Ibrance

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:

• •an aromatase inhibitor as initial endocrine-based therapy; or
• •fulvestrant in patients with disease progression following endocrine therapy.

IBRANCE capsules are taken orally with food in combination with an aromatase inhibitor, fulvestrant, or inavolisib and fulvestrant. (

• •Recommended starting dose: 125 mg once daily taken with food for 21 days followed by 7 days off treatment. (
  2.1 Recommended Dose and Schedule

  The recommended dose of IBRANCE is a 125 mg capsule taken orally once daily for 21 consecutive days followed by 7 days off treatment to comprise a complete cycle of 28 days. IBRANCE capsule should be taken with food

  [see Clinical Pharmacology (12.3)]

  .

  Administer the recommended dose of an aromatase inhibitor when given with IBRANCE. Please refer to the Full Prescribing Information for the aromatase inhibitor being used.

  When given with IBRANCE, the recommended dose of fulvestrant is 500 mg administered on Days 1, 15, 29, and once monthly thereafter. Please refer to the Full Prescribing Information of fulvestrant.

  Refer to the Full Prescribing Information for inavolisib and fulvestrant for dosing information.

  Advise patients

  to take their dose of IBRANCE at approximately the same time each day.

  If the patient vomits or misses a dose, an additional dose should not be taken. The next prescribed dose should be taken at the usual time. IBRANCE capsules should be swallowed whole (do not chew, crush, or open them prior to swallowing). Capsules should not be ingested if they are broken, cracked, or otherwise not intact.

  Pre/perimenopausal women treated with the combination IBRANCE plus an aromatase inhibitor or fulvestrant

  or IBRANCE plus inavolisib and fulvestrant

  therapy should also be treated with luteinizing hormone-releasing hormone (LHRH) agonists according to current clinical practice standards.

  For men treated with combination IBRANCE plus aromatase inhibitor

  or IBRANCE plus inavolisib and fulvestrant

  therapy, consider treatment with an LHRH agonist according to current clinical practice standards.
  )
• •Dosing interruption and/or dose reductions are recommended based on individual safety and tolerability. (
  2.2 Dose Modification

  The recommended dose modifications for adverse reactions are listed in Tables 1, 2, and 3.

  Table 1. Recommended Dose Modification for Adverse Reactions

  Dose Level	Dose
  Recommended starting dose	125 mg/day
  First dose reduction	100 mg/day
  Second dose reduction	75 mg/dayIf further dose reduction below 75 mg/day is required, discontinue.

  Table 2. Dose Modification and Management – Hematologic ToxicitiesTable applies to all hematologic adverse reactions except lymphopenia (unless associated with clinical events, e.g., opportunistic infections).

  Grading according to CTCAE 4.0. CTCAE=Common Terminology Criteria for Adverse Events; LLN=lower limit of normal.
  Monitor complete blood counts prior to the 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. For patients who experience a maximum of Grade 1 or 2 neutropenia in the first 6 cycles, monitor complete blood counts for subsequent cycles every 3 months, prior to the beginning of a cycle and as clinically indicated.
  CTCAE Grade	Dose Modifications
  Grade 1 or 2	No dose adjustment is required.
  Grade 3	Day 1 of cycle : Withhold IBRANCE, repeat complete blood count monitoring within 1 week. When recovered to Grade ≤2, start the next cycle at the same dose . Day 15 of first 2 cycles : If Grade 3 on Day 15, continue IBRANCE at current dose to complete cycle and repeat complete blood count on Day 22. If Grade 4 on Day 22, see Grade 4 dose modification guidelines below. Consider dose reduction in cases of prolonged (>1 week) recovery from Grade 3 neutropenia or recurrent Grade 3 neutropenia on Day 1 of subsequent cycles.
  Grade 3 neutropeniaAbsolute neutrophil count (ANC): Grade 1: ANC < LLN - 1500/mm3; Grade 2: ANC 1000 - <1500/mm3; Grade 3: ANC 500 - <1000/mm3; Grade 4: ANC <500/mm3.with fever ≥38.5 ºC and/or infection	At any time : Withhold IBRANCE until recovery to Grade ≤2. Resume at the next lower dose .
  Grade 4	At any time : Withhold IBRANCE until recovery to Grade ≤2. Resume at the next lower dose .

  Grade ≤1;

  Grade ≤2 (if not considered a safety risk for the patient)

  Resume at the

  next lower dose

  .

  Table 3. Dose Modification and Management – Non-Hematologic Toxicities

  •

  •

  CTCAE Grade	Dose Modifications
  Grading according to CTCAE 4.0. CTCAE=Common Terminology Criteria for Adverse Events.
  Grade 1 or 2	No dose adjustment is required.
  Grade ≥3 non-hematologic toxicity (if persisting despite optimal medical treatment)	Withhold until symptoms resolve to:

  Permanently discontinue IBRANCE in patients with severe interstitial lung disease (ILD)/pneumonitis.

  Refer to the Full Prescribing Information for coadministered endocrine therapy

  and/or inavolisib

  dose adjustment guidelines in the event of toxicity and other relevant safety information or contraindications.

  Dose Modifications for Use With Strong CYP3A Inhibitors

  Avoid concomitant use of strong CYP3A inhibitors and consider an alternative concomitant medication with no or minimal CYP3A inhibition. If patients must be coadministered a strong CYP3A inhibitor, reduce the IBRANCE dose to 75 mg once daily. If the strong inhibitor is discontinued, increase the IBRANCE dose (after 3 to 5 half-lives of the inhibitor) to the dose used prior to the initiation of the strong CYP3A inhibitor

  [see Drug Interactions (7.1)and Clinical Pharmacology (12.3)].

  Dose Modifications for Hepatic Impairment

  No dose adjustment is required for 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 Use in Specific Populations (8.6)and Clinical Pharmacology (12.3)].
  )

125 mg capsules: opaque, hard gelatin capsules, size 0, with caramel cap and body, printed with white ink "Pfizer" on the cap, "PBC 125" on the body.

100 mg capsules: 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.

75 mg capsules: 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.

• •Lactation: Advise not to breastfeed. (
  8.2 Lactation

  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.
  )