Les renseignements du Formulaire de médicaments s’adressent aux professionnels de la santé. Il ne s’agit pas d’un avis médical. Certains des renseignements, y compris ceux sur le financement des médicaments anticancéreux, ne s’appliquent pas à tous les patients. Les plans de traitement du cancer sont propres à chaque patient. Si vous êtes un patient, veuillez parler avec votre équipe soignante pour comprendre comment ces renseignements s’appliquent à vous.
ribociclib
Ribociclib is an inhibitor of cyclin-dependent kinase (CDK) 4 and 6. The cyclin D-CDK4/6 complex regulates cell cycle progression through phosphorylation of the retinoblastoma protein (pRb). Inhibition of pRb phosphorylation arrests the cell cycle in the G1 phase, suppressing DNA synthesis and inhibiting cancer cell growth.
| Effects with food |
No clinically significant effect on Cmax and AUC when administered with a high-fat, high-calorie meal |
| Peak plasma levels |
1 to 4 hours |
| Time to reach steady state |
8 days |
| Bioavailability |
66% (after a single dose) |
| PPB |
70% |
| Distribution Sites |
Equally distributed between red blood cells and plasma |
| Cross blood brain barrier? |
Relatively low brain penetration observed in animals with intact blood brain barriers. |
- Ribociclib undergoes extensive hepatic metabolism mainly via CYP3A4.
- No major metabolite was considered to have clinically relevant contribution to efficacy and safety.
| Active metabolites |
No |
| Inactive metabolites |
Yes |
Ribociclib is eliminated mainly via the feces, with a small contribution from the renal route.
| Half-life |
32 hours |
| Feces |
69% (total dose); 17% unchanged |
| Urine |
23% (total dose); 12% unchanged |
- Breast cancer
Refer to the product monograph for a full list and details of approved indications.
Emetogenic Potential:
The adverse effects reported below were based on a phase III study of postmenopausal women with breast cancer, receiving ribociclib plus letrozole or placebo plus letrozole, where the incidence was > 2% more than placebo. Severe or life-threatening adverse effects from other sources and post-marketing are also included.
| ORGAN SITE | SIDE EFFECT* (%) | ONSET** | |||
|---|---|---|---|---|---|
| Cardiovascular | QT interval prolonged (5%) (1% severe) | E | |||
| Venous thromboembolism (4%) (may be severe) | E | ||||
| Dermatological | Alopecia (35%) | E | |||
| Rash, pruritus (24%) (may be severe) | I E | ||||
| Toxic epidermal necrolysis (rare) | E | ||||
| Gastrointestinal | Abdominal pain (21%) | E | |||
| Anorexia, weight loss (22%) | E | ||||
| Constipation (30%) | E | ||||
| Diarrhea (41%) (2% severe) | E | ||||
| Dry mouth (14%) | E | ||||
| Dyspepsia (11%) | I E | ||||
| Mucositis (16%) | E | ||||
| Nausea, vomiting (55%) (3% severe) | I | ||||
| General | Edema - limbs (19%) | E | |||
| Fatigue (43%) | E | ||||
| Hematological | Myelosuppression ± infection, bleeding (77%) (64% severe) | E | |||
| Hepatobiliary | ↑ LFTs (23%) (12% severe; <1% hepatotoxicity) | D | |||
| Metabolic / Endocrine | Abnormal electrolyte(s) (5%) (↓ Ca, ↓ K, ↓ PO4; 4% severe) | E | |||
| Musculoskeletal | Musculoskeletal pain (27%) | E | |||
| Nervous System | Dysgeusia (10%) | E | |||
| Headache (29%) | E | ||||
| Insomnia (17%) | E | ||||
| Syncope (2%) | E | ||||
| Ophthalmic | Dry eye (6%) | E | |||
| Watering eyes (12%) | E | ||||
| Renal | Creatinine increased (11%) (< 1% severe) | E | |||
| Respiratory | Dyspnea (16%) | E | |||
| Pneumonitis (rare) (may be severe) | E D | ||||
* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare"
may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal
reports.
** I = immediate (onset in hours to days)
E = early (days to weeks)
D = delayed (weeks to months)
L = late (months to years)
The most common side effects for ribociclib include myelosuppression ± infection, bleeding, nausea, vomiting, fatigue, diarrhea, alopecia, constipation, headache, musculoskeletal pain, rash, pruritus, and ↑ LFTs.
Neutropenia was the most frequently reported side effect in patients treated with ribociclib plus any combination. The median time to onset for Grade > 2 neutropenia was 17 days, while the median time to resolution to Grade < 3 was 12 days.
Drug induced liver injury [ALT or AST > 3 x upper limit of normal (ULN) and total bilirubin > 2 x ULN, without cholestasis] or Hy’s Law has been reported with ribociclib combination therapy. In patients treated with ribociclib plus letrozole or fulvestrant, recovery to normal levels occurred within 154 days or within 121 to 532 days, respectively, after ribociclib discontinuation.
Median time to onset of QTcF > 480 msec was 15 days regardless of combination and these changes were reversible upon withholding the dose or modification. QTc prolongation is expected to be maximal between days 8 to 21 of the 28-day cycle during steady state treatment.
Refer to protocol by which the patient is being treated.
Screen for hepatitis B virus in all cancer patients starting systemic treatment. Refer to the hepatitis B virus screening and management guideline.
Hypokalemia, hypomagnesemia and hypocalcemia should be corrected prior to starting or continuing ribociclib.
Ribociclib should be started only in patients with QTcF < 450 msec.
Pre/perimenopausal women, and men, treated with ribociclib and an aromatase inhibitor or fulvestrant should also be treated with luteinizing hormone-releasing hormone (LHRH) agonists according to local clinical practice.
Advanced or Metastatic Breast Cancer:
Oral: 600 mg/day on Days 1 to 21, followed by 7 days off treatment, in 28-day cycles
In combination with an aromatase inhibitor (e.g., letrozole) or fulvestrant. Refer to regimen monographs for dosing details.
Early Breast Cancer:
Refer to the product monograph for details.
Advanced or Metastatic Breast Cancer:
| Dose Level | Ribociclib Dose (mg/day) (21 days on, 7 days off) |
| 0 | 600 |
| -1 | 400 |
| -2 | 200 |
| -3 | Discontinue |
| Toxicity | Severity | Ribociclib Dose | |
| Neutropenia |
Grade 3 |
Hold dose until ANC > 1 x 109/L, then restart at the same dose level. If recurs, hold dose until ANC > 1 x 109/L, then restart with 1 dose level ↓. |
|
|
Grade 4 |
Hold dose until ANC > 1 x 109/L, then restart with 1 dose level ↓. |
||
| QTcF | > 480 msec |
Hold dose until QTcF resolves to < 480 msec, then restart with 1 dose level ↓. If recurs, hold dose until QTcF resolves to < 480 msec, then restart with 1 dose level ↓. |
|
| > 500 msec | Hold dose until QTcF resolves to < 480 msec, then restart with 1 dose level ↓. | ||
|
Torsade de Pointes, or polymorphic ventricular tachycardia, unexplained syncope or Signs/symptoms of serious arrhythmia |
Any | Discontinue. | |
| Bilirubin ≤ 2 x ULN | and |
AST and/or ALT >3 to 5 x ULN (Grade 2) |
If Baseline Grade 2: continue at current dose. If Baseline Grade 0-1: hold dose until ≤ baseline, then restart at the same dose. If recurs, hold dose until ≤ baseline, then restart with 1 dose level ↓. |
| and |
AST and/or ALT >5 to 20 x ULN (Grade 3) |
Hold dose until ≤ baseline, then restart with 1 dose level ↓. If recurs, discontinue. |
|
| and |
AST and/or ALT >20 x ULN (Grade 4) |
Discontinue. | |
| Bilirubin > 2 x ULN, in the absence of cholestasis |
and |
AST and/or ALT >3 x ULN (Grade > 2) irrespective of baseline |
Discontinue. |
| Interstitial lung disease (ILD)/pneumonitis | Grade 2 (symptomatic) | Hold dose until recovery to Grade < 1, then restart with 1 dose level ↓. | |
| Grade 3 or 4 | Discontinue. | ||
| Severe cutaneous reactions (e.g. progressive widespread skin rash often with blisters or mucosal lesions) | Any | Discontinue. | |
| Other related toxicity | Grade 3 |
Hold dose until Grade ≤ 1, then restart at same dose. If recurs, hold dose until Grade ≤ 1, then restart with 1 dose level ↓. |
|
| Grade 4 | Discontinue. | ||
Ribociclib has not been studied in patients with moderate or severe hepatic impairment (ALT or AST > 5 x ULN or total serum bilirubin > ULN [except documented Gilbert’s syndrome]).
Advanced or Metastatic Breast Cancer:
| Hepatic Impairment | Ribociclib Starting Dose |
| Mild (Child-Pugh class A) | No dose adjustment recommended |
| Moderate (Child-Pugh class B) | 400 mg once daily; initiate treatment only if benefit outweighs risk |
| Severe (Child-Pugh class C) | 400 mg once daily; initiate treatment only if benefit outweighs risk |
Advanced or Metastatic Breast Cancer:
| Creatinine Clearance† | Ribociclib Starting Dose |
| ≥ 30 | No dose adjustment recommended. |
| 15 to < 30 |
200 mg daily*; initiate treatment only if benefit outweighs risk. |
| < 15 | No data available. |
†Reported as eGFR (mL/min/1.73m2)
*No data in breast cancer patients; data from healthy or non-cancer patients with severe renal impairment.
No adjustment of the starting dose is required. No overall difference in safety was observed between patients over 65 years of age and younger patients.
No clinically relevant effects of gender on ribociclib pharmacokinetics parameters.
No clinically relevant effects of race on ribociclib pharmacokinetics parameters.
The safety and efficacy of ribociclib in pediatric patients have not been established.
-
Administer ribociclib with or without food, approximately at the same time each day, preferably in the morning.
-
Tablets should be swallowed whole and not chewed, crushed or split prior to swallowing. Tablets that are broken, cracked, or otherwise not intact should not be ingested.
-
If the patient vomits after taking ribociclib, do not give an extra dose; give the next dose at the usual time.
-
If a dose is missed, it should be skipped and the next dose given at the usual time, the next day. Patients should not take extra doses to make up for a missed dose.
-
Grapefruit, starfruit, Seville oranges, their juices or products should be avoided during ribociclib treatment.
-
Confirm the storage information that is listed on the product packaging. There is a new ribociclib supply that requires storage in a refrigerator between 2-8°C. Once dispensed, patients should store ribociclib between 20-25°C for up to 2 months. Keep in the original package to protect from moisture.
- Patients with hypersensitivity to this drug or to any ingredient in the formulation.
- Patients with untreated congenital long QT syndrome, a QTcF interval of ≥ 450 msec at baseline, and those who are at significant risk of developing QTc prolongation (for example, uncontrolled or significant cardiac disease including recent myocardial infarction, congestive heart failure, unstable angina and bradyarrhythmia).
- Ribociclib is associated with concentration-dependent QTc prolongation, with expected maximal QTc prolongation during steady state treatment between days 8 and 21 of the 28-day cycle.
- Exercise caution in patients who are suspected to be at an increased risk of Torsades de Pointes during treatment with a QT-prolonging drug.
- Avoid use in patients with uncorrected hypokalemia, hypomagnesemia, or hypocalcemia and other risk factors.
- Use in caution in patients at risk of thromboembolic events.
- Patients should exercise caution when driving or operating machinery due to syncope.
Other Drug Properties:
-
Carcinogenicity:
Unknown
-
Phototoxicity:
Unlikely
-
Genotoxicity:
No
-
Embryotoxicity:
Documented in animals
-
Fetotoxicity:
Documented in animals
-
Teratogenicity:
Documented in animals
-
Pregnancy:
Ribociclib is not recommended for use in pregnancy. Adequate contraception should be used by patients and their partners during treatment, and for at least 21 days after the last dose.
-
Excretion into breast milk:
Documented in animals
-
Breastfeeding:
Breastfeeding is not recommended during treatment and for at least 21 days after the last dose.
-
Fertility effects:
Probable
Documented in animal studies in male animals
- Ribociclib is primarily metabolized by CYP3A is a time-dependent inhibitor of CYP3A. Therefore, medicinal products which can influence CYP3A enzyme activity may alter the pharmacokinetics of ribociclib and ribociclib can affect the pharmacokinetics of co-administered CYP3A substrates. Ribociclib has weak inhibitory effects on CYP1A2 substrates though no induction of CYP1A2, CYP2B6, CYP2C9 or CYP3A4 was observed in vitro.
- Ribociclib may inhibit BCRP, OCT2, Multidrug and Toxic Compound Extrusion Protein-1 (MATE1) and human Bile Salt Export Pump (BSEP). Monitor patients closely when co-administering ribociclib and substrates of these transporters.
- There is no clinically relevant interaction with letrozole, exemestane, anastrozole or fulvestrant.
- There is no expected interaction with goserelin.
| AGENT | EFFECT | MECHANISM | MANAGEMENT |
|---|---|---|---|
| CYP3A4 inhibitors (e.g. ketoconazole, clarithromycin, ritonavir, fruit or juice from grapefruit, Seville oranges or starfruit) | ↑ ribociclib exposure (e.g. ritonavir ↑ ribociclib exposure by 3.2-fold) | ↓ metabolism of ribociclib | Avoid strong CYP3A4 inhibitors. If unavoidable, ↓ ribociclib dose by 200mg (i.e. from 600mg to 400mg). After discontinuation of strong CYP3A4 inhibitor, resume ribociclib dose used prior to initiating the CYP3A4 inhibitor (after a washout period of at least 5 half-lives). Monitor closely. |
| CYP3A4 inducers (e.g. phenytoin, rifampin, dexamethasone, carbamazepine, phenobarbital, St. John’s Wort, etc) | ↓ ribociclib exposure (e.g. rifampin ↓ ribociclib exposure by 89%) | ↑ metabolism of ribociclib | Avoid strong CYP3A4 inducers. |
| CYP3A4 substrates with narrow therapeutic index (e.g. alfentanil, cyclosporine, dihydroergotamine, ergotamine, everolimus, fentanyl, midazolam, pimozide, quinidine, sirolimus and tacrolimus) | ↑ CYP3A4 Substrate exposure (e.g. ribociclib ↑ midazolam exposure by 280%) | ↓ metabolism of CYP3A4 Substrate | Avoid CYP3A4 substrates with a narrow therapeutic index. If unavoidable, consider reducing dose of substrate. |
| Drugs that may prolong QT (e.g. amiodarone, procainamide, sotalol, venlafaxine, amitriptyline, sunitinib, methadone, chloroquine, clarithromycin, haloperidol, fluconazole, moxifloxacin, domperidone, ondansetron, etc) | ↑ risk of QT prolongation | Additive | Avoid concomitant use. If must co-administer, monitor as clinically indicated. |
| Drugs that disrupt electrolyte levels (e.g. loop/thiazide diuretics, laxatives, amphotericin B, high dose corticosteroids) | serum electrolyte imbalance | ↓ electrolyte levels | Avoid to the extent possible. |
| Drugs that reduce heart rate (e.g. beta blockers, calcium channel blockers, digoxin) | ↑ risk of arrhythmia | Avoid to the extent possible. | |
| Tamoxifen | ↑ risk of QT prolongation | ↑ tamoxifen exposure by 2-fold with co-administration | Combined use is not recommended. |
| Statins | ↑ risk of rhabdomyolysis | CDK inhibitors may ↑ statin exposure (Health Canada, 2025) | Consider close monitoring |
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
Refer to the hepatitis B virus screening and management guideline for monitoring during and after treatment.
| Monitor Type | Monitor Frequency |
|---|---|
CBC |
Baseline, every 2 weeks for the first 2 cycles, at the beginning of each subsequent 4 cycles and as clinically indicated |
Liver function tests |
Baseline, every 2 weeks for the first 2 cycles, at the beginning of each subsequent 4 cycles and as clinically indicated (more frequent monitoring required in patients with ≥ Grade 2 LFTs) |
Electrolytes, including potassium, magnesium, calcium, and phosphorous |
Baseline, at regular intervals during steady-state treatment in later cycles and as clinically indicated (for example, patients with QTc prolongation) |
ECG |
Baseline, repeat on day 14 of cycle 1, and then as clinically indicated (more frequent monitoring in patients at risk) |
Renal function tests |
Baseline and as clinically indicated |
Clinical toxicity assessment of infection, bleeding, thromboembolism (close monitoring in patients at risk), pneumonitis, gastrointestinal and skin effects, and fatigue |
At each visit |
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
Exceptional Access Program (EAP Website )
- ribociclib - For the treatment of patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER 2)-negative, unresectable locally advanced or metastatic breast cancer in combination with an aromatase inhibitor or fulvestrant according to clinical criteria
Hortobagyi, G. N. et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. New Engl. J. Med. 375, 1738–1748 (2016).
Product monograph: Kasqali (ribociclib). Novartis Pharmaceuticals. June 12, 2025.
Summary Safety Review - Cyclin-dependent Kinase Inhibitors (abemaciclib, palbociclib and ribociclib) and HMG-CoA Reductase Inhibitors (atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin and simvastatin) (Statins) - Assessing the Potential Risk of Rhabdomyolysis Due to Drug Interaction. Health Canada. Accessed April 25, 2025.
September 2025 Updated Pharmacokinetics, Adverse Effects, Dosing, Administration Guidelines, Pregnancy/Lactation, Interactions, and Monitoring sections
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
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