bendamustine

Action and Spectrum

Actions and spectrum:

bendamustine is an alkylating agent that exerts its cytotoxic effects by causing DNA damage, primarily through the formation of DNA crosslinks. It is classified as a bifunctional nitrogen mustard alkylating agent, meaning that it has two alkylating groups that can react with the DNA molecule. This leads to the inhibition of DNA synthesis and cell division, resulting in cell death.

bendamustine has a broad spectrum of activity against both hematologic malignancies and solid tumors. It is primarily used to treat non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, and multiple myeloma. It has also shown activity in the treatment of other types of cancer, including breast cancer, lung cancer, and ovarian cancer.

Drug Interaction

Adverse Reaction

Frequency defined

1-10%

Febrile neutropenia (3-6%)

Pruritus (5-6%)

Rash (5%)

Arthralgia (<6%)

Depression (<6%)

pain at Injection site (<6%)

Chest pain (<6%)

Hypotension (<6%)

Pain (<6%)

Hyperuricemia (<7%)

Taste alteration (<7%)

Tachycardia (<7%)

Anxiety (8%)

Hypokalemia (<9%)

Xerostomia (9%)

URI (10%)

UTI (<10%)

GERD (<10%)

>10%

Leukopenia (61-94%)

Thrombocytopenia (77-86%)

Nausea (20-75%)

Vomiting (16-40%)

Bilirubin increased (<34%)

Fever (24-34%)

Anorexia (<23%)

Headache (<21%)

Dehydration (<16%)

Stomatitis (<15%)

Dizziness (<14%)

Peripheral edema (13%)

Insomnia (<13%)

Weakness (8-11%)

Lymphopenia (68-99%)

Anemia (88-89%)

Neutropenia (75-86%)

Fatigue (9-57%)

Diarrhea (9-37%)

Constipation (<29%)

Pyrexia (24%)

Cough (4-22%)

Weight loss (7-18%)

Rash (8-16%)

Back pain (<14%)

Chills (6-14%)

Abdominal pain (5-13%)

Dyspepsia (<11%)

Post marketing Reports

Tumor lysis syndrome

Hepatotoxicity

Extravasation Injury

Progressive multifocal leukoencephalopathy

Skin reactions

Other malignancies

Non-melanoma skin cancer

Nephrogenic diabetes insipidus

phlebitis

lymphatic system and Blood disorders: myelosuppression, Pancytopenia

General disorders: Injection site reactions

Respiratory, mediastinal and thoracic disorders: Pneumonitis

Cardiovascular disorders: congestive heart failure, palpitation, Atrial fibrillation, myocardial infarction

Black Box Warning

Black Box Warning:

bendamustine can cause severe myelosuppression, including neutropenia, thrombocytopenia, and anemia. Myelosuppression can increase the risk of infection, bleeding, and anemia.

Contraindication / Caution

Contraindication/Caution:

Contraindication:

bendamustine is contraindicated in patients with known hypersensitivity (e.g., anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis) to bendamustine or any of its components. It is also contraindicated in patients with severe bone marrow suppression (less than 2,000 cells/mm³ for neutrophils and less than 50,000 cells/mm³ for platelets) and severe hepatic impairment (Child-Pugh score C).

Caution:

• Infections: bendamustine may weaken the immune system, making the patient more susceptible to infections.
• Myelosuppression: bendamustine can cause a decrease in the number of WBC, RBC, and platelets, which can lead to an increased risk of anemia, infection, and bleeding.
• Hepatic Impairment: bendamustine is primarily metabolized in the liver, and patients with liver impairment may have an increased risk of side effects.
• Renal Impairment: bendamustine is excreted primarily in the urine, and patients with renal impairment may have an increased risk of side effects.
• Tumor lysis syndrome: bendamustine may cause the rapid breakdown of cancer cells, which can lead to an increase in potassium, phosphorus, and uric acid levels in the blood.
• Cardiovascular effects: bendamustine can cause arrhythmias and changes in blood pressure.
• Allergic reactions: bendamustine can cause severe allergic reactions in some patients, including anaphylaxis.

Comorbidities:

• Infections: bendamustine may increase the risk of infections, and patients with a history of recurrent infections may need close monitoring during treatment.
• Liver disease: Patients with liver disease may experience more severe side effects from bendamustine, and dosage adjustments may be required.
• Renal impairment: bendamustine is primarily eliminated through the kidneys, and patients with renal impairment may need dosage adjustments.
• Cardiovascular disease: bendamustine may cause fluid retention and increase the risk of cardiovascular events, such as heart failure or myocardial infarction.

Blood disorders: bendamustine may cause bone marrow suppression, which can lead to anemia, leukopenia, and thrombocytopenia. Patients with pre-existing blood disorders may need careful monitoring during treatment.

Pregnancy / Lactation

Pregnancy consideration: US FDA pregnancy category: Not assigned.

Lactation: bendamustine is excreted in human milk.

Pregnancy category:

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester.
• Category B: There is no evidence of risk to the fetus found in animal reproduction studies and there are not enough studies on pregnant women.
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for an effect in humans, care must be taken for potential risks in pregnant women.
• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite potential risks may be used only in emergency cases for potential benefits.
• Category X: Drugs listed in this category outweigh risks over benefits These category drugs should be prohibited for pregnant women.
• Category N: There is no data available for the drug under this category.

Pharmacology

Pharmacology:

bendamustine is a bifunctional alkylating agent with properties of both a purine analog and an alkylating agent. It is converted intracellularly to an active metabolite, a nitrogen mustard derivative, which has cytotoxic effects on both dividing and non-dividing cells. The drug forms covalent bonds with DNA, leading to cross-linking of DNA strands, inhibition of DNA synthesis, and DNA damage. bendamustine also inhibits RNA and protein synthesis. The drug has a short plasma half-life and is rapidly eliminated from the body.

bendamustine has also been shown to have immunomodulatory effects, including activation of T and B cells and inhibition of regulatory T cells. It has been suggested that these immunomodulatory effects may contribute to the drug’s efficacy in the treatment of certain malignancies.

Pharmacodynamics:

bendamustine is an alkylating agent and a purine analog. Its mechanism of action is not known, but it is believed to work through a combination of alkylating DNA and RNA, inhibiting DNA synthesis, and inducing apoptosis (programmed cell death) in rapidly dividing cells.

bendamustine has a broad spectrum of activity against both hematologic malignancies and solid tumors. It has been effective against non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, multiple myeloma, and breast cancer.

In addition to its direct cytotoxic effects, bendamustine can enhance the activity of other chemotherapeutic agents, including rituximab, by sensitizing cells to their effects.

Pharmacokinetics:

Absorption

bendamustine is administered intravenously and is rapidly absorbed by the body. The mean maximum concentration (Cmax) of bendamustine is achieved within 30 minutes to 2 hours after intravenous infusion.

Distribution

bendamustine has a moderate volume of distribution (Vd) of approximately 20 L to 25 L. It is distributed mainly in the extracellular fluid compartment and has a low binding to plasma proteins (less than 30%).

Metabolism

bendamustine undergoes extensive metabolism in the liver, primarily via hydrolysis, to form the active metabolite, monohydroxyethyl bendamustine (MHEB), and other metabolites, including gamma-hydroxy-bendamustine (GHB) and N-desmethyl-bendamustine (DMB). MHEB is the major active metabolite responsible for the cytotoxic activity of bendamustine.

Elimination and excretion

bendamustine and its metabolites are primarily excreted in the urine, with approximately 60% to 70% of the administered dose recovered within five days. The terminal elimination half-life of bendamustine is approximately 30 minutes to 2 hours.

bendamustine does not appear to be a substrate, inhibitor, or inducer of cytochrome P450 enzymes.

Adminstartion

Administration:

bendamustine is administered intravenously (IV) as a solution. The infusion should be given slowly over a period of 60-90 minutes, depending on the dose and the indication. The dose and schedule may vary depending on the specific condition being treated and other factors such as the patient’s age, weight, and overall health.

Patient Information Leaflet

Patient information leaflet

Generic Name: bendamustine

Pronounced: [ BEN-da-MUS-teen]

Why do we use bendamustine?

bendamustine is a chemotherapy medication that is used to treat various types of cancer, including non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, multiple myeloma, and others. It is usually given as an injection into a vein (intravenous) by a healthcare professional. The specific duration and dosage of treatment depend on several factors, including the patient’s age and overall health and other individualized factors.