IMPORTANT SAFETY INFORMATION


Interstitial lung disease/pneumonitis. Severe, life-threatening, or fatal interstitial lung disease (ILD) and/or pneumonitis can occur in patients treated with KISQALI and other CDK4/6 inhibitors...

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Indications. KISQALI® (ribociclib) 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

Straightforward 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 tablets) 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 tablets) 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

 

Only KISQALI—dose adjustments with no need for a new prescription or additional cost to your patient mid-cycle1

Single-strength 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 a stepwise order by reducing the number of tablets taken
  • Dose modification of KISQALI is recommended based on individual safety and tolerability
  • If dose reduction below 200 mg/day is required, discontinue treatment

 

Convenient Packaging Options

2 preferred treatments in 1 simple package

Available for first-line use in premenopausal and postmenopausal women

Available in all 3 approved dose options: KISQALI® (ribociclib) 600 mg (three 200-mg tablets), 400 mg (two 200-mg tablets), and 200 mg (one 200-mg tablet), with FEMARA® (letrozole) 2.5 mg (one 2.5-mg tablet).

 

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

1 Package

  • contains a 28-day supply of both KISQALI and FEMARA

1 Prescription

  • for convenient prescription writing

1 Co-pay

  • covers both KISQALI and FEMARA

Prescribe the KISQALI FEMARA Co-Pack with 1 prescription.

- Write the prescription 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 Adjustments

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

Dose Modification and Management for Interstitial Lung Disease/Pneumonitis
ILD/PNEUMONITIS1
Grade 1 (asymptomatic)
   • No dose interruption or adjustment is required
   • Initiate appropriate medical therapy and monitor as clinically indicated
Grade 2 (asymptomatic)
Dose interruption until recovery to Grade ≤ 1 then consider resuming KISQALI at the next lower dose level
   • If Grade 2 recurs, discontinue KISQALI
Grade 3 (severe symptomatic) or Grade 4
Discontinue KISQALI


Grading according to CTCAE Version 4.03.
An individualized benefit-risk assessment should be performed when considering resuming KISQALI.

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

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.

 

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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; ILD=interstitial lung disease; LHRH=luteinizing hormone-releasing hormone; mPFS=median progression-free survival; QTcF=QT interval corrected by Fridericia's formula; TB=total bilirubin; ULN=upper limit of normal.

References: 1. Kisqali [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2019. 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; 2019. 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.

 

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 

The KISQALI® (ribociclib) FEMARA® (letrozole) Co-Pack 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
Interstitial lung disease/pneumonitis. Severe, life-threatening, or fatal interstitial lung disease (ILD) and/or pneumonitis can occur in patients treated with KISQALI and other CDK4/6 inhibitors.

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”), 1.1% of KISQALI-treated patients had ILD/pneumonitis of any grade, 0.3% had grade 3 or 4, and 0.1% had a fatal outcome. Additional cases of ILD/pneumonitis have been observed in the postmarketing setting, with fatalities reported.

Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis, which may include hypoxia, cough, and dyspnea. In patients who have new or worsening respiratory symptoms suspected to be due to ILD or pneumonitis, interrupt treatment with KISQALI immediately and evaluate the patient. Permanently discontinue treatment with KISQALI in patients with recurrent symptomatic or severe ILD/pneumonitis.

QT interval prolongation. KISQALI® (ribociclib) and the KISQALI® (ribociclib) FEMARA® (letrozole) 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 (MRHD) 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.