Natdox-LP — Pegylated Liposomal Doxorubicin 20 mg/10 ml Vial Cold chain · Storage +2…+8 °C

Natdox-LP is supplied as a concentrate for solution for infusion (pegylated liposomal).

Qualitative and Quantitative Composition per 10 ml Vial:

• Active Ingredient: Doxorubicin hydrochloride (in pegylated liposomal form) — 20 mg (2 mg/ml).
• Lipid Components & Excipients: N-(carbonyl-methoxypolyethylene glycol 2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine sodium salt (MPEG-DSPE), fully hydrogenated soy phosphatidylcholine (HSPC), cholesterol, histidine, sucrose, sodium hydroxide or hydrochloric acid (for pH adjustment), water for injections.

Packaging and Presentation: Sterile, translucent red liposomal suspension for infusion. 10 ml concentrate in a colorless glass vial sealed with a rubber stopper and aluminum flip-off seal. 1 vial with prescribing information per outer carton displaying Natdox-LP (Pegylated Liposomal Doxorubicin Hydrochloride Injection 20 mg/10 ml) and Natco Pharma corporate graphics.

Pharmacodynamics:
Doxorubicin is a cytotoxic anthracycline antibiotic. Its mechanism of action involves DNA base-pair intercalation, inhibition of topoisomerase II, and free radical generation leading to DNA strand breaks and cell cycle arrest. Liposome pegylating protects against rapid reticuloendothelial system clearance, enabling prolonged circulation and selective extravasation into tumor tissue through compromised tumor vessel walls.

Pharmacokinetics:

• Distribution: Pegylated liposomal doxorubicin exhibits a small volume of distribution approaching blood plasma volume, indicating intravascular containment with gradual tumor tissue penetration.
• Metabolism: Intraliposomal doxorubicin is protected from metabolic degradation. Once released into tumor tissues, it undergoes metabolism identical to conventional doxorubicin, yielding the active metabolite doxorubicinol.
• Elimination: Plasma clearance is extremely low (~0.041 L/h/m²). Terminal elimination half-life ($T_{1/2}$) averages 50 to 80 hours, significantly exceeding non-liposomal doxorubicin parameters.

Natdox-LP is indicated in adult patients for:

• Ovarian Cancer: Second-line treatment of advanced ovarian cancer in women following failure of first-line platinum-based chemotherapy.
• Breast Cancer: Monotherapy for metastatic breast cancer in patients with heightened cardiac risk.
• Multiple Myeloma: In combination with bortezomib for patients with progressive disease who have received at least one prior therapy.
• Kaposi's Sarcoma: Treatment of AIDS-related Kaposi's sarcoma in patients with severe immunocompromise who have failed or cannot tolerate systemic combination chemotherapy.

Natdox-LP must be administered strictly by intravenous infusion. Do not administer as a bolus or undiluted injection!

Preparation & Administration:

• Dilute the prescribed dose in 250 ml or 500 ml of 5% Dextrose Injection. Do not dilute in 0.9% Sodium Chloride Injection or mix with other drugs!
• To minimize infusion-related reactions, initiate the initial infusion at a rate not exceeding 1 mg/min. If no reaction occurs, subsequent infusions may be administered over 60 minutes.

Dosing Regimen:

• Ovarian / Breast Cancer: 50 mg/m² body surface area once every 4 weeks.
• Multiple Myeloma: 30 mg/m² administered on day 4 of a 21-day bortezomib treatment cycle.
• Kaposi's Sarcoma: 20 mg/m² once every 2 to 3 weeks.

Administration of Natdox-LP is contraindicated in:

• Hypersensitivity: Known hypersensitivity to doxorubicin hydrochloride, pegylated liposomal components, or any excipient.
• Pregnancy and Lactation: Contraindicated during pregnancy and breastfeeding.
• Severe Myelosuppression: Severe baseline bone marrow suppression (neutrophils < 1,500/µl, platelets < 100,000/µl).
• Kaposi's Sarcoma: Manageable with local therapy or systemic alpha-interferon.

Evaluated drug interactions for pegylated liposomal doxorubicin include:

• Cardiotoxic Agents (trastuzumab, paclitaxel, cyclophosphamide): Concurrent or prior use increases cardiotoxicity risk. Cardiac monitoring is mandatory.
• Myelosuppressive Drugs: Co-administration exacerbates bone marrow toxicity.
• Infusion Diluents: Incompatible with 0.9% Sodium Chloride Injection or alkaline solutions (causes liposomal precipitation).

Pregnancy:
Natdox-LP is contraindicated during pregnancy due to inherent mutagenic, embryotoxic, and teratogenic risks of doxorubicin. Men and women of childbearing potential must utilize effective contraception during treatment and for 6 months post-therapy.

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

The adverse event profile of pegylated liposomal doxorubicin differs from conventional doxorubicin:

• Palmar-Plantar Erythrodysesthesia (PPE / Hand-Foot Syndrome) (Very Common): Dose-limiting toxicity manifesting as palmar/plantar erythema, edema, tenderness, and desquamation.
• Infusion-Related Reactions: Dyspnea, facial flushing, rash, chest/back pain, hypotension (associated with rapid initial infusion rates).
• Gastrointestinal Tract: Stomatitis, mucositis, nausea, vomiting, diarrhea, anorexia.
• Hematologic Toxicity: Leukopenia, neutropenia, anemia, thrombocytopenia.
• Cardiotoxicity: Significantly lower frequency than conventional formulations; however, arrhythmias and LFEV reductions may occur at high cumulative doses.
• Dermatologic: Rash, mild to moderate alopecia (unlike severe alopecia seen with conventional doxorubicin).

Symptoms:
Acute overdose exacerbates toxicities, causing severe mucositis, pronounced hand-foot syndrome, and severe myelosuppression (neutropenia, thrombocytopenia).

Treatment:
No specific antidote exists. Hospitalization in a protective environment, supportive care, blood component transfusions, and G-CSF administration are indicated.

Storage Requirements for Natdox-LP (Critical!):

• 🌡️ Temperature Range: Store refrigerated protected from light at temperatures between 2 °C and 8 °C. Do not freeze! Freezing damages liposomal integrity.
• 💧 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. Diluted 5% Dextrose solutions should be used immediately or stored at 2–8 °C for no more than 24 hours. Prescription-only hospital medicine.

To verify the authenticity of genuine Natdox-LP (20 mg/10 ml) 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 Natdox-LP (Pegylated Liposomal Doxorubicin Hydrochloride Injection 20 mg/10 ml).
• ✅ Suspension Appearance: Sterile, translucent red homogeneous liposomal suspension without visible precipitates or separation.
• ✅ Vial Quantity: Carton contains exactly 1 glass vial of 10 ml.