Venetoclax

Venetoclax
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Martin Nino, M.D. [2]

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Overview

Venetoclax is a BCL-2 inhibitor that is FDA approved for the treatment of patients with chronic lymphocytic leukemia (CLL) with 17p deletion, as detected by an FDA approved test, who have received at least one prior therapy. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Common adverse reactions include neutropenia, diarrhea, nausea, anemia, upper respiratory tract infection, thrombocytopenia, and fatigue (≥20%).

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Patient Selection

Select patients for the treatment of relapsed or refractory CLL with Venetoclax based on the presence of 17p deletions in blood specimens. Patients without 17p deletion at diagnosis should be retested at relapse because acquisition of 17p deletion can occur.

Dosage

Venetoclax should be taken orally once daily until disease progression or unacceptable toxicity is observed. 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 Venetoclax to reduce risk of TLS. Administer the Venetoclax 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. Once the ramp-up phase is completed, the 400 mg dose is achieved using 100 mg tablets.

• Table 1: Dosing Schedule for Ramp-Up Phase

This image is provided by the National Library of Medicine.

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

Risk Assessment and Prophylaxis for Tumor Lysis Syndrome

Venetoclax 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 Venetoclax. Reduced renal function (creatinine clearance [CrCl] <80 mL/min) further increases the risk. The risk may decrease as tumor burden decreases.

Table 2 below describes the recommended TLS prophylaxis and monitoring during Venetoclax 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)

This image is provided by the National Library of Medicine.

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 Venetoclax, 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).

• Table 3: Recommended Dose Modifications for Toxicities (a)

This image is provided by the National Library of Medicine.

• Table 4: Dose Modification for Toxicity During Venetoclax Treatment

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Dose Modifications for Use with CYP3A and P-gp Inhibitors

Concomitant use of Venetoclax with strong CYP3A inhibitors at initiation and during ramp-up phase is contraindicated. Concomitant use of Venetoclax 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. For patients who have completed the ramp-up phase and are on a steady daily dose of Venetoclax, reduce the Venetoclax dose by at least 75% when strong CYP3A inhibitors must be used concomitantly.

Avoid concomitant use of Venetoclax 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 Venetoclax dose by at least 50%. Monitor these patients more closely for signs of toxicities.

Resume the Venetoclax dose that was used prior to initiating the CYP3A inhibitor or P-gp inhibitor 2 to 3 days after discontinuation of the inhibitor.

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

• Table 5: Management of Potential Venetoclax Interactions with CYP3A and P-gp Inhibitors

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Missed Dose

If the patient misses a dose of Venetoclax 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.

Ixekizumab is intended for use under the guidance and supervision of a physician. Patients may self-inject after training in subcutaneous injection technique using the autoinjector or prefilled syringe. Administer each injection at a different anatomic location (such as upper arms, thighs or any quadrant of abdomen) than the previous injection, and not into areas where the skin is tender, bruised, erythematous, indurated or affected by psoriasis. Administration of Ixekizumab in the upper, outer arm may be performed by a caregiver or healthcare provider.

If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time.

Preparation for Use of Ixekizumab Autoinjector and Prefilled Syringe

Before injection, remove Ixekizumab autoinjector or Ixekizumab prefilled syringe from the refrigerator and allow Ixekizumab to reach room temperature (30 minutes) without removing the needle cap.

Inspect Ixekizumab formulation visually for particulate matter and discoloration prior to administration. Ixekizumab formulation is a clear and colorless to slightly yellow solution. Do not use if the liquid contains visible particles, is discolored or cloudy (other than clear and colorless to slightly yellow). Ixekizumab formulation does not contain preservatives, therefore discard any unused product remaining in the autoinjector or prefilled syringe.

Instruct patients using the autoinjector or prefilled syringe to inject the full amount (1 mL), which provides 80 mg of Ixekizumab, according to the directions.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Ixekizumab in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Ixekizumab in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

FDA Package Insert for Ixekizumab contains no information regarding Pediatric Indications and Dosage.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Ixekizumab in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Ixekizumab in pediatric patients.

Contraindications

There is limited information regarding Venetoclax Contraindications in the drug label.

Warnings

There is limited information regarding Venetoclax Warnings' in the drug label.

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Venetoclax Clinical Trials Experience in the drug label.

Postmarketing Experience

There is limited information regarding Venetoclax Postmarketing Experience in the drug label.

Drug Interactions

There is limited information regarding Venetoclax Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): There is no FDA guidance on usage of Venetoclax in women who are pregnant.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Venetoclax in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Venetoclax during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Venetoclax in women who are nursing.

Pediatric Use

There is no FDA guidance on the use of Venetoclax in pediatric settings.

Geriatic Use

There is no FDA guidance on the use of Venetoclax in geriatric settings.

Gender

There is no FDA guidance on the use of Venetoclax with respect to specific gender populations.

Race

There is no FDA guidance on the use of Venetoclax with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Venetoclax in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Venetoclax in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Venetoclax in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Venetoclax in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Venetoclax Administration in the drug label.

Monitoring

There is limited information regarding Venetoclax Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Venetoclax and IV administrations.

Overdosage

There is limited information regarding Venetoclax overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Venetoclax Pharmacology in the drug label.

Mechanism of Action

There is limited information regarding Venetoclax Mechanism of Action in the drug label.

Structure

There is limited information regarding Venetoclax Structure in the drug label.

Pharmacodynamics

There is limited information regarding Venetoclax Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Venetoclax Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Venetoclax Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Venetoclax Clinical Studies in the drug label.

How Supplied

There is limited information regarding Venetoclax How Supplied in the drug label.

Storage

There is limited information regarding Venetoclax Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Venetoclax Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Venetoclax interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Venetoclax Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Venetoclax Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.