2.1 General Dosing Information
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 should be taken with food [see Clinical Pharmacology (12.3)] in combination with letrozole 2.5 mg once daily given continuously throughout the 28-day cycle. 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 (do not chew, crush or open them prior to swallowing). No capsule should be ingested if it is broken, cracked, or otherwise not intact.
2.2 Dose Modification
Dose modification of IBRANCE is recommended based on individual safety and tolerability [see Warnings and Precautions (5)].
Management of some adverse reactions [see Warnings and Precautions (5)] may require temporary dose interruptions/delays and/or dose reductions, or permanent discontinuation as per dose reduction schedules provided in Tables 1, 2 and 3 [see Warnings and Precautions (5), Adverse Reactions (6) and Clinical Studies (14)].
Table 1. Recommended Dose Modification for Adverse Reactions
Dose Level
Dose
*
If further dose reduction below 75 mg/day is required, discontinue the treatment.
Recommended starting dose
125 mg/day
First dose reduction
100 mg/day
Second dose reduction
75 mg/day*
Table 2. Dose Modification and Management* – Hematologic Toxicities
CTCAE Grade
Dose Modifications
Grading according to CTCAE Version 4.0.
ANC=absolute neutrophil count; CTCAE=Common Terminology Criteria for Adverse Events.
*
Monitor complete blood count prior to the start of IBRANCE therapy and at the beginning of each cycle, as well as on Day 14 of the first two cycles, and as clinically indicated.
†
Except lymphopenia (unless associated with clinical events, e.g., opportunistic infections).
Grade 1 or 2
No dose adjustment is required.
Grade 3†
No dose adjustment is required.
Consider repeating complete blood count monitoring one week later. Withhold initiation of next cycle until recovery to Grade ≤2.
Grade 3 ANC (<1000 to 500/mm3) + Fever ≥38.5ºC and/or infection
Withhold IBRANCE and initiation of next cycle until recovery to Grade ≤2 (≥1000/mm3).
Resume at next lower dose.
Grade 4†
Withhold IBRANCE and initiation of next cycle until recovery to Grade ≤2.
Resume at next lower dose.
Table 3. Dose Modification and Management – Non-Hematologic Toxicities
CTCAE Grade
Dose Modifications
Grading according to CTCAE Version 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 medical treatment)
Withhold until symptoms resolve to:
Grade ≤1;
Grade ≤2 (if not considered a safety risk for the patient)
Resume at the next lower dose.
See manufacturer's prescribing information for the coadministered product, letrozole, 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 3–5 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)].
