Aliqopa

Small Molecule Antineoplastic Phosphatidylinositol-3-Kinase (PI3K) Inhibitors

Emetic Risk
Low
Administer routine antiemetic prophylaxis prior to treatment.

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

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.

hyperglycemia / Delayed / 0-41.0
lymphopenia / Delayed / 0-29.0
hypertension / Early / 0-27.0
leukopenia / Delayed / 0-27.0
neutropenia / Delayed / 0-25.0
hyperuricemia / Delayed / 25.0-25.0
infection / Delayed / 0-19.0
hypophosphatemia / Delayed / 15.0-15.0
thrombocytopenia / Delayed / 0-8.0
hypertriglyceridemia / Delayed / 5.0-5.0
diarrhea / Early / 5.0-5.0
anemia / Delayed / 0-4.0
asthenia / Delayed / 0-4.0
fatigue / Early / 0-4.0
rash / Early / 0-2.0
stomatitis / Delayed / 2.0-2.0
nausea / Early / 0-1.0
pruritus / Rapid / 0-0.9
exfoliative dermatitis / Delayed / 0-0.9
maculopapular rash / Early / 0-0.9

pneumonitis / Delayed / 5.0-9.0
dyspnea / Early / Incidence not known
hypoxia / Early / Incidence not known

vomiting / Early / 13.0-13.0
paresthesias / Delayed / 7.0-7.0
dysesthesia / Delayed / 7.0-7.0
cough / Delayed / Incidence not known

Aliqopa

Rx

A phosphatidylinositol-3-kinase (PI3K) inhibitor
Used in adults with relapsed follicular lymphoma
Severe hyperglycemia and hypertension have been reported

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.

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.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

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.

Aliqopa Intravenous Inj Pwd: 60mg

60 mg IV.

60 mg IV.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

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.

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.

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.