umbralisib

Action and Spectrum

Actions and Spectrum 

Action: 

The drug acts as a selective inhibitor of PI3Kδ, which is primarily expressed in hematopoietic cells, including B cells and T cells. By inhibiting PI3Kδ, drug interferes with the PI3K signaling pathway, which regulates cell proliferation, survival, and migration. 

Spectrum:  

The drug has demonstrated activity against various types of cancer, particularly hematological malignancies.   

Chronic Lymphocytic Leukemia (CLL): The drug  has been evaluated in CLL patients, including those with relapsed or refractory disease.   

Follicular Lymphoma: Extensive research has been conducted on this medication as a potential treatment for individuals experiencing relapsed or refractory follicular lymphoma. Clinical trials have consistently demonstrated favorable results, including long-lasting responses. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

(All grades) 

Upper respiratory tract infection (21%) 

Platelets decreased (26%) 

Fatigue (41%) 

Creatinine increased (79%) 

Diarrhea (58%) 

Neutrophils decreased (33%) 

Potassium decreased (21%) 

AST increased (32%) 

Hemoglobin decreased (27%) 

ALT increased (33%) 

Nausea (38%) 

Musculoskeletal pain (27%) 

Vomiting (21%) 

(Grade 3 or 4) 

Neutrophil decreased (16%) 

1-10% 

(All grades) 

Pyrexia (10%) 

Colitis (2%) 

Sepsis (3%) 

Urinary tract infection (9%) 

Pneumonia (6%) 

Dyspnea (7%) 

(Grade 3 or 4) 

Abdominal pain (3%) 

Potassium decreased (4%) 

Rash (3%) 

AST increased (7%) 

Hemoglobin decreased (3%) 

ALT increased (8%) 

Fatigue (3%) 

Diarrhea (10%) 

Platelets decreased (4%) 

<1% 

(Grade 3 or 4) 

Insomnia 

Upper respiratory tract infection 

Exfoliative dermatitis 

Vomiting 

Pneumonitis 

Nausea 

Edema 

Black Box Warning

Black Box Warning:  

None  

Contraindication / Caution

Contraindication/Caution: Hypersensitivity: 

The drug should not be used in individuals with a known hypersensitivity or allergy to umbralisib or any of its components. Allergic reactions can range from mild symptoms, such as rash and itching, to severe reactions, including difficulty breathing and anaphylaxis.  

Active Infections: The drug is generally contraindicated in individuals with active bacterial, fungal, or viral infections.  

Pregnancy and Breastfeeding: The drug can potentially harm the developing fetus and may pass into breast milk. Therefore, it is generally not recommended for use during pregnancy or while breastfeeding.   

Severe Liver Dysfunction: The drug is metabolized by the liver, so individuals with severe liver dysfunction may experience increased exposure to the drug. It is generally recommended to avoid umbralisib in patients with severe hepatic impairment.   

Concomitant Use of Strong CYP3A4 Inhibitors: The drug is metabolized by the enzyme CYP3A4. Concurrent use of strong CYP3A4 inhibitors, such as certain antifungal medications (e.g., ketoconazole) or HIV protease inhibitors (e.g., ritonavir), can significantly increase umbralisib blood levels.

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: N/A 

Lactation: Excreted into human milk is unknown 

Pregnancy Categories:         

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester. 

Category B: There were a lack of studies on pregnant women and no evidence of risk to the fetus in animal experiments.   

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.   

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category

Pharmacology

Pharmacology:  

umbralisib is a small molecule inhibitor that targets multiple signaling pathways involved in the growth and survival of cancer cells. It is primarily used as a targeted therapy for certain types of lymphomas. 

Pharmacodynamics:  

PI3Kδ Inhibition: The drug selectively inhibits phosphoinositide 3-kinase delta (PI3Kδ), an enzyme that plays a crucial role in signaling pathways involved in the proliferation and survival of malignant cells. By inhibiting PI3Kδ, umbralisib disrupts these pathways, leading to the suppression of cancer cell growth and survival. 

Dual Inhibition of CK1ε and CK1δ: In addition to PI3Kδ inhibition, The drug also inhibits the activity of casein kinase 1 epsilon (CK1ε) and casein kinase 1 delta (CK1δ). These kinases regulate various cellular processes, including cell cycle progression and gene expression. Inhibition of CK1ε and CK1δ by umbralisib further contributes to its anti-cancer effects.   

Pharmacokinetics: 

Absorption 

After oral ingestion, it is absorbed from the gastrointestinal tract into the bloodstream.  

Distribution 

The drug is expected to distribute throughout the body after absorption. It may bind to plasma proteins to varying degrees, which can influence its distribution.  

Metabolism 

 The drug is primarily metabolized in the liver by enzymes belonging to the cytochrome P450 (CYP) family, particularly CYP3A4. metabolism results in the formation of several metabolites, including active and inactive forms.  

Excretion and elimination 

The drug and its metabolites are eliminated from the body predominantly through feces (via biliary excretion) and to a lesser extent through urine. The exact percentages of excretion through each route and the elimination half-life of umbralisib have not been extensively reported. 

Adminstartion

Administration:  

The administration of this drug should always be done under the qualified professional. 

The drug is available in the form of oral tablets, which are typically taken once daily with or without food.

Patient Information Leaflet

Patient information leaflet 

Generic Name: umbralisib 

Why do we use umbralisib?  

Mantle cell lymphoma (MCL): The drug is approved for the treatment mantle cell lymphoma.It can be used as a single-agent treatment or in combination with other medications. 

Marginal zone lymphoma (MZL): The drug is approved for the treatment of adult patients marginal zone lymphoma.  

Chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL): The drug is investigated in clinical trials for the treatment of CLL/SLL. Preliminary results have shown promising activity in this setting, but further research is needed to establish its efficacy and safety.