IBRANCE- palbociclib capsule

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

PALBOCICLIB (UNII: G9ZF61LE7G) (PALBOCICLIB - UNII:G9ZF61LE7G)

Available from:

Pfizer Laboratories Div Pfizer Inc

INN (International Name):

PALBOCICLIB

Composition:

PALBOCICLIB 75 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

IBRANCE is indicated for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in combination with: None. Risk Summary Based on findings from animal studies and its mechanism of action, IBRANCE can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)] . There are no available data in pregnant women to inform the drug-associated risk. In animal reproduction studies, administration of palbociclib to pregnant rats and rabbits during organogenesis resulted in embryo-fetal toxicity at maternal exposures that were ≥4 times the human clinical exposure based on AUC [see Data] . Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%–4% and 15%–20%, respectively. Data Animal Data In a fertility and early embryonic development study in female rats, palbociclib was administered orally for 15 days before mating through to Day 7 of pregnancy, which did not cause embryo toxicity at doses up to 300 mg/kg/day with maternal systemic exposures approximately 4 times the human exposure (AUC) at the recommended dose. In embryo-fetal development studies in rats and rabbits, pregnant animals received oral doses of palbociclib up to 300 mg/kg/day and 20 mg/kg/day, respectively, during the period of organogenesis. The maternally toxic dose of 300 mg/kg/day was fetotoxic in rats, resulting in reduced fetal body weights. At doses ≥100 mg/kg/day in rats, there was an increased incidence of a skeletal variation (increased incidence of a rib present at the seventh cervical vertebra). At the maternally toxic dose of 20 mg/kg/day in rabbits, there was an increased incidence of skeletal variations, including small phalanges in the forelimb. At 300 mg/kg/day in rats and 20 mg/kg/day in rabbits, the maternal systemic exposures were approximately 4 and 9 times the human exposure (AUC) at the recommended dose, respectively. CDK4/6 double knockout mice have been reported to die in late stages of fetal development (gestation Day 14.5 until birth) due to severe anemia. However, knockout mouse data may not be predictive of effects in humans due to differences in degree of target inhibition. Risk Summary There is no information regarding the presence of palbociclib in human milk, its effects on milk production, or the breastfed infant. Because of the potential for serious adverse reactions in breastfed infants from IBRANCE, advise a lactating woman not to breastfeed during treatment with IBRANCE and for 3 weeks after the last dose. Pregnancy Testing Based on animal studies, IBRANCE can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. Females of reproductive potential should have a pregnancy test prior to starting treatment with IBRANCE. Contraception Females IBRANCE can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)] . Advise females of reproductive potential to use effective contraception during treatment with IBRANCE and for at least 3 weeks after the last dose. Males Because of the potential for genotoxicity, advise male patients with female partners of reproductive potential to use effective contraception during treatment with IBRANCE and for 3 months after the last dose [see Nonclinical Toxicology (13.1)] . Infertility Males Based on animal studies, IBRANCE may impair fertility in males of reproductive potential [see Nonclinical Toxicology (13.1)] . The safety and efficacy of IBRANCE in pediatric patients have not been studied. Altered glucose metabolism (glycosuria, hyperglycemia, decreased insulin) associated with changes in the pancreas (islet cell vacuolation), eye (cataracts, lens degeneration), kidney (tubule vacuolation, chronic progressive nephropathy) and adipose tissue (atrophy) were identified in a 27 week repeat-dose toxicology study in rats that were immature at the beginning of the studies and were most prevalent in males at oral palbociclib doses ≥30 mg/kg/day (approximately 11 times the adult human exposure [AUC] at the recommended dose). Some of these findings (glycosuria/hyperglycemia, pancreatic islet cell vacuolation, and kidney tubule vacuolation) were present with lower incidence and severity in a 15 week repeat-dose toxicology study in immature rats. Altered glucose metabolism or associated changes in the pancreas, eye, kidney and adipose tissue were not identified in a 27-week repeat-dose toxicology study in rats that were mature at the beginning of the study and in dogs in repeat-dose toxicology studies up to 39 weeks duration. Toxicities in teeth independent of altered glucose metabolism were observed in rats. Administration of 100 mg/kg palbociclib for 27 weeks (approximately 15 times the adult human exposure [AUC] at the recommended dose) resulted in abnormalities in growing incisor teeth (discolored, ameloblast degeneration/necrosis, mononuclear cell infiltrate). Other toxicities of potential concern to pediatric patients have not been evaluated in juvenile animals. Of 444 patients who received IBRANCE in PALOMA-2, 181 patients (41%) were ≥65 years of age and 48 patients (11%) were ≥75 years of age. Of 347 patients who received IBRANCE in PALOMA-3, 86 patients (25%) were ≥65 years of age and 27 patients (8%) were ≥75 years of age. No overall differences in safety or effectiveness of IBRANCE were observed between these patients and younger patients. No dose adjustment is required in patients with mild or moderate hepatic impairment (Child-Pugh classes A and B). For patients with severe hepatic impairment (Child-Pugh class C), the recommended dose of IBRANCE is 75 mg once daily for 21 consecutive days followed by 7 days off treatment to comprise a complete cycle of 28 days [see Dosage and Administration (2.2)] . Based on a pharmacokinetic trial in subjects with varying degrees of hepatic function, the palbociclib unbound exposure (unbound AUCINF ) decreased by 17% in subjects with mild hepatic impairment (Child-Pugh class A), and increased by 34% and 77% in subjects with moderate (Child-Pugh class B) and severe (Child-Pugh class C) hepatic impairment, respectively, relative to subjects with normal hepatic function. Peak palbociclib unbound exposure (unbound Cmax ) increased by 7%, 38% and 72% for mild, moderate and severe hepatic impairment, respectively, relative to subjects with normal hepatic function [see Clinical Pharmacology (12.3)] . Review the Full Prescribing Information for the aromatase inhibitor or fulvestrant for dose modifications related to hepatic impairment. No dose adjustment is required in patients with mild, moderate, or severe renal impairment (CrCl >15 mL/min). Based on a pharmacokinetic trial in subjects with varying degrees of renal function, the total palbociclib exposure (AUCINF ) increased by 39%, 42%, and 31% with mild (60 mL/min ≤ CrCl <90 mL/min), moderate (30 mL/min ≤ CrCl <60 mL/min), and severe (CrCl <30 mL/min) renal impairment, respectively, relative to subjects with normal renal function. Peak palbociclib exposure (Cmax ) increased by 17%, 12%, and 15% for mild, moderate, and severe renal impairment, respectively, relative to subjects with normal renal function. The pharmacokinetics of palbociclib have not been studied in patients requiring hemodialysis [see Clinical Pharmacology (12.3)] .

Product summary:

IBRANCE is supplied in the following strengths and package configurations: Bottles of 21 capsules 125 NDC 0069-0189-21 opaque, hard gelatin capsules, size 0, with caramel cap and body, printed with white ink "Pfizer" on the cap, "PBC 125" on the body Bottles of 21 capsules 100 NDC 0069-0188-21 opaque, hard gelatin capsules, size 1, with caramel cap and light orange body, printed with white ink "Pfizer" on the cap, "PBC 100" on the body Bottles of 21 capsules 75 NDC 0069-0187-21 opaque, hard gelatin capsules, size 2, with light orange cap and body, printed with white ink "Pfizer" on the cap, "PBC 75" on the body Store at 20 °C to 25 °C (68 °F to 77 °F); excursions permitted between 15 °C to 30 °C (59 °F to 86 °F) [see USP Controlled Room Temperature] .

Authorization status:

New Drug Application

Summary of Product characteristics

IBRANCE- PALBOCICLIB CAPSULE
PFIZER LABORATORIES DIV PFIZER INC
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
IBRANCE SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR IBRANCE.
IBRANCE (PALBOCICLIB) CAPSULES, FOR ORAL USE
INITIAL U.S. APPROVAL: 2015
RECENT MAJOR CHANGES
Indications and Usage (1)
12/2022
Dosage and Administration (2.1)
12/2022
INDICATIONS AND USAGE
IBRANCE is a kinase inhibitor indicated for the treatment of adult
patients with hormone receptor (HR)-
positive, human epidermal growth factor receptor 2 (HER2)-negative
advanced or metastatic breast
cancer in combination with:
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•
DOSAGE AND ADMINISTRATION
IBRANCE capsules are taken orally with food in combination with an
aromatase inhibitor or fulvestrant. (2)
•
•
DOSAGE FORMS AND STRENGTHS
Capsules: 125 mg, 100 mg, and 75 mg. (3)
CONTRAINDICATIONS
None. (4)
WARNINGS AND PRECAUTIONS
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•
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ADVERSE REACTIONS
Most common adverse reactions (incidence ≥10%) were neutropenia,
infections, leukopenia, fatigue,
nausea, stomatitis, anemia, alopecia, diarrhea, thrombocytopenia,
rash, vomiting, decreased appetite,
asthenia, and pyrexia. (6)
TO REPORT SUSPECTED ADVERSE REACTIONS, CONTACT PFIZER INC AT
1-800-438-1985 OR FDA AT
1-800-FDA-1088 OR WWW.FDA.GOV/MEDWATCH.
DRUG INTERACTIONS
•
•
•
®
an aromatase inhibitor as initial endocrine-based therapy (1); or
fulvestrant in patients with disease progression following endocrine
therapy. (1)
Recommended starting dose: 125 mg once daily taken with food for 21
days followed by 7 days off
treatment. (2.1)
Dosing interruption and/or dose reductions are recommended based on
individual safety and
tolerability. (2.2)
Neutropenia: Monitor complete blood count prior to start of IBRANCE
therapy and at the beginning of
each cycle, as well as on Day 15 of the first 2 cycles, and as
clinically indicated. (2.2, 5.1)
Interstitial Lung Disease (ILD)/Pneumonitis: Severe and fatal cases of
ILD/pneumonitis have been
reported. Monitor fo