Copanlisib is a phosphatidylinositol-3-kinase (PI3K) inhibitor approved for the treatment of adults with relapsed follicular lymphoma who have received at least 2 prior systemic treatments. It was granted an accelerated approval for use in these patients. Severe hyperglycemia and hypertension have been reported.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Emetic Risk
-Low
-Administer routine antiemetic prophylaxis prior to treatment.
Route-Specific Administration
Injectable Administration
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
Reconstitution
-Add 4.4 mL of sterile 0.9% Sodium Chloride injection to the 60-mg lyophilized powder vial by injecting the measured volume through the disinfected stopper surface using a 5-mL sterile syringe; the final concentration of the reconstituted vial is 15 mg/mL.
-Gently shake the vial for 30 seconds to dissolve the powder and then allow the vial to stand for 1 minute letting the bubbles rise to the surface; repeat this procedure if any undissolved powder is observed.
-The solution will be colorless to slightly yellowish after reconstitution.
-Storage of reconstituted vial: if not diluted immediately, store refrigerated at 2 to 8 degrees C (36 to 46 degrees F) for up to 24 hours before use; protect from direct sunlight.
Dilution
-Into an infusion bag containing 100 mL of sterile 0.9% Sodium Chloride injection, add the appropriate volume (based on the desired dose) from the reconstituted vial as follows:
60-mg dose: 4 mL
45-mg dose: 3 mL
30-mg dose: 2 mL
-Invert the infusion bag to mix.
-Discard any unused contents from the reconstituted vial.
-Storage of diluted admixture: if not used immediately, store refrigerated at 2 to 8 degrees C (36 to 46 degrees F) for up to 24 hours (from vial reconstitution) before use; protect from direct sunlight.
Intravenous (IV) Infusion
-Allow the diluted admixture in the infusion bag to warm to room temperature (if stored in refrigerator) prior to administration.
-Administer as an IV infusion over 1 hour.
-Do not mix or inject copanlisib with other drugs or diluents.
Serious infection occurred in 19% of patients who received copanlisib monotherapy (n = 317); some cases were fatal. Monitor patients for signs and symptoms of infection; hold therapy for grade 3 or higher infection. Pneumocystis jiroveci pneumonia (PJP) was reported in 0.6% of patients treated with copanlisib monotherapy. Hold therapy if PJP is suspected. If PJP diagnosis is confirmed, treat the infection until resolution and then resume copanlisib at the previous dose and give PJP prophylaxis for the duration of therapy. Additionally, grade 1 or 2 cytomegalovirus (CMV) reactivation or infection occurred in 0.97% of patients who received copanlisib monotherapy. Monitor for CMV infection in patients with a history of CMV; interrupt therapy if CMV infection or viremia occurs. After resolution of viremia, treatment with copanlisib may be resumed at the previous dose with CMV monitoring by PCR or antigen test at least monthly. In a pooled analysis from clinical trials, lower respiratory tract infection (e.g., pneumonia, bronchopulmonary aspergillosis) occurred in 21% of patients with follicular lymphoma or other hematologic malignancies who received copanlisib (n = 168); grade 3 or 4 lower respiratory tract infection was reported in 14% of patients.
Hyperglycemia has been reported commonly with copanlisib therapy. Monitor blood glucose levels before and after the copanlisib infusion. Therapy interruption, dose reduction, or therapy discontinuation may be necessary in patients who develop hyperglycemia. Grade 3 or 4 hyperglycemia (i.e., blood glucose level of 250 mg/dL or higher) occurred in 41% of patients who received copanlisib monotherapy (n = 317); serious hyperglycemic events were reported in 2.8% of patients. Infusion-related hyperglycemia has been reported, typically 5 to 8 hours after the copanlisib infusion; additionally, 17.7% of patients had persistent blood glucose level elevations at 1 day post infusion. Of the 155 patients who had a baseline HbA1c level less than 5.7%, 10% of patients had a HbA1c level greater than 6.5% at the end of copanlisib treatment. In a pooled analysis from clinical trials, hyperglycemia occurred in 54% of patients with follicular lymphoma or other hematologic malignancies who received copanlisib (n = 168); grade 3 or 4 hyperglycemia was reported in 39% of patients. In a multicenter, phase II trial, 7 of 20 patients (35%) with diabetes mellitus developed grade 4 hyperglycemia following treatment with copanlisib.
Grade 3 hypertension (i.e., systolic blood pressure (SBP) of 160 mmHg or greater or diastolic blood pressure (DBP) of 100 mmHg or greater) occurred in 26% of patients who received copanlisib monotherapy (n = 317); serious hypertensive events occurred in 0.9% of patients. Monitor blood pressure before and after the copanlisib infusion; optimal blood pressure control should be achieved prior to each dose. Therapy interruption, dose reduction, or therapy discontinuation may be necessary in patients who develop hypertension. The mean increase in systolic (+16.8 mmHg) and diastolic (+7.8 mmHg) blood pressure has been observed at 2 hours post-infusion on day of cycle 1 of copanlisib therapy; blood pressure typically remained elevated for 6 to 8 hours after the start of the infusion. In a pooled analysis from clinical trials, hypertension (including secondary hypertension) occurred in 35% of patients with follicular lymphoma or other hematologic malignancies who received copanlisib (n = 168); grade 3 hypertension was reported in 27% of patients.
Noninfectious pneumonitis occurred in 5% of patients who received copanlisib monotherapy (n = 317). Hold therapy and evaluate patients who experience signs or symptoms of pneumonitis (e.g., cough, dyspnea, hypoxia, interstitial infiltrates on X-ray exam). Therapy interruption, dose reduction, or therapy discontinuation may be necessary in patients who develop noninfectious pneumonitis. The use of systemic corticosteroid may be beneficial in these patients. In a pooled analysis from clinical trials, pneumonitis was reported in 9% of patients with follicular lymphoma or other hematologic malignancies who received copanlisib (n = 168).
Grade 3 or 4 cutaneous reactions occurred in 3.4% of patients who received copanlisib monotherapy (n = 317); serious cutaneous reaction events (e.g., exfoliative dermatitis or rash, pruritus, and maculopapular rash) were reported in 0.9% of patients. Therapy interruption, dose reduction, or therapy discontinuation may be necessary in patients who develop severe skin reactions. In a pooled analysis from clinical trials, rash (unspecified) excluding exfoliative skin reactions occurred in 15% of patients with follicular lymphoma or other hematologic malignancies who received copanlisib (n = 168); grade 3 or 4 rash was reported in less than 2% of patients.
Hematologic toxicity has been reported with copanlisib therapy. Monitor complete blood counts at least weekly during treatment. Therapy interruption, dose reduction, or therapy discontinuation may be necessary in patients who develop severe neutropenia or thrombocytopenia. Grade 3 or 4 neutropenia occurred in 24% of patients who received copanlisib monotherapy (n = 317); serious neutropenic events were reported in 1.3% of patients. In a pooled analysis from clinical trials, leukopenia (36%; grade 3 or 4, 27%), neutropenia including febrile neutropenia (32%; grade 3 or 4, 25%), thrombocytopenia (22%; grade 3 or 4, 8%), anemia/decreased hemoglobin level (78%; grade 3, 4%), and lymphopenia/decreased lymphocyte level (78%; grade 3 or 4, 29%) were reported in patients with follicular lymphoma or other hematologic malignancies who received copanlisib (n = 168).
In a pooled analysis from clinical trials, hypertriglyceridemia occurred in 58% of patients with follicular lymphoma or other hematologic malignancies who received copanlisib (n = 168); grade 3 hypertriglyceridemia was reported in 5% of patients.
In a pooled analysis from clinical trials, hypophosphatemia occurred in 44% of patients with follicular lymphoma or other hematologic malignancies who received copanlisib (n = 168); grade 3 hypophosphatemia was reported in 15% of patients.
In a pooled analysis from clinical trials, grade 3 or 4 hyperuricemia occurred in 25% of patients with follicular lymphoma or other hematologic malignancies who received copanlisib (n = 168).
In a pooled analysis from clinical trials, diarrhea (36%; grade 3, 5%), nausea (26%; grade 3, less than 1%), stomatitis (14%; grade 3, 2%), vomiting (13%), mucosal inflammation (8%), and increased lipase level (21%; grade 3 or 4, 8%) were reported in patients with follicular lymphoma or other hematologic malignancies who received copanlisib (n = 168).
In a pooled analysis from clinical trials, paresthesias and dysesthesia occurred in 7% of patients with follicular lymphoma or other hematologic malignancies who received copanlisib (n = 168).
Decreased general strength and energy (including fatigue and asthenia) occurred in 36% of patients with follicular lymphoma or other hematologic malignancies who received copanlisib (n = 168); grade 3 toxicity was reported in 4% of patients.
Serious infection has occurred in patients receiving copanlisib therapy; some cases were fatal. Monitor patients for signs and symptoms of infection; hold therapy for grade 3 or higher infection. Serious cases of pneumocystis jiroveci pneumonia (PJP) have occurred with copanlisib use; consider PJP prophylaxis in at-risk patients before initiating therapy. Hold therapy if PJP is suspected. If PJP diagnosis is confirmed, treat the infection until resolution and then resume copanlisib at the previous dose and give PJP prophylaxis for the duration of therapy. Cytomegalovirus (CMV) reactivation or infection has also occurred. Monitor for CMV infection during treatment in patients with a history of CMV; interrupt therapy if CMV infection or viremia occurs. After resolution of viremia, treatment with copanlisib may be resumed at the previous dose with CMV monitoring by PCR or antigen test at least monthly.
Severe hyperglycemia, elevated HbA1c, and infusion-related hyperglycemia have occurred with copanlisib therapy; additionally, serious hyperglycemic events have been reported. Monitor blood glucose levels before and after the copanlisib infusion. Therapy interruption, dose reduction, or therapy discontinuation may be necessary in patients who develop hyperglycemia. Blood glucose levels typically peak at 5 to 8 hours post infusion and then decline to baseline levels in most patients. Use copanlisib with caution in patients with diabetes mellitus. Initiate copanlisib therapy only after these patients have achieved optimal blood glucose control; monitor blood glucose levels in these patients closely.
Severe hypertension and infusion-related hypertension have occurred with copanlisib therapy; use copanlisib with caution in patients with pre-existing hypertension. Monitor blood pressure before and after the copanlisib infusion; optimal blood pressure control should be achieved prior to each dose. Therapy interruption, dose reduction, or therapy discontinuation may be necessary in patients who develop hypertension. A mean increase in systolic (+16.8 mmHg) and diastolic (+7.8 mmHg) blood pressure was observed at 2 hours post infusion on day 1 of cycle 1 of copanlisib therapy; blood pressure typically remained elevated for 6 to 8 hours after the start of the infusion.
Non-infectious pneumonitis has occurred with copanlisib therapy; use copanlisib with caution in patients with pre-existing pulmonary disease. Hold therapy and evaluate patients who experience signs or symptoms of pneumonitis (e.g., cough, dyspnea, hypoxia, and interstitial infiltrates on X-ray exam). Therapy interruption, dose reduction, or therapy discontinuation may be necessary in patients who develop pneumonitis. The use of systemic corticosteroid may be beneficial in these patients.
Severe hematologic toxicity including neutropenia and thrombocytopenia has occurred with copanlisib therapy. Monitor complete blood counts at least weekly during treatment. Therapy interruption, dose reduction, or therapy discontinuation may be necessary in patients who develop severe neutropenia or thrombocytopenia.
Severe cutaneous reactions (e.g., serious rash) have occurred with copanlisib therapy. Therapy interruption, dose reduction, or therapy discontinuation may be necessary in patients who develop severe skin reactions.
Reduce the dose of copanlisib in patients with moderate hepatic disease/impairment (Child-Pugh class B). Copanlisib has not been studied in patients with severe hepatic impairment (Child-Pugh class C). Evaluate liver function tests at baseline and as clinically appropriate during therapy.
Geriatric patients with follicular lymphoma or other hematologic malignancies had a higher incidence of serious adverse reactions compared with patients aged less than 65 years (30% vs. 23%) after treatment with single-agent copanlisib in a pooled analysis from clinical trials (n = 168). However, an initial dose adjustment is not necessary in patients 65 years or older.
Copanlisib can cause fetal harm when administered during pregnancy, based on its mechanism of action and data from animal studies. Females of reproductive potential should avoid becoming pregnant while receiving copanlisib. Advise patients to notify their healthcare provider immediately if they become pregnant or if pregnancy is suspected during treatment. Embryo-fetal toxicities including embryo-fetal death and fetal abnormalities (e.g., domed head, malformed eyeballs or eyeholes, hydrocephalus internus, ventricular septal defects, major vessel malformations, dysplastic forelimb bones, malformed ribs and vertebrae, and pelvis shift) were observed when copanlisib was administered to pregnant rats during organogenesis at doses corresponding to approximately 12% the recommended dose in humans.
Counsel patients about the reproductive risk and contraception requirements during copanlisib treatment. Pregnancy testing prior to starting therapy is recommended for females of reproductive potential. These patients should avoid pregnancy and use highly effective contraception during therapy and for 1 month after the last copanlisib dose. Due to the risk of male-mediated teratogenicity, men with female partners of reproductive potential should avoid fathering a child and use effective contraception during and for 1 month after copanlisib therapy. Adverse effects on male and female reproduction (e.g., infertility) are expected based on findings from animal studies.
It is not known whether copanlisib or its metabolites are secreted in human milk or if it has effects on the breast-fed infant or on milk production. Because of the potential for serious adverse reactions in nursing infants, women should discontinue breast-feeding during copanlisib therapy and for 1 month after the last dose.
For the treatment of non-Hodgkin's lymphoma (NHL):
-for the treatment of relapsed follicular lymphoma in patients who have received at least 2 prior systemic therapies:
NOTE: Copanlisib has been designated an orphan drug by the FDA for the treatment of follicular lymphoma.
Intravenous dosage:
Adults: 60 mg IV over 1 hour on days 1, 8, and 15 repeated every 28 days until disease progression. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Therapy interruption, dose reduction, or therapy discontinuation may be necessary in patients who develop toxicity. The overall response rate was 59% (complete response rate, 14%) in 104 patients with relapsed follicular B-cell non-Hodgkin lymphoma who received copanlisib in a multicenter, phase II trial (the CHRONOS-1 trial). The median time to response was 1.7 months (range, 1.3 to 9.7 months) and the median duration of response was 12.2 months (range, up to 22.6 months). Patients (median age, 62 years; range, 25 to 81 years) in this study had received a median of 3 prior treatments (range, 2 to 8 treatments) including rituximab and an alkylating agent.
Therapeutic Drug Monitoring:
Management of Treatment-Related Toxicity
Infection
Grade 3 or higher toxicity: Hold therapy until the infection resolves.
Cytomegalovirus infection or viremia (any grade): Hold therapy. When infection or viremia resolves, resume copanlisib at the previous dose and monitor patients for CMV reactivation by PCR or antigen test at least monthly.
Suspected pneumocystis jiroveci pneumonia (PJP) infection (any grade): Hold therapy. If PJP diagnosis is confirmed, treat the infection until resolution and then resume copanlisib at the previous dose. PJP prophylaxis is recommended for the duration of therapy.
Hyperglycemia
Pre-dose fasting blood glucose of 160 mg/dL or higher or a random/nonfasting blood glucose of 200 mg/dL or higher: Hold therapy until the fasting glucose is 160 mg/dL or less or a random/nonfasting blood glucose is 200 mg/dL or less.
Pre- or post-dose blood glucose of 500 mg/dL or higher (first occurrence): Hold therapy until fasting glucose is 160 mg/dL or less or a random/nonfasting blood glucose is 200 mg/dL or less; resume copanlisib at a reduced dose of 45 mg.
Pre- or post-dose blood glucose of 500 mg/dL or higher (subsequent occurrences): Hold therapy until fasting glucose is 160 mg/dL or less or a random/nonfasting blood glucose is 200 mg/dL or less; resume copanlisib at a reduced dose of 30 mg. Discontinue therapy if hyperglycemia persists at the 30-mg dose.
Hypertension
Pre-dose systolic blood pressure of 150 mmHg or higher or pre-dose diastolic blood pressure of 90 mmHg or higher: Hold therapy until blood pressure is less than 150/90 mmHg based on 2 consecutive measurements (taken at least 15 minutes apart).
Post-dose blood pressure of 150/90 mmHg or higher (non-life-threatening): Continue copanlisib at the previous dose if antihypertensive treatment is not required. Consider a copanlisib dose reduction (from 60 mg to 45 mg or from 45 mg to 30 mg) if antihypertensive treatment is required. Discontinue therapy if hypertension persists despite antihypertensive treatment.
Post-dose blood pressure (life-threatening): Discontinue therapy.
Non-Infectious Pneumonitis
Grade 2 toxicity: Hold therapy and treat with systemic corticosteroids. Resume copanlisib at a reduced dose of 45 mg when the toxicity recovers to grade 1 or less. Discontinue therapy if grade 2 toxicity recurs.
Grade 3 or higher toxicity: Discontinue therapy.
Neutropenia
Absolute neutrophil count (ANC) of 0.5 to 1 x 103 cells/mm3: Continue copanlisib at the previous dose and monitor the ANC at least weekly.
ANC less than of 0.5 x 103 cells/mm3: Hold therapy and monitor the ANC at least weekly until the ANC is 0.5 x 103 cells/mm3 or greater; resume copanlisib at the previous dose. Reduce the copanlisib dose to 45 mg if an ANC of 0.5 x 103 cells/mm3 or less recurs.
Thrombocytopenia
Platelet count less than 25 x 109 cells/L: Hold therapy. Resume copanlisib at a reduced dose (from 60 mg to 45 mg or from 45 mg to 30 mg) if the platelet count recovers to 75 x 109 cells/L or greater within 21 days. Discontinue therapy if the platelet count does not recover to 75 x 109 cells/L within 21 days.
Severe Cutaneous Reactions
Grade 3 toxicity: Hold therapy until the toxicity resolves. Resume copanlisib at a reduced dose (from 60 mg to 45 mg or from 45 mg to 30 mg).
Life-threatening (grade 4) toxicity: Discontinue therapy.
Other Severe and Non-Life-Threatening Toxicities
Grade 3 toxicity: Hold therapy until the toxicity resolves. Resume copanlisib at a reduced dose (from 60 mg to 45 mg or from 45 mg to 30 mg).
Grade 4 or life-threatening toxicity: Discontinue therapy.
Maximum Dosage Limits:
-Adults
60 mg IV.
-Geriatric
60 mg IV.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Mild hepatic impairment (total bilirubin level of 1 times the ULN or less and AST level greater than the ULN, or a total bilirubin level greater than 1 to 1.5 times the ULN and any AST level): No dosage adjustment necessary.
Moderate hepatic impairment (Child-Pugh class B): Reduce the copanlisib dose to 45 mg IV.
Severe hepatic impairment (Child-Pugh class C): Reduce the copanlisib dose to 30 mg IV.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Adagrasib: (Major) Avoid the concomitant use of copanlisib and adagrasib if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; adagrasib is a strong CYP3A inhibitor.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid the concomitant use of copanlisib and clarithromycin if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; clarithromycin is a strong CYP3A inhibitor.
Apalutamide: (Major) Avoid the concomitant use of copanlisib and apalutamide; decreased copanlisib exposure and loss of efficacy may occur. Copanlisib is a CYP3A substrate and apalutamide is a strong CYP3A inducer. Coadministration with another strong CYP3A4 inducer decreased exposure after a single dose of copanlisib by 60%.
Atazanavir: (Major) Avoid the concomitant use of copanlisib and atazanavir if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; atazanavir is a strong CYP3A inhibitor.
Atazanavir; Cobicistat: (Major) Avoid the concomitant use of copanlisib and atazanavir if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; atazanavir is a strong CYP3A inhibitor. (Major) Avoid the concomitant use of copanlisib and cobicistat if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; cobicistat is a strong CYP3A inhibitor. The AUC of copanlisib increased by 53% when a single IV dose of copanlisib 60 mg was administered following 10 days of another strong CYP3A4 inhibitor in a drug interaction study in patients with cancer.
Carbamazepine: (Major) Avoid the concomitant use of copanlisib and carbamazepine; decreased copanlisib exposure and loss of efficacy may occur. Copanlisib is a CYP3A substrate; carbamazepine is a strong CYP3A inducer. The AUC and Cmax values of copanlisib decreased by 60% and 12%, respectively, when a single IV dose of copanlisib 60 mg was administered following 12 days of another strong CYP3A4 inducer in a drug interaction study in patients with cancer.
Ceritinib: (Major) Avoid the concomitant use of copanlisib and ceritinib if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; ceritinib is a strong CYP3A inhibitor.
Chloramphenicol: (Major) Avoid the concomitant use of copanlisib and chloramphenicol if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; chloramphenicol is a strong CYP3A inhibitor.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Clarithromycin: (Major) Avoid the concomitant use of copanlisib and clarithromycin if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; clarithromycin is a strong CYP3A inhibitor.
Cobicistat: (Major) Avoid the concomitant use of copanlisib and cobicistat if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; cobicistat is a strong CYP3A inhibitor. The AUC of copanlisib increased by 53% when a single IV dose of copanlisib 60 mg was administered following 10 days of another strong CYP3A4 inhibitor in a drug interaction study in patients with cancer.
Darunavir: (Major) Avoid the concomitant use of copanlisib and darunavir if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; darunavir is a strong CYP3A inhibitor.
Darunavir; Cobicistat: (Major) Avoid the concomitant use of copanlisib and cobicistat if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; cobicistat is a strong CYP3A inhibitor. The AUC of copanlisib increased by 53% when a single IV dose of copanlisib 60 mg was administered following 10 days of another strong CYP3A4 inhibitor in a drug interaction study in patients with cancer. (Major) Avoid the concomitant use of copanlisib and darunavir if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; darunavir is a strong CYP3A inhibitor.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid the concomitant use of copanlisib and cobicistat if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; cobicistat is a strong CYP3A inhibitor. The AUC of copanlisib increased by 53% when a single IV dose of copanlisib 60 mg was administered following 10 days of another strong CYP3A4 inhibitor in a drug interaction study in patients with cancer. (Major) Avoid the concomitant use of copanlisib and darunavir if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; darunavir is a strong CYP3A inhibitor.
Delavirdine: (Major) Avoid the concomitant use of copanlisib and delavirdine if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; delavirdine is a strong CYP3A inhibitor.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid the concomitant use of copanlisib and cobicistat if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; cobicistat is a strong CYP3A inhibitor. The AUC of copanlisib increased by 53% when a single IV dose of copanlisib 60 mg was administered following 10 days of another strong CYP3A4 inhibitor in a drug interaction study in patients with cancer.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid the concomitant use of copanlisib and cobicistat if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; cobicistat is a strong CYP3A inhibitor. The AUC of copanlisib increased by 53% when a single IV dose of copanlisib 60 mg was administered following 10 days of another strong CYP3A4 inhibitor in a drug interaction study in patients with cancer.
Encorafenib: (Major) Avoid the concomitant use of copanlisib and encorafenib; decreased copanlisib exposure and loss of efficacy may occur. Copanlisib is a CYP3A substrate and encorafenib is a strong CYP3A inducer. Coadministration with another strong CYP3A inducer decreased exposure after a single dose of copanlisib by 63%.
Enzalutamide: (Major) Avoid the concomitant use of copanlisib and enzalutamide; decreased copanlisib exposure and loss of efficacy may occur. Copanlisib is a CYP3A substrate and enzalutamide is a strong CYP3A inducer. Coadministration with another strong CYP3A4 inducer decreased exposure after a single dose of copanlisib by 60%.
Fosamprenavir: (Major) Avoid the concomitant use of copanlisib and fosamprenavir if possible due to an unpredictable effect on copanlisib exposure. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash) and/or decreased copanlisib efficacy. Copanlisib is a CYP3A substrate; fosamprenavir is a strong CYP3A4 inhibitor with the potential to also induce CYP3A4.
Fosphenytoin: (Major) Avoid the concomitant use of copanlisib and fosphenytoin; decreased copanlisib exposure and loss of efficacy may occur. Copanlisib is a CYP3A substrate; fosphenytoin is a strong CYP3A inducer. The AUC and Cmax values of copanlisib decreased by 60% and 12%, respectively, when a single IV dose of copanlisib 60 mg was administered following 12 days of another strong CYP3A4 inducer in a drug interaction study in patients with cancer.
Grapefruit juice: (Major) Avoid the concomitant use of copanlisib and grapefruit juice if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; grapefruit juice is a strong CYP3A inhibitor.
Idelalisib: (Major) Avoid the concomitant use of copanlisib and idelalisib if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; idelalisib is a strong CYP3A inhibitor.
Indinavir: (Major) Avoid the concomitant use of copanlisib and indinavir if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; indinavir is a strong CYP3A inhibitor.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid the concomitant use of copanlisib and rifampin; decreased copanlisib exposure occurred in a drug interaction study. Copanlisib is a substrate of CYP3A and P-glycoprotein (P-gp); rifampin is a strong CYP3A inducer and also induces P-gp. The AUC and Cmax values of copanlisib decreased by 60% and 12%, respectively, when a single IV dose of copanlisib 60 mg was administered following 12 days of rifampin 600 mg/day in a drug interaction study in patients with cancer.
Isoniazid, INH; Rifampin: (Major) Avoid the concomitant use of copanlisib and rifampin; decreased copanlisib exposure occurred in a drug interaction study. Copanlisib is a substrate of CYP3A and P-glycoprotein (P-gp); rifampin is a strong CYP3A inducer and also induces P-gp. The AUC and Cmax values of copanlisib decreased by 60% and 12%, respectively, when a single IV dose of copanlisib 60 mg was administered following 12 days of rifampin 600 mg/day in a drug interaction study in patients with cancer.
Itraconazole: (Major) Avoid the concomitant use of copanlisib and itraconazole if possible; increased copanlisib exposure occurred in a drug interaction study. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a substrate of CYP3A, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP); itraconazole is a strong CYP3A inhibitor and also inhibits P-gp and BCRP. The AUC of copanlisib increased by 53% when a single IV dose of copanlisib 60 mg was administered following 10 days of itraconazole 200 mg/day in a drug interaction study in patients with cancer; the Cmax of copanlisib was not significantly increased.
Ketoconazole: (Major) Avoid the concomitant use of copanlisib and ketoconazole if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; ketoconazole is a strong CYP3A inhibitor.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid the concomitant use of copanlisib and clarithromycin if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; clarithromycin is a strong CYP3A inhibitor.
Letermovir: (Moderate) Administering letermovir with copanlisib may increase copanlisib concentration and risk for adverse events. Avoid coadministration in patients who are also receiving treatment with cyclosporine, because the magnitude of this interaction may be amplified. If concurrent use of copanlisib with both letermovir and cyclosporine cannot be avoided, reduce the copanlisib dose to 45 mg and monitor for toxicity. Copanlisib is predominately metabolized by CYP3A4. Letermovir a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of copanlisib by 53% with no effect on Cmax.
Levoketoconazole: (Major) Avoid the concomitant use of copanlisib and ketoconazole if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; ketoconazole is a strong CYP3A inhibitor.
Lonafarnib: (Major) Avoid the concomitant use of copanlisib and lonafarnib if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; lonafarnib is a strong CYP3A inhibitor.
Lopinavir; Ritonavir: (Major) Avoid the concomitant use of copanlisib and ritonavir if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; ritonavir is a strong CYP3A inhibitor.
Lumacaftor; Ivacaftor: (Major) Avoid the concomitant use of copanlisib and lumacaftor; ivacaftor; decreased copanlisib exposure and loss of efficacy may occur. Copanlisib is a CYP3A substrate; lumacaftor is a strong CYP3A inducer. The AUC and Cmax values of copanlisib decreased by 60% and 12%, respectively, when a single IV dose of copanlisib 60 mg was administered following 12 days of another strong CYP3A4 inducer in a drug interaction study in patients with cancer.
Lumacaftor; Ivacaftor: (Major) Avoid the concomitant use of copanlisib and lumacaftor; ivacaftor; decreased copanlisib exposure and loss of efficacy may occur. Copanlisib is a CYP3A substrate; lumacaftor is a strong CYP3A inducer. The AUC and Cmax values of copanlisib decreased by 60% and 12%, respectively, when a single IV dose of copanlisib 60 mg was administered following 12 days of another strong CYP3A4 inducer in a drug interaction study in patients with cancer.
Mitotane: (Major) Avoid the concomitant use of copanlisib and mitotane; decreased copanlisib exposure and loss of efficacy may occur. Copanlisib is a CYP3A substrate; mitotane is a strong CYP3A inducer.
Nefazodone: (Major) Avoid the concomitant use of copanlisib and nefazodone if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; nefazodone is a strong CYP3A inhibitor.
Nelfinavir: (Major) Avoid the concomitant use of copanlisib and nelfinavir if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; nelfinavir is a strong CYP3A inhibitor.
Nirmatrelvir; Ritonavir: (Major) Avoid the concomitant use of copanlisib and ritonavir if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; ritonavir is a strong CYP3A inhibitor.
Phenobarbital: (Major) Avoid the concomitant use of copanlisib and phenobarbital; decreased copanlisib exposure and loss of efficacy may occur. Copanlisib is a CYP3A substrate; phenobarbital is a strong CYP3A inducer. The AUC and Cmax values of copanlisib decreased by 60% and 12%, respectively, when a single IV dose of copanlisib 60 mg was administered following 12 days of another strong CYP3A4 inducer in a drug interaction study in patients with cancer.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid the concomitant use of copanlisib and phenobarbital; decreased copanlisib exposure and loss of efficacy may occur. Copanlisib is a CYP3A substrate; phenobarbital is a strong CYP3A inducer. The AUC and Cmax values of copanlisib decreased by 60% and 12%, respectively, when a single IV dose of copanlisib 60 mg was administered following 12 days of another strong CYP3A4 inducer in a drug interaction study in patients with cancer.
Phenytoin: (Major) Avoid the concomitant use of copanlisib and phenytoin; decreased copanlisib exposure and loss of efficacy may occur. Copanlisib is a CYP3A substrate; phenytoin is a strong CYP3A inducer. The AUC and Cmax values of copanlisib decreased by 60% and 12%, respectively, when a single IV dose of copanlisib 60 mg was administered following 12 days of another strong CYP3A4 inducer in a drug interaction study in patients with cancer.
Posaconazole: (Major) Avoid the concomitant use of copanlisib and posaconazole if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; posaconazole is a strong CYP3A inhibitor.
Primidone: (Major) Avoid the concomitant use of copanlisib and primidone; decreased copanlisib exposure and loss of efficacy may occur. Copanlisib is a CYP3A substrate; primidone is a strong CYP3A inducer. The AUC and Cmax values of copanlisib decreased by 60% and 12%, respectively, when a single IV dose of copanlisib 60 mg was administered following 12 days of another strong CYP3A4 inducer in a drug interaction study in patients with cancer.
Rifampin: (Major) Avoid the concomitant use of copanlisib and rifampin; decreased copanlisib exposure occurred in a drug interaction study. Copanlisib is a substrate of CYP3A and P-glycoprotein (P-gp); rifampin is a strong CYP3A inducer and also induces P-gp. The AUC and Cmax values of copanlisib decreased by 60% and 12%, respectively, when a single IV dose of copanlisib 60 mg was administered following 12 days of rifampin 600 mg/day in a drug interaction study in patients with cancer.
Rifapentine: (Major) Avoid the concomitant use of copanlisib and rifapentine; decreased copanlisib exposure and loss of efficacy may occur. Copanlisib is a CYP3A substrate and rifapentine is a strong CYP3A inducer. Coadministration with another strong CYP3A4 inducer decreased exposure after a single dose of copanlisib by 63%.
Ritonavir: (Major) Avoid the concomitant use of copanlisib and ritonavir if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; ritonavir is a strong CYP3A inhibitor.
Saquinavir: (Major) Avoid the concomitant use of copanlisib and saquinavir if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; saquinavir boosted with ritonavir is a strong CYP3A inhibitor.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
St. John's Wort, Hypericum perforatum: (Major) Avoid the concomitant use of copanlisib and St. John's Wort; decreased copanlisib exposure and loss of efficacy may occur. Copanlisib is a CYP3A substrate; St. John's Wort is a strong CYP3A inducer. The AUC and Cmax values of copanlisib decreased by 60% and 12%, respectively, when a single IV dose of copanlisib 60 mg was administered following 12 days of another strong CYP3A4 inducer in a drug interaction study in patients with cancer.
Tipranavir: (Major) Avoid the concomitant use of copanlisib and tipranavir if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; tipranavir boosted with ritonavir is a strong CYP3A inhibitor.
Tucatinib: (Major) Avoid the concomitant use of copanlisib and tucatinib if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; tucatinib is a strong CYP3A inhibitor.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid the concomitant use of copanlisib and clarithromycin if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; clarithromycin is a strong CYP3A inhibitor.
Voriconazole: (Major) Avoid the concomitant use of copanlisib and voriconazole if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; voriconazole is a strong CYP3A inhibitor.
Copanlisib is an inhibitor of phosphatidylinositol 3-kinase (PI3K); it works primarily to inhibit PI3K-alpha and PI3K-delta isoforms expressed in malignant B-cells. Copanlisib induces tumor cell death by apoptosis and by inhibiting the proliferation of primary malignant B-cell lines. It also inhibits B-cell receptor (BCR) signaling, CXCR12-mediated chemotaxis of malignant B-cells, and nuclear factor (NF) kappa B signaling in lymphoma cell lines.
Copanlisib is administered intravenously (IV). It is 84.2% bound to plasma proteins, primarily albumin. The mean blood-to-plasma ratio is 1.7 (range, 1.5 to 2.1). The geometric mean volume of distribution of copanlisib is 871 L (range, 423 to 2,150 L), the geometric mean terminal elimination half-life is 39.1 hours (range, 14.6 to 82.4 hours), and the geometric mean clearance is 17.9 L/hour (range, 7.3 to 51.4 L/hour). Following a single radiolabeled dose of copanlisib 12 mg IV, approximately 64% of the dose was excreted in the feces and 22% in the urine within 20 to 34 days; about 30% and 15% of the dose was recovered as unchanged copanlisib in the feces and urine, respectively. The M-1 metabolite accounted for 5% of the total radioactivity. Copanlisib is primarily metabolized by CYP3A; a minor pathway for metabolism is CYP1A1. The M-1 metabolite has pharmacological activity comparable to the parent compound copanlisib for the tested kinases PI3K-alpha and PI3K-delta.
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A, CYP1A1, P-gp, BCRP, MATE2-K
Copanlisib is a substrate of CYP3A (greater than 90%) and CYP1A1 (less than 10%). Avoid the concomitant use of copanlisib with strong CYP3A inhibitors or inducers. If copanlisib is administered with a strong CYP3A inhibitor, reduce the dose and monitor for signs of copanlisib toxicity. Copanlisib is a substrate of the P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) transporters and a multidrug and toxin extrusion member 2 (MATE2)-K inhibitor.
-Route-Specific Pharmacokinetics
Intravenous Route
When administered at approximately the recommended dose of 60 mg, the geometric mean steady-state Cmax and AUC(0-25 hr) values of copanlisib were 463 ng/mL (range, 105 to 1,670 ng/mL) and 1,570 ng X hour/mL (range, 536 to 3,410 ng X hour/mL), respectively. The Cmax and AUC values increased proportionally and exhibited linear pharmacokinetics over a copanlisib dose range of 5 to 93 mg; there was no accumulation.
-Special Populations
Hepatic Impairment
Following a single dose of copanlisib 12 mg IV (0.2 times the recommended approved dose of 60 mg), the geometric mean Cmax and AUC values increased by 1.38-fold and 1.71-fold, respectively, in subjects with moderate hepatic impairment (Child-Pugh class B) and by 1.44-fold and 2.71-fold, respectively, in subjects with severe hepatic impairment (Child-Pugh class C) compared to subjects with normal hepatic function in a pharmacokinetic study. Additionally, the geometric mean unbound AUC values were increased by 1.23-fold and 3.77-fold in patients with moderate and severe hepatic impairment, respectively; the geometric mean unbound Cmax value did not increase with moderate hepatic impairment and increased 1.92-fold with severe impairment.
Renal Impairment
Mild to severe renal impairment (defined as a creatinine clearance (CrCl) of 15 mL/min or greater) did not have a clinically significant impact on the pharmacokinetic (PK) parameters of copanlisib in a population PK analysis. There is insufficient PK data regarding the use of copanlisib in patients with end-stage renal disease (CrCl less than 15 mL/min).
Geriatric
Age (range, 20 to 90 years) had no clinically significant impact on the pharmacokinetic (PK) parameters of copanlisib in a population PK analysis.
Gender Differences
Gender had no clinically significant impact on the pharmacokinetic (PK) parameters of copanlisib in a population PK analysis.
Ethnic Differences
Ethnicity had no clinically significant impact on the pharmacokinetic (PK) parameters of copanlisib in a population PK analysis.
Obesity
Body weight (range, 41 to 130 kg) had no clinically significant impact on the pharmacokinetic (PK) parameters of copanlisib in a population PK analysis.
Other
Tobacco Users
Tobacco use had no clinically significant impact on the pharmacokinetic (PK) parameters of copanlisib in a population PK analysis.