Palbociclib

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom).

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

Mechanism of Action

Cyclin dependent kinases (CDK) 4,6 inhibitor

Reduces cellular proliferation of ER-positive breast cancer cell lines by blocking progression of the cell from G1 into S phase of the cell cycle

Absorption

Bioavailability: 46%

Peak plasma time: 6-12 hr

Steady-state achieved: 8 days

Distribution

Protein bound: 85%

Vd: 2583 L

Metabolism

Extensively metabolized, primarily by CYP3A and SULT2A1

Elimination

Half-life: 29 hr

Oral clearance: 63.1 L/hr

Excretion: 74.1% feces (2.3% unchanged); 17.5% urine (6.9% unchanged)

Before taking palbociclib, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• are allergic to palbociclib or to any of its ingredients
• have liver problems
• have or have had problems with fertility (for males)
• are pregnant or plan to become pregnant
• are breastfeeding

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Take palbociclib as prescribed.

Palbociclib comes in a capsule form and is taken once a day with food.

If you miss a dose, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of palbociclib at the same time.

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

• The dose your doctor recommends may be based on the following:
• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your weight
• your height
• your age
• your gender

The recommended dose of Ibrance (palbociclib) for the treatment of advanced (metastatic) breast cancer is 125 mg once daily for 21 days, followed by 7 days of being off of the medication. This medication should be used in combination with letrozole. Changes in dose or schedule may be required depending on how well the medication is tolerated. 

Metabolized principally by CYP3A and sulfotransferase (SULT) 2A1.1

In vitro, not an inhibitor of CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, and 2D6 or inducer of CYP1A2, 2B6, 2C8, and 3A4 at clinically relevant concentrations.1 In vivo, weak time-dependent inhibitor of CYP3A.1

In vitro, low potential for inhibition of P-gp, breast cancer resistance protein (BCRP), organic cation transporter (OCT) 2, organic anion transporter (OAT) 1, OAT 3, organic anion transport protein (OATP) 1B1 and OATP1B3 at clinically relevant concentrations.1

Drugs Affecting Hepatic Microsomal Enzymes

Potent CYP3A inhibitors: Possible pharmacokinetic interaction (increased plasma concentrations and AUC of palbociclib).1 Avoid concomitant use; consider choosing alternative agent with no or minimal CYP3A inhibition potential.1 If concomitant use cannot be avoided, reduce palbociclib dosage to 75 mg once daily.1

If potent CYP3A inhibitor is discontinued, resume palbociclib (after 3–5 terminal half-lives of the CYP3A inhibitor) at dosage used prior to initiation of the potent CYP3A inhibitor.1 (See Specific Drugs and Foods under Interactions.)

Moderate and potent CYP3A inducers: Possible pharmacokinetic interaction (decreased plasma concentrations and AUC of palbociclib).1 Avoid concomitant use.1 (See Specific Drugs and Foods under Interactions.)

Drugs Metabolized by Hepatic Microsomal Enzymes

Substrates of CYP3A: Possible pharmacokinetic interaction (increased plasma concentrations of CYP3A substrate).1 If concomitant use of palbociclib and CYP3A substrates with a narrow therapeutic index cannot be avoided, consider dosage reduction of the CYP3A substrate.1 (See Specific Drugs and Foods under Interactions.)

Drugs Affecting Gastric Acidity

Potential pharmacokinetic interaction (decreased plasma concentrations and AUC of palbociclib) with drugs that increase gastric pH.1 (See Specific Drugs and Foods under Interactions.)

Specific Drugs and Foods

• It is used to treat breast cancer.
• It may be given to you for other reasons. Talk with the doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Not hungry.
• Loose stools (diarrhea).
• Hair thinning.
• Hair loss.
• Mouth irritation or mouth sores.
• Upset stomach or throwing up.
• Feeling tired or weak.
• Dry skin.
• Change in taste.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

• Ibrance

Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

ARIPiprazole: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Palbociclib. Management: The US label does not provide specific recommendations concerning use with moderate CYP3A4 inducers, but the Canadian label recommends avoiding use of moderate CYP3A4 inducers. Consider therapy modification

CYP3A4 Inducers (Strong): May decrease the serum concentration of Palbociclib. Avoid combination

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Palbociclib. Avoid combination

CYP3A4 Substrates: Palbociclib may increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Avoid combination

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination

Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Monitor therapy

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Monitor therapy

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Grapefruit Juice: May increase the serum concentration of Palbociclib. Avoid combination

HYDROcodone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of HYDROcodone. Monitor therapy

Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Consider therapy modification

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Monitor therapy

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Avoid combination

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy

St John's Wort: May decrease the serum concentration of Palbociclib. Avoid combination

Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Consider therapy modification

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience lack of appetite, diarrhea, hair thinning or loss, mouth sores, mouth irritation, nausea, vomiting, dry skin, or change in taste. Have patient report immediately to prescriber signs of infection, bruising, bleeding, dizziness, nosebleed, severe loss of strength and energy, or shortness of breath (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Applies to palbociclib: oral capsule

Hematologic

Very common (10% or more): Decreased white blood cells (up to 95%), decreased neutrophils (up to 94%), decreased hemoglobin (up to 83%), decreased lymphocytes (up to 81%), neutropenia (up to 75%), decreased platelets (up to 61%), leukopenia (up to 43%), anemia (up to 35%), thrombocytopenia (up to 17%)
Frequency not reported: Febrile neutropenia[Ref]

Respiratory

Very common (10% or more): Upper respiratory infection (up to 31%), epistaxis (up to 11%)
Common (1% to 10%): Pulmonary embolism[Ref]

Other

Very common (10% or more): Infections (up to 55%), fatigue (up to 41%), asthenia (up to 13%)[Ref]

General

Most common adverse reactions (10% or greater incidence): neutropenia, leukopenia, fatigue, anemia, infections, nausea, stomatitis, alopecia, diarrhea, thrombocytopenia, decreased appetite, vomiting, asthenia, peripheral neuropathy, and epistaxis.[Ref]

Gastrointestinal

Very common (10% or more): Stomatitis (up to 25%), nausea (up to 25%), diarrhea (up to 25%), vomiting (up to 15%)[Ref]

Dermatologic

Very common (10% or more): Alopecia (up to 22%)[Ref]

Metabolic

Very common (10% or more): Decreased appetite (up to 16%)[Ref]

Nervous system

Very common (10% or more): Peripheral neuropathy (up to 13%)[Ref]

Some side effects of palbociclib may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

No adjustment recommended

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.