Palbociclib
FDA Drug Information • Also known as: Ibrance
- Brand Names
- Ibrance
- Dosage Form
- POWDER
- Product Type
- BULK INGREDIENT
Description
11 DESCRIPTION IBRANCE tablets for oral administration contain 125 mg, 100 mg, or 75 mg of palbociclib, a kinase inhibitor. The molecular formula for palbociclib is C 24 H 29 N 7 O 2 . The molecular weight is 447.54 daltons. The chemical name is 6-acetyl-8-cyclopentyl-5-methyl-2-{[5-(piperazin-1-yl)pyridin-2-yl]amino}pyrido[2,3- d ]pyrimidin-7(8 H )-one, and its structural formula is: Palbociclib is a yellow to orange powder. At or below pH 4, palbociclib behaves as a high-solubility compound. Above pH 4, the solubility of the drug substance reduces significantly. Inactive Ingredients: Microcrystalline cellulose, colloidal silicon dioxide, crospovidone, magnesium stearate, succinic acid, HPMC 2910/hypromellose, titanium dioxide, triacetin, and FD&C Blue #2/Indigo Carmine Aluminum Lake. In addition, the 75 mg and 125 mg tablets contain red iron oxide and the 100 mg tablets contain yellow iron oxide. Chemical Structure
What Is Palbociclib Used For?
1 INDICATIONS AND USAGE IBRANCE is indicated for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (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. IBRANCE is indicated in combination with inavolisib and fulvestrant for the treatment of adult patients with endocrine-resistant, PIK3CA -mutated, HR-positive, HER2-negative, locally advanced or metastatic breast cancer, as detected by an FDA-approved test, following recurrence on or after completing adjuvant endocrine therapy. IBRANCE is a kinase inhibitor indicated: for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in combination with: o an aromatase inhibitor as initial endocrine-based therapy ( 1 ); or o fulvestrant in patients with disease progression following endocrine therapy. ( 1 ) in combination with inavolisib and fulvestrant for the treatment of adult patients with endocrine-resistant, PIK3CA -mutated, HR-positive, HER2-negative, locally advanced or metastatic breast cancer, as detected by an FDA-approved test, following recurrence on or after completing adjuvant endocrine therapy. ( 1 )Dosage and Administration
2 DOSAGE AND ADMINISTRATION IBRANCE tablets are taken orally with or without food in combination with an aromatase inhibitor, fulvestrant, or inavolisib and fulvestrant. ( 2 )
Recommended starting dose: 125 mg once daily taken with or without food for 21 days followed by 7 days off treatment. ( 2.1 ) Dosing interruption and/or dose reductions are recommended based on individual safety and tolerability. ( 2.2 ) 2.1 Recommended Dose and Schedule The recommended dose of IBRANCE is a 125 mg tablet taken orally once daily for 21 consecutive days followed by 7 days off treatment to comprise a complete cycle of 28 days. IBRANCE tablet may be taken with or without food [see Clinical Pharmacology (12.3) ] . Administer the recommended dose of an aromatase inhibitor when given with IBRANCE. Please refer to the Full Prescribing Information for the aromatase inhibitor being used. When given with IBRANCE, 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. Refer to the Full Prescribing Information for inavolisib and fulvestrant for dosing information . Advise patients to take their dose of IBRANCE 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. IBRANCE tablets should be swallowed whole (do not chew, crush, or split them prior to swallowing). Tablets should not be ingested if they are broken, cracked, or otherwise not intact. Pre/perimenopausal women treated with the combination IBRANCE plus an aromatase inhibitor or fulvestrant therapy or IBRANCE plus inavolisib and fulvestrant should also be treated with luteinizing hormone-releasing hormone (LHRH) agonists according to current clinical practice standards. For men treated with combination IBRANCE plus aromatase inhibitor or IBRANCE plus inavolisib and fulvestrant therapy, consider treatment with an LHRH agonist according to current clinical practice standards. 2.2 Dose Modification The recommended dose modifications for adverse reactions are listed in Tables 1, 2, and 3. Table 1. Recommended Dose Modification for Adverse Reactions Dose Level Dose Recommended starting 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. Table 2. Dose Modification and Management – Hematologic Toxicities Table applies to all hematologic adverse reactions except lymphopenia (unless associated with clinical events, e.g., opportunistic infections). Grading according to CTCAE 4.0. CTCAE=Common Terminology Criteria for Adverse Events; LLN=lower limit of normal. Monitor complete blood counts 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. For patients who experience a maximum of Grade 1 or 2...Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling:
Neutropenia [see Warnings and Precautions (5.1) ] ILD/Pneumonitis [see Warnings and Precautions (5.2) ] Most common adverse reactions (incidence ≥20%) in combination with either letrozole or fulvestrant, including laboratory abnormalities, were white blood cell count decreased, neutrophils decreased, blood creatinine increased, hemoglobin decreased, platelets decreased, infections, aspartate aminotransferase increased, alanine aminotransferase increased, fatigue, nausea, stomatitis, diarrhea, and alopecia. ( 6.1 ) The most common adverse reactions (incidence ≥20%) in combination with inavolisib and fulvestrant, including laboratory abnormalities, were neutrophils decreased, hemoglobin decreased, fasting glucose increased, platelets decreased, lymphocytes decreased, stomatitis, diarrhea, calcium decreased, fatigue, potassium decreased, creatinine increased, alanine aminotransferase (ALT) increased, nausea, sodium decreased, magnesium decreased, rash, decreased appetite, COVID-19 infection, and headache. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Studies Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. PALOMA-2: IBRANCE plus Letrozole Patients with estrogen receptor (ER)-positive, HER2-negative advanced or metastatic breast cancer for initial endocrine-based therapy The safety of IBRANCE (125 mg/day) plus letrozole (2.5 mg/day) versus placebo plus letrozole was evaluated in PALOMA-2. The data described below reflect exposure to IBRANCE in 444 out of 666 patients with ER-positive, HER2-negative advanced breast cancer who received at least 1 dose of IBRANCE plus letrozole in PALOMA-2. The median duration of treatment for IBRANCE plus letrozole was 19.8 months while the median duration of treatment for placebo plus letrozole arm was 13.8 months. Dose reductions due to an adverse reaction of any grade occurred in 36% of patients receiving IBRANCE plus letrozole. No dose reduction was allowed for letrozole in PALOMA-2. Permanent discontinuation associated with an adverse reaction occurred in 43 of 444 (10%) patients receiving IBRANCE plus letrozole and in 13 of 222 (6%) patients receiving placebo plus letrozole. Adverse reactions leading to permanent discontinuation for patients receiving IBRANCE plus letrozole included neutropenia (1.1%) and alanine aminotransferase increase (0.7%). The most common adverse reactions (≥10%) of any grade reported in patients in the IBRANCE plus letrozole arm by descending frequency were neutropenia, infections, leukopenia, fatigue, nausea, alopecia, stomatitis, diarrhea, anemia, rash, asthenia, thrombocytopenia, vomiting, decreased appetite, dry skin, pyrexia, and dysgeusia. The most frequently reported Grade ≥3 adverse reactions (≥5%) in patients receiving IBRANCE plus letrozole by descending frequency were neutropenia, leukopenia, infections, and anemia. Adverse reactions (≥10%) reported in patients who received IBRANCE plus letrozole or placebo plus letrozole in PALOMA-2 are listed in Table 4. Table 4. Adverse Reactions (≥10%) in PALOMA-2 IBRANCE plus Letrozole (N=444) Placebo plus Letrozole (N=222) Adverse Reaction All Grades % Grade 3 % Grade 4 % All Grades % Grade 3 % Grade 4 % Grading according to CTCAE 4.0. CTCAE=Common Terminology Criteria for Adverse Events; N=number of patients; N/A=not applicable; Infections and infestations Infections Infections includes all reported preferred terms (PTs) that are part of the System Organ Class Infections and infestations. 60 Most common infections (≥1%) include: nasopharyngitis, upper respiratory tract...Drug Interactions
7 DRUG INTERACTIONS Palbociclib is primarily metabolized by CYP3A and sulfotransferase (SULT) enzyme SULT2A1. In vivo, palbociclib is a time-dependent inhibitor of CYP3A.
CYP3A Inhibitors: Avoid concurrent use of IBRANCE with strong CYP3A inhibitors. If the strong inhibitor cannot be avoided, reduce the IBRANCE dose. ( 2.2 , 7.1 ) CYP3A Inducers: Avoid concurrent use of IBRANCE with strong CYP3A inducers. ( 7.2 ) CYP3A Substrates: The dose of sensitive CYP3A4 substrates with narrow therapeutic indices may need to be reduced when given concurrently with IBRANCE. ( 7.3 ) 7.1 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 IBRANCE treatment. If coadministration of IBRANCE with a strong CYP3A inhibitor cannot be avoided, reduce the dose of IBRANCE [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3) ] . 7.2 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) [see Clinical Pharmacology (12.3) ] . 7.3 Drugs That May Have Their Plasma Concentrations Altered by Palbociclib Coadministration of midazolam with multiple doses of IBRANCE 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 IBRANCE may increase its exposure [see Clinical Pharmacology (12.3) ] .Contraindications
4 CONTRAINDICATIONS None. None. ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action, IBRANCE can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . 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 (see Data ) . 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. Data Animal Data In a fertility and early embryonic development study in female rats, palbociclib was administered orally for 15 days before mating through to Day 7 of pregnancy, which did not cause embryo toxicity at doses up to 300 mg/kg/day with maternal systemic exposures approximately 4 times the human exposure (AUC) at the recommended dose. In embryo-fetal development studies in rats and rabbits, pregnant animals received oral doses of palbociclib up to 300 mg/kg/day and 20 mg/kg/day, respectively, during the period of organogenesis. The maternally toxic dose of 300 mg/kg/day was fetotoxic in rats, resulting in reduced fetal body weights. At doses ≥100 mg/kg/day in rats, there was an increased incidence of a skeletal variation (increased incidence of a rib present at the seventh cervical vertebra). At the maternally toxic dose of 20 mg/kg/day in rabbits, there was an increased incidence of skeletal variations, including small phalanges in the forelimb. At 300 mg/kg/day in rats and 20 mg/kg/day in rabbits, the maternal systemic exposures were approximately 4 and 9 times the human exposure (AUC) at the recommended...
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING IBRANCE is supplied in the following strengths and package configurations: IBRANCE Tablets Package Configuration Tablet Strength (mg) NDC Tablet Description Monthly box containing 3 weekly blister packs of 7 tablets each (21 tablets total) 125 NDC 0069-0688-03 Oval, light purple, film-coated tablets debossed with "Pfizer" on one side and "PBC 125" on the other side. Monthly box containing 3 weekly blister packs of 7 tablets each (21 tablets total) 100 NDC 0069-0486-03 Oval, green, film-coated tablets debossed with "Pfizer" on one side and "PBC 100" on the other side. Monthly box containing 3 weekly blister packs of 7 tablets each (21 tablets total) 75 NDC 0069-0284-03 Round, light purple, film-coated tablets debossed with "Pfizer" on one side and "PBC 75" on the other side. Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature] . Store in the original blister pack.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.