Tibsovo Special Precautions

Differentiation syndrome in patients with acute myeloid leukaemia: Differentiation syndrome has been reported following treatment with ivosidenib (see Adverse Reactions). Differentiation syndrome may be life-threatening or fatal if not treated (see as follows and Dosage & Administration). Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells. Symptoms include: non-infectious leukocytosis, peripheral oedema, pyrexia, dyspnoea, pleural effusion, hypotension, hypoxia, pulmonary oedema, pneumonitis, pericardial effusion, rash, fluid overload, tumour lysis syndrome and creatinine increased.
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.
If differentiation syndrome is suspected, administer systemic corticosteroids and initiate hemodynamic monitoring until symptom resolution and for a minimum of 3 days.
If leukocytosis is observed, initiate treatment with hydroxycarbamide according to institutional standards of care and leukapheresis as clinically indicated (see Dosage & Administration).
Taper corticosteroids and hydroxycarbamide only after resolution of symptoms. Symptoms of differentiation syndrome may recur with premature discontinuation of corticosteroid and/or hydroxycarbamide treatment. Interrupt treatment with Tibsovo if severe signs/symptoms persist for more than 48 hours after the initiation of systemic corticosteroids and resume treatment at 500 mg ivosidenib once daily when the signs/symptoms are moderate or lower and upon improvement in the patient's clinical condition.
QTc interval prolongation: QTc interval prolongation has been reported following treatment with ivosidenib (see Adverse Reactions).
An ECG must be performed prior to treatment initiation, at least weekly during the first 3 weeks of therapy and then monthly thereafter if the QTc interval remains ≤480 msec (see Dosage & Administration). Any abnormalities should be managed promptly (see Dosage & Administration). In case of suggestive symptomatology, an ECG should be performed as clinically indicated. In case of severe vomiting and/or diarrhoea, an assessment of serum electrolytes abnormalities, especially hypokalaemia and magnesium, must be performed.
Patients should be informed of the risk of QT prolongation, its signs and symptoms (palpitation, dizziness, syncope or even cardiac arrest) and be advised to contact their physician immediately if these occur.
Concomitant administration of medicinal products known to prolong the QTc interval, or moderate or strong CYP3A4 inhibitors 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. ECG should be performed prior to co-administration, weekly monitoring for at least 3 weeks and then as clinically indicated. The recommended dose of ivosidenib should be reduced to 250 mg once daily if use of moderate or strong CYP3A4 inhibitors cannot be avoided (see Dosage & Administration and Interactions).
If administration of furosemide (an OAT3 substrate) is clinically indicated to manage signs/symptoms of differentiation syndrome, patients should be closely monitored for electrolyte imbalances and QTc interval prolongation.
Patients with congestive heart failure or electrolyte abnormalities should be monitored closely, with periodic monitoring of ECGs and electrolytes, during treatment with ivosidenib.
Treatment with Tibsovo should be permanently discontinued if patients develop QTc interval prolongation with signs or symptoms of life-threatening arrhythmia (see Dosage & Administration).
Ivosidenib should be used with caution in patients who have either albumin levels below the normal range or are underweight.
Severe renal impairment: The safety and efficacy of ivosidenib have not been established in patients with severe renal impairment (eGFR ˂30 mL/min/1.73 m²). Tibsovo should be used with caution in patients with severe renal impairment and this patient population should be closely monitored (see Dosage & Administration and Pharmacology: Pharmacokinetics under Actions).
Hepatic impairment: The safety and efficacy of ivosidenib have not been established in patients with moderate and severe hepatic impairment (Child-Pugh classes B and C). Tibsovo should be used with caution in patients with moderate and severe hepatic impairment and this patient population should be closely monitored (see Dosage & Administration and Pharmacology: Pharmacokinetics under Actions).
Tibsovo should be used with caution in patients with mild hepatic impairment (Child-Pugh class A) (see Adverse Reactions).
CYP3A4 substrates: Ivosidenib induces CYP3A4 and it may, therefore, decrease systemic exposure to CYP3A4 substrates. Patients should be monitored for loss of antifungal efficacy if use of itraconazole or ketoconazole cannot be avoided (see Interactions).
Lactose intolerance: Tibsovo contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should avoid this medicinal product.
Sodium content: This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 'sodium-free'.
Effects on ability to drive and use machines: Ivosidenib has minor influence on the ability to drive and use machines. Fatigue and dizziness have been reported in some patients taking ivosidenib (see Adverse Reactions) and should be considered when assessing a patient's ability to drive or operate machines.
Use in Pregnancy & Lactation: Women of childbearing potential/contraception: Women of childbearing potential should have a pregnancy test prior to starting treatment with Tibsovo and should avoid becoming pregnant during therapy (see Use in Pregnancy & Lactation).
Women of childbearing potential and males with female partners of childbearing potential should use effective contraception during treatment with Tibsovo and for at least 1 month after the last dose.
Ivosidenib may decrease the systemic concentrations of hormonal contraceptives and, therefore, concomitant use of a barrier method of contraception is recommended (see Interactions and Use in Pregnancy & Lactation).