Medicine > All about Abra-bound (Albumin-bound paclitaxel) injection

All about Abra-bound (Albumin-bound paclitaxel) injection

Name of Medicine:- Abra-bound

Chemical Formula:- Albumin-bound paclitaxel

Active Ingredient:- C47H51NO14

Description:- Abra-bound is indicated for the treatment of certain types of cancers (Breast Cancer, Lung Cancer, and Pancreatic Cancer).

What is Abra-bound

Abra-bound comprises Albumin-bound paclitaxel as an active ingredient and this anti-cancer medication is used to treat multiple types of cancers (Breast Cancer, Lung Cancer, and Pancreatic Cancer). This injection helps in preventing the growth of cancer cells and eventually kills them and it is available in the strength of 100mg. 

Clinical relevance 

Abra-bound is a valuable treatment option in managing the underlying effects of certain types of cancers (Breast Cancer, Lung Cancer, and Pancreatic Cancer). 

  • Breast cancer:- this injection helps in relieving the signs of breast cancer such as breast lumps, bloody discharge, and changes in the shape or texture of the breast. The abra-bound medication stops the multiplication of cancer cells. 

  • Lung cancer:- Abra-bound injection helps to treat non-small cell lung cancer and it may be given alone or in combination for the treatment. Avoid drinking alcohol during the treatment with Abra-bound (albumin-bound paclitaxel). 

  • Pancreatic cancer:- This medication helps in controlling pancreatic cancer and it works by blocking the action of a chemical that helps in the growth of cancer cells.

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. 

Clinical Pharmacology 

Pharmacodynamics 

Albumin-bound paclitaxel is a taxoid antineoplastic agent used to treat advanced ovarian carcinoma, as well as other cancers such as breast cancer, as a first-line and subsequent therapy. Paclitaxel is a novel antimicrotubule agent that promotes the formation of microtubules from tubulin dimers and prevents depolymerization of microtubules. The normal dynamic reorganization of the microtubule network, which is needed for vital interphase and mitotic cellular functions, is inhibited as a result of this stability. Albumin-bound paclitaxel also causes irregular microtubule clusters or "bundles'' during the cell cycle, as well as several asters of microtubules throughout mitosis.

Mechanism of action 

Albumin-bound paclitaxel intervenes with the normal function of microtubule growth. Whereas medicines including colchicine tend to cause the microtubules depolymerization in the study, paclitaxel restricts their function by having the opposite effect; it hyper-stabilizes their structure. This destroys the cell's ability to use its cytoskeleton flexibly. Paclitaxel is specifically bound to the subunit of tubulin. Tubulin is also known as a "building block" of microtubules, and paclitaxel binds to these building blocks, locking them in place. The microtubule/paclitaxel complex that results is incapable of disassembly. Since the shortening and lengthening of microtubules (known as dynamic instability) are required for their role as a cell's transportation highway, this harms cell function. Research has indicated that paclitaxel induces programmed cell death (apoptosis) in cancer cells by binding to an apoptosis-stopping protein called Bcl-2 (B-cell leukemia 2) and stop it from functioning.

Metabolism 

Studies with tissue slices and human liver microsomes showed that Albumin-bound paclitaxel was metabolized initially to 6αhydroxypaclitaxel by CYP2C8; and to two minor metabolites, 3’-p-hydroxypaclitaxel and 6α, 3’-p-dihydroxypaclitaxel, by CYP3A4.

In the clinical study, the metabolism of albumin-bound paclitaxel to 6α-hydroxypaclitaxel was inhibited by various agents (ketoconazole, verapamil, diazepam, quinidine, dexamethasone, cyclosporin, teniposide, etoposide, and vincristine) but the concentrations used exceeded those found in vivo following normal therapeutic doses. 

In the experiment, testosterone, 17-Ethinyl estradiol, retinoic acid, and quercetin, a CYP2C8 unique inhibitor, all inhibited the formation of 6-hydroxypaclitaxel. Interactions with compounds that are substrates, inducers, or inhibitors of CYP2C8 and/or CYP3A4 can also alter the pharmacokinetics of paclitaxel in vivo.

Absorption 

Clinical trials were conducted to assess the pharmacokinetics of complete paclitaxel after 30 and 180-minute infusions of Abra-bound at dose levels ranging from 80 to 375 mg/m2. mg/m2 dose levels apply to mg of paclitaxel in Abra-bound form. Intravenous administration of Abra-bound, albumin-bound paclitaxel resulted in a biphasic decrease in plasma concentrations, with the first step representing drug delivery and the second phase representing drug removal. The terminal half-life was estimated to be about 27 hours.

Over a dosage range of 80 to 375 mg/m2, the drug exposure (AUCs) was proportional, and the pharmacokinetics of Albumin-bound paclitaxel were unaffected by the period of administration. The mean maximum dose for metastatic breast cancer was 260 mg/m2.

After the infusion, the concentration of paclitaxel was 18,741 ng/mL. The average total clearance rate per square meter was 15 L/hr/m2. The average volume of delivery was 632L/m2, suggesting that paclitaxel had widespread extravascular distribution and/or tissue binding.

The pharmacokinetics of 260 mg/m2 Abra-bound injection given over a 30-minute infusion were compared to 175 mg/m2 albumin-bound paclitaxel injection given over a 3-hour infusion. For Abra-bound paclitaxel injection, the clearance was higher (43%) and the rate of delivery was also higher (53%) than for albumin-bound paclitaxel injection. Differences in overall dose and rate of infusion were expressed in differences in maximum concentration (Cmax) and dose-corrected Cmax. The terminal half-lives did not vary in any way.

Interactions 

When albumin-bound paclitaxel is combined with other medications it causes various and different interactions with other medications. During the drug interaction study, when  Abra-bound is inhibited with other medications, some activities are observed in the absorption of  Albumin-bound paclitaxel and the reported reactions are - 

  • Severe risk myopathy, rhabdomyolysis, and myoglobinuria can be increased

  • Metabolism can be decreased or increased depending on the ingredient of the medication. 

  • Increases the neurotoxic activities

  • Risk of severe bleeding 

CYP2C8 and CYP3A4 are responsible for albumin-bound paclitaxel metabolism. In the absence of systematic clinical drug interaction trials, when using Abra-bound (albumin-bound paclitaxel) with known CYP2C8 and CYP3A4 substrates or inhibitors, caution should be exercised.

Hematology:- Patients with neutrophil counts of less than 1,500 cells/mm3 should not receive Abra-bound therapy. It is recommended that frequent blood cell counts tests should be performed on all patients receiving Abra-bound (Albumin-bound paclitaxel) to closely monitor the occurrence of myelotoxicity. 

Nervous system:- during a course of Abra-bound therapy, sensory neuropathy can occur. The occurrence of grade 1 or 2 sensory neuropathy does not require dose modification or alteration. If grade 3 sensory neuropathy develops, treatment should be withheld until resolution to grade 1 or 2 followed by a dose reduction for all subsequent courses of Abra-bound

Drug-Drug interactions

Atazanavir:- using this medication with Abra-bound can increase the risk of some side effects like- itching, diarrhea, mouth sores, nerve pain, numbness, tingling, vision abnormalities, muscle pain, or weakness. Your healthcare professional may closely monitor your blood cell counts to avoid side effects like anemia or bleeding problems. 

Cladribine:- it may increase the chance of developing serious infections. 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. 

Natalizumab:- using abra-bound and natalizumab may cause some life-threatening infections. To minimize the risk of such side effects your medical practitioner may perform some special tests and monitor them closely, if he/she finds anything unusual several dose adjustments may be required.   

Ipilimumab:- using this medication in combination with abra-bound may increase the risk of nerve damage. Your healthcare provider may prescribe you some alternatives which won't interact with each other or dosage alteration may require to avoid certain side effects. 

Drug-Disease Interactions 

Conduction disorders:- Close monitoring of cardiac function is required during the time of therapy with Abra-bound (Albumin-bound paclitaxel). Extreme caution is required in patients suffering from conduction abnormalities. 

Hepatic dysfunction:- Patients during treatment with Abra-bound may experience some problems. Your doctor will adjust your dosage especially for patients who are suffering from compromised hepatic function.

Dosage and administration 

Recommended dose - In breast cancer, the recommended dose for Abra-bound is 260mg/m2 administered intravenously over 30 minutes every 3 weeks. 

In non-small cell lung cancer, the recommended dose of Aba-bound is 100 mg/m2 administered as an intravenous infusion over 30 minutes on Days 1, 8, and 15 of each 21-day cycle. 

In pancreatic cancer, the recommended dose of Abra-bound is 125 mg/m2 administered as an intravenous infusion over 30-40 minutes on Days 1, 8, and 15 of each 28-day cycle.

Overdose - In case of an overdose of Abra-bound (albumin-bound paclitaxel) 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.

Dose adjustment - 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

  • For breast cancer, Abra-bound dose can be increased from 130 mg/m2 up to 200 mg/m2 in patients with severe hepatic impairment. 

  • For non-small cell lung cancer, decrease the dose of Abra-bound to 50 mg/m2 in patients with severe hepatic impairment.

Adverse reactions 

Side effects may occur during the course of Abra-bound. Some patients experience mild, moderate, or severe adverse reactions. The effect of the medicine depends upon the patient’s medical history and the body’s reaction to the medicines you consume.

Abra-bound can cause a severe decrease in neutrophils (a type of white blood cells important in fighting against bacterial infections) and platelets (important for clotting and controlling bleeding). 

Some common and allergic side effects like nausea, vomiting, diarrhea, mouth sores, headache, muscle pain, joint pain, numbness, tingling sensation on the hands or feet, weakness, dizziness, or hair loss may occur in some patients. 

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. 

Other common side effects of Abra-bound injection are Lightheadedness, difficulty in breathing, rapid weight gain, vision changes, seizures,  abdominal pain, pale skin, fever, chills, and swelling of ankles and feet. 

Some side effects (neurological and psychological) may be experienced by patients receiving Abra-bound (Albumin-bound paclitaxel) injection 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 

Hypersensitivity- Severe and sometimes fatal hypersensitivity reactions can occur in some patients, including anaphylactic reactions (severe allergic reactions), which have been reported. Patients who experience a severe hypersensitivity reaction to Abra-bound should not receive this drug. 

Neurological disorder:- during a course of Abra-bound therapy, sensory neuropathy can occur. The occurrence of grade 1 or 2 sensory neuropathy does not require dose modification or alteration. If grade 3 sensory neuropathy develops, treatment should be withheld until resolution to grade 1 or 2 followed by a dose reduction for all subsequent courses of Abra-bound.

Pregnant Women

Abra-bound (albumin-bound paclitaxel) 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 Abra-bound (albumin-bound paclitaxel) 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 Abra-bound.

Pediatric and Geriatric Use

The safety and efficacy of Abra-bound have not been established in patients below the age of 18.  In patients, aged 65 and above, Abra-bound (albumin-bound paclitaxel) has been used in several clinical trials. No notable differences in the efficacy and safety of this medicine have been observed. 

Packaging and Storage

Abra-band 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.