Dosing & Uses
Dosage Forms & Strengths
injection, lyophilized powder for reconstitution
- 60 mg (single 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
Dosage Modifications
Coadministration of CYP3A4 inducers or inhibitors
Avoid concomitant use with strong CYP3A inducers
Concomitant use with strong CYP3A4 inhibitors: Reduce copanlisib dose to 45 mg
Infections
- Grade ≥3: Withhold until resolution
- Suspected pneumocystis jiroveci pneumonia (PJP) infection (all grades): Withhold treatment; if confirmed, treat infection until resolution, and then resume treatment at previous dose with concomitant PJP prophylaxis
Hyperglycemia
- Predose fasting blood glucose (FBG) ≥160 mg/dL or random/non-FBG ≥200 mg/dL: Withhold treatment until predose FBG ≤160 mg/dL or random/non-FBG ≤200 mg/dL
-
Predose or postdose blood glucose ≥500 mg/dL
- First occurrence: Withhold treatment until FBG is ≤160 mg/dL, or a random/non-FBG ≤200 mg/dL; then reduce dose from 60 mg to 45 mg and maintain at 45 mg
- Subsequent occurrences: Withhold treatment until FBG is ≤160 mg/dL, or a random/non-FBG ≤200 mg/dL; then reduce dose from 45 mg to 30 mg and maintain at 30 mg
- Discontinue treatment if it persists at 30 mg
Hypertension
- Predose blood pressure (BP) ≥150/90 mm Hg: Withhold treatment until BP <150/90 mm Hg based on 2 consecutive BP measurements at least 15 minutes apart
- Postdose elevated BP with life-threatening consequences: Discontinue treatment
-
Non-life threatening postdose blood pressure (BP) ≥150/90 mm Hg
- Antihypertensive treatment is not required: Continue treatment at previous dose
- Antihypertensive treatment is required: Consider dose reduction from 60 mg to 45 mg or from 45 mg to 30 mg
- Discontinue treatment if BP remains uncontrolled (BP >150/90 mm Hg) despite antihypertensive treatment
Noninfectious pneumonitis (NIP)
- Grade 2: Withhold copanlisib and treat NIP; resume treatment at 45 mg once NIP recovers to grade 1 or less
- Grade 2 recurs: Discontinue treatment
- Grade ≥3: Discontinue treatment
Neutropenia
- Absolute neutrophil count (ANC) 0.5-1.0 x 103 cells/mm3: Maintain dose; monitor ANC at least weekly
- ANC <0.5 x 103 cells/mm3: Withhold treatment; monitor ANC at least weekly until ANC ≥0.5 x 103 cells/mm3, then resume treatment at previous dose
- If ANC ≤0.5 x 103 cells/mm3 recurs, then reduce dose to 45 mg
Severe cutaneous reactions
- Grade 3: Withhold treatment until toxicity is resolved and reduce dose from 60 mg to 45 mg, or from 45 mg to 30 mg
- Life-threatening: Discontinue treatment
Thrombocytopenia
- <25 X 109/L: Withhold treatment; resume when platelet levels return to ≥75 x 109/L; reduce dose from 60 mg to 45 mg, or from 45 mg to 30 mg if recovery occurs within 21 days
- If recovery does not occur within 21 days, discontinue treatment
Other severe and non-life-threatening toxicities
- Grade 3: Withhold until toxicity is resolved and reduce dose from 60 mg to 45 mg, or from 45 mg to 30 mg
Hepatic impairment
- Mild (total bilirubin ≤1x ULN and AST >ULN, or total bilirubin >1-1.5x ULN and any AST): No dosage adjustment necessary
- Moderate (Child-Pugh B): Reduce dose to 45 mg
- Severe (Child-Pugh C): Not studied
Marginal Zone Lymphoma (Orphan)
Orphan designation for splenic, nodal, and extranodal subtypes of marginal zone lymphoma
Sponsor
- Bayer HealthCare Pharmaceuticals, Inc; 100 Bayer Boulevard, PO Box 915; Hanover, New Jersey 07981
Safety and efficacy has not been established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
>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
Warnings
Contraindications
None
Cautions
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) 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, rash [including maculopapular rash]) may occur; withhold, reduce dose, or discontinue treatment depending on the severity and persistence of severe cutaneous reactions
Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose
Drug interaction overview
- Concomitant use of copanlisib with strong CYP3A4 inducers may decrease copanlisib’s AUC and peak plasma concentrations
- Coadministration with strong CYP3A5 inhibitors may increase the AUC of copanlisib
Pregnancy
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
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Nutrition
Pharmacology
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
Absorption
Peak plasma concentration: 463 ng/mL
AUC (0-25): 1570 ng·hr/mL
Distribution
Protein binding: 84.2% (mainly albumin)
Vd: 871 L
Metabolism
Metabolism is mediated by CYP3A (~90%) and CYP1A1 (<10%)
Elimination
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%)
Administration
IV Compatibilities
0.9% NaCl
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 (see prescribing information for further information)
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
Storage
Unused vials: Refrigerate at 2-8°C (36-46°F)
Diluted solutions: Refrigerate at 2-8°C (36-46°F) for up to 24 hours before use
Protect from direct sunlight
Images
Patient Handout
Formulary
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