Venetoclax, also known as Venclexta, is a targeted cancer therapy. It works by inhibiting the B-cell lymphoma 2 (BCL-2) protein, which helps cancer cells survive and grow. This article simplifies information from the official package insert, covering approved uses, administration, and safety considerations.
Approved Medical Uses
Venetoclax is approved for specific blood cancers. It treats adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), including both initial treatment and cases where previous therapies have been tried.
It is also approved for newly-diagnosed acute myeloid leukemia (AML) in adults aged 75 or older, or those with health conditions preventing intensive chemotherapy. For AML, venetoclax is prescribed in combination with medications like azacitidine, decitabine, or low-dose cytarabine.
Dosage and Administration
Venetoclax tablets are taken orally once daily with a meal and water, at approximately the same time each day. Swallow tablets whole; do not chew, crush, or break them.
A distinctive aspect of venetoclax treatment is the 5-week “dose ramp-up” schedule. This involves starting with a low dose and gradually increasing it weekly. The ramp-up begins with 20 milligrams (mg) once daily for the first week, increasing weekly to 50 mg, 100 mg, 200 mg, and finally 400 mg daily. This slow increase helps minimize the risk of Tumor Lysis Syndrome (TLS).
Patients continue taking the 400 mg daily dose after the ramp-up. If a dose is missed by less than 8 hours, take it as soon as remembered. If more than 8 hours have passed, skip the missed dose and resume the regular schedule the next day; do not take a double dose. If vomiting occurs after a dose, do not take an additional dose that day; take the next dose at the usual time the following day.
Significant Safety Warnings
Tumor Lysis Syndrome (TLS)
A primary safety concern with venetoclax is Tumor Lysis Syndrome (TLS). This condition occurs when cancer cells break down too quickly, releasing contents like uric acid, potassium, and phosphate into the bloodstream. These substances can overwhelm the body, leading to kidney failure, irregular heartbeat, and seizures. Blood chemistry changes consistent with TLS can appear as early as 6 to 8 hours after the initial dose or any dose increase.
To prevent TLS, healthcare providers take precautions. Patients often receive medications like allopurinol to reduce uric acid levels and are advised to drink plenty of water (6 to 8 glasses daily), starting two days before the first dose and continuing with each dose increase. Regular blood tests monitor for early signs of TLS, such as electrolyte changes. Patients should immediately report symptoms that can indicate TLS, including:
- Fever
- Chills
- Nausea
- Vomiting
- Confusion
- Shortness of breath
- Seizures
- Irregular heartbeat
- Dark or cloudy urine
- Unusual tiredness or muscle or joint pain
Neutropenia
Another safety warning is neutropenia, a decrease in white blood cells. Low white blood cell counts are common and can be severe, increasing the risk of serious infections like pneumonia and sepsis. Regular blood count monitoring is performed throughout treatment. Dose adjustments or interruptions may be necessary if neutropenia becomes severe. Patients should be vigilant for signs of infection, including fever, and report them promptly to their healthcare team.
Common Side Effects and Drug Interactions
Common Side Effects
Patients taking venetoclax may experience common side effects. These include low blood cell counts (neutropenia, anemia, and thrombocytopenia). Gastrointestinal issues like diarrhea and nausea are also common. Other common effects include upper respiratory tract infections and fatigue.
Drug Interactions
Venetoclax is broken down by the CYP3A enzyme system. Other medications or foods can interfere with this process, increasing venetoclax levels and the risk of side effects, including TLS.
Strong CYP3A inhibitors are avoided during the initiation and ramp-up phases of venetoclax treatment, especially for CLL/SLL patients, due to an increased risk of TLS. These include:
- Itraconazole
- Ketoconazole
- Posaconazole
- Voriconazole
- Clarithromycin
- Ritonavir
If these medications are used after the ramp-up phase, the venetoclax dose is reduced by at least 75%.
Moderate CYP3A inhibitors also require caution. Their use during the initial and ramp-up phases should be avoided. If used later, the venetoclax dose may be reduced by at least 50%. These include:
- Ciprofloxacin
- Diltiazem
- Erythromycin
- Fluconazole
- Verapamil
Patients should also avoid consuming grapefruit, grapefruit juice, Seville oranges, and starfruit during treatment, as these foods contain natural CYP3A inhibitors that can increase venetoclax levels and the risk of adverse reactions.
Use in Specific Patient Groups
Pregnancy and Contraception
Venetoclax can harm an unborn baby, so its use is not recommended during pregnancy. Females who can become pregnant should undergo a pregnancy test before starting treatment. They must use effective contraception throughout treatment and for at least 30 days after the last dose.
If hormonal contraceptives are used, an additional barrier method, such as condoms, should also be used, as venetoclax may reduce their effectiveness. Venetoclax may impair male fertility. Male patients with female partners of reproductive potential should use effective contraception. Specific guidance should be discussed with a healthcare provider.
Breastfeeding
Patients should not breastfeed during venetoclax treatment and for at least one week after the final dose. It is unknown if venetoclax passes into breast milk, but due to its prolonged presence, accumulation in an infant is possible. Healthcare providers can offer guidance on safe feeding alternatives.