Medicine > All about Bortecine (bortezomib) injection

All about Bortecine (bortezomib) injection

Name of Medicine:- Bortecine 

Chemical Formula:- C19H25BN4O4 

Active Ingredient:- Bortezomib

Pharmacologic category:- Antineoplastic Agent and Proteasome Inhibitor

Description:- Bortecine is used to treat multiple myeloma (blood plasma cell cancer) and it is also indicated for the treatment of mantle cell lymphoma. 

What is Bortecine? 

Bortecine comprises Bortezomib as an active ingredient and it is an anti-cancer agent which is used to treat Multiple myeloma (a cancer of the bone marrow) and mantle cell lymphoma. This medication helps to block the action of cancer cells and prevent them from multiplying and it is available in the strength of 2mg in the form of injection. 

Clinical relevance 

Bortezomib is a valuable treatment option in managing the underlying effects of multiple myeloma and mantle cell lymphoma.

  • Multiple myeloma:- makes the bone weaker and painful. It destroys the bone rapidly. Bortecine injection plays an important part in the treatment. It helps to improve the survival rate of people suffering from multiple myeloma. 

  • Mantle cell lymphoma:- is a cancer of white blood cells in the body. Bortecine (Bortezomib) prevents the growth and spread of cancer cells and helps to fight against the infection. 

Clinical Pharmacology

Mechanism of Action 

Bortezomib may be a reversible inhibitor of the chymotrypsin-like activity of the 26S proteasome in human cells. The 26S proteasome may be a large protein complex that degrades ubiquitinated proteins. The ubiquitin-proteasome pathway plays an important role in regulating the intracellular concentration of specific proteins, thereby maintaining homeostasis within cells. Inhibition of the 26S proteasome prevents this targeted proteolysis, which may affect multiple signaling cascades within the cell. This disruption of normal homeostatic mechanisms can cause necrobiosis. Experiments have demonstrated that bortezomib is cytotoxic to a spread of neoplastic cell types in vitro. Bortezomib causes a delay in tumor growth in vivo in nonclinical tumor models, including myeloma.

Absorption 

Following intravenous administration of 1 mg/m2 and 1.3 mg/m2 doses, the mean Cmax of bortezomib were 57 and 112 ng/mL, respectively. During a twice-weekly dosing treatment, the Cmax ranged from 67 to 106 ng/mL at the dose of 1 mg/m2 and 89 to 120 ng/mL for the 1.3 mg/m2 dose. In patients with myeloma, the Cmax of bortezomib following subcutaneous administration was less than that of intravenously administered dose; however, the entire systemic exposure of the drug was equivalent for both routes of administration. there's wide interpatient variability in drug plasma concentrations.

Volume of Distribution 

The mean conveyance volume of bortezomib went from around 498 to 1884 L/m2 following single-or rehash portion organization of 1 mg/m2 or 1.3mg/m2 to patients with numerous myeloma. This proposes bortezomib disseminates broadly to fringe tissues. The limiting of bortezomib to human plasma proteins found the middle value of 83% over the fixation scope of 100 to 1000 ng/mL.

Metabolism

In vitro concentrates with human liver microsomes and human cDNA-communicated cytochrome P450 isozymes demonstrate that bortezomib is principally oxidatively used through cytochrome P450 catalysts 3A4, 2C19, and 1A2. Bortezomib digestion by CYP 2D6 and 2C9 chemicals is minor. The major metabolic pathway is deboronation to frame 2 deboronated metabolites that hence go through hydroxylation to a few metabolites. Deboronated bortezomib metabolites are inert as 26S proteasome inhibitors. Pooled plasma information from 8 patients at 10 min and 30 min in the wake of dosing demonstrate that the plasma levels of metabolites are low contrasted with the parent drug.

Clinical Trials 

Bortezomib (Bortecine) may be a proteasome inhibitor that not only targets the myeloma cell but also acts within the bone marrow microenvironment, inhibiting the binding of myeloma cells to bone marrow stromal cells, also demonstrating anabolic effects on bone. Intravenous bortezomib, with or without dexamethasone, is effective and well-tolerated in patients with relapsed/refractory myeloma, as demonstrated within the phase II clinical trial CREST and SUMMIT trials, and therefore the phase III clinical trial APEX trial, and maybe a recommended treatment for this patient group. supported the outcomes of another phase III clinical trial, the mixture of bortezomib plus pegylated liposomal doxorubicin is additionally a recommended regimen for patients with relapsed/refractory myeloma. Other bortezomib-combination treatments have shown promising response data in phase II clinical trials in patients suffering from relapsed/refractory disease, although response and survival data for these combinations got to be confirmed in larger phase III clinical trial trials. Bortezomib was proved to be effective and tolerated when administered as a part of the first-line regimen in previously untreated patients with myeloma. Within the phase, III VISTA trial in elderly patients with previously untreated myeloma not eligible for transplantation, bortezomib together with melphalan and prednisone was effective and well-tolerated and may be a recommended treatment regimen for this group of patients. Preliminary responses from phase II/III trials in patients with previously untreated myeloma show a promising role for the utilization of Bortecine combined with various other chemotherapeutic drugs as induction therapy before transplantation.

Drug Category 

  • Antineoplastic Agents:- is an effective treatment of malignant, or cancerous, disease. These drugs come in various forms like liquid that are easily injected and oral pills such as capsules and tablets. 

  • Immunosuppressive Agents:- these are called anti-rejection drugs and it is used to control transplant rejections. It belongs to a class of drugs that suppresses or reduces the activity of the immune system.

  • Myelosuppressive Agents:- these drugs kill and stop the growth of cancerous cells in the body and tend to decrease the number of red blood cells and white blood cells. 

Interactions 

Drug-Drug interactions 

Do not receive live vaccines during treatment with Bortecine (Bortezomib) medicine. Your doctor may also want to delay the vaccine, in order to recover from the effects of bortezomib therapy. It is always necessary to discuss the risks and benefits of medication and never forget to share your previous medical history with your healthcare professional or medical practitioner. 

  • Adalimumab:- this medication may increase the risk of serious bacterial infections while using in combination with bortezomib and it may interact vigorously. It can also cause some side effects like fever, chills, diarrhea, sore throat, muscle aches, shortness of breath, and weight loss. Do not use any other tablets without consulting with your healthcare professional. 

  • Carbamazepine:- it may reduce your blood levels and it will affect your treatment with bortezomib. Your doctor may monitor you closely and decide the adjustments of dosage as per your health concern and recommend medicines that don't interact with each other. 

  • Lomitapide:- This medication causes liver problems and using Lomitapide with bortezomib also increases the risk of liver impairment. Avoid the use of alcohol during treatment with this medication. Side effects like unusual bleeding or bruising, skin rash, itching, and loss of appetite may occur. Discontinuation of these medications may cause certain adverse reactions therefore do not stop using this medication as per your own will. 

Drug-Disease interactions 

  • Cardiac toxicity:- congestive heart failure can occur in some patients during treatment with bortezomib. Due to this risk factor, your healthcare professional may monitor you closely. If you have existing heart disease do not forget to share it with your medical practitioner.

  • Peripheral neuropathy:- Bortecine (Bortezomib) medicine can cause peripheral neuropathy and if you experience signs and symptoms like:- pain in your hand or feet and numbness your physician may adjust your dosing schedule to lower the effects.  

  • Hepatotoxicity:- Patients during treatment with Bortezomib can experience liver failure and hepatic reactions like - hepatitis and increased liver enzymes. Close monitoring of liver function is required.  

  • Diabetes:- While using Bortezomib monitoring of blood glucose levels is required and alteration of dose of their antidiabetic medication is required in diabetic patients.

  • Hypotension:- Extreme caution is required when treating patients with a history of hypotension, syncope, dehydration, or taking antihypertensive medication.

  • Pulmonary toxicity:- patients receiving Bortecine (Bortezomib) medicine can experience ARDS (Acute Respiratory Distress Syndrome) and acute diffuse infiltrative pulmonary disease of unknown etiology such as pneumonitis, interstitial pneumonia, and lung infiltration. 

Dosage and Administration 

Recommended Dosage:- The recommended dosage of Bortecine injection is 1.3 mg/m2. This medication is administered twice a week for two weeks following a 10-day rest period. However, dose adjustments may be needed if the patient’s medical history or current medical condition includes any severe disorder. 

Dose Adjustments:- Patients suffering from mild Hepatic Impairment do not primarily require dose adjustments during the start of the course of this medicine. However, patients suffering from moderate and severe Hepatic Impairment should start the administration of Bortecine at a reduced dose. A subsequent escalation further may be suggested by the physician as per your body’s response to the medicine. 

Overdosage:- In case of an overdose of Bortecine injection, the patients may experience multiple symptoms that might cause fetal harm. Hence, it is important to contact a qualified physician in order to receive supportive care and regular monitoring as per the current medical condition.

Adverse Reactions 

Certain side effects may occur during the course of Bortecine. Some patients experience mild, moderate, or severe adverse reactions; however, others do not even face any. This depends upon the patient’s medical history and the body’s reaction to the medicines you consume.

Gastrointestinal diseases may occur in some patients such as diarrhea, constipation, dyspepsia (indigestion), tiredness, unusual weakness, nausea, incontinence (involuntary leakage of urine), vomiting, and severe tiredness. 

This medication may lead to a severe decrease in blood cells that may cause anemia, easy bruising/bleeding, low white blood cell count (decreased ability to fight infections), sore throat, and other infection-like symptoms. 

Severe allergic effects or injection-site reactions such as skin rash, swelling, itching, pain, shortness of breath, and severe dizziness may occur in some patients administering Bortezomib. 

Other common side effects of Bortecine injection are severe headache, symptoms of heart failure (including difficulty in breathing, sudden weight gain, vision changes, seizures,  severe stomach pain), pale skin, fever, chills, and swelling of ankles and feet. 

Some side effects (neurological and psychological) may be experienced by patients receiving Bortecine therapy such as depression, changes in mood, increased thirst/urination, tremors (shaking), rapid or irregular heartbeat, unexpected tiredness, and lack of interest. 

Warnings and Precautions 

Reactions that may occur 

  • Neurological disorder:- Bortecine (Bortezomib) medicine can cause peripheral neuropathy and if you experience signs and symptoms like- pain in your hand or feet and numbness your physician may adjust your dosing schedule to lower the effects.  

  • Hepatic dysfunction:- Patients during treatment with Bortezomib can experience liver failure and hepatic reactions like - hepatitis and increased liver enzymes. Close monitoring of liver function is required.  

  • Respiratory tract infection:- patients receiving Bortecine (Bortezomib) medicine can experience ARDS (Acute Respiratory Distress Syndrome) and acute diffuse infiltrative pulmonary disease of unknown etiology such as pneumonitis, interstitial pneumonia, and lung infiltration. 

  • Hypotension:- Extreme caution is required when treating patients with a history of hypotension, syncope, dehydration, or taking antihypertensive medication.

  • Cardiovascular disorder:- congestive heart failure can occur in some patients during treatment with bortezomib. Due to this risk factor, your healthcare professional may monitor you closely.

Special Population

  • Pregnant Women
    Bortecine (Bortezomib) injection may cause fetal harm when administered to a pregnant woman. This medicine is not indicated to patients who are pregnant and planning to become pregnant. Women possessing child-bearing potential are advised to start using proper contraceptive measures 28 days before the course of Bortecine.

  • Nursing Mothers
    It is unknown whether Bortecine (Bortezomib) is excreted in human milk or not. Since most other drugs are excreted in human milk, it is necessary to take precautions to avoid adverse reactions. Hence, breastfeeding should be discontinued while receiving treatment with Bortecine.

  • Pediatric Use
    The safety and efficacy of Bortecine have not been established in patients below the age of 18. 

  • Geriatric Use
    In patients, aged 65 and above, Bortecine (Bortezomib) has been used in several clinical trials. No notable differences in the efficacy and safety of this medicine have been observed. 

Packaging and Storage

Bortecine is available as an injection packed in a single-use vial. Store this medication at 20°C - 25°C; excursions permitted to 15°C - 30°C. Keep Bortecine Injection away from the reach of children and pets. Protect them from direct heat, light, and moisture. Proper care should be exercised while handling this drug. Women who are pregnant should not handle Bortecine Injection without protection (gloves). Know the procedure to dispose of the used and expired bottles of medicines from a pharmacist.