Umbralisib
Umbralisib Uses, Dosage, Side Effects, Food Interaction and all others data.
Marginal zone lymphoma is a rare, slowly progressing type of non-Hodgkin lymphoma initially treated with rituximab (an anti-CD20 drug), either alone or in combination with chemotherapy. Unfortunately, many patients experience a relapse or develop resistance to these drugs. Treatment options then become limited, and alternate treatments for the lymphoma are required to control disease progression. Follicular lymphoma is also treated with rituximab and other chemotherapeutic agents, but may show similar progression.
On February 5, 2021, the Food and Drug Administration granted accelerated approval to umbralisib, a kinase inhibitor for PI3K-delta and casein kinase CK1-epsilon, based on promising results from clinical trials. It is marketed as Ukoniq by TG Therapeutics and is approved for treating relapsing and refractory marginal cell lymphoma and follicular lymphoma in adults. Umbralisib inhibits casein kinase, a primary regulator of protein translation, kinase-1ε, distinguishing it from other lymphoma treatments and offering a promising therapy for patients experiencing relapsing or refractory disease. Continued approval may depend on confirmation of efficacy in clinical trials.
Umbralisib acts against against marginal zone lymphoma by interrupting the PI3K pathway; this is an essential pathway for B-cell receptor signaling responsible for the progression of lymphoma. In addition, Umbralisib inhibits other pathways involved in specific types of lymphoma, including the casein kinase pathway. An overall response rate of 55% was recorded during clinical trials and the rate of 1-year progression free survival from marginal zone lymphoma was 71%.
| Trade Name | Umbralisib |
| Availability | Discontinued |
| Generic | Umbralisib |
| Umbralisib Other Names | Umbralisib |
| Weight | 200mg |
| Type | Oral tablet |
| Formula | C31H24F3N5O3 |
| Weight | Average: 571.56 Monoisotopic: 571.183124142 |
| Protein binding | Umbralisib is more than 99.7% protein bound. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Umbralisib is a kinase inhibitor used to treat rare forms of refractory lymphoma.
Umbralisib is indicated to treat relapsed or refractory marginal zone lymphoma (MZL) in patients who have received at least one prior anti-CD20-based regimen. It is also indicated for the treatment of relapsed or refractory follicular lymphoma (FL) who have received at least three prior lines of systemic therapy.
Umbralisib is also used to associated treatment for these conditions: B-cell Follicular Lymphoma, Marginal Zone Lymphoma (MZL)
How Umbralisib works
The PI3K pathway is a deregulated in malignancies, leading to the overexpression of p110 isoforms (p110α, p110β, p110δ, p110γ) that induces malignant transformation in cells. Umbralisib inhibits several protein kinases, including PI3Kδ and casein kinase CK1ε. PI3Kδ is expressed in both healthy cells and malignant B-cells. CK1ε is believed to be involved in the pathogenesis of malignant cells, including lymphomas. This results in reduced progression of relapsed or refractory lymphoma. In biochemical assays, umbralisib inhibited a mutated form of ABL1. In vitro, umbralisib inhibits malignant cell proliferation, CXCL12-mediated cell adhesion, and CCL19-mediated cell migration.
Toxicity
The oral LD50 of umbralisib in rats is 3320 mg/kg. Overdose information is not readily available on prescribing information or the literature. In any overdose, supportive and symptomatic treatment should be provided as required.
Food Interaction
- Take with food. Food increases the bioavailability and concentration of umbralisib.
[Moderate] ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of umbralisib.
When a single oral dose of umbralisib was administered with a high-fat, high-calorie meal (approximately 917 calories; 171 calories from protein, 232 calories from carbohydrate, 502 calories from fat) in healthy subjects, umbralisib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 115% and 61%, respectively, compared to administration under fasted conditions.
MANAGEMENT: Umbralisib should be administered with food at approximately the same time each day.
Umbralisib Disease Interaction
Moderate: cutaneous reactions, infections, liver dysfunction, renal dysfunction
Volume of Distribution
The average apparent central volume of distribution of umbralisib is 312 L.
Elimination Route
Umbralisib is rapidly absorbed in the GI tract. The Tmax of umbralisib is about 4 hours. After consumption of a high-fat, high calorie meal with umbralisib, the AUC increased by 61% and the Cmax increased by 115%.
Half Life
The effective half-life of Umbralisib is about 91 hours.
Clearance
The average apparent clearance of umbralisib is 15.5 L/h.
Elimination Route
During pharmacokinetic studies, about 81% of the umbralisib dose was recovered in feces (17% unchanged). Approximately 3% was detected in the urine (0.02% unchanged) after a radiolabeled dose of 800 mg in healthy volunteers.
Innovators Monograph
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