Palbociclib

Palbociclib is used to treat a certain type of breast cancer. It is a chemotherapy drug that works by slowing or stopping the growth of cancer cells.

Palbociclib is available under the following different brand names: Ibrance.

Dosages of Palbociclib

Capsules

• 75 mg
• 100 mg
• 125 mg

Tablets

• 75 mg
• 100 mg
• 125 mg

Dosing Modifications

Breast Cancer

Indication

• Indicated for the treatment of adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer as follows:
• Men or postmenopausal women
  • Use in combination with an aromatase inhibitor as initial endocrine-based therapy
• Patients with disease progression following endocrine therapy
  • Use in combination with fulvestrant

Combination therapy with an aromatase inhibitor

• Palbociclib 125 mg orally once daily for Days 1-21 of each 28-day cycle
• Aromatase inhibitor: See prescribing information
• Continue until disease progression or unacceptable toxicity
• Men treated with combination palbociclib plus aromatase inhibitor therapy, consider treatment with a luteinizing hormone-releasing hormone (LHRH) agonist according to current clinical practice standards

Combination therapy with fulvestrant

• Palbociclib 125 mg orally once daily for Days 1-21 of each 28-day cycle
• Fulvestrant 500 mg IM on Days 1, 15, and 29, and then once monthly thereafter
• Continue until disease progression or unacceptable toxicity
• Pre/perimenopausal women treated with the combination palbociclib plus fulvestrant should also be treated with an LHRH agonist according to current clinical practice standards

Dosage Modifications

Dose reduction for adverse reaction

• First dose reduction: Reduce to 100 mg/day
• Second dose reduction: Reduce to 75 mg/day
• If further dose reduction below 75 mg/day is required, discontinue treatment

Hematologic toxicities

• Grade 1 or 2: No dose adjustment required
• Grade 3*:
  • Day 1 of the cycle: Withhold dose, repeat CBC within 1 week; when recovered to grade less than or equal to 2, start next cycle at the same dose
  • Day 15 of first 2 cycles: If grade 3 on Day 15, continue at a current dose to complete cycle; repeat CBC on Day 22; if grade 4 on Day 22, see grade 4 dose modifications below
  • Prolonged (more than 1 week) recovery from grade 3 or recurrent Grade 3 neutropenia in subsequent cycles: Consider dose reduction
• Grade 3 ANC (less than 1000 to 500/mm³) + fever 38.5ºC or greater and/or infection: Withhold drug until recovery to grade less than or equal to 2 (1000/mm³ or greater); resume at next lower dose
• Grade 4*: Withhold drug until recovery to grade less than or equal to 2; resume at next lower dose
• *Above refers to all hematologic adverse reactions except lymphopenia, unless associated with the clinical event (e.g., opportunistic infections)

Nonhematologic toxicities

• Grade 1 or 2: No dose adjustment required
• Grade 3 or greater (if persisting despite medical treatment): Withhold until symptoms resolve to grade less than or equal to 1 or grade less than or equal to 2 (if not considered a safety risk for the patient to resume); resume at next lower dose

Coadministration with strong CYP3A inhibitors

• Avoid use with strong CYP3A inhibitors and consider an alternative with no or minimal CYP3A inhibition
• If coadministration cannot be avoided, reduce palbociclib dose to 75 mg/day
• If the strong inhibitor is discontinued, increase the palbociclib dose (after 3-5 half-lives of the inhibitor) to the dose used before the initiation of the strong CYP3A inhibitor

Hepatic impairment

• Mild or moderate (Child-Pugh A or B): No dose adjustment required
• Severe (Child-Pugh C): Reduce dose to 75 mg/day for Days 1-21 of each 28-day cycle

Renal impairment

• Mild, moderate, or severe (CrCl greater than 15 mL/min): No dose adjustment is required
• Hemodialysis: Not studied

Interstitial lung disease (ILD) or pneumonitis

• Permanently discontinue treatment in patients with severe ILD/pneumonitis

Dosing Considerations

• Monitor CBC at baseline and at the beginning of each cycle, as well as on Day 14 of the first 2 cycles, and as clinically indicated
• Pediatric patients: Safety and efficacy have not been established

Common side effects of Palbociclib include:

• WBC decreased
• Neutrophils decreased
• Neutropenia
• Platelets decreased
• Infections
• AST increased
• ALT increased
• Leukopenia
• Fatigue
• Nausea
• Hair loss
• Inflammation of the mouth and lips
• Diarrhea
• Anemia
• Rash
• Weakness/lethargy
• Vomiting
• Thrombocytopenia
• Dry skin
• Fever

Common side effects of palbociclib with fulvestrant include:

WBC decreased
• Neutrophils decreased
• Neutropenia
• Anemia
• Platelets decreased
• Leukopenia
• Infections
• AST increased
• Fatigue
• ALT increased
• Nausea
• Inflammation of the mouth and lips
• Diarrhea
• Vomiting
• Thrombocytopenia
• Hair loss
• Rash
• Decreased appetite
• Fever

Less common side effects of palbociclib with letrozole include:

• Neutropenia, Grade 4
• Anemia, Grade 3
• Infections, Grade 3 or 4
• AST increased, Grade 3
• ALT increased, Grade 3
• Thrombocytopenia, Grade 3
• Stomatitis, Grade 3
• Diarrhea, Grade 3
• Vomiting, Grade 3
• Leukopenia, Grade 4
• Rash, Grade 3
• WBC decreased, Grade 4
• Neutrophils decreased, Grade 4
• Platelets decreased, Grade 3 or 4

Less common side effects of palbociclib with fulvestrant include:

• Weakness/lethargy
• Changes in taste
• Nosebleed
• Increased tearing
• Dry skin
• ALT increased
• Vision blurred
• Anemia, Grade 3
• AST increased, Grade 3
• Dry eye
• Infections, Grade 3 or 4
• Anemia, Grade 3
• Platelets decreased, Grade 3
• ALT increased, Grade 3
• Thrombocytopenia, Grade 3
• Fatigue, Grade 3
• Leukopenia, Grade 4
• Decreased appetite, Grade 3
• Vomiting, Grade 3
• Stomatitis, Grade 3
• Rash, Grade 3
• WBC decreased, Grade 4

Rare side effects of palbociclib with letrozole include:

• Anemia, Grade 4
• Thrombocytopenia, Grade 4
• Nausea, Grade 3
• ALT increased, Grade 4

Rare side effects of palbociclib with fulvestrant include:

• Fever, Grade 3
• Infections, Grade 4
• Febrile neutropenia

Postmarketing side effects of palbociclib reported include:

• Interstitial lung disease (ILD)/non-infectious pneumonitis

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

• Palbociclib has serious interactions with at least 48 different drugs.
• Palbociclib has moderate interactions with at least 66 different drugs.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

Warnings

• This medication contains palbociclib. Do not take Ibrance if you are allergic to palbociclib or any ingredients contained in this drug.

Contraindications

• None.

Effects of Drug Abuse

• No information is available.

Short-Term Effects

• See "What Are Side Effects Associated with Using Palbociclib?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Palbociclib?"

Cautions

• Neutropenia observed in clinical trials; febrile neutropenia also reported; monitor CBC count prior to starting the drug and at the beginning of each cycle, as well as on Day 14 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
• Grade 3 and 4 infections reported when administered in combination with an antiestrogen compared to patients receiving antiestrogen only; monitor and manage appropriately symptoms and signs of infection
• Nausea, vomiting, diarrhea, and grade 1 or 2 stomatitis were reported in clinical trials
• Severe, life-threatening, or fatal ILD and/or pneumonitis can occur; additional cases of ILD/pneumonitis have been observed in the postmarketing setting, with fatalities reported; monitor for pulmonary symptoms indicative of ILD/pneumonitis which may include hypoxia, cough, and dyspnea; permanently discontinue therapy in patients with severe ILD or pneumonitis
• Based on findings in animals and mechanism of action, palbociclib can cause fetal harm

Drug interaction overview

• In vitro data indicate that CYP3A and SULT enzyme SULT2A1 are mainly involved in the metabolism of palbociclib
• Palbociclib is also a weak time-dependent inhibitor of CYP3A following daily 125 mg dosing to steady-state in humans
• Avoid use with strong CYP3A inhibitors; if coadministration cannot be avoided, reduce the palbociclib dose (see Dosage Modifications)
• Avoid use with moderate or strong CYP3A inducers
• Palbociclib may increase sensitive CYP3A substrates with a narrow therapeutic index (e.g., alfentanil, cyclosporine, dihydroergotamine, ergotamine, everolimus, fentanyl, midazolam, pimozide, quinidine

Pregnancy and Lactation

• Based on findings in animals and mechanism of action, palbociclib can cause fetal harm when administered to a pregnant woman. Females of reproductive potential should have a pregnancy test before starting treatment with palbociclib. Females of reproductive potential are advised to use effective contraception during treatment with palbociclib and for at least 3 weeks after the last dose. Male patients with female partners of reproductive potential are advised to use effective contraception during treatment with palbociclib and for 3 months after the last dose.
• It is unknown if palbociclib is distributed in human breast milk. Owing to the potential for serious adverse reactions in breastfed infants, lactating women are advised not to breastfeed while taking palbociclib and for at least 3 weeks after the last dose.