Copanlisib
Indications
Copanlisib is used for:
Follicular Lymphoma
Adult Dose
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)
Continue treatment until disease progression or unacceptable toxicity
Child Dose
Renal Dose
Administration
IV Preparation
IV infusion only
Do not mix or inject copanlisib with other drugs or other diluents
Reconstitute copanlisib with 4.4 mL of sterile 0.9% NaCl solution for a concentration of 15 mg/mL
Inspect visually for discoloration and particulate matter; the solution should be colorless to slightly yellowish after reconstitution
Further dilute the reconstituted solution in 100 mL sterile 0.9% NaCl solution for injection
Withdraw required amount of the reconstituted solution for the desired dosage
Inject the contents of the syringe into the patient infusion bag of 100 mL sterile 0.9% NaCl solution
Mix the dose well by inverting
Use reconstituted and diluted copanlisib immediately or store the reconstituted solution in the vial or diluted solution in the infusion bag at 2-8°C (36-46°F) for up to 24 hours before use
Avoid exposure of the diluted solution to direct sunlight
IV Administration
Allow the product to come to room temperature before use following refrigeration
Infuse over 1 hr
Contra Indications
Precautions
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
Pregnancy-Lactation
Pregnancy
Based on animal studies and the mechanism of action, copanlisib can cause fetal harm when administered to a pregnant woman
Advise pregnant women of the potential risk to a fetus
Conduct pregnancy testing prior to initiation of treatment
Contraception
Advise female patients of reproductive potential to use highly effective contraception during treatment and for at least 1 month after the last dose
Advise male patients with female partners of reproductive potential to use highly effective contraception during and for at least 1 month after the last dose
Lactation
There are no data on the presence of copanlisib and/or metabolites in human milk, the effects on the breastfed child, or on milk production
Because of the potential for serious adverse reactions in a breastfed child from copanlisib, advise a lactating woman not to breastfeed during treatment with copanlisib and for at least 1 month after the last dose
Interactions
Adverse Effects
Side effects of Copanlisib :
>10%
Any grade
Hyperglycemia (54-95%)
Decreased hemoglobin and lymphocytes (78%)
Decreased white blood cells (WBCs) (71%)
Decreased platelets (65%)
Decreased neutrophils (63%)
Hypertriglyceridemia (58%)
Hypophosphatemia (44%)
Leukopenia (36%)
Decreased general strength and energy (36%)
Diarrhea (36%)
Hypertension (35%)
Neutropenia (32%)
Nausea (26%)
Hyperuricemia (25%)
Thrombocytopenia (22%)
Grade 3
Hyperglycemia (43%)
Decreased lymphocytes (27%)
Hypertension (27%)
Hyperuricemia (24%)
Decreased WBCs (18%)
Hyperphosphatemia (15%)
Leukopenia (12%)
Lower respiratory tract infections (12%)
Decreased neutrophils (12%)
Grade 4
Leukopenia (15%)
Neutropenia (15%)
1-10%
Pneumonitis (9%)
Mucosal inflammation (8%)
Paresthesia and dysesthesia (7%)
Grade 3
Neutropenia (10%)
Thrombocytopenia (7%)
Serum lipase increased (7%)
Decreased platelets (7%)
Hypertriglyceridemia (5%)
Diarrhea (5%)
Decreased general strength and energy (4%)
Decreased hemoglobin (4%)
Stomatitis (2%)
Rash (1%)
Grade 4
Hyperglycemia (5%)
Lower respiratory tract infections (2%)
Decreased lymphocytes (2%)
Decreased WBCs (2%)
Decreased platelets (2%)
Thrombocytopenia (1%)
Hyperuricemia (1%)
Serum lipase increased (1%)
<1%
Nausea, grade 3
Rash, grade 4
Mechanism of Action
Pan class I phosphatidylinositol-3-kinase (PI3K) inhibitor with predominant inhibitory activity against PI3K-alpha and PI3K-delta isoforms expressed in malignant B cells; by inhibiting several key cell-signaling pathways may induce apoptosis and inhibition of proliferation of premalignant B cells and in turn cause tumor cell death