Drug information of Idelalisib

Mechanism of effect

Idelalisib specifically inhibits P110δ, the delta isoform of the enzyme phosphatidylinositol-4,5-bisphosphate 3-kinase, also known as PI-3K. The PI-3Ks are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer.

In contrast to the other class IA PI3Ks p110α and p110β, p110δ is principally expressed in leukocytes (white blood cells) and is important for the function of T cells, B cell, mast cells and neutrophils. By inhibiting this enzyme, idelalisib induces apoptosis of malignant cells and inhibits several cell signaling pathways, including B-cell receptor (BCR) signaling and C-X-C chemokine receptors type 5 and type 4 signalling, which are involved in trafficking and homing of B-cells to the lymph nodes and bone marrow. Treatment of lymphoma cells with idelalisib has been shown to result in inhibition of chemotaxis and adhesion, and reduced cell viability

Pharmacokinetics

Absorption: Following oral administration, the median Tmax was observed at 1.5 hours.

Volume of distribution:23 L

Protein binding: Idelalisib is greater than 84% bound to human plasma proteins with no concentration dependence.

Metabolism:Idelalisib is metabolized by aldehyde oxidase and CYP3A to its major metabolite GS-563117, which is inactive against P110δ. Idelalisib is also metabolized to a minor extent by UGT1A4.

Route of elimination:Following a single dose of 150 mg of [14C] idelalisib, 78% and 14% of the radioactivity was excreted in feces and urine, respectively. GS-563117, idelalisib's major metabolite, accounted for 49% of the radioactivity in the urine and 44% in the feces.

Half life:The terminal elimination half-life is 8.2 hours.

Clearance:14.9 L/hr

Dosage

Adult

Chronic Lymphocytic Leukemia

Indicated, in combination with rituximab, for relapsed chronic lymphocytic leukemia (CLL) in patients for whom rituximab alone would be considered appropriate therapy due to other comorbidities

Starting dose: 150 mg PO BID; continue treatment until disease progression or unacceptable toxicity

Follicular B-cell Non-Hodgkin Lymphoma

Accelerated approval for relapsed follicular B-cell non-Hodgkin lymphoma (FL) in patients who have received at least 2 prior systemic therapies

Starting dose: 150 mg PO BID; continue treatment until disease progression or unacceptable toxicity

Small Lymphocytic Lymphoma

Accelerated approval for relapsed small lymphocytic lymphoma (SLL) in patients who have received at least 2 prior systemic therapies

Starting dose: 150 mg PO BID; continue treatment until disease progression or unacceptable toxicity

Side effects

Sinusitis , Pain , Diarrhea , Headache , nausea , fever , Increased ALT , pneumonia , Rash

Interactions

Cetuximab , Midazolam , Chlordiaze poxide , Calcitriol , fentanyl , Ranolazine , Axitinib , nelfinavir , eletriptan , Apomorphine , Apixaban , Quinine , Mefloquine , Felbamate , Erythromycin , Irinotecan , Infliximab , Budesonide , Deferiprone , Deflazacort , Adalimumab , Mifepristone , Alfentanil , Nimodipine , Carbamazepine , Colchicine , Clozapine , Daclatasvir , eplerenone , Docetaxel , Cisapride , Cilostazol , Cyclosporine , Fingolimod , Lovastatin , brigatinib , Rasburicase , Linagliptin , nasal Mometasone , Efavirenz , Necitumumab , Copanlisib , Tipranavir , Simeprevir , Ulipristal , Etravirine , Dabrafenib , Estropipate , Acalabrutinib , Saxagliptin , Maraviroc , Halofantrine , Darifenacin , Nicardipine , Nisoldipine , Fostamatinib , Fesoterodine , Apremilast , Alfuzosin , Pazopanib , Palbociclib , Benzphetamine , Isradipine , Ixazomib , Pimavanserin , Tasimelteon , Dexlansoprazole , trabectedine , trametinib , Ramucirumab , Duvelisib , Apalutamide , elagolix , Flibanserin , Crizotinib , Avanafil , Entrectinib , atovaquone/proguanil , Cabozantinib , Cariprazine , Cobimetinib , Levomilnacipran , Temsirolimus , ELBASVIR/GRAZOPREVIR , Larotrectinib , gilteritinib , glasdegib , Abemaciclib , Nitrendipine , Triphasic , Eliglustat , riociguat , Gefitinib , Dasatinib , Remdesivir , Cannabidiol , vemurafenib , Meningococcal conjugate vaccine , voxelotor , silodosin , Asunaprevir , Capmatinib

Alerts

• Fatal and/or serious hepatotoxicity occurred in 16-18% of treated patients; monitor hepatic function before and during treatment; interrupt and then reduce or discontinue as recommended (see Dosage Modifications)
• Fatal and/or serious diarrhea, or colitis occurred in 14-20% of treated patients; monitor prior to and during treatment; interrupt and then reduce or discontinue idelalisib if symptoms/laboratory evidence appears (see Dosage Modifications)
• Fatal and serious pneumonitis reported in 4% of treated patients; monitor for pulmonary symptoms and bilateral interstitial infiltrates; interrupt or discontinue idelalisib if pneumonitis suspected (see Dosage Modifications)
• Fatal and/or serious infections occurred in 21-48% of treated patients; monitor for signs and symptoms of infection; interrupt if infection is suspected (see Dosage modifications)
• Fatal and serious intestinal perforation reported; discontinue if intestinal perforation is suspected

Points of recommendation

You may have more chance of getting an infection. Wash hands often. Stay away from people with infections, colds, or flu.

Have blood work checked as you have been told by the doctor. Talk with the doctor.

If you are 65 or older, use idelalisib with care. You could have more side effects.

This medicine may cause harm to the unborn baby if you take it while you are pregnant.

Use birth control that you can trust during treatment and for 1 month after treatment ends.

If you get pregnant while taking this medicine or within 1 month after your last dose, call your doctor right away.

Take with or without food.

Swallow whole. Do not chew, break, or crush.

To gain the most benefit, do not miss doses.

Keep taking this medicine as you have been told by your doctor or other health care provider, even if you feel well.

Pregnancy level

D

Related drugs

Copanlisib