Tibsovo^® ▼ (ivosidenib)

This medicinal product is subject to additional monitoring.

Abbreviated Prescribing Information: Please refer to the Summary of Product Characteristics before prescribing.

COMPOSITION* Tibsovo: film-coated tablets containing 250 mg of ivosidenib.

INDICATIONS* In combination with azacitidine for the treatment of adult patients with newly diagnosed acute myeloid leukaemia (AML) with an isocitrate dehydrogenase-1 (IDH1) R132 mutation who are not eligible to receive standard induction chemotherapy. In monotherapy for the treatment of adult patients with locally advanced or metastatic cholangiocarcinoma (CCA) with an IDH1 R132 mutation who were previously treated by at least one prior line of systemic therapy.

DOSAGE AND ADMINISTRATION* Treatment should be initiated under the supervision of physicians experienced in the use of anti-cancer medicinal products. Before taking Tibsovo, patients must have confirmation of an IDH1 R132 mutation using an appropriate diagnostic test. ECG, complete blood count and blood chemistries should be assessed prior to treatment initiation and during treatment. Heart rate corrected QT (QTc) should be less than 450 msec prior to treatment initiation. Recommended dose in AML: 500 mg ivosidenib (2 x 250 mg tablets) taken orally once daily. Ivosidenib should be started on Cycle 1 Day 1 in combination with azacitidine at 75 mg/m 2 of body surface area, intravenously or subcutaneously, once daily on Days 1-7 of each 28-day cycle. It is recommended that patients be treated for a minimum of 6 cycles. Recommended dose in cholangiocarcinoma: 500 mg ivosidenib (2 x 250 mg tablets) taken orally once daily. Patients should not eat anything for 2 hours before and through 1 hour after taking the tablets. Dose modifications are recommended to manage concomitant administration of moderate or strong CYP3A4 inhibitors, differentiation syndrome, leukocytosis, QTc interval prolongation and grade 3 or higher adverse reactions.

CONTRAINDICATIONS* Hypersensitivity to the active substance or to any of the excipients. Concomitant administration of strong CYP3A4 inducers or dabigatran (see ‘Interactions’). Congenital long QT syndrome. Familial history of sudden death or polymorphic ventricular arrhythmia. QT/QTc interval > 500 msec, regardless of the correction method.

WARNINGS* Differentiation syndrome in patients with AML: Differentiation syndrome may be life- threatening or fatal if not treated. Patients must be informed of signs and symptoms of differentiation syndrome, be advised to contact their physician immediately if these occur and the need to carry the Patient Alert Card with them at all times. Interrupt treatment with Tibsovo if severe signs/symptoms persist for more than 48 hours after the initiation of systemic corticosteroids. QTc interval prolongation: Any abnormalities should be managed promptly. In case of suggestive symptomatology, an ECG should be performed. In case of severe vomiting and/or diarrhoea, an assessment of serum electrolytes abnormalities must be performed. Patients should be informed of the risk of QT prolongation, its signs and symptoms and be advised to contact their physician immediately if these occur. Patients should be treated with caution and closely monitored for QTc interval prolongation if use of a suitable alternative to medicinal products known to prolong the QTc interval, or moderate or strong CYP3A4 inhibitors is not possible. Closely monitor patients with congestive heart failure, electrolyte abnormalities or if administration of furosemide is clinically indicated to manage differentiation syndrome. Treatment should be permanently discontinued if patients develop QTc interval prolongation with signs or symptoms of life-threatening arrhythmia. Use with caution in patients who have either albumin levels below the normal range or are underweight. Severe renal impairment: use with caution and closely monitor. Hepatic impairment: use with caution and closely monitor in patients with moderate and severe hepatic impairment (Child- Pugh classes B and C). Use with caution in patients with mild hepatic impairment (Child-Pugh class A). Excipients: contains lactose and sodium (essentially ‘sodium free’).

INTERACTION(S)* Contraindicated: strong CYP3A4 inducers; dabigatran. Not recommended: moderate or strong CYP3A4 inhibitors; medicinal products known to prolong QTc interval; OAT3 or OATP1B1/1B3 substrates; CYP3A4, CYP2B6, CYP2C8 or CYP2C9 substrates with a narrow therapeutic index, or CYP2C19 substrates; itraconazole or ketoconazole; UGT substrates. Precautions: hormonal contraceptives.

FERTILITY* PREGNANCY* Not recommended.

BREASTFEEDING* Should be discontinued during treatment and for at least 1 month after the last dose.

CONTRACEPTION* Women of childbearing potential should have a pregnancy test prior to starting treatment and should avoid becoming pregnant during therapy. Effective contraception should be used during treatment and for at least 1 month after the last dose.

DRIVE & USE MACHINES* Minor influence. Fatigue and dizziness should be considered when assessing a patient’s ability to drive or operate machines.

UNDESIRABLE EFFECTS* In AML: Very common: differentiation syndrome, leukocytosis, thrombocytopenia, neutropenia, insomnia, headache, dizziness, vomiting, pain in extremity, arthralgia, back pain, electrocardiogram QT prolonged. Common: leukopenia, neuropathy peripheral, oropharyngeal pain. In CCA: Very common: anaemia, decreased appetite, neuropathy peripheral, headache, ascites, diarrhoea, vomiting, nausea, abdominal pain, rash, fatigue, aspartate aminotransferase increased, blood bilirubin increased. Common: jaundice cholestatic, hyperbilirubinemia, fall, electrocardiogram QT prolonged, alanine aminotransferase increased, white blood cell count decreased, platelet count decreased.

OVERDOSE* PROPERTIES* Ivosidenib is an inhibitor of the mutant IDH1 enzyme. Mutant IDH1 converts alpha-ketoglutarate (α-KG) to 2-hydroxyglutarate (2-HG) which blocks cellular differentiation and promotes tumorigenesis in both hematologic and non-hematologic malignancies. The mechanism of action of ivosidenib beyond its ability to reduce 2-HG and restore cellular differentiation is not fully understood across indications.

PRESENTATION* Pack of 60 film-coated tablets. Marketing Authorisation Holder LES LABORATOIRES SERVIER, 50 rue Carnot, 92284 Suresnes cedex France. www.servier.com. Marketing Authorisation: EU/1/23/1728/001. Legal Classification for Supply: POM. Further information available from:Servier Laboratories (Ireland) Ltd. 1st Floor, Building Two, The Green Dublin Airport Central. Dublin Airport,Swords Co. Dublin K67 E2H3., Ireland, Tel (01) 6638110, www.servier.ie.

*For complete information, please refer to the Summary of Product Characteristics available on medicines.ie.

Date of last revision of text: March 2024