CARFIMED

CARFIMED

Carfilzomib 60mg
Net Qty- 1 Injection
Self-Life- 2 Years

Carfimed (Carfilzomib 60mg) is a proteasome inhibitor used primarily in the treatment of multiple myeloma, a type of blood cancer that affects plasma cells in the bone marrow.

USE

🎯 Carfimed (Carfilzomib 60mg) is primarily used in the treatment of multiple myeloma, a type of blood cancer affecting plasma cells.

✅ Approved Medical Uses

  1. Multiple Myeloma (MM)
  • Indicated for adults with multiple myeloma who have received at least one prior therapy.
  • Used in combination regimens or as monotherapy.

💊 Common Carfilzomib-Based Combinations:

➤ Carfilzomib + Lenalidomide + Dexamethasone (KRd)

  • Standard regimen for relapsed or refractory multiple myeloma.
  • Shown to improve progression-free survival and overall response rate.

➤ Carfilzomib + Dexamethasone (Kd)

  • Alternative for patients intolerant to lenalidomide or in second-line treatment.

➤ Carfilzomib + Daratumumab + Dexamethasone (KDd)

  • Powerful triplet therapy for relapsed/refractory MM.
  • Offers deeper and longer-lasting responses.

🧪 Investigational/Off-label Uses

While not formally approved, carfilzomib is also being studied in:

  • Newly diagnosed multiple myeloma
  • High-risk myeloma subtypes
  • Smoldering multiple myeloma (under investigation)
  • Combination with monoclonal antibodies or immunotherapies

Mechanism
of Action

Carfilzomib is a second-generation proteasome inhibitor designed to selectively and irreversibly inhibit the 20S proteasome, a key component in the cellular protein degradation machinery.

🧬 How It Works

  • Proteasomes are structures inside cells that break down damaged or misfolded proteins.
  • Cancer cells—especially multiple myeloma cells—produce large amounts of abnormal proteins.
  • Carfilzomib binds irreversibly to the chymotrypsin-like active site of the 20S proteasome.
  • This inhibits protein degradation, leading to:
    • Accumulation of toxic proteins
    • Cellular stress
    • Activation of apoptosis (programmed cell death)

🎯 Why It’s Effective in Multiple Myeloma

  • Myeloma cells rely heavily on proteasome activity to survive due to their high protein production.
  • Blocking this system causes a build-up of misfolded proteins, which myeloma cells can’t handle—triggering cell death.

Dosage and Administration

💉 Carfimed (Carfilzomib 60mg) is administered intravenously (IV) and given on a cyclical schedule depending on the combination regimen used. The dosage is based on body surface area (mg/m²).

 

📅 General Dosing Schedules

✅ Carfilzomib + Dexamethasone (Kd)

  • Days: Administered on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle
  • Dosage:
    • Cycle 1: 20 mg/m² (Days 1–2), then 56 mg/m² (Days 8, 9, 15, 16)
    • Subsequent Cycles: 56 mg/m² (all doses)
  • Dexamethasone: Given with each Carfilzomib dose (typically 20 mg orally or IV)

✅ Carfilzomib + Lenalidomide + Dexamethasone (KRd)

  • Days: Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle
  • Dosage:
    • Cycle 1: 20 mg/m² (Days 1–2)
    • Subsequent Cycles: 27 mg/m² (Days 8, 9, 15, 16)
  • Lenalidomide: Days 1–21
  • Dexamethasone: Weekly or with each Carfilzomib dose

✅ Once-Weekly High-Dose Carfilzomib (Alternative Regimen)

  • Days: Days 1, 8, and 15 of a 28-day cycle
  • Dosage: 70 mg/m² once weekly (after tolerability at 20 mg/m²)
  • Often used in combination with daratumumab or dexamethasone

💧 Hydration

  • Pre- and post-infusion hydration is recommended to reduce the risk of:
    • Tumor lysis syndrome (TLS)
    • Kidney toxicity

🛡️ Premedication

  • Dexamethasone: To reduce infusion reactions
  • Antiviral prophylaxis (e.g., acyclovir) is often recommended to prevent herpes zoster reactivation

⏱️ Infusion Time

  • Typically infused over 10 to 30 minutes, depending on the dose
  • Monitor vital signs during and after infusion, especially blood pressure and cardiac status

⚠️ Important Notes

  • Do NOT administer on consecutive days outside scheduled cycles
  • Dose adjustments may be required for:
    • Cardiac events
    • Liver/kidney issues
    • Hematologic toxicity (e.g., neutropenia, thrombocytopenia)

Common Side Effects

Carfilzomib (Kyprolis) is generally well-tolerated, but like most cancer therapies, it can cause a range of side effects—some common and manageable, others more serious.

 

🧍‍♂️ Most Common Side Effects

 

System/CategorySide Effect
GeneralFatigue, fever
GastrointestinalNausea, vomiting, diarrhea, constipation
HematologicAnemia, thrombocytopenia, neutropenia
CardiovascularHigh blood pressure (hypertension), shortness of breath
RespiratoryCough, dyspnea
MusculoskeletalMuscle cramps, joint pain
Renal/MetabolicIncreased creatinine (kidney stress), low potassium or calcium
Infection-RelatedUpper respiratory tract infections, pneumonia

💉 Infusion-Related Reactions

 

  • May include fever, chills, flushing, or shortness of breath during or shortly after infusion.
  • Premedication with dexamethasone is often given to reduce these reactions.

🧠 Neurological Side Effects

 

  • Peripheral neuropathy is less common with carfilzomib than with bortezomib.
  • Dizziness or headache may occur.

🚨 When to Contact Your Doctor Immediately

  • Chest pain, heart palpitations, or swelling in legs (possible heart issues)
  • Trouble breathing or rapid breathing
  • Unusual bruising or bleeding
  • Signs of infection: persistent fever, chills, sore throat
  • Severe diarrhea or vomiting

 

Monitoring

Careful and consistent monitoring is essential during Carfilzomib (Kyprolis) therapy to ensure safety and effectiveness. Below are the key parameters and assessments that healthcare providers regularly track:

🔍 Cardiac Monitoring

  • Carfilzomib is associated with cardiac toxicity, including heart failure and ischemia.
  • Baseline & periodic ECG
  • Echocardiogram (if history of cardiac issues)
  • Monitor for:
  • Chest pain
  • Shortness of breath
  • Edema (swelling in legs)
  • Fatigue on exertion

💉 Blood Pressure

  • Check before and after each infusion
  • Manage hypertension aggressively
  • Adjust treatment if BP is uncontrolled

🩸 Complete Blood Count (CBC)

  • Regular monitoring for:
  • Neutropenia (risk of infection)
  • Thrombocytopenia (risk of bleeding)
  • Anemia (may cause fatigue)

🧪 Kidney Function

  • Serum creatinine, BUN, and urine output
  • Hydration before and after infusion is important
  • Monitor especially in:
  • Elderly patients
  • Pre-existing kidney disease

🧬 Liver Function Tests (LFTs)

  • ALT, AST, bilirubin
  • Monitor for hepatotoxicity, especially if baseline liver dysfunction is present

💧 Fluid Balance & Hydration

  • Monitor for signs of fluid overload (especially in cardiac patients)
  • Ensure adequate hydration to reduce renal toxicity and tumor lysis syndrome (TLS) risk

🌡️ Infection Surveillance

  • Watch for signs of infection (e.g., fever, sore throat)
  • Prophylactic antivirals (e.g., acyclovir) may be used to prevent herpes zoster

📆 Other Considerations

  • Tumor lysis syndrome (TLS) monitoring in patients with high tumor burden
  • Infusion reactions: observe during and after infusion (especially during the first cycle)

Precautions

Carfilzomib is a powerful anti-cancer agent that requires careful handling and monitoring to ensure safe and effective treatment. Below are key precautions to consider for patients receiving Carfilzomib.

❤️ Cardiac Risk

  • Use with caution in patients with:
    • Congestive heart failure
    • Ischemic heart disease
    • Uncontrolled hypertension
  • Monitor for:
    • Shortness of breath
    • Chest pain
    • Swelling (edema)
  • May cause arrhythmias or sudden cardiac events

💧 Tumor Lysis Syndrome (TLS)

  • Can occur due to rapid breakdown of cancer cells
  • Hydration before and after infusion is essential
  • Monitor electrolytes and uric acid levels

🩸 Hematologic Toxicity

  • Can cause:
    • Anemia
    • Neutropenia (infection risk)
    • Thrombocytopenia (bleeding risk)
  • Regular CBC monitoring is required

🧪 Renal Impairment

  • Use with caution in patients with reduced kidney function
  • Adjust dose as needed
  • Ensure adequate hydration

🌬️ Pulmonary Toxicity

  • May cause pulmonary hypertension or respiratory distress
  • Monitor for new or worsening shortness of breath

🦠 Risk of Infections

  • Immunosuppressive effect can increase infection risk
  • Prophylactic antiviral therapy may be recommended
  • Avoid exposure to infectious individuals

🧠 Infusion Reactions

  • May occur during or after administration
  • Premedicate with dexamethasone
  • Monitor closely during first few infusions

🧬 Liver Dysfunction

  • Monitor ALT, AST, bilirubin
  • Use cautiously in patients with existing liver disease

🚫 Contraindications in Pregnancy

  • Not safe during pregnancy – may harm the fetus
  • Use effective contraception during and for 6 months after therapy
  • Not recommended during breastfeeding

❗ Drug Interactions

  • Avoid strong CYP3A4 inducers/inhibitors
  • Monitor for enhanced side effects with other nephrotoxic or cardiotoxic drugs

Drug Interactions

While Carfilzomib is not extensively metabolized by the cytochrome P450 system, it still poses risks of clinically relevant drug interactions, especially when used with other agents that impact organ systems or immune function.

⚠️ Cardiovascular Drugs

  • Caution with antihypertensives, especially:
    • Diuretics: ↑ risk of dehydration and kidney stress
    • Beta-blockers or calcium channel blockers: may exacerbate hypotension or bradycardia
  • QT-prolonging drugs: Monitor ECG if combined with medications like amiodarone, sotalol, etc.

🧪 Nephrotoxic Drugs

  • Avoid or monitor closely when used with:
    • NSAIDs
    • Aminoglycosides
    • Contrast agents
  • These combinations can increase the risk of kidney injury

🧬 Hepatotoxic Drugs

Use caution with drugs that affect liver function:

    • Acetaminophen (high doses)
    • Methotrexate
    • Antifungals like ketoconazole

🦠 Immunosuppressants

Increased risk of infections when combined with:

  • Corticosteroids (e.g., dexamethasone – often co-administered)
  • Lenalidomide or thalidomide
  • Monoclonal antibodies (e.g., daratumumab)

💊 CYP450 Interactions

Carfilzomib is not a strong substrate or inhibitor of CYP enzymes, but caution is advised:

  • Strong CYP3A4 inducers (e.g., rifampin, phenytoin): may decrease efficacy
  • Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin): limited direct effect, but monitor for enhanced toxicity from co-administered drugs

🧫 Antiviral & Antibacterial Agents

  • Antivirals like acyclovir are often used prophylactically and are generally safe
  • Monitor for renal toxicity if combined with nephrotoxic antibiotics

🧠 CNS Depressants

Additive fatigue, dizziness, or sedation when combined with:

  • Opioids
  • Benzodiazepines
  • Sedating antiemetics

✅ Safe Co-administration

Frequently used drugs with careful monitoring:

  • Lenalidomide
  • Dexamethasone
  • Daratumumab
  • Acyclovir

Clinical Effectiveness

✅ Carfilzomib (Kyprolis) has shown strong clinical effectiveness in treating relapsed and/or refractory multiple myeloma (RRMM), especially when used in combination regimens. Its irreversible proteasome inhibition and favorable safety profile make it a potent option after initial therapies.

📊 Key Clinical Trials Supporting Effectiveness

🔬 ASPIRE Trial (KRd vs. Rd)

  • Regimen: Carfilzomib + Lenalidomide + Dexamethasone (KRd) vs. Lenalidomide + Dexamethasone (Rd)
  • Results:
    • Progression-Free Survival (PFS): 26.3 months (KRd) vs. 17.6 months (Rd)
    • Overall Response Rate (ORR): 87.1% (KRd) vs. 66.7% (Rd)
    • Overall Survival (OS): Significantly improved in KRd arm

✅ Conclusion: KRd regimen significantly improves PFS, ORR, and OS in RRMM patients.

🔬 ENDEAVOR Trial (Kd vs. Vd)

  • Regimen: Carfilzomib + Dexamethasone (Kd) vs. Bortezomib + Dexamethasone (Vd)
  • Results:
    • PFS: 18.7 months (Kd) vs. 9.4 months (Vd)
    • ORR: 77% (Kd) vs. 63% (Vd)
    • Lower rates of peripheral neuropathy in Kd arm

✅ Conclusion: Kd is more effective and better tolerated than Vd in relapsed myeloma.

🧠 Clinical Highlights

  • Effective in bortezomib-refractory or lenalidomide-refractory myeloma
  • Provides deeper and more durable responses when used in triplet or quadruplet combinations
  • Increasingly used in earlier lines of therapy based on emerging data
  • Lower risk of peripheral neuropathy vs. bortezomib, improving patient quality of life

👩‍⚕️ Patient Outcomes

  • Improved depth of response (including complete responses and MRD-negativity)
  • Extended time to progression
  • Tolerable safety profile with manageable side effects
  • Good option for patients with high-risk cytogenetics

Tips for Patients

👩‍⚕️ If you’re receiving Carfimed (Carfilzomib 60mg) for multiple myeloma, it’s important to take steps to stay safe, reduce side effects, and improve your treatment experience. Here are practical tips and advice to help you navigate therapy.

💧 Stay Well-Hydrated

  • Before and after each infusion, drink plenty of water (unless your doctor says otherwise).
  • Proper hydration helps protect your kidneys and reduce the risk of tumor lysis syndrome.

🛏️ Rest, but Stay Active

  • Fatigue is common—rest when needed.
  • Light exercise (like walking) can improve energy, mood, and circulation.

🩺 Monitor Your Blood Pressure

  • Carfilzomib can cause high blood pressure.
  • If you have a BP monitor at home, track your readings regularly and report any significant changes to your healthcare provider.

❤️ Watch for Signs of Heart or Lung Problems

  • Let your doctor know right away if you experience:
  • Shortness of breath
  • Swelling in your legs or feet
  • Chest pain or rapid heartbeat

🦠 Avoid Infections

  • Wash hands frequently and avoid crowded places during peak infection seasons.
  • Stay up-to-date on recommended vaccines (but avoid live vaccines unless approved by your doctor).
  • Prophylactic antivirals like acyclovir may be prescribed—take them as directed.

🧪 Don’t Skip Lab Appointments

  • Regular blood and kidney tests are vital to monitor for:
  • Anemia or low platelets
  • Kidney function
  • Liver health

🗓️ Stick to Your Schedule

  • Carfilzomib is usually given on a specific infusion schedule (like 2 or 3 times per week).
  • Set reminders and arrive on time for infusions to stay on track with your treatment plan.

🚫 Avoid Certain Medications

  • Don’t take NSAIDs (like ibuprofen) or other over-the-counter drugs without talking to your doctor.
  • Tell all your providers you’re on Carfilzomib.

🚻 Track Side Effects

  • Keep a side effect diary to note symptoms like fatigue, nausea, or numbness.
  • Bring this diary to your appointments—it helps your care team tailor your treatment.

🍼 Avoid Pregnancy or Breastfeeding

  • Carfilzomib can harm an unborn baby.
  • Use reliable contraception during treatment and for at least 6 months afterward.