Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

capsules

  • 200mg
  • 250mg

Non-Small Cell Lung Cancer

Indicated for metastatic non-small cell lung cancer (NSCLC) in adults whose tumors are anaplastic lymphoma kinase (ALK)- or ROS1-positive

250 mg PO BID

Continue until disease progression or unacceptable toxicity

Dosage Modifications

Dosage reductions

  • First dose reduction: 200 mg PO BID
  • Second dose reduction: 250 mg PO qDay
  • Unable to tolerate 250 mg PO qDay: Permanently discontinue

Hematologic toxicities

  • For all hematologic toxicities except lymphopenia (unless associated with clinical events, eg, opportunistic infections)
  • Grade 3: Withhold until recovery to Grade ≤2, then resume at same dose
  • Grade 4: Withhold until recovery to Grade ≤2, then resume at next dose reduction

Hepatotoxicity

  • ALT or AST >5x ULN with total bilirubin [TB] ≤1.5x ULN: Withhold until recovery to baseline or ≤3x ULN, then resume at next dose reduction
  • ALT or AST >3x with concurrent TB >1.5x ULN (in the absence of cholestasis or hemolysis): Permanently discontinue

Interstitial lung disease

  • Any grade pneumonitis: Permanently discontinue

QT prolongation

  • Correct QT (QTc) >500 ms on at least 2 separate electrocardiograms (ECGs): Withhold until recovery to baseline or at QTc <481 ms, then resume at next dose reduction
  • QTc >500 ms or ≥60 ms change from baseline with Torsade de pointes or polymorphic ventricular tachycardia or signs/symptoms of serious arrhythmia: Permanently discontinue

Bradycardia

Symptomatic, may be severe and medically intervention indicated
  • Withhold until recovery to asymptomatic bradycardia or HR ≥60 bpm
  • Evaluate concomitant medications known to cause bradycardia (eg, antihypertensives)
  • Discontinue or adjust dose of any contributing medication; resume at previous dose upon recovery to asymptomatic bradycardia or HR ≥60 bpm
  • Contributing medication not identified, or if contributing medications not discontinue or dose modified: Resume at next dose reduction upon recovery to asymptomatic bradycardia or to a HR ≥60 bpm
Life-threatening consequences, urgent intervention indicated
  • No contributing medications identified: Permanently discontinue
  • If contributing medication identified AND discontinued, or its dose adjusted: Resume at 250 mg qDay upon recovery to asymptomatic bradycardia or to a HR ≥60 bpm, closely monitor
  • Permanently discontinue for recurrence

Visual loss

  • Grade 4 ocular disorder: Discontinue during evaluation of severe visual loss

Strong CYP3A4 inhibitors

  • Avoid coadministration
  • If use is unavoidable, reduce crizotinib dose to 250 mg PO qDay
  • After discontinuation of strong CYP3A inhibitor, resume crizotinib dose used before initiating strong CYP3A inhibitor

Renal impairment

  • Mild-to-moderate (CrCl 30-89 mL/min): No dosage adjustment necessary
  • Severe (CrCl <30 mL/min) and not requiring dialysis: 250 mg PO qDay

Hepatic impairment

  • Mild (AST >ULN and TB ≤1x ULN or any AST and TB >1x to ≤1.5x ULN): Steady-state mean AUC and Cmax decreased by 9%
  • Moderate (any AST and TB >1.5x ULN and ≤3x ULN): 200 mg PO BID
  • Severe (any AST and TB>3x ULN): 250 mg PO qDay

Dosing Considerations

Verify pregnancy status in females of reproductive potential before initiation

Monitoring parameters

  • CBC including differential WBC counts: Monthly and as clinically indicated, more frequently test if Grade 3 or 4 abnormalities are observed or if fever or infection occurs
  • Liver function tests: Every 2 weeks during the first 2 months of treatment, then monthly, and as clinically needed

Limitation of use

  • Safety and efficacy not established in adults with relapsed or refractory, systemic ALK-positive ALCL

Patient selection

Dosage Forms & Strengths

capsules

  • 200mg
  • 250mg

Anaplastic Large Cell Lymphoma

Indicated for relapsed or refractory, systemic ALK-positive anaplastic large cell lymphoma (ALCL) in children and young adults aged ≥1 year

Assess the ability to swallow intact capsules before prescribing

280 mg/m2 PO BID

Continue until disease progression or unacceptable toxicity

Recommended dosage based on BSA

<0.6 m2: Dose not established

0.6-0.8 m2: 200 mg PO BID

0.81-1.16 m2: 250 mg PO BID

1.17-1.51 m2: 400 mg PO BID

1.52-1.69 m2: 450 mg PO BID

≥1.70 m2: 500 mg PO BID

Dosage Modifications

Dose reductions based on BSA

  • First dose reduction
    • 0.6-0.8 m2: 250 mg PO qDay
    • 0.81-1.16 m2: 200 mg PO BID
    • 1.17-1.69 m2: 250 mg PO BID
    • ≥1.70 m2: 400 mg PO BID
  • Second dose reduction
    • 0.6-0.8 m2: Permanently discontinue
    • 0.81-1.16 m2: 250 mg PO qDay
    • 1.17-1.69 m2: 200 mg PO BID
    • ≥1.70 m2: 250 mg PO BID
  • Unable to tolerate after 2 dose reductions
    • Permanently discontinue

Absolute neutrophil count (ANC)

  • ANC <0.5 x 109/L
  • First occurrence
    • Withhold until recovery to ANC >1 x 109/L, then resume at next dose reduction
  • Second occurrence
    • Recurrence complicated by febrile neutropenia: Permanently discontinue
    • Uncomplicated Grade 4: Either permanently discontinue or withhold until recovery to ANC >1 x 109/L, then resume at next dose reduction
    • Unable to tolerate 2 dose reductions: Permanently discontinue

Platelet count

  • 25-50 x 109/L with concurrent bleeding: Withhold until recovery to platelet count >50 x 109/L and bleeding resolves, then resume at same dose
  • <25 x 109/L: Withhold until recovery to platelet count >50 x 109/L and bleeding resolves, then resume at next dose reduction
  • Permanently discontinue for recurrence

Anemia

  • Hemoglobin (Hgb) <8 g/dL: Withhold until recovery to Hgb >8 g/dL, then resume at same dose
  • Life-threatening anemia (urgent intervention indicated): Withhold until recovery to Hgb >8 g/dL, then resume at next dose reduction
  • Permanently discontinue for recurrence

Hepatotoxicity

  • ALT or AST >5x ULN with total bilirubin [TB] ≤1.5x ULN: Withhold until recovery to baseline or ≤3x ULN, then resume at next dose reduction
  • ALT or AST >3x AND TB >1.5x ULN (in the absence of cholestasis or hemolysis): Permanently discontinue

Interstitial lung disease/pneumonitis

  • Any grade (drug-related): Permanently discontinue

QT prolongation

  • Correct QT (QTc) >500 ms on at least 2 separate ECG: Withhold until recovery to baseline or at QTc <481 ms, then resume at next dose reduction
  • QTc >500 ms or ≥60 ms change from baseline with torsade de pointes or polymorphic ventricular tachycardia or signs/symptoms of serious arrhythmia: Permanently discontinue

Bradycardia

  • Resting HR <2.5th percentile per age-specific norms
    • 1 to <2 years: ≥91 bpm
    • 2-3 years: ≥82 bpm
    • 4-5 years: ≥72 bpm
    • 6-8 years: ≥64 bpm
    • >8 years: ≥60 bpm
  • Symptomatic, may be severe and medically intervention indicated
    • Withhold until recovery to resting HR according to age (based on 2.5th percentile per age-specific norms)
  • Life-threatening consequences (urgent intervention indicated)
  • No contributing medications identified: Permanently discontinue
  • If contributing medication is identified, and discontinued, or its dose adjusted: Resume at second dose reduction upon recovery to asymptomatic bradycardia or manage HR based on criteria of symptomatic or severe, medically significant bradycardia, with frequent monitoring
  • Permanently discontinue for recurrence

Ocular toxicity

  • Grade 1 or 2 (mild or moderate visual symptoms affecting ability to perform age-appropriate activities of daily living)
    • Monitor and report any symptoms to an eye specialist
    • Grade 2 visual disorders: Consider dose reduction
  • Grade 3 or 4 ocular disorder (marked decrease in vision)
    • Withhold pending evaluation of severe visual loss
    • Permanently discontinue, if no other cause found on evaluation

Gastrointestinal toxicity

  • Occurs despite maximum medical therapy
  • Grade 3 nausea (inadequate oral intake for >3 days, medical intervention required)
  • Grade 3 vomiting (> 6 episodes in 24 hr for >3 days, medical intervention required [eg, tube feeding or hospitalization)
  • Grade 3 diarrhea (increase of ≥7 stools/day over baseline; incontinence; hospitalization indicated)
  • Grade 4 vomiting or diarrhea (life-threatening consequences, urgent intervention indicated)
  • Withhold until resolved for any of of above descriptions, then resume at next dose reduction
  • Permanently discontinue if unable to tolerate after 2 dose reductions, unless otherwise indicated

Strong CYP3A4 inhibitors

  • Avoid coadministration
  • If use is unavoidable, reduce criztotinib dose to second dose reduction
  • After discontinuation of strong CYP3A inhibitor, resume crizotinib dose used before initiating strong CYP3A inhibitor

Renal impairment

  • Calculate CrCl with Schwartz equation
  • Mild-to-moderate (CrCl 30-89 mL/min): No dosage adjustment necessary
  • Severe (CrCl <30 mL/min) and not requiring dialysis: Second dose reduction

Hepatic impairment

  • Moderate (any AST and TB >1.5x ULN and ≤3x ULN): First dose reduction
  • Severe (any AST and TB >3x ULN): Second dose reduction

Dosing Considerations

Verify pregnancy status in females of reproductive potential before initiation

Monitoring parameters

  • CBC including differential WBC counts: Monthly and as clinically indicated, more frequently if Grade 3 or 4 abnormalities are observed or if fever or infection occurs
  • Ophthalmologic examination: Obtain at baseline before initiation; consider follow-up including retinal examination within 1 month of initiation, every 3 months thereafter, and upon any new visual symptoms; assess symptoms regularly during treatment
  • Liver function tests: Every 2 weeks during the first 2 months of treatment, then monthly, and as clinically needed

Supportive care

  • Provide standard antiemetic and antidiarrheal agents before and during treatment
  • Consider IV or oral hydration and replace electrolytes as clinically indicated

Limitation of use

  • Safety and efficacy not established in older adults with relapsed or refractory, systemic ALK-positive ALCL

No overall differences in safety or efficacy were observed in comparison with younger patients

Next:

Interactions

Interaction Checker

and crizotinib

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 

            Contraindicated (9)

            • dronedarone

              crizotinib and dronedarone both increase QTc interval. Contraindicated. Dronedarone is contraindicated with drugs that may prolong the QT interval. Coadministration of crizotinib with CYP3A substrates with narrow therapeutic indices should be avoided.

            • flibanserin

              crizotinib will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of flibanserin with moderate or strong CYP3A4 inhibitors is contraindicated. Severe hypotension or syncope can occur.

            • lefamulin

              lefamulin will increase the level or effect of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lefamulin is contraindicated with CYP3A substrates know to prolong the QT interval.

            • lomitapide

              crizotinib increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Increases lomitapide levels several folds.

            • lonafarnib

              crizotinib 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.

            • pimozide

              crizotinib and pimozide both increase QTc interval. Contraindicated. Pimozide is contraindicated with drugs that may prolong the QT interval. Coadministration of crizotinib with CYP3A substrates with narrow therapeutic indices should be avoided.

            • posaconazole

              crizotinib and posaconazole both increase QTc interval. Contraindicated.

            • saquinavir

              crizotinib and saquinavir both increase QTc interval. Contraindicated.

            • thioridazine

              crizotinib and thioridazine both increase QTc interval. Contraindicated. Thioridazine is contraindicated with drugs that may prolong the QT interval.

            Serious - Use Alternative (114)

            • abametapir

              abametapir increases levels of crizotinib 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.

            • alfuzosin

              alfuzosin and crizotinib both increase QTc interval. Avoid or Use Alternate Drug.

            • amiodarone

              crizotinib and amiodarone both increase QTc interval. Avoid or Use Alternate Drug.

            • anagrelide

              crizotinib and anagrelide both increase QTc interval. Avoid or Use Alternate Drug.

            • apalutamide

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

            • aripiprazole

              aripiprazole and crizotinib both increase QTc interval. Avoid or Use Alternate Drug.

            • artemether

              artemether and crizotinib both increase QTc interval. Avoid or Use Alternate Drug.

            • atomoxetine

              atomoxetine and crizotinib both increase QTc interval. Avoid or Use Alternate Drug.

            • avapritinib

              crizotinib will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

            • bosutinib

              crizotinib increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • buprenorphine

              crizotinib and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.

            • ceritinib

              ceritinib and crizotinib both increase QTc interval. Avoid or Use Alternate Drug.

            • chloramphenicol

              chloramphenicol will increase the level or effect of crizotinib by aldehyde dehydrogenase inhibition. Avoid or Use Alternate Drug.

            • citalopram

              citalopram and crizotinib both increase QTc interval. Avoid or Use Alternate Drug.

            • clarithromycin

              clarithromycin and crizotinib both increase QTc interval. Avoid or Use Alternate Drug.

            • clozapine

              clozapine and crizotinib both increase QTc interval. Avoid or Use Alternate Drug.

            • cobicistat

              cobicistat will increase the level or effect of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Increase in crizotinib levels may result in QT prolongation; May reduce crizotinib dose to 250 mg PO qDay if concomitant administration cannot be avoided.

            • cobimetinib

              crizotinib will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

            • conivaptan

              conivaptan will increase the level or effect of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Increase in crizotinib levels may result in QT prolongation

            • dasatinib

              crizotinib and dasatinib both increase QTc interval. Avoid or Use Alternate Drug.

            • deutetrabenazine

              crizotinib and deutetrabenazine both increase QTc interval. Avoid or Use Alternate Drug.

            • disopyramide

              crizotinib increases levels of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of crizotinib with CYP3A substrates with narrow therapeutic indices should be avoided. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

              crizotinib and disopyramide both increase QTc interval. Avoid or Use Alternate Drug.

            • edoxaban

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

            • eliglustat

              crizotinib increases levels of eliglustat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Moderate CYP3A4 inhibitors are not recommended with eliglustat poor or intermediate metabolizers; reduce eliglustat dose from 84 mg BID to 84 mg once daily in extensive metabolizers .

              crizotinib and eliglustat both increase QTc interval. Avoid or Use Alternate Drug.

            • encorafenib

              crizotinib will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a moderate CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-half of the dose (eg, reduce from 450 mg/day to 225 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

              crizotinib and encorafenib both increase QTc interval. Avoid or Use Alternate Drug.

            • entrectinib

              crizotinib and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

              crizotinib will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • erdafitinib

              erdafitinib will increase the level or effect of crizotinib 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.

            • eribulin

              crizotinib and eribulin both increase QTc interval. Avoid or Use Alternate Drug.

            • erythromycin base

              crizotinib and erythromycin base both increase QTc interval. Avoid or Use Alternate Drug.

            • erythromycin ethylsuccinate

              crizotinib and erythromycin ethylsuccinate both increase QTc interval. Avoid or Use Alternate Drug.

            • erythromycin lactobionate

              crizotinib and erythromycin lactobionate both increase QTc interval. Avoid or Use Alternate Drug.

            • erythromycin stearate

              crizotinib and erythromycin stearate both increase QTc interval. Avoid or Use Alternate Drug.

            • escitalopram

              escitalopram increases toxicity of crizotinib by QTc interval. Avoid or Use Alternate Drug.

            • eslicarbazepine acetate

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

            • fentanyl

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

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

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

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

              fexinidazole and crizotinib both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of fexinidazole with drugs known to block potassium channels or prolong QT interval.

              fexinidazole will increase the level or effect of crizotinib 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.

            • gilteritinib

              crizotinib and gilteritinib both increase QTc interval. Avoid or Use Alternate Drug.

            • glasdegib

              crizotinib and glasdegib both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, monitor for increased risk of QTc interval prolongation.

            • granisetron

              crizotinib and granisetron both increase QTc interval. Avoid or Use Alternate Drug.

            • haloperidol

              crizotinib and haloperidol both increase QTc interval. Avoid or Use Alternate Drug.

            • hydroxychloroquine sulfate

              hydroxychloroquine sulfate and crizotinib both increase QTc interval. Avoid or Use Alternate Drug.

            • hydroxyzine

              crizotinib and hydroxyzine both increase QTc interval. Avoid or Use Alternate Drug.

            • idelalisib

              idelalisib will increase the level or effect of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates

            • indacaterol, inhaled

              crizotinib and indacaterol, inhaled both increase QTc interval. Avoid or Use Alternate Drug.

            • infigratinib

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

            • inotuzumab

              inotuzumab and crizotinib both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.

            • irinotecan

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

            • irinotecan liposomal

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

            • isoflurane

              crizotinib and isoflurane both increase QTc interval. Avoid or Use Alternate Drug.

            • itraconazole

              itraconazole increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If combination cannot be avoided, decrease crizotinib dose to 250 mg daily. Monitor for increased crizotinib toxicities, including QTc interval prolongation and ventricular arrhythmias. .

              crizotinib and itraconazole both increase QTc interval. Avoid or Use Alternate Drug.

            • ivabradine

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

            • ivosidenib

              ivosidenib and crizotinib both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of QTc prolonging drugs with ivosidenib or replace with alternate therapies. If coadministration of a QTc prolonging drug is unavoidable, monitor for increased risk of QTc interval prolongation.

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

            • lasmiditan

              lasmiditan increases levels of crizotinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

            • lefamulin

              crizotinib and lefamulin both increase QTc interval. Avoid or Use Alternate Drug.

            • lemborexant

              crizotinib 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.

            • lithium

              crizotinib and lithium both increase QTc interval. Avoid or Use Alternate Drug.

            • lofexidine

              crizotinib and lofexidine both increase QTc interval. Avoid or Use Alternate Drug.

            • loperamide

              crizotinib and loperamide both increase QTc interval. Avoid or Use Alternate Drug.

            • lopinavir

              crizotinib and lopinavir both increase QTc interval. Avoid or Use Alternate Drug.

            • lurbinectedin

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

            • macimorelin

              macimorelin and crizotinib both increase QTc interval. Avoid or Use Alternate Drug. Macimorelin causes an increase of ~11 msec in the corrected QT interval. Avoid coadministration with drugs that prolong QT interval, which could increase risk for developing torsade de pointes-type ventricular tachycardia. Allow sufficient washout time of drugs that are known to prolong the QT interval before administering macimorelin.

            • mefloquine

              crizotinib and mefloquine both increase QTc interval. Avoid or Use Alternate Drug.

            • methadone

              crizotinib and methadone both increase QTc interval. Avoid or Use Alternate Drug.

            • midazolam intranasal

              crizotinib will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of moderate CYP3A4 inhibitors with midazolam intranasal causes higher midazolam systemic exposure, which may prolong sedation.

            • midostaurin

              crizotinib and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.

            • mifepristone

              mifepristone will increase the level or effect of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Increase in crizotinib levels may result in QT prolongation

            • mirtazapine

              crizotinib and mirtazapine both increase QTc interval. Avoid or Use Alternate Drug.

            • mobocertinib

              crizotinib 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.

              mobocertinib and crizotinib both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, reduce mobocertinib dose and monitor QTc interval more frequently.

            • naloxegol

              crizotinib will increase the level or effect of naloxegol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministation of naloxegol with moderate CYP3A4 inhibitors is unavoidable, reduce naloxegol dose to 12.5 mg qDay

            • neratinib

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

            • nilotinib

              crizotinib and nilotinib both increase QTc interval. Avoid or Use Alternate Drug.

            • olanzapine

              crizotinib and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • olaparib

              crizotinib will increase the level or effect of olaparib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A inhibitors cannot be avoided, reduce olaparib dose to 200 mg (capsule) or 150 mg (tablet) PO BID. Do not substitute tablets with capsules.

            • ondansetron

              crizotinib and ondansetron both decrease QTc interval. Avoid or Use Alternate Drug. Avoid with congenital long QT syndrome; ECG monitoring recommended with concomitant medications that prolong QT interval, electrolyte abnormalities, CHF, or bradyarrhythmias.

            • oxaliplatin

              crizotinib and oxaliplatin both increase QTc interval. Avoid or Use Alternate Drug.

            • palifermin

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

            • panobinostat

              crizotinib and panobinostat both increase QTc interval. Avoid or Use Alternate Drug. Panobinostat is known to significantly prolong QT interval. Panobinostat prescribing information states use with drugs known to prolong QTc is not recommended.

            • pazopanib

              crizotinib and pazopanib both increase QTc interval. Avoid or Use Alternate Drug.

            • pemigatinib

              crizotinib 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.

            • pexidartinib

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

            • pimavanserin

              crizotinib and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

            • pitolisant

              crizotinib and pitolisant both increase QTc interval. Avoid or Use Alternate Drug.

            • ponesimod

              ponesimod, crizotinib. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Consult cardiologist if considering treatment. Coadministration of ponesimod with drugs that decrease HR may have additive effects on decreasing HR and should generally not be initiated in these patients.

              crizotinib and ponesimod both increase QTc interval. Avoid or Use Alternate Drug.

            • primaquine

              crizotinib and primaquine both increase QTc interval. Avoid or Use Alternate Drug.

            • primidone

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

            • quetiapine

              crizotinib and quetiapine both increase QTc interval. Avoid or Use Alternate Drug.

            • quinidine

              crizotinib increases levels of quinidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of crizotinib with CYP3A substrates with narrow therapeutic indices should be avoided. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

              crizotinib and quinidine both increase QTc interval. Avoid or Use Alternate Drug.

            • ranolazine

              crizotinib and ranolazine both increase QTc interval. Avoid or Use Alternate Drug.

            • ribociclib

              ribociclib will increase the level or effect of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Increase in crizotinib levels may result in QT prolongation

              ribociclib increases toxicity of crizotinib by QTc interval. Avoid or Use Alternate Drug.

            • selumetinib

              crizotinib 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.

            • sertraline

              crizotinib and sertraline both increase QTc interval. Avoid or Use Alternate Drug.

            • sevoflurane

              crizotinib and sevoflurane both increase QTc interval. Avoid or Use Alternate Drug.

            • sildenafil

              crizotinib increases levels of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid use of strong CYP3A4 inhibitors. If concomitant use of strong CYP3A inhibitors is unavoidable, reduce crizotnib to 250 mg PO qDay. After discontinuation of a strong CYP3A inhibitor, resume crizotinib dose used prior to initiating the strong CYP3A4 inhibitor.

            • siponimod

              crizotinib 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.

              crizotinib and siponimod both increase QTc interval. Avoid or Use Alternate Drug.

            • solifenacin

              crizotinib and solifenacin both increase QTc interval. Avoid or Use Alternate Drug.

            • sotorasib

              sotorasib will decrease the level or effect of crizotinib 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.

            • sunitinib

              crizotinib and sunitinib both increase QTc interval. Avoid or Use Alternate Drug.

            • tacrolimus

              crizotinib increases levels of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of crizotinib with CYP3A substrates with narrow therapeutic indices should be avoided. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

              crizotinib and tacrolimus both increase QTc interval. Avoid or Use Alternate Drug.

            • tazemetostat

              crizotinib 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 crizotinib 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.

            • tetrabenazine

              crizotinib and tetrabenazine both increase QTc interval. Avoid or Use Alternate Drug.

            • topotecan

              crizotinib will increase the level or effect of topotecan by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Product labeling for PO topotecan recommends avoiding concomitant use of P-gp inhibitors; the interaction with IV topotecan may be less severe but is still likely of clinical significance

            • trazodone

              crizotinib and trazodone both increase QTc interval. Avoid or Use Alternate Drug.

            • triclabendazole

              crizotinib and triclabendazole both increase QTc interval. Avoid or Use Alternate Drug.

            • tucatinib

              tucatinib will increase the level or effect of crizotinib 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.

            • umeclidinium bromide/vilanterol inhaled

              crizotinib increases toxicity of umeclidinium bromide/vilanterol inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.

            • vardenafil

              crizotinib and vardenafil both increase QTc interval. Avoid or Use Alternate Drug.

            • venetoclax

              crizotinib will increase the level or effect of venetoclax by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If a moderate CYP3A inhibitor must be used, reduce the venetoclax dose by at least 50%. Monitor more closely for signs of venetoclax toxicities.

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

            • vilanterol/fluticasone furoate inhaled

              crizotinib increases toxicity of vilanterol/fluticasone furoate inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.

            • voriconazole

              crizotinib and voriconazole both increase QTc interval. Avoid or Use Alternate Drug.

            • voxelotor

              voxelotor will increase the level or effect of crizotinib 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 (302)

            • abiraterone

              crizotinib increases levels of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

              abiraterone increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution should be exercised with concomitant use of moderate CYP3A inhibitors. .

            • acalabrutinib

              crizotinib will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease acalabrutinib dose to 100 mg once daily if coadministered with a moderate CYP3A inhibitor.

            • albuterol

              albuterol and crizotinib both increase QTc interval. Use Caution/Monitor.

            • alfentanil

              crizotinib increases levels of alfentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of crizotinib with CYP3A substrates with narrow therapeutic indices should be avoided.

            • alfuzosin

              crizotinib increases levels of alfuzosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

              crizotinib and alfuzosin both increase QTc interval. Use Caution/Monitor.

            • aliskiren

              crizotinib increases levels of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • alprazolam

              crizotinib increases levels of alprazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • aluminum hydroxide

              aluminum hydroxide decreases levels of crizotinib by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor. Drugs that elevate the gastric pH may decrease the solubility of crizotinib and subsequently reduce its bioavailability. However, no formal studies have been conducted. .

            • amiodarone

              crizotinib increases levels of amiodarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

              amiodarone increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution should be exercised with concomitant use of moderate CYP3A inhibitors. .

            • amitriptyline

              crizotinib and amitriptyline both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • amlodipine

              crizotinib increases levels of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • amoxapine

              crizotinib and amoxapine both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • apomorphine

              crizotinib and apomorphine both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • aprepitant

              aprepitant increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution should be exercised with concomitant use of moderate CYP3A inhibitors. .

              crizotinib increases levels of aprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution should be exercised with concomitant use of moderate CYP3A inhibitors. .

            • arformoterol

              arformoterol and crizotinib both increase QTc interval. Use Caution/Monitor.

            • aripiprazole

              crizotinib increases levels of aripiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • armodafinil

              crizotinib increases levels of armodafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • arsenic trioxide

              crizotinib and arsenic trioxide both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • artemether/lumefantrine

              crizotinib and artemether/lumefantrine both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • asenapine

              crizotinib and asenapine both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • atazanavir

              atazanavir increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use of strong CYP3A inducers should be avoided. .

              crizotinib increases levels of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • atogepant

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

            • atorvastatin

              crizotinib increases levels of atorvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

              crizotinib increases levels of atorvastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • avanafil

              crizotinib increases levels of avanafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • azithromycin

              crizotinib and azithromycin both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

              azithromycin increases toxicity of crizotinib by QTc interval. Use Caution/Monitor.

            • bedaquiline

              crizotinib and bedaquiline both increase QTc interval. Modify Therapy/Monitor Closely. ECG should be monitored closely

            • belzutifan

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

            • berotralstat

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

            • betrixaban

              crizotinib increases levels of betrixaban by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Decrease betrixaban dose to 80 mg PO once, then 40 mg PO qDay if coadministered with a P-gp inhibitor.

            • bicalutamide

              bicalutamide increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution should be exercised with concomitant use of moderate CYP3A inhibitors. .

            • bortezomib

              crizotinib increases levels of bortezomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • bosentan

              crizotinib increases levels of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • brexpiprazole

              crizotinib will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

            • bromocriptine

              crizotinib increases levels of bromocriptine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • budesonide

              crizotinib increases levels of budesonide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • buprenorphine

              crizotinib increases levels of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • buprenorphine buccal

              crizotinib increases levels of buprenorphine buccal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • buprenorphine subdermal implant

              crizotinib will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

            • buprenorphine, long-acting injection

              crizotinib will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • buspirone

              crizotinib increases levels of buspirone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • cabazitaxel

              crizotinib increases levels of cabazitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • cabozantinib

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

            • calcium carbonate

              calcium carbonate decreases levels of crizotinib by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor. Drugs that elevate the gastric pH may decrease the solubility of crizotinib and subsequently reduce its bioavailability. However, no formal studies have been conducted. .

            • cannabidiol

              crizotinib will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP3A4 inhibitor.

            • carbamazepine

              carbamazepine decreases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use of strong CYP3A inducers should be avoided. .

              crizotinib increases levels of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of crizotinib with CYP3A substrates with narrow therapeutic indices should be avoided.

            • carvedilol

              crizotinib increases levels of carvedilol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • cenobamate

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

            • ceritinib

              crizotinib increases levels of ceritinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • cetirizine

              crizotinib increases levels of cetirizine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • chloroquine

              crizotinib increases levels of chloroquine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

              chloroquine increases toxicity of crizotinib by QTc interval. Use Caution/Monitor.

            • chlorpromazine

              crizotinib and chlorpromazine both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • ciclesonide inhaled

              crizotinib increases levels of ciclesonide inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • cilostazol

              crizotinib increases levels of cilostazol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • cimetidine

              cimetidine decreases levels of crizotinib by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor. Drugs that elevate the gastric pH may decrease the solubility of crizotinib and subsequently reduce its bioavailability. However, no formal studies have been conducted. .

            • cinacalcet

              crizotinib increases levels of cinacalcet by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • ciprofloxacin

              crizotinib and ciprofloxacin both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • citalopram

              crizotinib increases levels of citalopram by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • clarithromycin

              clarithromycin increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use of strong CYP3A inhibitors should be avoided. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • clofazimine

              crizotinib and clofazimine both increase QTc interval. Use Caution/Monitor.

            • clomipramine

              crizotinib and clomipramine both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • clonazepam

              crizotinib increases levels of clonazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • conivaptan

              crizotinib increases levels of conivaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • crofelemer

              crofelemer increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.

            • cyclobenzaprine

              crizotinib and cyclobenzaprine both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • cyclosporine

              crizotinib increases levels of cyclosporine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of crizotinib with CYP3A substrates with narrow therapeutic indices should be avoided.

              cyclosporine increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution should be exercised with concomitant use of moderate CYP3A inhibitors. .

            • dabigatran

              crizotinib will increase the level or effect of dabigatran by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Atrial fibrillation: Avoid coadministering dabigatran with P-gp inhibitors if CrCl <30 mL/min. DVT/PE treatment: Avoid coadministering dabigatran with P-gp inhibitors if CrCl <50 mL/min

            • dabrafenib

              dabrafenib will increase the level or effect of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • dapsone

              crizotinib increases levels of dapsone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • darifenacin

              crizotinib increases levels of darifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • darunavir

              darunavir increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use of strong CYP3A inhibitors should be avoided. .

              crizotinib increases levels of darunavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • dasatinib

              crizotinib increases levels of dasatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • daunorubicin

              crizotinib increases levels of daunorubicin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • deflazacort

              crizotinib will increase the level or effect of deflazacort by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease deflazacort dose to one-third of the recommended dose if coadministered with moderate or strong CYP3A4 inhibitors.

            • degarelix

              crizotinib and degarelix both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • desipramine

              crizotinib and desipramine both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • desloratadine

              crizotinib increases levels of desloratadine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • dexamethasone

              dexamethasone decreases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use of strong CYP3A inducers should be avoided. .

              crizotinib increases levels of dexamethasone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

              crizotinib increases levels of dexamethasone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • dexlansoprazole

              dexlansoprazole decreases levels of crizotinib by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor. Drugs that elevate the gastric pH may decrease the solubility of crizotinib and subsequently reduce its bioavailability. However, no formal studies have been conducted. .

            • diazepam

              crizotinib increases levels of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • diazepam intranasal

              crizotinib 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.

            • dichlorphenamide

              dichlorphenamide and crizotinib both decrease serum potassium. Use Caution/Monitor.

            • digoxin

              crizotinib increases levels of digoxin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of crizotinib with CYP3A substrates with narrow therapeutic indices should be avoided.

              crizotinib increases levels of digoxin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • dihydroergotamine

              crizotinib increases levels of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of crizotinib with CYP3A substrates with narrow therapeutic indices should be avoided.

            • dihydroergotamine intranasal

              crizotinib increases levels of dihydroergotamine intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of crizotinib with CYP3A substrates with narrow therapeutic indices should be avoided.

            • diltiazem

              crizotinib increases levels of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

              diltiazem increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution should be exercised with concomitant use of moderate CYP3A inhibitors. .

            • docetaxel

              crizotinib increases levels of docetaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

              crizotinib increases levels of docetaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • dofetilide

              crizotinib and dofetilide both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

              dofetilide increases toxicity of crizotinib by QTc interval. Use Caution/Monitor.

            • dolasetron

              crizotinib and dolasetron both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • doxorubicin

              crizotinib increases levels of doxorubicin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

              crizotinib increases levels of doxorubicin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • doxorubicin liposomal

              crizotinib increases levels of doxorubicin liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • droperidol

              crizotinib and droperidol both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • duvelisib

              duvelisib will increase the level or effect of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. will increase the level or effect of

            • efavirenz

              efavirenz increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution should be exercised with concomitant use of moderate CYP3A inhibitors. .

            • elagolix

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

              elagolix will decrease the level or effect of crizotinib 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.

            • eletriptan

              crizotinib increases levels of eletriptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP3A4 inhibitor; contraindicated with CYP3A4 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.

            • encorafenib

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

            • ergotamine

              crizotinib increases levels of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of crizotinib with CYP3A substrates with narrow therapeutic indices should be avoided.

            • erlotinib

              crizotinib increases levels of erlotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • erythromycin base

              crizotinib increases levels of erythromycin base by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

              crizotinib increases levels of erythromycin base by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

              erythromycin base increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution should be exercised with concomitant use of moderate CYP3A inhibitors. .

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution should be exercised with concomitant use of moderate CYP3A inhibitors. .

              crizotinib increases levels of erythromycin ethylsuccinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

              crizotinib increases levels of erythromycin ethylsuccinate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • erythromycin lactobionate

              erythromycin lactobionate increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution should be exercised with concomitant use of moderate CYP3A inhibitors. .

              crizotinib increases levels of erythromycin lactobionate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

              crizotinib increases levels of erythromycin lactobionate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • erythromycin stearate

              erythromycin stearate increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution should be exercised with concomitant use of moderate CYP3A inhibitors. .

              crizotinib increases levels of erythromycin stearate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

              crizotinib increases levels of erythromycin stearate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • escitalopram

              crizotinib increases levels of escitalopram by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

              crizotinib and escitalopram both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • esomeprazole

              esomeprazole decreases levels of crizotinib by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor. Drugs that elevate the gastric pH may decrease the solubility of crizotinib and subsequently reduce its bioavailability. However, no formal studies have been conducted. .

            • eszopiclone

              crizotinib increases levels of eszopiclone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce eszopiclone starting dose to 1 mg/day.

            • ethosuximide

              crizotinib increases levels of ethosuximide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • etoposide

              crizotinib increases levels of etoposide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

              crizotinib increases levels of etoposide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • etravirine

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

            • everolimus

              crizotinib increases levels of everolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • famotidine

              famotidine decreases levels of crizotinib by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor. Drugs that elevate the gastric pH may decrease the solubility of crizotinib and subsequently reduce its bioavailability. However, no formal studies have been conducted. .

            • fedratinib

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

            • felodipine

              crizotinib increases levels of felodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • fesoterodine

              crizotinib increases levels of fesoterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • fexofenadine

              crizotinib increases levels of fexofenadine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • finerenone

              crizotinib 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.

            • flecainide

              crizotinib and flecainide both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • fluconazole

              crizotinib and fluconazole both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

              fluconazole increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution should be exercised with concomitant use of moderate CYP3A inhibitors. .

            • fluoxetine

              crizotinib and fluoxetine both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • fluphenazine

              crizotinib and fluphenazine both increase QTc interval. Use Caution/Monitor.

            • flurazepam

              crizotinib increases levels of flurazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • fosamprenavir

              fosamprenavir increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use of strong CYP3A inhibitors should be avoided. .

              crizotinib increases levels of fosamprenavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • foscarnet

              crizotinib and foscarnet both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • fosphenytoin

              fosphenytoin decreases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use of strong CYP3A inducers should be avoided. .

              crizotinib increases levels of fosphenytoin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of crizotinib with CYP3A substrates with narrow therapeutic indices should be avoided.

            • fostemsavir

              crizotinib and fostemsavir both increase QTc interval. Use Caution/Monitor. QTc prolongation reported with higher than recommended doses of fostemsavir.

            • gadobenate

              crizotinib and gadobenate both increase QTc interval. Use Caution/Monitor.

            • gemifloxacin

              crizotinib and gemifloxacin both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • gemtuzumab

              crizotinib and gemtuzumab both increase QTc interval. Use Caution/Monitor.

            • glecaprevir/pibrentasvir

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

            • goserelin

              goserelin increases toxicity of crizotinib by QTc interval. Use Caution/Monitor. Increases risk of torsades de pointes.

            • grapefruit

              grapefruit increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use of strong CYP3A inhibitors should be avoided. .

            • guanfacine

              crizotinib will increase the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong or moderate CYP3A4 inhibitors significantly increase guanfacine plasma concentrations. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if coadministered, the guanfacine dosage should be decreased to half of the recommended dose. Specific recommendations for immediate-release (IR) guanfacine are not available.

            • haloperidol

              crizotinib increases levels of haloperidol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • hawthorn

              crizotinib and hawthorn both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • histrelin

              histrelin increases toxicity of crizotinib by QTc interval. Use Caution/Monitor. Increases risk of torsades de pointes.

            • hydroxyprogesterone caproate

              crizotinib increases levels of hydroxyprogesterone caproate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • ibrutinib

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

            • ibuprofen/famotidine

              ibuprofen/famotidine decreases levels of crizotinib by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor. Drugs that elevate the gastric pH may decrease the solubility of crizotinib and subsequently reduce its bioavailability. However, no formal studies have been conducted. .

            • ibutilide

              crizotinib and ibutilide both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • ifosfamide

              crizotinib will decrease the level or effect of ifosfamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Use of a CYP3A4 inhibitor may decrease metabolism of ifosfamide, potentially reducing ifosfamide therapeutic effects.

            • iloperidone

              crizotinib and iloperidone both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

              iloperidone increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.

            • imatinib

              imatinib increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use of strong CYP3A inhibitors should be avoided. .

              crizotinib increases levels of imatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

              crizotinib increases levels of imatinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • indapamide

              crizotinib and indapamide both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • indinavir

              indinavir increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use of strong CYP3A inhibitors should be avoided. .

              crizotinib increases levels of indinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • irinotecan

              crizotinib increases levels of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • irinotecan liposomal

              crizotinib increases levels of irinotecan liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • isavuconazonium sulfate

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

            • isoniazid

              isoniazid increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use of strong CYP3A inhibitors should be avoided. .

            • isradipine

              crizotinib and isradipine both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

              crizotinib increases levels of isradipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • istradefylline

              istradefylline will increase the level or effect of crizotinib 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.

              istradefylline will increase the level or effect of crizotinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of P-gp substrates in clinical trials. Consider dose reduction of sensitive P-gp substrates.

            • ivacaftor

              crizotinib will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

            • ivosidenib

              crizotinib will increase the level or effect of ivosidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with moderate CYP3A4 inhibitors may increase ivosidenib plasma concentrations, thus increasing the risk of QTc prolongation. Monitor for increased risk of QTc interval prolongation.

            • ixabepilone

              crizotinib increases levels of ixabepilone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • ketoconazole

              ketoconazole increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use of strong CYP3A inhibitors should be avoided. .

            • lansoprazole

              lansoprazole decreases levels of crizotinib by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor. Drugs that elevate the gastric pH may decrease the solubility of crizotinib and subsequently reduce its bioavailability. However, no formal studies have been conducted. .

            • lapatinib

              crizotinib increases levels of lapatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

              crizotinib increases levels of lapatinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

              lapatinib increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution should be exercised with concomitant use of moderate CYP3A inhibitors. .

            • lefamulin

              crizotinib 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.

            • lenvatinib

              crizotinib and lenvatinib both increase QTc interval. Use Caution/Monitor. Lenvatinib prescribing information recommends monitoring ECG closely when coadministered with QT prolonging drugs.

            • leuprolide

              leuprolide increases toxicity of crizotinib by QTc interval. Use Caution/Monitor. Increases risk of torsades de pointes.

            • levalbuterol

              crizotinib and levalbuterol both increase QTc interval. Use Caution/Monitor.

            • levamlodipine

              crizotinib 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.

            • levofloxacin

              crizotinib and levofloxacin both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • loperamide

              crizotinib increases levels of loperamide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • lopinavir

              lopinavir increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use of strong CYP3A inhibitors should be avoided. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • loratadine

              crizotinib increases levels of loratadine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • lorlatinib

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

            • lovastatin

              crizotinib increases levels of lovastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

              crizotinib increases levels of lovastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • lumefantrine

              crizotinib and lumefantrine both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • magnesium hydroxide

              magnesium hydroxide decreases levels of crizotinib by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor. Drugs that elevate the gastric pH may decrease the solubility of crizotinib and subsequently reduce its bioavailability. However, no formal studies have been conducted. .

            • magnesium oxide

              magnesium oxide decreases levels of crizotinib by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor. Drugs that elevate the gastric pH may decrease the solubility of crizotinib and subsequently reduce its bioavailability. However, no formal studies have been conducted. .

            • maprotiline

              crizotinib and maprotiline both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • maraviroc

              crizotinib increases levels of maraviroc by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • mefloquine

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

            • methadone

              crizotinib increases levels of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • methylergonovine

              crizotinib increases levels of methylergonovine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • midazolam

              crizotinib increases levels of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of crizotinib with CYP3A substrates with narrow therapeutic indices should be avoided.

            • mifepristone

              mifepristone, crizotinib. QTc interval. Modify Therapy/Monitor Closely. Use alternatives if available.

            • mirtazapine

              crizotinib increases levels of mirtazapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • mitomycin

              crizotinib increases levels of mitomycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • mitotane

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

            • modafinil

              crizotinib increases levels of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • moxifloxacin

              crizotinib and moxifloxacin both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • nafcillin

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

            • naldemedine

              crizotinib increases levels of naldemedine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor naldemedine for potential adverse effects if coadministered with strong or moderate CYP3A4 inhibitors.

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

            • nefazodone

              nefazodone increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use of strong CYP3A inhibitors should be avoided. .

            • nelfinavir

              nelfinavir increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use of strong CYP3A inhibitors should be avoided. .

              crizotinib increases levels of nelfinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • nicardipine

              nicardipine increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use of strong CYP3A inhibitors should be avoided. .

              crizotinib increases levels of nicardipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • nifedipine

              crizotinib increases levels of nifedipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • nilotinib

              crizotinib increases levels of nilotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • nimodipine

              crizotinib increases levels of nimodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • nintedanib

              crizotinib increases levels of nintedanib by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. If nintedanib adverse effects occur, management may require interruption, dose reduction, or discontinuation of therapy.

            • nisoldipine

              crizotinib increases levels of nisoldipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • nizatidine

              nizatidine decreases levels of crizotinib by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor. Drugs that elevate the gastric pH may decrease the solubility of crizotinib and subsequently reduce its bioavailability. However, no formal studies have been conducted. .

            • nortriptyline

              crizotinib and nortriptyline both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • octreotide

              crizotinib and octreotide both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • ofloxacin

              crizotinib and ofloxacin both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • oliceridine

              crizotinib 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.

            • olodaterol inhaled

              crizotinib and olodaterol inhaled both increase QTc interval. Use Caution/Monitor.

            • omeprazole

              omeprazole will decrease the level or effect of crizotinib by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor. Drugs that elevate the gastric pH may decrease the solubility of crizotinib and subsequently reduce its bioavailability. However, no formal studies have been conducted.

            • ondansetron

              crizotinib increases levels of ondansetron by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • osilodrostat

              osilodrostat and crizotinib both increase QTc interval. Use Caution/Monitor.

            • osimertinib

              osimertinib and crizotinib both increase QTc interval. Use Caution/Monitor. Conduct periodic monitoring with ECGs and electrolytes in patients taking drugs known to prolong the QTc interval.

            • oxaliplatin

              oxaliplatin will increase the level or effect of crizotinib by Other (see comment). Use Caution/Monitor. Monitor for ECG changes if therapy is initiated in patients with drugs known to prolong QT interval.

            • oxcarbazepine

              oxcarbazepine decreases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use of strong CYP3A inducers should be avoided. .

            • oxycodone

              crizotinib increases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • ozanimod

              ozanimod and crizotinib both increase QTc interval. Modify Therapy/Monitor Closely. The potential additive effects on heart rate, treatment with ozanimod should generally not be initiated in patients who are concurrently treated with QT prolonging drugs with known arrhythmogenic properties.

            • paclitaxel

              crizotinib increases levels of paclitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

              crizotinib increases levels of paclitaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • paclitaxel protein bound

              crizotinib increases levels of paclitaxel protein bound by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

              crizotinib increases levels of paclitaxel protein bound by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • palbociclib

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

            • paliperidone

              crizotinib and paliperidone both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • pantoprazole

              pantoprazole decreases levels of crizotinib by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor. Drugs that elevate the gastric pH may decrease the solubility of crizotinib and subsequently reduce its bioavailability. However, no formal studies have been conducted. .

            • pasireotide

              crizotinib and pasireotide both increase QTc interval. Modify Therapy/Monitor Closely.

            • pazopanib

              crizotinib increases levels of pazopanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

              crizotinib increases levels of pazopanib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • pentamidine

              crizotinib and pentamidine both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • perphenazine

              crizotinib and perphenazine both increase QTc interval. Use Caution/Monitor.

            • phenobarbital

              phenobarbital decreases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use of strong CYP3A inducers should be avoided. .

            • phenytoin

              phenytoin decreases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use of strong CYP3A inducers should be avoided. .

              crizotinib increases levels of phenytoin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of crizotinib with CYP3A substrates with narrow therapeutic indices should be avoided.

            • posaconazole

              posaconazole increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use of strong CYP3A inhibitors should be avoided. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • pravastatin

              crizotinib increases levels of pravastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • praziquantel

              crizotinib increases levels of praziquantel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • procainamide

              crizotinib and procainamide both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • propafenone

              crizotinib and propafenone both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • protriptyline

              crizotinib and protriptyline both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • quetiapine

              crizotinib increases levels of quetiapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • quinine

              crizotinib increases levels of quinine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

              crizotinib and quinine both increase QTc interval. Use Caution/Monitor.

            • rabeprazole

              rabeprazole decreases levels of crizotinib by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor. Drugs that elevate the gastric pH may decrease the solubility of crizotinib and subsequently reduce its bioavailability. However, no formal studies have been conducted. .

            • ranolazine

              crizotinib increases levels of ranolazine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • repaglinide

              crizotinib increases levels of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • rifabutin

              rifabutin decreases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use of strong CYP3A inducers should be avoided. .

            • rifampin

              rifampin decreases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use of strong CYP3A inducers should be avoided. .

              crizotinib increases levels of rifampin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • rifapentine

              rifapentine decreases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use of strong CYP3A inducers should be avoided. .

            • rifaximin

              crizotinib increases levels of rifaximin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • rilpivirine

              crizotinib increases levels of rilpivirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • rimegepant

              crizotinib will increase the level or effect of rimegepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid repeating rimegepant dose within 48 hr if coadministered with a moderate CYP3A4 inhibitor.

            • risperidone

              crizotinib and risperidone both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • ritonavir

              ritonavir increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use of strong CYP3A inhibitors should be avoided. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

              crizotinib increases levels of ritonavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • rivaroxaban

              crizotinib increases levels of rivaroxaban by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • romidepsin

              crizotinib increases levels of romidepsin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

              crizotinib increases levels of romidepsin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

              crizotinib and romidepsin both increase QTc interval. Use Caution/Monitor.

            • rucaparib

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

            • salmeterol

              crizotinib and salmeterol both increase QTc interval. Use Caution/Monitor.

            • saquinavir

              saquinavir increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use of strong CYP3A inhibitors should be avoided. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

              crizotinib increases levels of saquinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • sarecycline

              sarecycline will increase the level or effect of crizotinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for toxicities of P-gp substrates that may require dosage reduction when coadministered with P-gp inhibitors.

            • saxagliptin

              crizotinib increases levels of saxagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • selpercatinib

              selpercatinib increases toxicity of crizotinib by QTc interval. Use Caution/Monitor.

            • silodosin

              crizotinib increases levels of silodosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

              crizotinib increases levels of silodosin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • simvastatin

              crizotinib increases levels of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • siponimod

              siponimod and crizotinib 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.

            • sirolimus

              crizotinib increases levels of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of crizotinib with CYP3A substrates with narrow therapeutic indices should be avoided.

              crizotinib increases levels of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • sitagliptin

              crizotinib increases levels of sitagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • sodium bicarbonate

              sodium bicarbonate decreases levels of crizotinib by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor. Drugs that elevate the gastric pH may decrease the solubility of crizotinib and subsequently reduce its bioavailability. However, no formal studies have been conducted. .

            • sodium zirconium cyclosilicate

              sodium zirconium cyclosilicate will decrease the level or effect of crizotinib by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Check specific recommendations for drugs that exhibit pH-dependent solubility that may affect their systemic exposure and efficacy. In general, administer drugs at least 2 hr before or after sodium zirconium cyclosilicate.

            • solifenacin

              crizotinib increases levels of solifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • sonidegib

              crizotinib will increase the level or effect of sonidegib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of sonidegib with moderate CYP3A4 inhibitors. If a moderate CYP3A inhibitor must be used, administer the moderate CYP3A inhibitor for <14 days and monitor closely for adverse reactions, particularly musculoskeletal adverse reactions.

            • sorafenib

              sorafenib and crizotinib both increase QTc interval. Use Caution/Monitor.

            • sotalol

              crizotinib and sotalol both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • St John's Wort

              St John's Wort decreases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use of strong CYP3A inducers should be avoided. .

            • stiripentol

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

              stiripentol will increase the level or effect of crizotinib by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing the dose of P-glycoprotein (P-gp) substrates, if adverse reactions are experienced when administered concomitantly with stiripentol.

            • sufentanil

              crizotinib increases levels of sufentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • sufentanil SL

              crizotinib will increase the level or effect of sufentanil SL by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of sufentanil SL with any CYP3A4 inhibitor may increase sufentanil plasma concentration, and, thereby increase or prolonged adverse effects, including potentially fatal respiratory depression.

            • sunitinib

              crizotinib increases effects of sunitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • suvorexant

              crizotinib will increase the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease suvorexant starting dose to 5 mg HS if coadministered with moderate CYP3A4 inhibitors

            • tacrolimus

              crizotinib increases levels of tacrolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • tadalafil

              crizotinib increases levels of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • tamoxifen

              crizotinib, tamoxifen. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inhibition decreases metabolism of tamoxifen to N-desmethyl tamoxifen (active metabolite with similar biologic activity).

            • tamsulosin

              crizotinib increases levels of tamsulosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • tazemetostat

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

            • tecovirimat

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

            • telavancin

              crizotinib and telavancin both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • temsirolimus

              crizotinib increases levels of temsirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • teniposide

              crizotinib increases levels of teniposide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

              crizotinib increases levels of teniposide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • tezacaftor

              crizotinib will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a moderate CYP3A inhibitor.

            • theophylline

              crizotinib increases levels of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of crizotinib with CYP3A substrates with narrow therapeutic indices should be avoided.

            • thiothixene

              crizotinib and thiothixene both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • tiagabine

              crizotinib increases levels of tiagabine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • tinidazole

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

            • tipranavir

              tipranavir increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use of strong CYP3A inhibitors should be avoided. .

            • tofacitinib

              crizotinib increases levels of tofacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No specific dose adjustment recommended when tofacitinib coadministered with moderate CYP3A4 inhibitors; decrease tofacitinib dose if coadministered with both moderate CYP3A4 and potent CYP2C19 inhibitors.

            • tolterodine

              crizotinib increases levels of tolterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • tolvaptan

              crizotinib increases levels of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • toremifene

              crizotinib and toremifene both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • trabectedin

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

            • tramadol

              crizotinib increases levels of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • trazodone

              crizotinib increases levels of trazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • triazolam

              crizotinib increases levels of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • trimipramine

              crizotinib and trimipramine both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

              crizotinib increases levels of trimipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • triptorelin

              triptorelin increases toxicity of crizotinib by QTc interval. Use Caution/Monitor. Increases risk of torsades de pointes.

            • tucatinib

              tucatinib will increase the level or effect of crizotinib 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.

            • vandetanib

              crizotinib and vandetanib both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • vardenafil

              crizotinib increases levels of vardenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • vemurafenib

              crizotinib and vemurafenib both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • verapamil

              crizotinib increases levels of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

              crizotinib increases levels of verapamil by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              verapamil increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution should be exercised with concomitant use of moderate CYP3A inhibitors. .

            • vinblastine

              crizotinib increases levels of vinblastine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

              crizotinib increases levels of vinblastine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • vincristine

              crizotinib increases levels of vincristine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

              crizotinib increases levels of vincristine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • vincristine liposomal

              crizotinib increases levels of vincristine liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

              crizotinib increases levels of vincristine liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • vinorelbine

              crizotinib increases levels of vinorelbine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • voclosporin

              crizotinib 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.

              voclosporin, crizotinib. Either increases effects of the other by QTc interval. Use Caution/Monitor.

            • voriconazole

              voriconazole increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use of strong CYP3A inhibitors should be avoided. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • vorinostat

              crizotinib and vorinostat both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • zanubrutinib

              crizotinib will increase the level or effect of zanubrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce zanubrutinib dose when coadministered with a moderate CYP3A4 inhibitor. Interrupt dose as recommended for adverse reactions. After discontinuing the CYP3A4 inhibitor, resume previous dose of zanubrutinib. See zanubrutinib Dosage Modifications for precise recommendation.

            • ziprasidone

              crizotinib and ziprasidone both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • zolpidem

              crizotinib increases levels of zolpidem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • zonisamide

              crizotinib increases levels of zonisamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            Minor (4)

            • entecavir

              crizotinib, entecavir. Either increases effects of the other by decreasing renal clearance. Minor/Significance Unknown. Coadministration with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of either entecavir or the coadministered drug.

            • estradiol vaginal

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

            • lapatinib

              crizotinib and lapatinib both increase QTc interval. Minor/Significance Unknown.

            • rilpivirine

              crizotinib and rilpivirine both increase QTc interval. Minor/Significance Unknown.

            Previous
            Next:

            Adverse Effects

            >10%

            ALK- or ROS1-positive metastatic NSCLC

            • Vision disorders (≥25%)
            • Nausea (≥25%)
            • Diarrhea (≥25%)
            • Vomiting (≥25%)
            • Edema (≥25%)
            • Constipation (≥25%)
            • Elevated transaminases (≥25%)
            • Fatigue (≥25%)
            • Decreased appetite (≥25%)
            • Upper respiratory infection (≥25%)
            • Dizziness (≥25%)
            • Neuropathy (≥25%)

            ALK-positive metastatic NSCLC

            • All grades
              • Increased ALT (76-79%)
              • Vision disorder (60-71%)
              • Increased AST (61-66%)
              • Diarrhea (60-61%)
              • Nausea (55-56%)
              • Neutropenia (49-52%)
              • Lymphopenia (48-51%)
              • Edema (31-49%)
              • Vomiting (46-47%)
              • Constipation (42-43%)
              • Upper respiratory tract infection (26-32%)
              • Hypophosphatemia (28-32%)
              • Decreased appetite (27-30%)
              • Fatigue (27-29%)
              • Abdominal pain (26%)
              • Dysgeusia (26%)
              • Headache (22%)
              • Dizziness (18-22%)
              • Neuropathy (19-21%)
              • Pyrexia (19%)
              • Hypokalemia (18%)
              • Pain in extremity (16%)
              • Bradycardia (5-14%)
              • Dyspepsia (8-14%)
              • Rash (9-11%)
            • Grade 3-4
              • Increased ALT (15-17%)
              • Neutropenia (11-12%)

            ALCL

            • All grades
              • Neutropenia (100%)
              • Blood creatinine increased (100%)
              • Diarrhea (92%)
              • Vomiting (92%)
              • ALT increased (81%)
              • Nausea (77%)
              • AST increased (65%)
              • Vision disorders (65%)
              • Hypocalcemia (62%)
              • Lymphopenia (58%)
              • Headache (58%)
              • Musculoskeletal pain (58%)
              • Hypoalbuminemia (54%)
              • Anemia (54%)
              • Abdominal pain (50%)
              • Stomatitis (46%)
              • Hyperglycemia (46%)
              • Hypomagnesemia (46%)
              • Fatigue (46%)
              • Decreased appetite (42%)
              • Thrombocytopenia (38%)
              • Pyrexia (38%)
              • Hypoglycemia (35%)
              • Pruritus (35%)
              • Cough (35%)
              • Hypokalemia (31%)
              • Constipation (31%)
              • Upper respiratory tract infection (31%)
              • Hypertension (31%)
              • Hypermagnesemia (27%)
              • Edema (27%)
              • Chills (27%)
              • Hyperkalemia (23%)
              • Dysgeusia (23%)
              • Dizziness (23%)
              • Rash (23%)
              • Rhinitis allergic (23%)
              • Bradycardia (19%)
              • Hypotension (19%)
              • Alkaline phosphatase increase (19%)
              • Hypernatremia (19%)
              • Hyponatremia (12%)
              • Hyperuricemia (12%)
              • Hypophosphatemia (12%)
              • Peripheral neuropathy (12%)
            • Grade 3-4
              • Neutropenia (77%)
              • Lymphopenia (38%)
              • Thrombocytopenia (19%)
              • Diarrhea (12%)
              • Musculoskeletal pain (12%)

            1-10%

            ALK-positive metastatic NSCLC

            • All grades
              • Dysphagia (10%)
              • Decreased weight (10%)
              • Increased weight (8%)
              • Esophagitis (2-6%)
              • Pulmonary embolism (6%)
              • QT prolonged (5-6%)
              • Renal cyst (4-5%)
              • ILD/pneumonitis (1-4%)
              • Syncope (1-3%)
              • Decreased blood testosterone (1%)
              • Hepatic failure (1%)
            • Grade 3-4
              • Hypophosphatemia (5-10%)
              • Increased AST (8-9%)
              • Lymphopenia (7-9%)
              • Pulmonary embolism (5%)
              • Hypokalemia (4%)
              • Syncope (3%)
              • QT prolonged (2-3%)
              • Diarrhea (2%)
              • Vomiting (1-2%)
              • Constipation (2%)
              • Esophagitis (2%)
              • Bradycardia (1%)
              • Vision disorder (1%)
              • Dysphagia (1%)
              • Edema (1%)
              • Increased weight (1%)
              • Headache (1%)
              • Dizziness (1%)
              • Decreased weight (1%)
              • Nausea (1%)

            ALCL

            • Grade 3-4
              • Stomatitis (8%)
              • QT prolonged (8%)
              • GGT increase (8%)
              • Esophagitis (8%)
              • Muscular weakness (8%)
              • Acute renal injury (8%)
              • Febrile neutropenia (3.8%)
              • Vomiting (3.8%)
              • Nausea (3.8%)
              • Anemia (3.8%)
              • ALT increased (3.8%)
              • AST increased (3.8%)
              • Hypocalcemia (3.8%)
              • Hypokalemia (3.8%)

            Postmarketing Reports

            Increased blood creatine phosphokinase

            Previous
            Next:

            Warnings

            Contraindications

            None

            Cautions

            Severe, including fatal, treatment-related ILD/pneumonitis reported; monitor for pulmonary symptoms indicative of pneumonitis; generally occurred within 3 months after initiation

            Drug-induced hepatoxicity reported; monitor liver function tests every 2 weeks during the first 2 months of treatment, then monthly, and as clinically needed; more frequently in patients who develop increased transaminases; withhold, reduce dose, or permanently discontinue for hepatotoxicity as recommended

            Symptomatic bradycardia reported, including syncope; monitor HR and blood pressure regularly

            Caution when driving or operating machinery because of vision disorder, dizziness, or fatigue associated with treatment

            May cause fetal harm when administered to pregnant females

            Interstitial lung disease (ILD)/Pneumonitis reported; permanently discontinue in patients with ILD/pneumonitis

            Visual loss

            • Visual field defect with vision loss reported; optic atrophy and optic nerve disorder have been reported as potential causes of vision loss; most common visual symptoms were blurred vision and visual impairment in ALCL patients
            • There is insufficient information to characterize risks of resumption of drug in patients who develop visual symptoms or visual loss; a decision to resume therapy should consider potential benefits versus risks to patient
            • Perform an ophthalmological evaluation consisting of best corrected visual acuity, retinal photographs, visual fields, optical coherence tomography (OCT), and other evaluations as appropriate for new onset of visual loss and for other visual symptoms as clinically warranted

            Gastrointestinal toxicity

            • Severe gastrointestinal toxicities (eg, diarrhea, nausea, vomiting, stomatitis) can occur in ALCL patients; provide standard antiemetic and antidiarrheal agents for gastrointestinal toxicities in patients with ALCL; antiemetics are recommended prior to and during treatment with drug to prevent nausea and vomiting; if patients develop Grade 3 nausea lasting 3 days or Grade 3 or 4 diarrhea or vomiting despite maximum medical therapy, withhold therapy until resolved, and then resume at next lower dose level; consider supportive care such as hydration, electrolyte supplementation, and nutritional support as clinically indicated

            QT interval prolongation

            • QTc prolongation reported
            • Avoid use with congenital long QT syndrome
            • Consider periodic ECG and electrolyte monitoring in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, or taking medications known to prolong QT interval

            Drug interaction overview

            • CYP3A4/5 and P-gp substrate; CYP3A4 inhibitor
            • Strong or moderate CYP3A inhibitors
              • Avoid coadministration
              • Strong CYP3A inhibitors increases crizotinib plasma concentration and risk of adverse reactions of crizotinib
              • If unavoidable, reduce crizotinib dosage
              • Avoid grapefruit or grapefruit
              • Use caution with concomitant use of moderate CYP3A4 inhibitors
            • Strong CYP3A inducers
              • Avoid coadministration
              • Strong CYP3A inducers decreases crizotinib plasma concentrations and efficacy of crizotinib
            • CYP3A substrates
              • Avoid coadministration
              • Crizotinib may increases plasma concentrations and rise of adverse effects of CYP3A substrates
              • If unavoidable, decrease CYP3A substrate dosage according to prescribing information
            • Drugs that prolong the QT interval
              • Avoid coadministration
            • Drugs that cause bradycardia
              • Avoid coadministration
              • Drugs include beta-blockers, nondihydropyridine calcium channel blockers, clonidine, and digoxin
            Previous
            Next:

            Pregnancy & Lactation

            Pregnancy

            Based on its mechanism of action, can cause fetal harm when administered to a pregnant woman

            Verify pregnancy status of females of reproductive potential before initiation

            Animal data

            • Oral administration in pregnant rats during organogenesis at exposures similar to those observed with maximum recommended human dose resulted in embryotoxicity and fetotoxicity

            Contraception

            • Females of reproductive potential: Use effective contraception during treatment and for at least 45 days following the final dose
            • Males with female partners of reproductive potential: Use condoms during treatment and for at least 90 days after final dose

            Infertility

            • Based on reproductive organ findings in animals, reduced fertility in females and males of reproductive potential may occur
            • Unknown whether these effects on fertility are reversible

            Lactation

            No information available on drug presence in human milk, effects on the breastfed infants, or effects on milk production

            Do not breastfeed during treatment and for 45 days after final dose

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

            Previous
            Next:

            Pharmacology

            Mechanism of Action

            Inhibitor of receptor tyrosine kinases including ALK, Hepatocyte Growth Factor Receptor (HGFR, c-Met), and Recepteur d’Origine Nantais (RON)

            ALK gene expression and signaling that contribute to increased cell proliferation and survival of the tumors become activated following formation of ALK oncogenic fusion proteins

            Inhibits signaling that promotes the expression of these oncogenic fusion proteins, thereby inhibiting tumor cell proliferation

            Absorption

            Adults

            • Bioavailability: 43% (mean absolute bioavailability)
            • Mean accumulation ratio: 4.8
            • Peak plasma time: 4-6 hr
            • Steady-state reached at 15 days (250 mg PO BID)
            • Effect of food
              • High-fat meal reduced AUC and peak plasma concentration by ~14%

            Children and young adults

            • Peak plasma concentration: 621 ng/mL
            • AUC: 6530 ng⋅hr/mL

            Distribution

            Protein Bound: 91% to human plasma proteins, independent of drug concentration

            Vd (steady-state): 1772 L (50-mg IV dose)

            Blood-to-plasma ratio: 1

            P-glycoprotein (P-gp) substrate and inhibitor

            Metabolism

            Predominantly metabolized by CYP3A4/5

            Time-dependent inhibitor of CYP3A

            Primary metabolic pathways in humans were oxidation of the piperidine ring to crizotinib lactam and O-dealkylation, with subsequent Phase 2 conjugation of O-dealkylated metabolites

            Elimination

            Half-life: 42 hr

            Total body clearance: 60 L/hr (250 mg PO q12hr at steady-state); 100 L/hr (250 mg PO qDay)

            Excretion: Feces 63%; urine 22%

            Pharmacogenomics

            Patient selection for treatment is based on presence of ALK fusion gene

            Verify presence of ALK fusion gene by using the diagnostic test, Abbott Molecular’s Vysis ALK Break Apart FISH Probe Kit

            Previous
            Next:

            Administration

            Oral Administration

            Take with or without food

            Swallow capsules whole

            ALCL

            • Administer under adult supervision
            • May combine different strengths capsules if necessary

            Before and during treatment

            • Provide standard antiemetic and antidiarrheal agents before and during treatment
            • Consider IV or oral hydration and replace electrolytes as clinically indicated

            Missed dose

            • Next dose >6 hr: Take as soon as possible
            • Next dose <6 hr: Skip missed dose; do NOT double dose to make up for missed dose
            • Vomited dose after administration: Do NOT take extra dose; take next dose at regularly scheduled time

            Storage

            Capsules: Store at room temperature (20-25ºC [68-77ºF]); excursions permitted to 15-30ºC (59-86ºF)

            Previous
            Next:

            Images

            BRAND FORM. UNIT PRICE PILL IMAGE
            Xalkori oral
            -
            250 mg capsule

            Copyright © 2010 First DataBank, Inc.

            Previous
            Next:

            Patient Handout

            Patient Education
            crizotinib oral

            CRIZOTINIB - ORAL

            (kriz-OH-ti-nib)

            COMMON BRAND NAME(S): Xalkori

            USES: Crizotinib is used to treat certain types of cancer (such as lung cancer, anaplastic large cell lymphoma - ALCL). Crizotinib works by slowing or stopping the growth of cancer cells. It belongs to a class of drugs known as kinase inhibitors.

            HOW TO USE: Read the Medication Guide provided by your pharmacist before you start taking crizotinib and each time you get a refill. If you have any questions, ask your doctor or pharmacist.Take this medication by mouth with or without food as directed by your doctor, usually once or twice daily. Swallow whole with a glass of water. Do not crush or chew this medication. If you vomit after taking your dose of the medication, do not take an extra dose. Take the next dose of your medication at the regular time.The dosage is based on your medical condition, laboratory tests, response to treatment, and other medications you may be taking. Be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products). For children, the dosage is also based on body size.To decrease the risk of side effects, your doctor may prescribe other medications to take along with this medication. Carefully follow your doctor's directions for all your medications.Avoid eating grapefruit or drinking grapefruit juice while using this medication unless your doctor or pharmacist says you may do so safely. Grapefruit can increase the chance of side effects with this medicine. Ask your doctor or pharmacist for more details.Do not increase your dose or use this drug more often or for longer than prescribed. Your condition will not improve any faster, and your risk of side effects will increase.Use this medication regularly to get the most benefit from it. To help you remember, use it at the same times each day.Tell your doctor if your condition persists or worsens.Since this drug can be absorbed through the skin and lungs and may harm an unborn baby, women who are pregnant or who may become pregnant should not handle this medication or breathe the dust from the capsules.

            SIDE EFFECTS: Nausea, diarrhea, vomiting, dizziness, tiredness, headache, heartburn, change in taste, loss of appetite, mouth sores, joint pain, trouble sleeping, or constipation may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.This medication may lower your ability to fight infections. This may make you more likely to get a serious (rarely fatal) infection or make any infection you have worse. Tell your doctor right away if you have any signs of infection (such as cough, sore throat, fever, chills).Tell your doctor right away if you have any serious side effects, including: vision changes (such as blurred/decreased vision, flashes of light, sensitivity to light, floaters), swelling of the legs/feet/hands.Get medical help right away if you have any very serious side effects, including: trouble breathing, cough with or without phlegm, eye pain/swelling/redness, fast/slow/irregular heartbeat, severe dizziness, fainting, easy bleeding/bruising, symptoms of liver problems (such as dark urine, persistent nausea/vomiting, stomach/abdominal pain, yellowing eyes/skin).A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.Crizotinib can commonly cause a rash that is usually not serious. However, you may not be able to tell it apart from a rare rash that could be a sign of a severe reaction. Tell your doctor right away if you develop any rash.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

            PRECAUTIONS: Before taking this medication, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney problems, liver problems.Crizotinib may cause a condition that affects the heart rhythm (QT prolongation). QT prolongation can rarely cause serious (rarely fatal) fast/irregular heartbeat and other symptoms (such as severe dizziness, fainting) that need medical attention right away.The risk of QT prolongation may be increased if you have certain medical conditions or are taking other drugs that may cause QT prolongation. Before using crizotinib, tell your doctor or pharmacist of all the drugs you take and if you have any of the following conditions: certain heart problems (heart failure, slow heartbeat, QT prolongation in the EKG), family history of certain heart problems (QT prolongation in the EKG, sudden cardiac death).Low levels of potassium or magnesium in the blood may also increase your risk of QT prolongation. This risk may increase if you use certain drugs (such as diuretics/"water pills") or if you have conditions such as severe sweating, diarrhea, or vomiting. Talk to your doctor about using crizotinib safely.Crizotinib can make you more likely to get infections or may worsen any current infections. Avoid contact with people who have infections that may spread to others (such as chickenpox, measles, flu). Consult your doctor if you have been exposed to an infection or for more details.Do not have immunizations/vaccinations without the consent of your doctor. Avoid contact with people who have recently received live vaccines (such as flu vaccine inhaled through the nose).This drug may make you dizzy or cause vision changes. Alcohol or marijuana (cannabis) can make you more dizzy. Do not drive, use machinery, or do anything that needs alertness or clear vision until you can do it safely. Limit alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).Older adults may be more sensitive to the side effects of this drug, especially QT prolongation (see above).This medication can affect fertility in both males and females. Ask your doctor for more details.Since this drug can be absorbed through the skin and lungs and may harm an unborn baby, women who are pregnant or who may become pregnant should not handle this medication or breathe the dust from the capsules.Tell your doctor if you are pregnant or plan to become pregnant. You should not become pregnant while taking crizotinib. Crizotinib may harm an unborn baby. Your doctor should order a pregnancy test before you start this medication. Women taking this medication should use reliable forms of birth control during treatment and for at least 45 days after stopping treatment. Men taking this medication should use reliable forms of birth control during treatment and for at least 90 days after stopping treatment. If you or your partner become pregnant, talk to your doctor right away about the risks and benefits of this medication.It is unknown if this drug passes into breast milk. Because of possible harm to a nursing infant, breast-feeding is not recommended while using this medication and for 45 days after stopping this medication. Consult your doctor before breast-feeding.

            DRUG INTERACTIONS: See also How to Use section.Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Some products that may interact with this drug include: drugs that may slow the heartbeat (including digoxin, clonidine, beta-blockers such as atenolol/metoprolol, calcium channel blockers such as diltiazem/verapamil).Other medications can affect the removal of crizotinib from your body, which may affect how crizotinib works. Examples include azole antifungals (such as itraconazole), macrolide antibiotics (such as erythromycin), rifamycins (such as rifabutin), drugs for seizures (such as carbamazepine, phenytoin), St. John's wort, among others.This medication can slow down the removal of other medications from your body, which may affect how they work. Examples of affected drugs include alfentanil, ergots (such as ergotamine), fentanyl, flibanserin, lomitapide, tacrolimus, among others.Many drugs besides crizotinib may affect the heart rhythm (QT prolongation), including amiodarone, dofetilide, quinidine, procainamide, sotalol, and certain antipsychotic medications (such as pimozide, thioridazine, ziprasidone), among others.

            OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

            NOTES: Do not share this medication with others.Laboratory and/or medical tests (such as liver/kidney function, EKG, complete blood counts, eye exams, blood pressure, heart rate) will be performed before starting and while you are taking this medication to monitor your progress or check for side effects. Consult your doctor for more details.

            MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is less than 6 hours before the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

            STORAGE: Store at room temperature. Keep this medication in the original container away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

            Information last revised September 2021. Copyright(c) 2021 First Databank, Inc.

            IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

            Previous
            Next:

            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
            Additional Offers
            Email to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Email Forms to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Previous
            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.