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).

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 ⬆ ⬇

Derm: alopecia

EENT: epistaxis

GI: stomatitis, vomiting, diarrhea, nausea

GU: ↓fertility

Hemat: anemia, leukopenia, neutropenia, thrombocytopenia

Metab: ↓appetite

Neuro: peripheral neuropathy, weakness

Resp: INTERSTITIAL LUNG DISEASE

Interactions ⬆ ⬇

Drug-drug:

Concurrent use with CYP3A inhibitors including clarithromycin, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, verapamil, and voriconazole↑ levels and the risk of toxicity; avoid, if possible (if unavoidable, ↓ dose of palbociclib [resume original dose after 3–5 half-lives of offending drug have passed following discontinuation]).
Strong CYP3A inducers including carbamazepine, phenytoin, rifampin can ↓ levels and effectiveness; concurrent use should be avoided.
Moderate CYP3A inducers including bosentan, efavirenz, etravirine, modafinil, and nafcillin may also ↓ levels and effectiveness; avoid concurrent use.
↑levels and effects/toxicity of cyclosporine, dihydroergotamine, ergotamine, everolimus, fentanyl, midazolam, pimozide, quinidine, sirolimus, and tacrolimus; if concurrent use is required dose ↓ may be necessary.

Drug-Natural Products:

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

Grapefruit/grapefruit juice↑ levels and the risk of toxicity, avoid ingestion.

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 and symptoms of infection (fever, chills, dizziness, shortness of breath, weakness, increased bleeding or bruising) during therapy. Treat as medically appropriate. No dose adjustment is needed for Grade 1 or 2 non-hematologic toxicities. For Grade ≥3 (if persisting despite medical treatment), withhold palbociclib until symptoms resolve to Grade ≤1; Grade ≤2 (if not considered a safety risk for patient). Resume at next lower dose.
Monitor for signs and symptoms of interstitial lung disease or pneumonitis (hypoxia, cough, dyspnea) during therapy. If symptoms are severe, permanently discontinue therapy.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.
- Monitor CBC prior to and at beginning of each cycle, on Day 15 of first 2 cycles, and as clinically indicated. May cause ↓ neutrophil counts; median time to first episode is 15 days and median duration of Grade ≥3 neutropenia was 7 days. May cause febrile neutropenia.
- No dose adjustment is needed for Grade 1 or 2 hematologic toxicities. For Grade 3 Day 1 of cycle: withhold palbociclib, repeat CBC monitoring within 1 wk. When recovered to Grade ≤2, start next cycle at same dose. For Grade 3 Day 15 of first 2 cycles: If Grade 3 on Day 15, continue palbociclib at current dose to complete cycle and repeat CBC on Day 22. If Grade 4 on Day 22, withhold palbociclib until recovery to Grade ≤2. Resume at next lower dose. Consider dose reduction 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 (500–<1000/mm³) plus fever ≥38.5°C and/or infection, withhold palbociclib until recovery to Grade ≤2. Resume at next lower dose. For Grade 4, withhold palbociclib until recovery to Grade ≤2. Resume at next lower dose.
- May cause ↓ WBC, lymphocytes, hemoglobin, and platelets.

Implementation ⬆ ⬇

PO: Administer once daily 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.
- If dose reduction needed for adverse reactions starting dose is 125 mg/day. 1st dose reduction is to 100 mg/day, 2nd dose reduction is to 75 mg/day; if further dose reduction needed, discontinue therapy.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take palbociclib 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 professional. 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; may increase amount of palbociclib in blood.
Advise patient to notify health care professional if signs and symptoms of infection occur.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially St. John's wort.
Rep: Advise females of reproductive potential to use effective contraception and avoid breastfeeding during and for at least 3 wk after last dose. Advise patient to notify health care professional if pregnancy is planned or suspected. Advise males with female partners of reproductive potential to use effective contraception during and for at least 3 wk after last dose. Inform male patient that palbociclib may impair fertility.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇