palbociclib (Rx)

Brand and Other Names:Ibrance
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule

  • 75mg
  • 100mg
  • 125mg

tablet

  • 75mg
  • 100mg
  • 125mg

Breast Cancer

Indication

  • Indicated for treatment of adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer as follows:
  • Men or postmenopausal women
    • Use in combination with aromatase inhibitor as initial endocrine-based therapy
  • Patients with disease progression following endocrine therapy
    • Use in combination with fulvestrant

Combination therapy with aromatase inhibitor

  • Palbociclib 125 mg PO qDay for Days 1-21 of each 28-day cycle
  • Aromatase inhibitor: See prescribing information
  • Continue until disease progression or unacceptable toxicity
  • Men treated with combination palbociclib plus aromatase inhibitor therapy, consider treatment with a luteinizing hormone-releasing hormone (LHRH) agonist according to current clinical practice standards

Combination therapy with fulvestrant

  • Palbociclib 125 mg PO qDay for Days 1-21 of each 28-day cycle
  • Fulvestrant 500 mg IM on Days 1, 15, and 29, and then once monthly thereafter
  • Continue until disease progression or unacceptable toxicity
  • Pre/perimenopausal women treated with the combination palbociclib plus fulvestrant should also be treated with an LHRH agonist according to current clinical practice standards

Dosage Modifications

Dose reduction for adverse reaction

  • First dose reduction: Reduce to 100 mg/day
  • Second dose reduction: Reduce to 75 mg/day
  • If further dose reduction below 75 mg/day is required, discontinue treatment

Hematologic toxicities

  • Grade 1 or 2: No dose adjustment required
  • Grade 3*:
    • Day 1 of cycle: Withhold dose, repeat CBC within 1 week; when recovered to grade ≤2, start next cycle at same dose
    • Day 15 of first 2 cycles: If grade 3 on Day 15, continue at current dose to complete cycle; repeat CBC on Day 22; if grade 4 on Day 22, see grade 4 dose modifications below
    • Prolonged (>1 week) recovery from grade 3 or recurrent grade 3 neutropenia in subsequent cycles: Consider dose reduction
  • Grade 3 ANC (<1000 to 500/mm³) + fever ≥38.5ºC and/or infection: Withhold drug until recovery to grade ≤2 (≥1000/mm³); resume at next lower dose
  • Grade 4*: Withhold drug until recovery to grade ≤2; resume at next lower dose
  • *Above refers to all hematologic adverse reactions except lymphopenia, unless associated with clinical event (eg, opportunistic infections)

Nonhematologic toxicities

  • Grade 1 or 2: No dose adjustment required
  • Grade ≥3 (if persisting despite medical treatment): Withhold until symptoms resolve to grade ≤1 or grade ≤2 (if not considered a safety risk for patient to resume); resume at next lower dose

Coadministration with strong CYP3A inhibitors

  • Avoid use with strong CYP3A inhibitors and consider an alternative with no or minimal CYP3A inhibition
  • If coadministration cannot be avoided, reduce palbociclib dose to 75 mg/day
  • If the strong inhibitor is discontinued, increase the palbociclib dose (after 3-5 half-lives of the inhibitor) to the dose used prior to the initiation of the strong CYP3A inhibitor

Hepatic impairment

  • Mild or moderate (Child-Pugh A or B): No dose adjustment required
  • Severe (Child-Pugh C): Reduce dose to 75 mg/day for Days 1-21 of each 28-day cycle

Renal impairment

  • Mild, moderate, or severe (CrCl >15 mL/min): No dose adjustment required
  • Hemodialysis: Not studied

Interstitial lung disease (ILD) or pneumonitis

  • Permanently discontinue treatment in patients with severe ILD/pneumonitis

Dosing Considerations

Monitor CBC at baseline and at the beginning of each cycle, as well as on Day 14 of the first 2 cycles, and as clinically indicated

Safety and efficacy not established

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Interactions

Interaction Checker

and palbociclib

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    No Interactions Found
    Interactions Found

    Contraindicated

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        Significant - Monitor Closely

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            Adverse Effects

            Adverse effects listed are for all grades of toxicity unless otherwise noted

            >10% (Palbociclib with Letrozole)

            WBC decreased (97%)

            Neutrophils decreased (95%)

            Neutropenia (80%)

            Platelets decreased (63%)

            Infections (60%)

            Neutropenia, Grade 3 (56%)

            Neutrophils decreased, Grade 3 (56%)

            AST increased (52%)

            ALT increased (43%)

            Leukopenia (39%)

            Fatigue (37%)

            Nausea (35%)

            WBC decreased, Grade 3 (35%)

            Alopecia (33%)

            Stomatitis (30%)

            Diarrhea (26%)

            Anemia (24%)

            Leukopenia, Grade 3 (24%)

            Rash (18%)

            Asthenia (17%)

            Vomiting (16%)

            Thrombocytopenia (16%)

            Dry skin (12%)

            Pyrexia (12%)

            >10% (Palbociclib with Fulvestrant)

            WBC decreased (99%)

            Neutrophils decreased (96%)

            Neutropenia (83%)

            Anemia (78%)

            Platelets decreased (62%)

            Neutrophils decreased, Grade 3 (56%)

            Neutropenia, Grade 3 (55%)

            Leukopenia (53%)

            Infections (47%)

            WBC decreased, Grade 3 (45%)

            AST increased (43%)

            Fatigue (41%)

            ALT increased (36%)

            Nausea (34%)

            Leukopenia, Grade 3 (30%)

            Anemia (30%)

            Stomatitis (28%)

            Diarrhea (24%)

            Vomiting (19%)

            Thrombocytopenia (23%)

            Alopecia (18%)

            Rash (17%)

            Decreased appetite (16%)

            Pyrexia (13%)

            Neutropenia, Grade 4 (11%)

            Neutrophils decreased, Grade 4 (11%)

            1-10% (Palbociclib with Letrozole)

            Neutropenia, Grade 4 (10%)

            Anemia, Grade 3 (5%)

            Infections, Grade 3 or 4 (1-6%)

            AST increased, Grade 3 (3%)

            ALT increased, Grade 3 (2%)

            Thrombocytopenia, Grade 3 (1%)

            Stomatitis, Grade 3 (1%)

            Diarrhea, Grade 3 (1%)

            Vomiting, Grade 3 (1%)

            Leukopenia, Grade 4 (1%)

            Rash, Grade 3 (1%)

            WBC decreased, Grade 4 (1%)

            Neutrophils decreased, Grade 4 (1%)

            Platelets decreased, Grade 3 or 4 (1%)

            1-10% (Palbociclib with Fulvestrant)

            Asthenia (7.5%)

            AST increased (7.5%)

            Dysgeusia (6.7%)

            Epistaxis (6.7%)

            Lacrimation increased (6.4%)

            Dry skin (6.1%)

            ALT increased (5.8%)

            Vision blurred (5.8%)

            Anemia, Grade 3 (4%)

            AST increased, Grade 3 (4%)

            Dry eye (3.8%)

            Infections, Grade 3 or 4 (1-3%)

            Anemia, Grade 3 (3%)

            Platelets decreased, Grade 3 (2%)

            ALT increased, Grade 3 (2%)

            Thrombocytopenia, Grade 3 (2%)

            Fatigue, Grade 3 (2%)

            Leukopenia, Grade 4 (1%)

            Decreased appetite, Grade 3 (1%)

            Vomiting, Grade 3 (1%)

            Stomatitis, Grade 3 (1%)

            Rash, Grade 3 (1%)

            WBC decreased, Grade 4 (1%)

            <1% (Palbociclib with Letrozole)

            Anemia, Grade 4

            Thrombocytopenia, Grade 4

            Nausea, Grade 3

            ALT increased, Grade 4

            <1% (Palbociclib with Fulvestrant)

            Pyrexia, Grade 3

            Infections, Grade 4

            Febrile neutropenia

            Postmarketing Reports

            Interstitial lung disease (ILD)/non-infectious pneumonitis

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            Warnings

            Contraindications

            None

            Cautions

            Neutropenia observed in clinical trials; febrile neutropenia also reported; monitor CBC count prior to starting drug and at the beginning of each cycle, as well as on Day 14 of the first 2 cycles, and as clinically indicated; dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop grade 3 or 4 neutropenia

            Grade 3 and 4 infections reported when administered in combination with an antiestrogen compared to patients receiving antiestrogen only; monitor and manage appropriately symptoms and signs of infection

            Nausea, vomiting, diarrhea, and grade 1 or 2 stomatitis reported in clinical trials

            Severe, life-threatening, or fatal ILD and/or pneumonitis can occur; additional cases of ILD/pneumonitis have been observed in the postmarketing setting, with fatalities reported; monitor for pulmonary symptoms indicative of ILD/pneumonitis which may include hypoxia, cough, and dyspnea; permanently discontinue therapy in patients with severe ILD or pneumonitis

            Based on findings in animals and mechanism of action, palbociclib can cause fetal harm (see Pregnancy)

            Drug interaction overview

            • In vitro data indicate that CYP3A and SULT enzyme SULT2A1 are mainly involved in the metabolism of palbociclib
            • Palbociclib is also a weak time-dependent inhibitor of CYP3A following daily 125 mg dosing to steady state in humans
            • Avoid use with strong CYP3A inhibitors; if coadministration cannot be avoided, reduce the palbociclib dose (see Dosage Modifications)
            • Avoid use with moderate or strong CYP3A inducers
            • Palbociclib may increase sensitive CYP3A substrates with a narrow therapeutic index (eg, alfentanil, cyclosporine, dihydroergotamine, ergotamine, everolimus, fentanyl, midazolam, pimozide, quinidine, sirolimus, and tacrolimus)
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            Pregnancy & Lactation

            Pregnancy

            Based on findings in animals and mechanism of action, palbociclib can cause fetal harm when administered to a pregnant woman

            In animal studies, palbociclib was teratogenic and fetotoxic at maternal exposures that were ≥4 times the human clinical exposure based on AUC at the recommended human dose

            Females of reproductive potential should have a pregnancy test before starting treatment

            Based on findings in animals, male fertility may be compromised by treatment

            Contraception

            • Females of reproductive potential: Use effective contraception during treatment and for at least 3 weeks after the last dose
            • Male patients with female partners of reproductive potential: Because of potential for genotoxicity, use effective contraception during treatment and for 3 months after the last dose

            Infertility

            • Males: Based on animal studies, may impair fertility in males of reproductive potential

            Lactation

            Unknown if distributed in human breast milk; because many drugs are excreted in human milk

            Owing to the potential for serious adverse reactions in breastfed infants, advise lactating women not to breastfeed while taking palbociclib and for at least 3 weeks after the last dose

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Cyclin dependent kinases (CDK) 4,6 inhibitor

            Reduces cellular proliferation of ER-positive breast cancer cell lines by blocking progression of the cell from G1 into S phase of the cell cycle

            Absorption

            Bioavailability: 46%

            Peak plasma time: 6-12 hr

            Steady-state achieved: 8 days

            Distribution

            Protein bound: 85%

            Vd: 2583 L

            Metabolism

            Extensively metabolized, primarily by CYP3A and SULT2A1

            Elimination

            Half-life: 29 hr (patients with advanced breast cancer)

            Oral clearance: 63.1 L/hr

            Excretion: 74.1% feces (2.3% unchanged); 17.5% urine (6.9% unchanged)

            Majority of the dose eliminated in feces was metabolites

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            Administration

            Oral Administration

            Take with food

            Swallow capsules whole; do not chew, crush, or open them prior to swallowing

            Do not ingest capsule if it is broken, cracked, or otherwise not intact

            Missed or vomited dose: An additional dose should NOT be taken that day; the next prescribed dose should be taken at the usual time

            Storage

            Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)

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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
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            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.