palbociclib

High Alert

Advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor 2 (HER2)-negative breast cancer as initial endocrine-based therapy (in combination with an aromatase inhibitor).
Advanced or metastatic HR-positive, HER2-negative breast cancer in patients with disease progression following endocrine therapy (in combination with fulvestrant).
Locally advanced or metastatic, HR-positive, HER2-negative, endocrine-resistant, PIK3CA-mutated breast cancer following recurrence on or after completing adjuvant endocrine therapy (in combination with inavolisib and fulvestrant).

Action ⬆ ⬇

Inhibits kinases (cyclin-dependent kinases 4 and 6) that are part of the signaling pathway for cell proliferation.

Therapeutic effects:

Improved survival and decreased spread of breast cancer.

Pharmacokinetics ⬆ ⬇

Absorption: 46% absorbed following oral administration.

Distribution: Unknown.

Metabolism/Excretion: Mostly metabolized (by CYP3A and sulfontransferase); 6.9% excreted unchanged in urine, 2.3% in feces.

Half-Life: 29 hr.

Time/Action Profile ⬆ ⬇

(improvement in progression-free survival)

ROUTE	ONSET	PEAK	DURATION
PO	within 4 mo	unknown	maintained throughout treatment

Contraind./Precautions ⬆ ⬇

Contraindicated in:

OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Severe renal impairment;
Severe hepatic impairment;
Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: DEEP VEIN THROMBOSIS (DVT)

Derm: alopecia

EENT: epistaxis

GI: ↓appetite, stomatitis, vomiting, diarrhea, nausea

GU: ↓fertility, ↑serum creatinine

Hemat: anemia, leukopenia, neutropenia, thrombocytopenia

Neuro: peripheral neuropathy, weakness

Resp: INTERSTITIAL LUNG DISEASE (ILD), PULMONARY EMBOLISM (PE)

Interactions ⬆ ⬇

Drug-drug:

CYP3A inhibitors, including clarithromycin, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, verapamil, and voriconazole, may ↑ levels and risk of toxicity; avoid concurrent use, if possible. If concurrent use necessary, ↓ palbociclib dose.
Strong CYP3A inducers, including carbamazepine, phenytoin, and rifampin, may ↓ levels and effectiveness; avoid concurrent use.
Moderate CYP3A inducers, including bosentan, efavirenz, etravirine, modafinil, and nafcillin, may ↓ levels and effectiveness; avoid concurrent use.
May ↑ levels and risk of toxicity of cyclosporine, dihydroergotamine, ergotamine, everolimus, fentanyl, midazolam, pimozide, quinidine, sirolimus, and tacrolimus; if concurrent use necessary, dose ↓ may be necessary.

Drug-Natural Products:

St. John's wort may ↓ levels and effectiveness; avoid concurrent use.

Drug-Food:

Grapefruit/grapefruit juice may ↑ levels and risk of toxicity; avoid concurrent use.

Route/Dosage ⬆ ⬇

PO (Adults ): 125 mg once daily for 21 days, followed by 7 days off; Concurrent use of strong CYP3A4 inhibitor: 75 mg once daily for 21 days, followed by 7 days off.

Hepatic Impairment

PO (Adults ): Severe hepatic impairment: 75 mg once daily for 21 days, followed by 7 days off.

Availability ⬆ ⬇

(Generic available)

Capsules: 75 mg; 100 mg; 125 mg

Assessment ⬆ ⬇

Monitor for signs/symptoms of infection (fever, chills, dizziness, shortness of breath, weakness) during therapy. Treat as medically appropriate. For Grade ≥3 (if persisting despite medical treatment), withhold palbociclib until symptoms resolve to Grade ≤1. Resume at next ↓ dose.
Monitor for signs/symptoms of venous thromboembolism such as PE (chest pain, dyspnea, tachycardia) or DVT (calf pain or tenderness, lower extremity edema, localized warmth or erythema). If DVT or PE suspected, discontinue palbociclib.
Monitor for signs/symptoms of ILD (dyspnea, cough, hypoxia, fever). CT scan or chest x-ray can confirm. If ILD suspected, hold palbociclib. If ILD confirmed, permanently discontinue palbociclib.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.
- Monitor CBC with differential at baseline and beginning of each cycle, on Day 15 of 1st 2 cycles, and as clinically indicated. May ↓ neutrophils, lymphocytes, hemoglobin, and platelets. Median time to 1st episode of neutropenia is 15 days, and median duration of Grade ≥3 neutropenia is 7 days. May cause febrile neutropenia. If Grade 3 hematologic toxicity occurs on Day 1 of cycle, hold palbociclib and repeat CBC within 1 wk. When recovered to Grade ≤2, start next cycle at same dose. If Grade 3 hematologic toxicity occurs on Day 15 of 1st 2 cycles, continue palbociclib at current dose to complete cycle and repeat CBC on Day 22. If Grade 4 hematologic toxicity occurs on Day 22, hold palbociclib until recovery to Grade ≤2. Resume at next ↓ dose. Consider dose ↓ in cases of prolonged (>1 wk) recovery from Grade 3 neutropenia or recurrent Grade 3 neutropenia on Day 1 of subsequent cycles. For Grade 3 ANC of 500–<1000/mm³plus fever ≥38.5°C and/or infection, hold palbociclib until recovery to Grade ≤2. Resume at next ↓ dose. For Grade 4 hematologic toxicity, hold palbociclib until recovery to Grade ≤2. Resume at next ↓ dose.
- May ↑ serum creatinine.

Implementation ⬆ ⬇

PO: Administer with food at the same time each day, for 21 consecutive days, followed by 7 days off treatment; combination with letrozole once daily given throughout 28-day cycle. DNC: Swallow capsules whole; do not open, crush, or chew; do not swallow capsules that are broken, cracked, or not intact.
- Pre/perimenopausal women treated with a combination of palbociclib + aromatase inhibitor or fulvestrant or palbociclib + inavolisib and fulvestrant should also be treated with luteinizing hormone-releasing hormone (LHRH) agonist. Men treated with a combination of palbociclib + aromatase inhibitor or palbociclib + inavolisib and fulvestrant therapy should be considered for treatment with LHRH agonist.
- Dose Reductions for Adverse Reactions: Starting dose is 125 mg/day. 1st dose ↓ is to 100 mg/day; 2nd dose ↓ is to 75 mg/day; if further dose ↓ needed, discontinue therapy.

Patient/Family Teaching ⬆ ⬇

Explain the purpose and side effects of palbociclib. Instruct to take as directed. If a dose is vomited or missed, omit dose and take next dose at usual time; do not take an additional dose that day. Do not change dose or stop taking without consulting health care provider. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
Advise patient to avoid grapefruit or grapefruit products during therapy.
Instruct patient to notify health care provider immediately and to seek medical care if fever or chills (even a low-grade fever can be serious) accompanied by weakness, tiredness, sore throat, mouth sores, rashes, flu-like symptoms, or respiratory illness occur; these could be associated with febrile neutropenia.
Instruct patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications, especially St. John's wort.
Rep: May cause fetal harm. Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding. Advise women of reproductive potential to use effective contraception and avoid breastfeeding during and for ≥3 wk after last dose. Advise men with female partners of reproductive potential to use effective contraception during and for ≥3 wk after last dose. Inform men that palbociclib may impair fertility.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇