Bleonix15 unit/vial

Bleonix is an antitumor antibiotic used, usually as part of combination chemotherapy regimens, for the following established indications:

FDA-approved / established uses

• Hodgkin lymphoma and non-Hodgkin lymphoma (used in combination regimens, e.g. with doxorubicin, vinblastine and dacarbazine)
• Squamous cell carcinoma of the head and neck (including tongue, tonsil, nasopharynx, oropharynx, sinus, palate, lip, buccal mucosa and gingiva), skin, cervix, and vulva
• Testicular carcinoma (embryonal cell carcinoma, choriocarcinoma, teratocarcinoma), typically combined with other cytotoxic agents
• Malignant pleural effusion — used as a sclerosing agent (pleurodesis) to prevent recurrent fluid accumulation

Bleonix is administered only under the supervision of a qualified oncologist as part of a defined chemotherapy protocol; it is not used as monotherapy for most solid tumor indications and requires cumulative-dose monitoring.

Bleonix is a water-soluble antitumor (cytotoxic) antibiotic derived from the fungus Streptomyces verticillus. It is chemically classified as a glycopeptide and is used intravenously, intramuscularly, subcutaneously, or intrapleurally as part of cancer chemotherapy.

Unlike many cytotoxic antibiotics, Bleonix causes minimal bone marrow suppression at usual doses, but is notable for dose-related pulmonary toxicity, which limits the total cumulative amount that can safely be given over a patient's lifetime.

Antineoplastic antibiotic (glycopeptide) — cytotoxic chemotherapy agent

Bleomycin Sulfate exerts its cytotoxic effect by binding to DNA and, in the presence of oxygen and metal ions (particularly iron), generating reactive oxygen free radicals that cause single- and double-strand breaks in DNA. This leads to chromosomal aberrations and inhibition of DNA synthesis and repair.

Bleomycin Sulfate is relatively cell-cycle-phase specific, with maximal activity against cells in the G2 and M phases, which makes it particularly useful in combination with cell-cycle non-specific agents.

After parenteral administration, Bleomycin Sulfate is widely distributed, with highest concentrations found in skin and lung tissue (organs that have low levels of the inactivating enzyme bleomycin hydrolase), which is thought to explain the characteristic cutaneous and pulmonary toxicity of the drug. It is eliminated predominantly by renal excretion.

Bleonix may be given by intravenous (IV) injection or infusion, intramuscular (IM) injection, subcutaneous (SC) injection, or, for pleurodesis, by intrapleural instillation. It must be reconstituted immediately before use (see Reconstitution).

• For IV use, the reconstituted solution is usually given slowly, over 10 minutes or as directed by protocol, to reduce the risk of an idiosyncratic reaction.
• For IM or SC injection, the solution is generally limited to a specified maximum volume per injection site.
• For intrapleural use, the solution is instilled into the pleural space after fluid drainage, and the patient is repositioned periodically to distribute the drug.
• Administration of Bleonix must occur under direct supervision of a physician experienced in cancer chemotherapy, with resuscitation equipment immediately available.

Clinically significant interactions with Bleonix include:

• Supplemental oxygen / general anesthesia: High inspired oxygen concentrations increase the risk of severe, potentially fatal pulmonary toxicity in patients who have received Bleonix. Anesthesia providers must be informed so that the lowest safe fraction of inspired oxygen (FiO2) is used during any surgery or procedure, sometimes for years after treatment.
• Cisplatin: Cisplatin-induced nephrotoxicity can reduce renal clearance of Bleonix, increasing systemic exposure and the risk of pulmonary toxicity.
• Other pulmonary-toxic drugs or thoracic radiation therapy: Concurrent or prior use with agents or radiation that damage lung tissue increases the risk of pulmonary toxicity with Bleonix.
• Granulocyte colony-stimulating factors (e.g., filgrastim): May increase the risk or severity of pulmonary toxicity when used with Bleonix.
• Live vaccines: Because Bleonix is immunosuppressive as part of combination chemotherapy, live vaccines should generally be avoided during and shortly after treatment.

Common and important adverse effects associated with Bleonix include:

• Mucocutaneous reactions (very common): hyperpigmentation, erythema, hyperkeratosis, striae, vesiculation, nail changes, and alopecia
• Pulmonary toxicity: pneumonitis progressing to pulmonary fibrosis, dose- and age-dependent (see Precautions and Warnings)
• Fever and chills, usually within a few hours of administration
• Idiosyncratic (anaphylactoid) reaction: hypotension, confusion, wheezing, fever — mainly in lymphoma patients (see Precautions and Warnings)
• Stomatitis, nausea, vomiting, and anorexia
• Weight loss with prolonged therapy
• Pain at the tumor site or injection site; phlebitis
• Rare: Raynaud's phenomenon, digital vasospasm

Bleonix can cause fetal harm when administered to a pregnant woman, based on its mechanism of action and animal data. Bleonix should be used during pregnancy only if clearly needed and if the potential benefit to the mother justifies the potential risk to the fetus; women of reproductive potential should be advised to use effective contraception during treatment. A physician must always be consulted before use in pregnancy.

It is not known whether Bleonix is excreted in human milk; because of the potential for serious adverse effects in nursing infants, breastfeeding should be discontinued during treatment with Bleonix, on physician advice.

Boxed warnings

• Pulmonary toxicity: Bleonix can cause potentially fatal pulmonary fibrosis. Risk increases with cumulative dose (particularly above approximately 400 units), older age, prior/concurrent chest radiation, and high supplemental-oxygen exposure. Pulmonary function (including diffusion capacity) and chest imaging should be monitored regularly during and after treatment, and the drug discontinued at the first sign of pulmonary toxicity.
• Idiosyncratic (anaphylactoid) reaction: An acute reaction with hypotension, confusion, fever, chills, and wheezing has occurred, particularly in lymphoma patients. A test dose is recommended before the first one to two doses, with close observation.
• Mucocutaneous toxicity: Severe skin reactions can occur and are generally dose-related, appearing after 50% of the total planned dose has been given.

Other precautions

• Bleonix must be administered only under the supervision of a physician experienced in cancer chemotherapy, in a setting equipped to manage anaphylactoid reactions and other emergencies; it is not intended for outpatient self-administration.
• Renal function should be assessed before and during treatment, as reduced clearance increases toxicity risk.
• Any anesthesia provider or surgical team must be informed of prior treatment with Bleonix so that inspired oxygen concentration can be minimized.
• Regular monitoring of lung, skin, and renal function, along with complete blood counts, is recommended throughout therapy with Bleonix.

There is no specific antidote for Bleonix overdose. Overdose or excessive cumulative dosing significantly increases the risk of severe pulmonary and mucocutaneous toxicity. Any suspected overdose must be treated as a medical emergency — the patient should receive immediate medical attention at a hospital or oncology unit, where supportive care, close monitoring of pulmonary and renal function, and symptomatic treatment can be provided. Contact emergency services or a poison control center immediately if an overdose is suspected.

Elderly patients (especially over 70 years): Increased risk of pulmonary toxicity with Bleonix; lower cumulative dose thresholds and closer monitoring are generally recommended.

Renal impairment: Because Bleonix is eliminated mainly by the kidneys, patients with reduced renal function require significant dose reduction and closer monitoring for toxicity (see Dosage and Administration).

Hepatic impairment: No well-established dose adjustment exists for Bleonix in hepatic impairment; use with general caution and clinical monitoring.

Pediatric patients: Used in pediatric oncology protocols (e.g., Hodgkin lymphoma, germ cell tumors) under specialist supervision, with dosing based on body surface area; see Pediatric Uses.

Bleonix powder for injection must be reconstituted immediately before use. It is typically dissolved in 0.9% sodium chloride injection, sterile water for injection, or 5% dextrose injection, as directed by the product labeling, to achieve the required concentration for IV, IM, SC, or intrapleural administration.

Reconstituted Bleonix solution should be used promptly; refer to the manufacturer's labeling for the specific storage time and temperature permitted for the reconstituted solution, and discard any unused portion appropriately as cytotoxic waste.

Antineoplastic agents; Antitumor antibiotics; Glycopeptide cytotoxic agents

D

Bleonix is used in children as part of established pediatric oncology protocols, most notably for Hodgkin lymphoma and germ cell (testicular/ovarian) tumors, always under the supervision of a pediatric oncology specialist. Dosing is calculated by body surface area using the same general principles as in adults.

Children may be particularly sensitive to the pulmonary and mucocutaneous toxicities of Bleonix; pulmonary function should be monitored where feasible, and cumulative dose tracked carefully throughout treatment. Safety and efficacy outside established pediatric oncology protocols have not been established.