venetoclax

Action and Spectrum

Actions and Spectrum: 

Venetoclax is a BCL-2 inhibitor used to treat certain blood cancers like CLL, SLL, and AML. It works by binding to BCL-2 and blocks its function and cause cancer cell death. It has shown promise in treating non-Hodgkin lymphoma, multiple myeloma, and certain solid tumors. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Pyrexia (18%) 

Thrombocytopenia (29%) 

Abdominal pain (18%) 

Edema (22%) 

Fatigue (32%) 

URT infection (36%) 

Neutropenia (50%) 

Anemia (33%) 

Nausea (42%) 

Constipation (16%) 

Thrombocytopenia, Grade 3 or 4 (20%) 

Neutropenia, Grade 3 or 4 (45%) 

Mucositis (13%) 

Vomiting (16%) 

Lymphopenia (11%) 

Anemia, Grade 3 or 4 (18%) 

1-10% 

Febrile neutropenia (6%) 

Abdominal pain, Grade 3 or 4 (3%) 

Fatigue, Grade 3 or 4 (4%) 

Nausea, Grade 3 or 4 (1%) 

Vomiting, Grade 3 or 4 (1%) 

URT infection, Grade 3 or 4 (1%) 

Edema, Grade 3 or 4 (2%) 

Diarrhea, Grade 3 or 4 (3%) 

<1% 

Mucositis, Grade 3 or 4 

Pyrexia, Grade 3 or 4 

Constipation, Grade 3 or 4 

Combination with rituximab 

>10% 

Lymphopenia (87%) 

Hypophosphatemia (57%) 

Hyperkalemia (24%) 

Leukopenia, Grade 3 or 4 (46%) 

Diarrhea (40%) 

Increased AST/SGOT (46%) 

Neutropenia, Grade 3 or 4 (62-64%) 

Constipation (14%) 

Anemia (16%) 

Hypophosphatemia, Grade 3 or 4 (14%) 

Hypokalemia (29%) 

Hypernatremia (24%) 

Increased alkaline phosphatase (35%) 

Nausea (21%) 

Hyperbilirubinemia (33%) 

Rash (13%) 

Neutropenia (65-86%) 

Musculoskeletal pain (19%) 

Thrombocytopenia (15%) 

Hyponatremia (30%) 

LRT infection (18%) 

URT infection (39%) 

Headache (11%) 

Insomnia (11%) 

Hypocalcemia (62%) 

Lymphopenia, Grade 3 or 4 (56%) 

Abdominal pain (13%) 

1-10% 

Febrile neutropenia (4%) 

Mucositis (10%) 

Hyperkalemia, Grade 3 or 4 (3%) 

Hyponatremia, Grade 3 or 4 (6%) 

Hypernatremia, Grade 3 or 4 (1%) 

Hypokalemia, Grade 3 or 4 (6%) 

LRT infection, Grade 3 or 4 (2%) 

TLS, Grade 3 or 4 (3%) 

Lymphopenia, Grade 3/4 (7%) 

Increased AST/SGOT (2%) 

Pneumonia (10%) 

Hyperbilirubinemia, Grade 3 or 4 (4%) 

URT infection, Grade 3/4 (2%) 

Diarrhea, Grade 3 or 4 (3%) 

Vomiting (8%) 

Hypocalcemia, Grade 3 or 4 (5%) 

Increased alkaline phosphatase, Grade 3/4 (1%) 

Musculoskeletal pain, Grade 3/4 (1%) 

Black Box Warning

Black Box Warning: 

Tumor lysis syndrome (TLS) 

Contraindication / Caution

Contraindication/Caution: 

Venetoclax cause hypersensitivity, pregnancy and breastfeeding risks, and potent CYP3A inhibitors.  

Pregnancy / Lactation

Pregnancy consideration:  

AU TGA pregnancy category: C
US FDA pregnancy category: Not assigned. 

Lactation:   

Excreted into human milk is Not known. 

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies do not show risk to the fetus in the first/later trimester.        

• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women        

• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.       

• Category D: adequate data 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 the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.        

• Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

Venetoclax is a small molecule inhibitor that selectively inhibits the B-cell lymphoma 2 (BCL-2) protein an anti-apoptotic protein that regulates programmed cell death. 

Pharmacodynamics: 

Venetoclax inhibits B-cell lymphoma 2 (Bcl-2) preventing apoptosis by binding to it displacing proapoptotic proteins and activating caspases thus restoring apoptosis in CLL cells preventing tumor cell survival and chemotherapy resistance. 

Pharmacokinetics: 

Absorption 

AUC is 32.8 mcg·hr/mL. 

Distribution 

It is highly protein bound with a binding rate of > 99.9%.  

Metabolism 

CYP3A4/5 enzyme metabolizes venetoclax. 

Elimination and Excretion 

Half-life of 26 hours and eliminated from the body by feces. 

Adminstartion

Administration: 

It is taken orally once daily and dose depends on the patientweight and other factors. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: venetoclax 

Pronounced: [ ven-ET-oh-klax ] 

Why do we use venetoclax? 

Venetoclax treats blood cancers like CLL, SLL, and AML. It targets B-cell lymphoma 2 (BCL-2) by inhibiting apoptosis and slowing cancer growth. It can be used alone or with other medications depending on the cancer type and stage.