Dosing and Therapy Management

Start IBRANCE when you start endocrine therapy

MBC=metastatic breast cancer.

IBRANCE: Once-daily oral dosing

Pill not actual size.
  • For additional details, please refer to the full Prescribing Information for the aromatase inhibitor being used

Administration considerations

IBRANCE should be taken with food. Patients should be encouraged to take their dose at approximately the same time each day
If the patient vomits or misses a dose, an additional dose should not be taken that day. The next prescribed dose should be taken at the usual time
IBRANCE capsules should be swallowed whole (patients should not chew, crush, or open them prior to swallowing). Capsules should not be ingested if they are broken, cracked, or otherwise not intact

Substrates: Doses of sensitive CYP3A substrates with a narrow therapeutic index may need to be reduced as IBRANCE may increase their exposure

Inducers: Avoid concurrent use of strong CYP3A inducers

Inhibitors: Avoid concurrent use of strong CYP3A inhibitors

–  If the strong inhibitor cannot be avoided, reduce the IBRANCE dose to 75 mg

–  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 inhibitor

–  Patients should avoid grapefruit or grapefruit juice during IBRANCE treatment

For patients with severe hepatic impairment (Child-Pugh class C), the recommended dosing of IBRANCE is 75 mg
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Proactively monitor patients to help manage potential side effects

Monitor complete blood counts (CBC) prior to the start of IBRANCE therapy, on Days 1 and 15 of the first 2 cycles, on Day 1 of subsequent cycles, and as clinically indicated

When scheduling Day 15 monitoring and subsequent follow-up visits, remember to consider when the patient actually receives her medication and initiates each cycle.

The frequency of monitoring can decrease over time

For patients who experience a maximum of Grade 1 or 2 neutropenia in the first 6 cycles, monitor CBCs for subsequent cycles every 3 months, prior to the beginning of a cycle, and as clinically indicated.

CBC is the only monitoring requirement in the current Prescribing Information for IBRANCE
  • ECG, serum electrolyte, or liver enzyme tests are not required in the current IBRANCE Prescribing Information
–   In a QTc substudy of 77 patients from PALOMA-2, no large effect (>20 ms) on the QTc interval was observed in patients taking IBRANCE
–   In this substudy, the mean change from baseline for QTc was <8 ms with IBRANCE at all post-baseline time points in the QTc assessment period vs <7 ms in the control arm1
  • Additional monitoring may be necessary based on the individual patient

Detecting and managing neutropenia

  • Neutropenia was the most frequently reported adverse event in PALOMA-1 (75%), PALOMA-2 (80%), and PALOMA-3 (83%). Grade ≥3 neutropenia was reported in 62% and 66% of patients receiving IBRANCE + letrozole in PALOMA-1 and PALOMA-2, respectively, and in 66% of patients receiving IBRANCE + fulvestrant in PALOMA-31
  • Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop Grade 3 or 4 neutropenia
  • Febrile neutropenia has been reported in 1.8% of patients exposed to IBRANCE. One death due to neutropenic sepsis was observed in the PALOMA clinical trials
  • Advise patients to immediately report any signs or symptoms of myelosuppression or infection, such as fever, chills, dizziness, shortness of breath, weakness, or any increased tendency to bleed and/or to bruise
  • Primary prophylactic use of granulocyte-colony stimulating factors (GCSFs) was not permitted in PALOMA-1, PALOMA-2, or PALOMA-3, but they could be used to treat treatment-emergent neutropenia, as indicated by the current American Society of Clinical Oncology guidelines1

Neutropenia management in PALOMA-2 and PALOMA-31

  • Dose reductions or dose modifications due to neutropenia occurred in 24.3% of patients taking IBRANCE + letrozole in PALOMA-2 and 21.2% of patients taking IBRANCE + fulvestrant in PALOMA-3
  • 1.1% of patients discontinued IBRANCE due to neutropenia in PALOMA-2 and no patients discontinued in PALOMA-3
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REFERENCE
1. Data on file. Pfizer Inc, New York, NY.
Modify the dose if needed based on individual safety and tolerability
Recommended dose modifications for IBRANCE

Starting dose:
125 mg/day

First reduction:
100 mg/day

Second reduction:
75 mg/day

If dose reduction below 75 mg/day is required, discontinue IBRANCE

Pills not actual size.

Refer to the full Prescribing Information for coadministered endocrine therapy dose adjustment guidelines in the event of toxicity and other relevant safety information or contraindications.
Refer to the full Prescribing Information for coadministered endocrine therapy dose adjustment guidelines in the event of toxicity and other relevant safety information or contraindications.
Dose modifications may help manage hematologic and nonhematologic toxicities, if they occur
HEMATOLOGIC TOXICITIES*
SEVERITY
ACTION
 
Grade 1 (eg, ANC <LLN-1500/mm3)
Grade 2 (eg, ANC 1000-<1500/mm3)
NO ACTION
NEXT ACTION
Grade 3 on Day 1
(eg, ANC 500-<1000/mm3)
WITHHOLD
REPEAT CBC within 1 week
Once recovered to Grade ≤2:
RESUME at SAME DOSE
Grade 3 on Day 15 of first 2 cycles
CONTINUE at SAME DOSE to
complete cycle
REPEAT CBC on Day 22
If Grade 4 on Day 22,
see Grade 4 dose modification
guidelines
Grade 3 neutropenia with fever ≥38.5°C and/or infection at any time
Grade 4 (eg, ANC <500/mm3) at any time
WITHHOLD
Once recovered to Grade ≤2:
RESUME at NEXT LOWER DOSE
Grading according to Common Terminology Criteria for Adverse Events (CTCAE) 4.0. ANC=absolute neutrophil count; CBC=complete blood count; LLN=lower limit of normal.
*Table applies to all hematologic adverse reactions except lymphopenia (unless associated with clinical events, eg, opportunistic infections).
Consider dose reduction in cases of prolonged (>1 week) recovery from Grade 3 neutropenia or recurrent Grade 3 neutropenia on Day 1 in subsequent cycles.
NONHEMATOLOGIC TOXICITIES
NO ACTION required for Grade 1 or 2
If Grade ≥ 3 nonhematologic toxicities persist despite medical treatment, WITHHOLD until
  • Grade ≤1
  • Grade ≤2 (if not considered a safety risk for the patient)
RESUME at NEXT LOWER DOSE
Grading according to CTCAE 4.0.
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