BOSULIF (bosutinib) tablet Drug Interactions

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Serious Drug and Drug-Food Interactions
  • Strong and moderate CYP3A inhibitors increase BOSULIF exposure.
    Avoid concomitant use of these inhibitors.
  • Strong and moderate CYP3A inducers decrease BOSULIF exposure.
    Avoid concomitant use of these inducers.


In vitro studies with human liver microsomes indicated that the major CYP450 isozyme involved in the metabolism of bosutinib is CYP3A4. No metabolism of bosutinib was observed with CYPs 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, or 3A5. Flavin-containing monooxygenase enzymes (FMO1, FMO3, and FMO5) are capable of metabolizing bosutinib to its N-oxide metabolite.

Drug-Drug Interactions

Drugs That May Increase Bosutinib Plasma Concentrations

CYP3A inhibitors: Avoid the concomitant use of strong CYP3A inhibitors (e.g., including but not limited to boceprevir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir,posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, troleandomycin, voriconazole), or moderate CYP3A inhibitors (e.g., including but not limited to amprenavir, aprepitant, atazanavir,cimetidine, ciprofloxacin, crizotinib, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fosamprenavir, imatinib, verapamil, grapefruit products including star fruit, pomegranate, Seville oranges and other similar fruits that are known to inhibit CYP3A4) with BOSULIF, as an increase in bosutinib plasma concentration is possible.

Use caution if mild CYP3A inhibitors are used concomitantly with BOSULIF.

Selection of an alternate concomitant medication with no or minimal enzyme inhibition potential, if possible, is recommended.

In a study of 24 healthy subjects in which five daily doses of 400 mg ketoconazole (a strong CYP3A inhibitor) were co-administered with a single dose of 100 mg of BOSULIF, ketoconazole increased BOSULIF Cmax by 5.2 (90% CI: [4.3, 6.2])-fold, and BOSULIF AUC in plasma by 8.6 (90% CI: [7.5, 9.9])-fold, as compared with administration of BOSULIF alone under fasting conditions.

In a study of 20 healthy subjects in which a single dose of 125 mg aprepitant (a moderate CYP3A inhibitor) was co-administered with a single dose of 500 mg BOSULIF, aprepitant increased bosutinib Cmax by 1.5 (90% CI= 1.3 to 1.8)-fold, and bosutinib AUC in plasma by 2.0 (90% CI = 1.7 to 2.4)-fold over a 5-day pharmacokinetic assessment period, as compared with administration of BOSULIF alone under fed conditions.

In vitro transporter studies demonstrated that bosutinib is a substrate for efflux transporters P-gp, BCRP and MRPs. Possible interactions with BOSULIF and concomitant drug efflux transporter inhibitors may occur.

Drugs That May Decrease Bosutinib Plasma Concentrations

CYP3A Inducers: Avoid the concomitant use of strong CYP3A inducers (e.g., including but not limited to carbamazepine, phenytoin, rifampin, St. John’s wort or moderate CYP3A inducers (e.g., including but not limited to bosentan, efavirenz, etravirine, modafinil, nafcillin) with BOSULIF.

Based on the large reduction in bosutinib exposure that occurred when BOSULIF was co-administered with rifampin (strong CYP3A inducer), increasing the dose of BOSULIF when co-administering with strong or moderate CYP3A inducers is unlikely to sufficiently compensate for the loss of exposure.

Use caution if mild CYP3A inducers are used concomitantly with BOSULIF.

Following concomitant administration of a single dose of 500 mg of BOSULIF with six daily doses of 600 mg of rifampin in 24 healthy subjects, bosutinib exposure (Cmax and AUC in plasma) decreased to 14% (90%CI: [12.0, 16.0]) and to 6% (90%CI: [5.0, 7.0]), respectively, of the values when 500 mg of BOSULIF was administered alone in the fed state.

Proton Pump Inhibitors: Use caution when administering BOSULIF concomitantly with proton pump inhibitors (PPIs). Short-acting antacids should be considered as an alternative to PPIs, administration times of BOSULIF and antacids should be separated (e.g take BOSULIF in the morning, and antacids in the evening) whenever possible. BOSULIF displays pH-dependent aqueous solubility in vitro. When a single-oral dose of 400 mg of BOSULIF was co-administered with multiple-oral doses of 60 mg of lansoprazole (a PPI) in a study of 24 healthy fasting subjects, bosutinib Cmax and AUC decreased to 54% (90%CI: [42.0, 70.0]) and 74% (90%CI: [60.0, 90.0]), respectively, of the values seen when 400 mg of BOSULIF was given alone.

Drugs That May Have Their Plasma Concentration Altered By Bosutinib

Substrates of CYP: An in vitro study indicates that clinical drug-drug interactions are unlikely to occur as a result of induction by BOSULIF on the metabolism of drugs that are substrates for CYP1A2, CYP2B6, CYP2C9, CYP2C19, and CYP3A4.

In vitro, bosutinib inhibited CYP2C19, CYP2D6, and CYP3A4/5 at concentrations that were 26- to 71-fold higher than the Cmax in humans at 500 mg once daily.

In vitro studies indicate that bosutinib has a low potential to inhibit breast cancer resistance protein (BCRP, systemically), organic anion transporting polypeptide (OATP)1B1, OATP1B3, organic anion transporter (OAT)1, OAT3, organic cation transporter (OCT)1, and OCT2 at clinically relevant concentrations, but may have the potential to inhibit BCRP in the gastrointestinal tract and OCT1.

Anti-arrhythmic Medicines and Other Drugs That May Prolong QT:

Concomitant use of BOSULIF with another QT/QTc-prolonging drug is discouraged. Drugs that have been associated with QT/QTc interval prolongation and/or torsade de pointes include, but are not limited to, the examples in the following list. Chemical/pharmacological classes are listed if some, although not necessarily all, class members have been implicated in QT/QTc prolongation and/or torsade de pointes:

  • Class IA antiarrhythmics (e.g., quinidine, procainamide, disopyramide);
  • Class III antiarrhythmics (e.g., amiodarone, sotalol, dronedarone, ibutilide);
  • Class 1C antiarrhythmics (e.g., flecainide, propafenone);
  • antipsychotics (e.g., chlorpromazine, pimozide, haloperidol, droperidol, ziprasidone);
  • antidepressants (e.g., fluoxetine, citalopram, venlafaxine, tricyclic/tetracyclic antidepressants e.g., amitriptyline, imipramine, maprotiline);
  • opioids (e.g., methadone);
  • macrolide antibiotics and analogues (e.g., erythromycin, clarithromycin, telithromycin, tacrolimus);
  • quinolone antibiotics (e.g., moxifloxacin, levofloxacin, ciprofloxacin);
  • antimalarials (e.g., quinine, chloroquine);
  • azole antifungals (e.g., ketoconazole, fluconazole, voriconazole);
  • domperidone;
  • 5-hydroxytryptamine (5-HT)3 receptor antagonists (e.g., dolasetron, ondansetron);
  • tyrosine kinase inhibitors (e.g., vandetanib, sunitinib, nilotinib, lapatinib);
  • histone deacetylase inhibitors (e.g., vorinostat);
  • beta-2 adrenoceptor agonists (e.g., salmeterol, formoterol). (See Warnings and Precautions, Cardiovascular, Action and Clinical Pharmacoogy, QT/QTc Prolongation)

The use of BOSULIF* is discouraged with drugs that can disrupt electrolyte levels, including, but not limited to, the following:

  • loop, thiazide, and related diuretics;
  • laxatives and enemas;
  • amphotericin B;
  • high dose corticosteroids.

The above lists of potentially interacting drugs are not comprehensive. Current information sources should be consulted for newly approved drugs that prolong the QT/QTc interval, inhibit metabolizing enzymes and/or transporters, or cause electrolyte disturbances, as well as for older drugs for which these effects have recently been established.

Drug-Food Interactions

Administration of BOSULIF with a meal increased BOSULIF Cmax 1.8- fold and AUC 1.7-fold, respectively at the dose of 400 mg in healthy subjects (see DOSAGE AND ADMINISTRATION and ACTION AND CLINICAL PHARMACOLOGY, Pharmacokinetics, Absorption and Special Populations). BOSULIF taken without a meal may decrease BOSULIF’s bioavailability.

Products and juices containing grapefruit, star fruit, pomegranate, Seville oranges and other similar fruits that are known to inhibit CYP3A4, should be avoided at any time as they may increase BOSULIF plasma concentrations.

Drug-Herb Interactions

St. John’s Wort is a strong CYP3A4 inducer. Avoid the concomitant use of strong CYP3A inducers with BOSULIF as this may lead to decreased plasma concentrations of BOSULIF (see DRUG INTERACTIONS, Drug-Drug Interaction and DOSAGE AND ADMINISTRATION).

Drug-Laboratory Test Interactions

Interactions between BOSULIF and laboratory tests have not been studied.

Drug-Lifestyle Interactions

Effects on ability to drive and use machinery

No studies on the effects of bosutinib on the ability to drive and operate machines have been performed. Patients experiencing dizziness or other undesirable effects with a potential impact on the ability to safely drive or use machines should refrain from these activities as long as these undesirable effects persist (see ADVERSE REACTIONS).


No studies have been performed on the potential interaction between bosutinib and alcohol consumption.