Bleocin (Bleomycin) 15 mg

Bleocin is supplied as a sterile lyophilized powder for solution for injection or infusion:

• Presentation and Packaging: Packaged in 1 clear Type I glass vial sealed with a rubber stopper and aluminum flip-off seal. Each vial contains 15 Units of sterile, white to off-white lyophilized Bleomycin powder. Each vial is encased in an outer cardboard box along with complete prescribing information.
• Active Ingredient: Bleomycin Sulfate I.P. — 15 Units per vial (representing a purified mixture of glycopeptide fractions Bleomycin A2 and B2).
• Excipients: Hydrochloric acid and/or sodium hydroxide (used in trace quantities strictly for pH adjustment during processing). Contains no added preservatives.

Pharmacodynamics: Bleomycin is a complex glycopeptide antibiotic. Its cytotoxic action involves DNA strand scission. Bleomycin chelates ferrous iron (Fe2+) to form an active enzyme-like complex. When this complex reacts with molecular oxygen, it generates reactive oxygen species (ROS), including superoxide and hydroxyl free radicals, which produce single- and double-strand DNA breaks. This leads to inhibition of DNA synthesis, chromosomal aberrations, and cell death. Bleocin acts specifically during the G2 and M phases of the cell cycle.

Pharmacokinetics: Peak plasma concentration (Cmax) occurs within 30 to 60 minutes following IM or SC injection. Intravenous administration provides immediate therapeutic plasma levels. It distributes widely, concentrating primarily in skin, lungs, kidneys, and tumor tissues. Protein binding is low (<10%). Bleomycin is degraded by the enzyme bleomycin hydrolase, which is widespread except in pulmonary and cutaneous tissues. The elimination half-life (T1/2) is 2 to 4 hours in patients with normal renal function. About 60% to 70% of the active dose is excreted unchanged in the urine within 24 hours.

Bleocin 15 Units is indicated as monotherapy or as part of combination chemotherapy protocols for:

• 🔹 Lymphomas: Hodgkin lymphoma and non-Hodgkin lymphomas (ABVD, BEACOPP, CHOP regimens).
• 🔹 Germ Cell Tumors: Testicular carcinomas (seminomas and non-seminomas) and malignant ovarian germ cell tumors.
• 🔹 Squamous Cell Carcinomas: Cancer of the skin, esophagus, cervix, penis, and vulva.
• 🔹 Head and Neck Cancers: Squamous cell carcinoma of the larynx, pharynx, oral cavity, and paranasal sinuses.
• 🔹 Malignant Effusions: Intrapleural instillation for the control of malignant pleural effusion (chemical pleurodesis).

Bleocin administration must be directed by a qualified oncologist tailored to body surface area (BSA) and renal status:

• 💊 Standard Dosage: The usual recommended dose is 10–15 Units/m² BSA (or 15–30 Units per dose) administered once or twice weekly.
• 💉 Reconstitution and Administration Routes:
  • Intramuscular/Subcutaneous: Reconstitute 15 Units in 1–5 mL of 0.9% Sodium Chloride Injection. 1% Lidocaine may be added to minimize localized discomfort.
  • Intravenous Bolus: Dissolve 15 Units in 5–10 mL of 0.9% NaCl and inject slowly over 5–10 minutes.
  • Intravenous Infusion: Dilute reconstituted solution in 100–500 mL of 0.9% NaCl or 5% Dextrose and infuse over 30–60 minutes.
• ⚠️ Maximum Lifetime Cumulative Dose: Total cumulative dose should not exceed 300–400 Units (and should be limited to 200 Units in patients over 60 years of age) to reduce the risk of pulmonary fibrosis.

Bleocin is contraindicated in the presence of:

• ❌ Known hypersensitivity or severe allergic reaction to Bleomycin.
• ❌ Existing severe pulmonary infection, pulmonary fibrosis, or severely impaired lung function.
• ❌ Severe renal impairment (creatinine clearance < 30 mL/min).
• ❌ Pregnancy and lactation.
• ❌ Severe decompensated cardiovascular disorders.

Important drug interaction profiles for Bleocin include:

• ⚠️ Pulmotoxic Agents: Concurrent use with carmustine, busulfan, cyclophosphamide, or thoracic radiation significantly increases the incidence of pulmonary toxicity.
• ⚠️ Platin-Based Drugs: Cisplatin decreases renal clearance of bleomycin, raising systemic toxicity risk even at conventional doses.
• ⚠️ Oxygen Therapy: Exposure to high concentrations of oxygen during surgery/anesthesia post-bleomycin treatment may trigger acute pulmonary damage.
• ⚠️ Live Vaccines: Live attenuated vaccinations during therapy pose a severe risk of generalized vaccine-induced infection.

Reproductive considerations during Bleocin treatment:

• 🤰 Pregnancy: Bleomycin is teratogenic, mutagenic, and embryotoxic. It is strictly contraindicated during pregnancy. Men and women of childbearing potential must use reliable contraception during treatment and for at least 6 months post-treatment.
• 🤱 Lactation: It is not fully documented whether bleomycin passes into human breast milk. Breastfeeding must be suspended during treatment due to potential toxicity.

Common and significant adverse effects reported with Bleocin include:

• 🔴 Pulmonary Toxicity: Interstitial pneumonitis (dry cough, dyspnea, rales), which can progress to irreversible pulmonary fibrosis.
• 🟡 Dermatologic Reactions: Hyperpigmentation (flagellate hyperpigmentation), hyperkeratosis, rash, alopecia, nail changes.
• 🟠 Pyrexia/Febrile Episodes: Fever and chills occurring 2 to 6 hours after administration (can often be prevented with pre-medication).
• 🟢 Other Effects: Nausea, vomiting, loss of appetite, stomatitis, Raynaud's phenomenon.

Management of overdose scenarios:

• Symptoms: Acute hypotension, high fever, rapid respiration, severe bronchospasm, and pulmonary symptoms.
• Treatment: No specific antidote exists. Treatment is supportive and symptomatic, including immediate cessation of the drug and administration of corticosteroids when indicated. Hemodialysis is ineffective.

Storage requirements and conditions for Bleocin:

• Temperature Range: Store the lyophilisate (powder) in the original packaging at a temperature not exceeding 30 °C. Do not freeze. After preparation (reconstitution), the solution should be stored in a refrigerator at 2 °C to 8 °C.
• Protection from Environmental Factors: Store in a dry place protected from light, avoiding direct exposure to sunlight and high humidity.
• Storage Safety: Keep out of reach of children and unauthorized persons.
• Shelf Life and Solution Stability: 24 months from the date of manufacture. Do not use after the expiration date indicated on the package. The prepared solution is recommended for immediate use after reconstitution; if necessary, the prepared solution may be stored in a refrigerator (2–8 °C) for no more than 24 hours.

Authenticity features of original Bleocin:

• packaging quality: Crisp offset printing on a green-and-white outer box clearly displaying Bleocin (Lyophilized).
• licensing details: Distinctly displays production by Khandelwal Laboratories Pvt. Ltd. (India) under agreement with Nippon Kayaku Co. Ltd. (Tokyo, Japan).
• batch identification: Includes embossed or laser-printed details of Batch No., Mfg. Date, and Exp. Date on the outer carton and vial label.