IBRANCE- palbociclib capsule

**Description**

IBRANCE capsules are taken by mouth and come in three strengths:
• 125 mg
• 100 mg
• 75 mg

Each capsule contains palbociclib, a medicine that works by blocking certain proteins (called kinases) that help cancer cells grow.

**About the Active Ingredient:**
• Palbociclib appears as a yellow to orange powder
• It dissolves better in acidic conditions (when pH is 4 or lower)
• It doesn’t dissolve as well when pH is above 4

**Other Ingredients:**
The capsules also contain inactive ingredients that help form the capsule:
• Microcrystalline cellulose
• Lactose monohydrate
• Sodium starch glycolate
• Colloidal silicon dioxide
• Magnesium stearate

**Capsule Shell:**
• Made of hard gelatin
• Colors range from light orange to caramel
• Contains coloring agents (iron oxides) and titanium dioxide
• Printing ink is used for labeling

**What IBRANCE is used for:**

IBRANCE is a cancer medicine used to treat adults with a specific type of breast cancer that has:
• Hormone receptors (HR-positive)
• No HER2 protein (HER2-negative)
• Spread to other parts of the body (advanced or metastatic)

IBRANCE is always used together with other cancer medicines.

IBRANCE can also be used with two other medicines (inavolisib and fulvestrant) for patients whose cancer:
• Has stopped responding to hormone therapy
• Has a specific gene change called PIK3CA mutation
• Has come back after completing hormone treatment after surgery

The PIK3CA mutation must be confirmed by an FDA-approved test before starting this treatment combination.

# How to Take IBRANCE

## Recommended Dose

**Standard Dose:**
• Take one 125 mg capsule by mouth once daily
• Take for 21 days in a row, then stop for 7 days
• This makes a complete 28-day cycle
• Always take with food
• Take at the same time each day

**Important Taking Instructions:**
• Swallow capsules whole – do not chew, crush, or open them
• Do not take broken or cracked capsules
• If you vomit or miss a dose, do not take an extra dose
• Just take your next dose at the regular time

**Other Medications:**
• You will also take hormone therapy medications as prescribed
• Pre/perimenopausal women may need additional hormone treatment
• Men may need additional hormone treatment

## Dose Changes

**Dose Levels:**
• Starting dose: 125 mg daily
• First reduction: 100 mg daily
• Second reduction: 75 mg daily
• If you need less than 75 mg daily, treatment will be stopped

## Managing Side Effects

### Blood Count Problems

**Your doctor will check your blood:**
• Before starting treatment
• At the start of each cycle
• On day 15 of your first 2 cycles
• Every 3 months if blood counts stay normal

**Dose changes based on blood counts:**
• **Mild to moderate low blood counts:** Continue same dose
• **Severe low blood counts:** Stop IBRANCE until blood counts improve, then restart at a lower dose
• **Low blood counts with fever or infection:** Stop IBRANCE until better, then restart at a lower dose

### Other Side Effects

• **Mild to moderate side effects:** Continue same dose
• **Severe side effects:** Stop IBRANCE until side effects get better, then restart at a lower dose
• **Severe lung problems:** Stop IBRANCE permanently

## Special Situations

**Taking Other Medications:**
• Some medications can affect how IBRANCE works
• If you must take certain medications, your dose may be reduced to 75 mg daily

**Liver Problems:**
• **Mild to moderate liver problems:** No dose change needed
• **Severe liver problems:** Reduce dose to 75 mg daily

**Dosage Forms and Strengths**

This medication comes in 3 different capsule strengths:

• **125 mg capsules**
– Hard capsules with caramel-colored cap and body
– “Pfizer” printed on cap, “PBC 125” printed on body

• **100 mg capsules**
– Hard capsules with caramel-colored cap and light orange body
– “Pfizer” printed on cap, “PBC 100” printed on body

• **75 mg capsules**
– Hard capsules with light orange cap and body
– “Pfizer” printed on cap, “PBC 75” printed on body

None.

## Warnings and Precautions

### 5.1 Low White Blood Cell Count (Neutropenia)

Low white blood cell count is the most common side effect with IBRANCE:
• Happens in 8 out of 10 patients taking IBRANCE
• Can be serious (Grade 3 or higher) in about 2 out of 3 patients
• Usually starts around 15 days after beginning treatment
• Serious cases typically last about 7 days

**What your doctor will do:**
• Check your blood before you start IBRANCE
• Check your blood at the start of each treatment cycle
• Check your blood on day 15 of your first 2 cycles
• May need to pause, lower your dose, or delay treatment if your white blood cell count gets too low

**Important:** Call your doctor right away if you get a fever. Low white blood cells can lead to serious infections. One patient died from infection in clinical trials.

### 5.2 Lung Problems (ILD/Pneumonitis)

IBRANCE can cause serious, life-threatening lung inflammation:
• Happens in about 1 out of 100 patients
• Can be fatal in rare cases

**Watch for these symptoms:**
• New or worsening cough
• Trouble breathing
• Shortness of breath

**Important:** Tell your doctor immediately if you have any new breathing problems. Your doctor may need to stop IBRANCE permanently if you develop serious lung problems.

### 5.3 Pregnancy Risks

IBRANCE can harm an unborn baby:
• Animal studies showed birth defects and pregnancy loss
• Can cause serious harm to developing babies

**If you can get pregnant:**
• Use effective birth control during treatment
• Continue birth control for at least 3 weeks after your last dose
• Tell your doctor right away if you become pregnant

**Side Effects**

This section lists the most important side effects you should know about. More detailed information about these side effects can be found in other parts of this medication guide.

• Check other sections of this guide for complete information about possible side effects
• Talk to your doctor if you experience any concerning symptoms while taking this medication

**Drug Interactions**

Palbociclib affects how your body processes other medications:

• Your liver breaks down palbociclib using specific enzymes (CYP3A and SULT2A1)

• Palbociclib can slow down how your body processes other drugs that use the same liver enzyme (CYP3A)

• This means other medications may stay in your body longer and could cause stronger side effects

• Always tell your doctor about all medications, supplements, and herbal products you take

# Use in Specific Populations

## 8.1 Pregnancy

**Risk Summary**
IBRANCE can harm an unborn baby. Animal studies showed the drug caused problems in developing babies when given to pregnant animals.

• There is no data on pregnant women taking this drug
• If you are pregnant, this drug could harm your baby
• In the general U.S. population, 2-4% of pregnancies have major birth defects and 15-20% end in miscarriage

**Animal Study Results**
• Pregnant rats and rabbits were given IBRANCE during pregnancy
• High doses caused reduced baby weight and bone problems
• The doses that caused problems were 4-9 times higher than human doses

## 8.2 Breastfeeding

• We don’t know if IBRANCE passes into breast milk
• Don’t breastfeed while taking IBRANCE
• Wait 3 weeks after your last dose before breastfeeding

## 8.3 Birth Control and Fertility

**Pregnancy Testing**
• Get a pregnancy test before starting IBRANCE if you can get pregnant

**Birth Control for Women**
• Use effective birth control during treatment
• Continue birth control for 3 weeks after your last dose

**Birth Control for Men**
• Men should use effective birth control if their partner can get pregnant
• Use birth control during treatment and for 3 months after the last dose

**Fertility**
• IBRANCE may reduce fertility in men

## 8.4 Children

• IBRANCE is not approved for children
• Studies in 140 children ages 2-17 showed the drug was processed similarly to adults
• Side effects were similar to those seen in adults

**Studies in Young Animals**
Young rats given IBRANCE developed:
• Blood sugar problems
• Eye problems (cataracts)
• Kidney problems
• Tooth problems

These problems were not seen in adult animals.

## 8.5 Older Adults

• IBRANCE works the same in older and younger patients
• Side effects are similar regardless of age
• No dose changes needed based on age alone

## 8.6 Liver Problems

**Dose Changes:**
• Mild or moderate liver problems: No dose change needed
• Severe liver problems: Take 75 mg daily for 21 days, then 7 days off

## 8.7 Kidney Problems

• No dose changes needed for any level of kidney problems
• This includes mild, moderate, or severe kidney disease
• Has not been studied in patients on dialysis

# How Palbociclib Works in Your Body

## 12.1 How the Medicine Works

Palbociclib blocks proteins called CDK4 and CDK6 that help cancer cells grow and multiply. Here’s what happens:

• The medicine stops breast cancer cells from dividing and making more cancer cells
• It works best when combined with hormone therapy drugs (antiestrogens)
• Together, these medicines cause cancer cells to stop growing and eventually die
• The combination works better than either medicine alone
• Studies show it shrinks tumors more effectively when medicines are used together
• Normal bone marrow cells are not permanently damaged and can recover after treatment stops

## 12.2 Effects on Your Heart

• Palbociclib does not cause dangerous heart rhythm problems
• Tests showed no serious effects on heart electrical activity at the standard dose

## 12.3 How Your Body Processes the Medicine

**Absorption (How it gets into your blood):**
• Peak levels in blood occur 6-12 hours after taking it
• Only 46% of the dose gets absorbed into your bloodstream
• Steady levels in your body are reached within 8 days
• The medicine builds up about 2.4 times with daily use

**Food Effects:**
• Taking with food helps the medicine work better and more consistently
• About 13% of people absorb very little when taking it without food
• Food increases absorption by 12-38% depending on the type of meal
• Always take with food as directed

**Distribution (How it spreads in your body):**
• About 85% binds to proteins in your blood
• Spreads widely throughout your body
• People with liver problems may have more active drug in their blood

**Breakdown (How your body breaks it down):**
• Your liver breaks down most of the medicine
• The original drug makes up 23% of what’s in your blood
• Most breakdown happens through two main processes: oxidation and sulfonation
• Only small amounts of unchanged medicine leave your body

**Elimination (How it leaves your body):**
• Takes about 29 hours for half the medicine to leave your blood
• Most (74%) leaves through bowel movements
• About 18% leaves through urine
• Nearly 92% is eliminated within 15 days

**Special Populations:**

*Age, Gender, and Weight:*
• Works the same in men and women
• Age (22-89 years) doesn’t significantly affect how it works
• Body weight doesn’t significantly change how it works

*Liver Problems:*
• Mild liver problems: 17% less active drug in blood
• Moderate liver problems: 34% more active drug in blood
• Severe liver problems: 77% more active drug in blood

*Kidney Problems:*
• Mild to severe kidney problems: 31-42% higher drug levels
• Not studied in people on dialysis

**Drug Interactions:**

*Strong CYP3A Inhibitors (like itraconazole):*
• Increase palbociclib levels by 87%
• May need dose adjustment

*Strong CYP3A Inducers (like rifampin):*
• Decrease palbociclib levels by 85%
• May make treatment less effective

*Moderate CYP3A Inducers (like modafinil):*
• Decrease palbociclib levels by 32%

*Other Medicines:*
• Can increase levels of some other medicines by 61%
• May affect how well other medicines work

*Stomach Acid Reducers:*
• Proton pump inhibitors (PPIs) with food: minimal effect
• PPIs without food: significantly reduce medicine levels (62-80%)
• Always take with food to avoid this problem

*Transport Proteins:*
• Low risk of affecting most drug transporters
• May affect some medicines that use certain transport systems

**13.1 Cancer Risk, Gene Changes, and Fertility Effects**

**Cancer Risk Studies**
Scientists tested palbociclib in animals to see if it might cause cancer:
• In male rats given the drug for 2 years, some developed brain tumors at high doses (8 times higher than what humans take)
• Female rats showed no cancer risk at doses up to 5 times higher than human doses
• Mice given the drug for 6 months showed no increased cancer risk

**Gene Changes**
Tests showed that palbociclib:
• Can cause problems with cell division in lab tests
• Does not directly damage DNA or cause gene mutations

**Effects on Fertility**

**Women:**
• No fertility problems were found in female rats at doses up to 4 times higher than human doses
• No harmful effects seen on female reproductive organs

**Men:**
• Studies in male rats and dogs showed problems with reproductive organs including:
– Smaller testicles and related organs
– Lower sperm count and movement
– Tissue damage in reproductive organs
• These effects were partly reversible when the drug was stopped
• Male fertility was slightly reduced in rats at high doses (20 times higher than human doses)
• Effects on mating ability were not seen

# Clinical Studies for IBRANCE

## PALOMA-2 Study: IBRANCE plus Letrozole

**Who was studied:** 666 postmenopausal women with ER-positive, HER2-negative advanced breast cancer who had not received previous treatment for their advanced disease.

**How the study worked:**
• Patients were randomly divided into two groups (2:1 ratio)
• Group 1: IBRANCE plus letrozole
• Group 2: placebo (inactive pill) plus letrozole
• IBRANCE dose: 125 mg daily for 21 days, then 7 days off (28-day cycle)
• Treatment continued until the cancer got worse or side effects became too severe

**Patient characteristics:**
• Average age: 62 years (range 28-89)
• Most patients were White (78%)
• 48% had received chemotherapy before
• 56% had received hormone therapy before
• 97% had cancer that had spread (metastatic)

**Results:**

| Outcome | IBRANCE + Letrozole | Placebo + Letrozole |
|———|——————-|——————-|
| **Time before cancer worsened** | 24.8 months | 14.5 months |
| **Response rate** | 55.3% | 44.4% |
| **Overall survival** | 53.8 months | 49.8 months |

**Key finding:** IBRANCE plus letrozole delayed cancer progression by about 10 months compared to letrozole alone.

—

## PALOMA-3 Study: IBRANCE plus Fulvestrant

**Who was studied:** 521 pre- and postmenopausal women with HR-positive, HER2-negative advanced breast cancer whose cancer had gotten worse after previous hormone therapy.

**How the study worked:**
• Patients were randomly divided into two groups (2:1 ratio)
• Group 1: IBRANCE plus fulvestrant
• Group 2: placebo plus fulvestrant
• IBRANCE dose: 125 mg daily for 21 days, then 7 days off (28-day cycle)
• Pre/perimenopausal women also received goserelin injections

**Patient characteristics:**
• Average age: 57 years (range 29-88)
• Most patients were White (74%)
• 80% were postmenopausal
• All had received previous treatment
• 75% had received chemotherapy before

**Results:**

| Outcome | IBRANCE + Fulvestrant | Placebo + Fulvestrant |
|———|———————|———————|
| **Time before cancer worsened** | 9.5 months | 4.6 months |
| **Response rate** | 24.6% | 10.9% |
| **Overall survival** | 34.9 months | 28.0 months |

**Key finding:** IBRANCE plus fulvestrant doubled the time before cancer got worse compared to fulvestrant alone.

—

## INAVO120 Study: IBRANCE plus Inavolisib and Fulvestrant

**Who was studied:** 325 adults with PIK3CA-mutated, HR-positive, HER2-negative advanced breast cancer whose disease got worse during or within 12 months of completing hormone therapy after surgery.

**Special requirements:**
• Patients needed specific blood sugar levels (HbA1C <6%, fasting glucose <126 mg/dL) • No diabetes requiring medication • Cancer must have a specific genetic change (PIK3CA mutation) **How the study worked:** • Patients were randomly divided into two equal groups • Group 1: IBRANCE + inavolisib + fulvestrant • Group 2: IBRANCE + placebo + fulvestrant • IBRANCE dose: 125 mg daily for 21 days, then 7 days off • Inavolisib: 9 mg daily • Fulvestrant: 500 mg injection on specific days **Patient characteristics:** • Average age: 54 years (range 27-79) • 98% female, 39% pre/perimenopausal • 59% White, 38% Asian • 64% had secondary hormone resistance • 83% had received chemotherapy before **Results:** | Outcome | IBRANCE + Inavolisib + Fulvestrant | IBRANCE + Placebo + Fulvestrant | |---------|----------------------------------|--------------------------------| | **Time before cancer worsened** | 15.0 months | 7.3 months | | **Response rate** | 58% | 25% | | **Duration of response** | 18.4 months | 9.6 months | **Key finding:** Adding inavolisib to IBRANCE and fulvestrant more than doubled the time before cancer got worse in patients with PIK3CA mutations.

**How IBRANCE Comes and How to Store It**

**How IBRANCE is supplied:**
• IBRANCE comes in different strengths and package sizes
• Your doctor will prescribe the right strength for you
• The medication comes in capsules

**Storage instructions:**
• Store at room temperature
• Keep in the original container
• Keep away from moisture and heat
• Keep out of reach of children
• Do not use if expired

**Important Reading Instructions**

• Read the Patient Information sheet that comes with your medication
• This information has been approved by the FDA (Food and Drug Administration)
• The Patient Information sheet contains important details about your medicine
• Make sure to read it before you start taking your medication
• Keep the information sheet so you can refer to it if you have questions