Kisqali Special Precautions

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 11 (see Dosage & Administration and Adverse Reactions).
Hepatobiliary toxicity: Liver function tests should be performed before initiating treatment with Kisqali. After initiating treatment, liver function should be monitored (see Dosage & Administration and Adverse Reactions).
Based on the severity of the transaminase elevations, treatment with Kisqali may have to be interrupted, reduced or discontinued as described in Table 12 (see Dosage & Administration and Adverse Reactions).
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 Adverse Reactions and Pharmacology: Pharmacodynamics under Actions).
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 Dosage & Administration and Adverse Reactions).
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 Dosage & Administration, Interactions and Pharmacology: Pharmacodynamics under Actions). If treatment with a strong CYP3A4 inhibitor cannot be avoided, the dose should be reduced to 400 mg once daily (see Dosage & Administration and Interactions).
Based on the observed QT prolongation during treatment, treatment with Kisqali may have to be interrupted, reduced or discontinued as described in Table 13 (see Dosage & Administration, Adverse Reactions and Pharmacology: Pharmacokinetics under Actions).
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: ILD/pneumonitis has been reported with CDK4/6 inhibitors including reports of fatal cases. In the 3 phase III clinical studies (MONALEESA-2 [A2301], MONALEESA-7 [E2301-NSAI] and MONALEESA-3 [F2301]), ILD (any grade 0.3%, including 0.1% grade 3) was reported in the Kisqali-treated group, with no cases in the placebo-treated group. Pneumonitis (any grade 0.6%, versus 0.4%) was reported in the Kisqali- and placebo-treated groups, respectively, with no grade 3 or 4 events in either treatment group. Additional cases of ILD/pneumonitis have been observed with Kisqali in the post-marketing setting (see Adverse Reactions).
Based on the severity of the ILD/pneumonitis, which may be fatal, Kisqali may require dose interruption, reduction or discontinuation as described in Table 14 (see Dosage & Administration).
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 14 (see Dosage & Administration).
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 Interactions). 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.
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 Interactions). Caution is recommended in case of concomitant use with sensitive CYP3A4 substrates with a narrow therapeutic index and the SmPC 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 Dosage & Administration and Pharmacology: Pharmacokinetics under Actions).
Soya lecithin: Kisqali contains soya lecithin. Patients who are hypersensitive to peanut or soya should not take Kisqali (see Contraindications).
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 Adverse Reactions).
Use in Pregnancy: 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 Use in Pregnancy & Lactation).