Version May 2024
The FDA has withdrawn its approval for Ukoniq (umbralisib) due to safety concerns. Health care providers should stop prescribing Ukoniq and switch patients to alternative treatments. Patients currently taking Ukoniq should be informed of the increased risk of death seen in the UNITY-CLL clinical trial and advised to stop taking the medicine. In limited circumstances in which a patient may be receiving benefit from Ukoniq, TG Therapeutics plans to make it available under expanded access.
Further information may be found at https://www.fda.gov/drugs/drug-safety-and-availability/fda-approval-lymphoma-medicine-ukoniq-umbralisib-withdrawn-due-safety-concerns.
Note: Updated findings from a clinical trial demonstrated safety concerns for umbralisib and as a result the FDA determined the risks of umbralisib treatment outweigh benefits; due to this, the manufacturer has voluntarily withdrawn umbralisib from the market.
Prophylaxis: Administer P. jirovecii pneumonia prophylaxis during umbralisib therapy; consider antiviral prophylaxis to prevent cytomegalovirus (CMV) infection, including CMV reactivation.
Follicular lymphoma, relapsed or refractory: Oral: 800 mg once daily until disease progression or unacceptable toxicity (Ref).
Marginal zone lymphoma, relapsed or refractory: Oral: 800 mg once daily until disease progression or unacceptable toxicity (Ref).
Missed dose: If a dose is missed, administer as soon as remembered if <12 hours until the next dose. If vomiting occurs, do not take an additional dose; continue with the next scheduled dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Kidney function estimated by the Cockcroft-Gault equation.
CrCl ≥30 mL/minute: No dosage adjustment is necessary.
CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Hepatic impairment prior to treatment initiation:
Mild impairment (total bilirubin ≤ ULN and AST > ULN or total bilirubin >1 to 1.5 times ULN and any AST): No dosage adjustment is necessary.
Moderate (total bilirubin >1.5 to 3 times ULN and any AST) or severe (total bilirubin >3 times ULN and any AST) impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Hepatotoxicity during treatment:
AST or ALT >5 to <20 times ULN: Withhold umbralisib until recovery to <3 times ULN, then resume at a reduced dose (see "Dosing: Adjustment for Toxicity" for dose reduction levels).
AST or ALT >20 times ULN: Discontinue umbralisib.
|
Dose level |
Dose |
|---|---|
|
Initial (usual) dose |
800 mg once daily |
|
First dose reduction |
600 mg once daily |
|
Second dose reduction |
400 mg once daily |
|
Subsequent |
Permanently discontinue umbralisib if unable to tolerate 400 mg once daily. |
|
Adverse reaction |
Severity |
Dose modification |
|---|---|---|
|
Hematologic toxicity | ||
|
Neutropenia |
ANC 500 to 1,000/mm3 |
Continue umbralisib; if ANC 500 to 1,000/mm3 recurs (or is persistent), then withhold umbralisib until ANC is ≥1,000/mm3, then resume at the same dose. Consider supportive care as appropriate. |
|
ANC <500/mm3 |
Withhold umbralisib until ANC is ≥500/mm3, then resume at the same dose. If ANC <500/mm3 recurs, withhold umbralisib until ANC is ≥500/mm3, then resume at a reduced dose. Consider supportive care as appropriate. | |
|
Thrombocytopenia |
Platelets 25,000 to <50,000/mm3 with bleeding or platelets <25,000/mm3 |
Withhold umbralisib until platelets are ≥25,000/mm3 and bleeding (if applicable) resolves, then resume at the same dose. If platelets 25,000 to <50,000/mm3 with bleeding or platelets <25,000/mm3 recurs, withhold umbralisib until platelets are ≥25,000/mm3 and bleeding resolves (if applicable), then resume at a reduced dose. |
|
Nonhematologic toxicity | ||
|
Diarrhea or noninfectious colitis |
Mild or moderate diarrhea (up to 6 stools/day over baseline) or asymptomatic (grade 1) colitis |
If persistent, withhold umbralisib until resolved, then resume at the same or reduced dose. If recurrence, withhold umbralisib until resolved, then resume at a reduced dose. |
|
Severe diarrhea (>6 stools/day over baseline) or abdominal pain, stool with mucus or blood, change in bowel habits, peritoneal signs |
Withhold umbralisib until resolved, then resume at a reduced dose. For recurrent severe diarrhea or recurrent colitis of any grade, discontinue umbralisib. Provide supportive care with antidiarrheals or enteric-acting steroids as indicated. | |
|
Life-threatening |
Discontinue umbralisib. Provide supportive care with antidiarrheals or enteric-acting steroids as indicated. | |
|
Infection (including opportunistic infection) |
Grade 3 or 4 |
Withhold umbralisib until resolved, then resume at the same or reduced dose. |
|
P. jirovecii pneumonia (PCP) |
For suspected PCP, withhold umbralisib until evaluated. For confirmed PCP, discontinue umbralisib. | |
|
Cytomegalovirus infection or viremia |
Withhold umbralisib until infection or viremia resolves, then resume at the same or reduced dose. | |
|
Severe cutaneous reactions |
Severe |
Withhold umbralisib until resolved, then resume at a reduced dose or discontinue. If recurrence after rechallenge, discontinue umbralisib. Evaluate all concomitant medications; if possible, discontinue those that may potentially contribute to cutaneous reactions. Administer supportive care as clinically necessary. |
|
Life-threatening |
Discontinue umbralisib. Administer supportive care as clinically necessary. | |
|
Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (any grade) |
Discontinue umbralisib. Administer supportive care as clinically necessary. | |
|
Other adverse reactions |
Severe |
Withhold umbralisib until resolved, then resume at the same or reduced dose. |
|
Life-threatening |
Discontinue umbralisib. | |
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Edema (14%)
Dermatologic: Skin rash (18%)
Endocrine & metabolic: Decreased serum potassium (21%)
Gastrointestinal: Abdominal pain (19%), decreased appetite (19%), diarrhea (≤58%; severe diarrhea: ≤4%), nausea (38%), vomiting (21%)
Hematologic & oncologic: Decreased hemoglobin (27%; grades 3/4: 3%), neutropenia (≥15%; grade 3: 9%; grade 4: 9%), thrombocytopenia (26%; grades 3/4: 4%)
Hepatic: Increased serum alanine aminotransferase (33%), increased serum aspartate aminotransferase (32%)
Nervous system: Fatigue (41%), insomnia (14%)
Neuromuscular & skeletal: Musculoskeletal pain (27%)
Renal: Increased serum creatinine (79%)
Respiratory: Upper respiratory tract infection (21%)
1% to 10%:
Dermatologic: Severe dermatological reaction (grade 3: 2%; including erythema of skin, maculopapular rash)
Gastrointestinal: Colitis (2%)
Genitourinary: Urinary tract infection (2% to 9%)
Infection: Infection (grade ≥3: 10%), sepsis (2% to 3%)
Respiratory: Dyspnea (7%), pneumonia (3% to 6%)
Miscellaneous: Fever (10%)
<1%:
Dermatologic: Exfoliative dermatitis
Respiratory: Pneumonitis
Frequency not defined: Hepatic: Severe hepatotoxicity
There are no contraindications listed in the manufacturer's labeling.
Concerns related to adverse effects:
• Bone marrow suppression: Serious neutropenia has occurred with umbralisib, including grade 3 and 4 cases. The median time to onset of ≥ grade 3 neutropenia was 45 days.
• Dermatologic toxicity: Serious cutaneous reactions, including grade 3 reactions and a fatal case of exfoliative dermatitis, have been reported with umbralisib. Grade 3 cutaneous reactions have included cases of exfoliative dermatitis, erythema, and rash (primarily maculopapular). The median time to ≥ grade 3 cutaneous reaction onset was 15 days (range: 9 days to 6.4 months). Evaluate all concomitant medications; discontinue those which may potentially contribute to cutaneous reactions.
• GI toxicity: Serious diarrhea or noninfectious colitis has occurred with umbralisib; any grade diarrhea or colitis was reported in ~50% of patients, while grade 3 toxicity occurred in <10%. The median time to any grade diarrhea or colitis was 1 month (range: 1 day to 23 months); 75% of cases occurred in the first 3 months of therapy.
• Hepatotoxicity: Serious hepatotoxicity has occurred with umbralisib, including grade 3 and 4 transaminase elevations. The median time to ≥ grade 3 AST and/or ALT elevations was 2.2 months (range: 15 days to 4.7 months).
• Infection: Serious and fatal infections have occurred with umbralisib, including ≥ grade 3 infection. The most commonly reported ≥ grade 3 infections were pneumonia, sepsis, and urinary tract infections. The median time to onset of ≥ grade 3 infection was 2.4 months (range: 1 day to 21 months). Administer Pneumocystis jirovecii pneumonia (PCP) prophylaxis during umbralisib treatment. Consider antiviral prophylaxis to prevent cytomegalovirus (CMV) infection, including CMV reactivation.
Special populations:
• Older adult: Patients ≥65 years of age experienced a higher incidence of serious adverse reactions (including infections) compared to patients <65 years of age.
Dosage form specific issues:
• Yellow dye: Umbralisib contains FD&C Yellow No. 5 (tartrazine), which may cause allergic-type reactions (including bronchial asthma) in some patients. Tartrazine sensitivity is frequently seen in patients who also have aspirin hypersensitivity.
The manufacturer of Ukoniq, TG Therapeutics, has voluntarily withdrawn this product from sale. Limited distribution will occur through June 2022.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, Oral, as tosylate:
Ukoniq: 200 mg [DSC] [contains fd&c blue #1 (brilliant blue), fd&c yellow #5 (tartrazine)]
No
Tablets (Ukoniq Oral)
200 mg (per each): $159.00
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
For patients receiving a benefit from umbralisib treatment prior to its market withdrawal, the manufacturer planned to allow continued access via an expanded access program; contact the manufacturer, TG Therapeutics, for information.
Oral: Administer with food at the same time each day. Swallow whole; do not crush, break, cut, or chew.
This medication is not on the NIOSH (2016) list; however, it may meet the criteria for a hazardous drug. Umbralisib may cause reproductive toxicity and teratogenicity.
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Ukoniq: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/213176s000lbl.pdf#page=19
Note: Updated findings from a clinical trial demonstrated safety concerns for umbralisib and as a result the FDA determined the risks of umbralisib treatment outweigh benefits; due to this, the manufacturer has voluntarily withdrawn umbralisib from the market.
Follicular lymphoma, relapsed or refractory: Treatment of relapsed or refractory follicular lymphoma in adults who have received at least 3 prior lines of systemic therapy.
Marginal zone lymphoma, relapsed or refractory: Treatment of relapsed or refractory marginal zone lymphoma in adults who have received at least 1 prior anti-CD20-based regimen.
Sound-alike/look-alike issues:
Umbralisib may be confused with alpelisib, copanlisib, duvelisib, idelalisib, upadacitinib.
High alert medication:
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
Substrate of CYP1A2 (minor), CYP2C9 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification
Mumps- Rubella- or Varicella-Containing Live Vaccines: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification
Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 3 after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Verify pregnancy status prior to treatment initiation. Patients who may become pregnant should use effective contraception during therapy and for 1 month after the last dose of umbralisib. Patients with partners who may become pregnant should also use effective contraception during therapy and for 1 month after the last umbralisib dose.
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to umbralisib may cause fetal harm.
It is not known if umbralisib is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during treatment and for 1 month after the last umbralisib dose.
CBC (obtain neutrophil counts at least every 2 weeks for the first 2 months and at least weekly if ANC <1,000/mm3); liver function tests. Evaluate pregnancy status prior to treatment initiation in females of reproductive potential. Monitor for signs/symptoms of new or worsening infection (including P. jirovecii pneumonia [PCP] and cytomegalovirus [CMV]; if treatment is resumed following CMV infection, monitor for CMV reactivation by PCR or antigen test at least monthly), GI toxicity (diarrhea or noninfectious colitis), and severe cutaneous reactions (new or worsening). Monitor adherence.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Umbralisib is a dual inhibitor of phosphatidylinositol-3-kinase-delta (PI3Kδ) and casein kinase 1 epsilon (CK1ε) with improved selectivity for the PI3Kδ isoform (Zinzani 2020). PI3Kδ is expressed in both normal and malignant B-cells; CK1ε may also be involved in the pathogenesis of cancer cells (including lymphoid malignancies). In vitro, umbralisib inhibited cell proliferation, CXCL12-mediated cell adhesion, and CCL19-mediated cell migration in lymphoma cell lines.
Absorption: Administration of a single umbralisib dose with a high-fat, high calorie meal (~917 calories with 171 calories from protein, 232 calories from carbohydrates, and 502 calories from fat) increased the umbralisib AUC and Cmax by 61% and 115%, respectively (compared to fasting conditions).
Distribution: Vd: 312 L.
Protein binding: ≥99.7%.
Metabolism: Primarily hepatic via CYP2C9, CYP3A4, and CYP1A2.
Half-life elimination: 91 hours.
Time to peak: ~4 hours.
Excretion: Feces: ~81% (17% as unchanged drug); urine: 3% (<1% as unchanged drug).
Clearance: 15.5 L/hour.
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