Carfilnat 60 — Carfilzomib for Injection 60 mg, 1 Vial Cold chain · Storage +2…+8 °C

Carfilnat 60 is supplied as a lyophilized powder for solution for infusion.

Qualitative and Quantitative Composition per Vial:

• Active Ingredient: Carfilzomib — 60 mg.
• Excipients: Sulfobutylether beta-cyclodextrin sodium (betadex sulfobutyl ether sodium), citric acid anhydrous, sodium hydroxide (for pH adjustment).

Packaging and Presentation: White to off-white lyophilized cake or powder in a colorless glass vial sealed with a rubber stopper and aluminum flip-off cap. 1 vial with prescribing information per outer carton displaying Carfilnat 60 (Carfilzomib for Injection) and Natco Pharma corporate graphics.

Pharmacodynamics:
Carfilzomib is a tetrapeptide epoxyketone proteasome inhibitor. Proteasomes play a crucial role in degrading damaged or unneeded cellular proteins. Inhibition of the chymotrypsin-like activity of the 20S proteasome by carfilzomib disrupts normal proteostasis, causes protein accumulation, activates endoplasmic reticulum stress, and induces apoptosis in multiple myeloma cells. Carfilzomib irreversibly binds its targets with high selectivity.

Pharmacokinetics:

• Absorption & Distribution: Administered intravenously, achieving 100% bioavailability. Human plasma protein binding averages 23% to 27%. Steady-state volume of distribution ranges from 7.8 to 8.3 L.
• Metabolism: Rapidly and extensively metabolized via peptide cleavage and epoxide hydrolysis into inactive metabolites. Cytochrome P450 isoenzyme involvement is minimal.
• Elimination: Eliminated predominantly via extrahepatic pathways. Total clearance ranges from 151 to 263 L/h. Terminal elimination half-life ($T_{1/2}$) is less than 1 hour following initial dosing.

Carfilnat 60 is indicated in adult patients for:

• Multiple Myeloma: Treatment of adult patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy (in combination with dexamethasone or lenalidomide plus dexamethasone).
• Refractory Myeloma (Monotherapy): Indicated as a single agent for patients with disease progression following two or more prior lines of therapy.

Carfilnat 60 is administered exclusively via intravenous infusion (over 10 to 30 minutes depending on regimen).

Preparation Instructions:
Reconstitute the 60 mg vial aseptically with 29 ml of sterile water for injections (resulting in a 2 mg/ml concentration). Do not shake! The resulting solution should be clear and colorless. Dilute the required dose in 50 or 100 ml of 5% dextrose injection prior to infusion.

Dosing Regimen (Standard Schedules):

• In Combination with Dexamethasone: Recommended starting dose is 20 mg/m² on days 1 and 2; if tolerated, escalate to 27 mg/m² (or 56 mg/m² in weekly schedules) on days 8, 9, 15, and 16 of each 28-day cycle.
• Premedication: To reduce infusion-related reactions, administer corticosteroids (e.g., oral or IV dexamethasone) prior to each dose in cycle 1 and as needed thereafter.

Administration of Carfilnat 60 is contraindicated in:

• Hypersensitivity: Known hypersensitivity to carfilzomib or any excipient.
• Pregnancy and Lactation: Strictly contraindicated in pregnant or breastfeeding women due to embryo-fetal toxicity and teratogenic risks.
• Severe Cardiac Conditions: Acute heart failure, severe arrhythmias, or recent myocardial infarction (within the past 3 to 6 months).

Because carfilzomib is metabolized via peptidases and epoxide hydrolases rather than cytochrome P450 (CYP450) enzymes:

• CYP450 Inhibitors and Inducers: Pharmacokinetic drug interactions with agents affecting CYP450 systems are unlikely.
• Oral Contraceptives: Efficacy of hormonal contraceptives may be reduced during carfilzomib therapy. Barrier methods are recommended.
• Cardiotoxic Agents: Caution is warranted during co-administration due to potential additive cardiac risks.

Pregnancy:
Carfilnat 60 is contraindicated during pregnancy. Carfilzomib may cause fetal harm. Women of childbearing potential and male partners must utilize effective contraception during treatment and for at least 3 months following the final dose.

Lactation:
Excretion into human breast milk is unstudied. Breastfeeding is strictly prohibited during treatment.

The most frequent and clinically significant adverse reactions include:

• Cardiovascular System: Heart failure, hypertension, myocardial ischemia, pulmonary edema, arrhythmias. Thorough cardiac monitoring is required.
• Infections: Upper respiratory tract infections (pneumonia, bronchitis), nasopharyngitis, herpes viral infections.
• Hematologic Toxicity: Anemia, thrombocytopenia, neutropenia, lymphopenia.
• Respiratory System: Dyspnea, cough, acute respiratory failure.
• Gastrointestinal Tract: Diarrhea, nausea, vomiting, constipation, abdominal pain, decreased appetite.
• General Disorders: Fatigue, peripheral edema, pyrexia, insomnia, muscle spasms.

Symptoms:
Clinical experience with carfilzomib overdose is limited. Acute onset of toxicity symptoms has been reported, including chills, hypotension, dehydration, confusion, elevated serum creatinine, and renal failure.

Treatment:
No specific antidote exists. Supportive and symptomatic care should be initiated, with close monitoring of hemodynamics and renal function.

Storage Requirements for Carfilnat 60 (Critical!):

• 🌡️ Temperature Range: Store in a refrigerator protected from light at temperatures between 2 °C and 8 °C. Do not freeze!
• 💧 Transportation: Transport in a cold chain thermal container (2–8 °C).
• 👶 Safety Precautions: Keep out of reach of children.
• ⏳ Shelf Life: Stated on carton and vial. Reconstituted infusion solutions should be used immediately (or stored refrigerated for up to 24 hours). Prescription-only hospital medicine.

To verify authenticity of genuine Carfilnat 60 manufactured by Natco Pharma, inspect the following features:

• ✅ Corporate Logo: Distinctive blue-green Natco Pharma corporate logo printed on the outer carton and vial label.
• ✅ Packaging Markings: Clear factory printing displaying Batch No., Mfg. Date, Exp. Date, and product designation Carfilnat 60 (Carfilzomib for Injection).
• ✅ Vial Quantity: Standard box contains exactly 1 vial of lyophilized powder (60 mg).
• ✅ Print Quality: High-grade packaging artwork with anti-counterfeit features, clear typography, and zero spelling errors.