PAT I E N T

ENROLMENT FORM
Kindly fill out this form with your complete details. After completing the enrolment form, please
e-mail the scanned form to info@inspire.com.ph and please call the Pfizer Inspire Hotline.

Don’t forget to insert your accomplished enrollment form in the attached envelope, seal, and mail
to INSPIRE Hotline Office, Unit 1739-1740, 17th Floor 6750 Ayala Avenue, Office Tower,
Makati City 1200.

mm dd yy
DATE: NOVEMBER 29 2022

INSPIRE MEMBER NUMBER:

FIRST NAME: NENILYN

MIDDLE NAME: DELA CRUZ

LAST NAME: PASCUAL

mm dd yy
BIRTHDAY: MAY 20 1970

MOBILE NUMBER: 09182178853

EMAIL ADDRESS: Dericknylpascual@gmail.com

DIAGNOSIS: HR+ HER2- Advanced / Metastatic Breast Cancer Others (not eligible)

IMPORTANT: Your name below should be consistent with the name on your prescription:
IMPORTANT:
By signing, I give consent to enroll my patient in the INSPIRE Patient Assistance Program under the terms and conditions of said program. I understand that should I prescribe Palbociclib (Ibrance) to patients who were enrolled in the INSPIRE Program by other doctors,
my prescription shall still be considered as covered by the INSPIRE Program and that my consent to the terms and conditions still apply.

I understand and acknowledge that I may be disclosing personal information which would be collected, processed and stored in an automated Pfizer-managed member data base system and/or in the member data base system of its affiliates or authorized third parties,
and which shall be used and administered solely by Pfizer, and its said affiliate companies and authorized third parties in connection with the implementation and enhancements of the INSPIRE Patient Assistance Program. I give my consent to Pfizer and its directors,
officers, employees, advisers, agents, affiliates and representatives’ a) collection, processing, storage and use of personal information; and b) outsourcing of the collection, processing, storage, and use of personal information to service providers whether within or outside
the Philippines.

The foregoing constitutes my express consent under the applicable confidentiality and data privacy law of the Philippines and other jurisdictions, and agree to hold Pfizer and relevant parties free and harmless from any and all liabilities, claims, damages and suits of
whatever kind and nature that may arise in connection with the implementation and compliance with the authorization I confer hereunder. The foregoing is without prejudice to my rights to reasonable access to, upon demand, and correction of my personal information,
as well as my right to lodge a complaint before the National Privacy Commission, under Section 16 of the Data Privacy Act. I likewise agree that the information referred to in this section may be disclosed to any of Pfizer-authorized affiliates and third parties for any
purposes that may include implementation and improvement of the INSPIRE Patient Assistance Program. For these purposes, Pfizer and its authorized affiliates or authorized third parties shall store personal information, as defined under Section 3 (g) of the Data Privacy
Act, up to five (5) years after the patient has discontinued from the program, or until the patient requires deletion of his or her personal information, whichever is earlier.

NICASIO G. RADOVAN III, MD

Doctor’s Name Signature

By signing, I hereby certify that the information given is true and correct. My enrolment to INSPIRE Patient Assistance Program shall be deemed my acceptance and agreement with the terms and conditions of the said program.

NENILYN D. PASCUAL 11/29/2022

Patient’s Name and Signature Date

PFIZER INSPIRE PROGRAM MECHANICS

The INSPIRE Patient Assistance Program is a Pfizer-initiated Patient Assistance Program that aims to help cancer patients gain access to HOW TO GET INSPIRE VOUCHER:
Pfizer cancer medicines.
Patients enrolled in the program will have access to medical education, coaching on possible sources of financial support for cancer 1. The member should call the INSPIRE Hotline prior to purchase or when claiming medicines through government funding (e.g. through
treatment, and free goods. a Guarantee Letter) with partner drugstore/s, to receive INSPIRE SMS voucher.
2. The SMS voucher is valid only for 7 days after issuance. The member must present the SMS voucher code to the partner drugstore prior
HOW TO JOIN: to purchase or claiming of free medicines.
3. If the SMS voucher code is valid, free medicine will be given for every out-of-pocket purchase. For government funded purchases, the
1. This program is open to HR+ HER2- advanced or metastatic breast cancer patients who have been prescribed Palbociclib (Ibrance) in partner drugstore will release the medicine quantity indicated in the letter.
combination with Letrozole or Fulvestrant by their doctor. 4. If the SMS voucher is invalid, the member should call the INSPIRE Hotline to address the validity of the SMS voucher.
2. The enrollment form will be provided by the Doctor and must be signed by both Patient and Doctor. 5. Pfizer and the partner drugstore have the right to refuse/reject fraudulent claims or transactions.
3. Scanned copy of the enrollment form must be emailed to info@inspire.com.ph. The actual copy of the enrollment form should be 6. For more information about the INSPIRE Program, the member may refer to the Program Terms and Conditions or call the INSPIRE
placed inside the INSPIRE envelope, sealed and send to Unit 1739-1740, 17th Floor 6750 Ayala Avenue, Office Tower, Hotline at 8662-2514, Globe: 0917 623-2862, Smart: 0998 591-7994 and for SMS/Text only: 0919 160-0720.
Makati City 1200.
4. Once the accomplished form has been emailed, the Patient should call the INSPIRE Program Hotline at (02) 8662-2514, CAPPING PROGRAM
Globe 0917 623-2862, or Smart 0998 591-7994 in order to proceed with the enrollment process.
5. After the successful enrollment, the Counsellor will brief the Patient into the INSPIRE Program and its benefits. 1. Once the member qualifies for the INSPIRE Capping Program, the Counsellor will call the Member to inform the additional benefits of
the program and briefs them on how to redeem his/her monthly supply.
BENEFITS OF THE PROGRAM: 2. Once the member has reached 252 capsules via out of pocket purchase, free goods, or government funding purchase, as tracked
through the INSPIRE SMS voucher presented to the partner drugstore, the member will be entitled to free Palbociclib (Ibrance)
1. Member may call the INSPIRE Hotline to ask for assistance on how to secure financial assistance from PCSO and other local capsules for the next five (5) years.
government units. 3. To claim the free medicine supply, the member should call the INSPIRE Hotline to request for the SMS voucher which will be presented
2. Member will be given free medicines for every out-of-pocket purchases with partner drugstore/s provided member presents an to the partner drugstore.
INSPIRE SMS voucher prior to purchase. 4. In order to claim free medicines for the succeeding months, the member must return the blister packs of the 21 capsules she consumed
3. All medicines received via out of pocket purchase, free goods, or government funding purchase (e.g. via Guarantee Letter) will be during the previous month. The blister packs should be mailed to Unit 1739-1740, 17th Floor 6750 Ayala Avenue, Office Tower,
considered for the INSPIRE Capping Program provided that a corresponding INSPIRE SMS voucher has been presented prior to Makati City 1200.
claiming of medicines with the partner drugstore/s.
4. Once the member has reached the 252 capsules, as tracked thru the INSPIRE SMS voucher presented to the partner drugstore/s, the
member will be entitled to free medicines within the next five (5) years.
Email address: info@inspire.com.ph
For more details, call our hotline: 8-6622514 REMEMBER:
PFIZER, INC. 18F - 20F 8 ROCKWELL BUILDING, For mobile numbers: Globe 0917-623 2862, Take a picture or scan
ROCKWELL CENTRE, HIDALGO DRIVE,
POBLACION, MAKATI CITY Smart 0998-591 7994, your enrolment form for
For SMS/Text only: 0919-160-0720 your personal copy.
PP-IBR-PHL-0028, August October
PP-IBR-PHL-0050 2020 2020

NEW INSPIRE—iBrance—Patient_Sept25.indd 1 01/10/2020 2:41 PM

 PAT I E N T
ENROLMENT FORM
TERMS & CONDITIONS
1. By enrolling and continued availment of the Inspire Patient Assistance Program (“INSPIRE Program”), the undersigned agrees to be
bound by these INSPIRE Program Terms and Conditions.
2. The INSPIRE Program is a Pfizer Patient Assistance Program with product access as one of its key components. Product access could
come in the form of free medicines and/or inclusion in the
capping program:
• Purchases using publicly available funding support (e.g. Philippine Charity Sweepstakes Office [PCSO]), shall be included in the
capping program.
• Purchases using out-of-pocket (OOP) funds will entitle patient to free capsules and inclusion in the capping program.
• Purchases using partly funding support and partly OOP funds will all be included in the capping program, but patient will only be
entitled to free products for the OOP purchases. A single capsule cannot be purchased partially with PCSO funds and partially with
OOP funds.
3. A doctor who, after consultation and diagnosis, opts to prescribe Palbociclib (Ibrance) [the “Product”] to a patient, may choose to
introduce the INSPIRE Program to the patient and enroll the latter. If the patient so desires, the patient could accept the enrollment
by filling out the enrollment form, signing it along with his/her doctor, and then calling the INSPIRE Hotline at (02) 8662-2514,
Globe: 0917 623-2862, Smart: 0998 591-7994 and for SMS/Text only: 0919 160-0720 for further instructions.
4. Both patient and doctor would have to sign the INSPIRE enrollment form in order to complete the enrollment.
5. This program is open to HR+ HER2- advanced or metastatic breast cancer patients who have been prescribed Palbociclib (Ibrance)
in combination with Letrozole or Fulvestrant by their doctor.
6. When patient calls the INSPIRE Hotline, the INSPIRE Program Counsellor (“Counsellor”) will request the patient to send advance
copies of the enrollment form and prescription via e-mail to info@inspire.com.ph. The patient should mail the hard copies of the
enrollment forms to the INSPIRE Hotline Office at Unit 1739-1740, 17th Floor 6750 Ayala Avenue, Office Tower, Makati City 1200.
7. If the form is complete, the Counsellor will brief the patient about the INSPIRE Program details. The Counsellor will also inform the
patient on possible publicly-available sources of the said funding support.
8. As soon as patient is ready to purchase the Product through publicly available funding support, OOP funds, or partly funding support
and partly OOP funds, the patient shall call the Counsellor who will instruct patient to email a copy of the latest prescription.
9. After Counsellor receives the prescription, Counsellor shall provide the patient with a voucher code through short messaging system
(SMS). Patient could then proceed to purchase the medicines from Globo Asiatico Enterprises, Inc. (“Globo Asiatico”) at 27 JDK Bldg.,
Maginhawa Street, Teachers Village 1100, Philippines, with telephone number +632 8982 7000. Patient should present to Globo
Asiatico upon purchase, the voucher code, prescription and, if applicable, proof of funding support (e.g. PCSO guarantee letter).
10. All voucher codes issued by the Counsellor under the INSPIRE Program shall be valid for seven (7) days after issuance. If the voucher
code expires prior to use, patient should call the Counsellor again for a new voucher code.
INSPIRE CAPPING PROGRAM
11. All purchases of the patient under the INSPIRE Program, regardless of fund source (i.e., publicly available funding support, OOP
funds, or partly funding support and partly OOP funds), are eligible to be counted as part of the INSPIRE Capping Program. The free
medication received by the patient under the INSPIRE Program shall also be counted as part of the INSPIRE Capping Program.
12. To be eligible for the INSPIRE Capping Program, the patient must adhere to the required medication as shown by purchases of
Palbociclib (Ibrance) totaling 252 capsules over the maximum period of two years. For purchases using OOP funds, the free
medication received by the patient shall also be counted as part of the INSPIRE Capping Program. Proof of such adherence and
purchase shall be shown by the documents in the possession of the Counsellor and Globo Asiatico (i.e., prescription, voucher code,
proof of funding support, enrollment form, official receipt, etc.).
13. If a patient qualifies for the INSPIRE Capping Program, patient will be advised by the Counsellor through phone call of the eligibility.
The following mechanics shall apply in order to claim the free medication under the capping program:
• Counsellor shall require patient to email the prescription to info@inspire.com.ph. Once the Counsellor receives the prescription by 7 days off treatment.
by email, the Counsellor shall provide the patient with a voucher code through SMS. Patient could then claim the free medication
from Globo Asiatico by presenting the prescription and the voucher code.
• A qualified patient shall be provided with maximum allocated capsules per month (i.e. 21 capsules for Palbociclib [Ibrance];
hereafter, the “Allocated Capsules”), or per prescription, whichever is lower, for free for the next 5 years for as long as the patient
is alive and is prescribed the Product by his physician.
• Free medicines will reset to the Allocated Capsules at the start of every calendar month. Unclaimed free medicines will not be
carried over to the following month.
• Patients availing of the capping program are required to submit fresh prescriptions monthly. Prescriptions issued more than 30
days ago will not be honored even if these have not yet been completely filled.
• In order to claim free medicines for the succeeding months, the member must return the blister packs of the 21 capsules he
consumed during the previous month. The blister packs should be mailed to Unit 1739-1740, 17th Floor 6750 Ayala Avenue,
Office Tower, Makati City 1200. Failure to return 21 blisters of Palbociclib (Ibrance) disqualifies the patient from receiving free
Palbociclib (Ibrance) for the succeeding months. In order to requalify for the capping program, the patient may complete the
required quantity of blisters by purchasing Palbociclib (Ibrance).
• Patients availing of the capping program will be required to have a video call with the counsellor before they will be given a
voucher code. The patient will be required to present a valid government ID during the video call. This video call will be recorded.
• If the prescribing doctor is not the signatory in the enrollment form, patient shall be required by Counsellor to have the
prescribing doctor sign off on an enrollment form, if necessary.
• At its option, Pfizer reserves the right to require the patient to submit other proof of eligibility to the capping program or
implement other control mechanisms to ensure eligibility such as, but not limited to, patient visit, videoconference with patient, etc.
FREE MEDICATION:
14. For every 1 capsule of the Product purchased using OOP funds through the INSPIRE Program, the patient shall be entitled to 1 free
capsule of the Product.
15. To avail of the free capsule, the following mechanics shall apply:
• Patient shall call the Counsellor prior to purchase and will be required to email the prescription to info@inspire.com.ph
• Once Counsellor receives the prescription by email, Counsellor shall provide the patient with a voucher code through SMS. Patient
could then purchase the Product and claim the free medication from Globo Asiatico by presenting the prescription and the
voucher code.
• The patient can only receive the maximum Allocated Capsules per month or per prescription whichever is lower, for both the
purchased and free Products.
• Free capsules balance will reset to the specified Allocated Capsules at the start of every calendar month. Unclaimed free capsules
will not be carried over to the following month.
• The doctor who prescribes the product should be enrolled in the INSPIRE Program. If the prescribing doctor is not enrolled in the
INSPIRE Program, the patient shall be required by Counsellor to have the prescribing doctor sign off on an enrollment form, if
necessary.
INSPIRE PATIENT EDUCATION
16. As a member of the INSPIRE Program, the patient agrees to receive periodic educational text messages.
OTHER TERMS & CONDITIONS
17. By having accepted the terms and conditions of the INSPIRE Program, the patient understands and acknowledges that the
information disclosed in the membership form as well as information obtained in the course of the INSPIRE Program, both of which
include personal information of the patient, are collected, processed and stored in an automated Pfizer-managed member data
base system and/or in the member data base system of its affiliates or authorized third parties, and which shall be used and
administered solely by Pfizer, and its said affiliate companies and authorized third parties in connection with the implementation
and enhancements of the INSPIRE Program. The patient gives his/her consent to Pfizer and its directors, officers, employees,
advisers, agents, affiliates and representatives (a) collection, processing, storage and use of personal information; and
(b) outsourcing of the collection, processing, storage and use of personal information to service providers whether within or outside
the Philippines. The foregoing constitutes the express consent of the patient under the applicable confidentiality and data privacy
law of the Philippines and other jurisdictions, and agree to hold Pfizer and relevant parties free and harmless from any and all
liabilities, claims, damages and suits of whatever kind and nature that may arise in connection with the implementation and
compliance with the authorization conferred by the patient hereunder.
The foregoing is without prejudice to the patient’s rights to reasonable access to, upon demand, and correction of his/her personal
information, as well as his/her right to lodge a complaint before the National Privacy Commission, under Section 16 of the Data
Privacy Act. The patient likewise agrees that the information referred to in this section may be disclosed to the patient’s attending
physician and to any of Pfizer- authorized affiliates and third parties for the implementation and improvement of the INSPIRE
Program and Pfizer’s other patient assistance programs. For these purposes, Pfizer and its authorized representatives and affiliates
shall store personal information of the patient, as defined under Section 3 (g) of the Data Privacy Act, up to five (5) years after the
patient has discontinued from the program, or until the patient requires deletion of his or her personal information, whichever is
earlier.
18. Any patient-specific and/or member-specific information may not be used in any form of publication or promotional material
without prior written approval by the patient. De-identified and aggregate patient data and/or member data may be analyzed and
used to provide basis to further improve the program.
19. By availing of the benefits granted by the program, the patient consents to receiving SMS, phone calls, e-mails and/or direct mail
and/or other means of communication from Pfizer and its affiliate companies or representatives on healthcare and adherence
which, by applicable regulations, they may refuse or decline at any time.
20. Pfizer and its affiliate companies shall not be responsible or liable to the patient-member for any loss or damage incurred or suffered
as a consequence of: (a) any malfunction, defect or error in any machine or system of authorization whether belonging to or Binding of Palbociclib to human plasma proteins in vitro was ~85%, with no concentration dependence over the
operated by Pfizer or any of its authorized vendors or third parties; (b) any delay or inability of Pfizer to perform any of its obligations
pursuant to these terms and conditions due to any mechanical, data processing, or telecommunication failure, act of God, civil
disturbance, or any event outside Pfizer, Inc.’s control or that of its authorized vendor or third party or as a consequence of any fraud
or forgery; and/ or (c) any damage to or loss of or inability to retrieve any data or information that may be stored in any device
whatsoever.
21. To the extent allowed by law and applicable regulations, Pfizer and its affiliate companies shall verify the identity of prescribing
doctors and member patients indicated in the form. In the event that a prescribing doctor and member patients or the information
relating to them is found to be fictitious or false, Pfizer reserves the right to cancel the patient’s membership to the INSPIRE Program,
including all benefits.
22. The benefits of the INSPIRE Program cannot be availed of in conjunction with other discount programs and benefits such as, but not
limited to, Senior Citizen’s Discount, Persons With Disability Discount, Pfizer Sampling Program, etc.
23. The benefits to the program may be availed of for the duration that Pfizer offers the same. Pfizer may opt to stop or continue the
program, in full or in part, at any time at its own discretion. Pfizer also reserves the right to change the program, its mechanics and
benefits, and these terms and conditions, in full or in part, any time. In case of patient-member’s death, the patient shall cease to
be a member of the program.
PP-IBR-PHL-0050 October 2020 PFIZER, INC. 18F - 20F 8 ROCKWELL BUILDING,
PP-XLK-PHL-0024, August 2020
ROCKWELL CENTRE, HIDALGO DRIVE, POBLACION, MAKATI CITY
NEW INSPIRE—iBrance—Patient_Sept25.indd 2
PALBOCICLIB (Ibrance®)
75 mg, 100 mg, 125 mg Capsules
INDICATION:
Palbociclib (Ibrance) is indicated for the treatment of 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
• fulvestrant in patients who have received prior therapy
DOSAGE AND METHOD OF ADMINISTRATION:
The recommended dose of Palbociclib (Ibrance) is a 125 mg capsule taken orally once daily for 21 consecutive days
followed by 7 days off treatment to comprise a complete cycle of 28 days. When coadministered with Palbociclib (Ibrance),
an aromatase inhibitor should be administered according to the dose schedule reported in the Product Information for
that aromatase inhibitor. When coadministered with Palbociclib (Ibrance), the recommended dose of fulvestrant is 500
mg administered intramuscularly on Days 1, 15, 29 and once monthly thereafter. Please refer to the Product Information
for fulvestrant.
Palbociclib (Ibrance) should be taken with food. Patients should be encouraged to take their dose at approximately the
same time each day. Palbociclib (Ibrance) capsules should be swallowed whole (do not chew, crush or open them prior to
swallowing).
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. Palbociclib (Ibrance) capsules should be swallowed whole (do not chew, crush or open them prior to
swallowing). No capsule should be ingested if it is broken, cracked or otherwise not intact.
Prior to the start of, and throughout treatment, pre/perimenopausal women treated with the combination of Palbociclib
(Ibrance) plus aromatase inhibitor/fulvestrant should also be treated with a luteinizing hormone-releasing hormone (LHRH)
agonist according to local clinical practice. Pre and perimenopausal women were not enrolled in PALOMA-1 and PALOMA-2.
For men treated with the combination of Palbociclib (Ibrance) plus aromatase inhibitor therapy, consider treatment with an
LHRH agonist according to current clinical practice standards.
CONTRAINDICATIONS:
Use of Palbociclib (Ibrance) is contraindicated in patients with hypersensitivity to Palbociclib or to any of the excipients.
SPECIAL WARNINGS AND PRECAUTIONS FOR USE:
Neutropenia, Anemia, and Thrombocytopenia have been observed very commonly in clinical studies with Palbociclib
(Ibrance).
Severe, life-threatening, or fatal ILD and/or pneumonitis can occur in patients treated with
cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, including Palbociclib (Ibrance) when taken in
combination with endocrine therapy. Since Palbociclib (Ibrance) has myelosuppressive properties, it may predispose to
infections.
No dose adjustment is required for patients with mild, moderate or severe renal impairment
(creatinine clearance [CrCl] ≥15 mL/min). Insufficient data are available in patients requiring haemodialysis to provide any
dosing recommendation in this patient population.
No dose adjustment is required for patients with mild or moderate hepatic impairment (Child-Pugh classes A and B). For
patients with severe hepatic impairment (Child-Pugh class C), the
recommended dose of Palbociclib (Ibrance) is 75 mg once daily for 21 consecutive days followed
No dose adjustment is necessary in patients ≥65 years of age.
The safety and efficacy of Palbociclib (Ibrance) in pediatric patients have not been established.
UNDESIRABLE EFFECTS:
The most common adverse reactions (≥20%) of any grade reported in patients in the Palbociclib (Ibrance) plus letrozole
arm by descending frequency were neutropenia, infections, leukopenia, nausea, fatigue, alopecia, stomatitis, anemia and
diarrhea.
The most frequently reported Grade >3 adverse reactions (≥5%) in patients receiving Palbociclib
(Ibrance) plus letrozole by descending frequency were neutropenia, leukopenia, infections and anemia.
The most frequently (≥1%) reported serious adverse drug reactions in patients receiving Palbociclib plus letrozole were
infections (4.6%) and febrile neutropenia (1.3%).
The most common adverse drug reactions of any grade reported in >20% of patients receiving Palbociclib in
combination with fulvestrant were neutropenia, leukopenia, infections, fatigue, nausea, anemia, stomatitis, diarrhea and
thrombocytopenia.
The most frequently (≥1%) reported serious adverse drug reactions in patients receiving Palbociclib plus fulvestrant
(PALOMA-3) were infections (4.1%), pyrexia (1.4%) and neutropenia (1.2%).
INTERACTION WITH OTHER MEDICINAL PRODUCTS AND OTHER FORMS OF
INTERACTION:
Palbociclib is primarily metabolized by CYP3A and sulfotransferase (SULT) enzyme SULT2A1. In vivo, Palbociclib is a time-
dependent inhibitor of CYP3A.
The concomitant use of strong CYP3A inhibitors including, but not limited to, amprenavir, atazanavir, boceprevir,
clarithromycin, conivaptan, delavirdine, diltiazem, erythromycin, fosamprenavir, indinavir, itraconazole, ketoconazole,
lopinavir, mibefradil, miconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin, voriconazole
and grapefruit or grapefruit juice should be avoided.
The concomitant use of strong CYP3A inducers including, but not limited to, carbamazepine, enzalutamide, felbamate,
nevirapine, phenobarbital, phenytoin, primidone, rifabutin, rifampin, rifapentin and St. John’s wort should be avoided.
Moderate CYP3A inducers (e.g., bosentan, efavirenz, etravirine, modafinil and nafcillin) can be used concurrently with
Palbociclib (Ibrance) when unavoidable. No dosing adjustments are required.
Palbociclib should be given with food. Under fed conditions, there is no clinically relevant effect of PPIs, H2-receptor
antagonists or local antacids on Palbociclib exposure.
Coadministration of midazolam with multiple doses of Palbociclib increased the midazolam AUCinf and Cmax values by
61% and 37%, respectively.
Clinical studies in patients with breast cancer showed that there was no clinically relevant drug interaction when Palbociclib
is co-administered with any of the following drugs: Letrozole, Fulvestrant, and Goserelin.
PHARMACODYNAMICS AND PHARMACOKINETICS:
Through inhibition of CDK4/6, Palbociclib reduced cellular proliferation by blocking progression of the cell from G1 into S
phase of the cell cycle. Testing of Palbociclib in a panel of molecularly profiled breast cancer cell lines revealed high efficacy
against luminal breast cancers, particularly estrogen receptor (ER)-positive breast cancers. Mechanistic analyses revealed
that the combination of Palbociclib with anti-estrogen agents enhanced the re-activation of retinoblastoma (Rb) through
inhibition of Rb phosphorylation resulting in reduced E2F signalling and growth arrest.
The enhanced growth arrest of the ER-positive breast cancer cell lines treated with Palbociclib and anti-estrogen agents is
accompanied by increased cell senescence resulting in a sustained cell cycle arrest following drug removal and increased
cell size associated with a senescent phenotype.
In the presence or absence of an anti-estrogen, Palbociclib-treated bone marrow cells did not become senescent and
resumed proliferation following Palbociclib withdrawal, consistent with pharmacologic quiescence. The in vitro breast cancer
cells, conversely, became senescent following Palbociclib or anti-estrogen treatment with additive effects in combination
and remained arrested in the presence of anti-estrogen.
Palbociclib is a small molecule inhibitor of cyclin-dependent kinases (CDK) 4 and 6. Cyclin D1 and CDK4/6 are downstream
of multiple signaling pathways which lead to cellular proliferation.
The time to Cmax (Tmax) of Palbociclib is generally between 6 to 12 hours following oral administration. The mean absolute
bioavailability of Palbociclib after an oral 125 mg dose is 46%. In the dosing range of 25 mg to 225 mg, the AUC and Cmax
increase proportionally with dose in general. Steady state was achieved within 8 days following repeated once daily dosing.
With repeated once daily administration, Palbociclib accumulates with a median accumulation ratio of 2.4 (range 1.5-4.2).
Palbociclib absorption and exposure were very low in approximately 13% of the population under the fasted condition.
Food intake increased the Palbociclib exposure in this small subset of the population, but did not alter Palbociclib exposure
in the rest of the population to a clinically relevant extent. Therefore, food intake reduced the intersubject variability of
Palbociclib exposure, which supports administration of Palbociclib (Ibrance) with food.
concentration range of 500 ng/mL to 5000 ng/mL. The mean fraction unbound (fu) of Palbociclib in human plasma in
vivo increased incrementally with worsening hepatic function. There was no obvious trend in the mean Palbociclib fu in
human plasma in vivo with worsening renal function. The geometric mean apparent volume of distribution (Vz/F) was
2583 (26%) L.
In vitro and in vivo studies indicate that Palbociclib undergoes extensive hepatic metabolism in humans.
The geometric mean apparent oral clearance (CL/F) of Palbociclib was 63.08 L/h and the mean plasma elimination half-life
was 28.8 hours in patients with advanced breast cancer.
For full prescribing information, please see package insert.
Reference: LPD Revision No. 1.1 date 12-May-2020
01/10/2020 2:41 PM