Sunitinib is metabolized primarily by CYP3A4. Potential interactions may occur with drugs/foods/herbs that are inhibitors or inducers of this enzyme system.
CYP3A4 Inhibitors: Co-administration of SUTENT (sunitinib malate) with inhibitors of the CYP3A4 family may increase SUTENT concentrations (see ACTION AND CLINICAL PHARMACOLOGY). Concomitant administration of SUTENT with CYP3A4 inhibitors should be avoided. These include, but are not limited to: non-dihydropyridine calcium channel blockers (e.g. diltiazem, verapamil); antifungals (e.g. ketoconazole, fluconazole, itraconazole, voriconazole); macrolide antibiotics (e.g. erythromycin, clarithromycin, telithromycin); fluoroquinolone antibiotics (e.g. ciprofloxacin, norfloxacin); and some HIV antivirals (e.g. ritonavir, indinavir).
CYP3A4 Inducers: Co-administration of SUTENT with inducers of the CYP3A4 family may decrease SUTENT concentrations (see ACTION AND CLINICAL PHARMACOLOGY). Concomitant administration of SUTENT with CYP3A4 inducers should be avoided. CYP3A4 inducers include, but are not limited to: barbiturates (e.g. phenobarbital); anticonvulsants (e.g. carbamazepine, phenytoin); rifampin; glucocorticoids; pioglitazone; and some HIV antivirals (e.g. efavirenz, nevirapine).
Drugs Which Prolong the QT/QTc Interval: The concomitant use of SUTENT with another QT/QTc-prolonging drug is discouraged. However, if it is necessary, particular care should be used. 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:
- Antiarrhythmics (Class IA, e.g., quinidine, procainamide, disopyramide; Class III, e.g. amiodarone, sotalol, ibutilide; Class IC, e.g. flecainide, propafenone)
- Antipsychotics (e.g. thioridazine, chlorpromazine, pimozide, haloperidol, droperidol)
- Antidepressants (e.g. amitriptyline, imipramine, maprotiline, fluoxetine, venlafaxine)
- Opioids (e.g. methadone)
- Macrolide antibiotics (e.g. erythromycin, clarithromycin, telithromycin)
- Quinolone antibiotics (e.g. moxifloxacin, gatifloxacin, ciprofloxacin)
- Antimalarials (e.g. quinine)
- Azole antifungals (e.g. ketoconazole, fluconazole, voriconazole)
- Gastrointestinal drugs (e.g. domperidone, 5HT3 antagonists, such as granisetron, ondansetron, dolasetron)
- Βeta 2-adrenoreceptor agonists (e.g. salmeterol, formoterol)
Drugs Which Prolong the PR Interval: Caution should be used if SUTENT is prescribed to patients in combination with other drugs that also cause PR interval prolongation, such as beta blockers, calcium channel blockers, digitalis, or HIV protease inhibitors (See WARNINGS AND PRECAUTIONS, Cardiovascular, QT Interval Prolongation).
The above list of potentially interacting drugs is not comprehensive. Current scientific literature should be consulted for more information.
Grapefruit juice has CYP3A4 inhibitory activity. Therefore, ingestion of grapefruit juice while on SUTENT therapy may lead to decreased SUTENT metabolism and increased SUTENT plasma concentrations (see Drug-Drug Interactions). Concomitant administration of SUTENT with grapefruit juice should be avoided.
St. John’s Wort is a potent CYP3A4 inducer. Co-administration with SUTENT may lead to increased SUTENT metabolism and decreased SUTENT plasma concentrations (see Drug-Drug Interactions). Patients receiving SUTENT should not take St. John’s Wort concomitantly.