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 Once-Daily Dosing

Flexible dosing with either an AI or with fulvestrant1

KISQALI + fulvestrant

 
WEEK 1
WEEK 2
WEEK 3
WEEK 4
SUBSEQUENT
CYCLES
KISQALI
600 mg (3 x 200-mg tablets) orally once daily (3 weeks on, 1 week off)
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 intramuscularly, administered on Days 1, 15, 29, and once monthly thereafter.1 Please refer to the full Prescribing Information for fulvestrant

 

KISQALI + AI

 
WEEK 1
WEEK 2
WEEK 3
WEEK 4
KISQALI
600 mg (3 x 200-mg tablets) orally once daily (3 weeks on, 1 week off)
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 patients, an LHRH agonist should be administered according to current clinical practice guidelines when given with KISQALI and an AI

 

The KISQALI FEMARA Co-Pack

THE ONLY CO-PACK IN METASTATIC BREAST CANCER2

Available for first-line use in premenopausal and postmenopausal women2

Co-pack including one 28-day cycle of FEMARA

A convenient prescription process for you and your patients:

  • 1 Package
  • contains a 28-day supply of both KISQALI and FEMARA
    • Separate packages not needed
  • 1 Prescription
  • for convenient prescription writing
  • 1 Co-pay
  • covers both KISQALI and FEMARA

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). When prescribing KISQALI and fulvestrant, 2 prescriptions are needed.

 

Dose Adjustments

KISQALI—the only CDK4/6 inhibitor THAT OFFERS dose adjustments with no need for a new prescription or additional cost to patient mid-cycle

ONE TABLET STRENGTH 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
  • Dose adjustments for adverse reactions 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
  • KISQALI can be taken with or without food

 

Straightforward dose adjustments1

Interstitial lung disease/pneumonitis
Grade 1 (asymptomatic)
  • No dose interruption or adjustment is required
  • Initiate appropriate medical therapy and monitor as clinically indicated
Grade 2 (symptomatic)

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

  • For grade 2 ILD/pneumonitis, an individualized benefit-risk assessment should be performed when considering resuming KISQALI

Neutropenia
Grade 1 or Grade 2
(ANC 1000/mm3 - < LLN)

No dose adjustment required

Grade 3 (afebrile)
(ANC 500/mm3 - <1000/mm3)

Interrupt dose until recovery to grade ≤2

  • Resume at same dose
  • If grade 3 recurs, interrupt dose until recovery; resume at next lower dose
Grade 3 (febrile)
or Grade 4 (ANC <500/mm3)

Interrupt dose until recovery to grade ≤2; resume at next lower dose

QT prolongation
ECGs with QTcF >480 ms

Interrupt dose until recovery to <481 ms

  • If first occurrence, resume at next lower dose
  • If QTcF ≥481 ms recurs, interrupt dose until QTcF resolves to <481 ms; then resume at next lower dose
ECGs with QTcF >500 ms

Interrupt dose if QTcF >500 ms; on recovery to <481 ms, resume at next lower dose

  • Permanently discontinue if QTcF interval prolongation is either >500 ms or >60 ms change from baseline AND associated with torsades de pointes, polymorphic ventricular tachycardia, unexplained syncope, or signs/symptoms of serious arrhythmia

ALT and/or AST elevation

ALT and/or AST elevation without TB increase >2 x ULN
Grade 1 (>ULN - 3 x ULN) or Grade 2 at baseline (>3 - 5 x ULN)

No dose adjustment required

New Grade 2
(>3 - 5 x ULN)

Interrupt dose until recovery to ≤ baseline; resume at same dose

  • If grade 2 recurs, resume at next lower dose
Grade 3
(>5 - 20 x ULN)

Interrupt dose until recovery to ≤ baseline; resume at next lower dose

  • If grade 3 recurs, discontinue
Grade 4 (>20 x ULN) or Grade ≥2 with TB >2 x ULN without cholestasis

Discontinue

Other Toxicities table

Other toxicities
Grade 1 or Grade 2

No dose adjustment required; initiate appropriate medical therapy and monitor as clinically indicated

Grade 3

Interrupt dose until recovery to grade ≤1; resume at same dose

  • If grade 3 recurs, resume at next lower dose
Grade 4

Discontinue

  • Grading criteria from CTCAE v4.03. Adverse reactions not requiring a dose adjustment are not shown. Initiate appropriate medical therapy as clinically indicated
  • Grade 3 neutropenia with single episode of fever >38.3°C or >38°C for more than 1 hour and/or concurrent infection
  • ECGs should be assessed prior to initiation of treatment. Repeat ECGs at approximately Day 14 of the first cycle and at the beginning of the second cycle, and as clinically indicated. In case of QTcF prolongation at any given time during treatment, more frequent ECG monitoring is recommended
  • Clinical judgment of the treating physician should guide the management plan of each patient based on individual benefit-risk assessment

 

For information about access, continue to the next page >

AI=aromatase inhibitor; ALT=alanine aminotransferase; ANC=absolute neutrophil count; AST=aspartate aminotransferase; CDK=cyclin-dependent kinase; CTCAE=Common Terminology Criteria for Adverse Events; ECG=electrocardiogram; ILD=interstitial lung disease; LHRH=luteinizing hormone-releasing hormone; LLN=lower limit of normal; 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; 2020. 2. Kisqali Femara Co-Pack [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2020.

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.