Ibrance

Treatment with IBRANCE should be initiated and supervised by a physician experienced in the use of anticancer medicinal products. Posology The recommended dose is 125 mg of palbociclib once daily for 21 consecutive days followed by 7 days off treatment (Schedule 3/1) to comprise a complete cycle of 28 days.

The treatment with IBRANCE should be continued as long as the patient is deriving clinical benefit from therapy or until unacceptable toxicity occurs. When coadministered with palbociclib, the aromatase inhibitor should be administered according to the dose schedule reported in the Summary of Product Characteristics.

4). When coadministered with palbociclib, the recommended dose of fulvestrant is 500 mg administered intramuscularly on Days 1, 15, 29, and once monthly thereafter. Please refer to the Summary of Product Characteristics of fulvestrant.

Prior to the start of treatment with the combination of palbociclib plus fulvestrant, and throughout its duration, pre/perimenopausal women should be treated with LHRH agonists according to local clinical practice. 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. Dose adjustments Dose modification of IBRANCE is recommended based on individual safety and tolerability.

8). Table 1. IBRANCE recommended dose modifications for adverse reactions Dose level Dose Recommended dose 125 mg/day First dose reduction 100 mg/day Second dose reduction 75 mg/day* *If further dose reduction below 75 mg/day is required, discontinue the treatment.

Complete blood count should be monitored 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. 4 For patients who experience a maximum of Grade 1 or 2 neutropenia in the first 6 cycles, complete blood counts for subsequent cycles should be monitored every 3 months, prior to the beginning of a cycle and as clinically indicated.

Absolute neutrophil counts (ANC) of ≥ 1,000/mm3 and platelet counts of ≥ 50,000/mm3 are recommended to receive IBRANCE. Table 2. IBRANCE dose modification and management – Haematological toxicities CTCAE grade Dose modifications Grade 1 or 2 No dose adjustment is required.

Summary of the safety profile The overall safety profile of IBRANCE is based on pooled data from 872 patients who received palbociclib in combination with endocrine therapy (N=527 in combination with letrozole and N=345 in combination with fulvestrant) in randomised clinical studies in HR-positive, HER2-negative advanced or metastatic breast cancer.

The most common (≥ 20%) adverse reactions of any grade reported in patients receiving palbociclib in randomised clinical studies were neutropenia, infections, leukopenia, fatigue, nausea, stomatitis, anaemia, diarrhoea, alopecia and thrombocytopenia.

The most common (≥ 2%) Grade ≥ 3 adverse 10 reactions of palbociclib were neutropenia, leukopenia, infections, anaemia, aspartate aminotransferase (AST) increased, fatigue, and alanine aminotransferase (ALT) increased. 4% of patients receiving IBRANCE in randomised clinical studies regardless of the combination.

2% of patients receiving IBRANCE in randomised clinical studies regardless of the combination. Tabulated list of adverse reactions Table 4 reports the adverse reactions from the pooled dataset of 3 randomised studies. 8 months. Table 5 reports the laboratory abnormalities observed in pooled datasets from 3 randomised studies.

The adverse reactions are listed by system organ class and frequency category. Frequency categories are defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10), and uncommon (≥ 1/1,000 to < 1/100). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 4. 0) 11 Table 4. 2) ALT=alanine aminotransferase; AST=aspartate aminotransferase; ILD=interstitial lung disease; N/n=number of patients; N/A=not applicable. 1. b Infections includes all PTs that are part of the System Organ Class Infections and infestations.

c Neutropenia includes the following PTs: Neutropenia, Neutrophil count decreased. d Leukopenia includes the following PTs: Leukopenia, White blood cell count decreased. e Anaemia includes the following PTs: Anaemia, Haemoglobin decreased, Haematocrit decreased.

Pre/perimenopausal women Ovarian ablation or suppression with an LHRH agonist is mandatory when pre/perimenopausal women are administered IBRANCE in combination with an aromatase inhibitor, due to the mechanism of action of aromatase inhibitors.

Palbociclib in combination with fulvestrant in pre/perimenopausal women has only been studied in combination with an LHRH agonist. 1). Haematological disorders Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop Grade 3 or 4 neutropenia.

8). 6 Interstitial lung disease/pneumonitis Severe, life-threatening, or fatal ILD and/or pneumonitis can occur in patients treated with IBRANCE when taken in combination with endocrine therapy. 1% had Grade 3, and no Grade 4 or fatal cases were reported.

8). g. hypoxia, cough, dyspnoea). In patients who have new or worsening respiratory symptoms and are suspected to have developed ILD/pneumonitis, IBRANCE should be immediately interrupted and the patient should be evaluated. 2). Infections Since IBRANCE has myelosuppressive properties, it may predispose patients to infections.

Infections have been reported at a higher rate in patients treated with IBRANCE in randomised clinical studies compared to patients treated in the respective comparator arm. 8). 2). Physicians should inform patients to promptly report any episodes of fever.

8). Patients should be monitored for signs and symptoms of deep vein thrombosis and pulmonary embolism, and treated as medically appropriate. 2). 2). 5). Concomitant use of strong CYP3A inhibitors during treatment with palbociclib should be avoided.

Coadministration should only be considered after careful evaluation of the potential benefits and risks. If coadministration with a strong CYP3A inhibitor is unavoidable, reduce the IBRANCE dose to 75 mg once daily. 5). 7 Coadministration of CYP3A inducers may lead to decreased palbociclib exposure and consequently a risk for lack of efficacy.

1. Use of preparations containing St. 5).