Please refer to the Summary of Product Characteristics (SmPC) before prescribing IBRANCE 75 mg, 100 mg or 125 mg. Presentation: Film-coated tablets containing 75 mg, 100 mg or 125 mg palbociclib. Indications: Treatment of hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative locally advanced or metastatic breast cancer: in combination with an aromatase inhibitor; or in combination with fulvestrant in women who have received prior endocrine therapy. In pre- or perimenopausal women, the endocrine therapy should be combined with a luteinizing hormone releasing hormone (LHRH) agonist. Dosage: Therapy should be initiated and supervised by a physician experienced in the administration of anti-cancer medicinal products. 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. When coadministered with palbociclib, the aromatase inhibitor should be administered according to the dose schedule reported in the SmPC. Treatment of pre/perimenopausal women with the combination of palbociclib plus endocrine therapy should always be combined with an LHRH agonist (see SmPC section 4.4). IBRANCE tablets should be swallowed whole (should not be chewed, crushed, split or opened prior to swallowing) and may be taken with or without food.Palbociclib should not be taken with grapefruit or grapefruit juice (see SmPC section 4.5). Dose modification of IBRANCE is recommended based on individual safety and tolerability. Management of some adverse reactions may require temporary dose interruptions/delays, and/or dose reductions, or permanent discontinuation. For dose reduction guidelines for management of adverse reactions, haematologic and non-haematologic toxicities, refer to SmPC section 4.2. IBRANCE should be permanently discontinued in patients with severe interstitial lung disease (ILD)/pneumonitis. 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. No dose adjustments of IBRANCE are 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 on Schedule 3/1 (see SmPC section 5.2). No dose adjustments of IBRANCE are required for patients with mild, moderate or severe renal impairment (creatinine clearance [CrCl] ≥15 mL/min) (see SmPC section 5.2). No dose adjustment of IBRANCE is necessary in patients ≥65 years of age (see SmPC section 5.2). Contraindications: Hypersensitivity to the active substance or to any of the excipients (see SmPC section 6.1), use of preparations containing St. John’s Wort (see SmPC section 4.5). Warnings and Precautions: 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. Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop Grade 3 or 4 neutropenia. Appropriate monitoring should be performed (see SmPC sections 4.2 and 4.8). Severe, life-threatening, or fatal ILD and/or pneumonitis can occur in patients treated with cyclin dependent kinase 4/6 (CDK4/6) inhibitors, including IBRANCE when taken in combination with endocrine therapy. Across clinical studies (PALOMA-1, PALOMA-2, PALOMA-3), 1.4% of IBRANCE-treated patients had ILD/pneumonitis of any grade, 0.1% had Grade 3, and no Grade 4 or fatal cases were reported. Additional cases of ILD/pneumonitis have been observed in the post-marketing setting, with fatalities reported. Patients should be monitored for pulmonary symptoms and IBRANCE treatment should be immediately interrupted in patients suspected to have developed ILD/pneumonitis, see SmPC sections 4.2, 4.4 and 4.8. 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. Grade 3 and Grade 4 infections occurred respectively in 5.6% and 0.9% of patients treated with IBRANCE in any combination (see SmPC section 4.8). Patients should be monitored for signs and symptoms of infection and treated as medically appropriate (see SmPC section 4.2). Physicians should inform patients to promptly report any episodes of fever. Venous thromboembolic events were reported in patients treated with IBRANCE (see SmPC sections 4.4, 4.8). Patients should be monitored for signs and symptoms of deep vein thrombosis and pulmonary embolism, and treated as medically appropriate. Strong inhibitors of CYP3A4 may lead to increased toxicity (see SmPC section 4.5). Avoid concomitant use of strong CYP3A inhibitors during treatment with palbociclib. 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. When the strong inhibitor is discontinued, the dose of IBRANCE should be increased (after 3–5 half-lives of the inhibitor) to the dose used prior to the initiation of the strong CYP3A inhibitor (see SmPC section 4.5). Coadministration of CYP3A inducers may lead to decreased palbociclib exposure and consequently a risk for lack of efficacy. Therefore, concomitant use of palbociclib with strong CYP3A4 inducers should be avoided. No dose adjustments are required for coadministration of palbociclib with moderate CYP3A inducers (see SmPC section 4.5). Women of childbearing potential or their male partners must use a highly effective method of contraception while taking IBRANCE (see SmPC section 4.6). Drug Interactions: The concomitant use of strong CYP3A inhibitors including, but not limited to: clarithromycin, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, saquinavir, telaprevir, telithromycin, voriconazole, and grapefruit or grapefruit juice, should be avoided (see SmPC sections 4.2 and 4.4). No dose adjustments are needed for mild and moderate CYP3A inhibitors. The concomitant use of strong CYP3A inducers including, but not limited to: carbamazepine, enzalutamide, phenytoin, rifampin, and St. John’s Wort should be avoided (see SmPC sections 4.3 and 4.4). No dose adjustments are required for moderate CYP3A inducers. The dose of sensitive CYP3A substrates with a narrow therapeutic index (e.g., alfentanil, cyclosporine, dihydroergotamine, ergotamine, everolimus, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus) may need to be reduced when coadministered with IBRANCE as IBRANCE may increase their exposure. Based on in vitro data, palbociclib is predicted to inhibit intestinal P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) mediated transport. Therefore, administration of palbociclib with medicinal products that are substrates of P-gp (e.g., digoxin, dabigatran, colchicine) or BCRP (e.g., pravastatin, rosuvastatin, fluvastatin, sulfasalazine) may increase their therapeutic effect and adverse reactions. Based on in vitro data, palbociclib may inhibit the uptake transporter organic cationic transporter OCT1 and then may increase the exposure of medical product substrates of this transporter (e.g., metformin). Concomitant use of palbociclib with statins which are substrates of CYP3A4 and/or BCRP may increase the risk of rhabdomyolysis due to increased statin plasma concentration. Cases of rhabdomyolysis including fatal cases have been reported following coadministration of palbociclib with simvastatin or atorvastatin. Pregnancy & Lactation: Females of childbearing potential who are receiving this medicinal product, or their male partners should use adequate contraceptive methods (e.g., double- barrier contraception) during therapy and for at least 3 weeks or 14 weeks after completing therapy for females and males, respectively (see SmPC section 4.5). There are no or limited amount of data from the use of palbociclib in pregnant women. Studies in animals have shown reproductive toxicity (see SmPC section 5.3). IBRANCE is not recommended during pregnancy and in women of childbearing potential not using contraception. Based on male reproductive organ findings (seminiferous tubule degeneration in testis, epididymal hypospermia, lower sperm motility and density, and decreased prostate secretion) in nonclinical safety studies, male fertility may be compromised by treatment with palbociclib (see SmPC section 5.3). Thus, men may consider sperm preservation prior to beginning therapy with IBRANCE. Driving and Operating Machinery: IBRANCE may cause fatigue and patients should exercise caution when driving or using machines. Side Effects: 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 reactions of palbociclib were neutropenia, leukopenia, anaemia, fatigue, infections, alanine aminotransferase (ALT) increased and aspartate aminotransferase (AST) increased. Dose reductions or dose modifications due to any adverse reaction occurred in 38.4% of patients receiving IBRANCE in randomised clinical studies regardless of the combination. Very common adverse events (>1/10) are neutropenia, infections, leukopenia, fatigue, nausea, stomatitis, anaemia, diarrhoea, alopecia, thrombocytopenia, vomiting, rash, decreased appetite, asthenia, pyrexia, AST increased, dry skin, and ALT increased. Commonly reported adverse events (>1/100 to <1/10), are dysgeusia, epistaxis, lacrimation increased, blood creatinine increased, vision blurred, dry eye, venous thromboembolism, Palmar-plantar erythrodysaesthesia syndrome, febrile neutropenia, ILD/pneumonitis. Refer to section 4.8 of the SmPC for further information on side effects, including description of selected adverse reactions. Legal Category: S1A. Marketing Authorisation Numbers: EU/1/16/1147/010 – 75 mg (21 tablets), EU/1/16/1147/012 – 100 mg (21 tablets) and EU/1/16/1147/014 – 125 mg (21 tablets). Marketing Authorisation Holder: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium. For further information on this medicine please contact: Pfizer Medical Information on 1800 633 363 or at [email protected]. For queries regarding product availability please contact: Pfizer Healthcare Ireland, Pfizer Building 9, Riverwalk, National Digital Park, Citywest Business Campus, Dublin 24 + 353 1 4676500.
Last revised: 05/2024

Ref: IB 12_0