Venetoclax is typically used as a second-line treatment for those suffering from chronic lymphocytic leukemia. It is only used if a 17p deletion has been determined by an approved assessment. The medication was granted Breakthrough Therapy Designation by the US Food & Drug Administration (FDA) in 2015 for patients with the 17p genetic mutation.
It is a BH3-mimetic and functions as a Bcl-2 inhibitor. It blocks the B-cell lymphoma-2 protein, and this leads to the programmed death of CLL cells. It is believed that the overexpression of Bcl-2 in patients with lymphoid malignancies results in a resistance to chemotherapy.
Although it has been approved for one specific use, physicians can elect to use Veneoclax for other uses if they feel it may be useful.
Patients who take Venetoclax are advised to inform all of their healthcare providers that they are using the medication; this includes nurses, doctors, dentists and pharmacists. Venetoclax is best taken with a meal, swallowed whole with a drink of water. When using Venetoclax, patients are advised to drink plenty of water (approximately 6 to 8 glasses per day), and to begin drinking an increased level of water at least two days prior to starting a course of the drug.
Venetoclax can cause a number of side effects, ranging from minor to life-threatening. Before commencing use of this medicine, you should consult a qualified health professional.
Many of the side effects of Venetoclax that occur do not require medical attention. The majority of minor side effects are likely to dissipate during the course of treatment, once the body gets used to the medication. Your doctor or healthcare provider may be able to advise you on ways in which you can reduce or completely prevent some or all of these side effects. If any side effects continue after prolonged use or are particularly bothersome, you should consult your doctor.
Venetoclax is available in doses of 10 mg, 50mg and 100mg.
The medication is typically administered over a course of weeks and ‘ramped-up’ in the following doses to allow the body to adjust:
After five weeks, a maintenance dose of 400mg per day, taken orally, should be administered either until noticeable progess is observed, or unacceptable toxicity renders administration of the drug untenable.
Prior to taking the medication, patients should be selected for treatment based on the detection of 17p deletions in blood plasma specimens. Patients without 17p deletion during relapse should be retested, as it is possible for acquisition of 17p deletion to occur.
Patients with severe kidney problems may require an adjustment in dosage, determined by a doctor or qualified healthcare professional and based on the circumstances of the individual concerned.
Patients with mild liver problems (total bilirubin and AST at larger levels than normal, or total bilirubin greater than 1.5 times the upper normal limit), may require dosage adjustments. Again, these adjustments should be determined by a qualified physician or healthcare practitioner.
Dosage adjustments of Venetoclax when resuming treatment after dose interruption as a result of toxicity
Patients whose treatment has been put on hold due to toxicity may elect to resume treatment after a period of abstinence, at the following doses:
When recommencing the five-week ramping-up phase after dose interruption, it is advisable to continue with the reduced dose for at least one extra week before the dose is increased.
If the dose has been disrupted for more than an entire week, the ramp-up phase can potentially need to be lengthened even further, based on the opinions of your doctor. Reassessment for Tumor Lysis Syndrome (TLS) should commence, in order to ascertain whether re-initiation with reduced doses is necessary – in certain instances, the earlier levels of the ramp-up schedule can be omitted if the patient is deemed to be capable of handling greater increases in ramp-up doses. Over the course of treatment, patients who wind down to a dose of 100mg or less for greater than two weeks should consider discontinuing use of Venetoclax entirely.
In the event of blood chemistry changes, or if the patient encounters symptoms suggestive of TLS, the following day’s dose of Venetoclax should be withheld. Resumption of the medication at the same dose should commence with 24 to 48 hours if symptoms are resolved. Patients with blood chemistry changes which take more than 48 hours to resolve should resume treatment at a reduced dose determined by a doctor.
At the first occurrence of grade 3 or 4 NHT, dosage should be stopped until the toxicity resolves to grade 1 or baseline. For all subsequent occurrences, dosage should be interrupted and resumed after baseline toxicity resolution. Larger dose reductions can be considered at the discretion of a healthcare professional.
Patients with grade 3 or 4 neutropenia with infection or fever may require the administration of granulocyte-colony stimulating factor, in order to reduce any infection risks associated with neutropenia. G-CSF should only be used as clinically indicated.
There is currently no specific antidote to treat Venetoclax overdose. In the event of overdose, the patient should be monitored closely with supportive treatment applied where appropriate. During monitoring, patients should be observed for the following symptoms, which are indicative of TLS: chills, fever, irregular heartbeat, cloudy or dark urine, joint pain, unusual tiredness (lethargy), abdominal pain.
Because Venetoclax is protein-binding and is distributed in large doses, dialysis is unlikely to result in a significant level of removal of the drug.
When taken in conjunction with other medications, potentially harmful interactions may occur. There are over 300 medications that Venetoclax is currently known to interact with.
Because the use of Venetoclax puts the patient at increased risk of infection, it is important to avoid any innoculations against infectious diseases (measles, mumps, rubella, meningitis, lyme disease, smallpox, rabies and more). This applies to both live and non-live vaccines, as a decreased immune system as a result of Venetoclax use means patients are more susceptible to becoming seriously ill as a result of an adverse reaction to a vaccine.
Nootropic medications, which are used to aid concentration, are known to interact with Venetoclax, and should be avoided when anti-cancer treatment commences.
Medicines which majorly interact with Venetoclax can result in increased blood levels of Venetoclax and infection. The following is a list of drugs which are known to cause these issues:
Other medications may have minor interactions with Venetoclax, resulting in side effects like nausea, vomiting and diarrhea. These medicines include:
Food helps the body to increase absorption of Venetoclax. Therefore, each dose of the medication should be taken with a meal and a glass of water, at roughly the same time every day. However, there are certain foods which should be avoided when being treated with Venetoclax, and these include:
These fruits and their associated juices can cause a significant increase in the blood levels of the medication, thereby amplifying its effects. As a result, the patient could be at a significantly increased risk of developing Tumor Lysis Syndrome (TLS), which is a serious condition that occurs when cancer cells break down rapidly. This can lead to renal problems and even death.
In addition to these serious side effects, patients may have an increased propensity to experience other, less serious side effects, like nausea, fatigue and diarrhea, as well as impaired bone marrow function, which can result in lower numbers of different blood cell types. This increases the risk of bleeding problems, infections and anemia. If you have any concerns, you should contact your doctor, informing them of any supplements, vitamins or herbs you are currently taking.
Studies on animals have revealed that fetotoxicity occurs at approximately 1.2 times when the standard human exposure of 400mg per day is administered. Fetotoxicity involves an increase in post-implantation loss, as well as decreased fetal body weight. However, teratogenicity was not observed. Other data from animal studies suggests that male human fertility could be negatively affected, based on evidence of testicular toxicity at doses as low as 200mg, or half a standard daily dose. With this in mind, males of reproductive age are encouraged to consider storing sperm at a sperm bank prior to commencing treatment with Venetoclax.
During studies, no effects were observed on mating, corpora lutea, uterine implants or live embryos, even at dosages of up to 600mg per day.
Mothers should discontinue breastfeeding before commencing treatment with Venetoclax. The drug can potentially be excreted into breast milk and can, therefore, put infants at risk of infection, bone marrow problems, and even death.
Tumor Lysis Syndrome, or TLS, has been reported to have occurred in numerous patients previously treated for CLL when treated with Venetoclax. This medication can cause rapid reduction in tumor levels, thereby posing a reasonable risk for TLS, particularly in the initial five-week initiation phase of the medicine's use. Changes in the level of electrolytes, which are consistent with TLS, have been observed in patients as early as six hours following first-level treatment with the drug.
Patients with high tumor burden (for example, any lymph node with a diameter in excess of 5mm) are at a higher risk of developing TLS when starting treatment with Venetoclax. Patients should always be assessed for TLS risk via blood chemistries prior to engaging in the treatment.
Venetoclax does not require any specific storage instructions. Patients are advised, as with all medicines, to keep Venetoclax tablets at room temperature in a cool, dry place away from the reach of children, and out of direct sunlight.
Venetoclax, often sold as Venclyxto or Venclexta, is used to treat CLL. It is a selective inhibitor of the anti-apoptotic protein B-cell lymphoma. It is a prescription-only medication available in tablet form in the following increments:
Each film coated tablet contains 100% of the advertised ingredient (Venetoclax). Treatment with this medication should only be initiated and supervised by a physician with experience and qualification in the administration of anti-cancer medicines.