Generic
Venetoclax
11 brands available in the market
At a glance
Venetoclax is indicated in combination with Rituximab for the treatment of adult patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy.
Description
Venetoclax is a selective and orally bioavailable small-molecule inhibitor of BCL-2, an antiapoptotic protein. Overexpression of BCL-2 has been demonstrated in CLL cells where it mediates tumor cell survival and has been associated with resistance to chemotherapeutics.
Indications
- Chronic lymphocytic leukemia (CLL)
Therapeutic class
Cytotoxic Chemotherapy
Pharmacological class
BCL-2 Inhibitor
Pharmacology
Venetoclax is a selective and orally bioavailable small-molecule inhibitor of BCL-2. Overexpression of BCL-2 has been demonstrated in CLL cells where it mediates tumor cell survival and has been associated with resistance to chemotherapeutics.
Mechanism of action
Binds directly to BCL-2 protein, displacing pro-apoptotic proteins like BIM, triggering mitochondrial outer membrane permeabilization and caspase activation, restoring apoptosis.
Dosage
Adult Dose (Oral):
- Starting dose: 20 mg once daily for 7 days
- Gradually increased over 5 weeks up to 400 mg daily
- Post-titration dose in combination with Rituximab: 400 mg once daily; Rituximab started after 400 mg Venetoclax for 7 days
- Post-titration dose for monotherapy: 400 mg once daily; continue until disease progression or no longer tolerated
Administration
- Take with food
- Swallow tablets whole
- Take at the same time each day
Missed dose
If you miss a dose, take it as soon as you remember; if almost time for next dose, skip it; do not double the dose.
Side effects
Common Side Effects:
- Neutropenia
- Diarrhea
- Upper respiratory tract infection
- Nausea
- Anemia
- Fatigue
Precautions & warnings
- Tumour lysis syndrome (TLS) can occur; prophylaxis with hydration and anti-hyperuricemics needed
- Monitor blood chemistries
- Monitor CBC for neutropenia
- Do not administer live vaccines
- Avoid CYP3A inhibitors and inducers
Contraindications
- Hypersensitivity to the active substance or to any of the excipients
- Concomitant use of strong CYP3A inhibitors at initiation and during dose-titration phase
- Concomitant use of preparations containing St. John's wort
Drug interactions
- Strong CYP3A inhibitors (itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, ritonavir): contraindicated at initiation and during dose-titration phase
- Moderate CYP3A inhibitors (ciprofloxacin, diltiazem, erythromycin, fluconazole, verapamil): avoid at initiation and during titration; if unavoidable, reduce dose by 50%
- P-gp and BCRP inhibitors: avoid at initiation and during titration phase
- Strong CYP3A inducers (carbamazepine, phenytoin, rifampin) or moderate CYP3A inducers: avoid
Food interactions
Avoid grapefruit products, Seville oranges, and starfruit (contain CYP3A inhibitors).
Use in pregnancy
Use in Pregnancy: Animal studies show embryo-fetal toxicity; not recommended during pregnancy; use effective contraception.
Pregnancy Category: D — always consult a doctor before taking during pregnancy.
Use in lactation
Use in Lactation: Unknown if excreted in human milk; discontinue breastfeeding during treatment.
Pediatric use
Safety and efficacy not established in children under 18 years
Geriatric use
No specific dose adjustment required for elderly patients (aged >65 years)
Renal / hepatic impairment
Renal Impairment: Mild or moderate (CrCl >30 mL/min): no dose adjustment; severe (CrCl <30 mL/min): not recommended
Hepatic Impairment: Mild or moderate: no dose adjustment; severe: reduce dose by at least 50%
Overdose effects
Symptoms: TLS (fever, chills, nausea, vomiting, confusion, shortness of breath, seizures, irregular heartbeat, dark or cloudy urine, unusual tiredness, muscle or joint pain, abdominal pain and distension).
Treatment: No specific antidote; monitor closely and provide supportive treatment.
Storage conditions
Store below 30°C. Keep out of the sight and reach of children. Protect from moisture and light.