KISQALI Film-coated tablet Ref.[8836] Active ingredients: Ribociclib

Treatment with Kisqali should be initiated by a physician experienced in the use of anticancer therapies.

HR-positive, HER2-negative testing

Patient selection for treatment with Kisqali based on the tumour expression of HR and HER2 should be assessed by a CE-marked in vitro diagnostic (IVD) medical device with the corresponding intended purpose. If the CE-marked IVD is not available, an alternative validated test should be used.

Posology

Early breast cancer

The recommended dose is 400 mg (two 200 mg film-coated tablets) of ribociclib once daily for 21 consecutive days followed by 7 days off treatment, resulting in a complete cycle of 28 days. In patients with early breast cancer, Kisqali should be taken until completion of 3 years of treatment or until disease recurrence or unacceptable toxicity occur.

When Kisqali is used in combination with an aromatase inhibitor (AI), the AI should be taken orally once daily continuously throughout the 28-day cycle. Please refer to the Summary of Product Characteristics (SmPC) of the AI for additional details.

In pre- or perimenopausal women, or in men, the aromatase inhibitor should be combined with a LHRH agonist.

Advanced or metastatic breast cancer

The recommended dose is 600 mg (three 200 mg film-coated tablets) of ribociclib once daily for 21 consecutive days followed by 7 days off treatment, resulting in a complete cycle of 28 days. In patients with advanced or metastatic breast cancer, the treatment should be continued as long as the patient is deriving clinical benefit from therapy or until unacceptable toxicity occurs.

When Kisqali is used in combination with an AI, the AI should be taken orally once daily continuously throughout the 28-day cycle. Please refer to the Summary of Product Characteristics (SmPC) of the AI for additional details.

When Kisqali is used in combination with fulvestrant, fulvestrant is administered intramuscularly on days 1, 15 and 29, and once monthly thereafter. Please refer to the SmPC of fulvestrant for additional details.

Treatment of pre- and perimenopausal women with the approved Kisqali combinations should also include an LHRH agonist in accordance with local clinical practice.

Dose modifications

Management of severe or intolerable adverse reactions (ARs) may require temporary dose interruption, reduction or discontinuation of Kisqali. If dose reduction is required, the recommended dose reduction guidelines are listed in Table 1.

Table 1. Recommended dose modification guidelines:

^* If further dose reduction below 200 mg/day is required, the treatment should be permanently discontinued.

Tables 2, 3, 4, 5 and 6 summarise recommendations for dose interruption, reduction or discontinuation of Kisqali in the management of specific ARs. The clinical judgement of the treating physician should guide the management plan of each patient based on individual benefit/risk assessment (see section 4.4).

Complete blood counts (CBC) should be performed before initiating treatment with Kisqali. After initiating treatment CBC should be monitored every 2 weeks for the first 2 cycles, at the beginning of each of the subsequent 4 cycles, then as clinically indicated.

Table 2. Dose modification and management – Neutropenia:

^* Grading according to CTCAE Version 4.03 (CTCAE = Common Terminology Criteria for Adverse Events)
^** Grade 3 neutropenia with a single fever >38.3°C (or 38°C and above for more than one hour and/or concurrent infection)
ANC = absolute neutrophil count; LLN = lower limit of normal

Liver function tests (LFTs) should be performed before initiating treatment with Kisqali. After initiating treatment LFTs should be performed every 2 weeks for the first 2 cycles, at the beginning of each of the subsequent 4 cycles, then as clinically indicated. If grade ≥2 abnormalities are noted, more frequent monitoring is recommended.

Table 3. Dose modification and management – Hepatobiliary toxicity:

^* Grading according to CTCAE Version 4.03 (CTCAE = Common Terminology Criteria for Adverse Events)
^** Baseline = prior to treatment initiation
ULN = upper limit of normal

ECG should be assessed before initiating treatment with Kisqali in all patients.

Treatment with Kisqali should be initiated only in patients with QTcF values less than 450 msec. After initiating treatment, ECG should be repeated at approximately day 14 of the first cycle, then as clinically indicated.

In case of QTcF prolongation during treatment, more frequent ECG monitoring is recommended in patients with early breast cancer and advanced or metastatic breast cancer.

Table 4. Dose modification and management – QT prolongation:

Note: If further dose reductions are required at the 200 mg dose, Kisqali should be discontinued.
^* QTcF = QT interval corrected by Fridericia’s formula.

Table 5. Dose modification and management – ILD/pneumonitis:

^* Grading according to CTCAE Version 4.03 (CTCAE = Common Terminology Criteria for Adverse Events)
^** An individualised benefit-risk assessment should be performed when considering resuming Kisqali.
ILD = interstitial lung disease

Table 6. Dose modification and management – Other toxicities*:

^* Excluding neutropenia, hepatotoxicity, QT interval prolongation and ILD/pneumonitis.
^** Grading according to CTCAE Version 4.03 (CTCAE = Common Terminology Criteria for Adverse Events)

Refer to the SmPC for the co-administered AI, fulvestrant or LHRH agonist for dose modification guidelines and other relevant safety information in the event of toxicity.

Dose modification for use of Kisqali with strong CYP3A4 inhibitors

Concomitant use of strong CYP3A4 inhibitors should be avoided and an alternative concomitant medicinal product with less potential to inhibit CYP3A4 inhibition should be considered. If patients must be given a strong CYP3A4 inhibitor concomitantly with ribociclib, the Kisqali dose should be reduced (see section 4.5).

In patients taking 600 mg ribociclib daily and in whom initiation of co-administration of a strong CYP3A4 inhibitor cannot be avoided, the dose should be reduced to 400 mg.

In patients taking 400 mg ribociclib daily and in whom initiation of co-administration of a strong CYP3A4 inhibitor cannot be avoided, the dose should be further reduced to 200 mg.

In patients who have had their dose reduced to 200 mg ribociclib daily and in whom initiation of co-administration of a strong CYP3A4 inhibitor cannot be avoided, Kisqali treatment should be interrupted.

Due to inter-patient variability, the recommended dose adjustments may not be optimal in all patients, therefore close monitoring of signs of toxicity is recommended. If the strong inhibitor is discontinued, the Kisqali dose should be changed to the dose used prior to the initiation of the strong CYP3A4 inhibitor after at least 5 half-lives of the strong CYP3A4 inhibitor (see sections 4.4, 4.5 and 5.2).

Special populations

Renal impairment

No dose adjustment is necessary in patients with mild or moderate renal impairment. A starting dose of 200 mg is recommended in patients with severe renal impairment. Kisqali has not been studied in breast cancer patients with severe renal impairment (see sections 4.4, 5.1 and 5.2).

Hepatic impairment

No dose adjustment is necessary in patients with early breast cancer with hepatic impairment (see section 5.2). In patients with advanced or metastatic breast cancer, no dose adjustment is necessary in patients with mild hepatic impairment (Child-Pugh class A); patients with moderate (Child-Pugh class B) and severe hepatic impairment (Child-Pugh class C) can have increased (less than 2-fold) exposure to ribociclib and the starting dose of 400 mg Kisqali once daily is recommended (see section 5.2).

Paediatric population

The safety and efficacy of Kisqali in children and adolescents aged below 18 years have not been established. No data are available.

Elderly

No dose adjustment is required in patients over 65 years of age (see section 5.2).

Method of administration

Kisqali should be taken orally once daily with or without food (see section 4.5). Patients should be encouraged to take their dose at approximately the same time each day, preferably in the morning. If the patient vomits after taking the dose or misses a dose, an additional dose should not be taken that day. The next prescribed dose should be taken at the usual time. The tablets should be swallowed whole and should not be chewed, crushed or split prior to swallowing. No tablet should be ingested if it is broken, cracked or otherwise not intact.

There is only limited experience with reported cases of overdose with Kisqali. In the event of an overdose, symptoms such as nausea and vomiting may occur. In addition, haematological (e.g. neutropenia, thrombocytopenia) toxicity and possible QTc prolongation may occur. General supportive care should be initiated in all cases of overdose as necessary.

1 year.

Pharmacy: Store in a refrigerator (2°C-8°C) for up to 10 months.

Patient: Store below 25°C for up to 2 months. Store in the original package.

PVC/PCTFE (polyvinylchloride/polychlorotrifluoroethylene) or PA/alu/PVC (polyamide/aluminium/polyvinylchloride) blisters containing 14 or 21 film-coated tablets.

Unit packs containing 21, 42 or 63 film-coated tablets and multipacks containing 63 (3 packs of 21), 126 (3 packs of 42) or 189 (3 packs of 63) film-coated tablets.

Not all pack sizes may be marketed.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.