Drug Formulary information is intended for use by healthcare professionals. It is not intended to be medical advice. Some of the information, including information about funding for cancer drugs, does not apply to all patients. Cancer treatment plans are unique to each patient. If you are a patient, please speak with your healthcare team to understand how this information applies to you.
Severe weather warning in your area. Please stay indoors and stay safe. Read more
drug-monograph
palbociclib
Cancer Type
Breast
Other Names
Ibrance™
Appearance
Tablet
Funding Program
Exceptional Access Program
B - Mechanism of Action and Pharmacokinetics
Palbociclib is a selective, reversible small molecule inhibitor of cyclin-dependent kinases (CDK) 4 and 6. The drug inhibits cyclin D-CDK 4/6 complex activity, blocking cell cycle progression from G1 to S phase. Palbociclib in combination with an anti-estrogen agent inhibits cell proliferation and induction of cell senescence in estrogen receptor (ER) positive breast cancer models.
Absorption
| Bioavailability | 46% (mean) |
| Peak plasma levels | 4 to 12 hours |
| Time to reach steady state | 8 days |
| Effects with food | When administered with food, AUC and Cmax increased up to 22% and 26%, respectively; food had no significant impact on exposure variability. Palbociclib tablets may be taken with or without food. |
Distribution
| PPB | 85% |
Metabolism
Palbociclib undergoes hepatic metabolism via oxidation and sulfonation, primarily by CYP3A and sulfotransferase (SULT2A1) enzymes; acylation and glucuronidation are minor metabolic pathways.
| Inactive metabolites | Yes |
Elimination
| Half-life | 29 hours (mean plasma) |
| Feces | 74% (2% unchanged) |
| Urine | 18% (7% unchanged) |
C - Indications and Status
Health Canada Approvals:
- Breast cancer
Refer to the product monograph for a full list and details of approved indications.
D - Adverse Effects
Emetogenic Potential:
Minimal – No routine prophylaxis; PRN recommended
The following adverse effects occurred in patients with breast cancer treated with palbociclib plus fulvestrant in a Phase III study, where the incidence was at least 2% greater than the placebo plus fulvestrant arm. The table also includes severe or life-threatening adverse effects from other sources or post-marketing.
| ORGAN SITE | SIDE EFFECT* (%) | ONSET** | |||
|---|---|---|---|---|---|
| Cardiovascular | Venous thromboembolism (2%) | E | |||
| Dermatological | Alopecia (15%) | E | |||
| Erythema multiforme (<1%) | E | ||||
| Rash, pruritus (14%) | E | ||||
| Gastrointestinal | Anorexia (13%) | E | |||
| Constipation (17%) | E | ||||
| Diarrhea (19%) | E | ||||
| Mucositis (25%) | E | ||||
| Nausea, vomiting (29%) | E | ||||
| General | Edema - limbs (8%) | E | |||
| Fatigue (38%) | E | ||||
| Hematological | Myelosuppression ± infection, bleeding (79%) (62% severe) | E | |||
| Nervous System | Dizziness (11%) | E | |||
| Dysgeusia (6%) | E | ||||
| Headache (21%) | E | ||||
| Insomnia (11%) | E | ||||
| Renal | Creatinine increased (6%) | E | |||
| Respiratory | Cough, dyspnea (13%) | E | |||
| Pneumonitis (1%) | E | ||||
* "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 palbociclib include myelosuppression ± infection, bleeding, fatigue, nausea, vomiting, mucositis, headache, diarrhea, constipation, alopecia, rash, pruritus and anorexia.
Neutropenia was the most frequently reported adverse effect with a median onset of 15 days. Febrile neutropenia, including one fatal case, has been reported in 2% of patients across clinical trials.
Infections were reported more frequently. Patients should be warned of the increased risk of infection and promptly report any occurrences of fever to their health care team.
Severe or life-threatening interstitial lung disease/pneumonitis has been reported in combination with endocrine therapy in clinical trials and post-marketing (including fatal cases).
E - Dosing
Refer to protocol by which 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.
Pre/perimenopausal women, and men, treated with palbociclib and an aromatase inhibitor or fulvestrant should also be treated with luteinizing hormone-releasing hormone (LHRH) agonists according to local clinical practice.
Adults:
Oral: 125 mg Daily on Days 1 to 21, every 28 days
in combination with an aromatase inhibitor (e.g., letrozole) or fulvestrant. Refer to regimen monographs for dosing details.
Dosage with Toxicity:
| Dose Level | Palbociclib Dose (mg/day) |
| 0 | 125 |
| -1 | 100 |
| -2 | 75 |
| -3 | If further dose reduction required, discontinue. |
| Toxicity | Grade | Palbociclib Dose |
| Hematologic | 3 | Day 1: Hold and repeat CBC within 1 week. When recovered to Grade ≤ 2, re-start next cycle at same dose. Day 15 of 1st 2 cycles: Continue current dose to complete the cycle. Repeat CBC day 22. If Grade 4 on Day 22, see Grade 4 recommendation below. Consider dose reduction if > 1 week recovery or recurrent Grade 3 neutropenia in subsequent cycles. |
| 3 with fever ≥ 38.5oC and/or infection | Hold until recovery to Grade ≤ 2. Restart at the next lower dose. | |
| 4 | Hold until recovery to Grade ≤ 2. Restart at the next lower dose. | |
Symptoms of interstitial lung disease (ILD)/pneumonitis (treatment–related) |
Any | Hold dose and investigate; discontinue if severe ILD confirmed. |
| Other non-hematologic | 3 or 4 (if persisting despite medical treatment) | Hold until recovery to Grade ≤ 1 or Grade ≤ 2 (if not considered a safety risk). Restart at the next lower dose. |
Dosage with Hepatic Impairment:
Mean fraction of unbound palbociclib in plasma increased with worsening hepatic function.
| Hepatic Impairment | Starting Dose |
| Mild - Moderate (Child-Pugh class A and B) | No dosage adjustment needed. |
| Severe (Child-Pugh class C) | 75 mg once daily (days 1 to 21; q28 days). Monitor for toxicity. |
Dosage with Renal Impairment:
No adjustment is required for CrCl ≥ 15 mL/min. There is no data available in patients requiring hemodialysis.
Dosage in the elderly:
No overall differences in efficacy were observed between patients aged 65 and older compared to younger patients. When combined with letrozole, patients ≥ 65 were more likely to experience anemia.
Dosage based on gender:
Gender and body weight had no significant effect on drug exposure.
Dosage based on ethnicity:
No dose modification is required based on pharmacokinetic, safety and efficacy data across Asian and non-Asian populations.
Children:
The safety and efficacy of palbociclib has not been studied in children under 18 years.
F - Administration Guidelines
Palbociclib may be given with or without food.
Tablets should be swallowed whole and not chewed, crushed, opened, or split prior to administration.
If a patient vomits or misses a dose, an extra dose should not be taken to make up for the vomited or missed dose. The next dose should be taken at the usual time.
Grapefruit, pomegranate, starfruit, Seville oranges, their juices or products should be avoided during palbociclib treatment.
Tablets should be stored at 15 to 30oC in original packaging to protect from moisture.
G - Special Precautions
Contraindications:
Other Drug Properties:
- Patients who are hypersensitive to palbociclib or any ingredient in the formulation or component in the container.
- As dizziness has been reported, patients should exercise caution when driving or operating machinery.
Other Drug Properties:
- Carcinogenicity: Unknown
An increased incidence of microglial cell tumors was observed male rats; the relevance to humans is unknown.
- Genotoxicity: Probable
- Mutagenicity: No
- Fetotoxicity: Documented in animals
- Pregnancy:
Palbociclib is not recommended for use in pregnancy.
- Adequate contraception should be used by patients who can become pregnant and their partners during treatment, and for at least 3 weeks after the last dose.
- Adequate contraception should be used by patients who produce sperm and their partners during treatment, and for at least 14 weeks after the last dose.
- Excretion into breast milk: Unknown
- Breastfeeding:
Breastfeeding is not recommended.
- Fertility effects: Probable
Animal data suggest that palbociclib may affect male fertility. Sperm preservation should be considered prior to starting treatment.
H - Interactions
Palbociclib is a substrate and weak inhibitor of CYP3A and a moderate substrate of P-gp. Drug interactions are possible with strong CYP3A inducers and inhibitors. Palbociclib is not an inhibitor of CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19 and 2D6 and not an inducer of CYP1A2, 2B6, 2C8 and 3A4 in vitro.
The drug has a low potential to inhibit drug transporters P-gp, BCRP, OAT1, OAT3, OCT2, OATP1B1 and OATP1B3. Palbociclib is not a substrate of OATP1B1 and OATP1B3 (in vitro studies).
There are no drug interactions with letrozole or goserelin.
| AGENT | EFFECT | MECHANISM | MANAGEMENT |
|---|---|---|---|
| CYP3A inhibitors (e.g. ketoconazole, clarithromycin, ritonavir, fruit or juice from grapefruit, Seville oranges or starfruit) | ↑ palbociclib concentration and/or toxicity (e.g. itraconazole ↑ palbociclib exposure by 87%) | ↓ metabolism of palbociclib | Avoid strong CYP3A inhibitors. |
| Strong and moderate CYP3A inducers (e.g. phenytoin, rifampin, dexamethasone, carbamazepine, phenobarbital, St. John’s Wort, etc) | ↓ palbociclib concentration and/or efficacy (e.g. rifampin ↓ palbociclib exposure by 85%) | ↑ metabolism of palbociclib | Avoid strong CYP3A inducers. If use of moderate inducer cannot be avoided, no dose adjustment to palbociclib is needed. |
| Sensitive CYP3A substrates with narrow therapeutic indices (e.g. midazolam, cyclosporine, everolimus, pimozide, fentanyl, quinidine, sirolimus, tacrolimus, ergotamine, dihydroergotamine) | ↑ substrate concentration and/or toxicity (e.g. palbociclib ↑ midazolam exposure by 61%) | Palbociclib is a weak inhibitor of CYP3A. | Consider reducing the dose of sensitive CYP3A substrates with narrow therapeutic indices |
| Statins which are substrates of CYP3A4 and/or BCRP (e.g. atorvastatin, lovastatin, rosuvastatin and simvastatin) | ↑ risk of rhabdomyolysis | Palbociclib may ↑ statin concentration | Close monitoring is recommended. |
I - Recommended Clinical 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.
Recommended Clinical Monitoring
| Monitor Type | Monitor Frequency |
|---|---|
CBC |
Baseline and before each cycle, on day 15 of the first 2 cycles, one week after Grade 3 neutropenia, and as clinically indicated. If neutropenia Grade 2 or less in the first 6 cycles, may monitor every 3rd cycle thereafter |
Liver function tests |
Baseline and as clinically indicated |
Renal function tests |
Baseline and as clinically indicated |
Clinical toxicity assessment for infection, bleeding, thromboembolism, pneumonitis, rash, headache, mucositis, fatigue and GI effects |
At each visit |
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
J - Supplementary Public Funding
Exceptional Access Program (EAP Website )
- palbociclib - 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
K - References
Finn RS, Crown JP, Lang I, et al. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol. 2015 Jan;16(1):25-35.
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.
Product Monograph: Ibrance (palbociclib). Pfizer Canada Inc. July 4, 2025.
September 2025 Updated Pharmacokinetics, Adverse Effects, Administration Guidelines, Warnings/Precautions, Pregnancy/Lactation and Interactions sections
L - Disclaimer
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.
CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.
Last Updated: July 21, 2026
