Medically reviewed by Drugs.com. Last updated on Jul 14, 2019.

• Overview
• Side Effects
• Dosage
• Professional
• Interactions
• Pregnancy
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Pronunciation

(pal boe SYE klib)

Index Terms

• Palbociclib Isethionate
• PD 0332991
• PD-0332991
• PD-332991

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Ibrance: 75 mg, 100 mg, 125 mg

Brand Names: U.S.

• Ibrance

Pharmacologic Category

• Antineoplastic Agent, Cyclin-Dependent Kinase Inhibitor

Pharmacology

Palbociclib is a reversible small molecule cyclin-dependent kinase (CDK) inhibitor which is selective for CDK 4 and 6. CDKs have a role in regulating progression through the cell cycle at the G1/S phase by blocking retinoblastoma (Rb) hyperphosphorylation (Finn 2015). Palbociclib reduces proliferation of breast cancer cell lines by preventing progression from the G1 to the S cell cycle phase. The combination of palbociclib with an antiestrogen provides for increased inhibition of Rb phosphorylation, downstream signaling, and tumor growth compared with each agent alone.

Absorption

Increased with high-fat, high-calorie food

Distribution

V_d (mean): 2,583 L

Metabolism

Extensively hepatic; Major pathways: Oxidation and sulfonation, primarily by CYP3A and sulfotransferase (SULT) enzyme SULT2A1; Minor pathways: Acylation and glucuronidation

Excretion

Feces (~74%, primarily as metabolites); Urine (~18%; primarily as metabolites)

Time to Peak

6 to 12 hours

Half-Life Elimination

29 ± 5 hours

Protein Binding

~85%

Special Populations: Renal Function Impairment

Total palbociclib exposure (AUC_INF) is increased by 39%, 42%, and 31% with mild (CrCl 60 to <90 mL/minute), moderate (CrCl 30 to <60 mL/minute), and severe (CrCl <30 mL/minute) impairment, respectively, relative to subjects with normal renal function. Peak palbociclib exposure (C_max) was increased by 17%, 12%, and 15% for mild, moderate, and severe impairment, respectively, relative to subjects with normal renal function.

Special Populations: Hepatic Function Impairment

Palbociclib unbound exposure (unbound AUC_INF) is decreased by 17% in subjects with mild impairment (Child-Pugh class A), and increased by 34% and 77% in subjects with moderate and severe (Child-Pugh classes B and C) impairment, respectively, relative to subjects with normal hepatic function. The mean fraction of unbound (f_u) palbociclib in human plasma increased incrementally in patients with worsening hepatic function. Peak palbociclib unbound exposure (unbound C_max) increased by 7%, 38%, and 72% for mild, moderate, and severe impairment, respectively, relative to subjects with normal hepatic function.

Use: Labeled Indications

Breast cancer, advanced (initial endocrine-based therapy): Treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer (in combination with an aromatase inhibitor) in postmenopausal females or in adult males as initial endocrine-based therapy.

Breast cancer, advanced (with disease progression following endocrine therapy): Treatment of HR-positive, HER2-negative advanced or metastatic breast cancer (in combination with fulvestrant) in adult patients with disease progression following endocrine therapy.

Contraindications

There are no contraindications listed in the manufacturer's US labeling.

Canadian labeling: Hypersensitivity to palbociclib or any component of the formulation

Dosing: Adult

Note: Refer to aromatase inhibitor or fulvestrant monographs for respective dosing in combination with palbociclib.

Breast cancer, advanced, initial endocrine-based therapy: HER-2 negative: Oral: 125 mg once daily for 21 days, followed by 7 days off, repeat every 28 days (in combination with continuous aromatase inhibitor therapy); continue until disease progression or unacceptable toxicity (Finn 2015). For males receiving palbociclib in combination with an aromatase inhibitor, also consider treatment with an LHRH agonist.

Breast cancer, advanced (with disease progression following endocrine therapy): HER-2 negative: Oral: 125 mg once daily for 21 days, followed by 7 days off, repeat every 28 days (in combination with fulvestrant [and an LHRH/GnRH agonist (eg, goserelin) if pre- or perimenopausal female]); continue until disease progression or unacceptable toxicity (Turner 2018).

Missed/vomited doses: If a dose is vomited or missed, an additional dose should not be taken that day. Resume dosing with the next scheduled daily dose.

Dosage adjustment for concomitant therapy:

Strong CYP3A inhibitors: Avoid concomitant use with strong CYP3A inhibitors and consider alternatives with no or minimal CYP3A inhibition. If coadministration with a strong CYP3A inhibitor cannot be avoided, reduce palbociclib dose to 75 mg once daily. If the strong inhibitor is discontinued, increase palbociclib dose (after 3 to 5 inhibitor half-lives have elapsed) to the dose used prior to initiating the strong CYP3A inhibitor.

CYP3A inducers: Avoid concomitant use with strong CYP3A inducers.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Adjustment for Toxicity

May require treatment interruption/delay, dose reduction, or discontinuation for some adverse reactions. The recommended first dose reduction is to 100 mg daily; if a second reduction is required, reduce dose to 75 mg daily. If dose reduction below 75 mg daily is required, discontinue treatment.

Hematologic toxicity (except lymphopenia unless associated with clinical events [eg, opportunistic infection]), according to Common Toxicity Criteria for Adverse Events Version 4:

Grade 1 or 2: No dosage adjustment required.

Grade 3:

Day 1 of cycle: Withhold palbociclib therapy and repeat CBC with differential within 1 week. When improved to ≤ grade 2, initiate the next cycle at the same dose.

Day 15 of first 2 cycles: If at grade 3, continue palbociclib therapy at current dose to complete the cycle. Repeat CBC with differential on day 22. If at grade 4 on day 22, withhold palbociclib treatment until resolved to ≤ grade 2. After resolution, resume at next lower dose. Consider dose reduction in future cycles if recovery from grade 3 neutropenia is prolonged (>1 week) or for recurrent grade 3 neutropenia on day 1 of subsequent cycles.

Grade 3 (ANC 500/mm³ to <1,000/mm³) plus fever ≥38.5°C and/or infection at any time: Withhold palbociclib treatment until resolved to ≤ grade 2. Resume at next lower dose upon restarting.

Grade 4 at any time: Withhold palbociclib treatment until resolved to ≤ grade 2. After resolution, resume at next lower dose.

Nonhematologic toxicity:

Pulmonary toxicity: Permanently discontinue palbociclib for severe interstitial lung disease/pneumonitis.

Other toxicity (according to Common Toxicity Criteria for Adverse Events Version 4):

Grade 1 or 2: No dosage adjustment required.

Grade 3 or higher (if persistent despite optimal medical management): Withhold palbociclib until symptoms resolve to ≤ grade 1 or ≤ grade 2 (if toxicity is not a safety risk); after resolution, resume at the next lower dose.

Administration

Oral: Administer with food. Take at approximately the same time each day. Swallow whole, do not crush, chew, or open capsules prior to swallowing (do not ingest if capsules are broken, cracked, or not fully intact).

Dietary Considerations

Avoid grapefruit.

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).

Drug Interactions

Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

ARIPiprazole: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy

Baricitinib: Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted. Consider therapy modification

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Monitor therapy

Cladribine: May enhance the immunosuppressive effect of Immunosuppressants. Avoid combination

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Avoid combination

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Palbociclib. Management: The US label does not provide specific recommendations concerning use with moderate CYP3A4 inducers, but the Canadian label recommends avoiding use of moderate CYP3A4 inducers. Consider therapy modification

CYP3A4 Inducers (Strong): May decrease the serum concentration of Palbociclib. Avoid combination

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Palbociclib. Avoid combination

CYP3A4 Substrates (High risk with Inhibitors): Palbociclib may increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Consider therapy modification

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination

Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Monitor therapy

Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Monitor therapy

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Grapefruit Juice: May increase the serum concentration of Palbociclib. Avoid combination

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Consider therapy modification

Lorlatinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. Consider therapy modification

Mesalamine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Monitor therapy

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Avoid combination

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Siponimod: Immunosuppressants may enhance the immunosuppressive effect of Siponimod. Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy. Consider therapy modification

St John's Wort: May decrease the serum concentration of Palbociclib. Avoid combination

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Consider therapy modification

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination

Adverse Reactions

Percentages reported as part of combination therapy.

>10%:

Central nervous system: Fatigue (37% to 41%)

Dermatologic: Alopecia (18% to 33%), skin rash (17% to 18%), xeroderma (6% to 12%)

Gastrointestinal: Nausea (34% to 35%), stomatitis (28% to 30%; grade 3: 1%), diarrhea (24% to 26%), vomiting (16% to 19%), decreased appetite (15% to 16%)

Hematologic & oncologic: Neutropenia (80% to 83%; grade 3: 55% to 56%; grade 4: 10% to 11%), anemia (24% to 78%; grade 3: 3% to 6%; grade 4: <1%), leukopenia (39% to 53%; grade 3: 24% to 30%; grade 4: 1%), thrombocytopenia (16% to 23%; grade 3: 1% to 2%; grade 4: ≤1%)

Hepatic: Increased serum aspartate aminotransferase (8% to 52%), increased serum alanine aminotransferase (6% to 43%)

Infection: Infection (47% to 60%)

Neuromuscular & skeletal: Asthenia (8% to 17%)

Miscellaneous: Fever (12% to 13%)

1% to 10%:

Gastrointestinal: Dysgeusia (7% to 10%)

Hematologic & oncologic: Febrile neutropenia (≤3%)

Ophthalmic: Blurred vision (4% to 6%), increased lacrimation (6%), dry eye syndrome (4%)

Respiratory: Epistaxis (7% to 9%)

<1%, postmarketing, and/or case reports: Interstitial pulmonary disease, pneumonia

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: Neutropenia was commonly observed in clinical studies, including grades 3 and 4 neutropenia. The median time to the first neutropenia episode (any grade) was 15 days; the median duration of grade 3 or higher neutropenia was 7 days. Leukopenia, anemia, lymphocytopenia, thrombocytopenia, neutropenic fever, and neutropenic sepsis have also been reported. Monitor blood counts prior to initiating therapy and at the beginning of each cycle (as well as on day 15 of the first 2 cycles), and as clinically necessary; if neutropenia is limited to grades 1 or 2 in the first 6 cycles, monitor every 3 months (prior to the beginning of a cycle) and as clinically indicated for subsequent cycles. Treatment interruption, delay, or dose reduction is recommended for grade 3 or 4 neutropenia.

• GI toxicity: Nausea, vomiting, diarrhea, and stomatitis (generally grade 1 or 2) were reported from clinical studies.

• Infection: Infections (including grades 3 and 4) were reported more frequently in patients receiving palbociclib and an antiestrogen compared with those receiving an antiestrogen only. Monitor for signs/symptoms of infection and manage appropriately.

• Pulmonary toxicity: Severe, life-threatening, and/or fatal interstitial lung disease (ILD) and/or pneumonitis may occur with palbociclib (and other cyclin-dependent kinase inhibitors). Monitor closely for symptoms of ILD/pneumonitis, which may include hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exam. Exclude infectious, neoplastic, and other causes for pulmonary toxicity. Interrupt palbociclib therapy immediately for new or worsening respiratory symptoms which may be indicative of pneumonitis. Permanently discontinue palbociclib for severe ILD/pneumonitis.

Disease-related concerns:

• Hepatic impairment: A reduced dose is recommended in patients with severe hepatic impairment.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Monitoring Parameters

CBC with differential (prior to treatment initiation, every 2 weeks for first 2 cycles, then prior to each cycle, and as clinically indicated; if neutropenia is limited to grades 1 or 2 in the first 6 cycles, monitor every 3 months [prior to the beginning of a cycle] and as clinically indicated for subsequent cycles); pregnancy test prior to treatment initiation (in females of reproductive potential); monitor for signs/symptoms of interstitial lung disease/pneumonitis and infection. Monitor adherence.

Pregnancy Considerations

Based on the mechanism of action and data from animal reproduction studies, palbociclib may be expected to cause fetal harm if used during pregnancy.

Evaluate pregnancy status prior to treatment initiation in females of reproductive potential. Females of reproductive potential should use effective contraception during treatment and for at least 3 weeks after the last dose. Males with female partners of reproductive potential should use effective contraception during treatment and for 3 months after the last dose.

Adverse effects to male reproductive function and fertility were observed in animal toxicology studies; males of reproductive potential may want to consider sperm preservation prior to palbociclib therapy.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience lack of appetite, diarrhea, hair thinning or loss, mouth sores, mouth irritation, nausea, vomiting, dry skin, or change in taste. Have patient report immediately to prescriber signs of infection, bruising, bleeding, dizziness, nosebleed, severe loss of strength and energy, or shortness of breath (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

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