Venetoclax

Generic Details

Generic Name

venetoclax

Other Names

  • Venclexta

Drug Class

  • BCL-2 Inhibitor
  • Antineoplastic Agent

Chemical Formula

C45H50ClN7O7S

Molecular Weight

868.44 g/mol

Mechanism of Action

  • Venetoclax is a selective inhibitor of B-cell lymphoma-2 (BCL-2), an anti-apoptotic protein. By inhibiting BCL-2, venetoclax promotes apoptosis (programmed cell death) in cancer cells.

Indications

  • Chronic lymphocytic leukemia (CLL)
  • Small lymphocytic lymphoma (SLL)
  • Acute myeloid leukemia (AML)

Common Dosage Forms

  • Tablet

Typical Dosage

  • CLL/SLL: Initial dose of 20 mg once daily, followed by gradual dose escalation over 5 weeks to a final dose of 400 mg once daily.
  • AML: The dosage depends on patient factors, often starting at 400 mg daily in combination with other agents.

Pediatric Dosage

  • Safety and efficacy have not been established in pediatric patients.

Geriatric Dosage

  • No specific adjustments are required solely based on age, but renal function and comorbidities should be considered.

Side Effects

  • Neutropenia
  • Anemia
  • Thrombocytopenia
  • Diarrhea
  • Nausea
  • Fatigue
  • Tumor lysis syndrome (TLS)
  • Upper respiratory tract infections

Contraindications

  • Patients with known hypersensitivity to venetoclax or any of its components.
  • Severe hepatic impairment.

Pregnancy Category

  • Category D (evidence of risk to the fetus, but the benefits may outweigh the risks in some cases)

Lactation Safety

  • Breastfeeding is not recommended during venetoclax treatment due to the potential for serious adverse reactions in nursing infants.

Drug Interactions

  • CYP3A inhibitors (e.g., ketoconazole, ritonavir): May increase venetoclax levels, requiring dosage adjustments.
  • CYP3A inducers (e.g., rifampin): May decrease venetoclax levels and reduce efficacy.
  • Anticoagulants (e.g., warfarin): Increased bleeding risk.

Overdose Symptoms

  • Severe myelosuppression (low blood counts)
  • Tumor lysis syndrome
  • Increased risk of infections

Antidote for Overdose

  • No specific antidote; treatment is supportive care and symptomatic management.
  • Discontinue venetoclax and monitor for severe adverse reactions.

Storage Conditions

  • Store at 20°C to 25°C (68°F to 77°F), with excursions permitted to 15°C to 30°C (59°F to 86°F).

Pharmacokinetics

  • Absorption: Oral bioavailability is enhanced when taken with a meal.
  • Distribution: Extensively bound to plasma proteins (~99%).
  • Metabolism: Metabolized primarily by CYP3A4 enzymes.
  • Excretion: Eliminated mainly through feces (~85%) and urine (~1%).

Precautions

  • Tumor lysis syndrome (TLS) is a potentially life-threatening complication. Patients at high risk should be hospitalized for prophylactic measures and monitoring.
  • Monitor complete blood counts regularly due to the risk of neutropenia, anemia, and thrombocytopenia.

Warnings

  • Tumor lysis syndrome (TLS): Risk is high in patients with large tumor burdens. Preventive measures (e.g., hydration, uric acid reducers) should be initiated.
  • Severe neutropenia: Monitor blood counts and consider prophylactic use of colony-stimulating factors.

Others

  • Venetoclax is often used in combination with other anticancer agents such as rituximab, azacitidine, or decitabine for enhanced efficacy.