Palbociclib

What is palbociclib used for?

Palbociclib is a prescription medicine that is used to treat breast cancer.

Description

IBRANCE tablets for oral administration contain 125 mg, 100 mg, or 75 mg of palbociclib, a kinase inhibitor. The molecular formula for palbociclib is C24H29N7O2. The molecular weight is 447.54 daltons. The chemical name is 6-acetyl-8-cyclopentyl-5-methyl-2-{[5-(piperazin-1-yl)pyridin-2-yl]amino}pyrido[2,3-d]pyrimidin-7(8H)-one, and its structural formula is:

Palbociclib is a yellow to orange powder. At or below pH 4, palbociclib behaves as a high-solubility compound. Above pH 4, the solubility of the drug substance reduces significantly.

Inactive Ingredients: Microcrystalline cellulose, colloidal silicon dioxide, crospovidone, magnesium stearate, succinic acid, HPMC 2910/hypromellose, titanium dioxide, triacetin, and FD&C Blue #2/Indigo Carmine Aluminum Lake. In addition, the 75 mg and 125 mg tablets contain red iron oxide and the 100 mg tablets contain yellow iron oxide.

 Mechanism of Action

Palbociclib is an inhibitor of cyclin-dependent kinases (CDK) 4 and 6. Cyclin D1 and CDK4/6 are downstream of signaling pathways which lead to cellular proliferation. In vitro, palbociclib reduced cellular proliferation of estrogen receptor (ER)-positive breast cancer cell lines by blocking progression of the cell from G1 into S phase of the cell cycle. Treatment of breast cancer cell lines with the combination of palbociclib and antiestrogens leads to decreased retinoblastoma (Rb) protein phosphorylation resulting in reduced E2F expression and signaling, and increased growth arrest compared to treatment with each drug alone.

In vitro treatment of ER-positive breast cancer cell lines with the combination of palbociclib and antiestrogens led to increased cell senescence compared to each drug alone, which was sustained for up to 6 days following palbociclib removal and was greater if antiestrogen treatment was continued. In vivo studies using a patient-derived ER-positive breast cancer xenograft model demonstrated that the combination of palbociclib and letrozole increased the inhibition of Rb phosphorylation, downstream signaling, and tumor growth compared to each drug alone.

Human bone marrow mononuclear cells treated with palbociclib in the presence or absence of an anti-estrogen in vitro did not become senescent and resumed proliferation following palbociclib withdrawal.

Before taking palbociclib, tell your doctor:

• If you are allergic to palbociclib; any part of this medicine; or any other drugs, foods, or substances. Tell your doctor about the allergy and what signs you had.
• If you take any other drugs (prescription or OTC, natural products, vitamins). There are many drugs that interact with palbociclib, like certain drugs that are used for HIV, infections, or seizures.
• If you are breast-feeding. Do not breast-feed while you take palbociclib and for 3 weeks after your last dose.

This is not a list of all drugs or health problems that interact with palbociclib.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take palbociclib with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

What are some things I need to know or do while I take palbociclib?

• 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 is taken with other drugs. Be sure you know about the warnings, benefits, and risks of these other drugs. Talk with the doctor if you have questions or concerns about any of the drugs.
• 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. Ask your doctor how long to use birth control. 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.

How is palbociclib best taken?

Use palbociclib as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take palbociclib with food.
• Swallow whole. Do not chew, open, or crush.
• Do not take palbociclib if it is broken, cracked, or looks 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.

What do I do if I miss a dose?

• Skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

What are the side effects of palbociclib that I need to call my doctor about immediately?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal.
• Any unexplained bruising or bleeding.
• Nosebleed.
• Dizziness.
• Some people have had lung problems with palbociclib. Sometimes, this has been deadly. Call your doctor right away if you have signs of lung problems like shortness of breath or other trouble breathing, cough that is new or worse, or fever.

What are some other side effects of palbociclib?

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:

• Hair loss.
• Hair thinning.
• Mouth irritation or mouth sores.
• Feeling tired or weak.
• Dry skin.
• Change in taste.
• Diarrhea, throwing up, upset stomach, and feeling less hungry are common with palbociclib. If these happen, talk with your doctor about ways to lower these side effects. Call your doctor right away if any of these effects bother you, do not get better, or get very bad.

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.

You may report side effects to the FDA at 1-800-332-1088. You may also report side effects at https://www.fda.gov/medwatch.

If overdose is suspected:

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

How do I store and/or throw out palbociclib?

• Store at room temperature in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.