Umbralisib

Umbralisib
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: Parth Vikram Singh, MBBS[2]

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Overview

Umbralisib is a a kinase inhibitor that is FDA approved for the treatment of adult patients with:

• Relapsed or refractory marginal zone lymphoma (MZL) who have

received at least one prior anti-CD20-based regimen.

• Relapsed or refractory follicular lymphoma (FL) who have received at

least three prior lines of systemic therapy.

These indications are approved under accelerated approval based on overall response rate. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial.. Common adverse reactions include increased creatinine, diarrhea-colitis, fatigue, nausea, neutropenia, transaminase elevation, musculoskeletal pain, anemia, thrombocytopenia, upper respiratory tract infection, Nausea and vomiting\ vomiting, abdominal pain, decreased appetite, and rash..

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Marginal Zone Lymphoma

UKONIQ is indicated for the treatment of adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least one prior anti-CD20-based regimen. 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(s).

Follicular Lymphoma

UKONIQ is indicated for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) who have received at least three prior lines of systemic 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(s).

DOSAGE AND ADMINISTRATION

Recommended Dosage

• The recommended dosage of UKONIQ is 800 mg taken orally once daily with food until disease progression or unacceptable toxicity.

Advise patients of the following:

• Swallow tablets whole. Do not crush, break, cut, or chew tablets.
• Take UKONIQ at the same time each day.
• If vomiting occurs, do not take an additional dose; continue with the next scheduled dose.
• If a dose is missed, take a missed dose unless it is less than 12 hours until the next scheduled

dose.

Recommended Prophylaxis

Provide prophylaxis for Pneumocystis jirovecii pneumonia (PJP) during treatment with UKONIQ.

Consider prophylactic antivirals during treatment with UKONIQ to prevent cytomegalovirus (CMV) infection, including CMV reactivation.

Dosage Modifications for Adverse Reactions

Recommended dosage

modifications of UKONIQ for adverse reactions are presented in Table 1

Recommended Dosage Modifications of UKONIQ for Adverse Reactions

Recommended Dosage Modifications of UKONIQ for Adverse Reactions

and the recommended dose reductions of UKONIQ for adverse reactions are presented in Table 2

Recommended Dose Reductions of UKONIQ for Adverse Reactions

DOSAGE FORMS AND STRENGTH

Tablets: 200 mg, green film-coated, oval-shaped with “L474” on one side and plain on the other side.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

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

Non–Guideline-Supported Use

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

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Umbralisib FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

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

Non–Guideline-Supported Use

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

Contraindications

None.

Warnings

Infections

• Serious, including fatal, infections occurred in patients treated with UKONIQ. Grade 3 or higher infections occurred in 10% of 335 patients, with fatal infections occurring in <1%. The most frequent Grade ≥3 infections included pneumonia, sepsis, and urinary tract infection. The median time to onset of Grade ≥3 infection was 2.4 months (range: 1 day to 21 months).

• Monitor for any new or worsening signs and symptoms of infection. For Grade 3 or 4 infection, withhold UKONIQ until infection has resolved. Resume UKONIQ at the same or a reduced dose.
• Provide prophylaxis for Pneumocystis jirovecii pneumonia (PJP) during treatment with UKONIQ.
• Withhold UKONIQ in patients with suspected PJP of any grade and permanently discontinue in patients with confirmed PJP.
• Monitor for cytomegalovirus (CMV) infection during treatment with UKONIQ in patients with a history of CMV infection. Consider prophylactic antivirals during treatment with UKONIQ to prevent CMV infection, including CMV reactivation.
• For clinical CMV infection or viremia, withhold UKONIQ until infection or viremia resolves. If UKONIQ is resumed, administer the same or reduced dose and monitor patients for CMV reactivation by PCR or antigen test at least monthly.

Neutropenia

• Serious neutropenia occurred in patients treated with UKONIQ. Grade 3 neutropenia developed in 9% of 335 patients and Grade 4 neutropenia developed in 9% .The median time to onset of Grade 3 or 4 neutropenia was 45 days.

• Monitor neutrophil counts at least every 2 weeks for the first 2 months of UKONIQ and at least weekly in patients with neutrophil counts (Grade 3-4). Consider supportive care as appropriate. Withhold, reduce dose, or discontinue UKONIQ depending on the severity and persistence of neutropenia.

Diarrhea or Non-infectious Colitis

• Serious diarrhea or non-infectious colitis occurred in patients treated with UKONIQ. Any grade diarrhea or colitis occurred in 53% of 335 patients and Grade 3 occurred in 9%.

• The median time to onset for any grade diarrhea or colitis was 1 month (range: 1 day to 23 months), with 75% of cases occurring by 2.9 months.

• For patients with severe diarrhea (Grade 3, i.e., >6stools per day over baseline) or abdominal pain, stool with mucus or blood, change in bowel habits, or peritoneal signs, withhold UKONIQ until resolved and provide supportive care with antidiarrheals or enteric acting steroids as appropriate. Upon resolution, resume UKONIQ at a reduced dose. For recurrent Grade 3 diarrhea or recurrent colitis of any grade, discontinue UKONIQ. Discontinue UKONIQ for lifethreatening diarrhea or colitis

Hepatotoxicity

• Serious hepatotoxicity occurred in patients treated with UKONIQ. Grade 3 and 4 transaminase elevations (ALT and/or AST) occurred in 8% and<1%,respectively, in 335 patients. The median time to onset for Grade 3 or higher transaminase elevations was 2.2 months (range: 15 days to 4.7 months).

• Monitor hepatic function at baseline and during treatment with UKONIQ. For ALT/AST greater than 5 to less than 20 times ULN, withhold UKONIQ until return to less than 3 times ULN, then resume at a reduced dose. For ALT/AST elevation greater than 20 times ULN, discontinue UKONIQ.

Severe Cutaneous Reactions

Severe cutaneous reactions, including a fatal case of exfoliative dermatitis, occurred in patients treated with UKONIQ. Grade 3 cutaneous reactions occurred in 2% of 335 patients and included exfoliative dermatitis, erythema, and rash (primarily maculo-papular) The median time to onset of Grade 3 or higher cutaneous reaction was 15 days (range: 9 days to 6.4 months).

• Monitor patients for new or worsening cutaneous reactions. Review all concomitant medications and discontinue any potentially contributing medications. Withhold UKONIQ for severe (Grade 3) cutaneous reactions until resolution. Monitor at least weekly until resolved. Upon resolution, resume UKONIQ at a reduced dose. Discontinue UKONIQ if severe cutaneous reaction does not improve, worsens, or recurs. Discontinue UKONIQ for life-threatening cutaneous reactions or SJS, TEN, or DRESS of any grade.Provide supportive care as appropriate.

Allergic Reactions Due to Inactive Ingredient FD&C Yellow No. 5

• UKONIQ contains FD&C Yellow No. 5 (tartrazine), which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. Although the overall incidence of FD&C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity.

Embryo-Fetal Toxicity

Based on findings in animals and its mechanism of action, UKONIQ can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of umbralisib to pregnant mice during the period of organogenesis caused adverse developmental outcomes including embryo-fetal mortality and fetal malformations at maternal exposures comparable to those in patients at the recommended dose of 800 mg. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment and for one month after the last dose.

Adverse Reactions

Clinical Trials Experience

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

Postmarketing Experience

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

Drug Interactions

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

Use in Specific Populations

Pregnancy

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

Labor and Delivery

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

Nursing Mothers

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

Pediatric Use

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

Geriatic Use

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

Gender

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

Race

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

Renal Impairment

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

Hepatic Impairment

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

Females of Reproductive Potential and Males

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

Immunocompromised Patients

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

Administration and Monitoring

Administration

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

Monitoring

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

IV Compatibility

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

Overdosage

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

Mechanism of Action

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

Structure

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

Pharmacodynamics

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

Pharmacokinetics

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

Nonclinical Toxicology

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

Clinical Studies

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

How Supplied

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

Storage

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

Precautions with Alcohol

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

Brand Names

UKONIQ

Look-Alike Drug Names

There is limited information regarding Umbralisib 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.