Tibsovo Drug Interactions

Effect of other medicinal products on ivosidenib: Strong CYP3A4 inducers: Ivosidenib is a CYP3A4 substrate. Concomitant administration of strong CYP3A4 inducers (e.g. carbamazepine, phenobarbital, phenytoin, rifampicin, St. John's wort (Hypericum perforatum)) is expected to decrease plasma concentrations of ivosidenib and is contraindicated during treatment with Tibsovo (see Contraindications). Clinical studies evaluating the pharmacokinetics of ivosidenib in the presence of a CYP3A4 inducer have not been conducted.
Moderate or strong CYP3A4 inhibitors: In healthy subjects, administration of a single dose of 250 mg ivosidenib and 200 mg itraconazole once daily for 18 days increased the ivosidenib AUC by 169% (90% CI: 145, 195) with no change in C_max. Concomitant administration of moderate or strong CYP3A4 inhibitors increases plasma concentrations of ivosidenib. This may increase the risk of QTc interval prolongation and suitable alternatives that are not moderate or strong CYP3A4 inhibitors should be considered whenever possible during treatment with Tibsovo. Patients should be treated with caution and closely monitored for QTc interval prolongation if use of a suitable alternative is not possible. If use of moderate or strong CYP3A4 inhibitors cannot be avoided, the recommended dose of ivosidenib should be reduced to 250 mg once daily (see Dosage & Administration and Precautions).
Moderate CYP3A4 inhibitors include: aprepitant, ciclosporin, diltiazem, erythromycin, fluconazole, grapefruit and grapefruit juice, isavuconazole, verapamil.
Strong CYP3A4 inhibitors include: clarithromycin, itraconazole, ketoconazole, posaconazole, ritonavir, voriconazole.
Medicinal products known to prolong the QTc interval: Concomitant administration of medicinal products known to prolong the QTc interval (e.g. anti-arrhythmics, fluoroquinolones, 5-HT3 receptor antagonists, triazole antifungals) may increase the risk of QTc interval prolongation and should be avoided whenever possible during treatment with Tibsovo. Patients should be treated with caution and closely monitored for QTc interval prolongation if use of a suitable alternative is not possible (see Dosage & Administration and Precautions).
Effect of ivosidenib on other medicinal products: Interactions with transporters: Ivosidenib inhibits P-gp and has the potential to induce P-gp. Therefore, it may alter systemic exposure to active substances that are predominantly transported by P-gp (e.g. dabigatran). Concomitant administration of dabigatran is contraindicated (see Contraindications).
Ivosidenib inhibits OAT3, organic anion-transporting polypeptide 1B1 (OATP1B1) and organic anion-transporting polypeptide 1B3 (OATP1B3). Therefore, it may increase systemic exposure to OAT3 or OATP1B1/1B3 substrates. Concomitant administration of OAT3 substrates (e.g. benzylpenicillin, furosemide) or sensitive OATP1B1/1B3 substrates (e.g. atorvastatin, pravastatin, rosuvastatin) should be avoided whenever possible during treatment with Tibsovo (see Pharmacology: Pharmacokinetics under Actions). Patients should be treated with caution if use of a suitable alternative is not possible. If administration of furosemide is clinically indicated to manage signs/symptoms of differentiation syndrome, patients should be closely monitored for electrolyte imbalances and QTc interval prolongation.
Enzyme induction: Cytochrome P450 (CYP) enzymes: Ivosidenib induces CYP3A4, CYP2B6, CYP2C8, CYP2C9 and may induce CYP2C19. Therefore, it may decrease systemic exposure to substrates of these enzymes. Suitable alternatives that are not CYP3A4, CYP2B6, CYP2C8 or CYP2C9 substrates with a narrow therapeutic index, or CYP2C19 substrates should be considered during treatment with Tibsovo. Patients should be monitored for loss of substrate efficacy if use of such medicinal products cannot be avoided (see Pharmacology: Pharmacokinetics under Actions).
CYP3A4 substrates with a narrow therapeutic index include: alfentanil, ciclosporin, everolimus, fentanyl, pimozide, quinidine, sirolimus, tacrolimus.
CYP2B6 substrates with a narrow therapeutic index include: cyclophosphamide, ifosfamide, methadone.
CYP2C8 substrates with a narrow therapeutic index include: paclitaxel, pioglitazone, repaglinide.
CYP2C9 substrates with a narrow therapeutic index include: phenytoin, warfarin.
CYP2C19 substrates include: omeprazole.
Itraconazole or ketoconazole should not be used concomitantly with Tibsovo due to the expected loss of antifungal efficacy.
Ivosidenib may decrease the systemic concentrations of hormonal contraceptives and, therefore, concomitant use of a barrier method of contraception is recommended for at least 1 month after the last dose (see Precautions and Use in Pregnancy & Lactation).
Uridine diphosphate glucuronosyltransferases (UGTs): Ivosidenib has the potential to induce UGTs and it may, therefore, decrease systemic exposure to substrates of these enzymes (e.g. lamotrigine, raltegravir). Suitable alternatives that are not UGT substrates should be considered during treatment with Tibsovo. Patients should be monitored for loss of UGT substrate efficacy if use of such medicinal products cannot be avoided (see Pharmacology: Pharmacokinetics under Actions).