Patients

INTRODUCTION

  • Brand NamePalbocap
  • Generic NamePalbociclib
  • Dosage FormCapsule
  • Dosage125 mg

Palbociclib is a kinase inhibitor indicated for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer

Mechanism of action and pharmacokinetics

Antineoplastic agents —> Protein kinase inhibitors

Mechanism of action: Palbociclib works by blocking proteins called cyclin-dependent kinase 4 and 6, which regulate cell growth and division. Blocking these proteins can slow down growth of cancer cells and delay the progression of your cancer. Palbociclib is used to treat patients with certain types of breast cancer (hormone receptor-positive, human epidermal growth factor receptor 2-negative) which have spread beyond the original tumor and/or to other organs. It is given together with aromatase inhibitors, which are used as hormonal anticancer therapies.

Absorption: The mean Cmax of palbociclib is generally observed between 6 to 12 hours (time to reach maximum concentration, Tmax) 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 increased proportionally with dose in general. Steady state was achieved within 8 days following repeated once daily dosing. With repeated once daily administration, palbociclib accumulated with a median accumulation ratio of 2.4 (range 1.5 to 4.2).

Distribution: Binding of palbociclib to human plasma proteins in vitro was approximately 85%, with no concentration dependence over the concentration range of 500 ng/mL to 5000 ng/mL. The geometric mean apparent volume of distribution (Vz/F) was 2583 L (26% CV).

Elimination: The geometric mean apparent oral clearance (CL/F) of palbociclib was 63.1 L/hr (29% CV), and the mean (± standard deviation) plasma elimination half-life was 29 (±5) hours in patients with advanced breast cancer. In 6 healthy male subjects given a single oral dose of [14C]palbociclib, a median of 91.6% of the total administered radioactive dose was recovered in 15 days; feces (74.1% of dose) was the major route of excretion, with 17.5% of the dose recovered in urine. The majority of the material was excreted as metabolites.

Indications

Palbocap is indicated for the treatment of HR-positive, HER2-negative advanced or metastatic breast cancer in combination with:

  • Letrozole as initial endocrine based therapy in postmenopausal women, or
  • Fulvestrant in women with disease progression following endocrine therapy.

The indication in combination with letrozole is approved under accelerated approval based on progression-free survival (PFS). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Contraindications

If you are allergic to palbociclib or any of the other ingredients of this medicine.

Use of preparations containing St. John’s Wort should be avoided while you are taking Palbociclib.

Warning and Precautions

  • Monitor complete blood count prior to start of Palbociclib therapy and at the beginning of each cycle, as well as on Day 14 of the first 2 cycles, and as clinically indicated.
  • Monitor patients for signs and symptoms of pulmonary embolism and treat as medically appropriate.
  • Can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception.
  • Avoid grapefruit and grapefruit juice while you are taking palbociclib as it may increase the side effects of palbociclib.
  • Tiredness is a very common side effect. If you feel unusually tired, take special care when driving or using machines.
    • Palbociclib is not to be used in children or adolescents (aged 18 years or under).

 

  • Do not stop taking palbociclib unless your doctor tells you to. If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

 

 

  • Patients should be encouraged to take their dose of Palbociclib at approximately the same time each day.

 

  • 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 capsules should be swallowed whole (do not chew, crush or open them prior to swallowing). Capsules should not be ingested if they are broken, cracked, or otherwise not intact.

Pregnancy and Lactation

  • Pregnancy: Should never be used palbociclib by pregnant woman.
  • Lactation: Advise not to breastfeed.

Drug Interactions

Consult with doctor the full prescribing information before use for contraindicated drugs and other potential drug-drug interactions. The following may increase the risk of side effects with palbociclib:Lopinavir, Indinavir, Nelfinavir, Ritonavir, Telaprevir, Saquinavir, Clarithromycin, Telithromycin, Voriconazole, Itraconazole, Ketoconazole, Posaconazole, Nefazodone, Quinidine Generally, Colchicine, Pravastatin, Rosuvastatin, Sulfasalazine, Alfetanil, Fentanyl, Ciclosporin, Everolimus, Tacrolimus, Sirolimus, Dihydroergotamine, Ergotamine, Pimozide, Carbamazepine, Phenytoin, Enzalutamide, Rifampin, St. John’s Wort, and An Herbal Product.

Adverse effects

Infections Reduction in white blood cells, Red blood cells and blood platelets, Feeling of tiredness, Decreased appetite Inflammation of the mouth and lips (stomatitis), Nausea, vomiting, diarrhea, Rash, Hair loss, Fever with a drop in the white blood cell count (febrile neutropenia), Blurred vision, increased tearing, dry eye, Abnormalities in liver blood tests Alteration in taste (dysgeusia), Nosebleed, Dry skin, Weakness, Fever

Dosage

The recommended dose of Palbociclib 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. Palbociclib should be taken with food. When coadministered with palbociclib, the recommended dose of letrozole is 2.5 mg taken once daily continuously throughout the 28-day cycle. Please refer to the full prescribing information of letrozole. When coadministered with palbociclib, the recommended dose of fulvestrant is 500 mg administered on Days 1, 15, 29, and once monthly thereafter. Please refer to the full prescribing information of fulvestrant. Pre/perimenopausal women treated with the combination Palbociclib plus fulvestrant therapy should be treated with luteinizing hormone-releasing hormone (LHRH) agonists according to current clinical practice standards.

Dose Modification

Table 1. Recommended Dose Modification for Adverse Reactions

Dose Level Dose
Recommended starting dose 125 mg/day
First dose reduction 100 mg/day
Second dose reduction 75 mg/day*

*If further dose reduction below 75 mg/day is required, discontinue.

Table 2. Dose Modification and Management – Hematologic Toxicitiesa

Monitor complete blood counts prior to the start of Palbociclib therapy and at the beginning of each cycle, as well as on Day 14 of the first 2 cycles, and as clinically indicated.
CTCAE Grade Dose Modifications
Grade 1 or 2 No dose adjustment is required.
Grade 3 Day 1 of cycle: Withhold Palbociclib, repeat complete blood count monitoring within 1 week. When recovered to Grade ≤2, start the next cycle at the same dose. Day 14 of first 2 cycles: Continue Palbociclib at current dose to complete cycle. Repeat complete blood count on Day 21. Consider dose reduction in cases of prolonged (>1 week) recovery from Grade 3 neutropenia or recurrent Grade 3 neutropenia in subsequent cycles.
Grade 3 neutropeniabb with fever ≥38.5 ºC and/or infection Withhold Palbociclib until recovery to Grade ≤2. Resume at the next lower dose.
Grade 4 Withhold Palbociclib until recovery to Grade ≤2. Resume at the next lower dose.

Grading according to CTCAE 4.0.

CTCAE=Common Terminology Criteria for Adverse Events; LLN=lower limit of normal.

a Table applies to all hematologic adverse reactions except lymphopenia (unless associated with clinical events, e.g., opportunistic infections).

b Absolute neutrophil count (ANC): Grade 1: ANC < LLN -1500/mm3; Grade 2: ANC 1000 -<1500/mm3; Grade 3: ANC 500 -<1000/mm3; Grade 4: ANC <500/mm3

Table 3. Dose Modification and Management – Non-Hematologic Toxicities

CTCAE Grade Dose Modifications
Grade 1 or 2 No dose adjustment is required.
Grade ≥3 non-hematologic toxicity (if persisting despite optimal medical treatment) Withhold until symptoms resolve to: • Grade ≤1; • Grade ≤2 (if not considered a safety risk for the patient) Resume at the next lower dose.

Grading according to CTCAE 4.0.

CTCAE=Common Terminology Criteria for Adverse Events.

Refer to the full prescribing information for coadministered endocrine therapy dose adjustment guidelines in the event of toxicity and other relevant safety information or contraindications.

How supplied

Palbocap 75mg is supplied as opaque, hard gelatin capsule, with a light orange body and cap.

Palbocap 100mg is supplied as opaque, hard gelatin capsule, with a light orange body and a caramel cap.

Palbocap 125 mg is supplied as opaque, hard gelatin capsule, with a pink body and cap.

Storage

  • Store between 15-30 C.
  • Protect from moisture.
  • Keep this medicine out of the sight and reach of children.