Bortezomib for injection

Bortezomib is a reversible inhibitor of the chymotrypsin-like activity of the 26S proteasome in mammalian cells. The 26S proteasome is a large protein complex that degrades ubiquitinated proteins. The ubiquitin proteasome pathway plays an important role in regulating the concentration of specific proteins in cells to maintain the stability of the intracellular environment. Proteolysis affects the multi-level signaling cascade within the cell, and this disruption of the normal intracellular environment can lead to cell death. Inhibition of the 26S proteasome prevents the hydrolysis of specific proteins. In vitro studies have shown that bortezomib is cytotoxic to multiple types of cancer cells. In vivo studies in preclinical tumor models have shown that bortezomib can delay the growth of tumors, including multiple myeloma.

Active ingredient: Bortezomib, excipients: mannitol, nitrogen

1. This product is used to treat patients with multiple myeloma who have received at least two treatments before using this product and whose disease is still progressing during the most recent treatment. 2. The effectiveness of this product is based on its effective rate. There is no clinical controlled trial to prove its clinical benefits, such as improvement in survival rate.

Recommended dose for adults: The recommended dose of this product is a single injection of 1.3 mg/m2, twice a week, for 2 consecutive weeks (i.e., injections on days 1, 4, 8, and 11), followed by a 10-day break (i.e., from day 12 to day 21). 3 weeks is a course of treatment, with at least 72 hours between two doses. In clinical studies, patients with confirmed complete remission received another 2 cycles of Velcade. Patients who have remitted are recommended to receive 8 cycles of Velcade. Dose adjustment and restart of treatment: When grade 3 non-hematological or any grade 4 hematological toxicity (excluding neuropathy discussed below) occurs, treatment with this product should be suspended. Once the toxic symptoms are relieved, treatment with this product can be restarted with a 25% dose reduction (e.g., 1.3 mg/m2 reduced to 1.0 mg/m2; 1.0 mg/m2 reduced to 0.7 mg/m2). If patients experience neuralgia or peripheral sensory neuropathy associated with treatment with this product, they should be treated with the dose adjustment recommended in the following table. If the patient suffers from severe neuropathy, this product can only be used after weighing the pros and cons. Administration: This product must be completely dissolved in 3.5 ml of normal saline and injected intravenously through the catheter within 3-5 seconds, followed by flushing with 0.9% sodium chloride solution for injection.

Summary of clinical trials for the treatment of patients with relapsed/refractory multiple myeloma: The efficacy and safety of this product at the recommended dose of 1.3 mg/m2 were evaluated in three clinical studies, including a randomized dexamethasone-controlled Phase 3 trial (M34101-039) to treat 669 patients with relapsed or refractory multiple myeloma after 1-3 lines of treatment; a single-arm, open-label, multicenter Phase 2 trial to treat 202 patients who had received 2 lines of treatment and had recently worsened their disease (M34100-025); a Phase 2 clinical trial evaluating the dose-response of this product to treat patients with relapsed multiple myeloma whose disease had worsened or relapsed or who had received 1 line of treatment with this product at 1.0 mg/m2 or 1.3 mg/m2 (M34100-024). Summary of clinical trials for the treatment of untreated multiple myeloma patients: 1. Recurrence of herpes zoster Among the untreated multiple myeloma patients participating in the Phase 3 study, 27% of the patients in the MP group received antiviral prophylaxis. In this study, recurrence of herpes zoster was more common in the MP group compared with the MP alone group (3% and 11%, respectively). Among the 91 patients (3%) who received antiviral prophylaxis in the MP group, 3 patients experienced a recurrence of herpes zoster. 2. Mantle cell lymphoma patients The safety of 155 mantle cell lymphoma patients receiving the recommended dose of 1.3 mg/m2 of this product was evaluated in a Phase 2 clinical study. The overall safety of this product in patients with mantle cell lymphoma was similar to that observed in patients with multiple myeloma. The obvious difference between the two patient groups is that although patients with mantle cell lymphoma reported more peripheral neuropathy, rash, and pruritus than patients with multiple myeloma, patients with multiple myeloma reported more thrombocytopenia, neutropenia, anemia, nausea, vomiting, and fever than patients with mantle cell lymphoma.

It is contraindicated in patients with hypersensitivity to bortezomib, boron, or mannitol.

Precautions for children: Not yet clear. Precautions for pregnancy and lactation: Pregnant women: Women of childbearing age should avoid pregnancy during treatment with this product. Preclinical toxicology studies have shown that the highest test dose of bortezomib, 0.075 mg/kg (0.5 mg/m2) injected into rats and 0.05 mg/kg (0.6 mg/m2) into rabbits during the period of organ development, did not cause malformations. The above dose is approximately half of the clinical dose of 1.3 mg/m2 (calculated based on body surface area). Injection of 0.05 mg/kg (0.6 mg/m2) into pregnant rabbits during the period of organ development showed obvious abortion and decreased fetal survival rate. The weight of surviving fetuses was significantly reduced. The above dose is approximately half of the clinical dose of 1.3 mg/m2 (calculated based on body surface area). Studies have not yet been conducted on whether bortezomib crosses the placental barrier. Adequate formal studies have not been conducted on pregnant women. If this product is used during pregnancy or pregnancy occurs during treatment, pregnant women should be informed of the possible harm of this product to the fetus. During treatment with this product, patients are advised to use effective contraceptive measures and avoid breastfeeding. Lactating women: It is not known whether bortezomib is secreted through human milk. In view of the fact that many drugs are secreted through human milk and that feeding infants with breast milk containing this product may cause potentially serious adverse reactions, lactating women should be advised not to breastfeed during treatment with this product. Elderly precautions: Among the 202 patients participating in the clinical trial, 35% of the patients were 265 years old. The remission rates for patients over 65 years old and under 65 years old were 19% and 32%, respectively. Safety analysis of 256 patients showed that the incidence of grade 3 and 4 adverse events was 74%, 80%, and 85%, respectively, for patients under 50 years old, patients aged 51-65 years old, and patients over 65 years old.

In vitro and animal studies have shown that bortezomib is a weak inhibitor of cytochrome P450 (CYP) enzymes 1A2, 2C9, 2C19, 2D6, and 3A4. Since CYP2D6 has a limited effect on bortezomib metabolism (7%), it is expected that the slow metabolizer CYP2D6 will not affect the overall distribution of bortezomib. In a drug interaction study, the effect of ketoconazole (a strong inhibitor of CYP3A4) on bortezomib was evaluated, and the data from 12 patients showed that the mean AUC of bortezomib increased by 35%. Therefore, patients should be closely monitored when bortezomib is co-administered with CYP3A4 inhibitors (e.g., ketoconazole, ritonavir). In a drug interaction study, the effect of omeprazole (a strong inhibitor of CYP2C19) on bortezomib was evaluated, and the data from 17 patients showed that it had no significant effect on the pharmacokinetics of bortezomib. In a drug interaction study, the effect of phenylalanine nitrogen mustard and prednisone combination therapy on bortezomib was evaluated. The data results of 21 patients showed that the mean AUC of bortezomib increased by 17%. This result is considered to be of no clinical relevance. In clinical trials, hypoglycemia and hyperglycemia have been reported in diabetic patients after oral hypoglycemic drugs. When using this product for treatment, blood glucose levels of patients taking oral antidiabetic drugs should be closely monitored, and attention should be paid to adjusting the dose of antidiabetic drugs. Inform patients that they should be cautious in combining drugs that may cause peripheral neuropathy (such as amiodarone, antiviral drugs, isoniazid, nitrofurantoin or statins) and drugs that cause lowering of blood pressure.

Store at 25℃ (15~30℃) away from light.

3.5 mg

36 months.