PALBOSIC

PALBOSIC

Palbociclib 75/100/125mg
Net Qty- 21 Tablets
Self-Life- 2 Years

Palbosic (Palbociclib) is an oral CDK4/6 inhibitor used primarily in the treatment of hormone receptor-positive, HER2-negative breast cancer. It works by blocking proteins (CDK4 and CDK6) that help cancer cells divide and proliferate, ultimately slowing the growth of cancer cells.

USE

Palbosic (Palbociclib) is primarily used for the treatment of hormone receptor-positive (HR+), HER2-negative breast cancer, particularly in combination with other therapies. Below are its main uses:

1. Advanced or Metastatic Breast Cancer

  • Indication: Palbociclib is used for advanced or metastatic HR-positive, HER2-negative breast cancer in adults.
  • Combination Therapy: Typically combined with:
  • Letrozole, Anastrozole, or Exemestane (aromatase inhibitors).
  • Fulvestrant in certain cases for patients who have previously received hormonal therapy.
  • Purpose: The goal is to slow cancer growth and extend progression-free survival (PFS).

2. Early-Stage HR-Positive, HER2-Negative Breast Cancer (Adjuvant Setting)

  • Clinical trials are evaluating Palbociclib in adjuvant therapy (early-stage breast cancer) to help prevent recurrence after surgery, particularly for high-risk patients with HR-positive and HER2-negative tumors.

3. In Combination with Other Targeted Therapies

  • Neoadjuvant Treatment: Palbociclib is being investigated for use in pre-surgical settings to reduce tumor size, allowing for easier removal and potentially improving surgical outcomes.
  • With Immunotherapy: Ongoing trials are examining its role in combination with checkpoint inhibitors for possible synergistic effects in breast cancer and other cancers.

4. Use in Postmenopausal Women

  • Palbociclib is frequently prescribed for postmenopausal women with HR-positive, HER2-negative breast cancer as part of combination therapy with aromatase inhibitors (e.g., letrozole).

5. Male Breast Cancer

  • While less common, males with HR-positive breast cancer can also benefit from Palbociclib as part of combination therapy, though the dosage and approach may differ based on clinical needs.
  • Palbociclib is part of a class of drugs called CDK4/6 inhibitors and works by inhibiting cancer cell cycle progression, particularly during the G1 phase, slowing the growth of HR-positive cancers.

Key Benefits

Key Benefits of Palbociclib offers several significant benefits, particularly for the treatment of HR-positive, HER2-negative breast cancer. Below are the key advantages of using Palbociclib in cancer treatment:

✅ Improved Progression-Free Survival (PFS)

  • Palbociclib has been shown to extend progression-free survival (PFS) in patients with advanced or metastatic HR-positive, HER2-negative breast cancer.
  • In clinical trials, Palbociclib in combination with aromatase inhibitors has demonstrated a significant improvement in PFS compared to endocrine therapy alone.

✅ Targeted Mechanism of Action

  • Palbociclib works by inhibiting CDK4/6, proteins that are critical for cancer cell cycle progression. This helps to slow the growth of tumor cells and can prevent their spread.
  • It is a targeted therapy, meaning it specifically works against cancer cells while minimizing damage to normal cells, resulting in fewer side effects compared to traditional chemotherapy.

✅ Combination Therapy Enhances Effectiveness

  • Palbociclib is highly effective when used in combination with other therapies, including aromatase inhibitors (e.g., letrozole) or fulvestrant, improving response rates and overall survival for many patients.
  • It enhances the efficacy of these therapies by targeting cancer cell division, offering a multi-pronged approach to cancer treatment.

✅ Oral Administration

  • Convenient oral form: Palbociclib is taken in pill form once daily, making it easier to administer at home compared to intravenous chemotherapy.
  • This improves patient compliance and quality of life, as patients do not need to visit a clinic or hospital frequently for injections.

✅ Improved Quality of Life

  • By combining Palbociclib with other hormonal therapies, many patients experience less aggressive side effects than with traditional chemotherapy, such as nausea, vomiting, and hair loss.
  • It helps to maintain a better quality of life, allowing patients to continue normal daily activities for longer periods during treatment.

✅ Well-Tolerated in Many Patients

  • Though side effects do occur (e.g., neutropenia, fatigue, and diarrhea), they are often manageable with dose adjustments and supportive care.
  • Regular blood tests allow doctors to monitor side effects, especially for low white blood cell counts, and adjust the treatment as necessary, making it a flexible therapy.

✅ Potential Use in Male Breast Cancer

  • Although breast cancer is more common in women, Palbociclib can also be effective for men with HR-positive, HER2-negative breast cancer.
  • This expands the benefits of Palbociclib beyond just female patients, offering a new treatment option for men with breast cancer.

✅ Investigational Benefits for Other Cancers

  • Clinical trials are exploring Palbociclib’s efficacy in other cancers, such as endometrial cancer and lung cancer.
  • The potential to treat a wider range of cancers in the future offers hope for additional therapeutic applications.

✅ Lower Risk of Cancer Progression

  • By slowing the progression of the disease, Palbociclib can delay the need for more aggressive treatments (such as chemotherapy) and improve long-term survival outcomes in patients with HR-positive, HER2-negative breast cancer.

✅ FDA-Approved and Proven in Clinical Trials

  • FDA approval for the treatment of HR-positive, HER2-negative breast cancer is supported by strong clinical trial data.
  • The combination of Palbociclib and letrozole has shown to significantly improve progression-free survival in phase 3 trials compared to standard treatments, making it a proven and effective therapy.

Mechanism
of Action

Mechanism of Action of Palbosic (Palbociclib) is a selective inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), which play essential roles in the regulation of the cell cycle. Here’s how it works in detail:

1. Role of CDK4/6 in the Cell Cycle

  • Cyclin-dependent kinases (CDKs) are enzymes that drive cell cycle progression. Specifically, CDK4 and CDK6 work together with cyclins to transition the cell from the G1 phase to the S phase of the cell cycle (the phase when DNA replication occurs).
  • In the G1 phase, cells grow and prepare for DNA replication. When CDK4/6 are activated, they phosphorylate the retinoblastoma (Rb) protein, a key tumor suppressor, which releases E2F transcription factors and promotes the transition to the S phase, allowing DNA replication and cell division.

2. Palbociclib Inhibition of CDK4/6

  • Palbociclib selectively inhibits CDK4 and CDK6 activity by binding to their ATP-binding site, preventing their activation.
  • By inhibiting CDK4/6, Palbociclib prevents the phosphorylation of Rb, thereby blocking the G1 to S phase transition.
  • Without CDK4/6 activity, Rb remains phosphorylated, and E2F transcription factors are suppressed, halting cell cycle progression. This results in cell cycle arrest in the G1 phase, preventing cancer cells from proliferating.

3. Impact on Tumor Cells

  • Tumor cells, which often have dysregulated cell cycle control, rely heavily on CDK4/6 for uncontrolled growth. By blocking CDK4/6, Palbociclib helps to stop or slow down the uncontrolled division of these cancer cells.
  • This cell cycle arrest also makes cancer cells more susceptible to other therapies, like endocrine therapy (e.g., aromatase inhibitors), making it especially effective in combination treatments.

4. Selectivity for Cancer Cells

  • While CDK4/6 inhibition affects both normal and cancerous cells, Palbociclib is particularly effective in cancers that are driven by hormone receptors (e.g., HR-positive breast cancer). These tumors often rely more on CDK4/6 for progression, making them more vulnerable to treatment with Palbociclib.

5. Role in HR-Positive Breast Cancer

  • Hormone receptor-positive (HR+) breast cancer cells are driven by estrogen or progesterone receptors. These cancer cells require constant cell cycle progression to grow.
  • Palbociclib, when combined with endocrine therapy (e.g., letrozole), effectively blocks both hormonal signals (by inhibiting estrogen receptors) and cell cycle progression, offering a two-pronged approach to stop cancer cell proliferation.

Dosage and Administration

💊 Palbosic (Palbociclib) is used primarily for HR-positive, HER2-negative advanced or metastatic breast cancer, often in combination with endocrine therapy. Here’s a clear and concise guide to its standard dosage and administration:

✅ Standard Dosage

  • Recommended starting dose:

125 mg taken once daily for 21 consecutive days,

followed by a 7-day break (no medication)

→ This forms a 28-day cycle.

✅ Treatment Cycle

  • Day 1–21: Take Palbociclib daily
  • Day 22–28: No Palbociclib (rest period)
  • Repeat the cycle every 4 weeks

(as long as the treatment is effective and side effects are manageable)

✅ How to Take It

  • Oral tablets (usually 125 mg, 100 mg, or 75 mg strengths)
  • Take once daily, with food (to improve absorption)
  • Swallow whole – do not chew, crush, or split
  • Take it at the same time each day

✅ If You Miss a Dose

  • Do NOT double the next dose to make up for a missed one
  • Skip the missed dose and take the next scheduled dose at the regular time
  • Always follow your oncologist’s guidance

✅ 5. Dose Modifications

If side effects occur, your doctor may reduce the dose to:

  • 100 mg/day
  • Or 75 mg/day

Temporary treatment interruptions or delays may also be recommended for:

  • Severe neutropenia
  • Liver enzyme elevations
  • Other significant side effects

✅ Use in Combination

Palbociclib is not used alone. It’s typically combined with:

  • Letrozole (for postmenopausal women/men as initial therapy)
  • Fulvestrant (for those whose disease has progressed after prior endocrine therapy)

✅ Monitoring Required

  • CBC (Complete Blood Count): especially during the first 2 cycles
  • Liver function tests
  • Signs of infection or neutropenia

✅ Special Populations

  • Hepatic impairment: Use with caution; dose adjustment may be needed
  • Renal impairment: Usually no adjustment required for mild/moderate issues
  • Pregnancy/Breastfeeding: Contraindicated

Common Side Effects

💊 Palbosic (Palbociclib) is a targeted cancer therapy, and while generally better tolerated than traditional chemotherapy, it can still cause some notable side effects, especially related to blood cells and the immune system.

🔹 Most Common Side Effects

Side EffectDescription
NeutropeniaLow white blood cell count → higher infection risk. Most frequent side effect.
FatigueFeeling unusually tired or weak. Can range from mild to severe.
NauseaStomach discomfort; usually mild and manageable with food or meds.
DiarrheaWatery stools; can lead to dehydration if not managed.
StomatitisMouth sores or inflammation; may cause discomfort while eating/talking.
Hair ThinningMild to moderate hair loss (not typically complete baldness).
Decreased AppetiteReduced interest in food; possible weight loss.
InfectionsDue to low white cell counts—watch for fever, chills, sore throat.
AnemiaLow red blood cells → tiredness, shortness of breath.
ThrombocytopeniaLow platelets → easy bruising or bleeding.
Elevated Liver EnzymesCan be detected in blood tests; may require dose adjustments.
RashOften mild; notify your doctor if it worsens or spreads.

⚠️ When to Call Your Doctor

  • Fever (≥100.4°F / 38°C)
  • Persistent or severe fatigue
  • Unusual bleeding or bruising
  • Shortness of breath
  • Signs of infection (cough, chills, pain when urinating)

🧪 Monitoring

  • Your doctor will frequently check:
  • Complete blood counts (CBC) – especially during the first 2 months
  • Liver function
  • Signs of infection or immune suppression

Monitoring

🩺 Palbosic (Palbociclib) affects blood cells and the immune system, routine monitoring is essential to ensure safe and effective treatment. Here’s what doctors typically watch during therapy:

🔬 Complete Blood Count (CBC)

  • Why: To detect neutropenia, anemia, or thrombocytopenia
  • How often:
    • Before starting treatment
    • Every 2 weeks during the first 2 cycles
    • Then before each new cycle
    • Additional checks if the patient shows symptoms of low blood counts

🧪 Liver Function Tests (LFTs)

  • Why: Palbociclib can increase liver enzymes
  • How often:
    • Before starting
    • Periodically during treatment, especially if dose changes are made or liver concerns arise

🧫 Renal Function (Optional)

  • Why: Not commonly affected, but helpful if the patient has underlying kidney issues
  • How often: Periodically, or as needed

💓 Signs of Infection

  • Watch for:
    • Fever ≥100.4°F (38°C)
    • Chills, sore throat
    • Persistent cough
    • Pain or burning during urination
  • Why: Due to neutropenia, infection risk is significantly increased

💊 Treatment Response

  • How:
    • Regular imaging (CT/MRI) to assess tumor size and progression
    • Physical exams and patient-reported symptoms
  • When: Every few months, or based on clinical judgment

📋 Adherence Monitoring

  • Ensuring the patient is:
    • Taking the medication correctly (daily, with food)
    • Following the 21-days-on / 7-days-off cycle
    • Not skipping or doubling doses

🧘‍♀️ Patient Well-being

  • Monitor for:
    • Fatigue
    • Appetite changes
    • Emotional health
  • Address supportive care needs (nutrition, mental health, etc.)

📌 Quick Summary Table

Test/CheckFrequency
CBC (WBC, RBC, Platelets)Baseline, every 2 weeks (first 2 cycles), then every cycle
Liver Function (ALT, AST)Baseline, periodically
Renal FunctionAs needed
Infection symptomsContinuously monitored
Tumor response (scans)Every 2–3 months

Precautions

⚠️ Palbosic (Palbociclib) is an effective targeted therapy, but there are several important precautions that patients and healthcare providers should keep in mind to ensure safety and treatment success.

🔹 Risk of Neutropenia (Low White Blood Cells)

  • Monitor blood counts regularly—especially in the first 2 cycles.
  • Watch for signs of infection (fever, chills, sore throat).
  • Treatment may need to be paused or dose reduced if severe neutropenia occurs.

🔹 Avoid Live Vaccines

  • Palbociclib may suppress the immune system.
  • Live vaccines (like measles, mumps, rubella, or yellow fever) should be avoided during treatment.
  • Inactivated vaccines (like flu shots) are generally safe—consult your doctor.

🔹 Pregnancy and Breastfeeding

  • Contraindicated in pregnancy – may cause fetal harm.
  • Use effective contraception during treatment and for:
    • At least 3 weeks after the last dose (for women)
    • At least 14 weeks after the last dose (for male partners of women of childbearing potential)
  • Avoid breastfeeding while taking Palbociclib and for 3 weeks after the last dose.

🔹 Drug Interactions

  • Avoid strong CYP3A inhibitors (e.g., ketoconazole, clarithromycin) and inducers (e.g., rifampin, carbamazepine), as they can affect Palbociclib levels.
  • Grapefruit and grapefruit juice can also interfere with drug metabolism.

🔹 Liver Function

  • Can cause elevated liver enzymes.
  • Monitor LFTs periodically.
  • May need dose adjustment or discontinuation if liver issues arise.

🔹 Risk of Thrombocytopenia and Anemia

  • Low platelets or red blood cells may occur.
  • Monitor blood counts and watch for symptoms like:
    • Easy bruising/bleeding
    • Fatigue or dizziness

🔹 Food Intake

  • Take with food to improve absorption.
  • Taking it at the same time daily helps maintain consistent drug levels.

🔹 Driving or Operating Machinery

  • Some patients may feel dizzy, tired, or weak.
  • Be cautious with activities requiring alertness until you know how the drug affects you.

🔹 Liver or Kidney Impairment

  • Mild to moderate liver/kidney impairment may be tolerated.
  • Severe impairment requires careful evaluation—dose adjustments may be needed.

📌 Patient Reminders

  • Keep all follow-up and blood test appointments.
  • Report any unusual symptoms promptly.
  • Never adjust or stop the dose on your own—always check with your doctor.

Drug Interactions

🔄 Palbosic (Palbociclib) is metabolized primarily by the CYP3A enzyme system, making it prone to interactions with many other drugs. Some interactions can increase toxicity, while others may reduce effectiveness.

Here’s what you need to know:

🔹 CYP3A Inhibitors

These can increase Palbociclib levels, raising the risk of side effects (especially neutropenia).

Avoid or use with caution:

  • Ketoconazole
  • Itraconazole
  • Clarithromycin
  • Ritonavir
  • Grapefruit / grapefruit juice 🍊

💡 If a strong CYP3A inhibitor is required, reduce the Palbociclib dose to 75 mg daily.

🔹 CYP3A Inducers

These may reduce Palbociclib effectiveness by increasing its breakdown in the liver.

Avoid these if possible:

  • Rifampin
  • Carbamazepine
  • Phenytoin
  • St. John’s Wort 🌿
  • Phenobarbital

⚠️ Use alternative medications that do not induce CYP3A.

🔹 Acid-Reducing Agents

Palbociclib is not highly pH-dependent, so antacids, PPIs (e.g., omeprazole), or H2 blockers (e.g., ranitidine) do not significantly affect its absorption.

✅ Generally safe to take together.

🔹 Endocrine Therapy Partners

Palbociclib is often used in combination with:

  • Letrozole (aromatase inhibitor)
  • Fulvestrant (estrogen receptor degrader)

These combinations are safe and standard—no negative interactions noted.

🔹 QT-Prolonging Drugs

Palbociclib has low risk for QT prolongation on its own. However, combining it with other QT-prolonging drugs may increase the risk:

  • Antipsychotics
  • Macrolide antibiotics
  • Certain antiarrhythmics

⚠️ Use caution and monitor ECGs in at-risk patients.

🔹 Hormonal Contraceptives

  • No known direct interaction.
  • Non-hormonal methods are preferred as effectiveness of hormonal contraceptives may be reduced.

📋 Always Inform Your Doctor If You’re Taking:

  • Herbal supplements
  • Over-the-counter medications
  • Antibiotics or antifungals
  • HIV medications
  • Anticonvulsants

Clinical Effectiveness

✅ Palbosic (Palbociclib) is a CDK4/6 inhibitor that has shown significant clinical benefit in treating hormone receptor-positive (HR+), HER2-negative advanced or metastatic breast cancer. It is typically used in combination with endocrine therapy.

Here’s a breakdown of its effectiveness backed by clinical trials and real-world outcomes:

🔬 Key Clinical Trials

1. PALOMA-2 Trial

  • Study Population: Postmenopausal women with HR+/HER2- advanced breast cancer
  • Treatment: Palbociclib + Letrozole vs. Letrozole alone
  • Outcome:
    • Progression-Free Survival (PFS) significantly improved:
      • 24.8 months (combo) vs. 14.5 months (letrozole alone)
    • Overall Response Rate (ORR): 42% vs. 35%

2. PALOMA-3 Trial

  • Study Population: Women with disease progression on prior endocrine therapy
  • Treatment: Palbociclib + Fulvestrant vs. Fulvestrant alone
  • Outcome:
    • PFS:
      • 9.5 months (combo) vs. 4.6 months (fulvestrant alone)
    • Benefit was consistent across premenopausal and postmenopausal patients

🧬 Mechanism Supports Clinical Benefit

  • Inhibits CDK4/6 → halts cell cycle at G1 phase
  • Specifically targets cancer cell proliferation in HR+ breast cancer
  • Works synergistically with endocrine therapy

📈 Real-World Outcomes

  • Real-world studies confirm the durability of response and better disease control
  • Often preferred in first-line therapy for advanced HR+/HER2- cases

💡 Clinical Advantages

  • Delays disease progression
  • Improves quality of life by delaying chemotherapy
  • Oral administration (easy to take at home)
  • Generally well-tolerated compared to traditional chemotherapy

⚠️ Limitations

  • Does not cure cancer—used for control and prolonged remission
  • Resistance may eventually develop
  • Requires regular blood monitoring due to potential for neutropenia

🏁 Conclusion

Palbociclib has become a cornerstone therapy in managing HR+/HER2- metastatic breast cancer due to its robust clinical effectiveness, particularly in extending progression-free survival and maintaining quality of life in patients.

Tips for Patients

💡 If you’re starting Palbosic (Palbociclib) a CDK4/6 inhibitor used for advanced breast cancer, here are practical and essential tips to help you stay safe, manage side effects, and get the most benefit from your treatment.

✅ Stick to the Schedule

  • Take once daily for 21 days, followed by 7 days off (this is 1 full treatment cycle).
  • Take with food at the same time every day.
  • Do not crush, chew, or split the capsule—swallow it whole.

⏰ Set Reminders

  • Use a pill organizer or phone alarm to help remember your doses.
  • Keep a treatment calendar to track your cycle (21 on / 7 off).

🧪 Get Regular Blood Tests

  • Routine CBC tests are essential to monitor for low white blood cells (neutropenia).
  • Stick to your lab schedule—even if you feel fine.

🤒 Watch for Infections

  • Call your doctor immediately if you develop:
    • Fever (≥100.4°F / 38°C)
    • Chills, sore throat, or cough
    • Any signs of infection
  • Avoid crowded places or sick contacts during low blood count periods.

🥗 Support Your Body

  • Eat well: small frequent meals can help if appetite is down.
  • Stay hydrated: especially if you experience diarrhea or nausea.
  • Rest regularly to manage fatigue.

🚫 Avoid These

  • Grapefruit juice – can increase Palbociclib levels in the body.
  • Live vaccines – your immune system may be weaker.
  • Over-the-counter/herbal meds without checking with your doctor (especially St. John’s Wort).

🧼 Practice Good Hygiene

  • Wash your hands often.
  • Use alcohol-based hand sanitizers when you’re out.
  • Be careful with cuts and scrapes—clean them well and monitor for infection.

🤰 Birth Control

  • Palbociclib can harm an unborn baby.
  • Use effective contraception during treatment and:
    • Women: for 3 weeks after the last dose
    • Men: if your partner could become pregnant, continue contraception for 14 weeks after your last dose

💬 Communicate with Your Doctor

  • Report any side effects, no matter how small.
  • Ask questions if anything feels off.
  • Don’t stop or adjust your dose unless advised.

🧘‍♀️ Take Care of Your Mental Health

  • Cancer treatment is tough—emotionally and physically.
  • Talk to a counselor, join a support group, or lean on loved ones when needed.