Paclieva 300 — Paclitaxel 300 mg/50 ml Injection, 1 Vial

Paclieva is supplied as a clear, viscous, colorless to slightly yellow concentrate for solution for IV infusion.

Qualitative and Quantitative Composition per 1 ml of Concentrate:

• • Active Ingredient: Paclitaxel IP — 6 mg.
• • Excipients: Polyoxyl castor oil (Cremophor EL / Macrogolglycerol ricinoleate) — 527 mg, absolute ethanol — q.s. to 1 ml.

Packaging Configuration: 300 mg / 50 ml concentrate is filled into clear glass vials of 50 ml capacity, sealed with a rubber stopper and aluminum flip-off seal with a blue plastic cap. Each trade carton contains 1 glass vial and prescribing information. The outer carton bears official Allieva Pharma branding, manufacturing license details, and a security hologram seal.

Pharmacodynamics:
Paclitaxel is an antimicrotubule antineoplastic agent derived semi-synthetically from Taxus species. It enhances the polymerization of tubulin dimers into microtubules and stabilizes microtubules by preventing depolymerization. This prevents normal dynamic reorganization of the microtubule network, inhibiting cell division. Paclitaxel also induces abnormal arrays or bundles of microtubules throughout the cell cycle and multiple asters during mitosis.

Pharmacokinetics:

• • Distribution: Following IV infusion, paclitaxel is extensively bound to plasma proteins (89–98%). It is widely distributed into body tissues and fluids.
• • Metabolism: Extensively metabolized in the liver by cytochrome P450 enzymes CYP2C8 and CYP3A4 to hydroxylated metabolites (primarily 6-alpha-hydroxypaclitaxel).
• • Elimination: Excreted predominantly via the biliary/fecal route (up to 70–80% as metabolites). Renal excretion accounts for approximately 14%. Terminal elimination half-life ($T_{1/2}$) ranges from 3 to 52 hours depending on dose and infusion duration.

Paclieva 300 mg / 50 ml is indicated for the treatment of:

• • Ovarian Carcinoma: First-line therapy of ovarian cancer in combination with platinum compounds, and second-line treatment of metastatic ovarian carcinoma after failure of standard therapy.
• • Breast Carcinoma: Adjuvant treatment of node-positive breast cancer administered sequentially to standard doxorubicin-containing combination chemotherapy; treatment of metastatic breast cancer after failure of combination chemotherapy.
• • Non-Small Cell Lung Cancer (NSCLC): First-line treatment of NSCLC in patients who are not candidates for potentially curative surgery and/or radiation therapy (in combination with cisplatin).
• • AIDS-Related Kaposi's Sarcoma: Second-line treatment of advanced AIDS-related Kaposi's sarcoma.

Paclieva 300 mg / 50 ml must be administered intravenously under the supervision of a physician experienced in the use of cancer chemotherapeutic agents.

Mandatory Premedication Protocol:
To prevent severe hypersensitivity reactions, all patients must be premedicated prior to paclitaxel infusion with corticosteroids (dexamethasone 20 mg orally or IV), antihistamines (diphenhydramine 50 mg IV), and $H_2$-receptor antagonists (ranitidine 50 mg IV or famotidine 20 mg IV) approximately 30–60 minutes before administration.

Preparation and Administration Guidelines:

• • Dilution Required: The concentrate must be diluted prior to infusion (To be diluted for IV Infusion) with 0.9% Sodium Chloride Injection or 5% Dextrose Injection to a final concentration of 0.3 to 1.2 mg/ml.
• • Infuse through an in-line filter with a microporous membrane not greater than 0.22 microns.
• • Do not use PVC-containing infusion sets or bags to prevent leaching of DEHP (di-2-ethylhexyl phthalate). Use non-PVC equipment such as glass, polypropylene, or polyolefin containers.

Dosage Regimen:

• • Ovarian / Breast Carcinoma: 175 mg/$m^2$ given IV over 3 hours every 3 weeks, or 135 mg/$m^2$ given as a 24-hour continuous infusion.
• • NSCLC: 175 mg/$m^2$ given IV over 3 hours followed by cisplatin every 3 weeks.

Administration of Paclieva 300 mg / 50 ml is contraindicated in:

• • Hypersensitivity: Patients with a history of severe hypersensitivity reactions to paclitaxel, polyoxyl castor oil (Cremophor EL), or any inactive ingredients.
• • Baseline Neutropenia: Patients with baseline neutrophil counts $< 1.5 \times 10^9$/L ($< 1,500/\text{mm}^3$) in solid tumors, or $< 1.0 \times 10^9$/L in AIDS-related Kaposi's sarcoma.
• • Pregnancy & Lactation: Contraindicated during pregnancy and breastfeeding.
• • Severe Infection: Patients with severe, uncontrolled concomitant infections.

Important drug interactions to consider during Paclieva therapy:

• • Platinum Compounds (Cisplatin): In combination regimens, Paclieva should be administered prior to cisplatin. Sequence administration of paclitaxel after cisplatin decreases paclitaxel clearance and increases myelosuppression.
• • CYP2C8 and CYP3A4 Inhibitors/Inducers: Co-administration with CYP2C8/CYP3A4 inhibitors (ketoconazole, erythromycin) may increase paclitaxel plasma levels. Inducers (rifampin, carbamazepine) may decrease paclitaxel exposure.
• • Doxorubicin: Paclitaxel may increase plasma concentrations of doxorubicin and its active metabolites.

Pregnancy:
Paclitaxel causes embryo-fetal lethality and teratogenicity. Paclieva is strictly contraindicated during pregnancy. Both male and female patients of reproductive potential must utilize effective contraception during treatment and for at least 6 months following treatment discontinuation.

Lactation:
It is unknown whether paclitaxel is excreted in human milk. Breastfeeding must be discontinued during Paclieva therapy.

Treatment with Paclieva 300 mg / 50 ml may cause adverse reactions attributable to paclitaxel or the polyoxyl castor oil vehicle.

Adverse Reactions:

• • Hematologic Toxicity (Very Common): Severe myelosuppression (neutropenia, anemia, thrombocytopenia). Neutrophil nadir typically occurs on days 8–11.
• • Hypersensitivity Reactions: Anaphylactoid reactions (hypotension, dyspnea, bronchospasm, urticaria, abdominal pain), predominantly occurring within the first minutes of infusion.
• • Nervous System: Peripheral neuropathy (paresthesia, numbness in hands and feet), arthralgia, myalgia.
• • Cardiovascular: Bradycardia, hypotension, ECG changes, rare cases of AV block.
• • Gastrointestinal: Nausea, vomiting, diarrhea, mucositis, stomatitis.
• • Dermatologic: Alopecia (hair loss occurs in nearly all patients), nail changes.

Symptoms:
Primary complications of overdose include severe myelosuppression (profound neutropenia), peripheral neurotoxicity, and severe mucositis.

Treatment:
No specific antidote for paclitaxel overdose is known. Patient management should consist of supportive measures including G-CSF administration, blood product transfusions, and broad-spectrum antibiotic therapy for febrile neutropenia.

Storage Requirements for Paclieva 300 mg / 50 ml:

• 🌡️ Temperature: Store below 30°C. Do not freeze (precipitation may occur upon freezing, which redissolves upon reaching room temperature).
• ☀️ Light & Moisture Protection: Store in original carton to protect from light and moisture.
• 👶 Safety: Keep out of reach of children.
• ⏳ Shelf Life: Stated on the packaging and vial label (Exp. Date). Caution: Prescription Only (Rx Only).

To verify original Paclieva 300 mg / 50 ml manufactured by Allieva Pharma, check the following packaging details:

• ✅ Security Hologram Seal: Official holographic security seal placed over the top flap of the outer carton.
• ✅ Allieva Pharma Corporate Logo: Stylized red and blue "A" Allieva Pharma logo printed on the box and vial label.
• ✅ Box Design Elements: White carton with curved green bottom accent and oval "300 mg" badge.
• ✅ Manufacturing Identification: Printed Batch Number (Batch No.), Manufacturing Date (Mfg. Date), Expiration Date (Exp. Date), Manufacturing License Numbers (Mfg. Lic. No.), and M.R.P. on the side panel.
• ✅ Vial and Cap: 50 ml clear glass vial fitted with a blue plastic flip-off seal over an aluminum crimp.