Mechanism of effect
Follicular lymphoma is a B-cell lymphoma that is one of the most common type of non-Hodgkin lymphoma (NHL). It involves unregulated growth and proliferation of lymphocytes that eventually may travel to other organs including the lymph nodes, spleen, and the bone marrow, to form tumors. The phosphatidylinositol 3-kinase (PI3K)-mediated pathway is involved in promoting cell survival proliferation and differentiation however abberant activation of this pathway may lead to tumorigenesis. Copanlisib mediates an inhibitory action on p110α and p110δ isoforms of phosphatidylinositol-3-kinase (PI3K) expressed in malignant B cells.
It induces tumor cell death via apoptosis and inhibits the proliferation of primary malignant B cell lines. Copanlisib inhibits several key cell-signaling pathways, including B-cell receptor (BCR) signaling, CXCR12 mediated chemotaxis of malignant B cells, and NFκB signaling in lymphoma cell lines.
Pharmacokinetics
Peak plasma concentration: 463 ng/mL
AUC (0-25): 1570 ng·hr/mL
Protein binding: 84.2% (mainly albumin)
Vd: 871 L
Metabolism is mediated by CYP3A (~90%) and CYP1A1 (<10%)
Half-life: 39.1 hr
Clearance: 17.9 L/hr
Excreted ~50% as unchanged compound and 50% as metabolites
Excretion, unchanged compound: Feces (30%), urine (15%)
Dosage
Adult
Follicular Lymphoma
Indicated for relapsed follicular lymphoma (FL) in patients who have received at least 2 prior systemic therapies
60 mg IV on Days 1, 8, and 15 of a 28-day treatment cycle on an intermittent schedule (21 days on and 7 days off)
Pediatric
Safety and efficacy has not been established
Side effects
High Blood Pressure , Diarrhea , nausea , pneumonia , Leukopenia , thrombocytopenia , RashInteractions
Efavirenz , Oxecarbazepin , Itraconazole , Isoniazid , Imatinib , Bosentan , Primidone , Apalutamide , Elvitegravir , nafcillin , st. john's wort , stiripentol , Idelalisib , Tipranavir , Nicardipine , cobicistat , Delavirdine , Secobarbital , Fosamprenavir , Lopinavir , Palifermin , Indinavir , Butalbital and Acetaminophen , Fosphenytoin , Nefazodone , ritonavir , saquinavir , nelfinavir , nevirapine , mitotane , Rifapentine , Atazanavir , Darunavir , Grapefruit , Pentobarbital , Amobarbital , Voriconazole , Carbamazepine , Ketoconazole , Clarithromycin , Enzalutamide , Rifabutin , Posaconazole , Dexamethasone , Diltiazem , Rifampin , Phenobarbital , Phenytoin , lumacaftor and Ivacaftor , Etravirine , Dabrafenib , Mibefradil , Butabarbital , Lopinavir and Ritonavir , oleandomycin , Meningococcal conjugate vaccineAlerts
Serious, including fatal, infections may occur; the most common serious infection was pneumonia; monitor patients for signs/symptoms of infection and withhold treatment for grade 3 and higher infection
Grade 3 or 4 hyperglycemia (blood glucose 250 mg/dL or greater) reported; achieve optimal blood glucose control before starting each infusion; withhold, reduce dose, or discontinue treatment depending on the severity and persistence of hyperglycemia
Grade 3 hypertension (systolic 160 mm Hg or greater or diastolic 100 mm Hg or greater) may occur; optimal BP control should be achieved before starting each infusion; monitor BP preinfusion and postinfusion; withhold, reduce dose, or discontinue copanlisib depending on severity and persistence of hypertension
Noninfectious pneumonitis reported; withhold treatment and conduct a diagnostic examination of a patient who is experiencing pulmonary symptoms (eg, cough, dyspnea, hypoxia, interstitial infiltrates) on radiologic examination; withhold, reduce dose, or discontinue treatment depending on the severity and persistence of noninfectious pneumonitis
Grade 3 or 4 neutropenia may occur; withhold, reduce dose, or discontinue copanlisib depending on the severity and persistence of neutropenia
Serious cutaneous reaction events (eg, exfoliative dermatitis, exfoliative rash, pruritus, and rash [including maculopapular rash]) may occur; withhold, reduce dose, or discontinue treatment depending on the severity and persistence of severe cutaneous reactions
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