sotorasib (Rx)

Brand and Other Names:Lumakras

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 120mg
  • 320mg

Non-Small Cell Lung Cancer

Indicated for KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC) in adults who have received ≥1 prior systemic therapy

960 mg PO qDay

Continue until disease progression or unacceptable toxicity

Dosage Modifications

Dosage reduction levels for adverse reactions

  • First dose reduction: 480 mg qDay
  • Second dose reduction: 240 mg qDay
  • Unable to tolerate 240 mg qDay: Discontinue

Hepatoxicity

  • Withhold until recovery to Grade ≤1 or baseline if
    • Grade 2 AST/ALT with symptoms
    • Grade 3 to 4 AST/ALT
    • Resume at next lower dose level
  • Permanently discontinue
    • AST/ALT >3x ULN with total bilirubin [TB] >2x ULN in absence of alternative causes

Interstitial lung disease (ILD)/pneumonitis (any grade)

  • Suspected ILD/pneumonitis: Withhold
  • Confirmed ILD/pneumonitis: Permanently discontinue

Nausea or vomiting

  • Occurs despite supportive care (eg, antiemetic therapy)
  • Grade 3 or 4 : Withhold until recovery to Grade ≤1 or baseline; resume at next lower dose level

Diarrhea

  • Occurs despite supportive care (eg, antidiarrheal therapy)
  • Grade 3 or 4: Withhold until recovery to Grade ≤1 or baseline; resume at next lower dose level

Other adverse reactions

  • Grade 3 or 4: Withhold until recovery to Grade ≤1 or baseline; resume at next lower dose level

Coadministration with acid-reducing agents

  • Avoid coadministration of proton pump inhibitors (PPIs), H2-receptor antagonists, and antacids
  • If use is unavoidable, take sotorasib 4 hr before or 10 hr after administration of antacids

Renal impairment

  • Mild-to-moderate (eGFR ≥30 mL/min/1.73 m2): No dosage adjustment necessary
  • Severe (eGFR <30 mL/min/1.73 m2): Not studied

Hepatic impairment

  • Mild-to-moderate (Child Pugh A or B): No dosage adjustment necessary
  • Severe (Child-Pugh C): Effect unknown; monitor more frequently; patients with severe hepatic impairment may be at increased risk for adverse effects, including hepatotoxicity

Dosing Considerations

Patient selection

  • Select patients based on presence of KRAS G12C mutation in tumor or plasma specimens
  • If no mutation is detected in a plasma specimen, test tumor tissue
  • Information on FDA-approved tests is available at: http://www.fda.gov/CompanionDiagnostics

Safety and efficacy not established

Next:

Interactions

Interaction Checker

and sotorasib

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

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             activity indicator 

            Contraindicated (2)

            • mavacamten

              sotorasib will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • pacritinib

              sotorasib will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            Serious - Use Alternative (194)

            • abemaciclib

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

            • afatinib

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

            • alfentanil

              sotorasib will decrease the level or effect of alfentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the CYP3A4 substrate for dosage modifications

            • aliskiren

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

            • aluminum hydroxide

              aluminum hydroxide will decrease the level or effect of sotorasib by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. If use with an acid-reducing agent cannot be avoided, administer sotorasib 4 hr before or 10 hr after administration of a locally-acting antacid.

            • aluminum hydroxide/magnesium carbonate

              aluminum hydroxide/magnesium carbonate will decrease the level or effect of sotorasib by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. If use with an acid-reducing agent cannot be avoided, administer sotorasib 4 hr before or 10 hr after administration of a locally-acting antacid.

            • aluminum hydroxide/magnesium trisilicate

              aluminum hydroxide/magnesium trisilicate will decrease the level or effect of sotorasib by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. If use with an acid-reducing agent cannot be avoided, administer sotorasib 4 hr before or 10 hr after administration of a locally-acting antacid.

            • ambrisentan

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

            • amiodarone

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

            • amobarbital

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

            • apalutamide

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

            • apixaban

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

            • artesunate

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

            • aspirin/citric acid/sodium bicarbonate

              aspirin/citric acid/sodium bicarbonate will decrease the level or effect of sotorasib by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. If use with an acid-reducing agent cannot be avoided, administer sotorasib 4 hr before or 10 hr after administration of a locally-acting antacid.

            • atazanavir

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

            • atorvastatin

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

            • avatrombopag

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

            • bendamustine

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

            • betrixaban

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

            • bosentan

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

            • brentuximab vedotin

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

            • budesonide

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

            • butabarbital

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

            • calcium carbonate

              calcium carbonate will decrease the level or effect of sotorasib by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. If use with an acid-reducing agent cannot be avoided, administer sotorasib 4 hr before or 10 hr after administration of a locally-acting antacid.

            • carbamazepine

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

              sotorasib will decrease the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the CYP3A4 substrate for dosage modifications

            • carfilzomib

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

            • carvedilol

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

            • ceritinib

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

            • cetirizine

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

            • cimetidine

              cimetidine will decrease the level or effect of sotorasib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use with an acid-reducing agent cannot be avoided, administer sotorasib 4 hr before or 10 hr after administration of a locally-acting antacid.

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

            • ciprofloxacin

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

            • citric acid/sodium bicarbonate

              citric acid/sodium bicarbonate will decrease the level or effect of sotorasib by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. If use with an acid-reducing agent cannot be avoided, administer sotorasib 4 hr before or 10 hr after administration of a locally-acting antacid.

            • clonidine

              sotorasib will decrease the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the CYP3A4 substrate for dosage modifications

            • colchicine

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

            • crizotinib

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

            • cyclosporine

              sotorasib will decrease the level or effect of cyclosporine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the CYP3A4 substrate for dosage modifications

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

            • dabigatran

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

            • dabrafenib

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

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

            • daridorexant

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

            • darolutamide

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

            • dasabuvir

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

            • daunorubicin

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

            • daunorubicin liposomal

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

            • desloratadine

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

            • dexamethasone

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

            • dexlansoprazole

              dexlansoprazole will decrease the level or effect of sotorasib by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. If use with an acid-reducing agent cannot be avoided, administer sotorasib 4 hr before or 10 hr after administration of a locally-acting antacid.

            • digoxin

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

            • dihydroergotamine

              sotorasib will decrease the level or effect of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the CYP3A4 substrate for dosage modifications

            • dihydroergotamine inhaled

              sotorasib will decrease the level or effect of dihydroergotamine inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the CYP3A4 substrate for dosage modifications

            • dihydroergotamine intranasal

              sotorasib will decrease the level or effect of dihydroergotamine intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the CYP3A4 substrate for dosage modifications

            • diltiazem

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

            • disopyramide

              sotorasib will decrease the level or effect of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the CYP3A4 substrate for dosage modifications

            • docetaxel

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

            • doxorubicin

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

            • duvelisib

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

            • edoxaban

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

            • efavirenz

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

            • elacestrant

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

            • eletriptan

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

            • enzalutamide

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

            • ergotamine

              sotorasib will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the CYP3A4 substrate for dosage modifications

            • erythromycin base

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

            • erythromycin ethylsuccinate

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

            • erythromycin lactobionate

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

            • erythromycin stearate

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

            • esomeprazole

              esomeprazole will decrease the level or effect of sotorasib by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. If use with an acid-reducing agent cannot be avoided, administer sotorasib 4 hr before or 10 hr after administration of a locally-acting antacid.

            • ethosuximide

              sotorasib will decrease the level or effect of ethosuximide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the CYP3A4 substrate for dosage modifications

            • etoposide

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

            • etravirine

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

            • everolimus

              sotorasib will decrease the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the CYP3A4 substrate for dosage modifications

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

            • famotidine

              famotidine will decrease the level or effect of sotorasib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use with an acid-reducing agent cannot be avoided, administer sotorasib 4 hr before or 10 hr after administration of a locally-acting antacid.

            • fentanyl

              sotorasib will decrease the level or effect of fentanyl by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the CYP3A4 substrate for dosage modifications

            • fentanyl intranasal

              sotorasib will decrease the level or effect of fentanyl intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the CYP3A4 substrate for dosage modifications

            • fentanyl iontophoretic transdermal system

              sotorasib will decrease the level or effect of fentanyl iontophoretic transdermal system by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the CYP3A4 substrate for dosage modifications

            • fentanyl transdermal

              sotorasib will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the CYP3A4 substrate for dosage modifications

            • fentanyl transmucosal

              sotorasib will decrease the level or effect of fentanyl transmucosal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the CYP3A4 substrate for dosage modifications

            • fexinidazole

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

            • fexofenadine

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

            • finerenone

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

            • fosphenytoin

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

            • ganaxolone

              sotorasib will decrease the level or effect of ganaxolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ganaxolone with moderate or strong CYP3A4 inducers. If coadministration unavoidable, consider increasing ganaxolone dose; however, do not exceed maximum daily dose for weight.

            • glecaprevir/pibrentasvir

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

            • hydrocortisone

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

            • idarubicin

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

            • imatinib

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

            • indinavir

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

            • infigratinib

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

            • irinotecan

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

            • ivermectin

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

            • ivosidenib

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

            • lansoprazole

              lansoprazole will decrease the level or effect of sotorasib by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. If use with an acid-reducing agent cannot be avoided, administer sotorasib 4 hr before or 10 hr after administration of a locally-acting antacid.

            • lapatinib

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

            • larotrectinib

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

            • ledipasvir/sofosbuvir

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

            • lefamulin

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

            • lenacapavir

              sotorasib will decrease the level or effect of lenacapavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lenacapavir with moderate CYP3A4 inducers.

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

            • leniolisib

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

            • lenvatinib

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

            • letermovir

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

            • linagliptin

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

            • loperamide

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

            • loratadine

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

            • lovastatin

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

            • lumacaftor/ivacaftor

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

            • lumateperone

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

            • magaldrate

              magaldrate will decrease the level or effect of sotorasib by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. If use with an acid-reducing agent cannot be avoided, administer sotorasib 4 hr before or 10 hr after administration of a locally-acting antacid.

            • magnesium hydroxide

              magnesium hydroxide will decrease the level or effect of sotorasib by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. If use with an acid-reducing agent cannot be avoided, administer sotorasib 4 hr before or 10 hr after administration of a locally-acting antacid.

            • magnesium oxide

              magnesium oxide will decrease the level or effect of sotorasib by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. If use with an acid-reducing agent cannot be avoided, administer sotorasib 4 hr before or 10 hr after administration of a locally-acting antacid.

            • maraviroc

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

            • methotrexate

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

            • midazolam

              sotorasib will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the CYP3A4 substrate for dosage modifications

            • midazolam intranasal

              sotorasib will decrease the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the CYP3A4 substrate for dosage modifications

            • mitomycin

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

            • mitotane

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

            • morphine

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

            • nadolol

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

            • nafcillin

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

            • naldemedine

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

            • nelfinavir

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

            • nizatidine

              nizatidine will decrease the level or effect of sotorasib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use with an acid-reducing agent cannot be avoided, administer sotorasib 4 hr before or 10 hr after administration of a locally-acting antacid.

            • olutasidenib

              sotorasib will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.

            • omaveloxolone

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

            • ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)

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

            • omeprazole

              omeprazole will decrease the level or effect of sotorasib by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. If use with an acid-reducing agent cannot be avoided, administer sotorasib 4 hr before or 10 hr after administration of a locally-acting antacid.

            • ondansetron

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

            • osimertinib

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

            • paclitaxel

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

            • paclitaxel protein bound

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

            • paliperidone

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

            • palovarotene

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

            • pantoprazole

              pantoprazole will decrease the level or effect of sotorasib by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. If use with an acid-reducing agent cannot be avoided, administer sotorasib 4 hr before or 10 hr after administration of a locally-acting antacid.

            • pazopanib

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

            • pentobarbital

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

            • phenobarbital

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

            • phenytoin

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

            • pimozide

              sotorasib will decrease the level or effect of pimozide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the CYP3A4 substrate for dosage modifications

            • pirtobrutinib

              sotorasib will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).

            • pomalidomide

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

            • posaconazole

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

            • pralsetinib

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

            • pravastatin

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

            • prednisone

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

            • primidone

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

            • quinidine

              sotorasib will decrease the level or effect of quinidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the CYP3A4 substrate for dosage modifications

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

            • quinine

              sotorasib will decrease the level or effect of quinine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the CYP3A4 substrate for dosage modifications

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

            • quizartinib

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

            • rabeprazole

              rabeprazole will decrease the level or effect of sotorasib by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. If use with an acid-reducing agent cannot be avoided, administer sotorasib 4 hr before or 10 hr after administration of a locally-acting antacid.

            • ranitidine

              ranitidine will decrease the level or effect of sotorasib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use with an acid-reducing agent cannot be avoided, administer sotorasib 4 hr before or 10 hr after administration of a locally-acting antacid.

            • ranolazine

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

            • rifabutin

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

            • rifampin

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

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

            • rifapentine

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

            • rifaximin

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

            • rimegepant

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

            • riociguat

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

            • risperidone

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

            • ritonavir

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

            • romidepsin

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

            • saquinavir

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

            • saxagliptin

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

            • secobarbital

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

            • silodosin

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

            • simethicone

              simethicone will decrease the level or effect of sotorasib by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. If use with an acid-reducing agent cannot be avoided, administer sotorasib 4 hr before or 10 hr after administration of a locally-acting antacid.

            • sirolimus

              sotorasib will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the CYP3A4 substrate for dosage modifications

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

            • sitagliptin

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

            • sofosbuvir

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

            • sofosbuvir/velpatasvir

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

            • St John's Wort

              St John's Wort will decrease the level or effect of sotorasib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • tacrolimus

              sotorasib will decrease the level or effect of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the CYP3A4 substrate for dosage modifications

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

            • talazoparib

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

            • tazemetostat

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

            • temsirolimus

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

            • teniposide

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

            • tenofovir AF

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

            • tenofovir DF

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

            • testosterone

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

            • testosterone buccal system

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

            • testosterone intranasal

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

            • testosterone topical

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

            • ticagrelor

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

            • tolvaptan

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

            • topotecan

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

            • trabectedin

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

            • triazolam

              sotorasib will decrease the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the CYP3A4 substrate for dosage modifications

            • ubrogepant

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

            • velpatasvir

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

            • vemurafenib

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

            • venetoclax

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

            • verapamil

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

            • vinblastine

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

            • vincristine

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

            • vincristine liposomal

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

            • vonoprazan

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

            • voxilaprevir

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

            Monitor Closely (6)

            • belumosudil

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

            • isavuconazonium sulfate

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

            • norgestrel

              sotorasib will decrease the level or effect of norgestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Moderate CYP3A4 inducers may decrease progestin concentration; consider use of additional barrier methods

            • ripretinib

              sotorasib will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration cannot be avoided, increase dosing frequency from recommended dose of 150 mg once daily to 150 mg twice daily during co-administration period; monitor for clinical response and tolerability

            • warfarin

              sotorasib will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.

            • zanubrutinib

              sotorasib will decrease the level or effect of zanubrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of zanubrutinib (a CYP3A4 substrate) with moderate CYP3A4 inhibitors. If unavoidable, increase zanubrutinib dose to 320 mg PO BID. After discontinuing the CYP3A4 inhibitor, resume previous dose of zanubrutinib.

            Minor (1)

            • atogepant

              sotorasib will decrease the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. Recommended atogepant dosage with concomitant use of strong or moderate CYP3A4 inducers is 30 mg or 60 mg qDay.

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            Adverse Effects

            >10%

            All grades

            • Decreased lymphocytes (48%)
            • Decreased hemoglobin (43%)
            • Diarrhea (42%)
            • Increased AST (39%)
            • Increased ALT (28%)
            • Musculoskeletal pain (35%)
            • Decreased calcium (35%)
            • Increased alkaline phosphatase (33%)
            • Increased urine protein (29%)
            • Decreased sodium (28%)
            • Nausea (26%)
            • Fatigue (26%)
            • Hepatoxicity (25%)
            • Decreased albumin (23%)
            • Increased activated partial thromboplastin time (aPTT) (23%)
            • Cough (20%)
            • Vomiting (17%)
            • Constipation (16%)
            • Dyspnea (16%)
            • Abdominal pain (15%)
            • Edema (15%)
            • Decreased appetite (13%)
            • Arthralgia (12%)
            • Pneumonia (12%)
            • Rash (12%)

            Grade 3 or 4

            • Hepatoxicity (12%)
            • Increased ALT (11%)

            1-10%

            Grade 3 or 4

            • Increased AST (9%)
            • Musculoskeletal pain (8%)
            • Pneumonia (7%)
            • Diarrhea (5%)
            • Increased urine protein (3.9%)
            • Dyspnea (2.9%)
            • Increased alkaline phosphatase (2.5%)
            • Decreased lymphocytes (2%)
            • Fatigue (2%)
            • Increased aPTT (1.5%)
            • Cough (1.5%)
            • Vomiting (1.5%)
            • Decreased sodium (1%)
            • Decreased appetite (1%)
            • Arthralgia (1%)
            • Abdominal pain (1%)
            • Nausea (1%)

            <1%

            Grade 3 or 4

            • Decreased hemoglobin (0.5%)
            • Decreased albumin (0.5%)
            • Constipation (0.5%)
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            Warnings

            Contraindications

            None

            Cautions

            Hepatotoxicity reported, which may lead to drug-induced liver injury and hepatitis; monitor liver function tests (ALT, AST, and TB) before initiation, every 3 weeks for first 3 months, then monthly or as clinically indicated, and more frequently in patients who develop transaminase and/or bilirubin elevations

            May cause ILD/pneumonitis that can be fatal; median time to first onset was 2 weeks; monitor for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (eg, dyspnea, cough, fever)

            Drug interaction overview

            • CYP3A4 substrate and inducer
            • May induce CYP2C8, CYP2C9, and CYP2B6
            • P-glycoprotein (P-gp) and BCRP inhibitor
            • Acid-reducing agents
              • Avoid coadministration
              • Proton pump inhibitors (PPIs), H2-receptor antagonists, and locally acting antacids decreased sotorasib concentrations and its efficacy
              • If unavoidable, administer sotorasib 4 hr before or 10 hr after administration of locally acting antacids
            • Strong CYP3A4 inducers
              • Avoid coadministration
              • Strong CYP3A4 inducers decreased sotorasib concentrations and its efficacy
            • CYP3A4 substrates
              • Avoid coadministration with CYP3A4 sensitive substrates, for which minimal concentration changes may lead to therapeutic failures of the substrate
              • CYP3A4 substrates decreased its plasma concentrations and its efficacy
              • If unavoidable, increase sensitive CYP3A4 substrate dosage in accordance with its prescribing information
            • P-gp substrates
              • Avoid coadministration with P-gp substrates for which minimal concentration changes may lead to serious toxicities
              • Sotorasib (P-gp inhibitor) increased digoxin (P-gp substrate) plasma concentrations and adverse reactions
              • If unavoidable, decrease P-gp substrate dosage in accordance with its prescribing information
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            Pregnancy & Lactation

            Pregnancy

            No data are available on use in pregnant females

            Animal data

            • In a rabbit embryofetal development study, oral administration of sotorasib during organogenesis resulted in lower fetal body weights and a reduction in the number of ossified metacarpals in fetuses at the 100-mg/kg dose level (~2.6x the human exposure based on AUC at the clinical dose of 960 mg), which was associated with maternal toxicity, including decreased body weight gain and food consumption during dosing phase

            Lactation

            There are no data on drug presence or its metabolites in human milk, effects on the breastfed children, or effects on milk production

            Advise women not to breastfeed during treatment and for 1 week after final dose

            Pregnancy Categories

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

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

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

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

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

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            KRASG21C inhibitor

            Forms an irreversible, covalent bond with the unique cysteine of KRASG12C, locking the protein in an inactive state that prevents downstream signaling without affecting wild-type KRAS

            Also, blocks KRAS signaling, inhibits cell growth, and promotes apoptosis only in KRASG12C tumor cell lines

            Absorption

            Steady-state reached at 22 days

            Peak plasma time: 1 hr

            Effect of food

            • 960-mg dose administered with a high-fat, high-calorie meal (containing ~800-1000 calories with 150, 250, and 500-600 calories from protein, carbohydrate, and fat, respectively): Sotorasib AUC increased by 25% compared with fasted conditions

            Distribution

            Vd (steady-state): 211 L

            Protein bound: 89%

            Metabolism

            Main metabolic pathways of sotorasib are nonenzymatic conjugation and oxidative metabolism with CYP3A

            Elimination

            Half-life: 5 hr

            Clearance (steady-state): 26.2 L

            Excretion: Feces (74% [53% unchanged]); urine (6% [1%unchanged])

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            Administration

            Oral Administration

            Take with or without food at same time each day

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

            Missed dose

            • Missed >6 hr: Take next dose as prescribed the next day; do not double dose
            • Vomited dose: Do not take an additional dose; take next dose as prescribed the next day

            Difficulty swallowing solids

            • Disperse tablets in 120 mL (4 ounces) of noncarbonated, room temperature water without crushing; do not use other liquids
            • Stir for ~ 3 minutes until tablets are dispersed into small pieces (NOTE: tablets will not completely dissolve) and drink immediately or within 2 hr; mixture appearance may range from pale to bright yellow
            • Swallow mixture; do not chew tablet pieces; rinse container with an additional 120 mL (4 ounces) of water and drink; if not consumed immediately, stir mixture again to ensure that tablets are dispersed

            Storage

            Store at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°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

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

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

            Adding plans allows you to:

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

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

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