Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

Critical visceral disease

The efficacy and safety of ribociclib have not been studied in patients with critical visceral disease.
Neutropenia

Based on the severity of the neutropenia, treatment with Kisqali may have to be interrupted, reduced or discontinued as described in Table 2 (see sections 4.2 and 4.8).

Hepatobiliary toxicity

Liver function tests should be performed before initiating treatment with Kisqali. After initiating treatment, liver function should be monitored (see sections 4.2 and 4.8).

Based on the severity of the transaminase elevations, treatment with Kisqali may have to be interrupted, reduced or discontinued as described in Table 3 (see sections 4.2 and 4.8).
Recommendations for patients who have elevated AST/ALT grade ≥ 3 at baseline have not been established.

QT interval prolongation

In study E2301 (MONALEESA-7), a QTcF interval increase >60 msec from baseline was observed in 14/87 (16.1%) patients receiving Kisqali plus tamoxifen and in 18/245 (7.3%) patients receiving Kisqali plus a non-steroidal aromatase inhibitor (NSAI). Kisqali is not recommended to be used in combination with tamoxifen (see sections 4.8 and 5.1).


KIS API JUL24 V9                                                            EU SmPC JUN 24 6
ECG should be assessed before initiating treatment. Treatment with Kisqali should be initiated only in patients with QTcF values less than 450 msec. ECG should be repeated at approximately day 14 of the first cycle and at the beginning of the second cycle, then as clinically indicated (see sections 4.2 and 4.8).

Appropriate monitoring of serum electrolytes (including potassium, calcium, phosphorus and magnesium) should be performed before initiating treatment, at the beginning of the first 6 cycles and then as clinically indicated. Any abnormality should be corrected before initiating treatment with Kisqali and during treatment with Kisqali.

The use of Kisqali should be avoided in patients who already have or who are at significant risk of developing QTc prolongation. This includes patients:


•     with long QT syndrome;
•     with uncontrolled or significant cardiac disease, including recent myocardial infarction, congestive heart failure, unstable angina and bradyarrhythmias;
•     with electrolyte abnormalities.

The use of Kisqali with medicinal products known to prolong QTc interval and/or strong CYP3A4 inhibitors should be avoided as this may lead to clinically meaningful prolongation of the QTcF interval (see sections 4.2, 4.5 and 5.1). If treatment with a strong CYP3A4 inhibitor cannot be avoided, the dose should be reduced to 400 mg once daily (see sections 4.2 and 4.5).

Based on the observed QT prolongation during treatment, treatment with Kisqali may have to be interrupted, reduced or discontinued as described in Table 4 (see sections 4.2, 4.8 and 5.2).

Thromboembolic events

Caution is advised in patients with risk factors for thromboembolic events while receiving the combination of Kisqali with endocrine treatment.
Monitor patients for signs and symptoms of thromboembolism and treat as medically appropriate.

Severe cutaneous reactions

Toxic epidermal necrolysis (TEN) has been reported with Kisqali treatment. If signs and symptoms suggestive of severe cutaneous reactions (e.g. progressive widespread skin rash often with blisters or mucosal lesions) appear, Kisqali should be discontinued immediately.

Interstitial lung disease/pneumonitis

Interstitial lung disease (ILD)/pneumonitis has been reported with Kisqali. Patients should be monitored for pulmonary symptoms indicative of ILD/pneumonitis which may include hypoxia, cough and dyspnoea and dose modifications should be managed in accordance with Table 5 (see section 4.2).
Based on the severity of the ILD/pneumonitis, which may be fatal, Kisqali may require dose interruption, reduction or discontinuation as described in Table 5 (see section 4.2).


Blood creatinine increase
Ribociclib may cause blood creatinine increase as an inhibitor of the renal transporters organic cation transporter 2 (OCT2) and multidrug and toxin extrusion protein 1 (MATE1), which are involved in the active secretion of creatinine from the proximal tubules (see section 4.5). In case of blood creatinine increase while on treatment, it is recommended that further assessment of the renal function be performed to exclude renal impairment.


KIS API JUL24 V9                                                          EU SmPC JUN 24 7
CYP3A4 substrates

Ribociclib is a strong CYP3A4 inhibitor at the 600 mg dose and a moderate CYP3A4 inhibitor at the 400 mg dose. Thus, ribociclib may interact with medicinal products which are metabolised via
CYP3A4, which may lead to increased serum concentrations of CYP3A4 substrates (see section 4.5).
Caution is recommended in case of concomitant use with sensitive CYP3A4 substrates with a narrow therapeutic index and the Prescribing information of the other product should be consulted for the recommendations regarding co-administration with CYP3A4 inhibitors.

Renal impairment

The recommended starting dose of 200 mg for patients with severe renal impairment is estimated to result in approximately 45% lower exposure compared with the standard starting dose in patients with normal renal function. The efficacy at this starting dose has not been studied. Caution should be used in patients with severe renal impairment with close monitoring for signs of toxicity (see sections 4.2 and 5.2).

Women of childbearing potential

Women of childbearing potential should be advised to use an effective method of contraception while taking Kisqali and for at least 21 days after the last dose (see section 4.6).

Soya lecithin

Kisqali contains soya lecithin. Patients who are hypersensitive to peanut or soya should not take Kisqali (see section 4.3).

Effects on Driving

4.7    Effects on ability to drive and use machines

Kisqali may have minor influence on the ability to drive and use machines. Patients should be advised to be cautious when driving or using machines in case they experience fatigue, dizziness or vertigo during treatment with Kisqali (see section 4.8).