New Drug Introduction: Ibrance / palbociclib
Pharmacology
Manufacturer
Approval Date
Indications
Contraindications
Warnings
And Precautions
Pregnancy/Lactation
Pharmacokinetics
Drug Interactions –
Object Drugs
Palbociclib is a reversible inhibitor of cyclin-dependent kinase (CDK) 4 and
6. CDK 4/6 are downstream of signaling pathways that regulate cellular
proliferation. Palbociclib reduces proliferation of estrogen receptor (ER)
positive breast cancer cells by blocking progression of the cell from G1 into
S phase of the cell cycle. The combination of palbociclib and letrozole
increased the inhibition of downstream signaling and tumor growth in ER
positive breast cancer xenograft models compared to either drug alone.
Pfizer Labs
February 2015
Palbocilib is indicated for use as initial endocrine based therapy (in
combination with letrozole) for the treatment of estrogen receptor (ER)positive, human epidermal growth factor receptor 2 (HER2)-negative
advanced breast cancer in postmenopausal women.
none
 Bone marrow suppression - neutropenia was commonly observed in
clinical studies, including grades 3 and 4 neutropenia Monitor blood
counts; treatment interruption, delay, or dose reduction is recommended
for patients developing grade 3 or 4 neutropenia.
 Infections (including grades 3 and 4) were reported more frequently in
patients receiving palbociclib and letrozole compared with those
receiving only letrozole. Monitor for signs/symptoms of infection and
manage appropriately.
 Thromboembolic events - pulmonary embolism was observed more
frequently in patients receiving palbociclib and letrozole compared with
those receiving letrozole alone. Monitor for signs/symptoms of
pulmonary embolism and manage appropriately.
 Gastrointestinal toxicity - nausea, vomiting, diarrhea, and stomatitis
(generally grade 1 or 2) were reported from clinical studies.
 Embryo-Fetal toxicity – can cause fetal harm. Advise patients of
potential risk to a fetus and to use effective contraception.
Category: Not currently determined (likely X) - Adverse events were
observed in animal reproduction studies
Lactation: Excretion in breast milk unknown/not recommended
A – Bioavialibility: 46%. Cmax: 6-12 hours
D – 85% protein bound with mean Vd of 2583 L
M – Undergoes extensive hepatic metabolism predominately via CYP3A4
and SULT2A1; major metabolite glucuronide conjugate of palbociclib
E –Feces (74% as metabolites); Urine (17.5% as metabolites); Palbociclib
has a mean plasma half-life of 29 +/- 5 hrs.
  levels of CYP3A4 substrates; dose adjustment may be required
for those agents with narrow therapeutic indices
midazolam
cyclosporine
fentanyl
everolimus
alfentanil
pimozide
ergotamine
sirolimus
tacrolimus
Drug Interactions –
Precipitant drugs
Adverse Effects
Monitoring Efficacy
Monitoring Toxicity
Dosing - Initial
Dosing - Usual
Dosing - Max
Renal Adjustment
Hepatic Adjustment

Strong CYP3A4 inhibitors  concentration of Ibrance
ketoconazole
itraconazole
clarithromycin
ritonavir
nefazodone
grapefruit
 Strong CYP3A4 inducers: ↓ concentration of Ibrance
phenytoin
rifampin
carbamazepine
St. John’s Wort
Nausea (25%) [13%]
Neutropenia (75%) [5%]
Diarrhea (21%) [10%]
Leukopenia (43%) [3%]
Vomiting (15%) [4%]
Anemia (35%) [7%]
Stomatitis (25%) [7%]
Thrombocytopenia (17%) [1%]
Fatigue (41%) [23%]
Decreased appetite (16%) [7%]
Asthenia (13%) [4%]
Peripheral neuropathy (13%) [5%]
URTI (31%) [18%]
Alopecia (22%) [3%]
Epistaxis (11%) [1%]
Monitor for signs of clinical improvement/lack of disease progression
CBC at baseline and start of each cycle; day 14 of first two cycles.
125 mg once daily for 21 days followed by 7 days off treatment to complete
28 day cycle. Letrozole 2.5 mg/day should be taken continuously during 28
day cycle.
125 mg/day unless neutropenia or other myelosupression develops. If ANC
<1000/mm2 + fever > 38.5 oC or infection withhold until ANC > 1000 mm2.
Resume at 100 mg/day. Dose can be further reduced to 75 mg/day on
second occurrence, however if third occurrence discontinue use.
125 mg once daily
No dosage adjustment required for patients with mild to moderate renal
impairment (30 ml/min < CrCl < 60 ml/min). Ibrance has not been studied
in patients with severe renal impairment.
No dosage adjustment required for mild hepatic impairment. Ibrance has
not been studied in patients with moderate or severe hepatic impairment.
Summary




Ibrance in combination with letrozole is indicated for the treatment of postmenopausal women
with estrogen positive, human epidermal growth factor negative metastatic breast cancer.
Ibrance is the only non-hormonal targeted therapy approved for use in women with ER-positive,
HER-2 negative advanced breast cancer.
First CDK inhibitor approved for use in oncology.
Significant side effects include neutropenia and leukopenia. Dose reduction is suggested as first
step in management.
References:
1. http://www.Ibrance.com
2. Ibrance full prescribing infromation. Pfizer. Feb. 2015.
3. Palbociclib. Drug information. Lexicomp Drug Information. Accessed through
UpToDate. Accessed on February 15, 2015.