ribociclib/letrozole (Rx)

Brand and Other Names:Kisqali/Femara Copack

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablets, copackaged cartons

  • Packaged for a 28-day medication cycle depending on the ribociclib daily dose
  • 3 Blister packs, containing 21 tablets (200mg/tablet; 600mg daily dose) of ribociclib plus one 28-tablet count bottle of letrozole 2.5mg/tablet
  • 3 Blister packs, containing 14 tablets (200mg/tablet; 400mg daily dose) of ribociclib plus one 28-tablet count bottle of letrozole 2.5mg/tablet
  • 1 blister pack, containing 21 tablets (200mg/tablet; 200mg daily dose) of ribociclib plus one 28-tablet count bottle of letrozole 2.5mg/tablet

Breast Cancer

Indicated as initial endocrine-based therapy for the treatment of pre/perimenopausal, postmenopausal women, or men with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)­-negative advanced or metastatic breast cancer

Ribociclib (initial dose): 600 mg PO qDay for 21 consecutive days followed by 7 days off treatment resulting in a 28-day cycle

Letrozole: 2.5 mg PO qDay taken through the 28-day cycle

Treat men or pre/perimenopausal women with a luteinizing hormone-releasing hormone (LHRH) agonist (eg, goserelin, leuprolide) according to clinical practice standards

Dosage Modifications (ribociclib)

Recommended dose modifications for adverse effects

  • Starting dose: 600 mg/day
  • First dose reduction: 400 mg/day
  • Second dose reduction: 200 mg/day
  • If further dose reduction below 200 mg/day is required, discontinue treatment

Neutropenia

  • Grade 1-2 (ANC 1000/mm3 to
  • Grade 3 (ANC 500 to <1000/mm3): Interrupt dose until recovery to Grade ≤2; resume at the same dose level; if toxicity recurs at Grade 3, interrupt dose until recovery, then resume at the next lower dose level
  • Grade 3 febrile neutropenia (Grade 3 ANC with fever and/or concurrent infection): Dose interruption until recovery of neutropenia to Grade ≤2; resume at the next lower dose level
  • Grade 4 (ANC <500/mm3): Dose interruption until recovery of neutropenia to Grade ≤2; resume at the next lower dose level

Hepatobiliary toxicity

  • AST and/or ALT increased from baseline WITHOUT increased total bilirubin >2 x ULN
    • Grade 1 (>ULN to 3 x ULN): No dose adjustment required
    • Grade 2 (>3-5 x ULN), baseline at
    • Grade 2 (>3-5 x ULN), baseline at Grade 2: No dose interruption
    • Grade 3 (>5-20 x ULN): Interrupt dose until recovery to baseline (or less) before initiating treatment, then resume at next lower dose level; if Grade 3 recurs, discontinue
    • Grade 4 (>20 x ULN): Discontinue
  • AST and/or ALT increased from baseline WITH increased total bilirubin, in the absence of cholestasis
    • Discontinue ribociclib if ALT and/or AST >3 x ULN plus total bilirubin >2 x ULN irrespective of baseline grade

QT prolongation

  • ECGs with QTcF >480 msec
    • Interrupt treatment If QTcF resolves to <481 msec, resume treatment at same dose level
    • If QTcF ≥481 msec recurs, interrupt dose until QTcF resolves to <481 msec; then resume at next lower dose level
  • ECGs with QTcF >500 msec
    • Interrupt KISQALI treatment if QTcF greater than 500 msec on at least 2 separate ECGs (within same visit)
    • If QTcF prolongation resolves to <481 msec, resume treatment at the next lower dose level
    • Permanently discontinue if QTcF interval prolongation is either >500 msec or >60 msec change from baseline AND associated with any of the following: torsades de pointes, polymorphic ventricular tachycardia, unexplained syncope, or signs/symptoms of serious arrhythmia

Interstitial lung disease/pneumonitis (ILD)

  • Grade 1 (asymptomatic): No dose interruption or adjustment required; initiate appropriate medical therapy and monitor as clinically indicated
  • Grade 2 (symptomatic): Dose interruption until recovery to Grade ≤1 then consider resuming at the next lower dose level; if Grade 2 recurs, discontinue treatment
  • Grade 3 (severe symptomatic) or 4 (life-threatening): Discontinue treatment

Other toxicities

  • Grade 1 or 2: No dose adjustment is required; initiate appropriate medical therapy and monitor as clinically indicated
  • Grade 3: Interrupt dose until recovery to Grade ≤1, then resume at the same dose level; if Grade 3 recurs, resume at the next lower dose level
  • Grade 4: Discontinue

Coadministration with strong CYP3A inhibitors

  • Avoid use with strong CYP3A inhibitors and consider an alternative drug with less potential for CYP3A inhibition
  • If a strong CYP3A inhibitor must be coadministered, reduce ribociclib dose to 400 mg/day
  • If the strong CYP3A inhibitor is discontinued, change ribociclib dose (after at least 5 half-lives of the strong CYP3A inhibitor) to the dose used before initiating the strong CYP3A inhibitor

Hepatic impairment

  • Ribociclib
    • Mild (Child-Pugh class A): No dose adjustment necessary
    • Moderate or severe (Child-Pugh classes B/C): Reduce starting dose to 400 mg/day
  • Letrozole
    • Mild (Child-Pugh classes A/B): No dose adjustment necessary
    • Patients with cirrhosis and severe hepatic dysfunction: Reduce dose by 50% (ie, 2.5 mg every other day)
    • Noncirrhotic patients with elevated bilirubin levels have not been studied

Renal impairment

  • Ribociclib
    • Mild-to-moderate (CrCl ≥30 mL/min): No dose adjustment necessary
    • Severe (CrCl 15-30 mL/min): Decrease starting dose to 200 mg/day; only studied healthy subjects and noncancer subjects with severe renal impairment
  • Letrozole
    • Mild-to-moderate (CrCl ≥30 mL/min): No dose adjustment necessary
    • Severe (CrCl 10-30 mL/min): No dose adjustment necessary

Dosing Considerations (ribociclib)

Complete blood count (CBC)

  • Perform CBC before initiating treatment
  • Monitor CBC q2wk for the first 2 cycles, at the beginning of each subsequent 4 cycles, and as clinically indicated

Liver function tests (LFTs)

  • Perform LFTs before initiating
  • Monitor LFTs q2wk for the first 2 cycles, at the beginning of each subsequent 4 cycles, and as clinically indicated
  • If Grade ≥2 abnormalities observed, more frequent monitoring is recommended

Electrocardiograms (ECGs) and electrolytes

  • ECGs should be assessed prior to initiation of treatment
  • Repeat ECGs at ~Day 14 of the first cycle and at the beginning of the second cycle, and as clinically indicated
  • In case of (QTcF) prolongation at any given time during treatment, more frequent ECG monitoring is recommended
  • Monitor serum electrolytes (including potassium, calcium, phosphorous and magnesium) before initiating, at the beginning of the first 6 cycles, and as clinically indicated; correct any abnormality before starting ribociclib

Safety and efficacy not established

Next:

Interactions

Interaction Checker

and ribociclib/letrozole

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            Contraindicated (13)

            • aprepitant

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

            • budesonide

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

            • conivaptan

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

            • elvitegravir

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

            • fluconazole

              ribociclib increases toxicity of fluconazole by QTc interval. Contraindicated.

            • fosaprepitant

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

            • lefamulin

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

            • lonafarnib

              ribociclib 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.

            • methadone

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

            • naloxegol

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

            • posaconazole

              ribociclib increases toxicity of posaconazole by QTc interval. Contraindicated.

            • ranolazine

              ribociclib increases toxicity of ranolazine by QTc interval. Contraindicated.

            • saquinavir

              ribociclib increases toxicity of saquinavir by QTc interval. Contraindicated.

            Serious - Use Alternative (80)

            • adagrasib

              adagrasib, ribociclib. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Each drug prolongs the QTc interval, which may increased the risk of Torsade de pointes, other serious arryhthmias, and sudden death. If coadministration unavoidable, more frequent monitoring is recommended for such patients.

            • alfuzosin

              alfuzosin and ribociclib both increase QTc interval. Contraindicated.

            • amiodarone

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

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

            • amitriptyline

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

            • anagrelide

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

            • apalutamide

              apalutamide will decrease the level or effect of ribociclib 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.

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

            • apomorphine

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

            • aripiprazole

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

            • arsenic trioxide

              ribociclib and arsenic trioxide both increase QTc interval. Avoid or Use Alternate Drug.

            • artemether

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

            • artemether/lumefantrine

              ribociclib and artemether/lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.

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

            • asenapine

              ribociclib and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

            • asenapine transdermal

              asenapine transdermal and ribociclib both increase QTc interval. Avoid or Use Alternate Drug.

            • atazanavir

              atazanavir will increase the level or effect of ribociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If a strong CYP3A inhibitor must be coadministered with ribociclib, reduce the ribociclib starting dose to 400 mg/day.

            • atomoxetine

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

            • avapritinib

              ribociclib 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.

            • azithromycin

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

            • bedaquiline

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

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

            • bosutinib

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

            • brigatinib

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

            • bromocriptine

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

            • buprenorphine

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

            • buprenorphine buccal

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

            • buprenorphine subdermal implant

              buprenorphine subdermal implant and ribociclib both increase QTc interval. Avoid or Use Alternate Drug.

            • buprenorphine transdermal

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

            • buprenorphine, long-acting injection

              buprenorphine, long-acting injection and ribociclib both increase QTc interval. Avoid or Use Alternate Drug.

            • carbamazepine

              carbamazepine will decrease the level or effect of ribociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of ribociclib with strong CYP3A inducers should be avoided.

            • ceritinib

              ribociclib, ceritinib. Either increases toxicity of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. May increase QT prolongation.

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

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

            • chloramphenicol

              chloramphenicol will increase the level or effect of ribociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If a strong CYP3A inhibitor must be coadministered with ribociclib, reduce the ribociclib starting dose to 400 mg/day.

            • chloroquine

              ribociclib and chloroquine both increase QTc interval. Avoid or Use Alternate Drug.

            • chlorpromazine

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

            • chlorpropamide

              ribociclib and chlorpropamide both increase QTc interval. Avoid or Use Alternate Drug.

            • ciprofloxacin

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

            • citalopram

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

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

            • clarithromycin

              clarithromycin will increase the level or effect of ribociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If a strong CYP3A inhibitor must be coadministered with ribociclib, reduce the ribociclib starting dose to 400 mg/day.

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

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

            • clofazimine

              ribociclib and clofazimine both increase QTc interval. Avoid or Use Alternate Drug.

            • clomipramine

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

            • clozapine

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

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

            • cobicistat

              cobicistat will increase the level or effect of ribociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If a strong CYP3A inhibitor must be coadministered with ribociclib, reduce the ribociclib starting dose to 400 mg/day.

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

            • cobimetinib

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

            • colchicine

              ribociclib will increase the level or effect of colchicine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid use of colchicine with strong CYP3A4 inhibitors. If coadministration is necessary, decrease colchicine dose or frequency as recommended in prescribing information. Use of any colchicine product in conjunction with strong CYP3A4 inhibitors is contraindicated in patients with renal or hepatic impairment.

            • conivaptan

              conivaptan will increase the level or effect of ribociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If a strong CYP3A inhibitor must be coadministered with ribociclib, reduce the ribociclib starting dose to 400 mg/day.

            • crizotinib

              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.

            • dabrafenib

              dabrafenib will decrease the level or effect of ribociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of ribociclib with strong CYP3A inducers should be avoided.

            • darifenacin

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

            • darunavir

              darunavir will increase the level or effect of ribociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If a strong CYP3A inhibitor must be coadministered with ribociclib, reduce the ribociclib starting dose to 400 mg/day.

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

            • dasatinib

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

            • deferiprone

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

            • deflazacort

              ribociclib will increase the level or effect of deflazacort by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Decrease dose by one third if combination cannot be avoided

            • degarelix

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

            • delavirdine

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

            • desflurane

              desflurane and ribociclib both increase QTc interval. Avoid or Use Alternate Drug.

            • desipramine

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

            • disopyramide

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

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

            • dofetilide

              ribociclib and dofetilide both increase QTc interval. Avoid or Use Alternate Drug.

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

            • dolasetron

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

            • donepezil

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

              donepezil and ribociclib both increase QTc interval. Avoid or Use Alternate Drug.

            • doxepin

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

              doxepin and ribociclib both increase QTc interval. Avoid or Use Alternate Drug.

            • doxorubicin

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

            • doxorubicin liposomal

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

            • dronedarone

              ribociclib and dronedarone both increase QTc interval. Avoid or Use Alternate Drug.

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

            • droperidol

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

            • efavirenz

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

              efavirenz and ribociclib both increase QTc interval. Avoid or Use Alternate Drug.

            • elacestrant

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

            • eliglustat

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

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of ribociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If a strong CYP3A inhibitor must be coadministered with ribociclib, reduce the ribociclib starting dose to 400 mg/day.

            • encorafenib

              ribociclib 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.

              encorafenib and ribociclib both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.

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

            • entrectinib

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

              ribociclib 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.

            • enzalutamide

              enzalutamide will decrease the level or effect of ribociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of ribociclib with strong CYP3A inducers should be avoided.

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

            • erdafitinib

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

            • eribulin

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

            • erythromycin base

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

            • erythromycin ethylsuccinate

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

            • erythromycin lactobionate

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

            • erythromycin stearate

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

            • escitalopram

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

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

            • ethinylestradiol

              ethinylestradiol decreases effects of letrozole by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Letrozole should not be given concurrently with any estrogens or estrogen-containing products.

            • etrasimod

              etrasimod, letrozole. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Risk of additive immune system effects with etrasimod has not been studied in combination with antineoplastic, immune-modulating, or noncorticosteroid immunosuppressive therapies. Avoid coadministration during and in the weeks following administration of etrasimod. .

              etrasimod, ribociclib. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Risk of additive immune system effects with etrasimod has not been studied in combination with antineoplastic, immune-modulating, or noncorticosteroid immunosuppressive therapies. Avoid coadministration during and in the weeks following administration of etrasimod. .

            • ezogabine

              ribociclib increases toxicity of ezogabine by QTc interval. Avoid or Use Alternate Drug. Slight and transient QT-prolongation observed, particularly when dose titrated to 1200mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.

            • tamoxifen

              tamoxifen decreases levels of letrozole by unspecified interaction mechanism. Contraindicated. Letrozole should not be given concurrently with tamoxifen. Letrozole therapy after the completion of standard tamoxifen treatment is not associated with impaired effects of letrozole.

            Monitor Closely (260)

            • abemaciclib

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

            • acalabrutinib

              ribociclib 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.

            • ado-trastuzumab emtansine

              ribociclib will increase the level or effect of ado-trastuzumab emtansine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • albuterol

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

            • alfentanil

              ribociclib will increase the level or effect of alfentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution if ribociclib is coadministered with sensitive CYP3A4 substrates that have a narrow therapeutic index. Dose reduction for sensitive CYP3A4 substrates may be needed.

            • alfuzosin

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

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

            • almotriptan

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

            • alosetron

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

            • alprazolam

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

            • amlodipine

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

            • apixaban

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

            • arformoterol

              ribociclib increases toxicity of arformoterol by QTc interval. Use Caution/Monitor.

            • aripiprazole

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

            • atazanavir

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

            • atogepant

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

            • atorvastatin

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

            • avanafil

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

            • axitinib

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

            • azithromycin

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

            • benzhydrocodone/acetaminophen

              ribociclib will increase the level or effect of benzhydrocodone/acetaminophen by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with strong CYP3A4 inhibitors may increase hydrocodone (benzhydrocodone is prodrug of hydrocodone) plasma concentrations and can result in potentially fatal respiratory depression.

            • bexarotene

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

            • bortezomib

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

            • bosentan

              bosentan will decrease the level or effect of ribociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of ribociclib with strong CYP3A inducers should be avoided.

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

            • brentuximab vedotin

              ribociclib will increase the level or effect of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • brexpiprazole

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

            • buprenorphine

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

            • buprenorphine subdermal implant

              ribociclib 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 transdermal

              ribociclib will increase the level or effect of buprenorphine transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • buprenorphine, long-acting injection

              ribociclib 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

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

            • cabozantinib

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

            • calcitriol

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

            • cannabidiol

              ribociclib 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.

            • capivasertib

              ribociclib will increase the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce capivasertib dose if coadministered with moderate CYP3A inhibitors.

            • capmatinib

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

            • carbamazepine

              ribociclib will increase the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution if ribociclib is coadministered with sensitive CYP3A4 substrates that have a narrow therapeutic index. Dose reduction for sensitive CYP3A4 substrates may be needed.

            • cariprazine

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

            • cenobamate

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

            • cevimeline

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

            • chlordiazepoxide

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

            • chloroquine

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

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

            • cholera vaccine

              letrozole decreases effects of cholera vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs and corticosteroids (used in greater than physiologic doses), may reduce the immune response to cholera vaccine.

            • cilostazol

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

            • cinacalcet

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

            • clonazepam

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

            • clonidine

              ribociclib will increase the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution if ribociclib is coadministered with sensitive CYP3A4 substrates that have a narrow therapeutic index. Dose reduction for sensitive CYP3A4 substrates may be needed.

            • clorazepate

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

            • codeine

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

            • conjugated estrogens

              ribociclib will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • copanlisib

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

            • cyclosporine

              ribociclib will increase the level or effect of cyclosporine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution if ribociclib is coadministered with sensitive CYP3A4 substrates that have a narrow therapeutic index. Dose reduction for sensitive CYP3A4 substrates may be needed.

            • dabrafenib

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

            • daclatasvir

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

            • daridorexant

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

            • dasatinib

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

            • dengue vaccine

              ribociclib decreases effects of dengue vaccine by immunosuppressive effects; risk of infection. Use Caution/Monitor. Immunosuppressive therapies (eg, irradiation, antimetabolites, alkylating agents, cytotoxic drugs, corticosteroids [greater than physiologic doses]) may reduce immune response to dengue vaccine.

              letrozole decreases effects of dengue vaccine by immunosuppressive effects; risk of infection. Use Caution/Monitor. Immunosuppressive therapies (eg, irradiation, antimetabolites, alkylating agents, cytotoxic drugs, corticosteroids [greater than physiologic doses]) may reduce immune response to dengue vaccine.

            • deutetrabenazine

              ribociclib increases toxicity of deutetrabenazine by QTc interval. Use Caution/Monitor. At the maximum recommended dose, deutetrabenazine does not prolong QT interval to a clinically relevant extent. Certain circumstances may increase risk of torsade de pointes and/or sudden death in association with drugs that prolong the QTc interval (eg, bradycardia, hypokalemia or hypomagnesemia, coadministration with other drugs that prolong QTc interval, presence of congenital QT prolongation).

            • eluxadoline

              letrozole increases levels of eluxadoline by decreasing metabolism. Use Caution/Monitor. As a precautionary measure due to incomplete information on the metabolism of eluxadoline, use caution when coadministered with strong CYP2A6 inhibitors.

            • dexamethasone

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

            • diazepam

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

            • diazepam intranasal

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

            • dihydroergotamine

              ribociclib will increase the level or effect of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution if ribociclib is coadministered with sensitive CYP3A4 substrates that have a narrow therapeutic index. Dose reduction for sensitive CYP3A4 substrates may be needed.

            • dihydroergotamine intranasal

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

            • diltiazem

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

            • docetaxel

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

            • donepezil transdermal

              ribociclib will increase the level or effect of donepezil transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • dronabinol

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

            • dutasteride

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

            • duvelisib

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

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

            • efavirenz

              efavirenz will decrease the level or effect of ribociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of ribociclib with strong CYP3A inducers should be avoided.

            • elagolix

              elagolix decreases levels of ribociclib 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.

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

            • elbasvir/grazoprevir

              ribociclib will increase the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • eletriptan

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

            • eliglustat

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

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              ribociclib will increase the level or effect of elvitegravir/cobicistat/emtricitabine/tenofovir DF by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • encorafenib

              encorafenib, ribociclib. 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.

            • eplerenone

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

            • ergoloid mesylates

              ribociclib will increase the level or effect of ergoloid mesylates by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ergonovine

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

            • ergotamine

              ribociclib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution if ribociclib is coadministered with sensitive CYP3A4 substrates that have a narrow therapeutic index. Dose reduction for sensitive CYP3A4 substrates may be needed.

            • erlotinib

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

            • erythromycin base

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

            • erythromycin ethylsuccinate

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

            • erythromycin lactobionate

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

            • erythromycin stearate

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

            • escitalopram

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

            • estradiol

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

            • estrogens conjugated synthetic

              ribociclib will increase the level or effect of estrogens conjugated synthetic by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • estrogens esterified

              ribociclib will increase the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • estropipate

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

            • eszopiclone

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

            • ethinylestradiol

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

            • ethosuximide

              ribociclib will increase the level or effect of ethosuximide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution if ribociclib is coadministered with sensitive CYP3A4 substrates that have a narrow therapeutic index. Dose reduction for sensitive CYP3A4 substrates may be needed.

            • etonogestrel

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

            • etoposide

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

            • etrasimod

              etrasimod, ribociclib. Either increases effects of the other by QTc interval. Modify Therapy/Monitor Closely. Transient decrease in heart rate and AV conduction delays may occur when initiating etrasimod. Owing to potential of additive effect on heart rate, etrasimod may increase risk of QT prolongation and Torsades de Pointes when coadministered with Class Ia or Class III antiarrhythmic drugs, or other drugs that prolong the QT interval. .

            • etravirine

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

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

            • everolimus

              ribociclib will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution if ribociclib is coadministered with sensitive CYP3A4 substrates that have a narrow therapeutic index. Dose reduction for sensitive CYP3A4 substrates may be needed.

            • exemestane

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

            • fedratinib

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

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

            • felbamate

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

            • felodipine

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

            • fentanyl

              ribociclib will increase the level or effect of fentanyl by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution if ribociclib is coadministered with sensitive CYP3A4 substrates that have a narrow therapeutic index. Dose reduction for sensitive CYP3A4 substrates may be needed.

            • fentanyl intranasal

              ribociclib will increase the level or effect of fentanyl intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution if ribociclib is coadministered with sensitive CYP3A4 substrates that have a narrow therapeutic index. Dose reduction for sensitive CYP3A4 substrates may be needed.

            • fentanyl transdermal

              ribociclib will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution if ribociclib is coadministered with sensitive CYP3A4 substrates that have a narrow therapeutic index. Dose reduction for sensitive CYP3A4 substrates may be needed.

            • fentanyl transmucosal

              ribociclib will increase the level or effect of fentanyl transmucosal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution if ribociclib is coadministered with sensitive CYP3A4 substrates that have a narrow therapeutic index. Dose reduction for sensitive CYP3A4 substrates may be needed.

            • finerenone

              ribociclib 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.

            • flunisolide inhaled

              ribociclib will increase the level or effect of flunisolide inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fluphenazine

              ribociclib increases toxicity of fluphenazine by QTc interval. Use Caution/Monitor.

            • flurazepam

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

            • fluticasone furoate

              ribociclib will increase the level or effect of fluticasone furoate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong CYP3A4 inhibitors may increase fluticasone systemic exposure

            • fluticasone inhaled

              ribociclib will increase the level or effect of fluticasone inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fluticasone intranasal

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

            • formoterol

              ribociclib increases toxicity of formoterol by QTc interval. Use Caution/Monitor.

            • fosamprenavir

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

            • fostamatinib

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

            • fostemsavir

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

            • gadobenate

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

            • gefitinib

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

            • gemtuzumab

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

            • gepirone

              ribociclib will increase the level or effect of gepirone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce gepirone dose by 50% when used concomitantly with a moderate CYP3A4 inhibitor.

              gepirone and ribociclib both increase QTc interval. Modify Therapy/Monitor Closely.

            • glasdegib

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

            • guanfacine

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

            • haloperidol

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

            • hydrocodone

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

            • hydroxyprogesterone caproate (DSC)

              ribociclib will increase the level or effect of hydroxyprogesterone caproate (DSC) by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ibrutinib

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

            • idelalisib

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

            • ifosfamide

              ribociclib decreases effects 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. .

            • imatinib

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

            • imipramine

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

            • indinavir

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

            • irinotecan

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

            • irinotecan liposomal

              ribociclib will increase the level or effect of irinotecan liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. UGT1A1 inhibitors decrease irinotecan metabolism

            • isavuconazonium sulfate

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

            • isosorbide dinitrate

              ribociclib will increase the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • isosorbide mononitrate

              ribociclib will increase the level or effect of isosorbide mononitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • isradipine

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

              ribociclib increases toxicity of isradipine by QTc interval. Use Caution/Monitor.

            • istradefylline

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

            • itraconazole

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

            • ivacaftor

              ribociclib 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

              ribociclib 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

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

            • ketamine

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

            • lapatinib

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

            • lefamulin

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

            • lenacapavir

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

            • letermovir

              letermovir increases levels of letrozole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

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

            • levamlodipine

              ribociclib 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.

            • mavacamten

              letrozole will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • levomilnacipran

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

            • levonorgestrel intrauterine

              ribociclib will increase the level or effect of levonorgestrel intrauterine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • levonorgestrel oral

              ribociclib will increase the level or effect of levonorgestrel oral by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lofexidine

              ribociclib and lofexidine both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended.

            • lopinavir

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

            • lorlatinib

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

            • lovastatin

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

            • lumateperone

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

            • lurasidone

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

            • maraviroc

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

            • marijuana

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

            • mavacamten

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

            • mefloquine

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

            • mestranol

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

            • methylergonovine

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

            • midazolam

              ribociclib will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution if ribociclib is coadministered with sensitive CYP3A4 substrates that have a narrow therapeutic index. Dose reduction for sensitive CYP3A4 substrates may be needed.

            • midostaurin

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

            • mifepristone

              ribociclib, mifepristone. Either increases toxicity of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • mirtazapine

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

            • modafinil

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

            • mometasone inhaled

              ribociclib will increase the level or effect of mometasone inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nafcillin

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

            • naldemedine

              ribociclib 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.

            • nefazodone

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

            • nelfinavir

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

            • netupitant/palonosetron

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

            • nevirapine

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

            • nicardipine

              ribociclib will increase the level or effect of nicardipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. If a strong CYP3A inhibitor must be coadministered with ribociclib, reduce the ribociclib starting dose to 400 mg/day.

            • nifedipine

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

            • nilotinib

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

            • nimodipine

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

            • nisoldipine

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

            • norgestrel

              ribociclib will increase the level or effect of norgestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong or moderate CYP3A4 inhibitors may increase systemic concentration of norgestrel, which may increase risk for adverse effects

            • ofatumumab SC

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

            • olaparib

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

            • oliceridine

              ribociclib 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.

            • ombitasvir/paritaprevir/ritonavir

              ribociclib will increase the level or effect of ombitasvir/paritaprevir/ritonavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)

              ribociclib will increase the level or effect of ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • ondansetron

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

            • osilodrostat

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

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

            • ospemifene

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

            • oxaliplatin

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

            • oxybutynin

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

            • oxybutynin transdermal

              ribociclib will increase the level or effect of oxybutynin transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • oxycodone

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

            • ozanimod

              ozanimod and ribociclib 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

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

            • paclitaxel protein bound

              ribociclib will increase the level or effect of paclitaxel protein bound by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • palbociclib

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

            • palovarotene

              ribociclib will increase the level or effect of palovarotene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of palovarotene, a CYP3A substrate, with moderate CYP3A inhibitors. If unavoidable, reduce palovarotene dose by 50%.

            • panobinostat

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

            • paricalcitol

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

            • pazopanib

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

            • pimavanserin

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

            • polatuzumab vedotin

              ribociclib will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • quazepam

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

            • quetiapine

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

            • quinidine

              ribociclib will increase the level or effect of quinidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution if ribociclib is coadministered with sensitive CYP3A4 substrates that have a narrow therapeutic index. Dose reduction for sensitive CYP3A4 substrates may be needed.

            • quinine

              ribociclib will increase the level or effect of quinine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution if ribociclib is coadministered with sensitive CYP3A4 substrates that have a narrow therapeutic index. Dose reduction for sensitive CYP3A4 substrates may be needed.

            • quizartinib

              quizartinib, ribociclib. Either increases effects of the other by QTc interval. Modify Therapy/Monitor Closely. Monitor patients more frequently with ECG if coadministered with QT prolonging drugs.

            • ramelteon

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

            • ranolazine

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

            • regorafenib

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

            • repaglinide

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

            • rifabutin

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

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

            • rifapentine

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

            • rimegepant

              ribociclib 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.

            • ritonavir

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

            • roflumilast

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

            • rucaparib

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

            • saxagliptin

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

            • sildenafil

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

            • simvastatin

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

            • siponimod

              siponimod and letrozole 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.

              siponimod and ribociclib 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

              ribociclib will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution if ribociclib is coadministered with sensitive CYP3A4 substrates that have a narrow therapeutic index. Dose reduction for sensitive CYP3A4 substrates may be needed.

            • sodium sulfate/?magnesium sulfate/potassium chloride

              sodium sulfate/?magnesium sulfate/potassium chloride increases toxicity of ribociclib by QTc interval. Use Caution/Monitor. Consider predose and post-colonoscopy ECGs in patients at increased risk of serious cardiac arrhythmias. .

            • sodium sulfate/potassium sulfate/magnesium sulfate

              sodium sulfate/potassium sulfate/magnesium sulfate increases toxicity of ribociclib by QTc interval. Use Caution/Monitor. Consider predose and post-colonoscopy ECGs in patients at increased risk of serious cardiac arrhythmias. .

            • solifenacin

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

            • sonidegib

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

            • sparsentan

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

            • stiripentol

              stiripentol, ribociclib. 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.

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

            • sufentanil

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

            • sufentanil SL

              ribociclib 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

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

            • suvorexant

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

            • tacrolimus

              ribociclib will increase the level or effect of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution if ribociclib is coadministered with sensitive CYP3A4 substrates that have a narrow therapeutic index. Dose reduction for sensitive CYP3A4 substrates may be needed.

            • tadalafil

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

            • tamsulosin

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

            • tazemetostat

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

            • tecovirimat

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

            • temsirolimus

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

            • tezacaftor

              ribociclib 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.

            • ticlopidine

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

            • tinidazole

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

            • trastuzumab

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

            • trastuzumab deruxtecan

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

            • triazolam

              ribociclib will increase the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution if ribociclib is coadministered with sensitive CYP3A4 substrates that have a narrow therapeutic index. Dose reduction for sensitive CYP3A4 substrates may be needed.

            • triclabendazole

              triclabendazole and ribociclib both increase QTc interval. Use Caution/Monitor.

            • ulipristal

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

            • umeclidinium bromide/vilanterol inhaled

              ribociclib will increase the level or effect of umeclidinium bromide/vilanterol inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • upadacitinib

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

            • vardenafil

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

            • verapamil

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

            • vilanterol/fluticasone furoate inhaled

              ribociclib increases toxicity of vilanterol/fluticasone furoate inhaled by QTc interval. Use Caution/Monitor.

            • vinblastine

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

            • vinorelbine

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

            • voclosporin

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

            • zaleplon

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

            • zanubrutinib

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

            • zolpidem

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

            Minor (68)

            • acetazolamide

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

            • alpelisib

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

            • ambrisentan

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

            • anastrozole

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

            • apremilast

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

            • armodafinil

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

            • avatrombopag

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

            • benzphetamine

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

            • busulfan

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

            • calcifediol

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

            • chlorpheniramine

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

            • ciclesonide inhaled

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

            • cisapride

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

            • cocaine topical

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

            • cyclophosphamide

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

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

            • dantrolene

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

            • dapsone

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

            • dexlansoprazole

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

            • doravirine

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

            • doxepin cream

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

            • enfortumab vedotin

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

            • esomeprazole

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

            • estradiol vaginal

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

            • fenofibrate

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

            • fenofibrate micronized

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

            • fenofibric acid

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

            • flutamide

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

            • glecaprevir/pibrentasvir

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

            • ixazomib

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

            • lacosamide

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

            • lansoprazole

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

            • linagliptin

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

            • losartan

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

            • macimorelin

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

            • metaxalone

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

            • methylprednisolone

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

            • miconazole oral

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

            • montelukast

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

            • norethindrone

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

            • omeprazole

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

            • osimertinib

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

            • perampanel

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

            • pitolisant

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

            • pomalidomide

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

            • praziquantel

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

            • primaquine

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

            • progesterone intravaginal gel

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

            • progesterone micronized

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

            • progesterone, natural

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

            • rabeprazole

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

            • riociguat

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

            • rivaroxaban

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

            • rolapitant

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

            • ropivacaine

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

            • ruxolitinib

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

            • ruxolitinib topical

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

            • salmeterol

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

            • sofosbuvir/velpatasvir

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

            • tasimelteon

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

            • teniposide

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

            • theophylline

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

            • tiagabine

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

            • trimethoprim

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

            • velpatasvir

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

            • vincristine liposomal

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

            • vortioxetine

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

            • voxilaprevir

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

            • zonisamide

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

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            Adverse Effects

            >10%

            Percentage includes all grades of toxicity unless otherwise stated

            Leukocyte count decreased (93%)

            Neutrophil count decreased (93%)

            Neutropenia (75%)

            Hemoglobin decreased (57%)

            Nausea (52%)

            Lymphocyte count decreased (51%)

            Neutropenia, grade 3 (50%)

            Neutrophil count decreased, grade 3 (49%)

            AST/ALT increased (44-46%)

            Fatigue (37%)

            Diarrhea (35%)

            Leukopenia (33%)

            Alopecia (33%)

            Leukocyte count decreased, grade 3 (31%)

            Platelets decreased (29%)

            Vomiting (29%)

            Constipation (25%)

            Headache (22%)

            Leukopenia, grade 3 (20%)

            Back pain (20%)

            Creatinine increased (20%)

            Decreased appetite (19%)

            Anemia (18%)

            Abnormal LFTs (18%)

            Rash (17%)

            Pruritus (14%)

            Pyrexia (13%)

            Phosphorus decreased (13%)

            Peripheral edema (12%)

            Stomatitis (12%)

            Insomnia (12%)

            Dyspnea (12%)

            Lymphopenia (11%)

            Urinary tract infection (11%)

            Abdominal pain (11%)

            Potassium decreased (11%)

            1-10%

            Neutropenia, grade 4 (10%)

            Postmarketing Reports

            Respiratory disorders: Interstitial lung disease (ILD)/pneumonitis

            Skin and subcutaneous tissue disorders: Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS)

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            Warnings

            Contraindications

            Hypersensitivity to active substance (letrozole), or to excipients of the formulation

            Cautions

            May cause fetal harm; advise women of reproductive potential to use effective contraception (see Pregnancy)

            Severe cutaneous reactions

            • Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis(TEN), and drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) can occur
            • If signs or symptoms occur, interrupt treatment until the etiology of the reaction determined
            • Early consultation with a dermatologist recommended to ensure greater diagnostic accuracy and appropriate management
            • If SJS, TEN, or DiHS/DRESS confirmed, permanently discontinue; do not reintroduce in patients who have experienced SCARs or other life threatening cutaneous reactions during treatment

            Interstitial lung disease/pneumonitis

            • Severe, life-threatening, or fatal ILD and/or pneumonitis can occur; additional cases of ILD/pneumonitis have been observed in the postmarketing setting, with fatalities reported; monitor for pulmonary symptoms indicative of ILD/pneumonitis which may include hypoxia, cough, and dyspnea
            • In patients who have new or worsening respiratory symptoms suspected to be due to ILD or pneumonitis, interrupt therapy immediately and evaluate patient; permanently discontinue therapy in patients with recurrent symptomatic or severe ILD/pneumonitis

            QT prolongation

            • Prolongs the QT interval in a concentration-dependent manner, with estimated mean increase in QTc interval exceeding 20 ms following administration at 600 mg once daily dose
            • Avoid use in patients who already have or who are at significant risk of developing QTc prolongation, including those with electrolyte abnormalities, long QT syndrome, or uncontrolled or significant cardiac disease including recent myocardial infarction, congestive heart failure, unstable angina, and bradyarrhythmias
            • Avoid use in patients taking drugs known to prolong QTc interval and/or strong CYP3A inhibitors as this may lead to prolongation of the QTcF interval
            • Based on observed QT prolongation during treatment, drug may require dose interruption, reduction or discontinuation
            • Increased in QT prolongation with concomitant use of tamoxifen; not indicated for concomitant use

            Hepatobiliary toxicity

            • Increased transaminases were observed in clinical trials; Grade 3 or 4 increases in ALT and AST reported
            • In patients who had Grade ≥3 ALT/AST elevation, median time-to-onset was 57 days; whereas, Grade ≤2 was 24 days

            Neutropenia

            • Neutropenia is the most frequently reported adverse effect
            • Among patients with neutropenia, the median time to Grade ≥2 is 17 days
            • Median time to resolution of Grade ≥3 (to normalization or Grade <3) is 12 days
            • Monitor CBC every 2 weeks for first 2 cycles, at the beginning of each subsequent 4 cycles, and as clinically indicated; based on the severity of the neutropenia, therapy may require dose interruption, reduction, or discontinuation

            Drug interaction overview

            • Ribociclib is a CYP3A4 substrate and CYP3A4 inhibitor
            • Drugs that may increase ribociclib plasma concentrations
              • Avoid concomitant use of strong CYP3A inhibitors (eg, clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, and voriconazole) and consider alternative concomitant medications with less potential for CYP3A inhibition
              • If coadministration with a strong CYP3A inhibitor cannot be avoided, reduce the ribociclib dose to 400 mg/day (also see Dosage Modifications)
              • Instruct patients to avoid pomegranates or pomegranate juice, grapefruit, all of which are known to inhibit cytochrome CYP3A enzymes and may increase the exposure to ribociclib
            • Drugs that may decrease ribociclib plasma concentrations
              • Avoid concomitant use of strong CYP3A inducers (eg, phenytoin, rifampin, carbamazepine, St John’s Wort) and consider an alternate concomitant medication with no or minimal potential to induce CYP3A
            • Effect of ribociclib on other drugs
              • Caution if ribociclib is coadministered with CYP3A4 substrates that have a narrow therapeutic index (NTI), as ribociclib can increase their systemic exposure
              • The dose of a sensitive CYP3A substrates with a NTI may need to be reduced
              • CYP3A substrates with a NTI include (but are not limited to) alfentanil, cyclosporine, dihydroergotamine, ergotamine, everolimus, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus
            • Drugs that prolong QT interval
              • Avoid coadministration of ribociclib with drugs with a known potential to prolong QT
              • Examples include antiarrhythmic medicines (including, but not limited to amiodarone, disopyramide, procainamide, quinidine and sotalol), and other drugs that are known to prolong the QT interval (eg, chloroquine, clarithromycin, haloperidol, methadone, moxifloxacin, pimozide, ondansetron IV)
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            Pregnancy & Lactation

            Pregnancy

            There are no available human data informing the drug-associated risk

            Based on findings from animal studies and the mechanism of action, can cause fetal harm when administered to a pregnant woman

            In animal reproduction studies, administration during organogenesis resulted in increased incidences of postimplantation loss and reduced fetal weights in rats and increased incidences of fetal abnormalities in rabbits at exposures 0.6 or 1.5 times the exposure in humans

            Infertility: Based on animal studies, may impair fertility in males Contraception

            • Females of reproductive potential should have a pregnancy test prior to starting treatment
            • Females: Advise females of reproductive potential to use effective contraception (methods that result in <1% pregnancy rates) during treatment and for at least 3 weeks after the last dose

            Lactation

            Unknown if distributed in human breast milk

            Because of the potential for serious adverse reactions in breastfed infants, advise lactating women not to breastfeed while taking ribociclib and for at least 3 weeks after the last dose

            In lactating rats administered a single dose of 50 mg/kg, exposure to ribociclib was 3.56-fold higher in milk compared to maternal plasma

            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.

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            Pharmacology

            Mechanism of Action

            The combination of ribociclib and antiestrogen (eg, letrozole) increases tumor growth inhibition compared with each drug alone

            Ribociclib

            • Inhibits cyclin dependent kinases (CDK) 4 and 6; blocks cellular proliferation of G1 into S phase of the cell cycle
            • These kinases are activated upon binding to D cyclins and play a crucial role in signaling pathways which lead to cell cycle progression and cellular proliferation; the cyclin D-CDK4/6 complex regulates cell cycle progression through phosphorylation of the retinoblastoma protein (pRb)

            Letrozole

            • Nonsteroidal competitive inhibitor of the aromatase enzyme system by competitively binding to the heme of the cytochrome P450 subunit of the enzyme, resulting in a reduction of estrogen biosynthesis in all tissues

            Absorption

            Peak plasma time: 1-4 hr (ribociclib)

            Distribution

            Protein bound

            • Ribociclib: 70%
            • Letrozole: Weakly protein bound

            Vd

            • Ribociclib: 1090 L
            • Letrozole: 1.9 L/kg

            Metabolism

            Ribociclib

            • Undergoes extensive hepatic metabolism mainly via CYP3A4 in humans
            • Primary metabolic pathways for ribociclib involved oxidation (dealkylation, C and/or N-oxygenation, oxidation (-2H)) and combinations thereof
            • Phase II conjugates of ribociclib Phase I metabolites involved N-acetylation, sulfation, cysteine conjugation, glycosylation and glucuronidation
            • Ribociclib was the major circulating drug-derived entity in plasma (44%)

            Letrozole

            • Metabolism to a pharmacologically-inactive carbinol metabolite (4,4'methanol-bisbenzonitrile) and renal excretion of the glucuronide conjugate of this metabolite is the major pathway of letrozole clearance

            Elimination

            Half-life (ribociclib): 32 hr; 29.7-54.7 hr (terminal half-life)

            Oral clearance (ribociclib): 25.5 L/hr

            Excretion

            • Ribociclib (within 22 days): 69% feces; 23% urine
            • Letrozole: 90% urine (75% as glucuronide of the carbinol metabolite; 9% 2 unidentified metabolites, 6% unchanged)
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            Administration

            Oral Administration

            Administer with or without food

            Take doses at about the same time each day, preferably in the morning

            Swallow tablets whole, do not chew, crush, or split

            Do not ingest tablets that are broken, cracked, or otherwise not intact

            Vomited or missed doses

            • Do not take an additional dose the remainder of the day if the dose if vomited or missed
            • The next prescribed dose should be taken at the usual time

            Storage

            Store in original package at 20-25°C (68-77°F)

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            Images

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            Patient Handout

            A Patient Handout is not currently available for this monograph.
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            Formulary

            FormularyPatient Discounts

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