IMPORTANT SAFETY INFORMATION


QT interval prolongation. KISQALI has been shown to prolong the QT interval in a concentration-dependent manner. Based on the observed QT prolongation during treatment, KISQALI may require...

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Indications. KISQALI is a kinase inhibitor indicated in combination with: an aromatase inhibitor for the treatment of pre/perimenopausal or postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer, as initial endocrine-based therapy; or fulvestrant for the treatment of postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer, as initial endocrine-based therapy or following disease progression on endocrine therapy

Dosing & Administration

Convenient Dosing

The only once-daily CDK4/6 inhibitor with no meal requirements1

Treatment-partner flexibility1

 
WEEK 1
WEEK 2
WEEK 3
WEEK 4
SUBSEQUENT
CYCLES
KISQALI
600 mg (3 x 200 mg) once daily for the first 21 consecutive days
Fulvestrant
500 mg
 
Day 1 injection
 
 
Day 15 injection (Cycle 1 only)
 
 
Repeat 28-day cycle
Once monthly
 
  • When given with KISQALI® (ribociclib) tablets, the recommended dose of fulvestrant is 500 mg, administered on Days 1, 15, 29, and once monthly thereafter. Please refer to the full Prescribing Information for fulvestrant1

 

 
WEEK 1
WEEK 2
WEEK 3
WEEK 4
KISQALI
600 mg (3 x 200 mg) once daily for the first 21 consecutive days
AI
Once daily throughout the 28-day cycle, may be taken at the same time as KISQALI
 
 
  • Please refer to the full Prescribing Information for the recommended dose of the chosen AI
  • In premenopausal women
    • An LHRH agonist should be administered according to current clinical practice guidelines when given with KISQALI and an AI
    • KISQALI, an AI, and an LHRH agonist can all be started on Day 1 with no need to wait 4 weeks after initiating the LHRH agonist1,2

 

The only CDK4/6 inhibitor to allow dose adjustments with no need for a new prescription or co-pay* mid-cycle1

CONVENIENT TABLETSa FOR SIMPLE DOSE ADJUSTMENTS1
KISQALI (ribociclib) dose adjustments to reduce the number of tablets taken KISQALI (ribociclib) dose adjustments to reduce the number of tablets taken

a200-mg tablets.

  • Dose adjustments for ARs should be made in stepwise order by reducing the number of tablets taken1
  • Dose modification of KISQALI is recommended based on individual safety and tolerability1
  • If dose reduction below 200 mg/day is required, discontinue treatment1

*May be applicable after appropriate treatment determination.

 

Convenient Packaging Options

Simplify prescribing with the first and only co-pack in mBC

Available for first-line use in premenopausal and postmenopausal women

Co-pack including one 28-day cycle of KISQALI (ribociclib) and one 28-day cycle of FEMARA

1 Package

  • One 28-day cycle of both KISQALI and FEMARA® (letrozole)

1 Prescription

  • One single package for convenient prescription writing

1 Co-pay

  • A single co-pay covers both KISQALI and FEMARA
For KISQALI + any AI or fulvestrant, 2 prescriptions should be written1,3
For KISQALI FEMARA Co-Pack, 1 prescription should be written1,3
600 mg
NDC 0078-0874-63
600 mg
NDC 0078-0923-61
400 mg
NDC 0078-0867-42
400 mg
NDC 0078-0916-61
200 mg
NDC 0078-0860-01
200 mg
NDC 0078-0909-61

Prescribe the KISQALI FEMARA Co-Pack with 1 prescription.

- Write the prescription as illustrated above and specify the KISQALI dose: 600 mg, 400 mg, or 200 mg
- For premenopausal patients, write a separate prescription for the LHRH agonist of your choice
- KISQALI is also available to be prescribed with the endocrine therapy of your choice

Dose Modifications

Dose modifications for specific adverse reactions1,a

Consistent first-line efficacy across the MONALEESA trials, including those with dose reductions4

Across all 3 phase III trials, 43% of women (352/818) experienced ≥1 dose reduction with first-line KISQALI + ET. For patients treated with KISQALI + ET and had ≥1 dose reduction, the mPFS in the MONALEESA-2, MONALEESA-3 (first-line cohort), and MONALEESA-7 trials were 25.3 months, not estimable, and 27.5 months, respectively. Results are based on a post-hoc analysis; efficacy in the placebo comparator arm was not assessed.4

Neutropenia
Neutropenia
Occurrence
Interrupt
Resume KISQALI
Grade 3 (afebrile)
First
Second
Until resolution to grade ≤2
At same dose
At next lower dose
Grade 3 (febrileb) or Grade 4
Any

Neutropenia

QT prolongation (QTcF by ECG)
Occurrence
Interrupt
Resume KISQALI
>480 ms
>500 ms
Any
Until resolution to <481 ms
At next lower dose
>500 ms with clinical symptomsc
>60 ms increase from baseline with clinical symptomsc
Any
Discontinue treatment

ALT and/or AST elevation without TB increase >2 x ULN (postbaseline)
Occurrence
Interrupt
Resume KISQALI
Grade 2
Grade 3
First
Second
First
Second
Until resolution to ≤ baseline levels
At same dose
At next dose
Discontinue treatment
Grade 4 or grade ≥2 with TB >2 X ULN without cholestasis
Any
Discontinue treatment

Other toxicities
Occurrence
Interrupt
Resume KISQALI
Grade 3
First
Second
Until resolution to grade ≤1
At same dose
At next lower dose
Grade 4
Any
Discontinue treatment

aGrading criteria from CTCAE v4.03. Adverse reactions not requiring a dose adjustment are not shown. Initiate appropriate medical therapy as clinically indicated.
bGrade 3 neutropenia with single episode of fever >38.3°C or >38°C for more than 1 hour and/or concurrent infection. Clinical judgment of the treating physician should guide the management plan of each patient based on individual benefit/risk assessment.
cIncludes clinical symptoms of torsades de pointes, polymorphic ventricular tachycardia, unexplained syncope, or signs/symptoms of serious arrhythmia.

 

For information about mechanism of action, continue to the next page >

AI=aromatase inhibitor; ALT=alanine aminotransferase; ARs=adverse reactions; AST=aspartate aminotransferase; CDK=cyclin-dependent kinase; CTCAE=Common Terminology Criteria for Adverse Events; ECG=electrocardiogram; ET=endocrine therapy; HER2-=human epidermal growth factor receptor 2-negative; HR+=hormone receptor-positive; LHRH=luteinizing hormone-releasing hormone; mBC=metastatic breast cancer; mPFS=median progression-free survival; QTcF=QT interval corrected by Friderica's formula; TB=total bilirubin; ULN=upper limit of normal.

References: 1. Kisqali [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2018. 2. Tripathy D, Im S–A, Colleoni M, et al. Ribociclib plus endocrine therapy for premenopausal women with hormone receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. Lancet Oncol. 2018;19(7):904-915. 3. Kisqali Femara Co-Pack [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2018. 4. Beck JT, Neven P, Sohn J, et al. Ribociclib treatment benefit in patients with advanced breast cancer with ≥1 dose reduction: data from the MONALEESA-2, -3, and -7 trials. Poster presented at: San Antonio Breast Cancer Symposium; December 4-8, 2018; San Antonio, TX. Poster P6-18-06.

 

Indication
KISQALI® (ribociclib) tablets is a kinase inhibitor indicated in combination with:
  • an aromatase inhibitor for the treatment of pre/perimenopausal or postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer, as initial endocrine-based therapy; or
  • fulvestrant for the treatment of postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer, as initial endocrine-based therapy or following disease progression on endocrine therapy

The KISQALI® (ribociclib) FEMARA® (letrozole) Co-Pack tablets is indicated as initial endocrine-based therapy for the treatment of pre/perimenopausal or postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer.

IMPORTANT SAFETY INFORMATION
QT interval prolongation. KISQALI and the KISQALI FEMARA Co-Pack have been shown to prolong the QT interval in a concentration-dependent manner. Based on the observed QT prolongation during treatment, KISQALI may require dose interruption, reduction, or discontinuation. Across clinical trials in patients with advanced or metastatic breast cancer treated with KISQALI in combination with an aromatase inhibitor or fulvestrant (“KISQALI treatment groups”), 14 of 1054 patients (1%) had >500 ms postbaseline QTcF value, and 59 of 1054 (6%) had a >60 ms increase from baseline in QTcF intervals. These ECG changes were reversible with dose interruption and most occurred within the first 4 weeks of treatment. No cases of torsades de pointes were reported. In MONALEESA-2, on the KISQALI + letrozole treatment arm, there was 1 (0.3%) sudden death in a patient with grade 3 hypokalemia and grade 2 QT prolongation. No cases of sudden death were reported in MONALEESA-7 or MONALEESA-3.

Assess ECG prior to initiation of treatment. Initiate treatment with KISQALI or the KISQALI FEMARA Co-Pack only in patients with QTcF values <450 ms. Repeat ECG at approximately Day 14 of the first cycle, at the beginning of the second cycle, and as clinically indicated. Monitor serum electrolytes (including potassium, calcium, phosphorus, and magnesium) prior to the initiation of treatment, at the beginning of each of the first 6 cycles, and as clinically indicated. Correct any abnormality before starting therapy with KISQALI or the KISQALI FEMARA Co-Pack therapy.

Avoid the use of KISQALI or the KISQALI FEMARA Co-Pack in patients who already have or who are at significant risk of developing QT prolongation, including patients with:
  • long QT syndrome
  • uncontrolled or significant cardiac disease including recent myocardial infarction, congestive heart failure, unstable angina, and bradyarrhythmias
  • electrolyte abnormalities

Avoid using KISQALI or the KISQALI FEMARA Co-Pack with drugs known to prolong the QT interval and/or strong CYP3A inhibitors, as this may lead to prolongation of the QTcF interval.

Increased QT Prolongation With Concomitant Use of Tamoxifen. KISQALI is not indicated for concomitant use with tamoxifen. In MONALEESA-7, the observed mean QTcF increase from baseline was ≥10 ms higher in the tamoxifen + placebo subgroup compared with the NSAI + placebo subgroup. In the placebo arm, an increase of >60 ms from baseline occurred in 6 of 90 patients (7%) receiving tamoxifen, and in no patients receiving an NSAI. An increase of >60 ms from baseline in the QTcF interval was observed in 14 of 87 (16%) patients in the KISQALI and tamoxifen combination and in 18 of 245 (7%) patients receiving KISQALI plus an NSAI.

Hepatobiliary toxicity. Across clinical trials in patients with advanced or metastatic breast cancer, increases in transaminases were observed. Across all trials, grade 3 or 4 increases in alanine aminotransferase (ALT) (10% vs 2%) and aspartate aminotransferase (AST) (7% vs 2%) were reported in the KISQALI and placebo arms, respectively.

Among the patients who had grade ≥3 ALT/AST elevation, the median time to onset was 85 days and median time to resolution to grade ≤2 was 22 days for the KISQALI treatment groups.

In MONALEESA-2 and MONALEESA-3, concurrent elevations in ALT or AST greater than 3 times the ULN and total bilirubin greater than 2 times the upper limit of normal (ULN), with normal alkaline phosphatase, in the absence of cholestasis occurred in 6 (1%) patients and all patients recovered after discontinuation of KISQALI. No cases occurred in MONALEESA-7.

Perform liver function tests (LFTs) before initiating therapy with KISQALI or the KISQALI FEMARA Co-Pack. Monitor LFTs every 2 weeks for the first 2 cycles, at the beginning of each of the subsequent 4 cycles, and as clinically indicated. Based on the severity of the transaminase elevations, KISQALI may require dose interruption, reduction, or discontinuation. Recommendations for patients who have elevated AST/ALT grade ≥3 at baseline have not been established.

Neutropenia. Across clinical trials in patients with advanced or metastatic breast cancer, neutropenia was the most frequently reported adverse reaction (AR) (74%), and a grade 3/4 decrease in neutrophil count (based on laboratory findings) was reported in 58% of patients in the KISQALI treatment groups. Among the patients who had grade 2, 3, or 4 neutropenia, the median time to grade ≥2 was 16 days. The median time to resolution of grade ≥3 (to normalization or grade <3) was 12 days in the KISQALI treatment groups. Febrile neutropenia was reported in 1% of patients in the KISQALI treatment groups. Treatment discontinuation due to neutropenia was 0.8%.

Perform complete blood count (CBC) before initiating therapy with KISQALI or the KISQALI FEMARA Co-Pack. Monitor CBC every 2 weeks for the first 2 cycles, at the beginning of each of the subsequent 4 cycles, and as clinically indicated. Based on the severity of the neutropenia, KISQALI may require dose interruption, reduction, or discontinuation.

Embryofetal toxicity. Based on findings from animal studies and the mechanism of action, KISQALI can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of KISQALI to pregnant rats and rabbits during organogenesis caused embryofetal toxicities at maternal exposures that were 0.6 and 1.5 times the human clinical exposure, respectively, based on area under the curve. Letrozole caused embryofetal toxicities in rats and rabbits at maternal exposures that were below the maximum recommended human dose (MHRD) on a milligrams per square meter basis. Advise pregnant women of the potential risk to a fetus. Advise women of reproductive potential to use effective contraception during therapy with KISQALI or the KISQALI FEMARA Co-Pack and for at least 3 weeks after the last dose.

Adverse reactions. Across clinical trials of patients with advanced or metastatic breast cancer, the most common ARs reported in the KISQALI treatment groups (pooled incidence ≥20%) were neutropenia (74% vs 5%), nausea (45% vs 27%), infections (41% vs 30%), fatigue (33% vs 30%), diarrhea (30% vs 22%), leukopenia (30% vs 3%), vomiting (27% vs 16%), alopecia (24% vs 12%), headache (24% vs 22%), constipation (24% vs 16%), rash (21% vs 9%), and cough (21% vs 16%). The most common grade 3/4 ARs (reported at a pooled frequency >5%) were neutropenia (59% vs 1%), leukopenia (16% vs 3%), abnormal LFTs (9% vs 2%), and lymphopenia (5% vs 1%).

Laboratory abnormalities. Across clinical trials of patients with advanced or metastatic breast cancer, the most common laboratory abnormalities reported in the KISQALI-containing arm vs placebo arm (all grades, pooled incidence ≥20% and ≥5% higher than placebo arm) were leukocyte count decrease (94% vs 30%), neutrophil count decrease (93% vs 25%), hemoglobin decrease (66% vs 38%), lymphocyte count decrease (61% vs 26%), AST increase (47% vs 38%), ALT increase (44% vs 36%), creatinine increase (38% vs 13%), and platelet count decrease (31% vs 9%). The most common grade 3/4 laboratory abnormalities (incidence >5%) were neutrophil count decrease (59% vs 2%), leukocyte count decrease (32% vs 1%), lymphocyte count decrease (15% vs 4%), ALT increase (10% vs 2%), and AST increase (7% vs 2%).

Please see full Prescribing Information.