Venclexta

Name: Venclexta

Venclexta and Lactation

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if Venclexta crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using Venclexta. Do not breastfeed during treatment with Venclexta.

Venclexta Interactions

Do not receive a "live" vaccine while using venetoclax. The vaccine may not work as well during this time, or you could develop a serious infection. Live vaccines include measles, mumps, rubella (MMR), polio, rotavirus, typhoid, yellow fever, varicella (chickenpox), zoster (shingles), and nasal flu (influenza) vaccine.

Grapefruit, Seville oranges, and starfruit products may interact with venetoclax and lead to unwanted side effects. Avoid the use of juice or other products that contain these fruits while you are taking venetoclax.

Many drugs can interact with venetoclax. Not all possible interactions are listed here. Tell your doctor about all your current medicines and any you start or stop using, especially:

  • aprepitant;
  • cimetidine;
  • cyclosporine;
  • haloperidol;
  • imatinib;
  • St. John's wort;
  • warfarin (Coumadin, Jantoven);
  • an antibiotic--azithromycin, ciprofloxacin, clarithromycin, doxycycline, erythromycin, metronidazole, norfloxacin, rifampin, tetracycline;
  • antifungal medicine--clotrimazole, fluconazole, itraconazole, ketoconazole, voriconazole;
  • an antidepressant--desipramine, sertraline;
  • heart or blood pressure medicine--amiodarone, captopril, carvedilol, diltiazem, dronedarone, felodipine, lidocaine, quinidine, ranolazine, verapamil; or
  • HIV/AIDS medicine--lopinavir with ritonavir.

This list is not complete and many other drugs can interact with venetoclax. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Give a list of all your medicines to any healthcare provider who treats you.

What is the most important information I should know about venetoclax?

Many drugs can interact with venetoclax, and some drugs should not be used together. Tell your doctor about all medicines you use. Do not start or stop using any medicine without asking your doctor.

What happens if I miss a dose?

Take the missed dose as soon as you remember. If you are more than 8 hours late, skip the missed dose. Do not take extra medicine to make up the missed dose.

Uses for Venclexta

Chronic Lymphocytic Leukemia (CLL)

Treatment of CLL with 17p deletion (as detected by an FDA-approved diagnostic test) in patients who have received at least one prior therapy.1 2

Accelerated approval based on overall response rate and duration of response; continued approval may be contingent on verification and description of clinical benefit in confirmatory studies.1

Designated an orphan drug by FDA for treatment of CLL.3

Stability

Storage

Oral

Tablets

≤30°C.1

Store tablets in original package during initial 4 weeks of therapy.1

Precautions While Using Venclexta

It is very important that your doctor check your progress at regular visits while you are using this medicine. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to take it. Blood and urine tests may be needed to check for unwanted effects.

Using this medicine while you are pregnant can harm your unborn baby. Women must have a negative pregnancy test before starting this medicine. Use an effective form of birth control during treatment and for at least 30 days after the last dose to prevent pregnancy. If you think you have become pregnant while taking this medicine, tell your doctor right away.

Do not use this medicine together with clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavir, posaconazole, ritonavir, telaprevir, and voriconazole. Using these medicines together may cause serious unwanted effects.

This medicine may cause a serious type of reaction called tumor lysis syndrome. Your doctor may give you a medicine to help prevent this. Call your doctor right away if you have a decrease or change in urine amount, joint pain, stiffness, or swelling, lower back, side, or stomach pain, a rapid weight gain, swelling of the feet or lower legs, or unusual tiredness or weakness.

Check with your doctor if you have symptoms of an infection such as a fever, chills, or sore throat. This medicine may decrease the amount of white blood cells in the blood. White blood cells help your immune system fight infections.

While you are being treated with venetoclax, and after you stop treatment with it, do not have any immunizations (vaccines) without your doctor's approval. Venetoclax may lower your body's resistance and the vaccine may not work as well or you might get the infection the vaccine is meant to prevent. In addition, you should not be around other persons living in your household who receive live virus vaccines because there is a chance they could pass the virus on to you. Some examples of live vaccines include measles, mumps, influenza (nasal flu vaccine), poliovirus (oral form), rotavirus, and rubella. Do not get close to them and do not stay in the same room with them for very long. If you have questions about this, talk to your doctor.

Talk with your doctor before using this medicine if you plan to have children. Some men who use this medicine may become infertile (unable to have children).

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal (eg, St. John's wort) or vitamin supplements.

How do I store and/or throw out Venclexta?

  • Store in the original container at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.

Venclexta Dosage and Administration

Patient Selection

Select patients for the treatment of relapsed or refractory CLL with Venclexta based on the presence of 17p deletions in blood specimens [see Indications and Usage (1) and Clinical Studies (14)]. Patients without 17p deletion at diagnosis should be retested at relapse because acquisition of 17p deletion can occur. Information on FDA-approved tests for the detection of 17p deletions in CLL is available at: http://www.fda.gov/CompanionDiagnostics.

Recommended Dosage

Assess patient-specific factors for level of risk of tumor lysis syndrome (TLS) and provide prophylactic hydration and anti-hyperuricemics to patients prior to first dose of Venclexta to reduce risk of TLS [see Dosage and Administration (2.3) and Warnings and Precautions (5.1)]. Administer the Venclexta dose according to a weekly ramp-up schedule over 5 weeks to the recommended daily dose of 400 mg as shown in Table 1. The 5-week ramp-up dosing schedule is designed to gradually reduce tumor burden (debulk) and decrease the risk of TLS.

Instruct patients to take Venclexta tablets with a meal and water at approximately the same time each day. Venclexta tablets should be swallowed whole and not chewed, crushed, or broken prior to swallowing.

Table 1. Dosing Schedule for Ramp-Up Phase
Week Venclexta
Daily Dose
1 20 mg
2 50 mg
3 100 mg
4 200 mg
5 and beyond 400 mg

The Starting Pack provides the first 4 weeks of Venclexta according to the ramp-up schedule. Once the ramp-up phase is completed, the 400 mg dose is achieved using 100 mg tablets supplied in bottles [see How Supplied/Storage and Handling (16)].

Venclexta should be taken orally once daily until disease progression or unacceptable toxicity is observed.

Risk Assessment and Prophylaxis for Tumor Lysis Syndrome

Venclexta can cause rapid reduction in tumor and thus poses a risk for TLS in the initial 5-week ramp-up phase. Changes in blood chemistries consistent with TLS that require prompt management can occur as early as 6 to 8 hours following the first dose of Venclexta and at each dose increase.

The risk of TLS is a continuum based on multiple factors, including tumor burden and comorbidities. Perform tumor burden assessments, including radiographic evaluation (e.g., CT scan), assess blood chemistry (potassium, uric acid, phosphorus, calcium, and creatinine) in all patients and correct pre-existing abnormalities prior to initiation of treatment with Venclexta. Reduced renal function (creatinine clearance [CrCl] <80 mL/min) further increases the risk. The risk may decrease as tumor burden decreases [see Warnings and Precautions (5.1) and Use in Specific Populations (8.6)].

Table 2 below describes the recommended TLS prophylaxis and monitoring during Venclexta treatment based on tumor burden determination from clinical trial data.

Table 2. Recommended TLS Prophylaxis Based on Tumor Burden From Clinical Trial Data (consider all patient co-morbidities before final determination of prophylaxis and monitoring schedule)
Tumor Burden Prophylaxis Blood Chemistry
Monitoringc,d
  Hydrationa Anti-hyperuricemics Setting and
Frequency of
Assessments
Low All LN <5 cm AND
ALC <25 x109/L
Oral
(1.5-2 L)
Allopurinolb Outpatient
  • Pre-dose, 6 to 8 hours, 24 hours at first dose of 20 mg and 50 mg
  • Pre-dose at subsequent ramp-up doses
Medium Any LN 5 cm to <10 cm
OR
ALC ≥25 x109/L
Oral
(1.5-2 L)
and consider additional intravenous
Allopurinol Outpatient
  • Pre-dose, 6 to 8 hours, 24 hours at first dose of 20 mg and 50 mg
  • Pre-dose at subsequent ramp-up doses
  • Consider hospitalization for patients with CrCl <80ml/min at first dose of 20 mg and 50 mg; see below for monitoring in hospital
High Any LN ≥10 cm OR
ALC ≥25 x109/L AND
any LN ≥5 cm
Oral (1.5-2L)
and intravenous
(150-200 mL/hr
as tolerated)
Allopurinol; consider rasburicase if baseline uric acid is elevated In hospital at first dose of 20 mg and 50 mg
  • Pre-dose, 4, 8,12 and 24 hours
Outpatient at subsequent ramp-up doses
  • Pre-dose, 6 to 8 hours, 24 hours
ALC = absolute lymphocyte count; LN = lymph node.
aAdminister intravenous hydration for any patient who cannot tolerate oral hydration.
bStart allopurinol or xanthine oxidase inhibitor 2 to 3 days prior to initiation of Venclexta.
cEvaluate blood chemistries (potassium, uric acid, phosphorus, calcium, and creatinine); review in real time.
dFor patients at risk of TLS, monitor blood chemistries at 6 to 8 hours and at 24 hours at each subsequent ramp-up dose.

Dose Modifications Based on Toxicities

Interrupt dosing or reduce dose for toxicities. See Table 3 for dose modifications for hematologic and other toxicities related to Venclexta, and Table 4 for dose. For patients who have had a dosing interruption greater than 1 week during the first 5 weeks of ramp-up phase or greater than 2 weeks when at the daily dose of 400 mg, reassess for risk of TLS to determine if reinitiation with a reduced dose is necessary (e.g., all or some levels of the dose ramp-up schedule) [see Dosage and Administration (2.2, 2.3)].

Table 3. Recommended Dose Modifications for Toxicitiesa
Event Occurrence Action
Tumor Lysis Syndrome
Blood chemistry changes or symptoms suggestive of TLS Any Withhold the next day’s dose. If resolved within 24 to 48 hours of last dose, resume at the same dose.
For any blood chemistry changes requiring more than 48 hours to resolve, resume at a reduced dose (see Table 4) [see Dosage and Administration (2.3)].
For any events of clinical TLS,b resume at a reduced dose following resolution (see Table 4) [see Dosage and Administration (2.3)].
Non-Hematologic Toxicities
Grade 3 or 4 non-hematologic toxicities 1st occurrence Interrupt Venclexta.
Once the toxicity has resolved to Grade 1 or baseline level, Venclexta therapy may be resumed at the same dose. No dose modification is required.
2nd and subsequent occurrences Interrupt Venclexta.
Follow dose reduction guidelines in Table 4 when resuming treatment with Venclexta after resolution. A larger dose reduction may occur at the discretion of the physician.
Hematologic Toxicities
Grade 3 or 4 neutropenia with infection or fever; or Grade 4 hematologic toxicities (except lymphopenia) [see Warnings and Precautions (5.2)] 1st occurrence Interrupt Venclexta.
To reduce the infection risks associated with neutropenia, granulocyte-colony stimulating factor (G-CSF) may be administered with Venclexta if clinically indicated. Once the toxicity has resolved to Grade 1 or baseline level, Venclexta therapy may be resumed at the same dose.
2nd and subsequent occurrences Interrupt Venclexta.
Consider using G-CSF as clinically indicated.
Follow dose reduction guidelines in Table 4 when resuming treatment with Venclexta after resolution. A larger dose reduction may occur at the discretion of the physician.
Consider discontinuing Venclexta for patients who require dose reductions to less than 100 mg for more than 2 weeks.
aAdverse reactions were graded using NCI CTCAE version 4.0.
bClinical TLS was defined as laboratory TLS with clinical consequences such as acute renal failure, cardiac arrhythmias, or sudden death and/or seizures.
Table 4. Dose Modification for Toxicity During Venclexta Treatment
Dose at Interruption, mg Restart Dose, mga
400 300
300 200
200 100
100 50
50 20
20 10
aDuring the ramp-up phase, continue the reduced dose for 1 week before increasing the dose.

Dose Modifications for Use with CYP3A and P-gp Inhibitors

Concomitant use of Venclexta with strong CYP3A inhibitors at initiation and during ramp-up phase is contraindicated. Concomitant use of Venclexta with strong CYP3A inhibitors increases venetoclax exposure (i.e., Cmax and AUC) and may increase the risk for TLS at initiation and during ramp-up phase [see Contraindications (4)]. For patients who have completed the ramp-up phase and are on a steady daily dose of Venclexta, reduce the Venclexta dose by at least 75% when strong CYP3A inhibitors must be used concomitantly.

Avoid concomitant use of Venclexta with moderate CYP3A inhibitors or P-gp inhibitors. Consider alternative treatments. If a moderate CYP3A inhibitor or a P-gp inhibitor must be used, reduce the Venclexta dose by at least 50%. Monitor these patients more closely for signs of toxicities [see Dosage and Administration (2.4)].

Resume the Venclexta dose that was used prior to initiating the CYP3A inhibitor or P-gp inhibitor 2 to 3 days after discontinuation of the inhibitor [see Dosage and Administration (2.4) and Drug Interactions (7.1)].

The recommendations for managing drug-drug interactions are summarized in Table 5.

Table 5. Management of Potential Venclexta Interactions with CYP3A and P-gp Inhibitors
Inhibitors Initiation and Ramp-Up
Phase
Steady Daily Dose
(After Ramp-Up Phase)
Strong CYP3A inhibitor Contraindicated Avoid inhibitor use or reduce the Venclexta dose by at least 75%
Moderate CYP3A inhibitor Avoid inhibitor use or reduce the Venclexta dose by at least 50%
P-gp inhibitor

Missed Dose

If the patient misses a dose of Venclexta within 8 hours of the time it is usually taken, the patient should take the missed dose as soon as possible and resume the normal daily dosing schedule. If a patient misses a dose by more than 8 hours, the patient should not take the missed dose and should resume the usual dosing schedule the next day.

If the patient vomits following dosing, no additional dose should be taken that day. The next prescribed dose should be taken at the usual time.

Venclexta - Clinical Pharmacology

Mechanism of Action

Venetoclax is a selective and orally bioavailable small-molecule inhibitor of BCL-2, an anti-apoptotic 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. Venetoclax helps restore the process of apoptosis by binding directly to the BCL-2 protein, displacing pro-apoptotic proteins like BIM, triggering mitochondrial outer membrane permeabilization and the activation of caspases. In nonclinical studies, venetoclax has demonstrated cytotoxic activity in tumor cells that overexpress BCL-2.

Pharmacodynamics

Cardiac Electrophysiology

The effect of multiple doses of Venclexta up to 1200 mg once daily on the QTc interval was evaluated in an open-label, single-arm study in 176 patients with previously treated hematologic malignancies. Venclexta had no large effect on QTc interval (i.e., > 20 ms) and there was no relationship between venetoclax exposure and change in QTc interval.

Pharmacokinetics

Absorption

Following multiple oral administrations under fed conditions, maximum plasma concentration of venetoclax was reached 5-8 hours after dose. Venetoclax steady state AUC increased proportionally over the dose range of 150-800 mg. Under low-fat meal conditions, venetoclax mean (± standard deviation) steady state Cmax was 2.1 ± 1.1 μg/mL and AUC0-24 was32.8 ± 16.9 μg•h/mL at the 400 mg once daily dose.

Food Effect

Administration with a low-fat meal increased venetoclax exposure by approximately 3.4-fold and administration with a high-fat meal increased venetoclax exposure by 5.1- to 5.3-fold compared to fasting conditions. Venetoclax should be administered with a meal [see Dosage and Administration (2.2)].

Distribution

Venetoclax is highly bound to human plasma protein with unbound fraction in plasma <0.01 across a concentration range of 1-30 µM (0.87-26 µg/mL). The mean blood-to-plasma ratio was 0.57. The population estimate for apparent volume of distribution (Vdss/F) of venetoclax ranged from 256-321 L in patients.

Elimination

The population estimate for the terminal elimination half-life of venetoclax was approximately 26 hours. The pharmacokinetics of venetoclax does not change over time.

Metabolism

In vitro studies demonstrated that venetoclax is predominantly metabolized by CYP3A4/5. M27 was identified as a major metabolite in plasma with an inhibitory activity against BCL-2 that is at least 58-fold lower than venetoclax in vitro.

Excretion

After single oral administration of 200 mg radiolabeled [14C]-venetoclax dose to healthy subjects, >99.9% of the dose was recovered in feces and <0.1% of the dose was excreted in urine within 9 days, indicating that hepatic elimination is responsible for the clearance of venetoclax from the systemic circulation. Unchanged venetoclax accounted for 20.8% of the administered radioactive dose excreted in feces.

Special Populations

Age, Race, Sex, and Weight

Based on population pharmacokinetic analyses, age, race, sex, and weight do not have a clinically meaningful effect on venetoclax clearance.

Renal Impairment

Based on a population pharmacokinetic analysis that included 211 subjects with mild renal impairment (CrCl ≥60 and <90 mL/min, calculated by Cockcroft-Gault equation), 83 subjects with moderate renal impairment (CrCl ≥30 and <60 mL/min) and 210 subjects with normal renal function (CrCl ≥90 mL/min), venetoclax exposures in subjects with mild or moderate renal impairment are similar to those with normal renal function. The pharmacokinetics of venetoclax has not been studied in subjects with severe renal impairment (CrCl <30 mL/min) or subjects on dialysis [see Use in Specific Populations (8.6)].

Hepatic Impairment

Based on a population pharmacokinetic analysis that included 69 subjects with mild hepatic impairment, 7 subjects with moderate hepatic impairment and 429 subjects with normal hepatic function, venetoclax exposures are similar in subjects with mild and moderate hepatic impairment and normal hepatic function. The NCI Organ Dysfunction Working Group criteria for hepatic impairment were used in the analysis. Mild hepatic impairment was defined as normal total bilirubin and aspartate transaminase (AST) > upper limit of normal (ULN) or total bilirubin >1.0 to 1.5 times ULN, moderate hepatic impairment as total bilirubin >1.5 to 3.0 times ULN, and severe hepatic impairment as total bilirubin >3.0 times ULN. The pharmacokinetics of venetoclax has not been studied in subjects with severe hepatic impairment [see Use in Specific Populations (8.7)].

Drug Interactions

Ketoconazole

Co-administration of 400 mg once daily ketoconazole, a strong CYP3A, P-gp and BCRP inhibitor, for 7 days in 11 previously treated NHL patients increased venetoclax Cmax by 2.3-fold and AUC∞ by 6.4-fold [see Drug Interactions (7.1)].

Rifampin multiple doses

Co-administration of 600 mg once daily rifampin, a strong CYP3A inducer, for 13 days in 10 healthy subjects decreased venetoclax Cmax by 42% and AUC∞ by 71% [see Drug Interactions (7.1)].

Rifampin single dose

Co-administration of a 600 mg single dose of rifampin, an OATP1B1/1B3 and P-gp inhibitor, in 11 healthy subjects increased venetoclax Cmax by 106% and AUC∞ by 78% [see Drug Interactions (7.1)].

Gastric Acid Reducing Agents

Based on population pharmacokinetic analysis, gastric acid reducing agents (e.g., proton pump inhibitors, H2-receptor antagonists, antacids) do not affect venetoclax bioavailability.

Warfarin

In a drug-drug interaction study in three healthy subjects, administration of a single 400 mg dose of venetoclax with 5 mg warfarin resulted in 18% to 28% increase in Cmax and AUC∞ of R-warfarin and S-warfarin [see Drug Interactions (7.2)].

In vitro Studies

In vitro studies indicated that venetoclax is not an inhibitor or inducer of CYP1A2, CYP2B6, CYP2C19, CYP2D6, or CYP3A4 at clinically relevant concentrations. Venetoclax is a weak inhibitor of CYP2C8, CYP2C9, and UGT1A1 in vitro, but it is not predicted to cause clinically relevant inhibition due to high plasma protein binding. Venetoclax is not an inhibitor of UGT1A4, UGT1A6, UGT1A9, or UGT2B7.

Venetoclax is a P-gp and BCRP substrate as well as a P-gp and BCRP inhibitor and weak OATP1B1 inhibitor in vitro. To avoid a potential interaction in the gastrointestinal tract, co-administration of narrow therapeutic index P-gp substrates such as digoxin with Venclexta should be avoided. If a narrow therapeutic index P-gp substrate must be used, it should be taken at least 6 hours before Venclexta. Venetoclax is not expected to inhibit OATP1B3, OCT1, OCT2, OAT1, OAT3, MATE1, or MATE2K at clinically relevant concentrations.

Clinical Studies

The efficacy of Venclexta was established in an open-label, single-arm, multicenter clinical trial of 106 patients with CLL with 17p deletion who had received at least one prior therapy. In the study, 17p deletion was confirmed in peripheral blood specimens from patients using Vysis CLL FISH Probe Kit, which is FDA approved for selection of patients for Venclexta treatment. Patients received Venclexta via a weekly ramp-up schedule starting at 20 mg and ramping to 50 mg, 100 mg, 200 mg and finally 400 mg once daily. Patients continued to receive 400 mg of Venclexta orally once daily until disease progression or unacceptable toxicity.

The efficacy of Venclexta was evaluated by overall response rate (ORR) as assessed by an Independent Review Committee (IRC) using the International Workshop for Chronic Lymphocytic Leukemia (IWCLL) updated National Cancer Institute-sponsored Working Group (NCI-WG) guidelines (2008).

Table 9 summarizes the baseline demographic and disease characteristics of the study population.

Table 9. Baseline Patient Characteristics
Characteristics N = 106
Age, years; median (range) 67 (37-83)
White; % 97.1
Male; % 65.1
ECOG performance status; %
     0
     1
     2

39.6
51.9
8.5
Tumor burden; %
     Absolute lymphocyte count ≥25 x 109/L
     One or more nodes ≥5 cm

50.0
52.8
Number of prior therapies; median (range) 2.5 (1-10)
Time since diagnosis, months; median (range)a 79.4 (1.2-385.6)
aN=105.

The median time on treatment at the time of evaluation was 12.1 months (range: 0 to 21.5 months). Efficacy results are shown in Table 10.

Table 10. Efficacy Results for Patients with Previously Treated CLL with 17p Deletion by IRC
  Venclexta
N=106
ORR, n (%)
     (95% CI)
85 (80.2)
(71.3, 87.3)
     CR + CRi, n (%)
       CR, n (%)
       CRi, n (%)
8 (7.5)
6 (5.7)
2 (1.9)
     nPR, n (%) 3 (2.8)
     PR, n (%) 74 (69.8)
CI = confidence interval; CR = complete remission; CRi = complete remission with incomplete marrow recovery; IRC = independent review committee; nPR = nodular partial remission; ORR = overall response rate (CR + CRi + nPR + PR); PR = partial remission.

The median time to first response was 0.8 months (range: 0.1 to 8.1 months). Median duration of response (DOR) has not been reached with approximately 12 months median follow-up. The DOR ranged from 2.9 to 19.0+ months.

Minimal residual disease (MRD) was evaluated in peripheral blood and bone marrow for patients who achieved CR or CRi, following treatment with Venclexta. Three percent (3/106) were MRD negative in the peripheral blood and bone marrow (less than one CLL cell per 104 leukocytes).

How Supplied/Storage and Handling

Venclexta is dispensed as follows:

Packaging Presentation Number of Tablets National Drug Code (NDC)
 Starting Pack  Each pack contains four weekly wallet blister packs:
  • Week 1 (14 x 10 mg tablets)
  • Week 2 (7 x 50 mg tablets)
  • Week 3 (7 x 100 mg tablets)
  • Week 4 (14 x 100 mg tablets)
 0074-0579-28
 10 mg Wallet  14 x 10 mg tablets  0074-0561-14
 50 mg Wallet  7 x 50 mg tablets  0074-0566-07
 10 mg Unit Dose  2 x 10 mg tablets  0074-0561-11
 50 mg Unit Dose  1 x 50 mg tablet  0074-0566-11
 100 mg Unit Dose  1 x 100 mg tablet  0074-0576-11
 100 mg Bottle  120 x 100 mg tablets  0074-0576-22

Venclexta 10 mg film-coated tablets are round, biconvex shaped, pale yellow debossed with “V” on one side and “10” on the other side.

Venclexta 50 mg film-coated tablets are oblong, biconvex shaped, beige debossed with “V” on one side and “50” on the other side.

Venclexta 100 mg film-coated tablets are oblong, biconvex shaped, pale yellow debossed with “V” on one side and “100” on the other side.

Store at or below 86°F (30°C).

Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

  • Tumor Lysis Syndrome
    Advise patients of the potential risk of TLS, particularly at treatment initiation and during ramp-up phase, and to immediately report any signs and symptoms associated with this event (fever, chills, nausea, vomiting, confusion, shortness of breath, seizure, irregular heartbeat, dark or cloudy urine, unusual tiredness, muscle pain, and/or joint discomfort) to their doctor for evaluation [see Warnings and Precautions (5.1)].

    Advise patients to be adequately hydrated every day when taking Venclexta to reduce the risk of TLS. The recommended volume is 6 to 8 glasses (approximately 56 ounces total) of water each day. Patients should drink water starting 2 days before and on the day of the first dose, and every time the dose is increased [see Dosage and Administration (2.3)].

    Advise patients of the importance of keeping scheduled appointments for blood work or other laboratory tests [see Dosage and Administration (2.3)].

    Advise patients that it may be necessary to take Venclexta in the presence of a doctor to allow monitoring for TLS.
  • Neutropenia
    Advise patients to contact their doctor immediately if they develop a fever or any signs of infection. Advise patients of the need for periodic monitoring of blood counts [see Warnings and Precautions (5.2)].
  • Drug Interactions
    Advise patients to avoid consuming grapefruit products, Seville oranges, or starfruit during treatment with Venclexta. Advise patients that Venclexta may interact with some drugs; therefore, advise patients to inform their doctor of the use of any prescription medication, over-the-counter drugs, vitamins and herbal products [see Contraindications (4) and Drug Interactions (7.1)].
  • Immunizations
    Advise patients to avoid vaccination with live vaccines because they may not be safe or effective during treatment with Venclexta [see Warnings and Precautions (5.3)].
  • Pregnancy and Lactation
    Advise women of the potential risk to the fetus and to avoid pregnancy during treatment with Venclexta. Advise female patients of reproductive potential to use effective contraception during therapy and for at least 30 days after completing of therapy. Advise females to contact their doctor if they become pregnant, or if pregnancy is suspected, during treatment with Venclexta. Also advise patients not to breastfeed while taking Venclexta [see Warnings and Precautions (5.4), and Use in Specific Populations (8.1, 8.2, and 8.3)].
  • Male Infertility
    Advise patients of the possibility of infertility and possible use of sperm banking for males of reproductive potential [see Use in Specific Populations (8.3)].

Instructions for Taking Venclexta

Advise patients to take Venclexta exactly as prescribed and not to change their dose or to stop taking Venclexta unless they are told to do so by their doctor. Advise patients to take Venclexta orally once daily, at approximately the same time each day, according to their doctor's instructions and that the tablets should be swallowed whole with a meal and water without being chewed, crushed, or broken [see Dosage and Administration (2.2)].

Advise patients to keep Venclexta in the original packaging during the first 4 weeks of treatment, and not to transfer the tablets to a different container.

Advise patients that if a dose of Venclexta is missed by less than 8 hours, to take the missed dose right away and take the next dose as usual. If a dose of Venclexta is missed by more than 8 hours, advise patients to wait and take the next dose at the usual time [see Dosage and Administration (2.6)].

Advise patients not to take any additional dose that day if they vomit after taking Venclexta, and to take the next dose at the usual time the following day.

Manufactured and Marketed by:
AbbVie Inc.
North Chicago, IL 60064

and

Marketed by:
Genentech USA, Inc.
A Member of the Roche Group
South San Francisco, CA 94080-4990

© 2016 AbbVie Inc.

© 2016 Genentech, Inc.

03-B232 April 2016

MEDICATION GUIDE

VenclextaTM (ven-KLEKS-tuh)

(venetoclax)

tablets

What is the most important information I should know about Venclexta?

Venclexta can cause serious side effects, including:

Tumor lysis syndrome (TLS). TLS is caused by the fast breakdown of cancer cells. TLS can cause kidney failure, the need for dialysis treatment, and may lead to death. Your doctor will do tests to check your risk of getting TLS before you start taking Venclexta. You will receive other medicines before starting and during treatment with Venclexta to help reduce your risk of TLS. You may also need to receive intravenous (IV) fluids into your vein. Your doctor will do blood tests in your first 5 weeks of treatment to check you for TLS during treatment with Venclexta. It is important to keep your appointments for blood tests. Tell your doctor right away if you have any symptoms of TLS during treatment with Venclexta, including:

  • fever
  • chills
  • nausea
  • vomiting
  • confusion
  • shortness of breath
  • seizures
  • irregular heartbeat
  • dark or cloudy urine
  • unusual tiredness
  • muscle or joint pain

Drink plenty of water when taking Venclexta to help reduce your risk of getting TLS. Drink 6 to 8 glasses (about 56 ounces total) of water each day, starting 2 days before your first dose, on the day of your first dose of Venclexta, and each time your dose is increased.

Your doctor may delay, decrease your dose, or stop treatment with Venclexta if you have side effects.

See "What are the possible side effects of Venclexta?" for more information about side effects.

What is Venclexta?

Venclexta is a prescription medicine used to treat people with chronic lymphocytic leukemia (CLL) with 17p deletion, who have received at least one prior treatment.

It is not known if Venclexta is safe and effective in children.

Who should not take Venclexta? Certain medicines must not be taken when you first start taking Venclexta and while your dose is being slowly increased.

  • Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Venclexta and other medicines may affect each other causing serious side effects.
  • Do not start new medicines during treatment with Venclexta without first talking with your doctor.

What should I tell my doctor before taking Venclexta?

Before taking Venclexta, tell your doctor about all of your medical conditions, including if you:

  • have kidney or liver problems
  • have problems with your body salts or electrolytes, such as potassium, phosphorus, or calcium
  • have a history of high uric acid levels in your blood or gout
  • are scheduled to receive a vaccine. You should not receive a “live vaccine” before, during, or after treatment with Venclexta, until your doctor tells you it is okay. If you are not sure about the type of immunization or vaccine, ask your doctor. These vaccines may not be safe or may not work as well during treatment with Venclexta.
  • are pregnant or plan to become pregnant. Venclexta may harm your unborn baby. If you are able to become pregnant, your doctor should do a pregnancy test before you start treatment with Venclexta. Females who are able to become pregnant should use effective birth control during treatment and for 30 days after the last dose of Venclexta. If you become pregnant or think you are pregnant, tell your doctor right away.
  • are breastfeeding or plan to breastfeed. It is not known if Venclexta passes into your breast milk. Do not breastfeed during treatment with Venclexta.

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Venclexta and other medicines may affect each other causing serious side effects. See “Who should not take Venclexta?”

How should I take Venclexta?

  • Take Venclexta exactly as your doctor tells you to take it. Do not change your dose of Venclexta or stop taking Venclexta unless your doctor tells you to.
  • When you first take Venclexta:
    • You may need to take Venclexta at the hospital or clinic to monitor for TLS.
    • Your doctor will start Venclexta at a low dose. Your dose will be slowly increased weekly over 5 weeks up to the full dose. Read the Quick Start Guide that comes with Venclexta before your first dose.
  • Follow the instructions about drinking water described in the section of this Medication Guide about TLS called “What is the most important information I should know about Venclexta?” and also in the Quick Start Guide.
  • Take Venclexta 1 time a day with a meal and water at about the same time each day.
  • Swallow Venclexta tablets whole. Do not chew, crush, or break the tablets.
  • If you miss a dose of Venclexta and it has been less than 8 hours, take your dose as soon as possible. If you miss a dose of Venclexta and it has been more than 8 hours, skip the missed dose and take the next dose at your usual time.
  • If you vomit after taking Venclexta, do not take an extra dose. Take the next dose at your usual time the next day.

What should I avoid while taking Venclexta?

  • You should not drink grapefruit juice, eat grapefruit, Seville oranges (often used in marmalades), or starfruit while you are taking Venclexta. These products may increase the amount of Venclexta in your blood.

What are the possible side effects of Venclexta?

Venclexta can cause serious side effects, including:

  • See "What is the most important information I should know about Venclexta?"
  • Low white blood cell count (neutropenia). Low white blood cell counts are common with Venclexta, but can also be severe. Your doctor will do blood tests to check your blood counts during treatment with Venclexta. Tell your doctor right away if you have a fever or any signs of an infection while taking Venclexta.

The most common side effects of Venclexta include:

  • diarrhea
  • nausea
  • low red blood cell count
  • upper respiratory tract infection
  • low platelet count
  • feeling tired

Venclexta may cause fertility problems in males. This may affect your ability to father a child. Talk to your doctor if you have concerns about fertility.

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Venclexta. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store Venclexta?

  • Store Venclexta at or below 86°F (30°C).
  • Keep Venclexta tablets in the original package during the first 4 weeks of treatment. Do not transfer the tablets to a pillbox or other container.

Keep Venclexta and all medicines out of reach of children.

General information about the safe and effective use of Venclexta.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Venclexta for a condition for which it was not prescribed. Do not give Venclexta to other people, even if they have the same symptoms that you have. It may harm them. You can ask your doctor or pharmacist for information about Venclexta that is written for health professionals.

What are the ingredients in Venclexta?

Active ingredient: venetoclax

Inactive ingredients: copovidone, colloidal silicon dioxide, polysorbate 80, sodium stearyl fumarate, and calcium phosphate dibasic.

The 10 mg and 100 mg coated tablets also include the following: iron oxide yellow, polyvinyl alcohol, polyethylene glycol, talc, titanium dioxide. The 50 mg coated tablets also include the following: iron oxide yellow, iron oxide red, iron oxide black, polyvinvyl alcohol, talc, polyethylene glycol, and titanium dioxide.


Manufactured and Marketed by:
AbbVie Inc.
North Chicago, IL 60064


© 2016 AbbVie Inc.

03-B232


Marketed by:
Genentech USA, Inc.
A member of the Roche Group
South San Francisco, CA 94080-4990

© 2016 Genentech, Inc.

This Medication Guide has been approved by the U.S. Food and Drug Administration. Issued: 04/2016

NDC 0074–0579–28

Rx only

Venclexta™

(venetoclax) tablets

10 mg, 50 mg, and 100 mg

Starting Pack

! WARNING

Contact your doctor when you receive this medication.

It may be necessary to take your first dose in the presence of your doctor to prevent a potential serious side effect.

DISPENSER: Each time Venclexta is dispensed give the patient the enclosed Medication Guide.

abbvie

Genentech

NDC 0074–0561–14

Rx only

Venclexta™

(venetoclax) tablets

10 mg

14 Tablets

Dispense the accompanying Medication Guide to each patient.

abbvie

Genentech

NDC 0074–0566–11

Rx only

Venclexta™

(venetoclax) tablets

50 mg

1 Tablet

Dispense the accompanying Medication Guide to each patient.

abbvie

Genentech

NDC 0074–0576–22

Rx only

Venclexta™

(venetoclax) tablets

100 mg

120 Tablets

Do not accept if seal over bottle opening is broken or missing.

Each film-coated tablet contains 100 mg of venetoclax.

Keep out of reach of children.

Store at or below 86°F (30°C).

abbvie

Genentech

Venclexta 
venetoclax kit
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0074-0579
Packaging
# Item Code Package Description
1 NDC:0074-0579-28 1 KIT in 1 CARTON
Quantity of Parts
Part # Package Quantity Total Product Quantity
Part 1 1 BLISTER PACK 14 
Part 2 1 BLISTER PACK
Part 3 1 BLISTER PACK
Part 4 1 BLISTER PACK 14 
Part 1 of 4
Venclexta 
venetoclax tablet, film coated
Product Information
Item Code (Source) NDC:0074-0561
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
Venetoclax (Venetoclax) Venetoclax 10 mg
Inactive Ingredients
Ingredient Name Strength
COPOVIDONE K25-31  
SILICON DIOXIDE  
POLYSORBATE 80  
SODIUM STEARYL FUMARATE  
ANHYDROUS DIBASIC CALCIUM PHOSPHATE  
FERRIC OXIDE YELLOW  
POLYVINYL ALCOHOL  
POLYETHYLENE GLYCOLS  
Talc  
TITANIUM DIOXIDE  
Product Characteristics
Color YELLOW (pale yellow) Score no score
Shape ROUND (round, biconvex) Size 6mm
Flavor Imprint Code V;10
Contains     
Packaging
# Item Code Package Description
1 14 TABLET, FILM COATED in 1 BLISTER PACK
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA208573
Part 2 of 4
Venclexta 
venetoclax tablet, film coated
Product Information
Item Code (Source) NDC:0074-0566
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
Venetoclax (Venetoclax) Venetoclax 50 mg
Inactive Ingredients
Ingredient Name Strength
COPOVIDONE K25-31  
SILICON DIOXIDE  
POLYSORBATE 80  
SODIUM STEARYL FUMARATE  
ANHYDROUS DIBASIC CALCIUM PHOSPHATE  
FERRIC OXIDE YELLOW  
POLYVINYL ALCOHOL  
POLYETHYLENE GLYCOLS  
Talc  
TITANIUM DIOXIDE  
FERRIC OXIDE RED  
FERROSOFERRIC OXIDE  
Product Characteristics
Color BROWN (beige) Score no score
Shape OVAL (oblong, biconvex) Size 14mm
Flavor Imprint Code V;50
Contains     
Packaging
# Item Code Package Description
1 7 TABLET, FILM COATED in 1 BLISTER PACK
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA208573
Part 3 of 4
Venclexta 
venetoclax tablet, film coated
Product Information
Item Code (Source) NDC:0074-0576
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
Venetoclax (Venetoclax) Venetoclax 100 mg
Inactive Ingredients
Ingredient Name Strength
COPOVIDONE K25-31  
SILICON DIOXIDE  
POLYSORBATE 80  
SODIUM STEARYL FUMARATE  
ANHYDROUS DIBASIC CALCIUM PHOSPHATE  
FERRIC OXIDE YELLOW  
POLYVINYL ALCOHOL  
POLYETHYLENE GLYCOLS  
Talc  
TITANIUM DIOXIDE  
Product Characteristics
Color YELLOW (pale yellow) Score no score
Shape OVAL (oblong, biconvex) Size 17mm
Flavor Imprint Code V;100
Contains     
Packaging
# Item Code Package Description
1 7 TABLET, FILM COATED in 1 BLISTER PACK
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA208573
Part 4 of 4
Venclexta 
venetoclax tablet, film coated
Product Information
Item Code (Source) NDC:0074-0576
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
Venetoclax (Venetoclax) Venetoclax 100 mg
Inactive Ingredients
Ingredient Name Strength
COPOVIDONE K25-31  
SILICON DIOXIDE  
POLYSORBATE 80  
SODIUM STEARYL FUMARATE  
ANHYDROUS DIBASIC CALCIUM PHOSPHATE  
FERRIC OXIDE YELLOW  
POLYVINYL ALCOHOL  
POLYETHYLENE GLYCOLS  
Talc  
TITANIUM DIOXIDE  
Product Characteristics
Color YELLOW (pale yellow) Score no score
Shape OVAL (oblong, biconvex) Size 17mm
Flavor Imprint Code V;100
Contains     
Packaging
# Item Code Package Description
1 14 TABLET, FILM COATED in 1 BLISTER PACK
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA208573
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA208573 04/11/2016
Venclexta 
venetoclax tablet, film coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0074-0576
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
Venetoclax (Venetoclax) Venetoclax 100 mg
Inactive Ingredients
Ingredient Name Strength
COPOVIDONE K25-31  
SILICON DIOXIDE  
POLYSORBATE 80  
SODIUM STEARYL FUMARATE  
ANHYDROUS DIBASIC CALCIUM PHOSPHATE  
FERRIC OXIDE YELLOW  
POLYVINYL ALCOHOL  
POLYETHYLENE GLYCOLS  
Talc  
TITANIUM DIOXIDE  
Product Characteristics
Color YELLOW (pale yellow) Score no score
Shape OVAL (oblong, biconvex) Size 17mm
Flavor Imprint Code V;100
Contains     
Packaging
# Item Code Package Description
1 NDC:0074-0576-22 120 TABLET, FILM COATED in 1 BOTTLE
2 NDC:0074-0576-11 1 BLISTER PACK in 1 CARTON
2 1 TABLET, FILM COATED in 1 BLISTER PACK
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA208573 04/11/2016
Venclexta 
venetoclax tablet, film coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0074-0561
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
Venetoclax (Venetoclax) Venetoclax 10 mg
Inactive Ingredients
Ingredient Name Strength
COPOVIDONE K25-31  
SILICON DIOXIDE  
POLYSORBATE 80  
SODIUM STEARYL FUMARATE  
ANHYDROUS DIBASIC CALCIUM PHOSPHATE  
FERRIC OXIDE YELLOW  
POLYVINYL ALCOHOL  
POLYETHYLENE GLYCOLS  
Talc  
TITANIUM DIOXIDE  
Product Characteristics
Color YELLOW (pale yellow) Score no score
Shape ROUND (round, biconvex) Size 6mm
Flavor Imprint Code V;10
Contains     
Packaging
# Item Code Package Description
1 NDC:0074-0561-14 1 BLISTER PACK in 1 CARTON
1 14 TABLET, FILM COATED in 1 BLISTER PACK
2 NDC:0074-0561-11 1 BLISTER PACK in 1 CARTON
2 2 TABLET, FILM COATED in 1 BLISTER PACK
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA208573 04/11/2016
Venclexta 
venetoclax tablet, film coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0074-0566
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
Venetoclax (Venetoclax) Venetoclax 50 mg
Inactive Ingredients
Ingredient Name Strength
COPOVIDONE K25-31  
SILICON DIOXIDE  
POLYSORBATE 80  
SODIUM STEARYL FUMARATE  
ANHYDROUS DIBASIC CALCIUM PHOSPHATE  
FERRIC OXIDE RED  
FERROSOFERRIC OXIDE  
FERRIC OXIDE YELLOW  
POLYVINYL ALCOHOL  
POLYETHYLENE GLYCOLS  
Talc  
TITANIUM DIOXIDE  
Product Characteristics
Color BROWN (beige) Score no score
Shape OVAL (oblong, biconvex) Size 14mm
Flavor Imprint Code V;50
Contains     
Packaging
# Item Code Package Description
1 NDC:0074-0566-07 1 BLISTER PACK in 1 CARTON
1 7 TABLET, FILM COATED in 1 BLISTER PACK
2 NDC:0074-0566-11 1 BLISTER PACK in 1 CARTON
2 1 TABLET, FILM COATED in 1 BLISTER PACK
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA208573 04/11/2016
Labeler - AbbVie Inc. (078458370)
Revised: 09/2017   AbbVie Inc.
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