetron

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

• osilodrostat

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

• osimertinib

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

• ospemifene

  Monitor Closely (1)larotrectinib will increase the level or effect of ospemifene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• oxycodone

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

• paclitaxel

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

• paclitaxel protein bound

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

• pacritinib

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

• palbociclib

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

• panobinostat

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

• paricalcitol

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

• pazopanib

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

• pemigatinib

  Serious - Use Alternative (1)larotrectinib will increase the level or effect of pemigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors is unavoidable, reduce pemigatinib dose (refer to drug monograph dosage modifications). After discontinuing the CYP3A4 inhibitor for 3 elimination half-lives, may resume previous pemigatinib dose.

• pentobarbital

  Serious - Use Alternative (1)pentobarbital will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• perampanel

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

• pexidartinib

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

• phenobarbital

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• phenytoin

  Serious - Use Alternative (1)phenytoin will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• pimavanserin

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

• pimozide

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

• pitolisant

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

• polatuzumab vedotin

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

• pomalidomide

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

• ponatinib

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

• posaconazole

  Serious - Use Alternative (1)posaconazole will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.

• praziquantel

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

• primaquine

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

• primidone

  Serious - Use Alternative (1)primidone will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• progesterone intravaginal gel

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

• progesterone micronized

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

• progesterone, natural

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

• quazepam

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

• quetiapine

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

• quinidine

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

• quinine

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

• rabeprazole

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

• ranolazine

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

• regorafenib

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

• repaglinide

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

• ribociclib

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

• rifabutin

  Serious - Use Alternative (1)rifabutin will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• rifampin

  Serious - Use Alternative (1)rifampin will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• rifapentine

  Serious - Use Alternative (1)rifapentine will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• rimegepant

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

• riociguat

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

• ritonavir

  Serious - Use Alternative (1)ritonavir will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.

• rivaroxaban

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

• roflumilast

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

• rolapitant

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

• romidepsin

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

• ropivacaine

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

• rucaparib

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

• ruxolitinib

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

• ruxolitinib topical

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

• salmeterol

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

• saquinavir

  Serious - Use Alternative (1)saquinavir will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.

• saxagliptin

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

• secobarbital

  Serious - Use Alternative (1)secobarbital will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• selpercatinib

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

• selumetinib

  Serious - Use Alternative (1)larotrectinib will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.

• sildenafil

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

• simvastatin

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

• siponimod

  Monitor Closely (1)siponimod and larotrectinib 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.Serious - Use Alternative (1)larotrectinib will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

• sirolimus

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

• sofosbuvir/velpatasvir

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

• solifenacin

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

• sonidegib

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

• sorafenib

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

• sotorasib

  Serious - Use Alternative (1)sotorasib will decrease the level or effect of larotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the P-gp substrate for dosage modifications.

• sparsentan

  Monitor Closely (1)larotrectinib will increase the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No dosage adjustment needed. Monitor blood pressure, serum potassium, edema, and kidney function regularly if sparsentan is coadministered with moderate CYP3A4 inhibitors.

• St John's Wort

  Serious - Use Alternative (1)St John's Wort will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• stiripentol

  Serious - Use Alternative (1)stiripentol will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.Minor (1)larotrectinib will increase the level or effect of stiripentol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• sufentanil

  Monitor Closely (1)larotrectinib will increase the level or effect of sufentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• sufentanil SL

  Monitor Closely (1)larotrectinib will increase the level or effect of sufentanil SL by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• sunitinib

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

• suvorexant

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

• tacrolimus

  Monitor Closely (1)larotrectinib will increase the level or effect of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tacrolimus ointment

  Monitor Closely (1)larotrectinib will increase the level or effect of tacrolimus ointment by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tadalafil

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

• tamoxifen

  Minor (1)larotrectinib decreases effects of tamoxifen by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• tamsulosin

  Monitor Closely (1)larotrectinib will increase the level or effect of tamsulosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tasimelteon

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

• tazemetostat

  Monitor Closely (1)tazemetostat will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)larotrectinib will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of tazemetostat with moderate CYP3A4 inhibitors. If coadministration is unavoidable, reduce tazemetostat current dose (see drug monograph Dosage Modifications).

• temsirolimus

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

• teniposide

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

• tepotinib

  Serious - Use Alternative (1)tepotinib will increase the level or effect of larotrectinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If concomitant use unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.

• tetracycline

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

• tezacaftor

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

• theophylline

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

• tiagabine

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

• ticagrelor

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

• ticlopidine

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

• tinidazole

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

• tipranavir

  Serious - Use Alternative (1)tipranavir will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.

• tofacitinib

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

• tolterodine

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

• tolvaptan

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

• toremifene

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

• trabectedin

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

• tramadol

  Monitor Closely (1)larotrectinib will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• trazodone

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

• triazolam

  Monitor Closely (1)larotrectinib will increase the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• trimethoprim

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

• trimipramine

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

• tucatinib

  Monitor Closely (1)tucatinib will increase the level or effect of larotrectinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.Serious - Use Alternative (1)tucatinib will increase the level or effect of larotrectinib 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.

• ubrogepant

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

• ulipristal

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

• umeclidinium bromide/vilanterol inhaled

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

• upadacitinib

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

• valbenazine

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

• vandetanib

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

• vardenafil

  Monitor Closely (1)larotrectinib will increase the level or effect of vardenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Vardenafil dose may need to be reduced if coadministered with moderate or strong CYP3A4 inhibitors

• velpatasvir

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

• vemurafenib

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

• venetoclax

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

• venlafaxine

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

• verapamil

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

• vilanterol/fluticasone furoate inhaled

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

• vilazodone

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

• vinblastine

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

• vincristine

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

• vincristine liposomal

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

• vinorelbine

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

• voclosporin

  Monitor Closely (1)larotrectinib will increase the level or effect of voclosporin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce voclosporin daily dosage to 15.8 mg PO in AM and 7.9 mg PO in PM.

• vorapaxar

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

• voriconazole

  Serious - Use Alternative (1)voriconazole will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.

• vortioxetine

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

• voxelotor

  Serious - Use Alternative (1)voxelotor will increase the level or effect of larotrectinib 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.

• voxilaprevir

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

• warfarin

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

• zanubrutinib

  Monitor Closely (1)larotrectinib will increase the level or effect of zanubrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce zanubrutinib (a CYP3A4 substrate) to 80 mg PO BID to when coadministered with a moderate CYP3A4 inhibitor. Interrupt dose as recommended for adverse reactions. After discontinuing the CYP3A4 inhibitor, resume previous dose of zanubrutinib.

• zolpidem

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

• zonisamide

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