Bortenat 3.5 — Bortezomib 3.5 mg (1 Vial)

Bortenat is manufactured in the form of a lyophilizate for preparation of a solution for injection, containing a strictly calibrated dose of components:

• Active Compound: Bortezomib — 3.5 mg in each vial.
• Excipients: Mannitol (acts as a stabilizing agent and bulking agent to form a porous lyophilized cake).
• Appearance: A sterile lyophilized powder or mass of white color, contained in a clear glass vial tightly sealed with a rubber stopper and a protective aluminum flip-off cap, packed in a cardboard box.

Pharmacodynamics: Bortezomib is a modified boric acid. The molecule reversibly inhibits the chymotrypsin-like activity of the 26S proteasome in mammalian cells, causing inhibition of proteolysis, accumulation of regulatory proteins, and subsequent activation of the caspase cascade, leading to the death of myeloma cells.

Pharmacokinetics: Following intravenous or subcutaneous administration, the drug rapidly distributes into body tissues. Peak concentrations after subcutaneous administration are reached in approximately 30 minutes. It is metabolized primarily in the liver by cytochrome P450 isoenzymes (CYP3A4, CYP2C19, CYP1A2). The elimination half-life with multiple dosing ranges from 40 to 193 hours.

Bortenat 3.5 mg is used strictly as prescribed by a specialized professional (oncohematologist or oncologist) for the therapy of the following conditions:

• 🔹 Multiple Myeloma: Treatment of patients who have not previously received therapy (as part of a combination regimen) or patients with relapsed/refractory disease course after at least one prior line of treatment.
• 🔹 Mantle Cell Lymphoma (MCL): Therapy of patients with previously untreated disease (in combination with standard chemotherapy regimens), as well as upon disease progression during preceding therapy.

Dose calculation and administration of the medication are carried out by medical personnel in a hospital setting. Alteration of treatment regimens without an oncologist is strictly prohibited:

• Recommended Dosage: The standard single dose is calculated individually and is 1.3 milligrams per square meter (1.3 mg/m2) of the patient's body surface area.
• Method of Administration: The solution is administered either as an intravenous bolus (over 3–5 seconds) or subcutaneously (into the thigh or abdomen). Intrathecal administration of the drug is completely excluded.
• Administration Schedule: In a standard 21-day cycle, the drug is administered twice weekly for two weeks (days 1, 4, 8, and 11), followed by a mandatory 10-day rest period (days 12–21). At least 72 hours must elapse between consecutive doses.
• Reconstitution of Solution: The powder is dissolved in sterile 0.9% sodium chloride solution: for intravenous use, add 3.5 ml of solvent (concentration 1 mg/ml); for subcutaneous use, add 1.4 ml of solvent (concentration 2.5 mg/ml).

The use of Bortenat lyophilizate is strictly prohibited in the presence of the following contraindications or physiological conditions:

• ⛔ Hypersensitivity: Individual intolerance to bortezomib, mannitol, or boron.
• ⛔ Intrathecal Route: Administration of the medication into the spinal canal is strictly prohibited (leads to severe neurological complications with a fatal outcome).
• ⛔ Acute Lung Disease: Diffuse infiltrative lung diseases and severe bilateral pericardial disease.
• ⛔ Pregnancy and Lactation: The drug possesses high teratogenic toxicity and is categorically contraindicated in pregnant and breastfeeding women.
• ⛔ Age Restrictions: Children and adolescents under 18 years of age (due to the lack of established safety data).

Bortezomib undergoes intensive metabolism in the liver, requiring careful monitoring when concomitantly administering other medications:

• ❌ Potent CYP3A4 Inhibitors: Drugs such as ketoconazole, ritonavir, or clarithromycin slow down the degradation of bortezomib, increasing its plasma blood concentration and toxicity risks.
• ❌ Potent CYP3A4 Inducers: Medicinal agents that induce this enzyme (rifampicin, carbamazepine, phenobarbital, St. John's wort) significantly lower the therapeutic efficacy of bortezomib.
• ⚠️ Hypoglycemic Agents: In patients with diabetes mellitus receiving oral antidiabetic drugs, either hypo- or hyperglycemia may be observed during therapy, necessitating frequent monitoring of blood glucose levels.

The drug possesses pronounced genotoxic and teratogenic actions, potentially hazardous to the reproductive system:

• Risks to the Fetus: The use of bortezomib by a pregnant woman causes irreversible intrauterine developmental defects or intrauterine fetal death.
• Contraception for Women: Female patients of childbearing potential must use highly effective methods of barrier and hormonal contraception during treatment and for 7 months after the final injection.
• Contraception for Men: Men undergoing treatment must use reliable contraceptive measures during sexual contact with women of childbearing potential throughout the entire therapy and for 4 months after its completion.

Therapy with Bortenat is associated with a risk of developing systemic adverse reactions requiring timely management by the treating medical staff:

• 🟢 Hematological Toxicity (Very Common): Reversible thrombocytopenia (decreased platelet count), anemia, neutropenia, which increase the risks of bleeding and infections.
• 🟡 Neurological Disorders: Peripheral neuropathy (defined as numbness, tingling, burning in the hands and feet), headache, paresthesia.
• 🟡 Gastrointestinal Tract: Decreased appetite, nausea, vomiting, diarrhea or constipation, abdominal pain.
• 🟠 General Symptoms: Increased body temperature (pyrexia), marked general weakness, fatigue, dehydration, muscle pain (myalgia).
• ⚠️ Urgent Medical Attention: Upon occurrence of progressive dyspnea, dry cough, pronounced limb numbness, or severe swelling of the face and legs, an immediate medical evaluation must be performed.

Exceeding the calculated dosages of bortezomib poses a direct threat to life and is characterized by acute systemic toxicity:

• Main Manifestations: Acute overdose (exceeding the dose by 2 times or more) leads to a sudden critical drop in blood pressure (severe hypotension) and the development of profound thrombocytopenia with a risk of internal bleeding.
• First Aid: Immediate discontinuation of solution administration, continuous monitoring of the body's vital functions.
• Treatment: No specific antidote exists. Intensive supportive therapy is provided: intravenous administration of fluids to stabilize blood pressure, prescription of vasopressors, blood parameter monitoring, and blood transfusions if needed.

Adherence to the regulated storage conditions of the lyophilized powder guarantees the preservation of its chemical stability:

• 🌡️ Temperature Regimen: Store in the original package in a dry, light-protected place at a temperature strictly not exceeding 30°C. Freezing of vials is prohibited.
• 📦 Environmental Protection: The vial must be kept inside the factory cardboard pack to prevent destructive effects of ultraviolet radiation.
• 👶 Accessibility: The medicinal product must be stored in a secure, locked cabinet, completely excluding access by children or pets.
• ⏳ Use of Reconstituted Solution: The factory vial contains 3.5 mg of lyophilizate for single use. The prepared solution is chemically stable for 8 hours at a temperature up to 25°C, but it is recommended to be administered immediately after reconstitution.