Drug information of Palbociclib
Palbociclib is a piperazine pyridopyrimidine that acts in the cell cycle machinery. It is a second generation cyclin-dependent kinase inhibitor selected from a group of pyridopyrimidine compounds due to its favorable physical and pharmaceutical properties. It was originally FDA approved on March 2015 for the treatment of HR-positive, HER2-negative advanced or metastatic breast cancer.
Mechanism of effect
Palbociclib is a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor that acts by binding to the ATP pocket. It is important to consider that it presents low to absent activity against other kinases.
The CDK4/6 kinase is involved, with coregulatory partner cyclin D, in the G1-S transition. Hence, inhibition of this step prevents cell cycle progression in cells in whose this pathway is functioning. This step includes the pathways of the phosphorylation of retinoblastoma protein and the E2F family of transcription factors.
palbociclib produces effective dephosphorylation of RB, reduce proliferation and induce senescence causing cell-cycle arrest.
Peak plasma time: 6-12 hr
Steady-state achieved: 8 days
Protein bound: 85%
Vd: 2583 L
Metabolism: Extensively metabolized, primarily by CYP3A and SULT2A1
Half-life: 29 hr (patients with advanced breast cancer)
Oral clearance: 63.1 L/hr
Excretion: 74.1% feces (2.3% unchanged); 17.5% urine (6.9% unchanged)
Majority of the dose eliminated in feces was metabolites
125 mg PO qDay for Days 1-21 of each 28-day cycle
Side effectsInfection , Diarrhea , Nosebleeds , nausea , vomiting , Blurred vision , asthenia , fever , dry eyes , Increased ALT , Increased AST , dry skin , tiredness , Leukopenia , Rash , taste disturbance
InteractionsOxecarbazepin , Itraconazole , Isoniazid , Imatinib , Primidone , Posaconazole , Dexamethasone , Rifampin , Phenytoin , Voriconazole , Carbamazepine , Ketoconazole , Clarithromycin , Enzalutamide , Rifabutin , Rifapentine , Atazanavir , Darunavir , Quinidine , Grapefruit , Pentobarbital , Nefazodone , ritonavir , saquinavir , nelfinavir , nevirapine , mitotane , Fosamprenavir , Lopinavir , Palifermin , Indinavir , Fosphenytoin , Idelalisib , Tipranavir , Dabrafenib , Mibefradil , Nicardipine , cobicistat , Delavirdine
Neutropenia observed in clinical trials; febrile neutropenia also reported; monitor CBC count prior to starting drug and at the beginning of each cycle, as well as on Day 14 of the first 2 cycles, and as clinically indicated; dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop grade 3 or 4 neutropenia
Grade 3 and 4 infections reported when administered in combination with an antiestrogen compared to patients receiving antiestrogen only; monitor and manage appropriately symptoms and signs of infection
Nausea, vomiting, diarrhea, and grade 1 or 2 stomatitis reported in clinical trials
Severe, life-threatening, or fatal ILD and/or pneumonitis can occur; monitor for pulmonary symptoms indicative of ILD/pneumonitis which may include hypoxia, cough, and dyspnea; permanently discontinue therapy in patients with severe ILD or pneumonitis
Based on findings in animals and mechanism of action, palbociclib can cause fetal harm (see Pregnancy)
Drug interaction overview
- In vitro data indicate that CYP3A and SULT enzyme SULT2A1 are mainly involved in the metabolism of palbociclib
- Palbociclib is also a weak time-dependent inhibitor of CYP3A following daily 125 mg dosing to steady state in humans
- Avoid use with strong CYP3A inhibitors; if coadministration cannot be avoided, reduce the palbociclib dose
- Avoid use with moderate or strong CYP3A inducers
- Palbociclib may increase sensitive CYP3A substrates with a narrow therapeutic index (eg, alfentanil, cyclosporine, dihydroergotamine, ergotamine, everolimus, fentanyl, midazolam, pimozide, quinidine, sirolimus, and tacrolimus)
Points of recommendation
- Tell all of your health care providers that you take palbociclib. This includes your doctors, nurses, pharmacists, and dentists.
- You may have more of a chance of getting an infection. Wash hands often. Stay away from people with infections, colds, or flu. Some infections have been very bad and even deadly.
- You may bleed more easily. Be careful and avoid injury. Use a soft toothbrush and an electric razor.
- Have blood work checked as you have been told by the doctor. Talk with the doctor.
- This medicine may affect being able to father a child. Talk with the doctor.
- This medicine may cause harm to an unborn baby. A pregnancy test will be done before you start palbociclib to show that you are NOT pregnant.
- Women must use birth control while taking palbociclib and for some time after the last dose. If you get pregnant, call your doctor right away.
- Men with a partner who may get pregnant must use birth control while taking palbociclib and for some time after the last dose. Ask your doctor how long to use birth control. If your partner gets pregnant, call the doctor right away.
- Follow how to take palbociclib as you have been told by your doctor. Do not use more than you were told to use.
- Take palbociclib with food.
- Swallow whole. Do not chew, open, or crush.
- Do not take capsules that are broken, cracked, or look damaged.
- Avoid grapefruit and grapefruit juice.
- Take palbociclib at the same time of day.
- Keep taking palbociclib as you have been told by your doctor or other health care provider, even if you feel well.
- If you throw up after taking a dose, do not repeat the dose. Take your next dose at your normal time.
- Skip the missed dose and go back to your normal time.
- Do not take 2 doses at the same time or extra doses.