Palbociclib

DAE Class; Rx

Common Brand Names; Ibrance

• Antineoplastics, CDK Inhibitors

Cyclin-dependent kinase (CDK) 4 and 6 inhibitor
Used for the treatment of HR-positive, HER2-negative metastatic breast cancer in combination with an aromatase inhibitor in men and postmenopausal women who have not yet received an endocrine-based therapy, and in combination with fulvestrant in patients with disease progression following endocrine therapy
Monitor complete blood counts; an interruption of therapy, dose reduction, or discontinuation may be necessary for neutropenia

Indicated for treatment of men or pre-/peri/postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer as follows:

• Use in combination with aromatase inhibitor as initial endocrine-based therapy
• Use in combination with fulvestrant in men or women with disease progression following endocrine therapy

None

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%)

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 15 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; patients should promptly report any episodes of fever

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 interstitial lung disease (ILD) and/or pneumonitis can occur in patients treated with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, when taken in combination with endocrine therapy

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)

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

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

Adults

125 mg/day PO.

Geriatric

125 mg/day PO.

Adolescents

Safety and efficacy have not been established.

Children

Safety and efficacy have not been established.

Infants

Not indicated.

Neonates

Not indicated.

Palbociclib