Ibrance 75, 100, 125 mg

/ Pfizer

The recommended dose 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. Should be taken with food. Administer the recommended dose of an aromatase inhibitor when given with Palbociclib . Please refer to the Full Prescribing Information for the aromatase inhibitor being used.
When given with Palbociclib, 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. Advise patients to take their dose of Palbociclib 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. Palbociclib 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 Palbociclib plus an aromatase inhibitor or fulvestrant therapy should be treated with luteinizing hormone-releasing hormone (LHRH) agonists according to current clinical practice standards.
For men treated with palbociclib combination  plus aromatase inhibitor therapy, consider treatment with an LHRH agonist according to current clinical practice standards.
See prescribing information for full details.

Palbociclib is indicated for the treatment of HR-positive, 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.

Hypersensitivity to Palbociclib or to any of the excipients.

Neutropenia:  Monitor complete blood counts before starting Palbociclib therapy and at the beginning of each cycle, as well as on Day 15 of the first 2 cycles, and as clinically indicated. 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 Palbociclib across Studies 1 and 2. One death due to neutropenic sepsis was observed in Study 2. Physicians should inform patients to report any episodes of fever promptly.
Interstitial Lung Disease (ILD)/Pneumonitis: Severe, life-threatening, or fatal interstitial lung disease (ILD) and/or pneumonitis can occur in patients treated with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, including Palbociclib when taken in combination with endocrine therapy. Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis (e.g. hypoxia, cough, dyspnea). In patients who have new or worsening respiratory symptoms and are suspected to have developed pneumonitis, interrupt Palbociclib immediately and evaluate the patient. Permanently discontinue Palbociclib in patients with severe ILD or pneumonitis.
Embryo-Fetal Toxicity: Based on findings from animal studies and its mechanism of action, Palbociclib can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with Palbociclib and for at least 3 weeks after the last dose.
Venous thromboembolism
Signs and symptoms of deep vein thrombosis and pulmonary embolism should be monitored and treated as medically appropriate
See prescribing information for full details.

Blood and lymphatic system disorders, Decreased appetite, Gastro-intestinal disorders, ILD/Pneumonitis.
See prescribing information for full details.

Palbociclib is primarily metabolized by CYP3A and sulfotransferase (SULT) enzyme SULT2A1. In vivo, palbociclib is a time-dependent inhibitor of CYP3A.
Agents That May Increase Palbociclib Plasma Concentrations
Effect of CYP3A Inhibitors: Coadministration of a strong CYP3A inhibitor (itraconazole) increased the plasma exposure of palbociclib in healthy subjects by 87%. Avoid concomitant use of strong CYP3A inhibitors (e.g., clarithromycin, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, and voriconazole). Avoid grapefruit or grapefruit juice during Palbociclib treatment. If coadministration of Palbociclib with a strong CYP3A inhibitor cannot be avoided, reduce the dose of Palbociclib.
Agents That May Decrease Palbociclib Plasma Concentrations
Effect of CYP3A Inducers: Coadministration of a strong CYP3A inducer (rifampin) decreased the plasma exposure of palbociclib in healthy subjects by 85%. Avoid concomitant use of strong CYP3A inducers (e.g., phenytoin, rifampin, carbamazepine, enzalutamide, and St John’s Wort).
Drugs That May Have Their Plasma Concentrations Altered by Palbociclib:Coadministration of midazolam with multiple doses of Palbociclib increased the midazolam plasma exposure by 61%, in healthy subjects, compared to administration of midazolam alone. The dose of the sensitive CYP3A substrate with a narrow therapeutic index (e.g., alfentanil, cyclosporine, dihydroergotamine, ergotamine, everolimus, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus) may need to be reduced, as Palbociclib may increase its exposure.

Pregnancy: Based on findings from animal studies and its mechanism of action, Palbociclib can cause fetal harm when administered to a pregnant woman. There are no available data in pregnant women to inform the drug-associated risk. In animal reproduction studies, administration of palbociclib to pregnant rats and rabbits during organogenesis resulted in embryo-fetal toxicity at maternal exposures that were 4 times the human clinical exposure based on AUC. Advise pregnant women of the potential risk to a fetus.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively.
See prescribing information for full details.
Lactation: 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 Palbociclib, advise a lactating woman not to breastfeed during treatment with Palbociclib and for 3 weeks after the last dose.

There is no known antidote for Palbociclib. The treatment of overdose of Palbociclib should consist of general supportive measures.

Shelf life after first opening: 6 months.
Driving and using machines: Fatigue is a very common side effect. Patients should take special care when driving or using machines.