brentuximab vedotin

Action and Spectrum

Actions and Spectrum:

Actions:

The actions of brentuximab vedotin include:

• Binding to CD30: brentuximab vedotin binds to the CD30 protein on the surface of cancer cells.
• Internalization of the drug: After binding to CD30, the drug is internalized into the cancer cells.
• Release of the cytotoxic agent: Once inside the cancer cells, the drug releases a cytotoxic agent, called monomethyl auristatin E (MMAE).
• Induction of cell death: The released MMAE binds to tubulin, a protein necessary for cell division, and disrupts the microtubule network, leading to cell death.

Spectrum:

The spectrum of brentuximab vedotin refers to the range of cancers that it is effective against. Currently, brentuximab vedotin is approved for the treatment of Hodgkin’s lymphoma and systemic anaplastic large cell lymphoma, but it may also be effective against other types of CD30-positive cancers.

Drug Interaction

Adverse Reaction

Adverse drug reactions:  

Frequency defined:  

>10% (not treated)

Peripheral motor neuropathy (11%)

Dyspnea (12%)

Rashes, eruptions, exanthems (13%)

Back pain (13%)

Decreased appetite (18%)

Insomnia (19%)

Bone pain (19%)

Febrile neutropenia (19%)

Abdominal pain (21%)

Stomatitis (21%)

Loss of weight (22%)

Pyrexia (27%)

Diarrhoea (27%)

Vomiting (33%)

Constipation (42%)

Peripheral sensory neuropathy (65%)

Neutropenia (91%)

Anemia (98%)

1% to 10%  

Cough (2%)

Pyrexia (2%)

Pruritis (2-5%)

Dyspnea (2-3%)

Nausea (3-4%)

Chills (4%)

Dry skin (4-10%)

Muscle spasms (9-10%)

Extremity pain (10%)

Black Box Warning

Black Box Warning:

• JC virus infection results in PML and may lead to death; cases of (PML) progressive multifocal leukoencephalopathy are reported
• This leukoencephalopathy is rare, but serious brain infection results in death
• Signs and symptoms of PML may develop over several weeks or months and may include mood changes, unusual behavior, confusion, thinking problems, memory loss, changes in vision, speech, or walking, and a unilateral decrease in strength or weakness
• Progressive multifocal leukoencephalopathy (PML) is a rare and serious viral infection of the brain that is caused by the JC virus. It typically occurs in people with weakened immune systems, such as those with HIV/AIDS or people who have received immunosuppressive therapy.
• The signs and symptoms of PML can develop gradually over a period of weeks or month

Contraindication / Caution

Contraindication/Caution:

Contraindications:

• Hypersensitivity: brentuximab vedotin should not be used in patients who have a known hypersensitivity to the drug or any of its components.
• Severe renal impairment: brentuximab vedotin has not been studied in patients with severe renal impairment, so it should be used with caution in this population.

Cautions:

• Hepatic impairment: brentuximab vedotin should be used with caution in patients with hepatic impairment, as the drug is metabolized in the liver.
• Neuropathy: Brentuximab vedotin can cause peripheral neuropathy, which can be severe in some patients. Patients who experience symptoms of neuropathy should have their treatment interrupted or discontinued.
• Infections: Brentuximab vedotin can increase the risk of serious infections, including opportunistic infections. Patients should be monitored closely for signs of infection during treatment.
• Tumor lysis syndrome: brentuximab vedotin can cause tumor lysis syndrome, which is a medical emergency. Patients should be monitored closely for signs of tumor lysis syndrome, and appropriate measures should be taken to prevent or manage it.
• Pregnancy and lactation: brentuximab vedotin can cause fetal harm when administered to a pregnant woman. It is recommended that women of childbearing age use effective contraception during treatment with brentuximab vedotin, and that breastfeeding be avoided.

Pregnancy / Lactation

Pregnancy

The animal study reports show brentuximab is not suitable for the ingrowing fetus; hence is not advised to be administered during pregnancy.

Breastfeeding warnings:  

The excretion of a drug into the breastmilk is unknown

Due to the potential adverse drug reactions reported, brentuximab is not recommended in lactating females during treatment.

Pregnancy Categories:    

• Category A: Satisfactory and well-controlled studies show no risk to the fetus.
• Category B: No evidence shown of risk to the fetus found in animal reproduction studies, and there are not enough studies on pregnant women
• Category C: No adequate evidence for a result in humans must take care of potential risks in pregnant women
• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits
• Category X: Drugs listed in this category outweigh risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. Apart from this medication, pregnant women can prefer better alternatives.
• Category N: There is no data available for the drug under this category

Pharmacology

Pharmacology:

brentuximab vedotin is a monoclonal antibody-drug conjugate that targets the CD30 antigen, which is expressed on the surface of Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) cells. It’s pharmacology targets the CD30 antigen expressed on cancer cells and delivers a cytotoxic agent to induce apoptosis, thereby reducing tumor growth.

Pharmacodynamics:

The pharmacodynamics of brentuximab vedotin can be summarized as follows:

• Targeting CD30: brentuximab vedotin binds to the CD30 antigen expressed on cancer cells, leading to the internalization of the drug-antibody complex.
• Delivery of cytotoxic agent: The internalized drug-antibody complex is processed by the cell, releasing the cytotoxic agent MMAE into the cancer cell.
• Inhibition of microtubule polymerization: MMAE binds to tubulin and inhibits microtubule polymerization, resulting in the disruption of the microtubule network and ultimately leading to apoptosis of the cancer cell.
• Reduction of tumor growth: brentuximab vedotin’s ability to induce apoptosis of cancer cells leads to a reduction in tumor growth.
• Induction of antibody-dependent cellular cytotoxicity (ADCC): brentuximab vedotin may also induce ADCC, which is a mechanism by which the immune system destroys cancer cells.

Pharmacokinetics:

Absorption

Peak plasma is achieved in 20-30 minutes

Steady-state is achieved in 21 days (for a dose of 1.8 mg/kg every 3 weeks); and 56 days (for a dose of 1.2 mg/kg every 2 weeks)

Distribution

The value of protein-bound is 68-82%

Volume of Distribution is 6-10L

Metabolism

The metabolism of the drug occurs through oxidation by CYP3A4/5

Elimination and excretion

Half-life is 4-6 days

The drug is excreted through feces (72%) and urine

Adminstartion

Administration:

The drug should not be mixed with different medicinal products

The compatible solutions for the intravenous fluid are: D5W, 0.9% NaCl and Ringer Lactate.

The drug should be reconstituted with 10.5 ml of sterile water for injection to produce 5 mg/ml of concentration

Do not shake the vial, rather gently swirl it

Discard unused solution left in the vial

Patient Information Leaflet

Patient information leaflet

Generic Name: brentuximab vedotin

Pronounced: bren-TUX-i-mab-ve-DOE-tin

Why do we use brentuximab vedotin?

brentuximab vedotin is a targeted therapy that is used to treat certain types of cancer, including Hodgkin’s lymphoma, systemic anaplastic large cell lymphoma, and primary cutaneous anaplastic large cell lymphoma. It works by binding to a protein called CD30, which is found on the surface of certain cancer cells. This binding triggers the release of a toxic substance that kills the cancer cells.

brentuximab vedotin is usually used in patients who have already received other treatments, such as chemotherapy or radiation therapy, but the cancer has either not responded to treatment or has come back. In some cases, it may also be used as a first-line treatment for certain types of cancer.