Ribociclib (Kisqali) Dosing, Monitoring, and Prescribing Responsibilities
Dosing Schedule
For advanced/metastatic breast cancer, start ribociclib at 600 mg orally once daily for 21 consecutive days followed by 7 days off in 28-day cycles, combined with either an aromatase inhibitor or fulvestrant. 1
- Take at approximately the same time each day, preferably in the morning 1
- Can be taken with or without food 1
- Swallow tablets whole; do not chew, crush, or split 1
- If a dose is vomited or missed, do not take an additional dose that day—resume at the usual time the next day 1
- Continue treatment until disease progression or unacceptable toxicity 1
Pre/perimenopausal women and men must receive concurrent LHRH agonist (e.g., goserelin) according to standard practice. 1
Baseline Monitoring Requirements
Before initiating ribociclib, obtain the following:
- Complete blood count (CBC) to assess baseline neutrophil count 1
- Liver function tests (LFTs): AST, ALT, and total bilirubin 1
- Electrocardiogram (ECG) to measure QTcF interval in all patients 1
- Pregnancy test in women of reproductive potential (ribociclib can cause fetal harm) 1
Ongoing Monitoring Schedule
Complete Blood Counts
- Every 2 weeks for the first 2 cycles 1
- At the beginning of each subsequent 4 cycles 1
- More frequently if Grade ≥3 neutropenia develops 1
Liver Function Tests
- Every 2 weeks for the first 2 cycles 1
- At the beginning of each subsequent 4 cycles 1
- More frequently if Grade ≥2 abnormalities are noted 1
Electrocardiograms
- At approximately Day 14 of the first cycle 1
- As clinically indicated thereafter 1
- More frequently if QTcF prolongation occurs at any time 1
Dose Adjustment Criteria
Neutropenia (Most Common Toxicity)
| Grade | ANC | Action |
|---|---|---|
| Grade 1–2 | 1000/mm³ to <LLN | No dose adjustment required [1] |
| Grade 3 | 500–<1000/mm³ | Interrupt until recovery to Grade ≤2, resume at same dose; if recurs, resume at next lower dose (400 mg) [1] |
| Grade 3 febrile neutropenia | Any ANC with fever >38.3°C or ≥38°C for >1 hour | Interrupt until recovery to Grade ≤2, resume at next lower dose (400 mg) [1] |
| Grade 4 | <500/mm³ | Interrupt until recovery to Grade ≤2, resume at next lower dose (400 mg) [1] |
Neutropenia occurred in 62% of patients (Grade 3/4) in pivotal trials but was manageable with dose modifications. 2
Hepatobiliary Toxicity
If AST/ALT >3× ULN with total bilirubin >2× ULN (in absence of cholestasis), permanently discontinue ribociclib regardless of baseline grade. 1
For isolated transaminase elevations without bilirubin elevation:
- Grade 2 (>3–5× ULN): Interrupt until recovery to ≤baseline grade, resume at same dose; if recurs, resume at next lower dose 1
- Grade 3 (>5–20× ULN): Interrupt until recovery to ≤baseline grade, resume at next lower dose; if recurs, discontinue 1
- Grade 4 (>20× ULN): Permanently discontinue 1
Abnormal liver function tests (Grade 3/4) occurred in 10.2% of patients receiving ribociclib plus letrozole. 2
QT Prolongation
| QTcF Interval | Action |
|---|---|
| >480 ms and ≤500 ms | Interrupt until QTcF ≤480 ms, resume at same dose; if recurs, resume at next lower dose [1] |
| >500 ms | Interrupt until QTcF ≤480 ms, resume at next lower dose; if recurs, discontinue [1] |
| >500 ms OR >60 ms change from baseline WITH Torsades de Pointes, polymorphic VT, syncope, or serious arrhythmia | Permanently discontinue [1] |
Dose Reduction Levels
| Level | Dose | Number of Tablets |
|---|---|---|
| Starting dose | 600 mg/day | Three 200 mg tablets [1] |
| First reduction | 400 mg/day | Two 200 mg tablets [1] |
| Second reduction | 200 mg/day | One 200 mg tablet [1] |
If dose reduction below 200 mg/day is required, discontinue ribociclib. 1
Real-world data demonstrate that dose reductions (occurring in 28–57% of patients) do not compromise efficacy, with no significant differences in 3-year PFS or OS between patients with and without dose reductions. 3, 4
Drug Interaction Precautions
Strong CYP3A Inhibitors
Avoid concomitant use of strong CYP3A inhibitors (e.g., clarithromycin, itraconazole, ketoconazole, ritonavir, voriconazole). 1
- If unavoidable, consider alternative medication with less CYP3A inhibition potential 1
- If no alternative exists, dose reduction may be necessary 1
QT-Prolonging Medications
Avoid concomitant use of medications known to prolong the QT interval. 1
- Review all concurrent medications for QT prolongation risk before initiating ribociclib 1
- If unavoidable, increase ECG monitoring frequency 1
Grapefruit Products
Instruct patients to avoid grapefruit and grapefruit juice, which can increase ribociclib exposure through CYP3A inhibition. 1
Prescribing Responsibilities
Patient Selection
Ribociclib is indicated for HR-positive, HER2-negative advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine-based therapy, or with fulvestrant as initial therapy or following disease progression on endocrine therapy. 1
NCCN guidelines designate aromatase inhibitor plus CDK4/6 inhibitor (including ribociclib) as a Category 1 first-line option for postmenopausal women and premenopausal women with ovarian ablation/suppression. 2
Efficacy Evidence
- Ribociclib plus letrozole improved median PFS to 25.3 months versus 16.0 months with letrozole alone (HR 0.56; 95% CI 0.45–0.70) in postmenopausal women. 2
- In premenopausal women (MONALEESA-7), ribociclib plus endocrine therapy improved median PFS to 24 months versus 13 months (HR 0.55; 95% CI 0.4–0.69) and 3.5-year OS to 70% versus 46% (HR 0.71; 95% CI 0.54–0.95). 2
Contraindications and Warnings
- Screen for pregnancy before initiating treatment; ribociclib can cause fetal harm. 1
- Assess baseline cardiac risk factors and obtain ECG in all patients. 1
- Monitor for interstitial lung disease/pneumonitis; permanently discontinue if Grade 3/4 occurs. 1
- Monitor for severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome and toxic epidermal necrolysis; permanently discontinue if confirmed. 1
Documentation Requirements
- Document baseline CBC, LFTs, and ECG results before first dose 1
- Document counseling regarding pregnancy prevention, drug interactions, and adverse event reporting 1
- Document concurrent LHRH agonist prescription for pre/perimenopausal women and men 1
Common Pitfalls to Avoid
Do not continue ribociclib after progression; there is no evidence supporting CDK4/6 inhibitor rechallenge or switching to another CDK4/6 inhibitor to overcome resistance. 5
Do not delay dose interruption for Grade 3 neutropenia; early intervention prevents febrile neutropenia without compromising efficacy. 1, 3
Do not overlook QTcF monitoring at Day 14 of Cycle 1; this is when QT prolongation typically manifests. 1
Do not prescribe ribociclib without confirming HR-positive, HER2-negative status; efficacy is limited to this molecular subtype. 2, 1
In older patients (≥70 years), anticipate higher rates of dose reduction (57% in real-world data) but recognize that efficacy is maintained regardless of frailty status. 4