Kisqali
(Ribociclib)Kisqali Prescribing Information
Indications and Usage (KISQALI is indicated in combination with an aromatase inhibitor for the adjuvant treatment of adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative stage II and III early breast cancer at high risk of recurrence. KISQALI is indicated for the treatment of adults with HR-positive, HER2-negative advanced or metastatic breast cancer in combination with:
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Dosage and Administration (Important Administration Instructions KISQALI can be taken with or without food [see Clinical Pharmacology (12.3)] .Pre/perimenopausal women, or men, treated with the combination KISQALI plus an aromatase inhibitor or fulvestrant, should be treated with a luteinizing hormone-releasing hormone (LHRH) agonist according to current clinical practice standards.Patients should take their dose of KISQALI at approximately the same time each day, preferably in the morning. If the patient vomits after taking the dose, or misses a dose, no additional dose should be taken that day. The next prescribed dose should be taken at the usual time. KISQALI tablets should be swallowed whole (tablets should not be chewed, crushed or split prior to swallowing). No tablet should be ingested if it is broken, cracked, or otherwise not intact. Early Breast Cancer The recommended dosage of KISQALI is 400 mg (two 200 mg film-coated tablets) taken orally, once daily for 21 consecutive days followed by 7 days off in 28-day treatment cycles. KISQALI should be given in combination with an aromatase inhibitor. Refer to the Full Prescribing Information for the recommended dosage of the aromatase inhibitor.In patients with early breast cancer, treatment with KISQALI should continue for 3 years or until disease recurrence or unacceptable toxicity occurs.Advanced or Metastatic Breast Cancer The recommended dosage of KISQALI is 600 mg (three 200 mg film-coated tablets) taken orally, once daily for 21 consecutive days followed by 7 days off in 28-day treatment cycles. KISQALI should be given in combination with endocrine therapy (fulvestrant or an aromatase inhibitor). Refer to the Full Prescribing Information for the recommended dose of endocrine therapy. Dose Modifications for Adverse Reactions The recommended dose modifications for adverse reactions are listed in Table 1.
Tables 2, 3, 4, 5, 6, and 7 summarize recommendations for dose interruption, reduction, or discontinuation of KISQALI in the management of specific adverse reactions. Dose modification of KISQALI is recommended based on individual patient safety and tolerability.
Refer to the Full Prescribing Information for the coadministered aromatase inhibitor or fulvestrant for dose modification guidelines in the event of toxicity and other relevant safety information. Dose Modification for Use with Strong CYP3A Inhibitors Avoid concomitant use of KISQALI with strong CYP3A inhibitors and consider an alternative concomitant medication with less potential for CYP3A inhibition [see Drug Interactions (7.1)] .If a strong CYP3A inhibitor must be coadministered, reduce the KISQALI dose as shown in Table 8.
If the strong inhibitor is discontinued, change the KISQALI dose (after at least 5 half-lives of the strong CYP3A inhibitor) to the dose used prior to the initiation of the strong CYP3A inhibitor [see Drug Interactions (7.1), Clinical Pharmacology (12.3)] .Dose Modification for Hepatic Impairment The recommended dose modifications for patients with hepatic impairment are shown in Table 9[see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)] .
Review the Full Prescribing Information for the co-administered aromatase inhibitor or fulvestrant for dose modifications related to hepatic impairment. Dose Modification for Severe Renal Impairment The recommended starting dose is 200 mg KISQALI once daily for patients with severe renal impairment [see Use in Specific Populations (8.7), Clinical Pharmacology (12.3)] . | 09/2024 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Warnings and Precautions (Severe, life-threatening, or fatal interstitial lung disease (ILD) and/or pneumonitis can occur in patients treated with KISQALI and other CDK 4/6 inhibitors. In patients with early breast cancer (NATALEE) who received 400 mg KISQALI plus a non-steroidal aromatase inhibitor (NSAI), 1.5% of patients had ILD/pneumonitis (Grade 1-2).In patients with advanced or metastatic breast cancer (MONALEESA-2, MONALEESA-3, MONALEESA-7), 1.6% of patients had ILD/pneumonitis (any Grade, 0.4% had Grade 3-4, and 0.1% had a fatal outcome). Additional cases of ILD/pneumonitis have occurred in the postmarketing setting, some resulting in death[see Adverse Reactions (6.2)] .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 KISQALI immediately and evaluate the patient. Permanently discontinue KISQALI in patients with severe ILD/pneumonitis or any recurrent symptomatic ILD/pneumonitis [see Dosage and Administration (2.2)] .KISQALI has been shown to prolong the QT interval in a concentration-dependent manner [see Clinical Pharmacology (12.2)] .Avoid KISQALI in patients who are at significant risk of developing Torsades de Pointes (TdP), including those with:
Based on the observed QT prolongation during treatment, KISQALI may require dose interruption, reduction or discontinuation as described in Table 4 [see Dosage and Administration (2.2), Drug Interactions (7.4)] .In patients with early breast cancer (NATALEE) who received 400 mg KISQALI plus NSAI, 8 out of 2494 patients (0.3%) had > 500 ms post-baseline QTcF interval value and 50 out of 2494 patients (2%) had > 60 ms QTcF increase from baseline. QTcF prolongation was reversible with dose interruption. The majority of QTcF prolongation occurred within the first four weeks of KISQALI. There were no reported cases of Torsades de Pointes.In patients with advanced or metastatic breast cancer (MONALEESA-2, MONALEESA-3, and MONALEESA-7) who received 600 mg KISQALI plus NSAI or fulvestrant, 15 out of 1054 patients (1.4%) had a > 500 ms post-baseline QTcF value and 61 out of 1054 patients (6%) had a > 60 ms QTcF increase from baseline. QTcF prolongation was reversible with dose interruption. The majority of QTcF prolongation occurred within the first four weeks of KISQALI. There were no reported cases of Torsades de Pointes.In MONALEESA-2, in the KISQALI plus letrozole treatment arm, there was one (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 [see Adverse Reactions (6)] .Perform ECG in all patients prior to starting KISQALI. Initiate treatment with KISQALI only in patients with QTcF values less than 450 ms. Repeat ECG at approximately Day 14 of the first cycle, and as clinically indicated. Monitor serum electrolytes (including potassium, calcium, phosphorous and magnesium) prior to the initiation of KISQALI at the beginning of the first 6 cycles, and as clinically indicated. Correct any abnormality before starting KISQALI [see Dosage and Administration (2.2)] .In patients with early and advanced or metastatic breast cancer, drug-induced liver injury and increases in transaminases occurred with KISQALI.In patients with early breast cancer (NATALEE) treated with KISQALI, drug-induced liver injury was reported in 9 patients (0.4%), of which 5 were Grade ≥ 3, and 8 had resolved as of the data cutoff. There were 8 (0.3%) clinically confirmed Hy’s Law cases (including 4 out of 9 drug-induced liver injury mentioned above), 6 of which had resolved within 303 days and 2 of which were improving, all after discontinuation of KISQALI. Grade 3 or 4 increases in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) occurred in 8% and 4.7% respectively; including Grade 4 increases in ALT (1.5%) and AST (0.8%). In patients with advanced or metastatic breast cancer (MONALEESA-2, MONALEESA-7 and MONALEESA-3) treated with KISQALI Grade 3 or 4 increases in ALT and AST occurred in 11% and 8%, respectively. Among the patients who had Grade ≥ 3 ALT/AST elevation, the median time-to-onset was 92 days for the KISQALI plus aromatase inhibitor or fulvestrant treatment arms. The median time to resolution to Grade ≤ 2 was 21 days in the KISQALI plus aromatase inhibitor or fulvestrant treatment arms. In MONALEESA-2 and MONALEESA-3, concurrent elevations in ALT or AST greater than three times the ULN and total bilirubin greater than two times the ULN, with normal alkaline phosphatase, in the absence of cholestasis (Hy’s Law) occurred in 6 (1%) patients and all patients recovered after discontinuation of KISQALI. Perform liver function tests (LFTs) in all patients before initiating KISQALI. Monitor LFTs every 2 weeks for first 2 cycles, at the beginning of each of the subsequent 4 cycles, and as clinically indicated [see Dosage and Administration (2.2)] .Based on the severity of the transaminase elevations, KISQALI may require dose interruption, reduction, or discontinuation as described in Table 5 (Dose Modification and Management for Hepatobiliary Toxicity) [see Dosage and Administration (2.2)] .KISQALI causes concentration-dependent neutropenia. In patients with early breast cancer (NATALEE) who received KISQALI plus NSAI, 94%, including 45% of Grade 3 or 4, had a decrease in neutrophil counts (based on laboratory findings), 63% had an adverse reaction of neutropenia, and 0.3% had febrile neutropenia. The median time to Grade ≥ 2 neutropenia was 18 days. The median time to resolution of Grade ≥ 3 neutropenia to Grade < 3 was 10 days. Treatment discontinuation due to neutropenia was required in 1.1% of patients.In patients with advanced or metastatic breast cancer (MONALEESA-2, MONALEESA-7, and MONALEESA-3) who received KISQALI plus NSAI or fulvestrant, 75% had neutropenia, 62% had Grade 3 or 4 decrease in neutrophil count (based on laboratory findings), and 1.7% had febrile neutropenia. The median time to Grade ≥ 2 neutropenia was 17 days. The median time to resolution of Grade ≥ 3 neutropenia to Grade < 3 was 12 days. Treatment discontinuation due to neutropenia was required in 1% of patients. Perform a complete blood count (CBC) in all patients before initiating KISQALI. Monitor CBC every 2 weeks for the first 2 cycles, at the beginning of each subsequent 4 cycles, and as clinically indicated. Based on the severity of the neutropenia, KISQALI may require dose interruption, reduction, or discontinuation as described in Table 6 [see Dosage and Administration (2.2)] . | 09/2024 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
KISQALI is a kinase inhibitor indicated:
- in combination with an aromatase inhibitor for the adjuvant treatment of adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative stage II and III early breast cancer at high risk of recurrence. ()
1 INDICATIONS AND USAGEKISQALI is a kinase inhibitor indicated:
- in combination with an aromatase inhibitor for the adjuvant treatment of adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative stage II and III early breast cancer at high risk of recurrence.
- for the treatment of adults with HR-positive, HER2-negative advanced or metastatic breast cancer in combination with:
- an aromatase inhibitor as initial endocrine-based therapy; or
- fulvestrant as initial endocrine-based therapy or following disease progression on endocrine therapy.
1.1 Early Breast CancerKISQALI is indicated in combination with an aromatase inhibitor for the adjuvant treatment of adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative stage II and III early breast cancer at high risk of recurrence.1.2 Advanced or Metastatic Breast CancerKISQALI is indicated for the treatment of adults with HR-positive, HER2-negative advanced or metastatic breast cancer in combination with:- an aromatase inhibitor as initial endocrine-based therapy; or
- fulvestrant as initial endocrine-based therapy or following disease progression on endocrine therapy.
- for the treatment of adults with HR-positive, HER2-negative advanced or metastatic breast cancer in combination with:
- an aromatase inhibitor as initial endocrine-based therapy; or
- fulvestrant as initial endocrine-based therapy or following disease progression on endocrine therapy. ()
1 INDICATIONS AND USAGEKISQALI is a kinase inhibitor indicated:
- in combination with an aromatase inhibitor for the adjuvant treatment of adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative stage II and III early breast cancer at high risk of recurrence.
- for the treatment of adults with HR-positive, HER2-negative advanced or metastatic breast cancer in combination with:
- an aromatase inhibitor as initial endocrine-based therapy; or
- fulvestrant as initial endocrine-based therapy or following disease progression on endocrine therapy.
1.1 Early Breast CancerKISQALI is indicated in combination with an aromatase inhibitor for the adjuvant treatment of adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative stage II and III early breast cancer at high risk of recurrence.1.2 Advanced or Metastatic Breast CancerKISQALI is indicated for the treatment of adults with HR-positive, HER2-negative advanced or metastatic breast cancer in combination with:- an aromatase inhibitor as initial endocrine-based therapy; or
- fulvestrant as initial endocrine-based therapy or following disease progression on endocrine therapy.
KISQALI tablets are taken orally with or without food in combination with an aromatase inhibitor or fulvestrant. (
KISQALI tablets are taken orally with or without food in combination with an aromatase inhibitor or fulvestrant.
- Recommended starting dose: 400 mg orally (two 200 mg tablets) taken once daily with or without food for 21 consecutive days followed by 7 days off treatment.
- Recommended starting dose: 600 mg orally (three 200 mg tablets) taken once daily with or without food for 21 consecutive days followed by 7 days off treatment.
Dose interruption, reduction, and/or discontinuation may be required based on individual safety and tolerability.
KISQALI can be taken with or without food
Patients should take their dose of KISQALI at approximately the same time each day, preferably in the morning.
If the patient vomits after taking the dose, or misses a dose, no additional dose should be taken that day. The next prescribed dose should be taken at the usual time. KISQALI tablets should be swallowed whole (tablets should not be chewed, crushed or split prior to swallowing). No tablet should be ingested if it is broken, cracked, or otherwise not intact.
The recommended dosage of KISQALI is 600 mg (three 200 mg film-coated tablets) taken orally, once daily for 21 consecutive days followed by 7 days off in 28-day treatment cycles. KISQALI should be given in combination with endocrine therapy (fulvestrant or an aromatase inhibitor). Refer to the Full Prescribing Information for the recommended dose of endocrine therapy.
Level | KISQALI | |
Dose | Number of tablets | |
Early breast cancer | ||
| Starting dose | 400 mg/day | two 200 mg tablets |
| Dose reduction | 200 mg/day* | one 200 mg tablet |
Advanced or metastatic breast cancer | ||
| Starting dose | 600 mg/day | three 200 mg tablets |
| First dose reduction | 400 mg/day | two 200 mg tablets |
| Second dose reduction | 200 mg/day* | one 200 mg tablet |
| *If dose reduction below 200 mg/day is required, discontinue KISQALI. | ||
Tables 2, 3, 4, 5, 6, and 7 summarize recommendations for dose interruption, reduction, or discontinuation of KISQALI in the management of specific adverse reactions. Dose modification of KISQALI is recommended based on individual patient safety and tolerability.
Grade 1 (asymptomatic) | Grade 2 (symptomatic) | Grade 3 (severe symptomatic) or 4 (life-threatening) | |
ILD/Pneumonitis [see Warnings and Precautions (5.1)] | No dose interruption or adjustment is required. Initiate appropriate medical therapy and monitor as clinically indicated. | Dose interruption until recovery to Grade ≤ 1 then consider resuming KISQALI at the next lower dose level*. If Grade 2 recurs, discontinue KISQALI. | Discontinue KISQALI. |
| Abbreviation: ILD, interstitial lung disease. Grading according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. *An individualized benefit-risk assessment should be performed when considering resuming KISQALI. | |||
Grade 1 (< 10% body surface area (BSA) with active skin toxicity, no signs of systemic involvement) | Grade 2 (10%-30% BSA with active skin toxicity, no signs of systemic involvement) | Grade 3 (severe rash not responsive to medical management; > 30% BSA with active skin toxicity, signs of systemic involvement present; SJS*) | Grade 4 (any % BSA associated with extensive superinfection, with IV antibiotics indicated; life threatening consequences; TEN**) | |
Cutaneous adverse reactions, including SCARs [see Warnings and Precautions (5.2)] | No dose adjustment is required. Initiate appropriate medical therapy and monitor as clinically indicated. | Interrupt KISQALI until the etiology of the reaction has been determined. If the etiology is a SCAR, permanently discontinue KISQALI. If the etiology is not a SCAR, interrupt dose until recovery to Grade ≤ 1, then resume KISQALI at same dose level. If the cutaneous adverse reaction still recurs at Grade 3, resume KISQALI at the next lower dose level. | Permanently discontinue KISQALI. | |
| Abbreviations: BSA, body surface area; SCARs, severe cutaneous adverse reactions; SJS, Stevens-Johnson syndrome; TEN, toxic epidermal necrolysis. *SJS (Grade 3 and 4) is defined as skin sloughing covering < 10% BSA and 10%-30% BSA, respectively, with associated signs (e.g., erythema, purpura, epidermal detachment, and mucous membrane detachment). **TEN (Grade 4) is defined as skin sloughing covering ≥ 30% BSA with associated symptoms (e.g., erythema, purpura, epidermal detachment, and mucous membrane detachment). Grading according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. | ||||
QTcF* prolongation | Early breast cancer | Advanced or metastatic breast cancer |
> 480 ms and ≤ 500 ms | Interrupt KISQALI treatment and wait until QTcF resolves to ≤ 480 ms | |
| Resume at the same dose | Reduce to the next lower dose level | |
| If QTcF > 480 ms recurs, interrupt KISQALI treatment and wait until QTcF resolves to ≤ 480 ms, then resume at next lower dose level. | ||
> 500 ms | Interrupt KISQALI treatment and wait until QTcF resolves to ≤ 480 ms, then resume at next lower dose level. If QTcF > 500 ms recurs, discontinue KISQALI. | |
| Permanently discontinue KISQALI if QTcF interval prolongation is either > 500 ms or > 60 ms change from baseline AND associated with any of the following: Torsades de Pointes, polymorphic ventricular tachycardia, syncope, or signs/symptoms of serious arrhythmia. | ||
Note: If dose reduction below 200 mg/day is required, discontinue KISQALI.Electrocardiograms (ECGs) should be assessed prior to initiation of treatment in all patients. Repeat ECGs at approximately Day 14 of the first cycle, and as clinically indicated. In case of QTcF prolongation at any given time during treatment, monitor ECG more frequently, and as clinically indicated *QTcF = QT interval corrected by Fridericia’s formula. | ||
Grade 1 (> ULN – 3 x ULN) | Grade 2 (> 3 to 5 x ULN) | Grade 3 (> 5 to 20 x ULN) | Grade 4 (> 20 x ULN) | |
AST and/or ALT elevations from baseline*, WITHOUT increase in total bilirubin above 2 x ULN [see Warnings and Precautions (5.5)] | No dose adjustment is required. | Baseline* at < Grade 2: Dose interruption until recovery to ≤ baseline grade, then resume KISQALI at same dose level. If Grade 2 recurs, resume KISQALI at next lower dose level. ----------------------------- Baseline* at Grade 2: No dose interruption. | Dose interruption until recovery to ≤ baseline* grade, then resume at next lower dose level. If Grade 3 recurs, discontinue KISQALI. | Discontinue KISQALI. |
Combined elevations in AST and/or ALT WITH total bilirubin increase, in the absence of cholestasis [see Warnings and Precautions (5.5)] | If patients develop ALT and/or AST > 3 x ULN along with total bilirubin > 2 x ULN irrespective of baseline grade, discontinue KISQALI. | |||
| Perform Liver Function Tests (LFTs) before initiating treatment with KISQALI. Monitor LFTs every 2 weeks for the first 2 cycles, at the beginning of each subsequent 4 cycles, and as clinically indicated. If Grade ≥ 2 abnormalities are noted, monitor more frequently, and as clinically indicated. | ||||
| Abbreviations: AST, aspartate aminotransferase; ALT, alanine aminotransferase; ULN, upper limit of normal. *Baseline = prior to treatment initiation. Grading according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. | ||||
Grade 1 or 2 (ANC 1000/mm3– < LLN) | Grade 3 (ANC 500 - < 1000/mm3) | Grade 3 febrile* neutropenia | Grade 4 (ANC < 500/mm3) | |
Neutropenia [see Warnings and Precautions (5.6)] | No dose adjustment is required. | Dose interruption until recovery to Grade ≤ 2. Resume KISQALI at the same dose level. If toxicity recurs at Grade 3, dose interruption until recovery, then resume KISQALI at the next lower dose level. | Dose interruption until recovery of neutropenia to Grade ≤ 2. Resume KISQALI at the next lower dose level. | Dose interruption until recovery to Grade ≤ 2. Resume KISQALI at the next lower dose level. |
| Perform complete blood counts (CBCs) before initiating treatment with KISQALI. Monitor CBC every 2 weeks for the first 2 cycles, at the beginning of each subsequent 4 cycles, and as clinically indicated. | ||||
| Abbreviations: ANC, absolute neutrophil count; LLN, lower limit of normal. *Grade 3 neutropenia with single episode of fever > 38.3°C (or) 38°C or above for more than one hour and/or concurrent infection. Grading according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. | ||||
Grade 1 or 2 | Grade 3 | Grade 4 | |
Other Toxicities | No dose adjustment is required. Initiate appropriate medical therapy and monitor as clinically indicated. | Dose interruption until recovery to Grade ≤ 1 then resume KISQALI at same dose level. If Grade 3 recurs, resume KISQALI at the next lower dose level. | Discontinue KISQALI. |
| *Excluding interstitial lung disease (ILD)/pneumonitis, cutaneous adverse reactions, including severe cutaneous adverse reactions (SCARs), QT interval prolongation, hepatobiliary toxicity, and neutropenia. Grading according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. | |||
Refer to the Full Prescribing Information for the coadministered aromatase inhibitor or fulvestrant for dose modification guidelines in the event of toxicity and other relevant safety information.
Avoid concomitant use of KISQALI with strong CYP3A inhibitors and consider an alternative concomitant medication with less potential for CYP3A inhibition
If a strong CYP3A inhibitor must be coadministered, reduce the KISQALI dose as shown in Table 8.
Indication | Co-administration with Strong CYP3A Inhibitors |
Early breast cancer | Reduce the KISQALI dose to 200 mg once daily. |
Advanced or metastatic breast cancer | Reduce the KISQALI dose to 400 mg once daily. |
If the strong inhibitor is discontinued, change the KISQALI dose (after at least 5 half-lives of the strong CYP3A inhibitor) to the dose used prior to the initiation of the strong CYP3A inhibitor
Indication | Mild hepatic impairment (Child-Pugh class A) | Moderate and severe hepatic impairment (Child-Pugh class B or C) |
Early breast cancer | No dose adjustment is necessary | No dose adjustment is necessary |
Advanced or metastatic breast cancer | No dose adjustment is necessary | KISQALI 400 mg once daily |
Review the Full Prescribing Information for the co-administered aromatase inhibitor or fulvestrant for dose modifications related to hepatic impairment.
The recommended starting dose is 200 mg KISQALI once daily for patients with severe renal impairment
- Recommended starting dose: 400 mg orally (two 200 mg tablets) taken once daily with or without food for 21 consecutive days followed by 7 days off treatment. ()
2.1 Recommended DosageImportant Administration InstructionsKISQALI can be taken with or without food
[see Clinical Pharmacology (12.3)].Pre/perimenopausal women, or men, treated with the combination KISQALI plus an aromatase inhibitor or fulvestrant, should be treated with a luteinizing hormone-releasing hormone (LHRH) agonist according to current clinical practice standards.Patients should take their dose of KISQALI at approximately the same time each day, preferably in the morning.
If the patient vomits after taking the dose, or misses a dose, no additional dose should be taken that day. The next prescribed dose should be taken at the usual time. KISQALI tablets should be swallowed whole (tablets should not be chewed, crushed or split prior to swallowing). No tablet should be ingested if it is broken, cracked, or otherwise not intact.
Early Breast CancerThe recommended dosage of KISQALI is 400 mg (two 200 mg film-coated tablets) taken orally, once daily for 21 consecutive days followed by 7 days off in 28-day treatment cycles. KISQALI should be given in combination with an aromatase inhibitor. Refer to the Full Prescribing Information for the recommended dosage of the aromatase inhibitor.In patients with early breast cancer, treatment with KISQALI should continue for 3 years or until disease recurrence or unacceptable toxicity occurs.Advanced or Metastatic Breast CancerThe recommended dosage of KISQALI is 600 mg (three 200 mg film-coated tablets) taken orally, once daily for 21 consecutive days followed by 7 days off in 28-day treatment cycles. KISQALI should be given in combination with endocrine therapy (fulvestrant or an aromatase inhibitor). Refer to the Full Prescribing Information for the recommended dose of endocrine therapy.
- Recommended starting dose: 600 mg orally (three 200 mg tablets) taken once daily with or without food for 21 consecutive days followed by 7 days off treatment. ()
2.1 Recommended DosageImportant Administration InstructionsKISQALI can be taken with or without food
[see Clinical Pharmacology (12.3)].Pre/perimenopausal women, or men, treated with the combination KISQALI plus an aromatase inhibitor or fulvestrant, should be treated with a luteinizing hormone-releasing hormone (LHRH) agonist according to current clinical practice standards.Patients should take their dose of KISQALI at approximately the same time each day, preferably in the morning.
If the patient vomits after taking the dose, or misses a dose, no additional dose should be taken that day. The next prescribed dose should be taken at the usual time. KISQALI tablets should be swallowed whole (tablets should not be chewed, crushed or split prior to swallowing). No tablet should be ingested if it is broken, cracked, or otherwise not intact.
Early Breast CancerThe recommended dosage of KISQALI is 400 mg (two 200 mg film-coated tablets) taken orally, once daily for 21 consecutive days followed by 7 days off in 28-day treatment cycles. KISQALI should be given in combination with an aromatase inhibitor. Refer to the Full Prescribing Information for the recommended dosage of the aromatase inhibitor.In patients with early breast cancer, treatment with KISQALI should continue for 3 years or until disease recurrence or unacceptable toxicity occurs.Advanced or Metastatic Breast CancerThe recommended dosage of KISQALI is 600 mg (three 200 mg film-coated tablets) taken orally, once daily for 21 consecutive days followed by 7 days off in 28-day treatment cycles. KISQALI should be given in combination with endocrine therapy (fulvestrant or an aromatase inhibitor). Refer to the Full Prescribing Information for the recommended dose of endocrine therapy.
Dose interruption, reduction, and/or discontinuation may be required based on individual safety and tolerability. (
Level | KISQALI | |
Dose | Number of tablets | |
Early breast cancer | ||
| Starting dose | 400 mg/day | two 200 mg tablets |
| Dose reduction | 200 mg/day* | one 200 mg tablet |
Advanced or metastatic breast cancer | ||
| Starting dose | 600 mg/day | three 200 mg tablets |
| First dose reduction | 400 mg/day | two 200 mg tablets |
| Second dose reduction | 200 mg/day* | one 200 mg tablet |
| *If dose reduction below 200 mg/day is required, discontinue KISQALI. | ||
Tables 2, 3, 4, 5, 6, and 7 summarize recommendations for dose interruption, reduction, or discontinuation of KISQALI in the management of specific adverse reactions. Dose modification of KISQALI is recommended based on individual patient safety and tolerability.
Grade 1 (asymptomatic) | Grade 2 (symptomatic) | Grade 3 (severe symptomatic) or 4 (life-threatening) | |
ILD/Pneumonitis [see Warnings and Precautions (5.1)] | No dose interruption or adjustment is required. Initiate appropriate medical therapy and monitor as clinically indicated. | Dose interruption until recovery to Grade ≤ 1 then consider resuming KISQALI at the next lower dose level*. If Grade 2 recurs, discontinue KISQALI. | Discontinue KISQALI. |
| Abbreviation: ILD, interstitial lung disease. Grading according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. *An individualized benefit-risk assessment should be performed when considering resuming KISQALI. | |||
Grade 1 (< 10% body surface area (BSA) with active skin toxicity, no signs of systemic involvement) | Grade 2 (10%-30% BSA with active skin toxicity, no signs of systemic involvement) | Grade 3 (severe rash not responsive to medical management; > 30% BSA with active skin toxicity, signs of systemic involvement present; SJS*) | Grade 4 (any % BSA associated with extensive superinfection, with IV antibiotics indicated; life threatening consequences; TEN**) | |
Cutaneous adverse reactions, including SCARs [see Warnings and Precautions (5.2)] | No dose adjustment is required. Initiate appropriate medical therapy and monitor as clinically indicated. | Interrupt KISQALI until the etiology of the reaction has been determined. If the etiology is a SCAR, permanently discontinue KISQALI. If the etiology is not a SCAR, interrupt dose until recovery to Grade ≤ 1, then resume KISQALI at same dose level. If the cutaneous adverse reaction still recurs at Grade 3, resume KISQALI at the next lower dose level. | Permanently discontinue KISQALI. | |
| Abbreviations: BSA, body surface area; SCARs, severe cutaneous adverse reactions; SJS, Stevens-Johnson syndrome; TEN, toxic epidermal necrolysis. *SJS (Grade 3 and 4) is defined as skin sloughing covering < 10% BSA and 10%-30% BSA, respectively, with associated signs (e.g., erythema, purpura, epidermal detachment, and mucous membrane detachment). **TEN (Grade 4) is defined as skin sloughing covering ≥ 30% BSA with associated symptoms (e.g., erythema, purpura, epidermal detachment, and mucous membrane detachment). Grading according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. | ||||
QTcF* prolongation | Early breast cancer | Advanced or metastatic breast cancer |
> 480 ms and ≤ 500 ms | Interrupt KISQALI treatment and wait until QTcF resolves to ≤ 480 ms | |
| Resume at the same dose | Reduce to the next lower dose level | |
| If QTcF > 480 ms recurs, interrupt KISQALI treatment and wait until QTcF resolves to ≤ 480 ms, then resume at next lower dose level. | ||
> 500 ms | Interrupt KISQALI treatment and wait until QTcF resolves to ≤ 480 ms, then resume at next lower dose level. If QTcF > 500 ms recurs, discontinue KISQALI. | |
| Permanently discontinue KISQALI if QTcF interval prolongation is either > 500 ms or > 60 ms change from baseline AND associated with any of the following: Torsades de Pointes, polymorphic ventricular tachycardia, syncope, or signs/symptoms of serious arrhythmia. | ||
Note: If dose reduction below 200 mg/day is required, discontinue KISQALI.Electrocardiograms (ECGs) should be assessed prior to initiation of treatment in all patients. Repeat ECGs at approximately Day 14 of the first cycle, and as clinically indicated. In case of QTcF prolongation at any given time during treatment, monitor ECG more frequently, and as clinically indicated *QTcF = QT interval corrected by Fridericia’s formula. | ||
Grade 1 (> ULN – 3 x ULN) | Grade 2 (> 3 to 5 x ULN) | Grade 3 (> 5 to 20 x ULN) | Grade 4 (> 20 x ULN) | |
AST and/or ALT elevations from baseline*, WITHOUT increase in total bilirubin above 2 x ULN [see Warnings and Precautions (5.5)] | No dose adjustment is required. | Baseline* at < Grade 2: Dose interruption until recovery to ≤ baseline grade, then resume KISQALI at same dose level. If Grade 2 recurs, resume KISQALI at next lower dose level. ----------------------------- Baseline* at Grade 2: No dose interruption. | Dose interruption until recovery to ≤ baseline* grade, then resume at next lower dose level. If Grade 3 recurs, discontinue KISQALI. | Discontinue KISQALI. |
Combined elevations in AST and/or ALT WITH total bilirubin increase, in the absence of cholestasis [see Warnings and Precautions (5.5)] | If patients develop ALT and/or AST > 3 x ULN along with total bilirubin > 2 x ULN irrespective of baseline grade, discontinue KISQALI. | |||
| Perform Liver Function Tests (LFTs) before initiating treatment with KISQALI. Monitor LFTs every 2 weeks for the first 2 cycles, at the beginning of each subsequent 4 cycles, and as clinically indicated. If Grade ≥ 2 abnormalities are noted, monitor more frequently, and as clinically indicated. | ||||
| Abbreviations: AST, aspartate aminotransferase; ALT, alanine aminotransferase; ULN, upper limit of normal. *Baseline = prior to treatment initiation. Grading according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. | ||||
Grade 1 or 2 (ANC 1000/mm3– < LLN) | Grade 3 (ANC 500 - < 1000/mm3) | Grade 3 febrile* neutropenia | Grade 4 (ANC < 500/mm3) | |
Neutropenia [see Warnings and Precautions (5.6)] | No dose adjustment is required. | Dose interruption until recovery to Grade ≤ 2. Resume KISQALI at the same dose level. If toxicity recurs at Grade 3, dose interruption until recovery, then resume KISQALI at the next lower dose level. | Dose interruption until recovery of neutropenia to Grade ≤ 2. Resume KISQALI at the next lower dose level. | Dose interruption until recovery to Grade ≤ 2. Resume KISQALI at the next lower dose level. |
| Perform complete blood counts (CBCs) before initiating treatment with KISQALI. Monitor CBC every 2 weeks for the first 2 cycles, at the beginning of each subsequent 4 cycles, and as clinically indicated. | ||||
| Abbreviations: ANC, absolute neutrophil count; LLN, lower limit of normal. *Grade 3 neutropenia with single episode of fever > 38.3°C (or) 38°C or above for more than one hour and/or concurrent infection. Grading according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. | ||||
Grade 1 or 2 | Grade 3 | Grade 4 | |
Other Toxicities | No dose adjustment is required. Initiate appropriate medical therapy and monitor as clinically indicated. | Dose interruption until recovery to Grade ≤ 1 then resume KISQALI at same dose level. If Grade 3 recurs, resume KISQALI at the next lower dose level. | Discontinue KISQALI. |
| *Excluding interstitial lung disease (ILD)/pneumonitis, cutaneous adverse reactions, including severe cutaneous adverse reactions (SCARs), QT interval prolongation, hepatobiliary toxicity, and neutropenia. Grading according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. | |||
Refer to the Full Prescribing Information for the coadministered aromatase inhibitor or fulvestrant for dose modification guidelines in the event of toxicity and other relevant safety information.
Avoid concomitant use of KISQALI with strong CYP3A inhibitors and consider an alternative concomitant medication with less potential for CYP3A inhibition
If a strong CYP3A inhibitor must be coadministered, reduce the KISQALI dose as shown in Table 8.
Indication | Co-administration with Strong CYP3A Inhibitors |
Early breast cancer | Reduce the KISQALI dose to 200 mg once daily. |
Advanced or metastatic breast cancer | Reduce the KISQALI dose to 400 mg once daily. |
If the strong inhibitor is discontinued, change the KISQALI dose (after at least 5 half-lives of the strong CYP3A inhibitor) to the dose used prior to the initiation of the strong CYP3A inhibitor
Indication | Mild hepatic impairment (Child-Pugh class A) | Moderate and severe hepatic impairment (Child-Pugh class B or C) |
Early breast cancer | No dose adjustment is necessary | No dose adjustment is necessary |
Advanced or metastatic breast cancer | No dose adjustment is necessary | KISQALI 400 mg once daily |
Review the Full Prescribing Information for the co-administered aromatase inhibitor or fulvestrant for dose modifications related to hepatic impairment.
The recommended starting dose is 200 mg KISQALI once daily for patients with severe renal impairment
Tablet: 200 mg ribociclib (equivalent to 254.40 mg ribociclib succinate).
Film coated, light greyish violet, round, curved with beveled edges, debossed with “RIC” on one side and “NVR” on the other side.
Lactation: Advise not to breastfeed. (
It is not known if ribociclib is present in human milk. There are no data on the effects of ribociclib on the breastfed infant or on milk production. Ribociclib and its metabolites readily passed into the milk of lactating rats. Because of the potential for serious adverse reactions in breastfed infants from KISQALI, advise lactating women not to breastfeed while taking KISQALI and for at least 3 weeks after the last dose.
In lactating rats administered a single dose of 50 mg/kg, exposure to ribociclib was 3.56-fold higher in milk compared to maternal plasma.
None.