Bendit — Bendamustine Hydrochloride 100 mg (1 Vial)

Bendit is available in the form of a lyophilized powder for the preparation of a concentrate for solution for infusion, supplied in an individual vial:

• Active Compound: Bendamustine Hydrochloride — 100 mg in each vial.
• Excipients: Mannitol (acts as a stabilizer and ensures the correct porous structure of the lyophilized powder for its rapid and complete dissolution).
• Appearance: A white to off-white lyophilized powder or solid mass in a dark glass vial with a protective plastic flip-off cap. Intended for single use only.

Pharmacodynamics: Bendamustine is an antineoplastic agent with alkylating activity. The mechanism of action is associated with the cross-linking of DNA macromolecules, which disrupts the template function of DNA and the synthesis of RNA and proteins. This leads to the death of both dividing and resting tumor cells.

Pharmacokinetics: After intravenous infusion, bendamustine is rapidly metabolized in the liver via hydrolysis and with the involvement of the CYP1A2 isoenzyme. The primary route of excretion is through the kidneys and intestines. The half-life of the active substance is approximately 30 minutes, and the drug does not accumulate in body tissues.

Bendit 100 mg is prescribed by an experienced hematologist or oncologist as monotherapy or as part of combination treatment regimens for:

• 🔹 Chronic Lymphocytic Leukemia (CLL): As a first-line therapy (the efficacy of use in patients with mutations or resistance is evaluated by the doctor individually).
• 🔹 Indolent Non-Hodgkin's Lymphomas (NHL): As monotherapy in patients who have shown disease progression during or within 6 months following treatment with rituximab.
• 🔹 Multiple Myeloma: As part of first-line combination therapy in combination with prednisone for patients over 65 years of age who are not eligible for autologous stem cell transplantation.

The dosage regimen, infusion duration, and number of cycles are determined exclusively by the treating physician based on the diagnosis and the patient's body surface area:

• Administration Route: The drug is administered exclusively intravenously via intravenous drip infusion. Direct intravenous bolus or intramuscular administration is strictly prohibited.
• Standard Dosages: In CLL, the dose is usually 100 mg/m² of body surface area on Days 1 and 2 of each 28-day cycle. In non-Hodgkin's lymphomas, the dose is 120 mg/m² on Days 1 and 2 of each 21-day cycle.
• Preparation Rules: The contents of the vial are dissolved in water for injection, and the resulting concentrate is then immediately diluted in 500 ml of 0.9% sodium chloride injection. Preparation must be conducted under aseptic conditions.
• Infusion Regimen: The solution must be administered immediately after preparation. The infusion is carried out over 30–60 minutes under continuous supervision of medical personnel.

The use of the drug is strictly contraindicated in the presence of the following concurrent clinical pathologies:

• ⛔ Severe Myelosuppression: Severe bone marrow depression (neutrophil count less than 1,500/µl and/or platelet count less than 75,000/µl).
• ⛔ Hepatic and Renal Impairment: Severe liver function impairment (bilirubin level over 300 µmol/l) or kidney function impairment (creatinine clearance less than 10 ml/min).
• ⛔ Infectious Processes: Acute, severe infections, including tuberculosis, hepatitis, and uncontrolled bacterial or viral diseases.
• ⛔ Pregnancy and Lactation: Pregnancy and breastfeeding periods are absolute contraindications.
• ⛔ Age and Sensitivity: Pediatric age under 18 years, as well as individual hypersensitivity to bendamustine or mannitol.

During combination therapy, the specific pathways of bendamustine metabolism in the liver must be taken into account:

• ❌ CYP1A2 Isoenzyme Inhibitors: Medicinal products that inhibit this enzyme (e.g., fluvoxamine, ciprofloxacin) can increase bendamustine plasma concentrations, enhancing its toxicity.
• ❌ CYP1A2 Isoenzyme Inducers: Drugs that induce this enzyme (e.g., omeprazole, rifampicin), as well as smoking, can reduce the efficacy of the anti-tumor therapy.
• ⚠️ Live Vaccines: Vaccination with live virus vaccines is strictly prohibited during treatment due to the risk of vaccine infection generalization under immunosuppression.

Bendamustine has proven genotoxic, teratogenic, and embryotoxic effects, requiring strict adherence to contraceptive rules:

• For Women: Female patients of childbearing potential must use highly effective contraceptive methods during therapy and for at least 6 months after receiving the last dose.
• For Men: Men are strongly advised to use reliable barrier methods of contraception during treatment and for 6 months after its completion when having sexual contacts with women of childbearing potential.
• Reproductive Planning: Due to the risk of developing irreversible infertility associated with chemotherapy, men are recommended to consider sperm preservation before starting treatment.

The anti-tumor action of bendamustine is frequently accompanied by side effects that require regular laboratory monitoring:

• 🟢 Hematological Toxicity (Very Common): Leukopenia, neutropenia, thrombocytopenia, and anemia. A weekly complete blood count is required.
• 🟡 Gastrointestinal: Nausea, vomiting (successfully managed with modern antiemetics), diarrhea, constipation, stomatitis.
• 🟡 General Disorders: Increased body temperature (pyrexia), chills, fatigue, weakness, headache.
• 🟠 Serious Complications: Tumor lysis syndrome, severe infections (including sepsis), allergic skin reactions (Stevens-Johnson syndrome).
• ⚠️ Urgent Doctor Consultation: If signs of infection (fever, sore throat), unusual bleeding, severe rash, or shortness of breath occur, the patient must be hospitalized immediately.

Specific cases of acute overdose in clinical practice are rare, as the drug is administered strictly under medical supervision:

• Main Manifestations: Severe dose-dependent bone marrow depression (critical drop in leukocyte and platelet levels), increased cardiotoxicity, and gastrointestinal disorders.
• First Aid: Immediate discontinuation of the infusion if acute severe reactions occur.
• Treatment: No specific antidote exists. Symptomatic therapy, hemotransfusions (platelet or red blood cell mass transfusions), administration of growth factors (G-CSF), and antibacterial support are provided.

Compliance with storage rules guarantees the preservation of the lyophilized powder stability until its reconstruction:

• 🌡️ Temperature Regimen: Store in a place protected from light at a stable temperature not exceeding 25°C. Do not freeze.
• 📦 Packaging: Keep the vial in the original cardboard box to protect it from direct sunlight and mechanical damage.
• 👶 Safety: The medicinal product must be stored in a secure, hidden place completely inaccessible to children and unauthorized persons.
• ⏳ Package Contents: The original package contains 1 glass vial with a dosage of 100 mg of bendamustine, designed exclusively for single use.